Sample records for cell delay variation

  1. Way-Scaling to Reduce Power of Cache with Delay Variation

    NASA Astrophysics Data System (ADS)

    Goudarzi, Maziar; Matsumura, Tadayuki; Ishihara, Tohru

    The share of leakage in cache power consumption increases with technology scaling. Choosing a higher threshold voltage (Vth) and/or gate-oxide thickness (Tox) for cache transistors improves leakage, but impacts cell delay. We show that due to uncorrelated random within-die delay variation, only some (not all) of cells actually violate the cache delay after the above change. We propose to add a spare cache way to replace delay-violating cache-lines separately in each cache-set. By SPICE and gate-level simulations in a commercial 90nm process, we show that choosing higher Vth, Tox and adding one spare way to a 4-way 16KB cache reduces leakage power by 42%, which depending on the share of leakage in total cache power, gives up to 22.59% and 41.37% reduction of total energy respectively in L1 instruction- and L2 unified-cache with a negligible delay penalty, but without sacrificing cache capacity or timing-yield.

  2. Compensation for Lithography Induced Process Variations during Physical Design

    NASA Astrophysics Data System (ADS)

    Chin, Eric Yiow-Bing

    This dissertation addresses the challenge of designing robust integrated circuits in the deep sub micron regime in the presence of lithography process variability. By extending and combining existing process and circuit analysis techniques, flexible software frameworks are developed to provide detailed studies of circuit performance in the presence of lithography variations such as focus and exposure. Applications of these software frameworks to select circuits demonstrate the electrical impact of these variations and provide insight into variability aware compact models that capture the process dependent circuit behavior. These variability aware timing models abstract lithography variability from the process level to the circuit level and are used to estimate path level circuit performance with high accuracy with very little overhead in runtime. The Interconnect Variability Characterization (IVC) framework maps lithography induced geometrical variations at the interconnect level to electrical delay variations. This framework is applied to one dimensional repeater circuits patterned with both 90nm single patterning and 32nm double patterning technologies, under the presence of focus, exposure, and overlay variability. Studies indicate that single and double patterning layouts generally exhibit small variations in delay (between 1--3%) due to self compensating RC effects associated with dense layouts and overlay errors for layouts without self-compensating RC effects. The delay response of each double patterned interconnect structure is fit with a second order polynomial model with focus, exposure, and misalignment parameters with 12 coefficients and residuals of less than 0.1ps. The IVC framework is also applied to a repeater circuit with cascaded interconnect structures to emulate more complex layout scenarios, and it is observed that the variations on each segment average out to reduce the overall delay variation. The Standard Cell Variability Characterization (SCVC) framework advances existing layout-level lithography aware circuit analysis by extending it to cell-level applications utilizing a physically accurate approach that integrates process simulation, compact transistor models, and circuit simulation to characterize electrical cell behavior. This framework is applied to combinational and sequential cells in the Nangate 45nm Open Cell Library, and the timing response of these cells to lithography focus and exposure variations demonstrate Bossung like behavior. This behavior permits the process parameter dependent response to be captured in a nine term variability aware compact model based on Bossung fitting equations. For a two input NAND gate, the variability aware compact model captures the simulated response to an accuracy of 0.3%. The SCVC framework is also applied to investigate advanced process effects including misalignment and layout proximity. The abstraction of process variability from the layout level to the cell level opens up an entire new realm of circuit analysis and optimization and provides a foundation for path level variability analysis without the computationally expensive costs associated with joint process and circuit simulation. The SCVC framework is used with slight modification to illustrate the speedup and accuracy tradeoffs of using compact models. With variability aware compact models, the process dependent performance of a three stage logic circuit can be estimated to an accuracy of 0.7% with a speedup of over 50,000. Path level variability analysis also provides an accurate estimate (within 1%) of ring oscillator period in well under a second. Another significant advantage of variability aware compact models is that they can be easily incorporated into existing design methodologies for design optimization. This is demonstrated by applying cell swapping on a logic circuit to reduce the overall delay variability along a circuit path. By including these variability aware compact models in cell characterization libraries, design metrics such as circuit timing, power, area, and delay variability can be quickly assessed to optimize for the correct balance of all design metrics, including delay variability. Deterministic lithography variations can be easily captured using the variability aware compact models described in this dissertation. However, another prominent source of variability is random dopant fluctuations, which affect transistor threshold voltage and in turn circuit performance. The SCVC framework is utilized to investigate the interactions between deterministic lithography variations and random dopant fluctuations. Monte Carlo studies show that the output delay distribution in the presence of random dopant fluctuations is dependent on lithography focus and exposure conditions, with a 3.6 ps change in standard deviation across the focus exposure process window. This indicates that the electrical impact of random variations is dependent on systematic lithography variations, and this dependency should be included for precise analysis.

  3. Low-power, high-speed 1-bit inexact Full Adder cell designs applicable to low-energy image processing

    NASA Astrophysics Data System (ADS)

    Zareei, Zahra; Navi, Keivan; Keshavarziyan, Peiman

    2018-03-01

    In this paper, three novel low-power and high-speed 1-bit inexact Full Adder cell designs are presented based on current mode logic in 32 nm carbon nanotube field effect transistor technology for the first time. The circuit-level figures of merits, i.e. power, delay and power-delay product as well as application-level metric such as error distance, are considered to assess the efficiency of the proposed cells over their counterparts. The effect of voltage scaling and temperature variation on the proposed cells is studied using HSPICE tool. Moreover, using MATLAB tool, the peak signal to noise ratio of the proposed cells is evaluated in an image-processing application referred to as motion detector. Simulation results confirm the efficiency of the proposed cells.

  4. Binaural interaction in low-frequency neurons in inferior colliculus of the cat. I. Effects of long interaural delays, intensity, and repetition rate on interaural delay function.

    PubMed

    Kuwada, S; Yin, T C

    1983-10-01

    Detailed, quantitative studies were made of the interaural phase sensitivity of 197 neurons with low best frequency in the inferior colliculus (IC) of the barbiturate-anesthetized cat. We analyzed the responses of single cells to interaural delays in which tone bursts were delivered to the two ears via sealed earphones and the onset of the tone to one ear with respect to the other was varied. For most (80%) cells the discharge rate is a cyclic function of interaural delay at a period corresponding to that of the stimulating frequency. The cyclic nature of the interaural delay curve indicates that these cells are sensitive to the interaural phase difference. These cells are distributed throughout the low-frequency zone of the IC, but they are less numerous in the medial and caudal zones. Cells with a wide variety of response patterns will exhibit interaural phase sensitivities at stimulating frequencies up to 3,100 Hz, although above 2,500 Hz the number of such cells decrease markedly. Using dichotic stimuli we could study the cell's sensitivity to the onset delay and interaural phase independently. The large majority of IC cells respond only to changes in interaural phase, with no sensitivity to the onset delay. However, a small number (7%) of cells exhibit a sensitivity to the onset delay as well as to the interaural phase disparity, and most of these cells show an onset response. The effects of changing the stimulus intensity equally to both ears or of changing the interaural intensity difference on the mean interaural phase were studied. While some neurons are not affected by level changes, others exhibit systematic phase shifts for both average and interaural intensity variations, and there is a continuous distribution of sensitivities between these extremes. A few cells also showed systematic changes in the shape of the interaural delay curves as a function of interaural intensity difference, especially at very long delays. These shifts can be interpreted as a form of time-intensity trading. A few cells demonstrated orderly changes in the interaural delay curve as the repetition rate of the stimulus was varied. Some of these changes are consonant with an inhibitory effect that occurs at stimulus offset. The responses of the neurons show a strong bias for stimuli that would originate from he contralateral sound field; 77% of the responses display mean interaural phase angles that are less than 0.5 of a cycle, which are delays to the ipsilateral tone.(ABSTRACT TRUNCATED AT 400 WORDS)

  5. Measurement method for determining the magnetic hysteresis effects of reluctance actuators by evaluation of the force and flux variation.

    PubMed

    Vrijsen, N H; Jansen, J W; Compter, J C; Lomonova, E A

    2013-07-01

    A measurement method is presented which identifies the magnetic hysteresis effects present in the force of linear reluctance actuators. The measurement method is applied to determine the magnetic hysteresis in the force of an E-core reluctance actuator, with and without pre-biasing permanent magnet. The force measurements are conducted with a piezoelectric load cell (Kistler type 9272). This high-bandwidth force measurement instrument is identified in the frequency domain using a voice-coil actuator that has negligible magnetic hysteresis and eddy currents. Specifically, the phase delay between the current and force of the voice-coil actuator is used for the calibration of the measurement instrument. This phase delay is also obtained by evaluation of the measured force and flux variation in the E-core actuator, both with and without permanent magnet on the middle tooth. The measured magnetic flux variation is used to distinguish the phase delay due to magnetic hysteresis from the measured phase delay between the current and the force of the E-core actuator. Finally, an open loop steady-state ac model is presented that predicts the magnetic hysteresis effects in the force of the E-core actuator.

  6. Reliability evaluation of high-performance, low-power FinFET standard cells based on mixed RBB/FBB technique

    NASA Astrophysics Data System (ADS)

    Wang, Tian; Cui, Xiaoxin; Ni, Yewen; Liao, Kai; Liao, Nan; Yu, Dunshan; Cui, Xiaole

    2017-04-01

    With shrinking transistor feature size, the fin-type field-effect transistor (FinFET) has become the most promising option in low-power circuit design due to its superior capability to suppress leakage. To support the VLSI digital system flow based on logic synthesis, we have designed an optimized high-performance low-power FinFET standard cell library based on employing the mixed FBB/RBB technique in the existing stacked structure of each cell. This paper presents the reliability evaluation of the optimized cells under process and operating environment variations based on Monte Carlo analysis. The variations are modelled with Gaussian distribution of the device parameters and 10000 sweeps are conducted in the simulation to obtain the statistical properties of the worst-case delay and input-dependent leakage for each cell. For comparison, a set of non-optimal cells that adopt the same topology without employing the mixed biasing technique is also generated. Experimental results show that the optimized cells achieve standard deviation reduction of 39.1% and 30.7% at most in worst-case delay and input-dependent leakage respectively while the normalized deviation shrinking in worst-case delay and input-dependent leakage can be up to 98.37% and 24.13%, respectively, which demonstrates that our optimized cells are less sensitive to variability and exhibit more reliability. Project supported by the National Natural Science Foundation of China (No. 61306040), the State Key Development Program for Basic Research of China (No. 2015CB057201), the Beijing Natural Science Foundation (No. 4152020), and Natural Science Foundation of Guangdong Province, China (No. 2015A030313147).

  7. Analysis of power gating in different hierarchical levels of 2MB cache, considering variation

    NASA Astrophysics Data System (ADS)

    Jafari, Mohsen; Imani, Mohsen; Fathipour, Morteza

    2015-09-01

    This article reintroduces power gating technique in different hierarchical levels of static random-access memory (SRAM) design including cell, row, bank and entire cache memory in 16 nm Fin field effect transistor. Different structures of SRAM cells such as 6T, 8T, 9T and 10T are used in design of 2MB cache memory. The power reduction of the entire cache memory employing cell-level optimisation is 99.7% with the expense of area and other stability overheads. The power saving of the cell-level optimisation is 3× (1.2×) higher than power gating in cache (bank) level due to its superior selectivity. The access delay times are allowed to increase by 4% in the same energy delay product to achieve the best power reduction for each supply voltages and optimisation levels. The results show the row-level power gating is the best for optimising the power of the entire cache with lowest drawbacks. Comparisons of cells show that the cells whose bodies have higher power consumption are the best candidates for power gating technique in row-level optimisation. The technique has the lowest percentage of saving in minimum energy point (MEP) of the design. The power gating also improves the variation of power in all structures by at least 70%.

  8. A Nonlinear Model for Transient Responses from Light-Adapted Wolf Spider Eyes

    PubMed Central

    DeVoe, Robert D.

    1967-01-01

    A quantitative model is proposed to test the hypothesis that the dynamics of nonlinearities in retinal action potentials from light-adapted wolf spider eyes may be due to delayed asymmetries in responses of the visual cells. For purposes of calculation, these delayed asymmetries are generated in an analogue by a time-variant resistance. It is first shown that for small incremental stimuli, the linear behavior of such a resistance describes peaking and low frequency phase lead in frequency responses of the eye to sinusoidal modulations of background illumination. It also describes the overshoots in linear step responses. It is next shown that the analogue accounts for nonlinear transient and short term DC responses to large positive and negative step stimuli and for the variations in these responses with changes in degree of light adaptation. Finally, a physiological model is proposed in which the delayed asymmetries in response are attributed to delayed rectification by the visual cell membrane. In this model, cascaded chemical reactions may serve to transduce visual stimuli into membrane resistance changes. PMID:6056011

  9. System for sensing droplet formation time delay in a flow cytometer

    DOEpatents

    Van den Engh, Ger; Esposito, Richard J.

    1997-01-01

    A droplet flow cytometer system which includes a system to optimize the droplet formation time delay based on conditions actually experienced includes an automatic droplet sampler which rapidly moves a plurality of containers stepwise through the droplet stream while simultaneously adjusting the droplet time delay. Through the system sampling of an actual substance to be processed can be used to minimize the effect of the substances variations or the determination of which time delay is optimal. Analysis such as cell counting and the like may be conducted manually or automatically and input to a time delay adjustment which may then act with analysis equipment to revise the time delay estimate actually applied during processing. The automatic sampler can be controlled through a microprocessor and appropriate programming to bracket an initial droplet formation time delay estimate. When maximization counts through volume, weight, or other types of analysis exists in the containers, the increment may then be reduced for a more accurate ultimate setting. This may be accomplished while actually processing the sample without interruption.

  10. A high resolution on-chip delay sensor with low supply-voltage sensitivity for high-performance electronic systems.

    PubMed

    Sheng, Duo; Lai, Hsiu-Fan; Chan, Sheng-Min; Hong, Min-Rong

    2015-02-13

    An all-digital on-chip delay sensor (OCDS) circuit with high delay-measurement resolution and low supply-voltage sensitivity for efficient detection and diagnosis in high-performance electronic system applications is presented. Based on the proposed delay measurement scheme, the quantization resolution of the proposed OCDS can be reduced to several picoseconds. Additionally, the proposed cascade-stage delay measurement circuit can enhance immunity to supply-voltage variations of the delay measurement resolution without extra self-biasing or calibration circuits. Simulation results show that the delay measurement resolution can be improved to 1.2 ps; the average delay resolution variation is 0.55% with supply-voltage variations of ±10%. Moreover, the proposed delay sensor can be implemented in an all-digital manner, making it very suitable for high-performance electronic system applications as well as system-level integration.

  11. Proliferation kinetics of cultured cells after irradiation with X-rays and 14 MeV neutrons studied by time-lapse cinematography.

    PubMed

    Kooi, M W; Stap, J; Barendsen, G W

    1984-06-01

    Exponentially growing cells of an established line derived from a mouse osteosarcoma (MOS) have been studied by time-lapse cinematography after irradiation with 3 Gy of 200 kV X-rays or 1.5 Gy of 14 MeV neutrons. Cell cycle times (Tc) of individual cells and their progeny in three subsequent generations as well as the occurrence of aberrant mitosis have been determined to evaluate the variation in expression of damage in relation to the stage in the intermitotic cycle and the radiation quality. The results show that the radiation doses applied cause an equal elongation of the mean Tc, which is largest in the irradiated cells but persists in the three subsequent generations. After 3 Gy of X-rays, mitotic delay is largest in cells irradiated in later stages of the cycle, but this difference is not observed after 1.5 Gy of 14 MeV neutrons. In subsequent generations the Tc values show larger variations among descendents of cells treated in the same stage of the cycle as compared to controls but this variation is equal for the doses of X-rays and neutrons applied. Division probability was significantly reduced in irradiated cells as well as in subsequent generations, whereby with neutrons as compared to X-rays the damage is expressed in earlier generations, with less variation as a function of the cell cycle.

  12. [Ca2+]i Elevation and Oxidative Stress Induce KCNQ1 Protein Translocation from the Cytosol to the Cell Surface and Increase Slow Delayed Rectifier (IKs) in Cardiac Myocytes*

    PubMed Central

    Wang, Yuhong; Zankov, Dimitar P.; Jiang, Min; Zhang, Mei; Henderson, Scott C.; Tseng, Gea-Ny

    2013-01-01

    Our goals are to simultaneously determine the three-dimensional distribution patterns of KCNQ1 and KCNE1 in cardiac myocytes and to study the mechanism and functional implications for variations in KCNQ1/KCNE1 colocalization in myocytes. We monitored the distribution patterns of KCNQ1, KCNE1, and markers for subcellular compartments/organelles using immunofluorescence/confocal microscopy and confirmed the findings in ventricular myocytes by directly observing fluorescently tagged KCNQ1-GFP and KCNE1-dsRed expressed in these cells. We also monitored the effects of stress on KCNQ1-GFP and endoplasmic reticulum (ER) remodeling during live cell imaging. The data showed that 1) KCNE1 maintained a stable cell surface localization, whereas KCNQ1 exhibited variations in the cytosolic compartment (striations versus vesicles) and the degree of presence on the cell surface; 2) the degree of cell surface KCNQ1/KCNE1 colocalization was positively correlated with slow delayed rectifier (IKs) current density; 3) KCNQ1 and calnexin (an ER marker) shared a cytosolic compartment; and 4) in response to stress ([Ca2+]i elevation, oxidative overload, or AT1R stimulation), KCNQ1 exited the cytosolic compartment and trafficked to the cell periphery in vesicles. This was accompanied by partial ER fragmentation. We conclude that the cellular milieu regulates KCNQ1 distribution in cardiac myocytes and that stressful conditions can increase IKs by inducing KCNQ1 movement to the cell surface. This represents a hitherto unrecognized mechanism by which IKs fulfills its function as a repolarization reserve in ventricular myocytes. PMID:24142691

  13. Group delay variations of GPS transmitting and receiving antennas

    NASA Astrophysics Data System (ADS)

    Wanninger, Lambert; Sumaya, Hael; Beer, Susanne

    2017-09-01

    GPS code pseudorange measurements exhibit group delay variations at the transmitting and the receiving antenna. We calibrated C1 and P2 delay variations with respect to dual-frequency carrier phase observations and obtained nadir-dependent corrections for 32 satellites of the GPS constellation in early 2015 as well as elevation-dependent corrections for 13 receiving antenna models. The combined delay variations reach up to 1.0 m (3.3 ns) in the ionosphere-free linear combination for specific pairs of satellite and receiving antennas. Applying these corrections to the code measurements improves code/carrier single-frequency precise point positioning, ambiguity fixing based on the Melbourne-Wübbena linear combination, and determination of ionospheric total electron content. It also affects fractional cycle biases and differential code biases.

  14. Oncolytic potency and reduced virus tumor-specificity in oncolytic virotherapy. A mathematical modelling approach.

    PubMed

    Mahasa, Khaphetsi Joseph; Eladdadi, Amina; de Pillis, Lisette; Ouifki, Rachid

    2017-01-01

    In the present paper, we address by means of mathematical modeling the following main question: How can oncolytic virus infection of some normal cells in the vicinity of tumor cells enhance oncolytic virotherapy? We formulate a mathematical model describing the interactions between the oncolytic virus, the tumor cells, the normal cells, and the antitumoral and antiviral immune responses. The model consists of a system of delay differential equations with one (discrete) delay. We derive the model's basic reproductive number within tumor and normal cell populations and use their ratio as a metric for virus tumor-specificity. Numerical simulations are performed for different values of the basic reproduction numbers and their ratios to investigate potential trade-offs between tumor reduction and normal cells losses. A fundamental feature unravelled by the model simulations is its great sensitivity to parameters that account for most variation in the early or late stages of oncolytic virotherapy. From a clinical point of view, our findings indicate that designing an oncolytic virus that is not 100% tumor-specific can increase virus particles, which in turn, can further infect tumor cells. Moreover, our findings indicate that when infected tissues can be regenerated, oncolytic viral infection of normal cells could improve cancer treatment.

  15. A Demonstration of Precise Calibration of Tropospheric Delay Fluctuations with Water Vapor Radiometers

    NASA Technical Reports Server (NTRS)

    Teitelbaum, L. P.; Keihm, S. J.; Linfield, R. P.; Mahoney, M. J.; Resch, G. M.

    1996-01-01

    The ability of water vapor radiometers (WVRs) to calibrate changes in tropospheric delay was demonstrated during very long baseline radio interferometer (VLBI) observations at Goldstone, California. WVR measurements reduced the observed VLBI delay variations over a 13 hr period by a factor of approx. = 2.5. When applied to shorter time scales, a approx. = 50% reduction in 100-700 s delay variations was achieved during conditions of high tropospheric activity. Thermal WVR noise precluded calibration of short time scale delay fluctuations during quiet tropospheric conditions.

  16. X-ray micro-computed tomography in willow reveals tissue patterning of reaction wood and delay in programmed cell death.

    PubMed

    Brereton, Nicholas James Beresford; Ahmed, Farah; Sykes, Daniel; Ray, Michael Jason; Shield, Ian; Karp, Angela; Murphy, Richard James

    2015-03-11

    Variation in the reaction wood (RW) response has been shown to be a principle component driving differences in lignocellulosic sugar yield from the bioenergy crop willow. The phenotypic cause(s) behind these differences in sugar yield, beyond their common elicitor, however, remain unclear. Here we use X-ray micro-computed tomography (μCT) to investigate RW-associated alterations in secondary xylem tissue patterning in three dimensions (3D). Major architectural alterations were successfully quantified in 3D and attributed to RW induction. Whilst the frequency of vessels was reduced in tension wood tissue (TW), the total vessel volume was significantly increased. Interestingly, a delay in programmed-cell-death (PCD) associated with TW was also clearly observed and readily quantified by μCT. The surprising degree to which the volume of vessels was increased illustrates the substantial xylem tissue remodelling involved in reaction wood formation. The remodelling suggests an important physiological compromise between structural and hydraulic architecture necessary for extensive alteration of biomass and helps to demonstrate the power of improving our perspective of cell and tissue architecture. The precise observation of xylem tissue development and quantification of the extent of delay in PCD provides a valuable and exciting insight into this bioenergy crop trait.

  17. Seasonal variations in water relations in current-year leaves of evergreen trees with delayed greening.

    PubMed

    Harayama, Hisanori; Ikeda, Takefumi; Ishida, Atsushi; Yamamoto, Shin-Ichi

    2006-08-01

    We investigated seasonal patterns of water relations in current-year leaves of three evergreen broad-leaved trees (Ilex pedunculosa Miq., Ligustrum japonicum Thunb., and Eurya japonica Thunb.) with delayed greening in a warm-temperate forest in Japan. We used the pressure-volume method to: (1) assess the extent to which seasonal variation in leaf water relations is attributable to leaf development processes in delayed greening leaves versus seasonal variation in environmental variables; and (2) investigate variation in leaf water relations during the transition from the sapling to the adult tree stage. Leaf mass per unit leaf area was generally lowest just after completion of leaf expansion in May (late spring), and increased gradually throughout the year. Osmotic potential at full turgor (Psi(o) (ft)) and leaf water potential at the turgor loss point (Psi(w) (tlp)) were highest in May, and lowest in midwinter in all species. In response to decreasing air temperature, Psi(o) (ft) dropped at the rate of 0.037 MPa degrees C(-1). Dry-mass-based water content of leaves and the symplastic water fraction of total leaf water content gradually decreased throughout the year in all species. These results indicate that reductions in the symplastic water fraction during leaf development contributed to the passive concentration of solutes in cells and the resulting drop in winter Psi(o) (ft). The ratio of solutes to water volume increased in winter in current-year leaves of L. japonicum and E. japonica, indicating that osmotic adjustment (active accumulation of solutes) also contributed to the drop in winter in Psi(o) (ft). Bulk modulus of elasticity in cell walls fluctuated seasonally, but no general trend was found across species. Over the growing season, Psi(o) (ft) and Psi(w) (tlp) were lower in adult trees than in saplings especially in the case of I. pedunculosa, suggesting that adult-tree leaves are more drought and cold tolerant than sapling leaves. The ontogenetic increase in the stress resistance of I. pedunculosa may be related to its characteristic life form because I. pedunculosa grows taller than the other species studied.

  18. An age-structured model of hiv infection that allows for variations in the production rate of viral particles and the death rate of productively infected cells.

    PubMed

    Nelson, Patrick W; Gilchrist, Michael A; Coombs, Daniel; Hyman, James M; Perelson, Alan S

    2004-09-01

    Mathematical models of HIV-1 infection can help interpret drug treatment experiments and improve our understanding of the interplay between HIV-1 and the immune system. We develop and analyze an age- structured model of HIV-1 infection that allows for variations in the death rate of productively infected T cells and the production rate of viral particles as a function of the length of time a T cell has been infected. We show that this model is a generalization of the standard differential equation and of delay models previously used to describe HIV-1 infection, and provides a means for exploring fundamental issues of viral production and death. We show that the model has uninfected and infected steady states, linked by a transcritical bifurcation. We perform a local stability analysis of the nontrivial equilibrium solution and provide a general stability condition for models with age structure. We then use numerical methods to study solutions of our model focusing on the analysis of primary HIV infection. We show that the time to reach peak viral levels in the blood depends not only on initial conditions but also on the way in which viral production ramps up. If viral production ramps up slowly, we find that the time to peak viral load is delayed compared to results obtained using the standard (constant viral production) model of HIV infection. We find that data on viral load changing over time is insufficient to identify the functions specifying the dependence of the viral production rate or infected cell death rate on infected cell age. These functions must be determined through new quantitative experiments.

  19. Characterization of Postinfusion Phenotypic Differences in Fresh Versus Cryopreserved TCR Engineered Adoptive Cell Therapy Products.

    PubMed

    Nowicki, Theodore S; Escuin-Ordinas, Helena; Avramis, Earl; Chmielowski, Bartosz; Chodon, Thinle; Berent-Maoz, Beata; Wang, Xiaoyan; Kaplan-Lefko, Paula; Yang, Lili; Baltimore, David; Economou, James S; Ribas, Antoni; Comin-Anduix, Begoña

    2018-06-01

    Adoptive cell therapy (ACT) consisting of genetically engineered T cells expressing tumor antigen-specific T-cell receptors displays robust initial antitumor activity, followed by loss of T-cell activity/persistence and frequent disease relapse. We characterized baseline and longitudinal T-cell phenotype variations resulting from different manufacturing and administration protocols in patients who received ACT. Patients with melanoma who enrolled in the F5-MART-1 clinical trial (NCT00910650) received infusions of MART-1 T-cell receptors transgenic T cells with MART-1 peptide-pulsed dendritic cell vaccination. Patients were divided into cohorts based on several manufacturing changes in the generation and administration of the transgenic T cells: decreasing ex vivo stimulation/expansion time, increased cell dose, and receiving fresh instead of cryopreserved cells. T-cell phenotypes were analyzed by flow cytometry at baseline and longitudinally in peripheral blood. Transgenic T cells with shorter ex vivo culture/expansion periods displayed significantly increased expression of markers associated with less differentiated naive/memory populations, as well as significantly decreased expression of the inhibitory receptor programmed death 1 (PD1). Patients receiving fresh infusions of transgenic cells demonstrated expansion of central memory T cells and delayed acquisition of PD1 expression compared with patients who received cryopreserved products. Freshly infused transgenic T cells showed persistence and expansion of naive and memory T-cell populations and delayed acquisition of PD1 expression, which correlated with this cohort's superior persistence of transgenic cells and response to dendritic cell vaccines. These results may be useful in designing future ACT protocols.

  20. Characterization of Postinfusion Phenotypic Differences in Fresh Versus Cryopreserved TCR Engineered Adoptive Cell Therapy Products

    PubMed Central

    Nowicki, Theodore S.; Escuin-Ordinas, Helena; Avramis, Earl; Chmielowski, Bartosz; Chodon, Thinle; Berent-Maoz, Beata; Wang, Xiaoyan; Kaplan-Lefko, Paula; Yang, Lili; Baltimore, David; Economou, James S.; Ribas, Antoni

    2018-01-01

    Adoptive cell therapy (ACT) consisting of genetically engineered T cells expressing tumor antigen-specific T-cell receptors displays robust initial antitumor activity, followed by loss of T-cell activity/persistence and frequent disease relapse. We characterized baseline and longitudinal T-cell phenotype variations resulting from different manufacturing and administration protocols in patients who received ACT. Patients with melanoma who enrolled in the F5-MART-1 clinical trial (NCT00910650) received infusions of MART-1 T-cell receptors transgenic T cells with MART-1 peptide-pulsed dendritic cell vaccination. Patients were divided into cohorts based on several manufacturing changes in the generation and administration of the transgenic T cells: decreasing ex vivo stimulation/expansion time, increased cell dose, and receiving fresh instead of cryopreserved cells. T-cell phenotypes were analyzed by flow cytometry at baseline and longitudinally in peripheral blood. Transgenic T cells with shorter ex vivo culture/expansion periods displayed significantly increased expression of markers associated with less differentiated naive/memory populations, as well as significantly decreased expression of the inhibitory receptor programmed death 1 (PD1). Patients receiving fresh infusions of transgenic cells demonstrated expansion of central memory T cells and delayed acquisition of PD1 expression compared with patients who received cryopreserved products. Freshly infused transgenic T cells showed persistence and expansion of naive and memory T-cell populations and delayed acquisition of PD1 expression, which correlated with this cohort’s superior persistence of transgenic cells and response to dendritic cell vaccines. These results may be useful in designing future ACT protocols. PMID:29470191

  1. Principles of cell-free genetic circuit assembly.

    PubMed

    Noireaux, Vincent; Bar-Ziv, Roy; Libchaber, Albert

    2003-10-28

    Cell-free genetic circuit elements were constructed in a transcription-translation extract. We engineered transcriptional activation and repression cascades, in which the protein product of each stage is the input required to drive or block the following stage. Although we can find regions of linear response for single stages, cascading to subsequent stages requires working in nonlinear regimes. Substantial time delays and dramatic decreases in output production are incurred with each additional stage because of a bottleneck at the translation machinery. Faster turnover of RNA message can relieve competition between genes and stabilize output against variations in input and parameters.

  2. Global model of zenith tropospheric delay proposed based on EOF analysis

    NASA Astrophysics Data System (ADS)

    Sun, Langlang; Chen, Peng; Wei, Erhu; Li, Qinzheng

    2017-07-01

    Tropospheric delay is one of the main error budgets in Global Navigation Satellite System (GNSS) measurements. Many empirical correction models have been developed to compensate this delay, and models which do not require meteorological parameters have received the most attention. This study established a global troposphere zenith total delay (ZTD) model, called Global Empirical Orthogonal Function Troposphere (GEOFT), based on the empirical orthogonal function (EOF, also known as geographically weighted PCAs) analysis method and the Global Geodetic Observing System (GGOS) Atmosphere data from 2012 to 2015. The results showed that ZTD variation could be well represented by the characteristics of the EOF base function Ek and associated coefficients Pk. Here, E1 mainly signifies the equatorial anomaly; E2 represents north-south asymmetry, and E3 and E4 reflects regional variation. Moreover, P1 mainly reflects annual and semiannual variation components; P2 and P3 mainly contains annual variation components, and P4 displays semiannual variation components. We validated the proposed GEOFT model using tropospheric delay data of GGOS ZTD grid data and the tropospheric product of the International GNSS Service (IGS) over the year 2016. The results showed that GEOFT model has high accuracy with bias and RMS of -0.3 and 3.9 cm, respectively, with respect to the GGOS ZTD data, and of -0.8 and 4.1 cm, respectively, with respect to the global IGS tropospheric product. The accuracy of GEOFT demonstrating that the use of the EOF analysis method to characterize ZTD variation is reasonable.

  3. Latitudinal dependence of diurnal and seasonal variations in the tropospheric zenith delay observed from GPS measurements within the longitudinal sector of 50oE to 130oE.

    NASA Astrophysics Data System (ADS)

    Raju, Suresh; Saha, Korak; Anupama, K.; Parameswaran, Krishnaswamy

    Ground based GPS finds potential applications in many atmospheric studies such as the spatial distribution of columnar water vapor as well as tidal oscillations in the atmosphere. As the zenith tropospheric delay (ZTD) derived from GPS data is a function of atmospheric pressure, temperature and watervapor, the effect of atmospheric oscillations could reflect more promi-nently in its temporal variations. The GPS data with very high temporal resolution (5 min.) from thirteen IGS stations in the longitudinal sector of 50o-130oE are used to establish its potential for studying the atmospheric tidal, intra-seasonal and planetary oscillations. Very prominent tidal (diurnal and semi-diurnal) oscillations observed at all these stations, with am-plitude of the diurnal variation as ˜0.5-12+0.5 mm and that of the semi-diurnal variation in the range ˜0.1-5+0.2 mm. Although 90% of the delay is contributed by the dry atmospheric pressure (which shows prominent semi-diurnal oscillations) the tidal oscillations in the ZTD is dominated by the diurnal component. This effect could be attributed to the temporal variations of atmospheric water vapor in a diurnal scale. The amplitude of these variations in general is largest near the equator and decreases with increase in latitude. Interestingly, this latitudinal trend matches very well with the latitude variation of the precipitable water vapor (as well as the actual precipitation) in this longitudinal region. Though the values of ZTD at stations very close to equator stations do not show any prominent seasonal variation, as the latitude increases the annual variation in ZTD becomes more distinct. A prominent peak in ZTD is observed during the July-August period, which matches well with the annual variation of atmospheric water vapor. This shows that the diurnal and seasonal variation of ZTD is mainly governed by the corresponding variations in atmospheric water vapor, even though its contribution to the total delay is around 10%. Keywords: GPS, Tropospheric delay, Atmospheric oscillations # Dr. K. Parameswaran is supported by CSIR through Emeritus Scientist Scheme. * corresponding author: koraksaha@gmail.com

  4. Multipath noise reduction spread spectrum signals

    NASA Technical Reports Server (NTRS)

    Meehan, Thomas K. (Inventor)

    1994-01-01

    The concepts of early-prompt delay tracking, multipath correction of early-prompt delay tracking from correlation shape, and carrier phase multipath correction are addressed. In early-prompt delay tracking, since multipath is always delayed with respect to the direct signals, the system derives phase and pseudorange observables from earlier correlation lags. In multipath correction of early-prompt delay tracking from correlation shape, the system looks for relative variations of amplitude across the code correlation function that do not match the predicted multipath-free code cross-correlation shape. The system then uses deviations from the multipath-free shape to infer the magnitude of multipath, and to generate corrections pseudorange observables. In carrier phase multipath correction, the system looks for variations of phase among plural early and prompt lags. The system uses the measured phase variations, along with the general principle that the multipath errors are larger for later lags, to infer the presence of multipath, and to generate corrections for carrier-phase observables.

  5. Cable delay compensator for microwave signal distribution over optical fibers

    NASA Astrophysics Data System (ADS)

    Primas, Lori E.

    1990-12-01

    The basic principles of microwave fiber-optic systems are outlined with emphasis on fiber-optic cable delay compensators (CDC). Degradation of frequency and phase stability is considered, and it is pointed out that the long-term stability of a fiber-optic link is degraded by group delay variations due to temperature fluctuations in the optical fiber and low-frequency noise characteristics of the laser. A CDC employing a voltage-controlled oscillator to correct for phase variations in the optical fiber is presented, and the static as well as dynamic closed-loop analyses of the fiber-optic CDC are discussed. A constructed narrow-band fiber-optic CDC is shown to reduce phase variations caused by temperature fluctuations by a factor of 400. A wide-band CDC utilizing a temperature-controlled coil of fiber to compensate for phase delay is also proposed.

  6. Hospital variation in time to defibrillation after in-hospital cardiac arrest.

    PubMed

    Chan, Paul S; Nichol, Graham; Krumholz, Harlan M; Spertus, John A; Nallamothu, Brahmajee K

    2009-07-27

    Delays to defibrillation are associated with worse survival after in-hospital cardiac arrest, but the degree to which hospitals vary in defibrillation response times and hospital predictors of delays remain unknown. Using hierarchical models, we evaluated hospital variation in rates of delayed defibrillation (>2 minutes) and its impact on survival among 7479 adult inpatients with cardiac arrests at 200 hospitals within the National Registry of Cardiopulmonary Resuscitation. Adjusted rates of delayed defibrillation varied substantially among hospitals (range, 2.4%-50.9%), with hospital-level effects accounting for a significant amount of the total variation in defibrillation delays after adjusting for patient factors. We found a 46% greater odds of patients with identical covariates getting delayed defibrillation at one randomly selected hospital compared with another. Among traditional hospital factors evaluated, however, only bed volume (reference category: <200 beds; 200-499 beds: odds ratio [OR], 0.62 [95% confidence interval {CI}, 0.48-0.80]; >or=500 beds: OR, 0.74 [95% CI, 0.53-1.04]) and arrest location (reference category: intensive care unit; telemetry unit: OR, 1.92 [95% CI, 1.65-2.22]; nonmonitored unit: OR, 1.90 [95% CI, 1.61-2.24]) were associated with differences in rates of delayed defibrillation. Wide variation also existed in adjusted hospital rates of survival to discharge (range, 5.3%-49.6%), with higher survival among hospitals in the top-performing quartile for defibrillation time (compared with the bottom quartile: OR for top quartile, 1.41 [95% CI, 1.11-1.77]). Rates of delayed defibrillation vary widely among hospitals but are largely unexplained by traditional hospital factors. Given its association with improved survival, future research is needed to better understand best practices in the delivery of defibrillation at top-performing hospitals.

  7. The measurement of atmospheric water vapor - Radiometer comparison and spatial variations

    NASA Technical Reports Server (NTRS)

    Rocken, C.; Johnson, J. M.; Ware, R. H.; Neilan, R. E.; Cerezo, M.; Jordan, J. R.; Falls, M. J..; Nelson, L. D.; Hayes, M.

    1991-01-01

    Two water vapor radiometer (WVR) experiments were conducted to evaluate whether such instruments are both suitable and necessary to correct for propagation effects that are induced by precipitable water vapor (PWV) on signals from GPS and VLBI. WVRs are suitable for these corrections if they provide wet path delays to better than 0.5 cm. They are needed if spatial variations of PWV result in complicated, direction-dependent propagation effects that are too complex to be parametrized in the GPS or VLBI geodetic solution. The suitability of radiometers was first addressed by comparing six airport WVRs for two weeks. While two WVRs showed an average wet path delay bias of only 0.1 cm, others were biased by 1-3 cm relative to each other and relative to radiosondes. The second experiment addressed the question whether radiometers are needed for the detection of inhomogeneities in the wet delay. Three JPL D-series radiometers were operated at three sites 50 km apart. The WVRs simultaneously sampled PWV at different azimuths and elevations in search of spatial variations of PWV. On one day of this second experiment evidence was found for spatial variations of the wet path delay as high as 20 percent of the total wet path delay.

  8. Radiation Hardened Structured ASIC Platform with Compensation of Delay for Temperature and Voltage Variations for Multiple Redundant Temporal Voting Latch Technology

    NASA Technical Reports Server (NTRS)

    Ardalan, Sasan (Inventor)

    2018-01-01

    The invention relates to devices and methods of maintaining the current starved delay at a constant value across variations in voltage and temperature to increase the speed of operation of the sequential logic in the radiation hardened ASIC design.

  9. A Low Power Linear Phase Programmable Long Delay Circuit.

    PubMed

    Rodriguez-Villegas, Esther; Logesparan, Lojini; Casson, Alexander J

    2014-06-01

    A novel linear phase programmable delay is being proposed and implemented in a 0.35 μm CMOS process. The delay line consists of N cascaded cells, each of which delays the input signal by Td/N, where Td is the total line delay. The delay generated by each cell is programmable by changing a clock frequency and is also fully independent of the frequency of the input signal. The total delay hence depends only on the chosen clock frequency and the total number of cascaded cells. The minimum clock frequency is limited by the maximum time a voltage signal can effectively be held by an individual cell. The maximum number of cascaded cells will be limited by the effects of accumulated offset due to transistor mismatch, which eventually will affect the operating mode of the individual transistors in a cell. This latter limitation has however been dealt with in the topology by having an offset compensation mechanism that makes possible having a large number of cascaded cells and hence a long resulting delay. The delay line has been designed for scalp-based neural activity analysis that is predominantly in the sub-100 Hz frequency range. For these signals, the delay generated by a 31-cell cascade has been demonstrated to be programmable from 30 ms to 3 s. Measurement results demonstrate a 31 stage, 50 Hz bandwidth, 0.3 s delay that operates from a 1.1 V supply with power consumption of 270 nW.

  10. Proton acceleration by a pair of successive ultraintense femtosecond laser pulses

    NASA Astrophysics Data System (ADS)

    Ferri, J.; Senje, L.; Dalui, M.; Svensson, K.; Aurand, B.; Hansson, M.; Persson, A.; Lundh, O.; Wahlström, C.-G.; Gremillet, L.; Siminos, E.; DuBois, T. C.; Yi, L.; Martins, J. L.; Fülöp, T.

    2018-04-01

    We investigate the target normal sheath acceleration of protons in thin aluminum targets irradiated at a relativistic intensity by two time-separated ultrashort (35 fs) laser pulses. When the full-energy laser pulse is temporally split into two identical half-energy pulses, and using target thicknesses of 3 and 6 μm, we observe experimentally that the second half-pulse boosts the maximum energy and charge of the proton beam produced by the first half-pulse for time delays below ˜0.6-1 ps. Using two-dimensional particle-in-cell simulations, we examine the variation of the proton energy spectra with respect to the time-delay between the two pulses. We demonstrate that the expansion of the target front surface caused by the first pulse significantly enhances the hot-electron generation by the second pulse arriving after a few hundreds of fs time delay. This enhancement, however, does not suffice to further accelerate the fastest protons driven by the first pulse once three-dimensional quenching effects have set in. This implies a limit to the maximum time delay that leads to proton energy enhancement, which we theoretically determine.

  11. Characterization of Arginase Expression in Glioma-Associated Microglia and Macrophages

    PubMed Central

    Zhang, Leying; Gao, Hang; Song, Yanyan; Ren, Hui; Ouyang, Mao; Wu, Xiwei; D’Apuzzo, Massimo; Badie, Behnam

    2016-01-01

    Microglia (MG) and macrophages (MPs) represent a significant component of the inflammatory response to gliomas. When activated, MG/MP release a variety of pro-inflammatory cytokines, however, they also secrete anti-inflammatory factors that limit their cytotoxic function. The balance between pro and anti-inflammatory functions dictates their antitumor activity. To evaluate potential variations in MG and MP function in gliomas, we isolated these cells (and other Gr1+ cells) from intracranial GL261 murine gliomas by FACS and evaluated their gene expression profiles by microarray analysis. As expected, arginase 1 (Arg1, M2 marker) was highly expressed by tumor-associated Gr1+, MG and MP. However, in contrast to MP and Gr1+ cells that expressed Arg1 shortly after tumor trafficking, Arg1 expression in MG was delayed and occurred in larger tumors. Interestingly, depletion of MPs in tumors did not prevent MG polarization, suggesting direct influence of tumor-specific factors on MG Arg1 upregulation. Finally, Arg1 expression was confirmed in human GBM samples, but most Arg1+ cells were neutrophils and not MPs. These findings confirm variations in tumor MG and MP polarization states and its dependency on tumor microenvironmental factors. PMID:27936099

  12. Characterization of Arginase Expression in Glioma-Associated Microglia and Macrophages.

    PubMed

    Zhang, Ian; Alizadeh, Darya; Liang, Junling; Zhang, Leying; Gao, Hang; Song, Yanyan; Ren, Hui; Ouyang, Mao; Wu, Xiwei; D'Apuzzo, Massimo; Badie, Behnam

    2016-01-01

    Microglia (MG) and macrophages (MPs) represent a significant component of the inflammatory response to gliomas. When activated, MG/MP release a variety of pro-inflammatory cytokines, however, they also secrete anti-inflammatory factors that limit their cytotoxic function. The balance between pro and anti-inflammatory functions dictates their antitumor activity. To evaluate potential variations in MG and MP function in gliomas, we isolated these cells (and other Gr1+ cells) from intracranial GL261 murine gliomas by FACS and evaluated their gene expression profiles by microarray analysis. As expected, arginase 1 (Arg1, M2 marker) was highly expressed by tumor-associated Gr1+, MG and MP. However, in contrast to MP and Gr1+ cells that expressed Arg1 shortly after tumor trafficking, Arg1 expression in MG was delayed and occurred in larger tumors. Interestingly, depletion of MPs in tumors did not prevent MG polarization, suggesting direct influence of tumor-specific factors on MG Arg1 upregulation. Finally, Arg1 expression was confirmed in human GBM samples, but most Arg1+ cells were neutrophils and not MPs. These findings confirm variations in tumor MG and MP polarization states and its dependency on tumor microenvironmental factors.

  13. Individual Variability in Delayed Auditory Feedback Effects on Speech Fluency and Rate in Normally Fluent Adults

    ERIC Educational Resources Information Center

    Chon, HeeCheong; Kraft, Shelly Jo; Zhang, Jingfei; Loucks, Torrey; Ambrose, Nicoline G.

    2013-01-01

    Purpose: Delayed auditory feedback (DAF) is known to induce stuttering-like disfluencies (SLDs) and cause speech rate reductions in normally fluent adults, but the reason for speech disruptions is not fully known, and individual variation has not been well characterized. Studying individual variation in susceptibility to DAF may identify factors…

  14. Ionizing radiation and cell cycle progression in ataxia telangiectasia

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

    Beamish, H.; Khanna, K.K.; Lavin, M.F.

    1994-04-01

    Exposure of mammalian cells to ionizing radiation causes delay in normal progress through the cell cycle at a number of different checkpoints. Abnormalities in these checkpoints have been described for ataxia telangiectasia cells after irradiation. In this report we show that these abnormalities occur at different phases in the cell cycle in several ataxia telangiectasia lymphoblastoid cells. Ataxia telangiectasia cells, synchronized in late G{sub 1} phase with either mimosine or aphidicolin and exposed to radiation, showed a reduced delay in entering S phase compared to irradiated control cells. Failure to exhibit G{sub 1}-phase delay in ataxia telangiectasia cells is accompaniedmore » by a reduced ability of radiation to activate the product of the tumor suppressor gene p53, a protein involved in G{sub 1}/S-phase delay. When the progress of irradiated G{sub 1}-phase cells was followed into the subsequent G{sub 2} and G{sub 1} phases ataxia telangiectasia cells showed a more pronounced accumulation in G{sub 2} phase than control cells. When cells were irradiated in S phase and extent of delay was more evident in G{sub 2} phase and ataxia telangiectasia cells were delayed to a greater extent. These results suggest that the lack of initial delay in both G{sub 1} and S phases to the radiosensitivity observed in this syndrome. 26 refs., 3 figs., 2 tabs.« less

  15. Image analysis supported moss cell disruption in photo-bioreactors.

    PubMed

    Lucumi, A; Posten, C; Pons, M-N

    2005-05-01

    Diverse methods for the disruption of cell entanglements and pellets of the moss Physcomitrella patens were tested in order to improve the homogeneity of suspension cultures. The morphological characterization of the moss was carried out by means of image analysis. Selected morphological parameters were defined and compared to the reduction of the carbon dioxide fixation, and the released pigments after cell disruption. The size control of the moss entanglements based on the rotor stator principle allowed a focused shear stress, avoiding a severe reduction in the photosynthesis. Batch cultures of P. patens in a 30.0-l pilot tubular photo-bioreactor with cell disruption showed no significant variation in growth rate and a delayed cell differentiation, when compared to undisrupted cultures. A highly controlled photoautotrophic culture of P. patens in a scalable photo-bioreactor was established, contributing to the development required for the future use of mosses as producers of relevant heterologous proteins.

  16. FLASH X-RAY (FXR) LINEAR INDUCTION ACCELERATOR (LIA) OPTIMIZATION Sensor Delay Correction

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

    Ong, M M; Houck, T L; Kreitzer, B R

    2006-05-01

    The radiographic goal of the FXR Optimization Project is to generate an x-ray pulse with peak energy of 19 MeV, spot-size of 1.5 mm, a dose of 500 rad, and duration of 60 ns. The electrical objectives are to generate a 3 kA electron-beam and refine our 16 MV accelerator so that the voltage does not vary more than 1%-rms. In a multi-cell linear induction accelerator, like FXR, the timing of the acceleration pulses relative to the beam is critical. The pulses must be timed optimally so that a cell is at full voltage before the beam arrives and doesmore » not drop until the beam passes. In order to stay within the energy-variation budget, the synchronization between the cells and beam arrival must be controlled to a couple of nanoseconds. Therefore, temporal measurements must be accurate to a fraction of a nanosecond. FXR Optimization Project developed a one-giga-sample per second (gs/s) data acquisition system to record beam sensor data. Signal processing algorithms were written to determine cell timing with an uncertainty of a fraction of a nanosecond. However, the uncertainty in the sensor delay was still a few nanoseconds. This error had to be reduced if we are to improve the quality of the electron beam. Two types of sensors are used to align the cell voltage pulse against the beam current. The beam current is measured with resistive-wall sensors. The cell voltages are read with capacitive voltage monitors. Sensor delays can be traced to two mechanisms: (1) the sensors are not co-located at the beam and cell interaction points, and (2) the sensors have different length jumper cables and other components that connect them to the standard-length coaxial cables of the data acquisition system. Using the physical locations and dimensions of the sensor components, and the dielectric constant of the materials, delay times were computed. Relative to the cell voltage, the beam current was theoretically reporting late by 7.7 ns. Two experiments were performed to verify and refine the sensor delay correction. In the first experiment, the beam was allowed to drift through a cell that was not pulsed. The beam induces a potential into the cell that is read by the voltage monitor. Analysis of the data indicated that the beam sensor signal was likely 7.1 ns late. In the second experiment, the beam current is calculated from the injector diode voltage that is the sum of the cell voltages. A 7 ns correction produced a very good match between the signals from the two types of sensors. For simplicity, we selected a correction factor that advanced the current signals by 7 ns. This should reduce the uncertainty in the temporal measurements to less than 1 ns.« less

  17. Importance of cell damage causing growth delay for high pressure inactivation of Saccharomyces cerevisiae

    NASA Astrophysics Data System (ADS)

    Nanba, Masaru; Nomura, Kazuki; Nasuhara, Yusuke; Hayashi, Manabu; Kido, Miyuki; Hayashi, Mayumi; Iguchi, Akinori; Shigematsu, Toru; Hirayama, Masao; Ueno, Shigeaki; Fujii, Tomoyuki

    2013-06-01

    A high pressure (HP) tolerant (barotolerant) mutant a2568D8 and a variably barotolerant mutant a1210H12 were generated from Saccharomyces cerevisiae using ultra-violet mutagenesis. The two mutants, a barosensitive mutant a924E1 and the wild-type strain, were pressurized (225 MPa), and pressure inactivation behavior was analyzed. In the wild-type strain, a proportion of the growth-delayed cells were detected after exposure to HP. In a924E1, the proportion of growth-delayed cells significantly decreased compared with the wild-type. In a2568D8, the proportion of growth-delayed cells increased and the proportion of inactivated cells decreased compared with the wild-type. In a1210H12, the growth-delayed cells could not be detected within 120 s of exposure to HP. The proportion of growth-delayed cells, which incurred the damage, would affect the survival ratio by HP. These results suggested that cellular changes in barotolerance caused by mutations are remarkably affected by the ability to recover from cellular damage, which results in a growth delay.

  18. Network models of frequency modulated sweep detection.

    PubMed

    Skorheim, Steven; Razak, Khaleel; Bazhenov, Maxim

    2014-01-01

    Frequency modulated (FM) sweeps are common in species-specific vocalizations, including human speech. Auditory neurons selective for the direction and rate of frequency change in FM sweeps are present across species, but the synaptic mechanisms underlying such selectivity are only beginning to be understood. Even less is known about mechanisms of experience-dependent changes in FM sweep selectivity. We present three network models of synaptic mechanisms of FM sweep direction and rate selectivity that explains experimental data: (1) The 'facilitation' model contains frequency selective cells operating as coincidence detectors, summing up multiple excitatory inputs with different time delays. (2) The 'duration tuned' model depends on interactions between delayed excitation and early inhibition. The strength of delayed excitation determines the preferred duration. Inhibitory rebound can reinforce the delayed excitation. (3) The 'inhibitory sideband' model uses frequency selective inputs to a network of excitatory and inhibitory cells. The strength and asymmetry of these connections results in neurons responsive to sweeps in a single direction of sufficient sweep rate. Variations of these properties, can explain the diversity of rate-dependent direction selectivity seen across species. We show that the inhibitory sideband model can be trained using spike timing dependent plasticity (STDP) to develop direction selectivity from a non-selective network. These models provide a means to compare the proposed synaptic and spectrotemporal mechanisms of FM sweep processing and can be utilized to explore cellular mechanisms underlying experience- or training-dependent changes in spectrotemporal processing across animal models. Given the analogy between FM sweeps and visual motion, these models can serve a broader function in studying stimulus movement across sensory epithelia.

  19. Stress-Induced Mutagenesis: Implications in Cancer and Drug Resistance.

    PubMed

    Fitzgerald, Devon M; Hastings, P J; Rosenberg, Susan M

    2017-03-01

    Genomic instability underlies many cancers and generates genetic variation that drives cancer initiation, progression, and therapy resistance. In contrast with classical assumptions that mutations occur purely stochastically at constant, gradual rates, microbes, plants, flies, and human cancer cells possess mechanisms of mutagenesis that are upregulated by stress responses. These generate transient, genetic-diversity bursts that can propel evolution, specifically when cells are poorly adapted to their environments-that is, when stressed. We review molecular mechanisms of stress-response-dependent (stress-induced) mutagenesis that occur from bacteria to cancer, and are activated by starvation, drugs, hypoxia, and other stressors. We discuss mutagenic DNA break repair in Escherichia coli as a model for mechanisms in cancers. The temporal regulation of mutagenesis by stress responses and spatial restriction in genomes are common themes across the tree of life. Both can accelerate evolution, including the evolution of cancers. We discuss possible anti-evolvability drugs, aimed at targeting mutagenesis and other variation generators, that could be used to delay the evolution of cancer progression and therapy resistance.

  20. Stress-Induced Mutagenesis: Implications in Cancer and Drug Resistance

    PubMed Central

    Fitzgerald, Devon M.; Hastings, P.J.; Rosenberg, Susan M.

    2017-01-01

    Genomic instability underlies many cancers and generates genetic variation that drives cancer initiation, progression, and therapy resistance. In contrast with classical assumptions that mutations occur purely stochastically at constant, gradual rates, microbes, plants, flies, and human cancer cells possess mechanisms of mutagenesis that are upregulated by stress responses. These generate transient, genetic-diversity bursts that can propel evolution, specifically when cells are poorly adapted to their environments—that is, when stressed. We review molecular mechanisms of stress-response-dependent (stress-induced) mutagenesis that occur from bacteria to cancer, and are activated by starvation, drugs, hypoxia, and other stressors. We discuss mutagenic DNA break repair in Escherichia coli as a model for mechanisms in cancers. The temporal regulation of mutagenesis by stress responses and spatial restriction in genomes are common themes across the tree of life. Both can accelerate evolution, including the evolution of cancers. We discuss possible anti-evolvability drugs, aimed at targeting mutagenesis and other variation generators, that could be used to delay the evolution of cancer progression and therapy resistance. PMID:29399660

  1. A 3.9 ps Time-Interval RMS Precision Time-to-Digital Converter Using a Dual-Sampling Method in an UltraScale FPGA

    NASA Astrophysics Data System (ADS)

    Wang, Yonggang; Liu, Chong

    2016-10-01

    Field programmable gate arrays (FPGAs) manufactured with more advanced processing technology have faster carry chains and smaller delay elements, which are favorable for the design of tapped delay line (TDL)-style time-to-digital converters (TDCs) in FPGA. However, new challenges are posed in using them to implement TDCs with a high time precision. In this paper, we propose a bin realignment method and a dual-sampling method for TDC implementation in a Xilinx UltraScale FPGA. The former realigns the disordered time delay taps so that the TDC precision can approach the limit of its delay granularity, while the latter doubles the number of taps in the delay line so that the TDC precision beyond the cell delay limitation can be expected. Two TDC channels were implemented in a Kintex UltraScale FPGA, and the effectiveness of the new methods was evaluated. For fixed time intervals in the range from 0 to 440 ns, the average RMS precision measured by the two TDC channels reaches 5.8 ps using the bin realignment, and it further improves to 3.9 ps by using the dual-sampling method. The time precision has a 5.6% variation in the measured temperature range. Every part of the TDC, including dual-sampling, encoding, and on-line calibration, could run at a 500 MHz clock frequency. The system measurement dead time is only 4 ns.

  2. Internet stream synchronization using Concord

    NASA Astrophysics Data System (ADS)

    Sreenan, Cormac J.; Narendran, B.; Agrawal, Prathima; Shivakumar, Narayanan

    1996-03-01

    Using packet networks to transport multimedia introduces delay variations within and across streams, necessitating synchronization at the receiver. This requires stream data to be buffered prior to presentation, which also increases its total end to end delay. Concord recognizes that applications may wish to influence the underlying synchronization policy in terms of its effect on quality of service. It provides a single framework for synchronization within and across streams and employs an application specific tradeoff between packet losses, delay and inter- stream skew. We present a new predictive approach for synchronization and a selection of results from an extensive evaluation of Concord for use in the Internet. A trace driven simulator is used, allowing a direct comparison with alternative approaches. We demonstrate that Concord can operate with lower maximum delay and less variation in total end to end delay, which in turn can allow receiver buffer requirements to be reduced.

  3. Modeling heterogeneous responsiveness of intrinsic apoptosis pathway

    PubMed Central

    2013-01-01

    Background Apoptosis is a cell suicide mechanism that enables multicellular organisms to maintain homeostasis and to eliminate individual cells that threaten the organism’s survival. Dependent on the type of stimulus, apoptosis can be propagated by extrinsic pathway or intrinsic pathway. The comprehensive understanding of the molecular mechanism of apoptotic signaling allows for development of mathematical models, aiming to elucidate dynamical and systems properties of apoptotic signaling networks. There have been extensive efforts in modeling deterministic apoptosis network accounting for average behavior of a population of cells. Cellular networks, however, are inherently stochastic and significant cell-to-cell variability in apoptosis response has been observed at single cell level. Results To address the inevitable randomness in the intrinsic apoptosis mechanism, we develop a theoretical and computational modeling framework of intrinsic apoptosis pathway at single-cell level, accounting for both deterministic and stochastic behavior. Our deterministic model, adapted from the well-accepted Fussenegger model, shows that an additional positive feedback between the executioner caspase and the initiator caspase plays a fundamental role in yielding the desired property of bistability. We then examine the impact of intrinsic fluctuations of biochemical reactions, viewed as intrinsic noise, and natural variation of protein concentrations, viewed as extrinsic noise, on behavior of the intrinsic apoptosis network. Histograms of the steady-state output at varying input levels show that the intrinsic noise could elicit a wider region of bistability over that of the deterministic model. However, the system stochasticity due to intrinsic fluctuations, such as the noise of steady-state response and the randomness of response delay, shows that the intrinsic noise in general is insufficient to produce significant cell-to-cell variations at physiologically relevant level of molecular numbers. Furthermore, the extrinsic noise represented by random variations of two key apoptotic proteins, namely Cytochrome C and inhibitor of apoptosis proteins (IAP), is modeled separately or in combination with intrinsic noise. The resultant stochasticity in the timing of intrinsic apoptosis response shows that the fluctuating protein variations can induce cell-to-cell stochastic variability at a quantitative level agreeing with experiments. Finally, simulations illustrate that the mean abundance of fluctuating IAP protein is positively correlated with the degree of cellular stochasticity of the intrinsic apoptosis pathway. Conclusions Our theoretical and computational study shows that the pronounced non-genetic heterogeneity in intrinsic apoptosis responses among individual cells plausibly arises from extrinsic rather than intrinsic origin of fluctuations. In addition, it predicts that the IAP protein could serve as a potential therapeutic target for suppression of the cell-to-cell variation in the intrinsic apoptosis responsiveness. PMID:23875784

  4. A variation of noncontingent reinforcement in the treatment of aberrant behavior.

    PubMed

    Britton, L N; Carr, J E; Kellum, K K; Dozier, C L; Weil, T M

    2000-01-01

    We examined the effectiveness of a variation of noncontingent reinforcement (NCR) that incorporated a stimulus-delay procedure in the reduction of aberrant behavior maintained by positive reinforcement. Functional analyses for three individuals diagnosed with developmental disabilities indicated that their behaviors were maintained by positive reinforcement: one in the form of access to a tangible item, another by attention, and the third by physical contact. We implemented NCR with the delay procedure with two participants using reversal designs to evaluate effects. We also compared this NCR variation and DRO with the third participant to evaluate reinforcer-delivery rates. The variation of NCR was successful in reducing all aberrant behavior to near-zero levels. A comparison of reinforcer delivery between NCR with the stimulus-delay procedure and DRO demonstrated that the participant accessed more reinforcement with NCR. Results are discussed in the context of enhancing decelerative interventions with emphases on minimizing response effort for caregivers and maximizing access to reinforcement for the individuals.

  5. Proteomic features of delayed ocular symptoms caused by exposure to sulfur mustard: As studied by protein profiling of corneal epithelium.

    PubMed

    Pajoohesh, Maryam; Naderi, Mostafa; Naderi-Manesh, Hossein

    2017-11-01

    Exposure to mustard gas can lead to variations in the proteome of corneal epithelium cells and after a latency period produces delayed symptoms in the eyes of chemical victims. Hence, a comparative proteome analysis was conducted between the corneal epithelial cells of chemical victims from Iran-Iraq war (1980-1988) and healthy donors. To this end, corneal epithelium samples from victims and healthy individuals were collected, and the proteome of these samples were prepared for two-dimensional electrophoresis and the analysis of spots by statistical software. Selected spots were further analyzed by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry. Twenty four proteins were identified of which eighteen proteins showed downregulation while six proteins were upregulated in the victims in comparison to the normal individuals. Also, six protein spots were confirmed by western-blot analysis. In conclusion, all the twenty-four identified proteins are involved in pathways which their up- or down-regulation leads to the accumulation of undesired substrates, cell death and apoptosis. Bioinformatics' tools indicated that these identified proteins were involved in various metabolic processes, DNA damage response, immune response and etc. The present study provides a suitable platform for further clinical studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Correlations between radiation-induced double strand breaks, cell division delay, and cyclin-dependent signaling in x-irradiated NIH3T3 fibroblasts

    NASA Astrophysics Data System (ADS)

    Cariveau, Mickael J.

    2005-07-01

    Molecular responses to radiation-induced DNA double strand breaks (DSB) are mediated by the phosphorylation of the histone variant H2AX which forms identifiable gamma-H2AX foci at the site of the DSB. This event is thought to be linked with the down-regulation of signaling proteins contributing to the checkpoints regulating cell cycle progression and, vis-a-vis , the induction of cell division delay. However, it is unclear whether this division delay is directly related to the number of DSB (gamma-H2AX foci) sustained by an irradiated cell and, if so, whether this number drives cells into cell cycle delay or apoptosis. For this reason, studies were conducted in the immortalized NIH/3T3 fibroblast cell in order to establish correlations between the temporal appearance of the gamma-H2AX foci (a DSB) and the expression of the cell cycle regulatory proteins, cyclin E, A, B1, and their cyclin kinase inhibitor, p21. Cell cycle kinetics and flow cytometry were used to establish radiation-induced division delay over a dose range of 1--6 Gy where a mitotic delay of 2.65 min/cGy was established. Correlations between the expression of cyclin E, A, B1, p21, and the generation of DSB were established in NIH/3T3 cells exposed to 2 or 4 Gy x-irradiation. The data suggest that the G1/S and S phase delay (cyclin E and cyclin A protein levels) are dependent on the dose of radiation while the G2/M (cyclin B1 protein levels) delay is dependent on the quantity of DSB sustained by the irradiated cell.

  7. 14 CFR 417.221 - Time delay analysis.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... occurs; (2) A flight safety official's decision and reaction time, including variation in human response... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Time delay analysis. 417.221 Section 417... OF TRANSPORTATION LICENSING LAUNCH SAFETY Flight Safety Analysis § 417.221 Time delay analysis. (a...

  8. 14 CFR 417.221 - Time delay analysis.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... occurs; (2) A flight safety official's decision and reaction time, including variation in human response... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 false Time delay analysis. 417.221 Section 417... OF TRANSPORTATION LICENSING LAUNCH SAFETY Flight Safety Analysis § 417.221 Time delay analysis. (a...

  9. 14 CFR 417.221 - Time delay analysis.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... occurs; (2) A flight safety official's decision and reaction time, including variation in human response... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Time delay analysis. 417.221 Section 417... OF TRANSPORTATION LICENSING LAUNCH SAFETY Flight Safety Analysis § 417.221 Time delay analysis. (a...

  10. Periodic and chaotic oscillations in a tumor and immune system interaction model with three delays

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

    Bi, Ping; Center for Partial Differential Equations, East China Normal University, 500 Dongchuan Rd., Shanghai 200241; Ruan, Shigui, E-mail: ruan@math.miami.edu

    2014-06-15

    In this paper, a tumor and immune system interaction model consisted of two differential equations with three time delays is considered in which the delays describe the proliferation of tumor cells, the process of effector cells growth stimulated by tumor cells, and the differentiation of immune effector cells, respectively. Conditions for the asymptotic stability of equilibria and existence of Hopf bifurcations are obtained by analyzing the roots of a second degree exponential polynomial characteristic equation with delay dependent coefficients. It is shown that the positive equilibrium is asymptotically stable if all three delays are less than their corresponding critical valuesmore » and Hopf bifurcations occur if any one of these delays passes through its critical value. Numerical simulations are carried out to illustrate the rich dynamical behavior of the model with different delay values including the existence of regular and irregular long periodic oscillations.« less

  11. Time delay and noise explaining the behaviour of the cell growth in fermentation process

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

    Ayuobi, Tawfiqullah; Rosli, Norhayati; Bahar, Arifah

    2015-02-03

    This paper proposes to investigate the interplay between time delay and external noise in explaining the behaviour of the microbial growth in batch fermentation process. Time delay and noise are modelled jointly via stochastic delay differential equations (SDDEs). The typical behaviour of cell concentration in batch fermentation process under this model is investigated. Milstein scheme is applied for solving this model numerically. Simulation results illustrate the effects of time delay and external noise in explaining the lag and stationary phases, respectively for the cell growth of fermentation process.

  12. Time delay and noise explaining the behaviour of the cell growth in fermentation process

    NASA Astrophysics Data System (ADS)

    Ayuobi, Tawfiqullah; Rosli, Norhayati; Bahar, Arifah; Salleh, Madihah Md

    2015-02-01

    This paper proposes to investigate the interplay between time delay and external noise in explaining the behaviour of the microbial growth in batch fermentation process. Time delay and noise are modelled jointly via stochastic delay differential equations (SDDEs). The typical behaviour of cell concentration in batch fermentation process under this model is investigated. Milstein scheme is applied for solving this model numerically. Simulation results illustrate the effects of time delay and external noise in explaining the lag and stationary phases, respectively for the cell growth of fermentation process.

  13. Lightning propagation and flash density in squall lines as determined with radar

    NASA Technical Reports Server (NTRS)

    Mazur, V.; Rust, W. D.

    1983-01-01

    Lightning echo rise times and range-time variations due to discharge propagation are determined using S and L band radars, and the evolution of precipitation reflectivity and the associated lightning activity in squall lines is investigated using VHF and L band radars. The rise time of radar echoes can be explained by ionized channel propagation through the radar beams. Speeds of at least 250,000 m/s are found from measurements of the radial velocity of streamer propagation along the antenna beam. The range-time variations in lightning echoes indicate that either new ionization occurs as streamers develop into different parts of the cloud, channel delay occurs during which adequate ionization exists for radar detection, or continuing current occurs. Determinations of the lightning flash density for a squall line in the U.S. show that the maximum lightning density tends to be near the leading edge of the precipitation cores in developing cells. Long discharges are produced as a cell in the squall line develops and the total lightning density increases, although short discharges predominate. As the cell dissipates, short flashes diminish or cease and the long flashes dominate the lightning activity.

  14. Time signal distribution in communication networks based on synchronous digital hierarchy

    NASA Technical Reports Server (NTRS)

    Imaoka, Atsushi; Kihara, Masami

    1993-01-01

    A new method that uses round-trip paths to accurately measure transmission delay for time synchronization is proposed. The performance of the method in Synchronous Digital Hierarchy networks is discussed. The feature of this method is that it separately measures the initial round trip path delay and the variations in round-trip path delay. The delay generated in SDH equipment is determined by measuring the initial round-trip path delay. In an experiment with actual SDH equipment, the error of initial delay measurement was suppressed to 30ns.

  15. A test of water vapor radiometer-based troposphere calibration using VLBI observations on a 21-kilometer baseline

    NASA Technical Reports Server (NTRS)

    Linfield, R. P.; Teitelbaum, L. P.; Skjerve, L. J.; Keihm, S. J.; Walter, S. J.; Mahoney, M. J.; Treuhaft, R. N.

    1995-01-01

    Simultaneous very long baseline interferometry (VLBI) and water vapor radiometer (WVR) measurements on a 21 km baseline showed that calibration by WVRs removed a significant fraction of the effect of tropospheric delay fluctuations for these experiments. From comparison of the residual delay variations within scans and between scans, the total tropospheric contribution t the delay residuals for each of the three 5 to 20 hour sessions was estimated as 1, 17, and 10%, with the first value being uncertain. The observed improvement in rms residual delay from WVR calibration during these three sessions was 4, 16, and 2%, respectively. The improvement is consistent with the estimated 2 to 3 mm path delay precision of current WVRs. The VLBI measurements, of natural radio sources, were conducted in April and May 1993 at Goldstone, California. Dual-frequency (2.3 and 8.4 GHz) observations were employed to remove the effects of charged particles from the data. Measurements with co-pointed WVRs, located within 50 m of the axis of each antenna, were performed to test the ability of the WVRs to calibrate line-of-sight path delays. Factors that made WVR performance assessment difficult included (1) the fact that the level of tropospheric fluctuations was smaller than is typical for Goldstone during these experiments and (2) VLBI delay variations on longer time scales (i.e., over multiple scans) contained uncalibrated instrumental effects (probably a result of slow temperature variations in the VLBI hardware) that were larger than the tropospheric effects.

  16. Low power digitally controlled oscillator designs with a novel 3-transistor XNOR gate

    NASA Astrophysics Data System (ADS)

    Kumar, Manoj; Arya, Sandeep K.; Pandey, Sujata

    2012-03-01

    Digital controlled oscillators (DCOs) are the core of all digital phase locked loop (ADPLL) circuits. Here, DCO structures with reduced hardware and power consumption having full digital control have been proposed. Three different DCO architectures have been proposed based on ring based topology. Three, four and five bit controlled DCO with NMOS, PMOS and NMOS & PMOS transistor switching networks are presented. A three-transistor XNOR gate has been used as the inverter which is used as the delay cell. Delay has been controlled digitally with a switch network of NMOS and PMOS transistors. The three bit DCO with one NMOS network shows frequency variations of 1.6141-1.8790 GHz with power consumption variations 251.9224-276.8591 μW. The four bit DCO with one NMOS network shows frequency variation of 1.6229-1.8868 GHz with varying power consumption of 251.9225-278.0740 μW. A six bit DCO with one NMOS switching network gave an output frequency of 1.7237-1.8962 GHz with power consumption of 251.928-278.998 μW. Output frequency and power consumption results for 4 & 6 bit DCO circuits with one PMOS and NMOS & PMOS switching network have also been presented. The phase noise parameter with an offset frequency of 1 MHz has also been reported for the proposed circuits. Comparisons with earlier reported circuits have been made and the present approach shows advantages over previous circuits.

  17. Planned Variation in Preanalytical Conditions to Evaluate Biospecimen Stability in the National Children’s Study (NCS)

    PubMed Central

    Mechanic, Leah; Mendez, Armando; Merrill, Lori; Rogers, John; Layton, Marnie; Todd, Deborah; Varanasi, Arti; O’Brien, Barbara; Meyer, William A.; Zhang, Ming; Schleicher, Rosemary L.; Moye, Jack

    2014-01-01

    BACKGROUND Preanalytical conditions encountered during collection, processing, and storage of biospecimens may influence laboratory results. The National Children’s Study (NCS) is a planned prospective cohort study of 100,000 families to examine the influence of a wide variety of exposures on child health. In developing biospecimen collection, processing, and storage procedures for the NCS, we identified several analytes of different biochemical categories for which it was unclear to what extent deviations from NCS procedures could influence measurement results. METHODS A pilot study was performed to examine effects of preanalytic sample handling conditions (delays in centrifugation, freezing delays, delays in separation from cells, additive delay, and tube type) on concentrations of eight different analytes. 2,825 measurements were made to assess 15 unique combinations of analyte and handling conditions in blood collected from 151 women of childbearing age (≥20 individuals per handling condition). RESULTS The majority of analytes were stable under the conditions evaluated. However, levels of plasma interleukin-6 and serum insulin were decreased in response to sample centrifugation delays of up to 5.5 hours post collection (P<0.0001). In addition, delays in freezing centrifuged plasma samples (comparing 24, 48 and 72 hours to immediate freezing) resulted in increased levels of adrenocorticotropic hormone (P=0.0014). CONCLUSIONS Determining stability of proposed analytes in response to preanalytical conditions and handling helps to ensure high-quality specimens for study now and in the future. The results inform development of procedures, plans for measurement of analytes, and interpretation of laboratory results. PMID:23924524

  18. The variation in breast density and its relationship to delayed wound healing: a prospective study of 40 reduction mammoplasties.

    PubMed

    Baldwin, C J; Kelly, E J; Batchelor, A G

    2010-04-01

    The proportions of glandular and adipose tissue within the breast vary. This study records the variation in density of breast tissue excised at 40 consecutive bilateral breast reductions. Age, body mass index (BMI), breast size and wound healing problems were related to breast density. The removed breast tissue was weighed and volume determined by water displacement. Delayed wound healing was defined as any breast unhealed after 2 weeks. The density of excised tissue varied between 0.8 and 1.2g/cm(3). There was no correlation between age or BMI and breast density. Delayed wound healing occurred in 32% of patients. There was no correlation between delayed wound healing and breast density. However, there was a direct relationship between increasing BMI and delayed wound healing. In this study, breast density varied by up to 50%. The density of breast tissue cannot be predicted by age, BMI or breast size. There is no relationship between delayed wound healing and breast density. Copyright 2009. Published by Elsevier Ltd.

  19. The relation between the cell-mediated immunological response and the induction of circulating antibodies to collagen in guinea-pigs.

    PubMed Central

    Gentner, G J; Adelmann, B C

    1976-01-01

    Cutaneous delayed hypersensitivity reactions to collagen in guinea-pigs were partially but specifically suppressed if the animals had been pretreated with collagen and Freund's incomplete adjuvant. Such animals responded normally to skin-reactive factor prepared with ovalbumin. Lymphoid cells from animals with normal delayed hypersensitivity to collagen functioned normally in animals with suppressed skin reactivity. Cells from animals with suppressed delayed hypersensitivity were specifically, functionally impaired since they transferred delayed hypersensitivity into neutral recipients efficiently for PPD but not for collagen. Suppression could be induced in Cy-treated animals, and it persisted for at least 143 days. It is concluded that guinea-pigs with depressed delayed hypersensitivity to collagen are functionally impaired with respect to those T cells normally generated by induction of delayed hypersensitivity. PMID:1088420

  20. Effects of Frequency Dependence of the External Quantum Efficiency of Perovskite Solar Cells.

    PubMed

    Ravishankar, Sandheep; Aranda, Clara; Boix, Pablo P; Anta, Juan A; Bisquert, Juan; Garcia-Belmonte, Germà

    2018-06-07

    Perovskite solar cells are known to show very long response time scales, on the order of milliseconds to seconds. This generates considerable doubt over the validity of the measured external quantum efficiency (EQE) and consequently the estimation of the short-circuit current density. We observe a variation as high as 10% in the values of the EQE of perovskite solar cells for different optical chopper frequencies between 10 and 500 Hz, indicating a need to establish well-defined protocols of EQE measurement. We also corroborate these values and obtain new insights regarding the working mechanisms of perovskite solar cells from intensity-modulated photocurrent spectroscopy measurements, identifying the evolution of the EQE over a range of frequencies, displaying a singular reduction at very low frequencies. This reduction in EQE is ascribed to additional resistive contributions hindering charge extraction in the perovskite solar cell at short-circuit conditions, which are delayed because of the concomitant large low-frequency capacitance.

  1. Loss of Gα12/13 exacerbates apical area dependence of actomyosin contractility

    PubMed Central

    Xie, Shicong; Mason, Frank M.; Martin, Adam C.

    2016-01-01

    During development, coordinated cell shape changes alter tissue shape. In the Drosophila ventral furrow and other epithelia, apical constriction of hundreds of epithelial cells folds the tissue. Genes in the Gα12/13 pathway coordinate collective apical constriction, but the mechanism of coordination is poorly understood. Coupling live-cell imaging with a computational approach to identify contractile events, we discovered that differences in constriction behavior are biased by initial cell shape. Disrupting Gα12/13 exacerbates this relationship. Larger apical area is associated with delayed initiation of contractile pulses, lower apical E-cadherin and F-actin levels, and aberrantly mobile Rho-kinase structures. Our results suggest that loss of Gα12/13 disrupts apical actin cortex organization and pulse initiation in a size-dependent manner. We propose that Gα12/13 robustly organizes the apical cortex despite variation in apical area to ensure the timely initiation of contractile pulses in a tissue with heterogeneity in starting cell shape. PMID:27489340

  2. Research on the effect of rainfall flood regulation and control of wetland park based on SWMM model—a case study of wetland park in Yuanjia village, Qishan county, Shaanxi province

    NASA Astrophysics Data System (ADS)

    Xu, Da; Liu, Yijie

    2018-02-01

    Taking the wetland park of Yuan Village in Qishan County of Shaanxi Province as the research object, this paper makes a reasonable generalization of the study area, and establishes two models of low impact development (LID) and traditional development in the park. Meantime, rainwater in the surrounding built up area is introduced to into the park for digestion. SWMM model is used to simulate the variation of the total runoff, peak flow and peak time of two development models in Wetland Park under one-hour rainfall at different recurrence periods.The runoff control effect in each single LID facility in the one-hour rainfall once during five years in the built-up area is simulated. The simulation results show that the SWMM model can not only quantify the runoff reduction effect of different LID facilities, but also provide theoretical basis and data support for the urban rainfall flood problem. LID facilities have effects on runoff reduction and peak delay. However, the combined LID facility has obvious advantages for the peak time delay and peak flow control. A single LID facility is more efficient in a single runoff volume control. The order of runoff reduction by various LID facilities is as follows: Rain garden>combined LID facility> vegetative swale> bio-retention cell > permeable pavement. The order of peak time delay effect by the LID facilities is as follows: combined LID facility> Rain garden> vegetative swale> bio-retention cell > permeable pavement. The order of peak flow reduction efficiency by various LID facilities is: combined LID facility> Rain garden> bio-retention cell > vegetative swale> permeable pavement.

  3. Global exponential stability of BAM neural networks with time-varying delays and diffusion terms

    NASA Astrophysics Data System (ADS)

    Wan, Li; Zhou, Qinghua

    2007-11-01

    The stability property of bidirectional associate memory (BAM) neural networks with time-varying delays and diffusion terms are considered. By using the method of variation parameter and inequality technique, the delay-independent sufficient conditions to guarantee the uniqueness and global exponential stability of the equilibrium solution of such networks are established.

  4. Temperature aspect of degradation of electrochemical double-layer capacitors (EDLC)

    NASA Astrophysics Data System (ADS)

    Baek, Dong-Cheon; Kim, Hyun-Ho; Lee, Soon-Bok

    2015-03-01

    Electric double layer capacitors (EDLC) cells have a process variation and temperature dependency in capacitance so that balancing is required when they are connected in series, which includes electronic voltage management based on capacitance monitoring. This paper measured temperature aspect of capacitance periodically to monitor health and degradation behavior of EDLC stressed under high temperatures and zero below temperatures respectively, which enables estimation of the state of health (SOH) regardless of temperature. At high temperature, capacitance saturation and delayed expression of degradation was observed. After cyclic stress at zero below temperature, less effective degradation and time recovery phenomenon were occurred.

  5. An efficient current-based logic cell model for crosstalk delay analysis

    NASA Astrophysics Data System (ADS)

    Nazarian, Shahin; Das, Debasish

    2013-04-01

    Logic cell modelling is an important component in the analysis and design of CMOS integrated circuits, mostly due to nonlinear behaviour of CMOS cells with respect to the voltage signal at their input and output pins. A current-based model for CMOS logic cells is presented, which can be used for effective crosstalk noise and delta delay analysis in CMOS VLSI circuits. Existing current source models are expensive and need a new set of Spice-based characterisation, which is not compatible with typical EDA tools. In this article we present Imodel, a simple nonlinear logic cell model that can be derived from the typical cell libraries such as NLDM, with accuracy much higher than NLDM-based cell delay models. In fact, our experiments show an average error of 3% compared to Spice. This level of accuracy comes with a maximum runtime penalty of 19% compared to NLDM-based cell delay models on medium-sized industrial designs.

  6. Maximum principle for a stochastic delayed system involving terminal state constraints.

    PubMed

    Wen, Jiaqiang; Shi, Yufeng

    2017-01-01

    We investigate a stochastic optimal control problem where the controlled system is depicted as a stochastic differential delayed equation; however, at the terminal time, the state is constrained in a convex set. We firstly introduce an equivalent backward delayed system depicted as a time-delayed backward stochastic differential equation. Then a stochastic maximum principle is obtained by virtue of Ekeland's variational principle. Finally, applications to a state constrained stochastic delayed linear-quadratic control model and a production-consumption choice problem are studied to illustrate the main obtained result.

  7. Array-CGH analysis in Rwandan patients presenting development delay/intellectual disability with multiple congenital anomalies.

    PubMed

    Uwineza, Annette; Caberg, Jean-Hubert; Hitayezu, Janvier; Hellin, Anne Cecile; Jamar, Mauricette; Dideberg, Vinciane; Rusingiza, Emmanuel K; Bours, Vincent; Mutesa, Leon

    2014-07-12

    Array-CGH is considered as the first-tier investigation used to identify copy number variations. Right now, there is no available data about the genetic etiology of patients with development delay/intellectual disability and congenital malformation in East Africa. Array comparative genomic hybridization was performed in 50 Rwandan patients with development delay/intellectual disability and multiple congenital abnormalities, using the Agilent's 180 K microarray platform. Fourteen patients (28%) had a global development delay whereas 36 (72%) patients presented intellectual disability. All patients presented multiple congenital abnormalities. Clinically significant copy number variations were found in 13 patients (26%). Size of CNVs ranged from 0,9 Mb to 34 Mb. Six patients had CNVs associated with known syndromes, whereas 7 patients presented rare genomic imbalances. This study showed that CNVs are present in African population and show the importance to implement genetic testing in East-African countries.

  8. Carbonate fuel cell and components thereof for in-situ delayed addition of carbonate electrolyte

    DOEpatents

    Johnsen, Richard [Waterbury, CT; Yuh, Chao-Yi [New Milford, CT; Farooque, Mohammad [Danbury, CT

    2011-05-10

    An apparatus and method in which a delayed carbonate electrolyte is stored in the storage areas of a non-electrolyte matrix fuel cell component and is of a preselected content so as to obtain a delayed time release of the electrolyte in the storage areas in the operating temperature range of the fuel cell.

  9. Understanding delayed T-cell priming, lung recruitment, and airway luminal T-cell responses in host defense against pulmonary tuberculosis.

    PubMed

    Shaler, Christopher R; Horvath, Carly; Lai, Rocky; Xing, Zhou

    2012-01-01

    Mycobacterium tuberculosis (M.tb), the causative bacterium of pulmonary tuberculosis (TB), is a serious global health concern. Central to M.tb effective immune avoidance is its ability to modulate the early innate inflammatory response and prevent the establishment of adaptive T-cell immunity for nearly three weeks. When compared with other intracellular bacterial lung pathogens, such as Legionella pneumophila, or even closely related mycobacterial species such as M. smegmatis, this delay is astonishing. Customarily, the alveolar macrophage (AM) acts as a sentinel, detecting and alerting surrounding cells to the presence of an invader. However, in the case of M.tb, this may be impaired, thus delaying the recruitment of antigen-presenting cells (APCs) to the lung. Upon uptake by APC populations, M.tb is able to subvert and delay the processing of antigen, MHC class II loading, and the priming of effector T cell populations. This delay ultimately results in the deferred recruitment of effector T cells to not only the lung interstitium but also the airway lumen. Therefore, it is of upmost importance to dissect the mechanisms that contribute to the delayed onset of immune responses following M.tb infection. Such knowledge will help design the most effective vaccination strategies against pulmonary TB.

  10. The use of cell phones and radio communication systems to reduce delays in getting help for pregnant women in low- and middle-income countries: a scoping review.

    PubMed

    Oyeyemi, Sunday O; Wynn, Rolf

    2015-01-01

    Delays in getting medical help are important factors in the deaths of many pregnant women and unborn children in the low- and middle-income countries (LMIC). Studies have suggested that the use of cell phones and radio communication systems might reduce such delays. We review the literature regarding the impact of cell phones and radio communication systems on delays in getting medical help by pregnant women in the LMIC. Cochrane Library, PubMed, Maternity and Infant care (Ovid), Web of Science (ISI), and Google Scholar were searched for studies relating to the use of cell phones for maternal and child health services, supplemented with hand searches. We included studies in LMIC and in English involving the simple use of cell phones (or radio communication) to either make calls or send text messages. Fifteen studies met the inclusion criteria. All the studies, while of various designs, demonstrated positive contributory effects of cell phones or radio communication systems in reducing delays experienced by pregnant women in getting medical help. While the results suggested that cell phones could contribute in reducing delays, more studies of a longer duration are needed to strengthen the finding.

  11. The use of cell phones and radio communication systems to reduce delays in getting help for pregnant women in low- and middle-income countries: a scoping review

    PubMed Central

    Oyeyemi, Sunday O.; Wynn, Rolf

    2015-01-01

    Background Delays in getting medical help are important factors in the deaths of many pregnant women and unborn children in the low- and middle-income countries (LMIC). Studies have suggested that the use of cell phones and radio communication systems might reduce such delays. Objectives We review the literature regarding the impact of cell phones and radio communication systems on delays in getting medical help by pregnant women in the LMIC. Design Cochrane Library, PubMed, Maternity and Infant care (Ovid), Web of Science (ISI), and Google Scholar were searched for studies relating to the use of cell phones for maternal and child health services, supplemented with hand searches. We included studies in LMIC and in English involving the simple use of cell phones (or radio communication) to either make calls or send text messages. Results Fifteen studies met the inclusion criteria. All the studies, while of various designs, demonstrated positive contributory effects of cell phones or radio communication systems in reducing delays experienced by pregnant women in getting medical help. Conclusions While the results suggested that cell phones could contribute in reducing delays, more studies of a longer duration are needed to strengthen the finding. PMID:26362421

  12. Three Profiles of Language Abilities in Toddlers with an Expressive Vocabulary Delay: Variations on a Theme

    ERIC Educational Resources Information Center

    Desmarais, Chantal; Sylvestre, Audette; Meyer, Francois; Bairati, Isabelle; Rouleau, Nancie

    2010-01-01

    Purpose: The presence of an expressive vocabulary delay (EVD) in the context of otherwise harmonious development has been the main criterion used to define language delay in 2-year-olds. To better understand the communicative functioning of these children, other variables must be considered. In this study, the aim was to delineate and characterize…

  13. Low-temperature Ignition-delay Characteristics of Several Rocket Fuels with Mixed Acid in Modified Open-cup-type Apparatus

    NASA Technical Reports Server (NTRS)

    Miller, Riley O

    1950-01-01

    Summaries of low-temperature self-ignition data of various rocket fuels with mixed acid (nitric plus sulfuric) are presented. Several fuels are shown to have shorter ignition-delay intervals and less variation in delay intervals at moderate and sub-zero temperatures than crude N-ethylaniline (monoethylaniline),a rocket fuel in current use.

  14. Variability of wet troposphere delays over inland reservoirs as simulated by a high-resolution regional climate model

    NASA Astrophysics Data System (ADS)

    Clark, E.; Lettenmaier, D. P.

    2014-12-01

    Satellite radar altimetry is widely used for measuring global sea level variations and, increasingly, water height variations of inland water bodies. Existing satellite radar altimeters measure water surfaces directly below the spacecraft (approximately at nadir). Over the ocean, most of these satellites use radiometry to measure the delay of radar signals caused by water vapor in the atmosphere (also known as the wet troposphere delay (WTD)). However, radiometry can only be used to estimate this delay over the largest inland water bodies, such as the Great Lakes, due to spatial resolution issues. As a result, atmospheric models are typically used to simulate and correct for the WTD at the time of observations. The resolutions of these models are quite coarse, at best about 5000 km2 at 30˚N. The upcoming NASA- and CNES-led Surface Water and Ocean Topography (SWOT) mission, on the other hand, will use interferometric synthetic aperture radar (InSAR) techniques to measure a 120-km-wide swath of the Earth's surface. SWOT is expected to make useful measurements of water surface elevation and extent (and storage change) for inland water bodies at spatial scales as small as 250 m, which is much smaller than current altimetry targets and several orders of magnitude smaller than the models used for wet troposphere corrections. Here, we calculate WTD from very high-resolution (4/3-km to 4-km) simulations of the Weather Research and Forecasting (WRF) regional climate model, and use the results to evaluate spatial variations in WTD. We focus on six U.S. reservoirs: Lake Elwell (MT), Lake Pend Oreille (ID), Upper Klamath Lake (OR), Elephant Butte (NM), Ray Hubbard (TX), and Sam Rayburn (TX). The reservoirs vary in climate, shape, use, and size. Because evaporation from open water impacts local water vapor content, we compare time series of WTD over land and water in the vicinity of each reservoir. To account for resolution effects, we examine the difference in WRF-simulated WTD averaged over ECMWF and NCEP-NCAR resolution grid cells and compare the magnitudes of each over reservoirs. Finally, we also test the degree to which, if uncorrected, the WTD would dampen or strengthen measured changes in water levels (and storage) at each reservoir.

  15. Effects of the gaseous and liquid water content of the atmosphere on range delay and Doppler frequency

    NASA Technical Reports Server (NTRS)

    Flock, W. L.

    1981-01-01

    When high precision is required for range measurement on Earth space paths, it is necessary to correct as accurately as possible for excess range delays due to the dry air, water vapor, and liquid water content of the atmosphere. Calculations based on representative values of atmospheric parameters are useful for illustrating the order of magnitude of the expected delays. Range delay, time delay, and phase delay are simply and directly related. Doppler frequency variations or noise are proportional to the time rate of change of excess range delay. Tropospheric effects were examined as part of an overall consideration of the capability of precision two way ranging and Doppler systems.

  16. Classifying and Analyzing 3d Cell Motion in Jammed Microgels

    NASA Astrophysics Data System (ADS)

    Bhattacharjee, Tapomoy; Sawyer, W. Gregory; Angelini, Thomas

    Soft granular polyelectrolyte microgels swell in liquid cell growth media to form a continuous elastic solid that can easily transition between solid to fluid state under a low shear stress. Such Liquid-like solids (LLS) have recently been used to create 3D cellular constructs as well as to support, culture and harvest cells in 3D. Current understanding of cell migration mechanics in 3D was established from experiments performed in natural and synthetic polymer networks. Spatial variation in network structure and the transience of degradable gels limit their usefulness in quantitative cell mechanics studies. By contrast, LLS growth media approximates a homogeneous continuum, enabling tractable cell mechanics measurements to be performed in 3D. Here, we introduce a process to understand and classify cytotoxic T cell motion in 3D by studying cellular motility in LLS media. General classification of T cell motion can be achieved with a very traditional statistical approach: the cell's mean squared displacement (MSD) as a function of delay time. We will also use Langevin approaches combined with the constitutive equations of the LLS medium to predict the statistics of T cell motion. National Science Foundation under Grant No. DMR-1352043.

  17. Binaural interaction in low-frequency neurons in inferior colliculus of the cat. II. Effects of changing rate and direction of interaural phase.

    PubMed

    Yin, T C; Kuwada, S

    1983-10-01

    We used the binaural beat stimulus to study the interaural phase sensitivity of inferior colliculus (IC) neurons in the cat. The binaural beat, produced by delivering tones of slightly different frequencies to the two ears, generates continuous and graded changes in interaural phase. Over 90% of the cells that exhibit a sensitivity to changes in the interaural delay also show a sensitivity to interaural phase disparities with the binaural beat. Cells respond with a burst of impulses with each complete cycle of the beat frequency. The period histogram obtained by binning the poststimulus time histogram on the beat frequency gives a measure of the interaural phase sensitivity of the cell. In general, there is good correspondence in the shapes of the period histograms generated from binaural beats and the interaural phase curves derived from interaural delays and in the mean interaural phase angle calculated from them. The magnitude of the beat frequency determines the rate of change of interaural phase and the sign determines the direction of phase change. While most cells respond in a phase-locked manner up to beat frequencies of 10 Hz, there are some cells tht will phase lock up to 80 Hz. Beat frequency and mean interaural phase angle are linearly related for most cells. Most cells respond equally in the two directions of phase change and with different rates of change, at least up to 10 Hz. However, some IC cells exhibit marked sensitivity to the speed of phase change, either responding more vigorously at low beat frequencies or at high beat frequencies. In addition, other cells demonstrate a clear directional sensitivity. The cells that show sensitivity to the direction and speed of phase changes would be expected to demonstrate a sensitivity to moving sound sources in the free field. Changes in the mean interaural phase of the binaural beat period histograms are used to determine the effects of changes in average and interaural intensity on the phase sensitivity of the cells. The effects of both forms of intensity variation are continuously distributed. The binaural beat offers a number of advantages for studying the interaural phase sensitivity of binaural cells. The dynamic characteristics of the interaural phase can be varied so that the speed and direction of phase change are under direct control. The data can be obtained in a much more efficient manner, as the binaural beat is about 10 times faster in terms of data collection than the interaural delay.

  18. Predicting memory performance under conditions of proactive interference: immediate and delayed judgments of learning.

    PubMed

    Wahlheim, Christopher N

    2011-07-01

    Four experiments examined the monitoring accuracy of immediate and delayed judgments of learning (JOLs) under conditions of proactive interference (PI). PI was produced using paired-associate learning tasks that conformed to variations of classic A-B, A-D paradigms. Results revealed that the relative monitoring accuracy of interference items was better for delayed than for immediate JOLs. However, delayed JOLs were overconfident for interference items, but not for items devoid of interference. Intrusions retrieved prior to delayed JOLs produced inflated predictions of performance. These results show that delayed JOLs enhance monitoring accuracy in PI situations, except when intrusions are mistaken for target responses.

  19. Apparatus and Method for Compensating for Process, Voltage, and Temperature Variation of the Time Delay of a Digital Delay Line

    NASA Technical Reports Server (NTRS)

    Seefeldt, James (Inventor); Feng, Xiaoxin (Inventor); Roper, Weston (Inventor)

    2013-01-01

    A process, voltage, and temperature (PVT) compensation circuit and a method of continuously generating a delay measure are provided. The compensation circuit includes two delay lines, each delay line providing a delay output. The two delay lines may each include a number of delay elements, which in turn may include one or more current-starved inverters. The number of delay lines may differ between the two delay lines. The delay outputs are provided to a combining circuit that determines an offset pulse based on the two delay outputs and then averages the voltage of the offset pulse to determine a delay measure. The delay measure may be one or more currents or voltages indicating an amount of PVT compensation to apply to input or output signals of an application circuit, such as a memory-bus driver, dynamic random access memory (DRAM), a synchronous DRAM, a processor or other clocked circuit.

  20. Surfactant protein D delays Fas- and TRAIL-mediated extrinsic pathway of apoptosis in T cells.

    PubMed

    Djiadeu, Pascal; Kotra, Lakshmi P; Sweezey, Neil; Palaniyar, Nades

    2017-05-01

    Only a few extracellular soluble proteins are known to modulate apoptosis. We considered that surfactant-associated protein D (SP-D), an innate immune collectin present on many mucosal surfaces, could regulate apoptosis. Although SP-D is known to be important for immune cell homeostasis, whether SP-D affects apoptosis is unknown. In this study we aimed to determine the effects of SP-D on Jurkat T cells and human T cells dying by apoptosis. Here we show that SP-D binds to Jurkat T cells and delays the progression of Fas (CD95)-Fas ligand and TRAIL-TRAIL receptor induced, but not TNF-TNF receptor-mediated apoptosis. SP-D exerts its effects by reducing the activation of initiator caspase-8 and executioner caspase-3. SP-D also delays the surface exposure of phosphatidylserine. The effect of SP-D was ablated by the presence of caspase-8 inhibitor, but not by intrinsic pathway inhibitors. The binding ability of SP-D to dying cells decreases during the early stages of apoptosis, suggesting the release of apoptotic cell surface targets during apoptosis. SP-D also delays FasL-induced death of primary human T cells. SP-D delaying the progression of the extrinsic pathway of apoptosis could have important implications in regulating immune cell homeostasis at mucosal surfaces.

  1. Induction of a G1-S checkpoint in fission yeast.

    PubMed

    Bøe, Cathrine A; Krohn, Marit; Rødland, Gro Elise; Capiaghi, Christoph; Maillard, Olivier; Thoma, Fritz; Boye, Erik; Grallert, Beáta

    2012-06-19

    Entry into S phase is carefully regulated and, in most organisms, under the control of a G(1)-S checkpoint. We have previously described a G(1)-S checkpoint in fission yeast that delays formation of the prereplicative complex at chromosomal replication origins after exposure to UV light (UVC). This checkpoint absolutely depends on the Gcn2 kinase. Here, we explore the signal for activation of the Gcn2-dependent G(1)-S checkpoint in fission yeast. If some form of DNA damage can activate the checkpoint, deficient DNA repair should affect the length of the checkpoint-induced delay. We find that the cell-cycle delay differs in repair-deficient mutants from that in wild-type cells. However, the duration of the delay depends not only on the repair capacity of the cells, but also on the nature of the repair deficiency. First, the delay is abolished in cells that are deficient in the early steps of repair. Second, the delay is prolonged in repair mutants that fail to complete repair after the incision stage. We conclude that the G(1)-S delay depends on damage to the DNA and that the activating signal derives not from the initial DNA damage, but from a repair intermediate(s). Surprisingly, we find that activation of Gcn2 does not depend on the processing of DNA damage and that activated Gcn2 alone is not sufficient to delay entry into S phase in UVC-irradiated cells. Thus, the G(1)-S delay depends on at least two different inputs.

  2. Cardiomyocyte Ca2+ handling and structure is regulated by degree and duration of mechanical load variation.

    PubMed

    Ibrahim, Michael; Kukadia, Punam; Siedlecka, Urszula; Cartledge, James E; Navaratnarajah, Manoraj; Tokar, Sergiy; Van Doorn, Carin; Tsang, Victor T; Gorelik, Julia; Yacoub, Magdi H; Terracciano, Cesare M

    2012-12-01

    Cardiac transverse (t)-tubules are altered during disease and may be regulated by stretch-sensitive molecules. The relationship between variations in the degree and duration of load and t-tubule structure remains unknown, as well as its implications for local Ca(2+)-induced Ca(2+) release (CICR). Rat hearts were studied after 4 or 8 weeks of moderate mechanical unloading [using heterotopic abdominal heart-lung transplantation (HAHLT)] and 6 or 10 weeks of pressure overloading using thoracic aortic constriction. CICR, cell and t-tubule structure were assessed using confocal-microscopy, patch-clamping and scanning ion conductance microscopy. Moderate unloading was compared with severe unloading [using heart-only transplantation (HAHT)]. Mechanical unloading reduced cardiomyocyte volume in a time-dependent manner. Ca(2+) release synchronicity was reduced at 8 weeks moderate unloading only. Ca(2+) sparks increased in frequency and duration at 8 weeks of moderate unloading, which also induced t-tubule disorganization. Overloading increased cardiomyocyte volume and disrupted t-tubule morphology at 10 weeks but not 6 weeks. Moderate mechanical unloading for 4 weeks had milder effects compared with severe mechanical unloading (37% reduction in cell volume at 4 weeks compared to 56% reduction after severe mechanical unloading) and did not cause depression and delay of the Ca(2+) transient, increased Ca(2+) spark frequency or impaired t-tubule and cell surface structure. These data suggest that variations in chronic mechanical load influence local CICR and t-tubule structure in a time- and degree-dependent manner, and that physiological states of increased and reduced cell size, without pathological changes are possible. © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  3. Neural correlates of sample-coding and reward-coding in the delay activity of neurons in the entopallium and nidopallium caudolaterale of pigeons (Columba livia).

    PubMed

    Johnston, Melissa; Anderson, Catrona; Colombo, Michael

    2017-01-15

    We recorded neuronal activity from the nidopallium caudolaterale, the avian equivalent of mammalian prefrontal cortex, and the entopallium, the avian equivalent of the mammalian visual cortex, in four birds trained on a differential outcomes delayed matching-to-sample procedure in which one sample stimulus was followed by reward and the other was not. Despite similar incidence of reward-specific and reward-unspecific delay cell types across the two areas, overall entopallium delay activity occurred following both rewarded and non-rewarded stimuli, whereas nidopallium caudolaterale delay activity tended to occur following the rewarded stimulus but not the non-rewarded stimulus. These findings are consistent with the view that delay activity in entopallium represents a code of the sample stimulus whereas delay activity in nidopallium caudolaterale represents a code of the possibility of an upcoming reward. However, based on the types of delay cells encountered, cells in NCL also code the sample stimulus and cells in ENTO are influenced by reward. We conclude that both areas support the retention of information, but that the activity in each area is differentially modulated by factors such as reward and attentional mechanisms. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Host genetic determinants of HIV pathogenesis: an immunologic perspective.

    PubMed

    Hunt, Peter W; Carrington, Mary

    2008-05-01

    The purpose of this review is to highlight recent advances in our understanding of host genetic determinants of HIV pathogenesis and to provide a theoretical framework for interpreting these studies in the context of our evolving understanding of HIV immunopathogenesis. The first genome-wide association analysis of host determinants of HIV pathogenesis and other recent studies evaluating the interaction between killer cell immunoglobulin-like receptors and human leukocyte antigen alleles have implicated both adaptive and innate immune responses in the control of HIV replication. Furthermore, genetic variation associated with the expression of CCR5 and its ligand have been strongly associated with both decreased susceptibility to HIV infection and delayed clinical progression, independent of their effects on viral replication, suggesting a potential role for CCR5 inhibitors as immune-based therapies in HIV disease. Host factors associated with the control of HIV replication may help identify important targets for vaccine design, while those associated with delayed clinical progression provide targets for future immune-based therapies against HIV infection.

  5. End-to-end QoS bounds for RTP-based service subnetworks

    NASA Astrophysics Data System (ADS)

    Pitts, Jonathan M.; Schormans, John A.

    1999-11-01

    With the increasing focus on traffic prioritization to support voice-data integration in corporate intranets, practical methods are needed to dimension and manage cost efficient service partitions. This is particularly important for the provisioning of real time, delay sensitive services such as telephony and voice/video conferencing applications. Typically these can be provided over RTP/UDP/IP or ATM DBR/SBR bearers but, irrespective of the specific networking technology, the switches or routers need to implement some form of virtual buffer management with queue scheduling mechanisms to provide partitioning. The key requirement is for operators of such networks to be able to dimension the partitions and virtual buffer sizes for efficient resource utilization, instead of simply over-dimensioning. This paper draws on recent work at Queen Mary, University of London, supported by the UK Engineering and Physical Sciences Research Council, to investigate approximate analytical methods for assessing end to end delay variation bounds in cell based and packet based networks.

  6. Red blood cell alloimmunization in sickle cell disease: pathophysiology, risk factors, and transfusion management.

    PubMed

    Yazdanbakhsh, Karina; Ware, Russell E; Noizat-Pirenne, France

    2012-07-19

    Red blood cell transfusions have reduced morbidity and mortality for patients with sickle cell disease. Transfusions can lead to erythrocyte alloimmunization, however, with serious complications for the patient including life-threatening delayed hemolytic transfusion reactions and difficulty in finding compatible units, which can cause transfusion delays. In this review, we discuss the risk factors associated with alloimmunization with emphasis on possible mechanisms that can trigger delayed hemolytic transfusion reactions in sickle cell disease, and we describe the challenges in transfusion management of these patients, including opportunities and emerging approaches for minimizing this life-threatening complication.

  7. An analog integrated circuit beamformer for high-frequency medical ultrasound imaging.

    PubMed

    Gurun, Gokce; Zahorian, Jaime S; Sisman, Alper; Karaman, Mustafa; Hasler, Paul E; Degertekin, F Levent

    2012-10-01

    We designed and fabricated a dynamic receive beamformer integrated circuit (IC) in 0.35-μm CMOS technology. This beamformer IC is suitable for integration with an annular array transducer for high-frequency (30-50 MHz) intravascular ultrasound (IVUS) imaging. The beamformer IC consists of receive preamplifiers, an analog dynamic delay-and-sum beamformer, and buffers for 8 receive channels. To form an analog dynamic delay line we designed an analog delay cell based on the current-mode first-order all-pass filter topology, as the basic building block. To increase the bandwidth of the delay cell, we explored an enhancement technique on the current mirrors. This technique improved the overall bandwidth of the delay line by a factor of 6. Each delay cell consumes 2.1-mW of power and is capable of generating a tunable time delay between 1.75 ns to 2.5 ns. We successfully integrated the fabricated beamformer IC with an 8-element annular array. Experimental test results demonstrated the desired buffering, preamplification and delaying capabilities of the beamformer.

  8. Quantitative assessment of image motion blur in diffraction images of moving biological cells

    NASA Astrophysics Data System (ADS)

    Wang, He; Jin, Changrong; Feng, Yuanming; Qi, Dandan; Sa, Yu; Hu, Xin-Hua

    2016-02-01

    Motion blur (MB) presents a significant challenge for obtaining high-contrast image data from biological cells with a polarization diffraction imaging flow cytometry (p-DIFC) method. A new p-DIFC experimental system has been developed to evaluate the MB and its effect on image analysis using a time-delay-integration (TDI) CCD camera. Diffraction images of MCF-7 and K562 cells have been acquired with different speed-mismatch ratios and compared to characterize MB quantitatively. Frequency analysis of the diffraction images shows that the degree of MB can be quantified by bandwidth variations of the diffraction images along the motion direction. The analytical results were confirmed by the p-DIFC image data acquired at different speed-mismatch ratios and used to validate a method of numerical simulation of MB on blur-free diffraction images, which provides a useful tool to examine the blurring effect on diffraction images acquired from the same cell. These results provide insights on the dependence of diffraction image on MB and allow significant improvement on rapid biological cell assay with the p-DIFC method.

  9. Hospital Variation in Time to Epinephrine for Non-Shockable In-Hospital Cardiac Arrest

    PubMed Central

    Khera, Rohan; Chan, Paul S.; Donnino, Michael; Girotra, Saket

    2016-01-01

    Background For patients with in-hospital cardiac arrests due to non-shockable rhythms, delays in epinephrine administration beyond 5 minutes is associated with worse survival. However, the extent of hospital variation in delayed epinephrine administration and its impact on hospital-level outcomes is unknown. Methods Within Get with the Guidelines-Resuscitation, we identified 103,932 adult patients (≥18 years) at 548 hospitals with an in-hospital cardiac arrest due to a non-shockable rhythm who received at least 1 dose of epinephrine between 2000 to 2014. We constructed two-level hierarchical regression models to quantify hospital variation in rates of delayed epinephrine administration (>5 minutes) and its association with hospital rates of survival to discharge and survival with functional recovery. Results Overall, 13,213 (12.7%) patients had delays to epinephrine, and this rate varied markedly across hospitals (range: 0% to 53.8%). The odds of delay in epinephrine administration were 58% higher at one randomly selected hospital compared to a similar patient at another randomly selected hospitals (median odds ratio [OR] 1.58; 95% C.I. 1.51 – 1.64). Median risk-standardized survival rate was 12.0% (range: 5.4% to 31.9%) and risk-standardized survival with functional recovery was 7.4% (range: 0.9% to 30.8%). There was an inverse correlation between a hospital’s rate of delayed epinephrine administration and its risk-standardized rate of survival to discharge (ρ= −0.22, P<0.0001) and survival with functional recovery (ρ= −0.14, P=0.001). Compared to a median survival rate of 12.9% (interquartile range 11.1% to 15.4%) at hospitals in the lowest quartile of epinephrine delay, risk-standardized survival was 16% lower at hospitals in the quartile with the highest rate of epinephrine delays (10.8%, interquartile range: 9.7% to 12.7%). Conclusions Delays in epinephrine administration following in-hospital cardiac arrest are common and varies across hospitals. Hospitals with high rates of delayed epinephrine administration had lower rates of overall survival for in-hospital cardiac arrest due to non-shockable rhythm. Further studies are needed to determine if improving hospital performance on time to epinephrine administration, especially at hospitals with poor performance on this metric will lead to improved outcomes. PMID:27908910

  10. Hospital Variation in Time to Epinephrine for Nonshockable In-Hospital Cardiac Arrest.

    PubMed

    Khera, Rohan; Chan, Paul S; Donnino, Michael; Girotra, Saket

    2016-12-20

    For patients with in-hospital cardiac arrests attributable to nonshockable rhythms, delays in epinephrine administration beyond 5 minutes is associated with worse survival. However, the extent of hospital variation in delayed epinephrine administration and its effect on hospital-level outcomes is unknown. Within Get With The Guidelines-Resuscitation, we identified 103 932 adult patients (≥18 years) at 548 hospitals with an in-hospital cardiac arrest attributable to a nonshockable rhythm who received at least 1 dose of epinephrine between 2000 and 2014. We constructed 2-level hierarchical regression models to quantify hospital variation in rates of delayed epinephrine administration (>5 minutes) and its association with hospital rates of survival to discharge and survival with functional recovery. Overall, 13 213 (12.7%) patients had delays to epinephrine, and this rate varied markedly across hospitals (range, 0%-53.8%). The odds of delay in epinephrine administration were 58% higher at 1 randomly selected hospital in comparison with a similar patient at another randomly selected hospital (median odds ratio, 1.58; 95% confidence interval, 1.51-1.64). The median risk-standardized survival rate was 12.0% (range, 5.4%-31.9%), and the risk-standardized survival with functional recovery was 7.4% (range, 0.9%-30.8%). There was an inverse correlation between a hospital's rate of delayed epinephrine administration and its risk-standardized rate of survival to discharge (ρ=-0.22, P<0.0001) and survival with functional recovery (ρ=-0.14, P=0.001). In comparison with a median survival rate of 12.9% (interquartile range, 11.1%-15.4%) at hospitals in the lowest quartile of epinephrine delay, risk-standardized survival was 16% lower at hospitals in the quartile with the highest rate of epinephrine delays (10.8%; interquartile range, 9.7%-12.7%). Delays in epinephrine administration following in-hospital cardiac arrest are common and variy across hospitals. Hospitals with high rates of delayed epinephrine administration had lower rates of overall survival for in-hospital cardiac arrest attributable to nonshockable rhythm. Further studies are needed to determine whether improving hospital performance on time to epinephrine administration, especially at hospitals with poor performance on this metric, will lead to improved outcomes. © 2016 American Heart Association, Inc.

  11. A direct evaluation of the Geosat altimeter wet atmospheric range delay using very long baseline interferometry observations

    NASA Technical Reports Server (NTRS)

    Koblinsky, C. J.; Ryan, J.; Braatz, L.; Klosko, S. M.

    1993-01-01

    The overall accuracy of the U.S. Navy Geosat altimeter wet atmospheric range delay caused by refraction through the atmosphere is directly assessed by comparing the estimates made from the DMSP Special Sensor Microwave/Imager and the U.S. Navy Fleet Numerical Ocean Center forecast model for Geosat with measurements of total zenith columnar water vapor content from four VLBI sites. The assessment is made by comparing time series of range delay from various methods at each location. To determine the importance of diurnal variation in water vapor content in noncoincident estimates, the VLBI measurements were made at 15-min intervals over a few days. The VLBI measurements showed strong diurnal variations in columnar water vapor at several sites, causing errors of the order 3 cm rms in any noncoincident measurement of the wet troposphere range delay. These errors have an effect on studies of annual and interannual changes in sea level with Geosat data.

  12. Postural control model interpretation of stabilogram diffusion analysis

    NASA Technical Reports Server (NTRS)

    Peterka, R. J.

    2000-01-01

    Collins and De Luca [Collins JJ. De Luca CJ (1993) Exp Brain Res 95: 308-318] introduced a new method known as stabilogram diffusion analysis that provides a quantitative statistical measure of the apparently random variations of center-of-pressure (COP) trajectories recorded during quiet upright stance in humans. This analysis generates a stabilogram diffusion function (SDF) that summarizes the mean square COP displacement as a function of the time interval between COP comparisons. SDFs have a characteristic two-part form that suggests the presence of two different control regimes: a short-term open-loop control behavior and a longer-term closed-loop behavior. This paper demonstrates that a very simple closed-loop control model of upright stance can generate realistic SDFs. The model consists of an inverted pendulum body with torque applied at the ankle joint. This torque includes a random disturbance torque and a control torque. The control torque is a function of the deviation (error signal) between the desired upright body position and the actual body position, and is generated in proportion to the error signal, the derivative of the error signal, and the integral of the error signal [i.e. a proportional, integral and derivative (PID) neural controller]. The control torque is applied with a time delay representing conduction, processing, and muscle activation delays. Variations in the PID parameters and the time delay generate variations in SDFs that mimic real experimental SDFs. This model analysis allows one to interpret experimentally observed changes in SDFs in terms of variations in neural controller and time delay parameters rather than in terms of open-loop versus closed-loop behavior.

  13. The ionospheric eclipse factor method (IEFM) and its application to determining the ionospheric delay for GPS

    NASA Astrophysics Data System (ADS)

    Yuan, Y.; Tscherning, C. C.; Knudsen, P.; Xu, G.; Ou, J.

    2008-01-01

    A new method for modeling the ionospheric delay using global positioning system (GPS) data is proposed, called the ionospheric eclipse factor method (IEFM). It is based on establishing a concept referred to as the ionospheric eclipse factor (IEF) λ of the ionospheric pierce point (IPP) and the IEF’s influence factor (IFF) bar{λ}. The IEF can be used to make a relatively precise distinction between ionospheric daytime and nighttime, whereas the IFF is advantageous for describing the IEF’s variations with day, month, season and year, associated with seasonal variations of total electron content (TEC) of the ionosphere. By combining λ and bar{λ} with the local time t of IPP, the IEFM has the ability to precisely distinguish between ionospheric daytime and nighttime, as well as efficiently combine them during different seasons or months over a year at the IPP. The IEFM-based ionospheric delay estimates are validated by combining an absolute positioning mode with several ionospheric delay correction models or algorithms, using GPS data at an international Global Navigation Satellite System (GNSS) service (IGS) station (WTZR). Our results indicate that the IEFM may further improve ionospheric delay modeling using GPS data.

  14. Studies on Instabilities in Long-Baseline Two-Way Satellite Time and Frequency Transfer (TWSTFT) Including a Troposphere Delay Model

    DTIC Science & Technology

    2007-11-01

    TRANSFER ( TWSTFT ) INCLUDING A TROPOSPHERE DELAY MODEL D. Piester, A. Bauch Physikalisch-Technische Bundesanstalt (PTB) Bundesallee 100...Abstract Two-way satellite time and frequency transfer ( TWSTFT ) is one of the leading techniques for remote comparisons of atomic frequency standards...nanosecond level. These achievements are due to the fact that many delay variations of the transmitted signals cancel out in TWSTFT because of the

  15. FBG wavelength demodulation based on a radio frequency optical true time delay method.

    PubMed

    Wang, Jin; Zhu, Wanshan; Ma, Chenyuan; Xu, Tong

    2018-06-01

    A new fiber Bragg grating (FBG) wavelength shift demodulation method based on optical true time delay microwave phase detection is proposed. We used a microwave photonic link (MPL) to transport a radio frequency (RF) signal over a dispersion compensation fiber (DCF). The wavelength shift of the FBG will cause the time delay change of the optical carrier that propagates in an optical fiber with chromatic dispersion, which will result in the variation of the RF signal phase. A long DCF was adopted to enlarge the RF signal phase variation. An IQ mixer was used to measure the RF phase variation of the RF signal propagating in the MPL, and the wavelength shift of the FBG can be obtained by the measured RF signal phase variation. The experimental results showed that the wavelength shift measurement resolution is 2 pm when the group velocity dispersion of the DCF is 79.5 ps/nm and the frequency of the RF signal is 18 GHz. The demodulation time is as short as 0.1 ms. The measurement resolution can be improved simply by using a higher frequency of the RF signal and a longer DCF or larger chromatic dispersion value of the DCF.

  16. HIGH SPEED KERR CELL FRAMING CAMERA

    DOEpatents

    Goss, W.C.; Gilley, L.F.

    1964-01-01

    The present invention relates to a high speed camera utilizing a Kerr cell shutter and a novel optical delay system having no moving parts. The camera can selectively photograph at least 6 frames within 9 x 10/sup -8/ seconds during any such time interval of an occurring event. The invention utilizes particularly an optical system which views and transmits 6 images of an event to a multi-channeled optical delay relay system. The delay relay system has optical paths of successively increased length in whole multiples of the first channel optical path length, into which optical paths the 6 images are transmitted. The successively delayed images are accepted from the exit of the delay relay system by an optical image focusing means, which in turn directs the images into a Kerr cell shutter disposed to intercept the image paths. A camera is disposed to simultaneously view and record the 6 images during a single exposure of the Kerr cell shutter. (AEC)

  17. Extreme phenophase delays and their relationship with natural forcings in Beijing over the past 260 years.

    PubMed

    Liu, Yang; Zhang, Mingqing; Fang, Xiuqi

    2018-03-20

    By merging reconstructed phenological series from published articles and observations of China Phenology Observation Network (CPON), the first blooming date of Amygdalus davidiana (FBA) in Beijing between 1741 and 2000 is reconstructed. The Butterworth method is used to remove the multi-year variations for generating the phenological series of annual variations in the first blooming date of A. davidiana. The extreme delay years in the phenological series are identified using the percentage threshold method. The characteristics of the extreme delays and the correspondence of these events with natural forcings are analysed. The main results are as follows. In annual phenological series, the extreme delays appeared in single year as main feature, only A.D.1800-1801, 1816-1817 and 1983-1984 were the events of two consecutively extreme years. Approximately 85% of the extreme delays occurred during 1-2 years after the large volcanic eruptions (VEI ≥ 4) in the eastern rim or the western rim of the Pacific Ocean, as the same proportion of the extreme delays followed El Niño events. About 73% years of the extreme delays fall in the valleys of sunspot cycles or the Dalton minimum period in the year or the previous year. According to the certainty factor (CF), the large eruptions have the greatest influence to the extreme delays; sunspot activity is the second, and ENSO is the last one. The extreme phenological delayed year is most likely to occur after a large eruption, which particularly occurs during El Niño year and its previous several years were in the descending portion or valley of sunspot phase.

  18. Extreme phenophase delays and their relationship with natural forcings in Beijing over the past 260 years

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Zhang, Mingqing; Fang, Xiuqi

    2018-03-01

    By merging reconstructed phenological series from published articles and observations of China Phenology Observation Network (CPON), the first blooming date of Amygdalus davidiana (FBA) in Beijing between 1741 and 2000 is reconstructed. The Butterworth method is used to remove the multi-year variations for generating the phenological series of annual variations in the first blooming date of A. davidiana. The extreme delay years in the phenological series are identified using the percentage threshold method. The characteristics of the extreme delays and the correspondence of these events with natural forcings are analysed. The main results are as follows. In annual phenological series, the extreme delays appeared in single year as main feature, only A.D.1800-1801, 1816-1817 and 1983-1984 were the events of two consecutively extreme years. Approximately 85% of the extreme delays occurred during 1-2 years after the large volcanic eruptions (VEI ≥ 4) in the eastern rim or the western rim of the Pacific Ocean, as the same proportion of the extreme delays followed El Niño events. About 73% years of the extreme delays fall in the valleys of sunspot cycles or the Dalton minimum period in the year or the previous year. According to the certainty factor (CF), the large eruptions have the greatest influence to the extreme delays; sunspot activity is the second, and ENSO is the last one. The extreme phenological delayed year is most likely to occur after a large eruption, which particularly occurs during El Niño year and its previous several years were in the descending portion or valley of sunspot phase.

  19. Estimation of heritability, evolvability and genetic correlations of two pollen and pistil traits involved in a sexual conflict over timing of stigma receptivity in Collinsia heterophylla (Plantaginaceae).

    PubMed

    Madjidian, Josefin A; Andersson, Stefan; Lankinen, Asa

    2012-07-01

    Heritable genetic variation is crucial for selection to operate, yet there is a paucity of studies quantifying such variation in interactive male/female sexual traits, especially those of plants. Previous work on the annual plant Collinsia heterophylla, a mixed-mating species, suggests that delayed stigma receptivity is involved in a sexual conflict: pollen from certain donors fertilize ovules earlier than others at the expense of reduced maternal seed set and lower levels of pollen competition. Parent-offspring regressions and sib analyses were performed to test for heritable genetic variation and co-variation in male and female interactive traits related to the sexual conflict. SOME heritable variation and evolvability were found for the female trait (delayed stigma receptivity in presence of pollen), but no evidence was found for genetic variation in the male trait (ability to fertilize ovules early). The results further indicated a marginally significant correlation between a male's ability to fertilize early and early stigma receptivity in offspring. However, despite potential indirect selection of these traits, antagonistic co-evolution may not occur given the lack of heritability of the male trait. To our knowledge, this is the first study of a plant or any hermaphrodite that examines patterns of genetic correlation between two interactive sexual traits, and also the first to assess heritabilities of plant traits putatively involved in a sexual conflict. It is concluded that the ability to delay fertilization in presence of pollen can respond to selection, while the pollen trait has lower evolutionary potential.

  20. Induction of a Mitosis Delay and Cell Lysis by High-Level Secretion of Mouse α-Amylase from Saccharomyces cerevisiae

    PubMed Central

    Wang, Bi-Dar; Kuo, Tsong-Teh

    2001-01-01

    Some foreign proteins are produced in yeast in a cell cycle-dependent manner, but the cause of the cell cycle dependency is unknown. In this study, we found that Saccharomyces cerevisiae cells secreting high levels of mouse α-amylase have elongated buds and are delayed in cell cycle completion in mitosis. The delayed cell mitosis suggests that critical events during exit from mitosis might be disturbed. We found that the activities of PP2A (protein phosphatase 2A) and MPF (maturation-promoting factor) were reduced in α-amylase-oversecreting cells and that these cells showed a reduced level of assembly checkpoint protein Cdc55, compared to the accumulation in wild-type cells. MPF inactivation is due to inhibitory phosphorylation on Cdc28, as a cdc28 mutant which lacks an inhibitory phosphorylation site on Cdc28 prevents MPF inactivation and prevents the defective bud morphology induced by overproduction of α-amylase. Our data also suggest that high levels of α-amylase may downregulate PPH22, leading to cell lysis. In conclusion, overproduction of heterologous α-amylase in S. cerevisiae results in a negative regulation of PP2A, which causes mitotic delay and leads to cell lysis. PMID:11472949

  1. Sensitivity of Rabbit Ventricular Action Potential and Ca2+ Dynamics to Small Variations in Membrane Currents and Ion Diffusion Coefficients

    PubMed Central

    Lo, Yuan Hung; Peachey, Tom; Abramson, David; McCulloch, Andrew

    2013-01-01

    Little is known about how small variations in ionic currents and Ca2+ and Na+ diffusion coefficients impact action potential and Ca2+ dynamics in rabbit ventricular myocytes. We applied sensitivity analysis to quantify the sensitivity of Shannon et al. model (Biophys. J., 2004) to 5%–10% changes in currents conductance, channels distribution, and ion diffusion in rabbit ventricular cells. We found that action potential duration and Ca2+ peaks are highly sensitive to 10% increase in L-type Ca2+ current; moderately influenced by 10% increase in Na+-Ca2+ exchanger, Na+-K+ pump, rapid delayed and slow transient outward K+ currents, and Cl− background current; insensitive to 10% increases in all other ionic currents and sarcoplasmic reticulum Ca2+ fluxes. Cell electrical activity is strongly affected by 5% shift of L-type Ca2+ channels and Na+-Ca2+ exchanger in between junctional and submembrane spaces while Ca2+-activated Cl−-channel redistribution has the modest effect. Small changes in submembrane and cytosolic diffusion coefficients for Ca2+, but not in Na+ transfer, may alter notably myocyte contraction. Our studies highlight the need for more precise measurements and further extending and testing of the Shannon et al. model. Our results demonstrate usefulness of sensitivity analysis to identify specific knowledge gaps and controversies related to ventricular cell electrophysiology and Ca2+ signaling. PMID:24222910

  2. Geodesy by radio interferometry - Water vapor radiometry for estimation of the wet delay

    NASA Technical Reports Server (NTRS)

    Elgered, G.; Davis, J. L.; Herring, T. A.; Shapiro, I. I.

    1991-01-01

    An important source of error in VLBI estimates of baseline length is unmodeled variations of the refractivity of the neutral atmosphere along the propagation path of the radio signals. This paper presents and discusses the method of using data from a water vapor radiomete (WVR) to correct for the propagation delay caused by atmospheric water vapor, the major cause of these variations. Data from different WVRs are compared with estimated propagation delays obtained by Kalman filtering of the VLBI data themselves. The consequences of using either WVR data or Kalman filtering to correct for atmospheric propagation delay at the Onsala VLBI site are investigated by studying the repeatability of estimated baseline lengths from Onsala to several other sites. The repeatability obtained for baseline length estimates shows that the methods of water vapor radiometry and Kalman filtering offer comparable accuracies when applied to VLBI observations obtained in the climate of the Swedish west coast. For the most frequently measured baseline in this study, the use of WVR data yielded a 13 percent smaller weighted-root-mean-square (WRMS) scatter of the baseline length estimates compared to the use of a Kalman filter. It is also clear that the 'best' minimum elevationi angle for VLBI observations depends on the accuracy of the determinations of the total propagation delay to be used, since the error in this delay increases with increasing air mass.

  3. AGN Space Telescope and Optical Reverberation Mapping Project. IV. Velocity-Delay Mapping of Broad Emission Lines in NGC 5548

    NASA Astrophysics Data System (ADS)

    Horne, Keith D.; Agn Storm Team

    2015-01-01

    Two-dimensional velocity-delay maps of AGN broad emission line regions can be recovered by modelling observations of reverberating emission-line profiles on the assumption that the line profile variations are driven by changes in ionising radiation from a compact source near the black hole. The observable light travel time delay resolves spatial structure on iso-delay paraboloids, while the doppler shift resolves kinematic structure along the observer's line-of-sight. Velocity-delay maps will be presented and briefly discussed for the Lyman alpha, CIV and Hbeta line profiles based on the HST and ground-based spectrophotometric monitoring of NGC 5548 during the 2014 AGN STORM campaign.

  4. Modeling the Transformational Communications System Urban Land Mobile Satellite Channel

    DTIC Science & Technology

    2007-12-01

    interference of time - delayed signals). The “slow” variations are usually associated with specific shadowing events by foliage, terrain or buildings. The...by F. P. Fontan et al. [24].......................11 Figure 4. Short, medium and long-term variation of signal strength with time . Long- term...long-term variation of signal strength with time . Long- term (“very slow”) variation is modeled by state transitions shown in Figure 3. C

  5. Staphylococcus aureus-Induced G2/M Phase Transition Delay in Host Epithelial Cells Increases Bacterial Infective Efficiency

    PubMed Central

    Almeida, Sintia; Legembre, Patrick; Edmond, Valérie; Azevedo, Vasco; Miyoshi, Anderson; Even, Sergine; Taieb, Frédéric; Arlot-Bonnemains, Yannick; Le Loir, Yves; Berkova, Nadia

    2013-01-01

    Staphylococcus aureus is a highly versatile, opportunistic pathogen and the etiological agent of a wide range of infections in humans and warm-blooded animals. The epithelial surface is its principal site of colonization and infection. In this work, we investigated the cytopathic effect of S. aureus strains from human and animal origins and their ability to affect the host cell cycle in human HeLa and bovine MAC-T epithelial cell lines. S. aureus invasion slowed down cell proliferation and induced a cytopathic effect, resulting in the enlargement of host cells. A dramatic decrease in the number of mitotic cells was observed in the infected cultures. Flow cytometry analysis revealed an S. aureus-induced delay in the G2/M phase transition in synchronous HeLa cells. This delay required the presence of live S. aureus since the addition of the heat-killed bacteria did not alter the cell cycle. The results of Western blot experiments showed that the G2/M transition delay was associated with the accumulation of inactive cyclin-dependent kinase Cdk1, a key inducer of mitosis entry, and with the accumulation of unphosphorylated histone H3, which was correlated with a reduction of the mitotic cell number. Analysis of S. aureus proliferation in asynchronous, G1- and G2-phase-enriched HeLa cells showed that the G2 phase was preferential for bacterial infective efficiency, suggesting that the G2 phase delay may be used by S. aureus for propagation within the host. Taken together, our results divulge the potential of S. aureus in the subversion of key cellular processes such as cell cycle progression, and shed light on the biological significance of S. aureus-induced host cell cycle alteration. PMID:23717407

  6. Minimally Invasive Radiation Biodosimetry and Evaluation of Organ Responses

    DTIC Science & Technology

    2016-10-01

    radiation exposure, potentially leading to Acute Radiation Syndromes (ARS) and Delayed Effects of Acute ...underlying conditions and inherent variations. 2. KEYWORDS Radiation Biodosimetry, Radiation Biomarkers, microRNA, Acute Radiation Syndromes ... syndromes and delayed effects of acute radiation exposure. We expect to identify the circulating miRNA biomarkers as early predictors of late effects

  7. Tsunami Speed Variations in Density-stratified Compressible Global Oceans

    NASA Astrophysics Data System (ADS)

    Watada, S.

    2013-12-01

    Recent tsunami observations in the deep ocean have accumulated unequivocal evidence that tsunami traveltime delays compared with the linear long-wave tsunami simulations occur during tsunami propagation in the deep ocean. The delay is up to 2% of the tsunami traveltime. Watada et al. [2013] investigated the cause of the delay using the normal mode theory of tsunamis and attributed the delay to the compressibility of seawater, the elasticity of the solid earth, and the gravitational potential change associated with mass motion during the passage of tsunamis. Tsunami speed variations in the deep ocean caused by seawater density stratification is investigated using a newly developed propagator matrix method that is applicable to seawater with depth-variable sound speeds and density gradients. For a 4-km deep ocean, the total tsunami speed reduction is 0.45% compared with incompressible homogeneous seawater; two thirds of the reduction is due to elastic energy stored in the water and one third is due to water density stratification mainly by hydrostatic compression. Tsunami speeds are computed for global ocean density and sound speed profiles and characteristic structures are discussed. Tsunami speed reductions are proportional to ocean depth with small variations, except for in warm Mediterranean seas. The impacts of seawater compressibility and the elasticity effect of the solid earth on tsunami traveltime should be included for precise modeling of trans-oceanic tsunamis. Data locations where a vertical ocean profile deeper than 2500 m is available in World Ocean Atlas 2009. The dark gray area indicates the Pacific Ocean defined in WOA09. a) Tsunami speed variations. Red, gray and black bars represent global, Pacific, and Mediterranean Sea, respectively. b) Regression lines of the tsunami velocity reduction for all oceans. c)Vertical ocean profiles at grid points indicated by the stars in Figure 1.

  8. Genetic variation in melatonin pathway enzymes in children with autism spectrum disorder and comorbid sleep onset delay.

    PubMed

    Veatch, Olivia J; Pendergast, Julie S; Allen, Melissa J; Leu, Roberta M; Johnson, Carl Hirschie; Elsea, Sarah H; Malow, Beth A

    2015-01-01

    Sleep disruption is common in individuals with autism spectrum disorder (ASD). Genes whose products regulate endogenous melatonin modify sleep patterns and have been implicated in ASD. Genetic factors likely contribute to comorbid expression of sleep disorders in ASD. We studied a clinically unique ASD subgroup, consisting solely of children with comorbid expression of sleep onset delay. We evaluated variation in two melatonin pathway genes, acetylserotonin O-methyltransferase (ASMT) and cytochrome P450 1A2 (CYP1A2). We observed higher frequencies than currently reported (p < 0.04) for variants evidenced to decrease ASMT expression and related to decreased CYP1A2 enzyme activity (p ≤ 0.0007). We detected a relationship between genotypes in ASMT and CYP1A2 (r(2) = 0.63). Our results indicate that expression of sleep onset delay relates to melatonin pathway genes.

  9. Representative Sinusoids for Hepatic Four-Scale Pharmacokinetics Simulations

    PubMed Central

    Schwen, Lars Ole; Schenk, Arne; Kreutz, Clemens; Timmer, Jens; Bartolomé Rodríguez, María Matilde; Kuepfer, Lars; Preusser, Tobias

    2015-01-01

    The mammalian liver plays a key role for metabolism and detoxification of xenobiotics in the body. The corresponding biochemical processes are typically subject to spatial variations at different length scales. Zonal enzyme expression along sinusoids leads to zonated metabolization already in the healthy state. Pathological states of the liver may involve liver cells affected in a zonated manner or heterogeneously across the whole organ. This spatial heterogeneity, however, cannot be described by most computational models which usually consider the liver as a homogeneous, well-stirred organ. The goal of this article is to present a methodology to extend whole-body pharmacokinetics models by a detailed liver model, combining different modeling approaches from the literature. This approach results in an integrated four-scale model, from single cells via sinusoids and the organ to the whole organism, capable of mechanistically representing metabolization inhomogeneity in livers at different spatial scales. Moreover, the model shows circulatory mixing effects due to a delayed recirculation through the surrounding organism. To show that this approach is generally applicable for different physiological processes, we show three applications as proofs of concept, covering a range of species, compounds, and diseased states: clearance of midazolam in steatotic human livers, clearance of caffeine in mouse livers regenerating from necrosis, and a parameter study on the impact of different cell entities on insulin uptake in mouse livers. The examples illustrate how variations only discernible at the local scale influence substance distribution in the plasma at the whole-body level. In particular, our results show that simultaneously considering variations at all relevant spatial scales may be necessary to understand their impact on observations at the organism scale. PMID:26222615

  10. Ground-Based GPS Sensing of Azimuthal Variations in Precipitable Water Vapor

    NASA Technical Reports Server (NTRS)

    Kroger, P. M.; Bar-Sever, Y. E.

    1997-01-01

    Current models for troposphere delay employed by GPS software packages map the total zenith delay to the line-of-sight delay of the individual satellite-receiver link under the assumption of azimuthal homogeneity. This could be a poor approximation for many sites, in particular, those located at an ocean front or next to a mountain range. We have modified the GIPSY-OASIS II software package to include a simple non-symmetric mapping function (MacMillan, 1995) which introduces two new parameters.

  11. Mechanisms mediating Nitroglycerin-induced Delayed Onset Hyperalgesia in the Rat

    PubMed Central

    Ferrari, Luiz F.; Levine, Jon D.; Green, Paul G.

    2016-01-01

    Nitroglycerin (glycerol trinitrate, GTN) induces headache in migraineurs, an effect that has been used both diagnostically and in the study of the pathophysiology of this neurovascular pain syndrome. An important feature of this headache is a delay from the administration of GTN to headache onset that, because of GTN’s very rapid metabolism, cannot be due to its pharmacokinetic profile. It has recently been suggested that activation of perivascular mast cells, which has been implicated in the pathophysiology of migraine, may contribute to this delay. We reported that hyperalgesia induced by intradermal GTN has a delay to onset of ~30 min in male and ~45 min in female rats. This hyperalgesia was greater in females, was prevented by pretreatment with the anti-migraine drug, sumatriptan, as well as by chronic pretreatment with the mast cell degranulator, compound 48/80. The acute administration of GTN and compound 48/80 both induced hyperalgesia that was prevented by pretreatment with octoxynol-9, which attenuates endothelial function, suggesting that GTN and mast cell-mediated hyperalgesia are endothelial cell-dependent. Furthermore, A-317491, a P2X3 antagonist, which inhibits endothelial cell-dependent hyperalgesia, also prevents GTN and mast cell-mediated hyperalgesia. We conclude that delayed onset mechanical hyperalgesia induced by GTN is mediated by activation of mast cells, which in turn release mediators that stimulate endothelial cells to release ATP, to act on P2X3, a ligand-gated ion channel, in perivascular nociceptors. A role of the mast and endothelial cell in GTN-induced hyperalgesia suggest potential novel risk factors and targets for the treatment of migraine. PMID:26779834

  12. Magma flow between summit and Pu`u `Ō`ō at K¯lauea Volcano, Hawai`i

    NASA Astrophysics Data System (ADS)

    Montagna, C. P.; Gonnermann, H. M.

    2013-07-01

    Volcanic eruptions are often accompanied by spatiotemporal migration of ground deformation, a consequence of pressure changes within magma reservoirs and pathways. We modeled the propagation of pressure variations through the east rift zone (ERZ) of K¯lauea Volcano, Hawai`i, caused by magma withdrawal during the early eruptive episodes (1983-1985) of the ongoing Pu`u `Ō`ō-Kupaianaha eruption. Eruptive activity at the Pu`u `Ō`ō vent was typically accompanied by abrupt deflation that lasted for several hours and was followed by a sudden onset of gradual inflation once the eruptive episode had ended. Similar patterns of deflation and inflation were recorded at K¯lauea's summit, approximately 15 km to the northwest, albeit with time delays of hours. These delay times can be reproduced by modeling the spatiotemporal changes in magma pressure and flow rate within an elastic-walled dike that traverses K¯lauea's ERZ. Key parameters that affect the behavior of the magma-dike system are the dike dimensions, the elasticity of the wall rock, the magma viscosity, and to a lesser degree the magnitude and duration of the pressure variations themselves. Combinations of these parameters define a transport efficiency and a pressure diffusivity, which vary somewhat from episode to episode, resulting in variations in delay times. The observed variations in transport efficiency are most easily explained by small, localized changes to the geometry of the magma pathway.

  13. Visualizing red blood cell sickling and the effects of inhibition of sphingosine kinase 1 using soft X-ray tomography

    DOE PAGES

    Darrow, Michele C.; Zhang, Yujin; Cinquin, Bertrand P.; ...

    2016-08-09

    Sickle cell disease is a destructive genetic disorder characterized by the formation of fibrils of deoxygenated hemoglobin, leading to the red blood cell (RBC) morphology changes that underlie the clinical manifestations of this disease. Here, using cryogenic soft X-ray tomography (SXT), we characterized the morphology of sickled RBCs in terms of volume and the number of protrusions per cell. We were able to identify statistically a relationship between the number of protrusions and the volume of the cell, which is known to correlate to the severity of sickling. This structural polymorphism allows for the classification of the stages of themore » sickling process. Recent studies have shown that elevated sphingosine kinase 1 (Sphk1)-mediated sphingosine 1-phosphate production contributes to sickling. Here, we further demonstrate that compound 5C, an inhibitor of Sphk1, has anti-sickling properties. Additionally, the variation in cellular morphology upon treatment suggests that this drug acts to delay the sickling process. SXT is an effective tool that can be used to identify the morphology of the sickling process and assess the effectiveness of potential therapeutics.« less

  14. Visualizing red blood cell sickling and the effects of inhibition of sphingosine kinase 1 using soft X-ray tomography

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

    Darrow, Michele C.; Zhang, Yujin; Cinquin, Bertrand P.

    Sickle cell disease is a destructive genetic disorder characterized by the formation of fibrils of deoxygenated hemoglobin, leading to the red blood cell (RBC) morphology changes that underlie the clinical manifestations of this disease. Here, using cryogenic soft X-ray tomography (SXT), we characterized the morphology of sickled RBCs in terms of volume and the number of protrusions per cell. We were able to identify statistically a relationship between the number of protrusions and the volume of the cell, which is known to correlate to the severity of sickling. This structural polymorphism allows for the classification of the stages of themore » sickling process. Recent studies have shown that elevated sphingosine kinase 1 (Sphk1)-mediated sphingosine 1-phosphate production contributes to sickling. Here, we further demonstrate that compound 5C, an inhibitor of Sphk1, has anti-sickling properties. Additionally, the variation in cellular morphology upon treatment suggests that this drug acts to delay the sickling process. SXT is an effective tool that can be used to identify the morphology of the sickling process and assess the effectiveness of potential therapeutics.« less

  15. Transmission of magmatic pressure changes at Kilauea volcano

    NASA Astrophysics Data System (ADS)

    Montagna, C. P.; Gonnermann, H. M.

    2012-12-01

    Volcanic eruptions are often accompanied by spatiotemporal migration of ground deformation, a consequence of pressure changes within magma reservoirs and pathways. We have modeled the propagation of such pressure variations, caused by eruptive magma withdrawal during the early eruptive episodes of the ongoing Pu`u `O`o-Kupaianaha eruption of Kilauea volcano. Tilt measurements show that the onset of eruptive episodes at Pu`u `O`o was typically accompanied by abrupt deflation and followed by a sudden onset of gradual re-inflation, once the eruptive episode ended. Tilt of Kilauea's summit underwent similar patterns of deflation and inflation, albeit with a time delay of several hours during most episodes. The observed delay times can be reproduced by a numerical model of pressure variations within an elastic-walled dike that connects Kilauea's summit to its east rift zone. As pressure changes travel through the dike, the interplay between elastic response of the dike wall and viscous resistance of the fluid determines the delay time. An example of the ability of the model to reproduce observed tilt data is presented in Figure 1, which shows measured tilt at Pu`u `O`o during episode 18, together with measured and modeled tilt at Kilauea's summit. Magma withdrawal beneath Pu`u `O`o causes a decrease in pressure and deflation. This pressure change is estimated from observed ground deformation, and it constitutes the time-dependent model boundary condition at Pu`u `O`o, which propagates to Kilauea's summit. The resultant increase in magma flux causes deflation of Kilauea's Halema`uma`u magma reservoir and the change and time delay of tilt are reproduced by the model. The time delay depends on elasticity of the wall rock, dike dimensions, magma viscosity, as well as magnitude and duration of the pressure variations themselves. In addition, these parameters also affect the attenuation of the amplitude of the pressure variation, as it travels between Puu Oo and summit. Pressure changes propagate noticeably faster (slower) in a slightly wider (narrower) dike, as a consequence of smaller (larger) viscous dissipation. Time delays and amplitude of deflation-inflation events at Kilauea have the potential to provide information on effective transport properties of magmatic pathways and changes thereof over time.bserved and modeled change in normalized tilt at Pu`u `O`o and summit for episode 18 of the Pu`u `O`o eruption

  16. The delayed luminescence spectroscopy as tool to investigate the cytotoxic effect on human cancer cells of drug-loaded nanostructured lipid carrier

    NASA Astrophysics Data System (ADS)

    Grasso, R.; Gulino, M.; Scordino, A.; Musumeci, F.; Campisi, A.; Bonfanti, R.; Carbone, C.; Puglisi, G.

    2016-05-01

    The first results concerning the possibility to use Delayed Luminescence spectroscopy to evaluate the in vitro induction of cytotoxic effects on human glioblastoma cells of nanostructured lipid carrier and drug-loaded nanostructured lipid carrier are showed in this contribution. We tested the effects of nanostructured lipid carrier, ferulic acid and ferulic acidloaded nanostructured lipid carrier on U-87MG cell line. The study seems to confirm the ability of Delayed Luminescence to be sensible indicator of alterations induced on functionality of the mitochondrial respiratory chain complex I in U-87MG cancer cells when treated with nanostructured lipid carriers.

  17. Sirtuin 7 promotes cellular survival following genomic stress by attenuation of DNA damage, SAPK activation and p53 response

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

    Kiran, Shashi; Oddi, Vineesha; Ramakrishna, Gayatri, E-mail: gayatrirama1@gmail.com

    2015-02-01

    Maintaining the genomic integrity is a constant challenge in proliferating cells. Amongst various proteins involved in this process, Sirtuins play a key role in DNA damage repair mechanisms in yeast as well as mammals. In the present work we report the role of one of the least explored Sirtuin viz., SIRT7, under conditions of genomic stress when treated with doxorubicin. Knockdown of SIRT7 sensitized osteosarcoma (U2OS) cells to DNA damage induced cell death by doxorubicin. SIRT7 overexpression in NIH3T3 delayed cell cycle progression by causing delay in G1 to S transition. SIRT7 overexpressing cells when treated with low dose ofmore » doxorubicin (0.25 µM) showed delayed onset of senescence, lesser accumulation of DNA damage marker γH2AX and lowered levels of growth arrest markers viz., p53 and p21 when compared to doxorubicin treated control GFP expressing cells. Resistance to DNA damage following SIRT7 overexpression was also evident by EdU incorporation studies where cellular growth arrest was significantly delayed. When treated with higher dose of doxorubicin (>1 µM), SIRT7 conferred resistance to apoptosis by attenuating stress activated kinases (SAPK viz., p38 and JNK) and p53 response thereby shifting the cellular fate towards senescence. Interestingly, relocalization of SIRT7 from nucleolus to nucleoplasm together with its co-localization with SAPK was an important feature associated with DNA damage. SIRT7 mediated resistance to doxorubicin induced apoptosis and senescence was lost when p53 level was restored by nutlin treatment. Overall, we propose SIRT7 attenuates DNA damage, SAPK activation and p53 response thereby promoting cellular survival under conditions of genomic stress. - Highlights: • Knockdown of SIRT7 sensitized cells to DNA damage induced apoptosis. • SIRT7 delayed onset of premature senescence by attenuating DNA damage response. • Overexpression of SIRT7 delayed cell cycle progression by delaying G1/S transition. • Upon DNA damage SIRT7 attenuated p38/JNK activation and also p53 response. • Overall, SIRT7 promoted cellular survival in conditions of genomic stress.« less

  18. Delayed blastocyst formation or an extra day culture increases apoptosis in pig blastocysts.

    PubMed

    Lin, Tao; Lee, Jae Eun; Oqani, Reza K; Kim, So Yeon; Cho, Eun Seok; Jeong, Yong Dae; Baek, Jun Jong; Jin, Dong Il

    2017-10-01

    In the present study, the timing was examined of blastocyst collection/formation or of how the duration of post-blastulation culture affected the quality and developmental competence of in vitro-produced pig parthenogenetic embryos. The earliest apoptotic signals were observed at the morula stage while the earliest cytoplasmic fragmentation was observed before the 4- to 8-cell stage of embryo development. Nuclear condensation was detected in morulae and blastocysts, but not all condensed nuclei were positive for the apoptotic signal (TUNEL staining). The mean blastocyst diameter increased with delayed blastocyst collection or extended post-blastulation culture, but decreased with delayed blastocyst formation. Delayed blastocyst collection/formation or an additional day of post-blastulation culture increased the frequencies of apoptosis, condensed nuclei, and low quality blastocysts (those showing a nuclear destruction that negated counting of the nuclei); increased the expression of the pro-apoptotic BAX gene; and reduced the ratio of ICM (inner cell mass) cells to TE (trophectoderm) cells. In addition, delayed blastocyst formation decreased POU5F1 gene expression. These results suggest that a delay in blastocyst collection/formation or an additional day of culture could increase the incidence of apoptosis, decrease the ICM:TE cell ratio, and influence the gene expression and diameter of blastocysts derived from in vitro-produced pig embryos. These findings provide a useful reference for improving the quality of in vitro-produced embryos. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Lithium Cell Reactions.

    DTIC Science & Technology

    1983-12-01

    Li/SOCL, cells in- dicate that up to PPM water can be added to the electrolyte without detrimental effects. At water levels ab 100 PPM voltage delay...48 2.3 THE EFFECT OF WATER AND HYDROLYSIS PRODUCTS ON PERFORMANCE ........ 51 2.4 THE...Li/SOCI, Cells with 0, 20 and 100 PPM Water added to the Electrolyte.* ..................................................... 52 51. Voltage Delay for

  20. Urocortin2 prolongs action potential duration and modulates potassium currents in guinea pig myocytes and HEK293 cells.

    PubMed

    Yang, Li-Zhen; Zhu, Yi-Chun

    2015-07-05

    We previously reported that activation of corticotropin releasing factor receptor type 2 by urocortin2 up-regulates both L-type Ca(2+) channels and intracellular Ca(2+) concentration in ventricular myocytes and plays an important role in cardiac contractility and arrhythmogenesis. This study goal was to further test the hypothesis that urocortin2 may modulate action potentials as well as rapidly and slowly activating delayed rectifier potassium currents. With whole cell patch-clamp techniques, action potentials and slowly activating delayed rectifier potassium currents were recorded in isolated guinea pig ventricular myocytes, respectively. And rapidly activating delayed rectifier potassium currents were tested in hERG-HEK293 cells. Urocortin2 produced a time- and concentration-dependent prolongation of action potential duration. The EC50 values of action potential duration and action potential duration at 90% of repolarization were 14.73 and 24.3nM respectively. The prolongation of action potential duration of urocortin2 was almost completely or partly abolished by H-89 (protein kinase A inhibitor) or KB-R7943 (Na(+)/Ca(2+) exchange inhibitor) pretreatment respectively. And urocortin2 caused reduction of rapidly activating delayed rectifier potassium currents in hERG-HEK293 cells. In addition, urocortin2 slowed the rate of slowly activating delayed rectifier potassium channel activation, and rightward shifted the threshold of slowly activating delayed rectifier potassium currents to more positive potentials. Urocortin2 prolonged action potential duration via activation of protein kinase A and Na(+)/ Ca(2+) exchange in isolated guinea pig ventricular myocytes in a time- and concentration- dependent manner. In hERG-HEK293 cells, urocortin2 reduced rapidly activating delayed rectifier potassium current density which may contribute to action potential duration prolongation. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. The influence of procedure delay on resource use: a national study of patients with open tibial fracture.

    PubMed

    Sears, Erika Davis; Burke, James F; Davis, Matthew M; Chung, Kevin C

    2013-03-01

    The purpose of this study was to (1) understand national variation in delay of emergency procedures in patients with open tibial fracture at the hospital level and (2) compare length of stay and cost in patients cared for at the best- and worst-performing hospitals for delay. The authors retrospectively analyzed the 2003 to 2009 Nationwide Inpatient Sample. Adult patients with open tibial fracture were included. Hospital probability of delay in performing emergency procedures beyond the day of admission was calculated. Multilevel linear regression random-effects models were created to evaluate the relationship between the treating hospital's tendency for delay (in quartiles) and the log-transformed outcomes of length of stay and cost. The final sample included 7029 patients from 332 hospitals. Patients treated at hospitals in the fourth (worst) quartile for delay were estimated to have 12 percent (95 percent CI, 2 to 21 percent) higher cost compared with patients treated at hospitals in the first quartile. In addition, patients treated at hospitals in the fourth quartile had an estimated 11 percent (95 percent CI, 4 to 17 percent) longer length of stay compared with patients treated at hospitals in the first quartile. Patients with open tibial fracture treated at hospitals with more timely initiation of surgical care had lower cost and shorter length of stay than patients treated at hospitals with less timely initiation of care. Policies directed toward mitigating variation in care may reduce unnecessary waste.

  2. QoS mapping algorithm for ETE QoS provisioning

    NASA Astrophysics Data System (ADS)

    Wu, Jian J.; Foster, Gerry

    2002-08-01

    End-to-End (ETE) Quality of Service (QoS) is critical for next generation wireless multimedia communication systems. To meet the ETE QoS requirements, Universal Mobile Telecommunication System (UMTS) requires not only meeting the 3GPP QoS requirements [1-2] but also mapping external network QoS classes to UMTS QoS classes. There are four Quality of Services (QoS) classes in UMTS; they are Conversational, Streaming, Interactive and Background. There are eight QoS classes for LAN in IEEE 802.1 (one reserved). ATM has four QoS categories. They are Constant Bit Rate (CBR) - highest priority, short queue for strict Cell Delay Variation (CDV), Variable Bit Rate (VBR) - second highest priority, short queues for real time, longer queues for non-real time, Guaranteed Frame Rate (GFR)/ Unspecified Bit Rate (UBR) with Minimum Desired Cell Rate (MDCR) - intermediate priority, dependent on service provider UBR/ Available Bit Rate (ABR) - lowest priority, long queues, large delay variation. DiffServ (DS) has six-bit DS codepoint (DSCP) available to determine the datagram's priority relative to other datagrams and therefore, up to 64 QoS classes are available from the IPv4 and IPv6 DSCP. Different organisations have tried to solve the QoS issues from their own perspective. However, none of them has a full picture for end-to-end QoS classes and how to map them among all QoS classes. Therefore, a universal QoS needs to be created and a new set of QoS classes to enable end-to-end (ETE) QoS provisioning is required. In this paper, a new set of ETE QoS classes is proposed and a mappings algorithm for different QoS classes that are proposed by different organisations is given. With our proposal, ETE QoS mapping and control can be implemented.

  3. Dynamics of human T-cell lymphotropic virus I (HTLV-I) infection of CD4+ T-cells.

    PubMed

    Katri, Patricia; Ruan, Shigui

    2004-11-01

    Stilianakis and Seydel (Bull. Math. Biol., 1999) proposed an ODE model that describes the T-cell dynamics of human T-cell lymphotropic virus I (HTLV-I) infection and the development of adult T-cell leukemia (ATL). Their model consists of four components: uninfected healthy CD4+ T-cells, latently infected CD4+ T-cells, actively infected CD4+ T-cells, and ATL cells. Mathematical analysis that completely determines the global dynamics of this model has been done by Wang et al. (Math. Biosci., 2002). In this note, we first modify the parameters of the model to distinguish between contact and infectivity rates. Then we introduce a discrete time delay to the model to describe the time between emission of contagious particles by active CD4+ T-cells and infection of pure cells. Using the results in Culshaw and Ruan (Math. Biosci., 2000) in the analysis of time delay with respect to cell-free viral spread of HIV, we study the effect of time delay on the stability of the endemically infected equilibrium. Numerical simulations are presented to illustrate the results.

  4. Teleseismic P-wave Delay Time Tomography of the southern Superior Province and Midcontinent Rift System (MRS) Region

    NASA Astrophysics Data System (ADS)

    Bollmann, T. A.; van der Lee, S.; Frederiksen, A. W.; Wolin, E.; Aleqabi, G. I.; Revenaugh, J.; Wiens, D. A.; Darbyshire, F. A.

    2014-12-01

    The Superior Province Rifting Earthscope Experiment (SPREE) and the northern midwest footprint of USArray's Transportable Array recorded continuous ground motion for a period of 2.5 years. From around 400 M>5.5 teleseismic earthquakes recorded at 337 stations, we measured body wave delay times for 255 of these earthquakes. The P wave delays are accumulated over more than 45 thousand wave paths with turning points in the lower mantle. We combine these delay times with a similar number delay times used in previous tomographic studies of the study region. The latter delay times stem from fewer stations, including Polaris and CNSN stations, and nearly a thousand earthquakes. We combine these two sets of delay times to image the three-dimensional distribution of seismic velocity variations beneath the southern Superior Province and surrounding provinces. This combined data coverage is illustrated in the accompanying figure for a total number of 447 stations . The coverage and the combined delays form the best configuration yet to image the three-dimensional distribution of seismic P and S-wave velocity variations beneath the southern Superior and surrounding provinces. Closely spaced stations (~12 km) along and across the MRS provide higher resolving power for lithospheric structure beneath the rift system. Conforming to expectations that the entire region is underlain by thick, cool lithosphere, a mean delay of -.55 +/- .54 s. This is very similar to the mean delays -.6s +/- .37s measured for this region before 2012. Event corrections range from -.2 +/-.54 s and correlate with tectonics for 80% of the earthquakes. An inversion of these nearly one hundred thousand P and around thirty thousand S-wave delay times for high-resolution P and S-wave velocity structure, respectively, does not show structures that are obviously related to the crustal signature of the MRS. None of structures imaged, align with or have a similar shape to the high Mid-continent Gravity Anomaly (MGA). However, a low-velocity structure is imaged in the lithosphere just east of the MGA.

  5. Mechanisms mediating nitroglycerin-induced delayed-onset hyperalgesia in the rat.

    PubMed

    Ferrari, L F; Levine, J D; Green, P G

    2016-03-11

    Nitroglycerin (glycerol trinitrate, GTN) induces headache in migraineurs, an effect that has been used both diagnostically and in the study of the pathophysiology of this neurovascular pain syndrome. An important feature of this headache is a delay from the administration of GTN to headache onset that, because of GTN's very rapid metabolism, cannot be due to its pharmacokinetic profile. It has recently been suggested that activation of perivascular mast cells, which has been implicated in the pathophysiology of migraine, may contribute to this delay. We reported that hyperalgesia induced by intradermal GTN has a delay to onset of ∼ 30 min in male and ∼ 45 min in female rats. This hyperalgesia was greater in females, was prevented by pretreatment with the anti-migraine drug, sumatriptan, as well as by chronic pretreatment with the mast cell degranulator, compound 48/80. The acute administration of GTN and compound 48/80 both induced hyperalgesia that was prevented by pretreatment with octoxynol-9, which attenuates endothelial function, suggesting that GTN and mast cell-mediated hyperalgesia are endothelial cell-dependent. Furthermore, A-317491, a P2X3 antagonist, which inhibits endothelial cell-dependent hyperalgesia, also prevents GTN and mast cell-mediated hyperalgesia. We conclude that delayed-onset mechanical hyperalgesia induced by GTN is mediated by activation of mast cells, which in turn release mediators that stimulate endothelial cells to release ATP, to act on P2X3, a ligand-gated ion channel, in perivascular nociceptors. A role of the mast and endothelial cell in GTN-induced hyperalgesia suggests potential novel risk factors and targets for the treatment of migraine. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Discovery of stimulation-responsive immune enhancers with CRISPR activation

    PubMed Central

    Simeonov, Dimitre R.; Gowen, Benjamin G.; Boontanrart, Mandy; Roth, Theodore L.; Gagnon, John D.; Mumbach, Maxwell R.; Satpathy, Ansuman T.; Lee, Youjin; Bray, Nicolas L.; Chan, Alice Y.; Lituiev, Dmytro S.; Nguyen, Michelle L.; Gate, Rachel E.; Subramaniam, Meena; Li, Zhongmei; Woo, Jonathan M.; Mitros, Therese; Ray, Graham J.; Curie, Gemma L.; Naddaf, Nicki; Chu, Julia S.; Ma, Hong; Boyer, Eric; Van Gool, Frederic; Huang, Hailiang; Liu, Ruize; Tobin, Victoria R.; Schumann, Kathrin; Daly, Mark J.; Farh, Kyle K; Ansel, K. Mark; Ye, Chun J.; Greenleaf, William J.; Anderson, Mark S.; Bluestone, Jeffrey A.; Chang, Howard Y.; Corn, Jacob E.; Marson, Alexander

    2017-01-01

    The majority of genetic variants associated with common human diseases map to enhancers, non-coding elements that shape cell-type-specific transcriptional programs and responses to extracellular cues1–3. Systematic mapping of functional enhancers and their biological contexts is required to understand the mechanisms by which variation in non-coding genetic sequences contributes to disease. Functional enhancers can be mapped by genomic sequence disruption4–6, but this approach is limited to the subset of enhancers that are necessary in the particular cellular context being studied. We hypothesized that recruitment of a strong transcriptional activator to an enhancer would be sufficient to drive target gene expression, even if that enhancer was not currently active in the assayed cells. Here we describe a discovery platform that can identify stimulus-responsive enhancers for a target gene independent of stimulus exposure. We used tiled CRISPR activation (CRISPRa)7 to synthetically recruit a transcriptional activator to sites across large genomic regions (more than 100 kilobases) surrounding two key autoimmunity risk loci, CD69 and IL2RA. We identified several CRISPRa-responsive elements with chromatin features of stimulus-responsive enhancers, including an IL2RA enhancer that harbours an autoimmunity risk variant. Using engineered mouse models, we found that sequence perturbation of the disease-associated Il2ra enhancer did not entirely block Il2ra expression, but rather delayed the timing of gene activation in response to specific extracellular signals. Enhancer deletion skewed polarization of naive T cells towards a pro-inflammatory T helper (TH17) cell state and away from a regulatory T cell state. This integrated approach identifies functional enhancers and reveals how non-coding variation associated with human immune dysfunction alters context-specific gene programs. PMID:28854172

  7. Discovery of stimulation-responsive immune enhancers with CRISPR activation.

    PubMed

    Simeonov, Dimitre R; Gowen, Benjamin G; Boontanrart, Mandy; Roth, Theodore L; Gagnon, John D; Mumbach, Maxwell R; Satpathy, Ansuman T; Lee, Youjin; Bray, Nicolas L; Chan, Alice Y; Lituiev, Dmytro S; Nguyen, Michelle L; Gate, Rachel E; Subramaniam, Meena; Li, Zhongmei; Woo, Jonathan M; Mitros, Therese; Ray, Graham J; Curie, Gemma L; Naddaf, Nicki; Chu, Julia S; Ma, Hong; Boyer, Eric; Van Gool, Frederic; Huang, Hailiang; Liu, Ruize; Tobin, Victoria R; Schumann, Kathrin; Daly, Mark J; Farh, Kyle K; Ansel, K Mark; Ye, Chun J; Greenleaf, William J; Anderson, Mark S; Bluestone, Jeffrey A; Chang, Howard Y; Corn, Jacob E; Marson, Alexander

    2017-09-07

    The majority of genetic variants associated with common human diseases map to enhancers, non-coding elements that shape cell-type-specific transcriptional programs and responses to extracellular cues. Systematic mapping of functional enhancers and their biological contexts is required to understand the mechanisms by which variation in non-coding genetic sequences contributes to disease. Functional enhancers can be mapped by genomic sequence disruption, but this approach is limited to the subset of enhancers that are necessary in the particular cellular context being studied. We hypothesized that recruitment of a strong transcriptional activator to an enhancer would be sufficient to drive target gene expression, even if that enhancer was not currently active in the assayed cells. Here we describe a discovery platform that can identify stimulus-responsive enhancers for a target gene independent of stimulus exposure. We used tiled CRISPR activation (CRISPRa) to synthetically recruit a transcriptional activator to sites across large genomic regions (more than 100 kilobases) surrounding two key autoimmunity risk loci, CD69 and IL2RA. We identified several CRISPRa-responsive elements with chromatin features of stimulus-responsive enhancers, including an IL2RA enhancer that harbours an autoimmunity risk variant. Using engineered mouse models, we found that sequence perturbation of the disease-associated Il2ra enhancer did not entirely block Il2ra expression, but rather delayed the timing of gene activation in response to specific extracellular signals. Enhancer deletion skewed polarization of naive T cells towards a pro-inflammatory T helper (T H 17) cell state and away from a regulatory T cell state. This integrated approach identifies functional enhancers and reveals how non-coding variation associated with human immune dysfunction alters context-specific gene programs.

  8. Discovery of stimulation-responsive immune enhancers with CRISPR activation

    NASA Astrophysics Data System (ADS)

    Simeonov, Dimitre R.; Gowen, Benjamin G.; Boontanrart, Mandy; Roth, Theodore L.; Gagnon, John D.; Mumbach, Maxwell R.; Satpathy, Ansuman T.; Lee, Youjin; Bray, Nicolas L.; Chan, Alice Y.; Lituiev, Dmytro S.; Nguyen, Michelle L.; Gate, Rachel E.; Subramaniam, Meena; Li, Zhongmei; Woo, Jonathan M.; Mitros, Therese; Ray, Graham J.; Curie, Gemma L.; Naddaf, Nicki; Chu, Julia S.; Ma, Hong; Boyer, Eric; van Gool, Frederic; Huang, Hailiang; Liu, Ruize; Tobin, Victoria R.; Schumann, Kathrin; Daly, Mark J.; Farh, Kyle K.; Ansel, K. Mark; Ye, Chun J.; Greenleaf, William J.; Anderson, Mark S.; Bluestone, Jeffrey A.; Chang, Howard Y.; Corn, Jacob E.; Marson, Alexander

    2017-09-01

    The majority of genetic variants associated with common human diseases map to enhancers, non-coding elements that shape cell-type-specific transcriptional programs and responses to extracellular cues. Systematic mapping of functional enhancers and their biological contexts is required to understand the mechanisms by which variation in non-coding genetic sequences contributes to disease. Functional enhancers can be mapped by genomic sequence disruption, but this approach is limited to the subset of enhancers that are necessary in the particular cellular context being studied. We hypothesized that recruitment of a strong transcriptional activator to an enhancer would be sufficient to drive target gene expression, even if that enhancer was not currently active in the assayed cells. Here we describe a discovery platform that can identify stimulus-responsive enhancers for a target gene independent of stimulus exposure. We used tiled CRISPR activation (CRISPRa) to synthetically recruit a transcriptional activator to sites across large genomic regions (more than 100 kilobases) surrounding two key autoimmunity risk loci, CD69 and IL2RA. We identified several CRISPRa-responsive elements with chromatin features of stimulus-responsive enhancers, including an IL2RA enhancer that harbours an autoimmunity risk variant. Using engineered mouse models, we found that sequence perturbation of the disease-associated Il2ra enhancer did not entirely block Il2ra expression, but rather delayed the timing of gene activation in response to specific extracellular signals. Enhancer deletion skewed polarization of naive T cells towards a pro-inflammatory T helper (TH17) cell state and away from a regulatory T cell state. This integrated approach identifies functional enhancers and reveals how non-coding variation associated with human immune dysfunction alters context-specific gene programs.

  9. Ectopic expression of Capsicum-specific cell wall protein Capsicum annuum senescence-delaying 1 (CaSD1) delays senescence and induces trichome formation in Nicotiana benthamiana.

    PubMed

    Seo, Eunyoung; Yeom, Seon-In; Jo, Sunghwan; Jeong, Heejin; Kang, Byoung-Cheorl; Choi, Doil

    2012-04-01

    Secreted proteins are known to have multiple roles in plant development, metabolism, and stress response. In a previous study to understand the roles of secreted proteins, Capsicum annuum secreted proteins (CaS) were isolated by yeast secretion trap. Among the secreted proteins, we further characterized Capsicum annuum senescence-delaying 1 (CaSD1), a gene encoding a novel secreted protein that is present only in the genus Capsicum. The deduced CaSD1 contains multiple repeats of the amino acid sequence KPPIHNHKPTDYDRS. Interestingly, the number of repeats varied among cultivars and species in the Capsicum genus. CaSD1 is constitutively expressed in roots, and Agrobacterium-mediated transient overexpression of CaSD1 in Nicotiana benthamiana leaves resulted in delayed senescence with a dramatically increased number of trichomes and enlarged epidermal cells. Furthermore, senescence- and cell division-related genes were differentially regulated by CaSD1-overexpressing plants. These observations imply that the pepper-specific cell wall protein CaSD1 plays roles in plant growth and development by regulating cell division and differentiation.

  10. The sensitivity of Turing self-organization to biological feedback delays: 2D models of fish pigmentation.

    PubMed

    Gaffney, E A; Lee, S Seirin

    2015-03-01

    Turing morphogen models have been extensively explored in the context of large-scale self-organization in multicellular biological systems. However, reconciling the detailed biology of morphogen dynamics, while accounting for time delays associated with gene expression, reveals aberrant behaviours that are not consistent with early developmental self-organization, especially the requirement for exquisite temporal control. Attempts to reconcile the interpretation of Turing's ideas with an increasing understanding of the mechanisms driving zebrafish pigmentation suggests that one should reconsider Turing's model in terms of pigment cells rather than morphogens (Nakamasu et al., 2009, PNAS, 106: , 8429-8434; Yamaguchi et al., 2007, PNAS, 104: , 4790-4793). Here the dynamics of pigment cells is subject to response delays implicit in the cell cycle and apoptosis. Hence we explore simulations of fish skin patterning, focussing on the dynamical influence of gene expression delays in morphogen-based Turing models and response delays for cell-based Turing models. We find that reconciling the mechanisms driving the behaviour of Turing systems with observations of fish skin patterning remains a fundamental challenge. © The Authors 2013. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  11. Neuroprotective effects of silymarin on ischemia-induced delayed neuronal cell death in rat hippocampus.

    PubMed

    Hirayama, Koki; Oshima, Hideki; Yamashita, Akiko; Sakatani, Kaoru; Yoshino, Atsuo; Katayama, Yoichi

    2016-09-01

    We examined the effects of silymarin, which was extracted from Silybum marianum, on delayed neuronal cell death in the rat hippocampus. Rats were divided into four groups: sham-operated rats (sham group), rats which underwent ischemic surgery (control group), rats which were treated with silymarin before and after ischemic surgery (pre group), and rats which were treated with silymarin after ischemic surgery only (post group). We performed the ischemic surgery by occluding the bilateral carotid arteries for 20min and sacrificed the rats one week after the surgery. Silymarin was administered orally at 200mg/kg body weight. Smaller numbers of delayed cell deaths were noted in the rat CA1 region of the pre- and post-groups, and no significant difference was observed between these groups. There were few apoptotic cell deaths in all groups. Compared to the control group, significantly fewer cell deaths by autophagy were found in the pre- and post-group. We concluded that silymarin exerts a preservation effect on delayed neuronal cell death in the rat hippocampus and this effect has nothing to do with the timing of administering of silymarin. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Describing-function analysis of a ripple regulator with slew-rate limits and time delays

    NASA Technical Reports Server (NTRS)

    Wester, Gene W.

    1990-01-01

    The effects of time delays and slew-rate limits on the steady-state operating points and performance of a free-running ripple regulator are evaluated using describing-function analysis. The describing function of an ideal comparator (no time delays or slew rate limits) has no phase shift and is independent of frequency. It is found that turn-on delay and turn-off delay have different effects on gain and phase and cannot be combined. Comparator hysteresis affects both gain and phase; likewise, time delays generally affect both gain and phase. It is found that the effective time delay around the feedback loop is one half the sum of turn-on and turn-off delays, regardless of whether the delays are caused by storage time or slew rate limits. Expressions are formulated for the switching frequency, switch duty ratio, dc output, and output ripple. For the case of no hysteresis, a simple, graphical solution for the switching frequency is possible, and the resulting switching frequency is independent of first-order variations of input or load.

  13. The consequence of delayed fixation on subsequent preservation of urine cells.

    PubMed

    Ahmed, Hussain G; Tom, Murtada Am

    2011-01-01

    Degenerative changes caused by delays in urine preservation contribute to false-negative and false-positive interpretation of urothelial disease in cytology. The aim of this study is to assess whether the delay of fixation of urine samples makes any significant difference to urine cytology and morphology, and the limit of acceptability of delay for routine use in the hospital laboratory. Three cell collection fluids were evaluated by analyzing the preservation and degeneration of cells in urine samples. In this study, 50 voided urine specimens were taken at random from females complaining of vaginal discharge. Each specimen was divided into three sterile containers. The first was immediately centrifugated and the deposit was smeared onto a cleaned micro slide and immediately fixed into 95% ethyl alcohol for 15 minutes. The remaining two were prepared in the same manner, however, the second after two hours of collection and the third after four hours of collection. The degree of degeneration and thus the preservation were assessed by a table of chosen criteria, then ranked and analyzed using Friedman's nonparametric test, at p=0.05. The results showed a significant difference between the preservation and the delay in urine fixation, p<0.0001. Any delay in fixation of urine specimen for cytology affects the preservation of cells, which may result in miss diagnosis. It is recommended that urine samples for cytology should be fixed immediately after collection.

  14. Bifurcation Analysis and Chaos Control in a Modified Finance System with Delayed Feedback

    NASA Astrophysics Data System (ADS)

    Yang, Jihua; Zhang, Erli; Liu, Mei

    2016-06-01

    We investigate the effect of delayed feedback on the finance system, which describes the time variation of the interest rate, for establishing the fiscal policy. By local stability analysis, we theoretically prove the existences of Hopf bifurcation and Hopf-zero bifurcation. By using the normal form method and center manifold theory, we determine the stability and direction of a bifurcating periodic solution. Finally, we give some numerical solutions, which indicate that when the delay passes through certain critical values, chaotic oscillation is converted into a stable equilibrium or periodic orbit.

  15. Chk1 and Wee1 kinases coordinate DNA replication, chromosome condensation, and anaphase entry

    PubMed Central

    Fasulo, Barbara; Koyama, Carol; Yu, Kristina R.; Homola, Ellen M.; Hsieh, Tao S.; Campbell, Shelagh D.; Sullivan, William

    2012-01-01

    Defects in DNA replication and chromosome condensation are common phenotypes in cancer cells. A link between replication and condensation has been established, but little is known about the role of checkpoints in monitoring chromosome condensation. We investigate this function by live analysis, using the rapid division cycles in the early Drosophila embryo. We find that S-phase and topoisomerase inhibitors delay both the initiation and the rate of chromosome condensation. These cell cycle delays are mediated by the cell cycle kinases chk1 and wee1. Inhibitors that cause severe defects in chromosome condensation and congression on the metaphase plate result in delayed anaphase entry. These delays are mediated by wee1 and are not the result of spindle assembly checkpoint activation. In addition, we provide the first detailed live analysis of the direct effect of widely used anticancer agents (aclarubicin, ICRF-193, VM26, doxorubicin, camptothecin, aphidicolin, hydroxyurea, cisplatin, mechlorethamine and x-rays) on key nuclear and cytoplasmic cell cycle events. PMID:22262459

  16. Influence of Ganoderma lucidum (Curt.: Fr.) P. Karst. on T-cell-mediated immunity in normal and immunosuppressed mice line CBA/Ca.

    PubMed

    Nizhenkovska, Iryna V; Pidchenko, Vitalii T; Bychkova, Nina G; Bisko, Nina A; Rodnichenko, Angela Y; Kozyko, Natalya O

    2015-09-01

    The article presents the results of the investigation of the effect of biomass powder of the fungus Ganoderma lucidum on T-cell-mediated immunity in normal and immunosuppressed mice CBA/Ca. Delayed-type hypersensitivity assay was used. Experimental immunodeficiency was established with intraperitoneal injection of the immunosuppressant cyclophosphamide at a single dose of 150 mg/kg on the first day of the experiment. Results of the study show that the administration of biomass powder of Ganoderma lucidum in a dose of 0.5 mg/kg orally for 10 days increases the delayed-type hypersensitivity response in normal mice CBA/Ca. Administration of 0.5 mg/kg of biomass powder of the fungus Ganoderma lucidum for 10 days blocked the development of the T-cell-mediated immunosuppression, induced by administration of cyclophosphamide and restored the delayed-type hypersensitivity response in immunosuppressed mice. Key words: fungus Ganoderma lucidum cyclophosphamide immunodeficiency T-cell-mediated immunity delayed-type hypersensitivity.

  17. National Airspace System Delay Estimation Using Weather Weighted Traffic Counts

    NASA Technical Reports Server (NTRS)

    Chatterji, Gano B.; Sridhar, Banavar

    2004-01-01

    Assessment of National Airspace System performance, which is usually measured in terms of delays resulting from the application of traffic flow management initiatives in response to weather conditions, volume, equipment outages and runway conditions, is needed both for guiding flow control decisions during the day of operations and for post operations analysis. Comparison of the actual delay, resulting from the traffic flow management initiatives, with the expected delay, based on traffic demand and other conditions, provides the assessment of the National Airspace System performance. This paper provides a method for estimating delay using the expected traffic demand and weather. In order to identify the cause of delays, 517 days of National Airspace System delay data reported by the Federal Aviation Administration s Operations Network were analyzed. This analysis shows that weather is the most important causal factor for delays followed by equipment and runway delays. Guided by these results, the concept of weather weighted traffic counts as a measure of system delay is described. Examples are given to show the variation of these counts as a function of time of the day. The various datasets, consisting of aircraft position data, enroute severe weather data, surface wind speed and visibility data, reported delay data and number of aircraft handled by the Centers data, and their sources are described. The procedure for selecting reference days on which traffic was minimally impacted by weather is described. Different traffic demand on each reference day of the week, determined by analysis of 42 days of traffic and delay data, was used as the expected traffic demand for each day of the week. Next, the method for computing the weather weighted traffic counts using the expected traffic demand, derived from reference days, and the expanded regions around severe weather cells is discussed. It is shown via a numerical example that this approach improves the dynamic range of the weather weighted traffic counts considerably. Time histories of these new weather weighted traffic counts are used for synthesizing two statistical features, six histogram features and six time domain features. In addition to these enroute weather features, two surface weather features of number of major airports in the United States with high mean winds and low mean visibility are also described. A least squares procedure for establishing a functional relation between the features, using combinations of these features, and system delays is explored using 36 days of data. Best correlations between the estimated delays using the functional relation and the actual delays provided by the Operations Network are obtained with two different combinations of features: 1) six time domain features of weather weighted traffic counts plus two surface weather features, and 2) six histogram features and mean of weather weighted traffic counts along with the two surface weather features. Correlation coefficient values of 0.73 and 0.83 were found in these two instances.

  18. Effects of cockpit lateral stick characteristics on handling qualities and pilot dynamics

    NASA Technical Reports Server (NTRS)

    Mitchell, David G.; Aponso, Bimal L.; Klyde, David H.

    1992-01-01

    This report presents the results of analysis of cockpit lateral control feel-system studies. Variations in feel-system natural frequency, damping, and command sensing reference (force and position) were investigated, in combination with variations in the aircraft response characteristics. The primary data for the report were obtained from a flight investigation conducted with a variable-stability airplane, with additional information taken from other flight experiments and ground-based simulations for both airplanes and helicopters . The study consisted of analysis of handling qualities ratings and extraction of open-loop, pilot-vehicle describing functions from sum-of-sines tracking data, including, for a limited subset of these data, the development of pilot models. The study confirms the findings of other investigators that the effects on pilot opinion of cockpit feel-system dynamics are not equivalent to a comparable level of added time delay, and until a more comprehensive set of criteria are developed, it is recommended that feel-system dynamics be considered a delay-inducing element in the aircraft response. The best correlation with time-delay requirements was found when the feel-system dynamics were included in the delay measurements, regardless of the command reference. This is a radical departure from past approaches.

  19. Geodesy by radio interferometry: Water vapor radiometry for estimation of the wet delay

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

    Elgered, G.; Davis, J.L.; Herring, T.A.

    1991-04-10

    An important source of error in very-long-baseline interferometry (VLBI) estimates of baseline length is unmodeled variations of the refractivity of the neutral atmosphere along the propagation path of the radio signals. The authors present and discuss the method of using data from a water vapor readiometer (WVR) to correct for the propagation delay caused by atmospheric water vapor, the major cause of these variations. Data from different WVRs are compared with estimated propagation delays obtained by Kalman filtering of the VLBI data themselves. The consequences of using either WVR data of Kalman filtering to correct for atmospheric propagation delay atmore » the Onsala VLBI site are investigated by studying the repeatability of estimated baseline lengths from Onsala to several other sites. The lengths of the baselines range from 919 to 7,941 km. The repeatability obtained for baseline length estimates shows that the methods of water vapor radiometry and Kalman filtering offer comparable accuracies when applied to VLBI observations obtained in the climate of the Swedish west coast. The use of WVR data yielded a 13% smaller weighted-root-mean-square (WRMS) scatter of the baseline length estimates compared to the use of a Kalman filter. It is also clear that the best minimum elevation angle for VLBI observations depends on the accuracy of the determinations of the total propagation delay to be used, since the error in this delay increases with increasing air mass. For use of WVR data along with accurate determinations of total surface pressure, the best minimum is about 20{degrees}; for use of a model for the wet delay based on the humidity and temperature at the ground, the best minimum is about 35{degrees}.« less

  20. A dual V t disturb-free subthreshold SRAM with write-assist and read isolation

    NASA Astrophysics Data System (ADS)

    Bhatnagar, Vipul; Kumar, Pradeep; Pandey, Neeta; Pandey, Sujata

    2018-02-01

    This paper presents a new dual V t 8T SRAM cell having single bit-line read and write, in addition to Write Assist and Read Isolation (WARI). Also a faster write back scheme is proposed for the half selected cells. A high V t device is used for interrupting the supply to one of the inverters for weakening the feedback loop for assisted write. The proposed cell provides an improved read static noise margin (RSNM) due to the bit-line isolation during the read. Static noise margins for data read (RSNM), write (WSNM), read delay, write delay, data retention voltage (DRV), leakage and average powers have been calculated. The proposed cell was found to operate properly at a supply voltage as small as 0.41 V. A new write back scheme has been suggested for half-selected cells, which uses a single NMOS access device and provides reduced delay, pulse timing hardware requirements and power consumption. The proposed new WARI 8T cell shows better performance in terms of easier write, improved read noise margin, reduced leakage power, and less delay as compared to the existing schemes that have been available so far. It was also observed that with proper adjustment of the cell ratio the supply voltage can further be reduced to 0.2 V.

  1. Delayed animal aging through the recovery of stem cell senescence by platelet rich plasma.

    PubMed

    Liu, Hen-Yu; Huang, Chiung-Fang; Lin, Tzu-Chieh; Tsai, Ching-Yu; Tina Chen, Szu-Yu; Liu, Alice; Chen, Wei-Hong; Wei, Hong-Jian; Wang, Ming-Fu; Williams, David F; Deng, Win-Ping

    2014-12-01

    Aging is related to loss of functional stem cell accompanying loss of tissue and organ regeneration potentials. Previously, we demonstrated that the life span of ovariectomy-senescence accelerated mice (OVX-SAMP8) was significantly prolonged and similar to that of the congenic senescence-resistant strain of mice after platelet rich plasma (PRP)/embryonic fibroblast transplantation. The aim of this study is to investigate the potential of PRP for recovering cellular potential from senescence and then delaying animal aging. We first examined whether stem cells would be senescent in aged mice compared to young mice. Primary adipose derived stem cells (ADSCs) and bone marrow derived stem cells (BMSCs) were harvested from young and aged mice, and found that cell senescence was strongly correlated to animal aging. Subsequently, we demonstrated that PRP could recover cell potential from senescence, such as promote cell growth (cell proliferation and colony formation), increase osteogenesis, decrease adipogenesis, restore cell senescence related markers and resist the oxidative stress in stem cells from aged mice. The results also showed that PRP treatment in aged mice could delay mice aging as indicated by survival, body weight and aging phenotypes (behavior and gross morphology) in term of recovering the cellular potential of their stem cells compared to the results on aged control mice. In conclusion these findings showed that PRP has potential to delay aging through the recovery of stem cell senescence and could be used as an alternative medicine for tissue regeneration and future rejuvenation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Involvement of Potassium and Cation Channels in Hippocampal Abnormalities of Embryonic Ts65Dn and Tc1 Trisomic Mice

    PubMed Central

    Stern, Shani; Segal, Menahem; Moses, Elisha

    2015-01-01

    Down syndrome (DS) mouse models exhibit cognitive deficits, and are used for studying the neuronal basis of DS pathology. To understand the differences in the physiology of DS model neurons, we used dissociated neuronal cultures from the hippocampi of Ts65Dn and Tc1 DS mice. Imaging of [Ca2+]i and whole cell patch clamp recordings were used to analyze network activity and single neuron properties, respectively. We found a decrease of ~ 30% in both fast (A-type) and slow (delayed rectifier) outward potassium currents. Depolarization of Ts65Dn and Tc1 cells produced fewer spikes than diploid cells. Their network bursts were smaller and slower than diploids, displaying a 40% reduction in Δf / f0 of the calcium signals, and a 30% reduction in propagation velocity. Additionally, Ts65Dn and Tc1 neurons exhibited changes in the action potential shape compared to diploid neurons, with an increase in the amplitude of the action potential, a lower threshold for spiking, and a sharp decrease of about 65% in the after-hyperpolarization amplitude. Numerical simulations reproduced the DS measured phenotype by variations in the conductance of the delayed rectifier and A-type, but necessitated also changes in inward rectifying and M-type potassium channels and in the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. We therefore conducted whole cell patch clamp measurements of M-type potassium currents, which showed a ~ 90% decrease in Ts65Dn neurons, while HCN measurements displayed an increase of ~ 65% in Ts65Dn cells. Quantitative real-time PCR analysis indicates overexpression of 40% of KCNJ15, an inward rectifying potassium channel, contributing to the increased inhibition. We thus find that changes in several types of potassium channels dominate the observed DS model phenotype. PMID:26501103

  3. Role of p53 in cdk Inhibitor VMY-1-103-induced Apoptosis in Prostate Cancer

    DTIC Science & Technology

    2013-11-01

    DAOY medulloblastoma cells, which have a p53 mutation (6). In order to examine if this holds true in prostate cancer cell lines, I stably transfected...disrupts chromosome organization and delays metaphase progression in medulloblastoma cells. Cancer Biol Ther. 2011 Nov 1;12(9):818-26  Other...1-103 is a novel CDK inhibitor that disrupts chromosome organization and delays metaphase progression in medulloblastoma cells. Cancer Biol Ther

  4. Delayed rectifier and A-type potassium channels associated with Kv 2.1 and Kv 4.3 expression in embryonic rat neural progenitor cells.

    PubMed

    Smith, Dean O; Rosenheimer, Julie L; Kalil, Ronald E

    2008-02-13

    Because of the importance of voltage-activated K(+) channels during embryonic development and in cell proliferation, we present here the first description of these channels in E15 rat embryonic neural progenitor cells derived from the subventricular zone (SVZ). Activation, inactivation, and single-channel conductance properties of recorded progenitor cells were compared with those obtained by others when these Kv gene products were expressed in oocytes. Neural progenitor cells derived from the subventricular zone of E15 embryonic rats were cultured under conditions that did not promote differentiation. Immunocytochemical and Western blot assays for nestin expression indicated that almost all of the cells available for recording expressed this intermediate filament protein, which is generally accepted as a marker for uncommitted embryonic neural progenitor cells. However, a very small numbers of the cells expressed GFAP, a marker for astrocytes, O4, a marker for immature oligodendrocytes, and betaIII-tubulin, a marker for neurons. Using immunocytochemistry and Western blots, we detected consistently the expression of Kv2.1, and 4.3. In whole-cell mode, we recorded two outward currents, a delayed rectifier and an A-type current. We conclude that Kv2.1, and 4.3 are expressed in E15 SVZ neural progenitor cells, and we propose that they may be associated with the delayed-rectifier and the A-type currents, respectively, that we recorded. These results demonstrate the early expression of delayed rectifier and A-type K(+) currents and channels in embryonic neural progenitor cells prior to the differentiation of these cells.

  5. An outer membrane protein (porin) as an eliciting antigen for delayed-type hypersensitivity in murine salmonellosis.

    PubMed Central

    Udhayakumar, V; Muthukkaruppan, V R

    1987-01-01

    The porin, an outer membrane protein of Salmonella typhimurium, was found to be a suitable antigen for eliciting delayed-type hypersensitivity in mouse salmonellosis. Histological examination of the reaction site revealed that the porin was superior to other antigenic preparations in eliciting a typical delayed-type hypersensitivity reaction consisting of mononuclear cell infiltration without polymorphonuclear cell contamination. This study indicates the importance of using a suitable protein antigen from S. typhi for human application. Images PMID:3028963

  6. Increased expression of cyclin B1 mRNA coincides with diminished G{sub 2}-phase arrest in irradiated HeLa cells treated with staurosporine or caffeine

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

    Bernhard, E.J.; Maity, A.; McKenna, W.G.

    1994-12-01

    The irradiation of cells results in delayed progression through the G{sub 2} phase of the cell cycle. Treatment of irradiated HeLa cells with caffeine greatly reduces the G{sub 2}-phase delay, while caffeine does not alter progression of cells through the cell cycle in unirradiated cells. In this report we demonstrate that treatment of HeLa cells with the kinase inhibitor staurosporine, but not with the inhibitor H7, also results in a reduction of the G{sub 2}-phase arrest after irradiation. Cell cycle progression in unirradiated cells is unaffected by 4.4 nM (2ng/ml) staurosporine, which releases the radiation-induced G{sub 2}-phase arrest. In HeLamore » cells, the G{sub 2}-phase delay after irradiation in S phase is accompanied by decreased expression of cyclin B1 mRNA. Coincident with the reduction in G{sub 2}-phase delay, we observed an increase in cyclin B1 mRNA accumulation in irradiated, staurosporine-treated cells compared to cells treated with irradiation alone. Caffeine treatment of irradiated HeLa cells also resulted in an elevation in the levels of cyclin B1 message. These results support the hypothesis that diminished cyclin B1 mRNA levels influence G{sub 2}-phase arrest to some degree. The findings that both staurosporine and caffeine treatments reverse the depression in cyclin B1 expression suggest that these two compounds may act on a common pathway of cell cycle control in response to radiation injury. 33 refs., 6 figs.« less

  7. Annual reproductive synchronization in ovary and pineal gland function of female short-nosed fruit bat, Cynopterus sphinx.

    PubMed

    Haldar, Chandana; Yadav, Rajesh; Alipreeta

    2006-08-01

    We studied the annual correlation of ovarian activity and pineal gland in relation with seasonal variation and gestation of a tropical zone short-nosed fruit bat Cynopterus sphinx. Female bats showed bimodal polyestry (February/March and September/October) in their reproductive cycle. Plasma estradiol concentration ran parallel with ovarian activity and had an inverse relation with pineal mass and peripheral melatonin concentration. Due to the delayed embryonic development in the uterus (October-March) of female bats, interestingly, the uterine activity did not show a parallel relation with ovarian activity and estradiol level. Further, compared with normal non-pregnant females, melatonin level was high during gestation and delayed embryonic development phase. This suggests that the reproductive synchrony and annual variation in ovarian activity of this nocturnal flying mammal differ from other common tropical mammals. The delayed embryonic development in bats might be an adaptive strategy for the unfavorable conditions of the seasons and might be regulated by high peripheral estradiol and melatonin concentration.

  8. Exonic deletions of AUTS2 in Chinese patients with developmental delay and intellectual disability.

    PubMed

    Fan, Yanjie; Qiu, Wenjuan; Wang, Lili; Gu, Xuefan; Yu, Yongguo

    2016-02-01

    Genomic rearrangements involving dosage change of genes have been implicated in a range of developmental disorders. Increasing evidences suggest copy number variations (CNVs) of autism susceptibility candidate gene 2 (AUTS2) are associated with a syndromic form of developmental delay and intellectual disability. However, the genetic and clinical profiles involving AUTS2 variations have not been fully characterized in Asian patients yet, and the outcome of treatments has not been reported. Here we report de novo exonic deletions of AUTS2 detected by chromosomal microarray analysis (CMA) in three Chinese children referred to the clinic for developmental delay, including two deletions involving only exon 6 (98.4 and 262 kb, respectively) and one deletion involving the C-terminal of AUTS2 (2147 kb). The phenotypic presentations of these three patients were described and compared with previous cases in literature. In addition, we presented the outcome of hormonal treatment for short stature in one patient. © 2015 Wiley Periodicals, Inc.

  9. Comments on Strontium-90 in Surface Air in Relation to Stratospheric Fallout.

    NASA Astrophysics Data System (ADS)

    Rangarajan, C.; Eapen, C. D.

    1984-08-01

    The time variation of the spring peak of stratospheric fallout is examined with surface air data of Cs-137 concentrations from about 30 stations in the zone 9 to 75°N and 80°W to 115°E. This study is likely to be more realistic than one derived from data confined to a particular meridian, such as the United States 80th meridian fallout sampling network. It is seen from an examination of the data that the spring peak of stratospheric fallout is progressively delayed with increasing latitude from 9 to 50°N. At latitudes beyond 50°N, no clear trend can be postulated due to limited data. The reason for this progressive delay in the appearance of the spring peak is likely to be due to changes in the circulation pattern, rather than variations in precipitation scavenging, as regions with different distributions of rainfall have the same progressive delay in the spring peak.

  10. Localization and Expression of Hsp27 and αB-Crystallin in Rat Primary Myocardial Cells during Heat Stress In Vitro

    PubMed Central

    Tang, Shu; Buriro, Rehana; Liu, Zhijun; Zhang, Miao; Ali, Islam; Adam, Abdelnasir; Hartung, Jörg; Bao, Endong

    2013-01-01

    Neonatal rat primary myocardial cells were subjected to heat stress in vitro, as a model for investigating the distribution and expression of Hsp27 and αB-crystallin. After exposure to heat stress at 42°C for different durations, the activities of enzymes expressed during cell damage increased in the supernatant of the heat-stressed myocardial cells from 10 min, and the pathological lesions were characterized by karyopyknosis and acute degeneration. Thus, cell damage was induced at the onset of heat stress. Immunofluorescence analysis showed stronger positive signals for both Hsp27 and αB-crystallin from 10 min to 240 min of exposure compared to the control cells. According to the Western blotting results, during the 480 min of heat stress, no significant variation was found in Hsp27 and αB-crystallin expression; however, significant differences were found in the induction of their corresponding mRNAs. The expression of these small heat shock proteins (sHsps) was probably delayed or overtaxed due to the rapid consumption of sHsps in myocardial cells at the onset of heat stress. Our findings indicate that Hsp27 and αB-crystallin do play a role in the response of cardiac cells to heat stress, but the details of their function remain to be investigated. PMID:23894407

  11. Aridity promotes bet hedging via delayed hatching: a case study with two temporary pond crustaceans along a latitudinal gradient.

    PubMed

    Pinceel, Tom; Vanschoenwinkel, Bram; Hawinkel, Wouter; Tuytens, Karen; Brendonck, Luc

    2017-05-01

    Climate change does affect not only average rainfall and temperature but also their variation, which can reduce the predictability of suitable conditions for growth and reproduction. This situation is problematic for inhabitants of temporary waters whose reproductive success depends on rainfall and evaporation that determine the length of the aquatic phase. For organisms with long-lived dormant life stages, bet hedging models suggest that a fraction of these should stay dormant during each growing season to buffer against the probability of total reproductive failure in variable environments. Thus far, however, little empirical evidence supports this prediction in aquatic organisms. We study geographic variation in delayed hatching of dormant eggs in natural populations of two crustaceans, Branchinella longirostris and Paralimnadia badia, that occur in temporary rock pools along a 725 km latitudinal aridity gradient in Western Australia. Consistent with bet hedging theory, populations of both species were characterised by delayed hatching under common garden conditions and hatching fractions decreased towards the drier end of the gradient where the probability of reproductive success was shown to be lower. This decrease was most pronounced in the species with the longer maturation time, presumably because it is more sensitive to the higher prevalence of short inundations. Overall, these findings illustrate that regional variation in climate can be reflected in differential investment in bet hedging and hints at a higher importance of delayed hatching to persist when the climate becomes harsher. Such strategies could become exceedingly relevant as determinants of vulnerability under climate change.

  12. Controlled environment life support system: Calcium-related leaf injuries on plants

    NASA Technical Reports Server (NTRS)

    Tibbitts, T. W.

    1986-01-01

    Calcium related injuries to plants grown in controlled environments under conditions which maximize plant growth rates are described. Procedures to encourage movement of calcium into developing leaves of lettuce plants were investigated. The time course and pattern of calcium accumulation was determined to develop effective control procedures for this injury, termed tipburn. Procedures investigated were: (1) increasing the relative humidity to saturation during the dark period and altering root temperatures, (2) maximizing water stress during light and minimizing water stress during dark periods, (3) shortening the light-dark cycle lengths in combination with elevated moisture levels during the dark cycles, (4) reducing nutrient concentrations and (5) vibrating the plants. Saturated humidities at night increased the rate of growth and the large fluctuation in plant water potential encouraged calcium movement to the young leaves and delayed tipburn. Root temperature regulation between 15 and 26 C was not effective in preventing tipburn. Attempts to modulate water stress produced little variation, but no difference in tipburn development. Variations in light-dark cycle lengths also had no effect on calcium concentrations within developing leaves and no variation in tipburn development. Low concentrations of nutrient solution delayed tipburn, presumably because of greater calcium transport in the low concentration plants. Shaking of the plants did not prevent tipburn, but did delay it slightly.

  13. Regional variations in upper mantle compressional velocities beneath southern California 1. Post-shock temperatures: Their experimental determination, calculation, and implications, 2.. Ph.D. Thesis

    NASA Technical Reports Server (NTRS)

    Raikes, S. A.

    1978-01-01

    The compressional velocity within the upper mantle beneath Southern California is investigated through observations of the dependence of teleseismic P-delays at all stations of the array on the distance and azimuth to the event. The variation of residuals with azimuth was found to be as large as 1.3 sec at a single station; the delays were stable as a function of time, and no evidence was found for temporal velocity variations related to seismic activity in the area. These delays were used in the construction of models for the upper mantle P-velocity structure to depths of 150 km, both by ray tracing and inversion techniques. The models exhibit considerable lateral heterogeneity including a region of low velocity beneath the Imperial Valley, and regions of increased velocity beneath the Sierra Nevada and much of the Transverse Ranges. The development is described of a technique for the experimental determination of post-shock temperatures, and its application to several metals and silicates shocked to pressures in the range 5 to 30 GPa. The technique utilizes an infra-red radiation detector to determine the brightness temperature of the free surface of the sample after the shock wave has passed through it.

  14. Generating synchrony from the asynchronous: compensation for cochlear traveling wave delays by the dendrites of individual brainstem neurons

    PubMed Central

    McGinley, Matthew J.; Liberman, M. Charles; Bal, Ramazan; Oertel, Donata

    2012-01-01

    Broadband transient sounds, such as clicks and consonants, activate a traveling wave in the cochlea. This wave evokes firing in auditory nerve fibers that are tuned to high frequencies several milliseconds earlier than in fibers tuned to low frequencies. Despite this substantial traveling wave delay, octopus cells in the brainstem receive broadband input and respond to clicks with submillisecond temporal precision. The dendrites of octopus cells lie perpendicular to the tonotopically organized array of auditory nerve fibers, placing the earliest arriving inputs most distally and the latest arriving closest to the soma. Here, we test the hypothesis that the topographic arrangement of synaptic inputs on dendrites of octopus cells allows octopus cells to compensate the traveling wave delay. We show that in mice the full cochlear traveling wave delay is 1.6 ms. Because the dendrites of each octopus cell spread across about one third of the tonotopic axis, a click evokes a soma directed sweep of synaptic input lasting 0.5 ms in individual octopus cells. Morphologically and biophysically realistic, computational models of octopus cells show that soma-directed sweeps with durations matching in vivo measurements result in the largest and sharpest somatic excitatory postsynaptic potentials (EPSPs). A low input resistance and activation of a low-voltage-activated potassium conductance that are characteristic of octopus cells are important determinants of sweep sensitivity. We conclude that octopus cells have dendritic morphologies and biophysics tailored to accomplish the precise encoding of broadband transient sounds. PMID:22764237

  15. Seismic velocity anisotropy and heterogeneity beneath the Mantle Electromagnetic and Tomography Experiment (MELT) region of the East Pacific Rise from analysis of P and S body waves

    USGS Publications Warehouse

    Hammond, W.C.; Toomey, D.R.

    2003-01-01

    We use teleseismic P and S delay times and shear wave splitting measurements to constrain isotropic and anisotropic heterogeneity in the mantle beneath the southern East Pacific Rise (SEPR). The data comprise 462 P and S delay times and 18 shear wave splitting observations recorded during the Mantle Electromagnetic and Tomography (MELT) Experiment. We estimate the mantle melt content (F) and temperature (T) variation from the isotropic velocity variation. Our results indicate that the maximum variation in F beneath our array is between zero and ???1.2%, and maximum variation in T is between zero and ???100 K. We favor an explanation having partial contributions from both T and F. We approximate the seismic anisotropy of the upper mantle with hexagonal symmetry, consistent with the assumption of two dimensionality of mantle flow. Our new tomographic technique uses a nonlinear inversion of P and slow S polarization delay times to simultaneously solve for coupled VP and VS heterogeneity throughout the model and for the magnitude of anisotropy within discrete domains. The domain dimensions and the dip of the anisotropy are fixed for each inversion but are varied in a grid search, obtaining the misfit of the models to the body wave delay data and to split times of vertically propagating S waves. The data misfit and the isotropic heterogeneity are sensitive to domain dimensions and dip of anisotropy. In a region centered beneath the SEPR the best average dip of the hexagonal symmetry axis is horizontal or dipping shallowly (<30??) west. Given the resolution of our data, a subaxial region characterized by vertically aligned symmetry axes may exist but is limited to be <80 km deep. We infer that the mantle flow beneath the SEPR is consistent with shallow asthenospheric return flow from the direction of the South Pacific superswell.

  16. LRRK2 delays degradative receptor trafficking by impeding late endosomal budding through decreasing Rab7 activity.

    PubMed

    Gómez-Suaga, Patricia; Rivero-Ríos, Pilar; Fdez, Elena; Blanca Ramírez, Marian; Ferrer, Isidro; Aiastui, Ana; López De Munain, Adolfo; Hilfiker, Sabine

    2014-12-20

    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset autosomal dominant Parkinson's disease (PD), and sequence variations at the LRRK2 locus are associated with increased risk for sporadic PD. LRRK2 contains both GTPase and kinase domains flanked by protein interaction motifs, and mutations associated with familial PD have been described for both catalytic domains. LRRK2 has been implicated in diverse cellular processes, and recent evidence pinpoints to an important role for LRRK2 in modulating a variety of intracellular membrane trafficking pathways. However, the underlying mechanisms are poorly understood. Here, by studying the classical, well-understood, degradative trafficking pathway of the epidermal growth factor receptor (EGFR), we show that LRRK2 regulates endocytic membrane trafficking in an Rab7-dependent manner. Mutant LRRK2 expression causes a slight delay in early-to-late endosomal trafficking, and a pronounced delay in trafficking out of late endosomes, which become aberrantly elongated into tubules. This is accompanied by a delay in EGFR degradation. The LRRK2-mediated deficits in EGFR trafficking and degradation can be reverted upon coexpression of active Rab7 and of a series of proteins involved in bridging the EGFR to Rab7 on late endosomes. Effector pulldown assays indicate that pathogenic LRRK2 decreases Rab7 activity both in cells overexpressing LRRK2, as well as in fibroblasts from pathogenic mutant LRRK2 PD patients when compared with healthy controls. Together, these findings provide novel insights into a previously unknown regulation of Rab7 activity by mutant LRRK2 which impairs membrane trafficking at very late stages of the endocytic pathway. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Measurement of multipath delay profile in land mobile satellite channels

    NASA Technical Reports Server (NTRS)

    Ikegami, Tetsushi; Arakaki, Yoshiya; Wakana, Hiromitsu; Suzuki, Ryutaro

    1993-01-01

    Mobile satellite communication channel has been evaluated mainly with fading statistics of signal. When bandwidth of transmitting signal becomes wider, frequency selectivity of fading becomes a significant factor of the channel. Channel characteristics, not only signal variation but multipath delay spread should be evaluated. A multipath measurement system is proposed and developed for mobile satellite applications. With this system and ETS-V satellite, multipath delay profiles are measured in various environments including Tokyo metropolis and Sapporo city at 1.5 GHz. Results show that the maximum excess delay is within 1 microsec and the maximum delay spread is 0.2 microsecs at elevation angles of 40 to 47 degrees. In wideband signal transmission of about 1 MHz and more, designers should consider the effect of selective fading due to the multipath of land mobile satellite channel.

  18. Dynamics of localized structures in reaction-diffusion systems induced by delayed feedback

    NASA Astrophysics Data System (ADS)

    Gurevich, Svetlana V.

    2013-05-01

    We are interested in stability properties of a single localized structure in a three-component reaction-diffusion system subjected to the time-delayed feedback. We shall show that variation in the product of the delay time and the feedback strength leads to complex dynamical behavior of the system, including formation of target patterns, spontaneous motion, and spontaneous breathing as well as various complex structures, arising from combination of different oscillatory instabilities. In the case of spontaneous motion, we provide a bifurcation analysis of the delayed system and derive an order parameter equation for the position of the localized structure, explicitly describing its temporal evolution in the vicinity of the bifurcation point. This equation is a subject to a nonlinear delay differential equation, which can be transformed to the normal form of the pitchfork drift bifurcation.

  19. Absence of Toll-like receptor 4 signaling results in delayed Yersinia enterocolitica YopP-induced cell death of dendritic cells.

    PubMed

    Gröbner, Sabine; Schulz, Sebastian; Soldanova, Irena; Gunst, Dani S J; Waibel, Michaela; Wesselborg, Sebastian; Borgmann, Stefan; Autenrieth, Ingo B

    2007-01-01

    In an initial period (< or =4 h) Toll-like receptor 4 (TLR4) signaling is required for Yersinia enterocolitica YopP-induced dendritic cell (DC) death. Later (>4 h), DC die independent of TLR4 signaling. In TLR4-deficient DC caspase 8 cleavage is delayed, indicating that TLR4 signaling accelerates caspase 8 activation, leading to DC death.

  20. Delay of T cell senescence by caloric restriction in aged long-lived nonhuman primates

    PubMed Central

    Messaoudi, Ilhem; Warner, Jessica; Fischer, Miranda; Park, Buyng; Hill, Brenna; Mattison, Julie; Lane, Mark A.; Roth, George S.; Ingram, Donald K.; Picker, Louis J.; Douek, Daniel C.; Mori, Motomi; Nikolich-Žugich, Janko

    2006-01-01

    Caloric restriction (CR) has long been known to increase median and maximal lifespans and to decreases mortality and morbidity in short-lived animal models, likely by altering fundamental biological processes that regulate aging and longevity. In rodents, CR was reported to delay the aging of the immune system (immune senescence), which is believed to be largely responsible for a dramatic increase in age-related susceptibility to infectious diseases. However, it is unclear whether CR can exert similar effects in long-lived organisms. Previous studies involving 2- to 4-year CR treatment of long-lived primates failed to find a CR effect or reported effects on the immune system opposite to those seen in CR-treated rodents. Here we show that long-term CR delays the adverse effects of aging on nonhuman primate T cells. CR effected a marked improvement in the maintenance and/or production of naïve T cells and the consequent preservation of T cell receptor repertoire diversity. Furthermore, CR also improved T cell function and reduced production of inflammatory cytokines by memory T cells. Our results provide evidence that CR can delay immune senescence in nonhuman primates, potentially contributing to an extended lifespan by reducing susceptibility to infectious disease. PMID:17159149

  1. Novel insights into a retinoic-acid-induced cleft palate based on Rac1 regulation of the fibronectin arrangement.

    PubMed

    Tang, Qinghuang; Li, Liwen; Lee, Min-Jung; Ge, Qing; Lee, Jong-Min; Jung, Han-Sung

    2016-03-01

    Retinoic acid (RA)-induced cleft palate results from both extrinsic obstructions by the tongue and internal factors within the palatal shelves. Our previous study showed that the spatiotemporal expression of Rac1 regulates the fibronectin (FN) arrangement through cell density alterations that play an important role in palate development. In this study, we investigate the involvement of the Rac1 regulation of the FN arrangement in RA-induced cleft palate. Our results demonstrate that RA-induced intrinsic alterations in palatal shelves, including a delayed progress of cell condensation, delay palate development, even after the removal of the tongue. Further analysis shows that RA treatment diminishes the region-distinctive expression of Rac1 within the palatal shelves, which reversely alters the fibrillar arrangement of FN. Furthermore, RA treatment disrupts the formation of lamellipodia, which are indicative structures of cell migration that are regulated by Rac1. These results suggest that the Rac1 regulation of the FN arrangement is involved in RA-induced cleft palate through the regulation of cell migration, which delays the progress of cell condensation and subsequently influences the FN arrangement, inducing a delay in palate development. Our study provides new insights into the RA-induced impairment of palatal shelf elevation based on cell migration dynamics.

  2. Ectopic Expression of Capsicum-Specific Cell Wall Protein Capsicum annuum Senescence-Delaying 1 (CaSD1) Delays Senescence and Induces Trichome Formation in Nicotiana benthamiana

    PubMed Central

    Seo, Eunyoung; Yeom, Seon-In; Jo, SungHwan; Jeong, Heejin; Kang, Byoung-Cheorl; Choi, Doil

    2012-01-01

    Secreted proteins are known to have multiple roles in plant development, metabolism, and stress response. In a previous study to understand the roles of secreted proteins, Capsicum annuum secreted proteins (CaS) were isolated by yeast secretion trap. Among the secreted proteins, we further characterized Capsicum annuum senescence-delaying 1 (CaSD1), a gene encoding a novel secreted protein that is present only in the genus Capsicum. The deduced CaSD1 contains multiple repeats of the amino acid sequence KPPIHNHKPTDYDRS. Interestingly, the number of repeats varied among cultivars and species in the Capsicum genus. CaSD1 is constitutively expressed in roots, and Agrobacterium-mediated transient overexpression of CaSD1 in Nicotiana benthamiana leaves resulted in delayed senescence with a dramatically increased number of trichomes and enlarged epidermal cells. Furthermore, senescence- and cell division-related genes were differentially regulated by CaSD1-overexpressing plants. These observations imply that the pepper-specific cell wall protein CaSD1 plays roles in plant growth and development by regulating cell division and differentiation. PMID:22441673

  3. Comparative effects of 60Co gamma-rays and neon and helium ions on cycle duration and division probability of EMT 6 cells. A time-lapse cinematography study.

    PubMed

    Collyn-d'Hooghe, M; Hemon, D; Gilet, R; Curtis, S B; Valleron, A J; Malaise, E P

    1981-03-01

    Exponentially growing cultures of EMT 6 cells were irradiated in vitro with neon ions, helium ions or 60Co gamma-rays. Time-lapse cinematography allowed the determination, for individual cells, of cycle duration, success of the mitotic division and the age of the cell at the moment of irradiation. Irradiation induced a significant mitotic delay increasing proportionally with the delivered dose. Using mitotic delay as an endpoint, the r.b.e. for neon ions with respect to 60Co gamma-rays was 3.3 +/- 0.2 while for helium ions it was 1.2 +/- 0.1. Mitotic delay was greatest in those cells that had progressed furthest in their cycle at the time of irradiation. No significant mitotic delay was observed in the post-irradiation generation. Division probability was significantly reduced by irradiation both in the irradiated and in the post-irradiated generation. The reduction in division probability obtained with 3 Gy of neon ions was similar to that obtained after irradiation with 6 Gy of helium ions or 60Co gamma-rays.

  4. Neural correlates of target selection for reaching movements in superior colliculus

    PubMed Central

    McPeek, Robert M.

    2014-01-01

    We recently demonstrated that inactivation of the primate superior colliculus (SC) causes a deficit in target selection for arm-reaching movements when the reach target is located in the inactivated field (Song JH, Rafal RD, McPeek RM. Proc Natl Acad Sci USA 108: E1433–E1440, 2011). This is consistent with the notion that the SC is part of a general-purpose target selection network beyond eye movements. To understand better the role of SC activity in reach target selection, we examined how individual SC neurons in the intermediate layers discriminate a reach target from distractors. Monkeys reached to touch a color oddball target among distractors while maintaining fixation. We found that many SC neurons robustly discriminate the goal of the reaching movement before the onset of the reach even though no saccade is made. To identify these cells in the context of conventional SC cell classification schemes, we also recorded visual, delay-period, and saccade-related responses in a delayed saccade task. On average, SC cells that discriminated the reach target from distractors showed significantly higher visual and delay-period activity than nondiscriminating cells, but there was no significant difference in saccade-related activity. Whereas a majority of SC neurons that discriminated the reach target showed significant delay-period activity, all nondiscriminating cells lacked such activity. We also found that some cells without delay-period activity did discriminate the reach target from distractors. We conclude that the majority of intermediate-layer SC cells discriminate a reach target from distractors, consistent with the idea that the SC contains a priority map used for effector-independent target selection. PMID:25505107

  5. A Reduced Antigen Load In Vivo, Rather Than Weak Inflammation, Causes a Substantial Delay in CD8+ T Cell Priming against Mycobacterium bovis (Bacillus Calmette-Guérin)1

    PubMed Central

    Russell, Marsha S.; Iskandar, Monica; Mykytczuk, Oksana L.; Nash, John H. E.; Krishnan, Lakshmi; Sad, Subash

    2014-01-01

    Regardless of the dose of Ag, Ag presentation occurs rapidly within the first few days which results in rapid expansion of the CD8+ T cell response that peaks at day 7. However, we have previously shown that this rapid priming of CD8+ T cells is absent during infection of mice with Mycobacterium bovis (bacillus Calmette-Guérin (BCG)). In this study, we have evaluated the mechanisms responsible for the delayed CD8+ T cell priming. Because BCG replicates poorly and survives within phagosomes we considered whether 1) generation of reduced amounts of Ag or 2) weaker activation by pathogen-associated molecular patterns (PAMPs) during BCG infection is responsible for the delay in CD8+ T cell priming. Using rOVA-expressing bacteria, our results indicate that infection of mice with BCG-OVA generates greatly reduced levels of OVA, which are 70-fold lower in comparison to the levels generated during infection of mice with Listeria monocytogenes-expressing OVA. Furthermore, increasing the dose of OVA, but not PAMP signaling during BCG-OVA infection resulted in rapid Ag presentation and consequent expansion of the CD8+ T cell response, indicating that the generation of reduced Ag levels, not lack of PAMP-associated inflammation, was responsible for delayed priming of CD8+ T cells. There was a strong correlation between the relative timing of Ag presentation and the increase in the level of OVA in vivo. Taken together, these results reveal that some slowly replicating pathogens, such as mycobacteria, may facilitate their chronicity by generating reduced Ag levels which causes a substantial delay in the development of acquired immune responses. PMID:17579040

  6. Tolerance and immunity in mice infected with herpes simplex virus: studies on the mechanism of tolerance to delayed-type hypersensitivity.

    PubMed

    Nash, A A; Phelan, J; Gell, P G; Wildy, P

    1981-06-01

    Tolerance to delayed-type hypersensitivity is produced in mice following an intravenous injection of herpes simplex virus. This form of tolerance is produced early on, following simultaneous injections of virus subcutaneously and intravenously, and is long lasting (greater than 100 days). The early tolerance mechanism is resistant to high doses of cyclophosphamide and is not transferable by serum or spleen cells taken after 7 days. However, spleen cells taken at 14 days onwards inhibit the induction of delayed hypersensitivity when transferred to normal syngeneic recipients. These cells are T lymphocytes and are specific for the herpes type used in the induction.

  7. Tolerance and immunity in mice infected with herpes simplex virus: studies on the mechanism of tolerance to delayed-type hypersensitivity.

    PubMed Central

    Nash, A A; Phelan, J; Gell, P G; Wildy, P

    1981-01-01

    Tolerance to delayed-type hypersensitivity is produced in mice following an intravenous injection of herpes simplex virus. This form of tolerance is produced early on, following simultaneous injections of virus subcutaneously and intravenously, and is long lasting (greater than 100 days). The early tolerance mechanism is resistant to high doses of cyclophosphamide and is not transferable by serum or spleen cells taken after 7 days. However, spleen cells taken at 14 days onwards inhibit the induction of delayed hypersensitivity when transferred to normal syngeneic recipients. These cells are T lymphocytes and are specific for the herpes type used in the induction. PMID:6265348

  8. Dynamics of an HBV/HCV infection model with intracellular delay and cell proliferation

    NASA Astrophysics Data System (ADS)

    Zhang, Fengqin; Li, Jianquan; Zheng, Chongwu; Wang, Lin

    2017-01-01

    A new mathematical model of hepatitis B/C virus (HBV/HCV) infection which incorporates the proliferation of healthy hepatocyte cells and the latent period of infected hepatocyte cells is proposed and studied. The dynamics is analyzed via Pontryagin's method and a newly proposed alternative geometric stability switch criterion. Sharp conditions ensuring stability of the infection persistent equilibrium are derived by applying Pontryagin's method. Using the intracellular delay as the bifurcation parameter and applying an alternative geometric stability switch criterion, we show that the HBV/HCV infection model undergoes stability switches. Furthermore, numerical simulations illustrate that the intracellular delay can induce complex dynamics such as persistence bubbles and chaos.

  9. The thin hot plume beneath Iceland

    USGS Publications Warehouse

    Allen, R.M.; Nolet, G.; Morgan, W.J.; Vogfjord, K.; Bergsson, B.H.; Erlendsson, P.; Foulger, G.R.; Jakobsdottir, S.; Julian, B.R.; Pritchard, M.; Ragnarsson, S.; Stefansson, R.

    1999-01-01

    We present the results of a seismological investigation of the frequency-dependent amplitude variations across Iceland using data from the HOTSPOT array currently deployed there. The array is composed of 30 broad-band PASSCAL instruments. We use the parameter t(*), defined in the usual manner from spectral ratios (Halderman and Davis 1991), to compare observed S-wave amplitude variations with those predicted due to both anelastic attenuation and diffraction effects. Four teleseismic events at a range of azimuths are used to measure t(*). A 2-D vertical cylindrical plume model with a Gaussian-shaped velocity anomaly is used to model the variations. That part of t(*) caused by attenuation was estimated by tracing a ray through IASP91, then superimposing our plume model velocity anomaly and calculating the path integral of 1/vQ. That part of t(*) caused by diffraction was estimated using a 2-D finite difference code to generate synthetic seismograms. The same spectral ratio technique used for the data was then used to extract a predicted t(*). The t(*) variations caused by anelastic attenuation are unable to account for the variations we observe, but those caused by diffraction do. We calculate the t(*) variations caused by diffraction for different plume models and obtain our best-fit plume, which exhibits good agreement between the observed and measured t(*). The best-fit plume model has a maximum S-velocity anomaly of - 12 per cent and falls to 1/e of its maximum at 100 km from the plume centre. This is narrower than previous estimates from seismic tomography, which are broadened and damped by the methods of tomography. This velocity model would suggest greater ray theoretical traveltime delays than observed. However, we find that for such a plume, wave-front healing effects at frequencies of 0.03-0.175 Hz (the frequency range used to pick S-wave arrivals) causes a 40 per cent reduction in traveltime delay, reducing the ray theoretical delay to that observed.

  10. Mycophenolate mofetil prevents the delayed T cell response after pilocarpine-induced status epilepticus in mice

    PubMed Central

    Engelmann, Robby; Sellmann, Tina; Köhling, Rüdiger; Müller-Hilke, Brigitte

    2017-01-01

    Growing clinical and laboratory evidence corroborates a role for the immune system in the pathophysiology of epilepsy. In order to delineate the immune response following pilocarpine-induced status epilepticus (SE) in the mouse, we monitored the kinetics of leukocyte presence in the hippocampus over the period of four weeks. SE was induced following a ramping protocol of pilocarpine injection into 4–5 weeks old C57BL/6 mice. Brains were removed at days 1–4, 14 or 28 after SE, and the hippocampi were analyzed via flow cytometry, via quantitative reverse transcriptase PCR (qRT-PCR) and via immunohistochemistry. Epileptogenesis was confirmed by Timm staining of mossy fiber sprouting in the inner molecular layer of the dentate gyrus. The flow cytometry data revealed a biphasic immune response following pilocarpine-induced SE with a transient increase in activated CD11b+ and F4/80+ macrophages within the first four days replaced by an increase in CD3+ T-lymphocytes around day 28. This delayed T cell response was confirmed via qRT-PCR and via immunohistochemistry. In addition, qRT-PCR data could show that the delayed T cell response was associated with an increased CD8/CD4 ratio indicating a cytotoxic T cell response after SE. Intriguingly, early intervention with mycophenolate mofetil administration on days 0–3 after SE prevented this delayed T cell response. These results show an orchestrated immunological sequela and provide evidence that the delayed T cell response is sensitive to early immunomodulatory intervention. PMID:29182639

  11. Dynein-deficient flagella respond to increased viscosity with contrasting changes in power and recovery strokes.

    PubMed

    Wilson, Kate S; Gonzalez, Olivia; Dutcher, Susan K; Bayly, Philip V

    2015-09-01

    Changes in the flagellar waveform in response to increased viscosity were investigated in uniflagellate mutants of Chlamydomonas reinhardtii. We hypothesized that the waveforms of mutants lacking different dynein arms would change in different ways as viscosity was increased, and that these variations would illuminate the feedback pathways from force to dynein activity. Previous studies have investigated the effects of viscosity on cell body motion, propulsive force, and power in different mutants, but the effect on waveform has not yet been fully characterized. Beat frequency decreases with viscosity in wild-type uniflagellate (uni1) cells, and outer dynein arm deficient (oda2) mutants. In contrast, the inner dynein arm mutant ida1 (lacking I1/f) maintains beat frequency at high viscosity but alters its flagellar waveform more than either wild-type or oda2. The ida1 waveform is narrower than wild-type, primarily due to an abbreviated recovery stroke; this difference is amplified at high viscosity. The oda2 mutant in contrast, maintains a consistent waveform at high and low viscosity with a slightly longer power stroke than wild-type. Analysis of the delays and shear displacements between bends suggest that direct force feedback in the outer dynein arm system may initiate switching of dynein activity. In contrast, I1/f dynein appears to delay switching, most markedly at the initiation of the power stroke, possibly by controlling inter-doublet separation. © 2015 Wiley Periodicals, Inc.

  12. Dynein-deficient flagella respond to increased viscosity with contrasting changes in power and recovery strokes

    PubMed Central

    Wilson, Kate S.; Gonzalez, Olivia; Dutcher, Susan K.; Bayly, P.V.

    2015-01-01

    Changes in the flagellar waveform in response to increased viscosity were investigated in uniflagellate mutants of Chlamydomonas reinhardtii. We hypothesized that the waveforms of mutants lacking different dynein arms would change in different ways as viscosity was increased, and that these variations would illuminate the feedback pathways from force to dynein activity. Previous studies have investigated the effects of viscosity on cell body motion, propulsive force, and power in different mutants, but the effect on waveform has not yet been fully characterized. Beat frequency decreases with viscosity in wild-type uniflagellate (uni1) cells, and outer dynein arm deficient (oda2) mutants. In contrast, the inner dynein arm mutant ida1 (lacking I1/f) maintains beat frequency at high viscosity but alters its flagellar waveform more than either wild-type or oda2. The ida1 waveform is narrower than wild-type, primarily due to an abbreviated recovery stroke; this difference is amplified at high viscosity. The oda2 mutant in contrast, maintains a consistent waveform at high and low viscosity with a slightly longer power stroke than wild-type. Analysis of the delays and shear displacements between bends suggest that direct force feedback in the outer dynein arm system may initiate switching of dynein activity. In contrast, I1/f dynein appears to delay switching, most markedly at the initiation of the power stroke, possibly by controlling inter-doublet separation. PMID:26314933

  13. Luteal cell steroidogenesis in relation to delayed embryonic development in the Indian short-nosed fruit bat, Cynopterus sphinx.

    PubMed

    Meenakumari, Karukayil J; Banerjee, Arnab; Krishna, Amitabh

    2009-01-01

    The primary aim of this study was to determine the possible cause of slow or delayed embryonic development in Cynopterus sphinx by investigating morphological and steroidogenic changes in the corpus luteum (CL) and circulating hormone concentrations during two pregnancies of a year. This species showed delayed post-implantational embryonic development during gastrulation of the first pregnancy. Morphological features of the CL showed normal luteinization during both pregnancies. The CL did not change significantly in luteal cell size during the delay period of the first pregnancy as compared with the second pregnancy. The circulating progesterone and 17beta-estradiol concentrations were significantly lower during the period of delayed embryonic development as compared with the same stage of embryonic development during the second pregnancy. We also showed a marked decline in the activity of 3beta-hydroxysteroid dehydrogenase, P450 side chain cleavage enzyme, and steroidogenic acute regulatory peptide in the CL during the delay period. This may cause low circulating progesterone and estradiol synthesis and consequently delay embryonic development. What causes the decrease in steroidogenic factors in the CL during the period of delayed development in C. sphinx is under investigation.

  14. Sporophytic and gametophytic functions of the cell cycle-associated Mob1 gene in Arabidopsis thaliana L.

    PubMed

    Galla, Giulio; Zenoni, Sara; Marconi, Gianpiero; Marino, Giada; Botton, Alessandro; Pinosa, Francesco; Citterio, Sandra; Ruperti, Benedetto; Palme, Klaus; Albertini, Emidio; Pezzotti, Mario; Mau, Martin; Sharbel, Timothy F; De Storme, Nico; Geelen, Danny; Barcaccia, Gianni

    2011-09-15

    Mob1 genes are primarily involved in the cell cycle progression and mitosis exit in yeasts and animals. The function of a Mob1-like gene (At5g45550) from Arabidopsis thaliana was investigated using RNAi and immunological staining. AtMob1-like RNAi silenced lines showed a reduced radial expansion of the inflorescence stem and a reduced elongation zone of the primary root. Morphological features of plant organs were accompanied by a reduction in cell size. The fertility of AtMob1-like RNAi silenced lines was very low as seed production was strongly reduced. About 2% of the progeny of AtMob1-like RNAi silenced plants were tetraploid. The female and male sporogenesis was affected differentially. The ovules developed irregularly and one third of the megaspores and embryo sacs degenerated prematurely. Up to 20% of the ovules produced binucleated megaspores that failed to develop further, being their degeneration likely accompanied with a delayed programmed cell death. The anthers produced about 30% of aborted pollen grains, showing also a strong variation in their size. Together, the results show that Arabidopsis MOB1-like is required to regulate cell expansion and cell division, presumably by affecting the mitotic as well as the meiotic cell cycle. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Comparative morphological characteristics of three Brettanomyces bruxellensis wine strains in the presence/absence of sulfur dioxide.

    PubMed

    Louw, Marli; du Toit, Maret; Alexandre, Hervé; Divol, Benoit

    2016-12-05

    The red wine spoilage yeast Brettanomyces bruxellensis has been the subject of numerous investigations. Some of these studies focused on spoilage mechanisms, sulfur dioxide tolerance and nutrient requirements. Pseudomycelium formation, although a striking feature of this species, has however been poorly investigated. Furthermore, literature regarding the induction mechanism of pseudomycelium formation in this yeast is limited and lacks clarity, as results published are contradictory. This study elucidates this phenomenon among strains from geographically different areas. Potential environmental cues were investigated, to attain a better understanding of this mechanism and its role as a survival strategy. SO 2 was previously reported to induce this morphological change however results obtained in this study did not support this. Nevertheless, the results obtained using scanning and transmission electron microscopy illustrate, for the first time in this yeast, deformity to the cell membrane and alterations to the fibrillar layers in SO 2 treated cells. In addition, the SO 2 exposed cultures displayed cell size variations, with cells displaying a decrease in length as well as delayed growth, with a prolonged lag phase. Fluorescence microscopy demonstrated a decrease in metabolic activity and the appearance of inclusion body-like structures in the cells following exposure to SO 2. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. A novel live cell imaging system reveals a reversible hydrostatic pressure impact on cell cycle progression.

    PubMed

    Brooker, Holly R; Gyamfi, Irene A; Wieckowska, Agnieszka; Brooks, Nicholas J; Mulvihill, Daniel P; Geeves, Michael A

    2018-06-21

    Life is dependent upon the ability of a cell to rapidly respond to changes in environment. Small perturbations in local environments change the ability of molecules to interact and hence communicate. Hydrostatic pressure provides a rapid non-invasive, fully-reversible method for modulating affinities between molecules both in vivo and in vitro We have developed a simple fluorescence imaging chamber that allows intracellular protein dynamics and molecular events to be followed at pressures up to 200 bar in living cells. Using yeast we investigate the impact of hydrostatic pressure upon cell growth and cell cycle progression. While 100 bar has no affect upon viability, it induces a delay in chromosome segregation, resulting in the accumulation of long-undivided-bent cells, consistent with disruption of the cytoskeletons. This delay is independent of stress signalling and induces synchronisation of cell-cycle progression. Equivalent affects were observed in Candida albicans , with pressure inducing a reversible cell-cycle delay and hyphal growth. We present a simple novel non-invasive fluorescence microscopy based approach to transiently impact molecular dynamics to visualise, dissect and study signalling pathways and cellular processes in living cells. © 2018. Published by The Company of Biologists Ltd.

  17. Subretinal transplantation of bone marrow mesenchymal stem cells delays retinal degeneration in the RCS rat model of retinal degeneration.

    PubMed

    Inoue, Yuji; Iriyama, Aya; Ueno, Shuji; Takahashi, Hidenori; Kondo, Mineo; Tamaki, Yasuhiro; Araie, Makoto; Yanagi, Yasuo

    2007-08-01

    Because there is no effective treatment for this retinal degeneration, potential application of cell-based therapy has attracted considerable attention. Several investigations support that bone marrow mesenchymal stem cells (MSCs) can be used for a broad spectrum of indications. Bone marrow MSCs exert their therapeutic effect in part by secreting trophic factors to promote cell survival. The current study investigates whether bone marrow MSCs secrete factor(s) to promote photoreceptor cell survival and whether subretinal transplantation of bone marrow MSCs promotes photoreceptor survival in a retinal degeneration model using Royal College of Surgeons (RCS) rats. In vitro, using mouse retinal cell culture, it was demonstrated that the conditioned medium of the MSCs delays photoreceptor cell apoptosis, suggesting that the secreted factor(s) from the MSCs promote photoreceptor cell survival. In vivo, the MSCs were injected into the subretinal space of the RCS rats and histological analysis, real-time RT-PCR and electrophysiological analysis demonstrated that the subretinal transplantation of MSCs delays retinal degeneration and preserves retinal function in the RCS rats. These results suggest that MSC is a useful cell source for cell-replacement therapy for some forms of retinal degeneration.

  18. Delayed Rectifier and A-Type Potassium Channels Associated with Kv 2.1 and Kv 4.3 Expression in Embryonic Rat Neural Progenitor Cells

    PubMed Central

    Smith, Dean O.; Rosenheimer, Julie L.; Kalil, Ronald E.

    2008-01-01

    Background Because of the importance of voltage-activated K+ channels during embryonic development and in cell proliferation, we present here the first description of these channels in E15 rat embryonic neural progenitor cells derived from the subventricular zone (SVZ). Activation, inactivation, and single-channel conductance properties of recorded progenitor cells were compared with those obtained by others when these Kv gene products were expressed in oocytes. Methodology/Principal Findings Neural progenitor cells derived from the subventricular zone of E15 embryonic rats were cultured under conditions that did not promote differentiation. Immunocytochemical and Western blot assays for nestin expression indicated that almost all of the cells available for recording expressed this intermediate filament protein, which is generally accepted as a marker for uncommitted embryonic neural progenitor cells. However, a very small numbers of the cells expressed GFAP, a marker for astrocytes, O4, a marker for immature oligodendrocytes, and βIII-tubulin, a marker for neurons. Using immunocytochemistry and Western blots, we detected consistently the expression of Kv2.1, and 4.3. In whole-cell mode, we recorded two outward currents, a delayed rectifier and an A-type current. Conclusions/Significance We conclude that Kv2.1, and 4.3 are expressed in E15 SVZ neural progenitor cells, and we propose that they may be associated with the delayed-rectifier and the A-type currents, respectively, that we recorded. These results demonstrate the early expression of delayed rectifier and A-type K+ currents and channels in embryonic neural progenitor cells prior to the differentiation of these cells. PMID:18270591

  19. Implementation of Basic and Universal Gates In a single Circuit Based On Quantum-dot Cellular Automata Using Multi-Layer Crossbar Wire

    NASA Astrophysics Data System (ADS)

    Bhowmik, Dhrubajyoti; Saha, Apu Kr; Dutta, Paramartha; Nandi, Supratim

    2017-08-01

    Quantum-dot Cellular Automata (QCA) is one of the most substitutes developing nanotechnologies for electronic circuits, as a result of lower force utilization, higher speed and smaller size in correlation with CMOS innovation. The essential devices, a Quantum-dot cell can be utilized to logic gates and wires. As it is the key building block on nanotechnology circuits. By applying simple gates, the hardware requirements for a QCA circuit can be decreased and circuits can be less complex as far as level, delay and cell check. This article exhibits an unobtrusive methodology for actualizing novel upgraded simple and universal gates, which can be connected to outline numerous variations of complex QCA circuits. Proposed gates are straightforward in structure and capable as far as implementing any digital circuits. The main aim is to build all basic and universal gates in a simple circuit with and without crossbar-wire. Simulation results and physical relations affirm its handiness in actualizing each advanced circuit.

  20. Ultrasound-targeted microbubble destruction enhances delayed BMC delivery and attenuates post-infarction cardiac remodelling by inducing engraftment signals.

    PubMed

    Chen, Yanmei; Zhang, Chuanxi; Shen, Shuxin; Guo, Shengcun; Zhong, Lintao; Li, Xinzhong; Chen, Guojun; Chen, Gangbin; He, Xiang; Huang, Chixiong; He, Nvqin; Liao, Wangjun; Liao, Yulin; Bin, Jianping

    2016-12-01

    Delayed administration of bone marrow cells (BMCs) at 2-4 weeks after successful reperfusion in patients with acute myocardial infarction (MI) does not improve cardiac function. The reduction in engraftment signals observed following this time interval might impair the effects of delayed BMC treatment. In the present study, we aimed to determine whether ultrasound-targeted microbubble destruction (UTMD) treatment could increase engraftment signals, enhance the delivery of delayed BMCs and subsequently attenuate post-infarction cardiac remodelling. A myocardial ischaemia/reperfusion (I/R) model was induced in Wistar rats via left coronary ligation for 45 min followed by reperfusion. Western blotting revealed that engraftment signals peaked at 7 days post-I/R and were dramatically lower at 14 days post-I/R. The lower engraftment signals at 14 days post-I/R could be triggered by UTMD treatment at a mechanical index of 1.0-1.9. The troponin I levels in the 1.9 mechanical index group were higher than in the other groups. Simultaneous haematoxylin and eosin staining and fluorescence revealed that the number of engrafted BMCs in the ischaemic zone was greater in the group treated with both UTMD and delayed BMC transplantation than in the control groups (P<0.05). Both UTMD and delayed BMC transplantation improved cardiac function and decreased cardiac fibrosis at 4 weeks after treatment, as compared with control groups (both P<0.05). Histopathology demonstrated that UTMD combined with delayed BMC transplantation increased capillary density, myocardial cell proliferation and c-kit + cell proliferation. These findings indicated that UTMD treatment could induce engraftment signals and enhance homing of delayed BMCs to ischaemic myocardium, attenuating post-infarction cardiac remodelling by promoting neovascularization, cardiomyogenesis and expansion of cardiac c-kit + cells. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  1. Cancer susceptibility and reproductive trade-offs: a model of the evolution of cancer defences

    PubMed Central

    Boddy, Amy M.; Kokko, Hanna; Breden, Felix; Wilkinson, Gerald S.; Aktipis, C. Athena

    2015-01-01

    The factors influencing cancer susceptibility and why it varies across species are major open questions in the field of cancer biology. One underexplored source of variation in cancer susceptibility may arise from trade-offs between reproductive competitiveness (e.g. sexually selected traits, earlier reproduction and higher fertility) and cancer defence. We build a model that contrasts the probabilistic onset of cancer with other, extrinsic causes of mortality and use it to predict that intense reproductive competition will lower cancer defences and increase cancer incidence. We explore the trade-off between cancer defences and intraspecific competition across different extrinsic mortality conditions and different levels of trade-off intensity, and find the largest effect of competition on cancer in species where low extrinsic mortality combines with strong trade-offs. In such species, selection to delay cancer and selection to outcompete conspecifics are both strong, and the latter conflicts with the former. We discuss evidence for the assumed trade-off between reproductive competitiveness and cancer susceptibility. Sexually selected traits such as ornaments or large body size require high levels of cell proliferation and appear to be associated with greater cancer susceptibility. Similar associations exist for female traits such as continuous egg-laying in domestic hens and earlier reproductive maturity. Trade-offs between reproduction and cancer defences may be instantiated by a variety of mechanisms, including higher levels of growth factors and hormones, less efficient cell-cycle control and less DNA repair, or simply a larger number of cell divisions (relevant when reproductive success requires large body size or rapid reproductive cycles). These mechanisms can affect intra- and interspecific variation in cancer susceptibility arising from rapid cell proliferation during reproductive maturation, intrasexual competition and reproduction. PMID:26056364

  2. Influence of emission threshold of explosive emission cathodes on current waveform in foilless diodes

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

    Wu, P.; Liu, G. Z.; Science and Technology on High Power Microwave Laboratory, Northwest Institute of Nuclear Technology, Xi'an 710024

    The emission threshold of explosive emission cathodes (EECs) is an important factor for beam quality. It can affect the explosive emission delay time, the plasma expansion process on the cathode surface, and even the current amplitude when the current is not fully space-charge-limited. This paper researches the influence of the emission threshold of an annular EEC on the current waveform in a foilless diode when the current is measured by a Rogowski coil. The particle-in-cell simulation which is performed under some tolerable and necessary simplifications shows that the long explosive emission delay time of high-threshold cathodes may leave an apparentmore » peak of displacement current on the rise edge of the current waveform, and this will occur only when the electron emission starts after this peak. The experimental researches, which are performed under a diode voltage of 1 MV and a repetitive frequency of 20 Hz, demonstrate that the graphite cathode has a lower emission threshold and a longer lifetime than the stainless steel cathode according to the variation of the peak of displacement current on the rise edge of the current waveform.« less

  3. Discovery of time-delayed gene regulatory networks based on temporal gene expression profiling

    PubMed Central

    Li, Xia; Rao, Shaoqi; Jiang, Wei; Li, Chuanxing; Xiao, Yun; Guo, Zheng; Zhang, Qingpu; Wang, Lihong; Du, Lei; Li, Jing; Li, Li; Zhang, Tianwen; Wang, Qing K

    2006-01-01

    Background It is one of the ultimate goals for modern biological research to fully elucidate the intricate interplays and the regulations of the molecular determinants that propel and characterize the progression of versatile life phenomena, to name a few, cell cycling, developmental biology, aging, and the progressive and recurrent pathogenesis of complex diseases. The vast amount of large-scale and genome-wide time-resolved data is becoming increasing available, which provides the golden opportunity to unravel the challenging reverse-engineering problem of time-delayed gene regulatory networks. Results In particular, this methodological paper aims to reconstruct regulatory networks from temporal gene expression data by using delayed correlations between genes, i.e., pairwise overlaps of expression levels shifted in time relative each other. We have thus developed a novel model-free computational toolbox termed TdGRN (Time-delayed Gene Regulatory Network) to address the underlying regulations of genes that can span any unit(s) of time intervals. This bioinformatics toolbox has provided a unified approach to uncovering time trends of gene regulations through decision analysis of the newly designed time-delayed gene expression matrix. We have applied the proposed method to yeast cell cycling and human HeLa cell cycling and have discovered most of the underlying time-delayed regulations that are supported by multiple lines of experimental evidence and that are remarkably consistent with the current knowledge on phase characteristics for the cell cyclings. Conclusion We established a usable and powerful model-free approach to dissecting high-order dynamic trends of gene-gene interactions. We have carefully validated the proposed algorithm by applying it to two publicly available cell cycling datasets. In addition to uncovering the time trends of gene regulations for cell cycling, this unified approach can also be used to study the complex gene regulations related to the development, aging and progressive pathogenesis of a complex disease where potential dependences between different experiment units might occurs. PMID:16420705

  4. Circulating carotenoid concentrations are positively correlated with later clutch initiation in Florida Scrub-Jays (Aphelocoma coerulescens).

    PubMed

    Heiss, Rebecca S; Cohen, Alan A; Bowman, Reed; Boughton, Raoul K; Bridge, Eli; McGraw, Kevin J; Schoech, Stephan J

    2011-02-01

    Antioxidants play key roles in preventing free radical damage to various molecules, cells, and tissues, but it is not well understood how variation in antioxidant levels may relate to the reproductive success or health of wild animals. We explored the relationship between circulating antioxidant concentrations and both body condition and timing of reproduction in male and female Florida Scrub-Jays (Aphelocoma coerulescens), a cooperatively breeding passerine bird. We examined whether levels of uric acid, vitamin E, and carotenoids (all potentially important antioxidants) were linked to body condition and timing of reproduction, two measures that are directly related to reproductive success. Antioxidant concentrations were not correlated with body condition, but they were related to timing of first clutch initiation, though not always in the predicted direction. Elevated circulating levels of carotenoids were associated with delayed clutch initiation in female breeders. Relatively higher vitamin E levels in control birds were associated with earlier clutch initiation, whereas male breeders that received long-term food supplementation had elevated levels of vitamin E and delayed reproduction. Several potential explanations for the link between elevated levels of antioxidants and delayed clutch initiation are discussed. Separate explanations for each sex include, but are not limited to, oxidative stress as a result of territory defense efforts in males, different dietary regimes due to supplementation, and mobilized plasma antioxidants in females that were coping with a stressor. © 2010 Wiley-Liss, Inc.

  5. A Robust and Multi-Weighted Approach to Estimating Topographically Correlated Tropospheric Delays in Radar Interferograms

    PubMed Central

    Zhu, Bangyan; Li, Jiancheng; Chu, Zhengwei; Tang, Wei; Wang, Bin; Li, Dawei

    2016-01-01

    Spatial and temporal variations in the vertical stratification of the troposphere introduce significant propagation delays in interferometric synthetic aperture radar (InSAR) observations. Observations of small amplitude surface deformations and regional subsidence rates are plagued by tropospheric delays, and strongly correlated with topographic height variations. Phase-based tropospheric correction techniques assuming a linear relationship between interferometric phase and topography have been exploited and developed, with mixed success. Producing robust estimates of tropospheric phase delay however plays a critical role in increasing the accuracy of InSAR measurements. Meanwhile, few phase-based correction methods account for the spatially variable tropospheric delay over lager study regions. Here, we present a robust and multi-weighted approach to estimate the correlation between phase and topography that is relatively insensitive to confounding processes such as regional subsidence over larger regions as well as under varying tropospheric conditions. An expanded form of robust least squares is introduced to estimate the spatially variable correlation between phase and topography by splitting the interferograms into multiple blocks. Within each block, correlation is robustly estimated from the band-filtered phase and topography. Phase-elevation ratios are multiply- weighted and extrapolated to each persistent scatter (PS) pixel. We applied the proposed method to Envisat ASAR images over the Southern California area, USA, and found that our method mitigated the atmospheric noise better than the conventional phase-based method. The corrected ground surface deformation agreed better with those measured from GPS. PMID:27420066

  6. A Robust and Multi-Weighted Approach to Estimating Topographically Correlated Tropospheric Delays in Radar Interferograms.

    PubMed

    Zhu, Bangyan; Li, Jiancheng; Chu, Zhengwei; Tang, Wei; Wang, Bin; Li, Dawei

    2016-07-12

    Spatial and temporal variations in the vertical stratification of the troposphere introduce significant propagation delays in interferometric synthetic aperture radar (InSAR) observations. Observations of small amplitude surface deformations and regional subsidence rates are plagued by tropospheric delays, and strongly correlated with topographic height variations. Phase-based tropospheric correction techniques assuming a linear relationship between interferometric phase and topography have been exploited and developed, with mixed success. Producing robust estimates of tropospheric phase delay however plays a critical role in increasing the accuracy of InSAR measurements. Meanwhile, few phase-based correction methods account for the spatially variable tropospheric delay over lager study regions. Here, we present a robust and multi-weighted approach to estimate the correlation between phase and topography that is relatively insensitive to confounding processes such as regional subsidence over larger regions as well as under varying tropospheric conditions. An expanded form of robust least squares is introduced to estimate the spatially variable correlation between phase and topography by splitting the interferograms into multiple blocks. Within each block, correlation is robustly estimated from the band-filtered phase and topography. Phase-elevation ratios are multiply- weighted and extrapolated to each persistent scatter (PS) pixel. We applied the proposed method to Envisat ASAR images over the Southern California area, USA, and found that our method mitigated the atmospheric noise better than the conventional phase-based method. The corrected ground surface deformation agreed better with those measured from GPS.

  7. Effective Desynchronization by Nonlinear Delayed Feedback

    NASA Astrophysics Data System (ADS)

    Popovych, Oleksandr V.; Hauptmann, Christian; Tass, Peter A.

    2005-04-01

    We show that nonlinear delayed feedback opens up novel means for the control of synchronization. In particular, we propose a demand-controlled method for powerful desynchronization, which does not require any time-consuming calibration. Our technique distinguishes itself by its robustness against variations of system parameters, even in strongly coupled ensembles of oscillators. We suggest our method for mild and effective deep brain stimulation in neurological diseases characterized by pathological cerebral synchronization.

  8. Propellant Crack Tip Ignition and Propagation under Rapid Pressurization

    DTIC Science & Technology

    1982-10-01

    that the ignition-delay time decreases and the heat flux to the propellant surface increases as the pressurization rate is increased. The decrease in...leading to ignition. The model predicts the experimental obseriation that the ignition delay time decreases as the pressurization rate is increased...pressurization rate on both crack propagation velocity and time variation of crack shape was studied. Experimental results indicated that the crack velocity

  9. Integrated Doppler Correction to TWSTFT Using Round-Trip Measurement

    DTIC Science & Technology

    2010-11-01

    42 nd Annual Precise Time and Time Interval (PTTI) Meeting 251 INTEGRATED DOPPLER CORRECTION TO TWSTFT USING ROUND-TRIP MEASUREMENT Yi...Frequency Transfer ( TWSTFT ) data. It is necessary to correct the diurnal variation for comparing the time-scale difference. We focus on the up-/downlink...delay difference caused by satellite motion. In this paper, we propose to correct the TWSTFT data by using round-trip delay measurement. There are

  10. Neuroanatomy of Individual Differences in Language in Adult Males with Autism

    PubMed Central

    Lai, Meng-Chuan; Lombardo, Michael V.; Ecker, Christine; Chakrabarti, Bhismadev; Suckling, John; Bullmore, Edward T.; Happé, Francesca; Murphy, Declan G. M.; Baron-Cohen, Simon

    2015-01-01

    One potential source of heterogeneity within autism spectrum conditions (ASC) is language development and ability. In 80 high-functioning male adults with ASC, we tested if variations in developmental and current structural language are associated with current neuroanatomy. Groups with and without language delay differed behaviorally in early social reciprocity, current language, but not current autistic features. Language delay was associated with larger total gray matter (GM) volume, smaller relative volume at bilateral insula, ventral basal ganglia, and right superior, middle, and polar temporal structures, and larger relative volume at pons and medulla oblongata in adulthood. Despite this heterogeneity, those with and without language delay showed significant commonality in morphometric features when contrasted with matched neurotypical individuals (n = 57). In ASC, better current language was associated with increased GM volume in bilateral temporal pole, superior temporal regions, dorsolateral fronto-parietal and cerebellar structures, and increased white matter volume in distributed frontal and insular regions. Furthermore, current language–neuroanatomy correlation patterns were similar across subgroups with or without language delay. High-functioning adult males with ASC show neuroanatomical variations associated with both developmental and current language characteristics. This underscores the importance of including both developmental and current language as specifiers for ASC, to help clarify heterogeneity. PMID:25249409

  11. Interaction of emitted sonar pulses and simulated echoes in a false killer whale: an evoked-potential study.

    PubMed

    Supin, Alexander Ya; Nachtigall, Paul E; Breese, Marlee

    2011-09-01

    Auditory evoked potentials (AEP) were recorded during echolocation in a false killer whale Pseudorca crassidens. An electronically synthesized and played-back (simulated) echo was triggered by an emitted biosonar pulse, and its intensity was proportional to that of the emitted click. The delay and transfer factor of the echo relative to the emitted click was controlled by the operator. The echo delay varied from 2 to 16 ms (by two-fold steps), and the transfer factor varied within ranges from -45 to -30 dB at the 2-ms delay to -60 to -45 dB at the 16-ms delay. Echo-related AEPs featured amplitude dependence both on echo delay at a constant transfer factor (the longer the delay, the higher amplitude) and on echo transfer factor at a constant delay (the higher transfer factor, the higher amplitude). Conjunctional variation of the echo transfer factor and delay kept the AEP amplitude constant when the delay to transfer factor trade was from -7.1 to -8.4 dB per delay doubling. The results confirm the hypothesis that partial forward masking of the echoes by the preceding emitted sonar pulses serves as a time-varying automatic gain control in the auditory system of echolocating odontocetes. © 2011 Acoustical Society of America

  12. CASSIA--a dynamic model for predicting intra-annual sink demand and interannual growth variation in Scots pine.

    PubMed

    Schiestl-Aalto, Pauliina; Kulmala, Liisa; Mäkinen, Harri; Nikinmaa, Eero; Mäkelä, Annikki

    2015-04-01

    The control of tree growth vs environment by carbon sources or sinks remains unresolved although it is widely studied. This study investigates growth of tree components and carbon sink-source dynamics at different temporal scales. We constructed a dynamic growth model 'carbon allocation sink source interaction' (CASSIA) that calculates tree-level carbon balance from photosynthesis, respiration, phenology and temperature-driven potential structural growth of tree organs and dynamics of stored nonstructural carbon (NSC) and their modifying influence on growth. With the model, we tested hypotheses that sink demand explains the intra-annual growth dynamics of the meristems, and that the source supply is further needed to explain year-to-year growth variation. The predicted intra-annual dimensional growth of shoots and needles and the number of cells in xylogenesis phases corresponded with measurements, whereas NSC hardly limited the growth, supporting the first hypothesis. Delayed GPP influence on potential growth was necessary for simulating the yearly growth variation, indicating also at least an indirect source limitation. CASSIA combines seasonal growth and carbon balance dynamics with long-term source dynamics affecting growth and thus provides a first step to understanding the complex processes regulating intra- and interannual growth and sink-source dynamics. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  13. Dynamics of landslide model with time delay and periodic parameter perturbations

    NASA Astrophysics Data System (ADS)

    Kostić, Srđan; Vasović, Nebojša; Franović, Igor; Jevremović, Dragutin; Mitrinovic, David; Todorović, Kristina

    2014-09-01

    In present paper, we analyze the dynamics of a single-block model on an inclined slope with Dieterich-Ruina friction law under the variation of two new introduced parameters: time delay Td and initial shear stress μ. It is assumed that this phenomenological model qualitatively simulates the motion along the infinite creeping slope. The introduction of time delay is proposed to mimic the memory effect of the sliding surface and it is generally considered as a function of history of sliding. On the other hand, periodic perturbation of initial shear stress emulates external triggering effect of long-distant earthquakes or some non-natural vibration source. The effects of variation of a single observed parameter, Td or μ, as well as their co-action, are estimated for three different sliding regimes: β < 1, β = 1 and β > 1, where β stands for the ratio of long-term to short-term stress changes. The results of standard local bifurcation analysis indicate the onset of complex dynamics for very low values of time delay. On the other side, numerical approach confirms an additional complexity that was not observed by local analysis, due to the possible effect of global bifurcations. The most complex dynamics is detected for β < 1, with a complete Ruelle-Takens-Newhouse route to chaos under the variation of Td, or the co-action of both parameters Td and μ. These results correspond well with the previous experimental observations on clay and siltstone with low clay fraction. In the same regime, the perturbation of only a single parameter, μ, renders the oscillatory motion of the block. Within the velocity-independent regime, β = 1, the inclusion and variation of Td generates a transition to equilibrium state, whereas the small oscillations of μ induce oscillatory motion with decreasing amplitude. The co-action of both parameters, in the same regime, causes the decrease of block's velocity. As for β > 1, highly-frequent, limit-amplitude oscillations of initial stress give rise to oscillatory motion. Also for β > 1, in case of perturbing only the initial shear stress, with smaller amplitude, velocity of the block changes exponentially fast. If the time delay is introduced, besides the stress perturbation, within the same regime, the co-action of Td (Td < 0.1) and small oscillations of μ induce the onset of deterministic chaos.

  14. Acute Cellular Rejection in ABO-Incompatible Renal Transplant Recipients Receiving Rituximab Is Associated with Delayed-Onset Neutropenia.

    PubMed

    Uchida, Junji; Iwai, Tomoaki; Nishide, Shunji; Kabei, Kazuya; Kuwabara, Nobuyuki; Yamasaki, Takeshi; Naganuma, Toshihide; Kumada, Norihiko; Takemoto, Yoshiaki; Nakatani, Tatsuya

    2017-07-25

    BACKGROUND Rituximab induces long-lasting B cell depletion in the peripheral blood and increases the levels of proinflammatory cytokines associated with regulatory B cell depletion. Previous reports showed that B cell-related cytokine release after administration of rituximab may induce acute cellular rejection (ACR) and delayed-onset neutropenia. The present study was conducted to investigate the correlation between acute rejection and delayed-onset neutropenia in ABO-incompatible renal transplant recipients who underwent administration of rituximab for 1 year after transplantation. MATERIAL AND METHODS From June 2006 to July 2015, 47 patients with chronic renal failure received ABO-incompatible renal transplant with rituximab induction at Osaka City University Hospital. All 47 patients underwent plasmapheresis due to removal of anti-A/B antibodies and administration of rituximab, and their transplants were carried out successfully. We investigated the correlation between ACR and delayed-onset neutropenia in ABO-incompatible renal transplant recipients who underwent administration of rituximab for 1 year after transplantation. RESULTS Fourteen patients (29.8%) experienced ACR (group A), and 33 recipients did not develop ACR (group B). The frequency of delayed-onset neutropenia was higher in group A than in group B (p=0.0503). Multivariate logistic regression analysis revealed that the frequency of ACR correlated significantly with the prevalence of delayed-onset neutropenia. CONCLUSIONS Our results indicated that ACR in ABO-incompatible renal transplant recipients receiving rituximab was associated with delayed-onset neutropenia.

  15. Variables affecting the quantitation of CD22 in neoplastic B cells.

    PubMed

    Jasper, Gregory A; Arun, Indu; Venzon, David; Kreitman, Robert J; Wayne, Alan S; Yuan, Constance M; Marti, Gerald E; Stetler-Stevenson, Maryalice

    2011-03-01

    Quantitative flow cytometry (QFCM) is being applied in the clinical flow cytometry laboratory for diagnosis, prognosis, and assessment of patients receiving antibody-based therapy. ABC values and the effect of technical variables on CD22 quantitation in acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), follicular lymphoma (FCL), hairy cell leukemia (HCL) and normal B cells were studied. The QuantiBrite System® was used to determine the level of CD22 expression (mean antibody bound per cell, ABC) by malignant and normal B cells. The intra-assay variability, number of cells required for precision, effect of delayed processing as well as shipment of peripheral blood specimens (delayed processing and exposure to noncontrolled environments), and the effect of paraformaldehyde fixation on assay results were studied. The QuantiBRITE method of measuring CD22 ABC is precise (median CV 1.6%, 95% confidence interval, 1.2-2.3%) but a threshold of 250 malignant cells is required for reliable CD22 ABC values. Delayed processing and overnight shipment of specimens resulted in significantly different ABC values whereas fixation for up to 12 h had no significant effect. ABC measurements determined that CD22 expression is lower than normal in ALL, CLL, FCL, and MCL but higher than normal in HCL. CD22 expression was atypical in the hematolymphoid malignancies studied and may have diagnostic utility. Technical variables such as cell number analyzed and delayed processing or overnight shipment of specimens impact significantly on the measurement of antigen expression by QFCM in the clinical laboratory. Published 2010 Wiley-Liss, Inc.

  16. Heat shock protein 27 overexpression in CHO cells modulates apoptosis pathways and delays activation of caspases to improve recombinant monoclonal antibody titre in fed-batch bioreactors.

    PubMed

    Tan, Janice G L; Lee, Yih Yean; Wang, Tianhua; Yap, Miranda G S; Tan, Tin Wee; Ng, Say Kong

    2015-05-01

    CHO cells are major production hosts for recombinant biologics including the rapidly expanding recombinant monoclonal antibodies (mAbs). Heat shock protein 27 (HSP27) expression was observed to be down-regulated towards the late-exponential and stationary phase of CHO fed-batch bioreactor cultures, whereas HSP27 was found to be highly expressed in human pathological cells and reported to have anti-apoptotic functions. These phenotypes suggest that overexpression of HSP27 is a potential cell line engineering strategy for improving robustness of CHO cells. In this work, HSP27 was stably overexpressed in CHO cells producing recombinant mAb and the effects of HSP27 on cell growth, volumetric production titer and product quality were assessed. Concomitantly, HSP27 anti-apoptosis functions in CHO cells were investigated. Stably transfected clones cultured in fed-batch bioreactors displayed 2.2-fold higher peak viable cell density, delayed loss of culture viability by two days and 2.3-fold increase in mAb titer without affecting the N-glycosylation profile, as compared to clones stably transfected with the vector backbone. Co-immunoprecipitation studies revealed HSP27 interactions with Akt, pro-caspase 3 and Daxx and caspase activity profiling showed delayed increase in caspase 2, 3, 8 and 9 activities. These results suggest that HSP27 modulates apoptosis signaling pathways and delays caspase activities to improve performance of CHO fed-batch bioreactor cultures. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. The renal cell carcinoma-associated oncogenic fusion protein PRCCTFE3 provokes p21{sup W{sup A{sup F{sup 1{sup /{sup C{sup I{sup P{sup 1}}}}}}}}}-mediated cell cycle delay

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

    Medendorp, Klaas; Groningen, Jan J.M. van; Vreede, Lilian

    2009-08-15

    Previously, we found that in t(X;1)(p11;q21)-positive renal cell carcinomas the bHLH-LZ transcription factor TFE3 is fused to a novel protein designated PRCC. In addition, we found that the PRCCTFE3 fusion protein, which has retained all known functional domains of TFE3, acts as a more potent transcriptional activator than wild type TFE3. We also found that PRCCTFE3 expression confers in vitro and in vivo transformation onto various cell types, including those of the kidney. Here we show that de novo expression of the PRCCTFE3 fusion protein provokes cell cycle delay. This delay, which is mediated by induction of the cyclin-dependent kinasemore » inhibitor p21{sup W{sup A{sup F{sup 1{sup /{sup C{sup I{sup P{sup 1}}}}}}}}}, affects both the G1/S and the G2/M phases of the cell cycle and prevents the cells from undergoing polyploidization. We also show that the PRCCTFE3 fusion protein binds directly to the p21{sup W{sup A{sup F{sup 1{sup /{sup C{sup I{sup P{sup 1}}}}}}}}} promoter and that the PRCCTFE3-induced up-regulation of p21{sup W{sup A{sup F{sup 1{sup /{sup C{sup I{sup P{sup 1}}}}}}}}} leads to activation of the pRB pathway. Finally, we show that in t(X;1)(p11;q21)-positive renal tumor cells several processes that link PRCCTFE3 expression to p21{sup W{sup A{sup F{sup 1{sup /{sup C{sup I{sup P{sup 1}}}}}}}}}-mediated cell cycle delay are abrogated. Our data suggest a scenario in which, during the course of renal cell carcinoma development, an initial PRCCTFE3-induced cell cycle delay must be numbed, thus permitting continued proliferation and progression towards full-blown malignancy.« less

  18. The Influence of Procedure Delay on Resource Utilization: A National Study of Patients with Open Tibial Fracture

    PubMed Central

    Sears, Erika Davis; Burke, James F.; Davis, Matthew M.; Chung, Kevin C.

    2016-01-01

    Background The purpose of this study is to 1) understand national variation in delay of emergency procedures in patients with open tibial fracture at the hospital level and 2) compare length of stay (LOS) and cost in patients cared for at the best and worst performing hospitals for delay. Methods We retrospectively analyzed the 2003 – 2009 Nationwide Inpatient Sample. Adult patients with primary diagnosis of open tibial fracture were selected for inclusion. We calculated hospital probability of delay of emergency procedures beyond the day of admission (day 0). Multilevel linear regression random effects models were created to evaluate the relationship between the treating hospital’s tendency for delay (in quartiles) and the log-transformed outcomes of LOS and cost, while adjusting for patient and hospital variables. Results The final sample included 7,029 patients from 332 hospitals. Adjusted analyses demonstrate that patients treated at hospitals in the fourth (worst) quartile for delay were estimated to have 12% (95% CI 2–21%) higher cost compared to patients treated at hospitals in the first quartile. In addition, patients treated at hospitals in the fourth quartile had an estimated 11% (CI 4–17%) longer LOS compared to patients treated at hospitals in the first quartile. Conclusions Patients with open tibial fracture treated at hospitals with more timely initiation of surgical care had lower cost and shorter LOS than patients treated at hospitals with less timely initiation of care. Policies directed toward mitigating variation in care are not only beneficial for patient outcomes, but may also reduce unnecessary waste. Level II (Prognostic) PMID:23142940

  19. Spatio-Temporal Variability of the Phase of Total Ozone Quasi-Decennial Oscillations

    NASA Astrophysics Data System (ADS)

    Visheratin, K. N.

    2017-12-01

    The SBUV/SBUV2 (65° S-65° N) and Bodeker Scientific (90° S-90° N) satellite databases have been used for composite and cross-wavelet analyses of the spatio-temporal variability of phase relations between a 11-year cycle of solar activity (SA) and quasi-decennial oscillations (QDOs) of total ozone content (TOC). For globally average TOC values, the QDO maxima coincide in phase with the solar-activity maxima, and amplitude variations of TOC correlate with those of the 11-year solar cycle. According to the analysis of amplitude and phase of QDOs for the zonal average TOC fields, a QDO amplitude is about 6-7 Dobson Units (DU) in the high northern and southern latitudes, and it does not exceed 2-3 DU in the tropic regions. The latitudinal TOC variations are distinguished by a delay of the quasi-decennial oscillation phase in the southern latitudes in comparison with the northern latitudes. The TOC maxima phase coincides with the SA maxima phase in the tropic regions; the TOC variations go ahead of the SA variations, on average, in moderate and high latitudes of the Northern Hemisphere; the TOC variations are behind the SA variations in the Southern Hemisphere. The phase delay between TOC QDO maxima in the northern and southern latitudes appears to increase in the course of time, and the TOC quasi-decennial variations in the Arctic and Antarctic subpolar regions occur approximately in an antiphase over the last two decades.

  20. Multi-objective LQR with optimum weight selection to design FOPID controllers for delayed fractional order processes.

    PubMed

    Das, Saptarshi; Pan, Indranil; Das, Shantanu

    2015-09-01

    An optimal trade-off design for fractional order (FO)-PID controller is proposed with a Linear Quadratic Regulator (LQR) based technique using two conflicting time domain objectives. A class of delayed FO systems with single non-integer order element, exhibiting both sluggish and oscillatory open loop responses, have been controlled here. The FO time delay processes are handled within a multi-objective optimization (MOO) formalism of LQR based FOPID design. A comparison is made between two contemporary approaches of stabilizing time-delay systems withinLQR. The MOO control design methodology yields the Pareto optimal trade-off solutions between the tracking performance and total variation (TV) of the control signal. Tuning rules are formed for the optimal LQR-FOPID controller parameters, using median of the non-dominated Pareto solutions to handle delayed FO processes. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

  1. An Efficient Offloading Scheme For MEC System Considering Delay and Energy Consumption

    NASA Astrophysics Data System (ADS)

    Sun, Yanhua; Hao, Zhe; Zhang, Yanhua

    2018-01-01

    With the increasing numbers of mobile devices, mobile edge computing (MEC) which provides cloud computing capabilities proximate to mobile devices in 5G networks has been envisioned as a promising paradigm to enhance users experience. In this paper, we investigate a joint consideration of delay and energy consumption offloading scheme (JCDE) for MEC system in 5G heterogeneous networks. An optimization is formulated to minimize the delay as well as energy consumption of the offloading system, which the delay and energy consumption of transmitting and calculating tasks are taken into account. We adopt an iterative greedy algorithm to solve the optimization problem. Furthermore, simulations were carried out to validate the utility and effectiveness of our proposed scheme. The effect of parameter variations on the system is analysed as well. Numerical results demonstrate delay and energy efficiency promotion of our proposed scheme compared with another paper’s scheme.

  2. Premixed autoignition in compressible turbulence

    NASA Astrophysics Data System (ADS)

    Konduri, Aditya; Kolla, Hemanth; Krisman, Alexander; Chen, Jacqueline

    2016-11-01

    Prediction of chemical ignition delay in an autoignition process is critical in combustion systems like compression ignition engines and gas turbines. Often, ignition delay times measured in simple homogeneous experiments or homogeneous calculations are not representative of actual autoignition processes in complex turbulent flows. This is due the presence of turbulent mixing which results in fluctuations in thermodynamic properties as well as chemical composition. In the present study the effect of fluctuations of thermodynamic variables on the ignition delay is quantified with direct numerical simulations of compressible isotropic turbulence. A premixed syngas-air mixture is used to remove the effects of inhomogeneity in the chemical composition. Preliminary results show a significant spatial variation in the ignition delay time. We analyze the topology of autoignition kernels and identify the influence of extreme events resulting from compressibility and intermittency. The dependence of ignition delay time on Reynolds and turbulent Mach numbers is also quantified. Supported by Basic Energy Sciences, Dept of Energy, United States.

  3. Delay compensation - Its effect in reducing sampling errors in Fourier spectroscopy

    NASA Technical Reports Server (NTRS)

    Zachor, A. S.; Aaronson, S. M.

    1979-01-01

    An approximate formula is derived for the spectrum ghosts caused by periodic drive speed variations in a Michelson interferometer. The solution represents the case of fringe-controlled sampling and is applicable when the reference fringes are delayed to compensate for the delay introduced by the electrical filter in the signal channel. Numerical results are worked out for several common low-pass filters. It is shown that the maximum relative ghost amplitude over the range of frequencies corresponding to the lower half of the filter band is typically 20 times smaller than the relative zero-to-peak velocity error, when delayed sampling is used. In the lowest quarter of the filter band it is more than 100 times smaller than the relative velocity error. These values are ten and forty times smaller, respectively, than they would be without delay compensation if the filter is a 6-pole Butterworth.

  4. Time-delayed feedback control of breathing localized structures in a three-component reaction-diffusion system.

    PubMed

    Gurevich, Svetlana V

    2014-10-28

    The dynamics of a single breathing localized structure in a three-component reaction-diffusion system subjected to time-delayed feedback is investigated. It is shown that variation of the delay time and the feedback strength can lead either to stabilization of the breathing or to delay-induced periodic or quasi-periodic oscillations of the localized structure. A bifurcation analysis of the system in question is provided and an order parameter equation is derived that describes the dynamics of the localized structure in the vicinity of the Andronov-Hopf bifurcation. With the aid of this equation, the boundaries of the stabilization domains as well as the dependence of the oscillation radius on delay parameters can be explicitly derived, providing a robust mechanism to control the behaviour of the breathing localized structure in a straightforward manner. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  5. Impact of time delay on the dynamics of SEIR epidemic model using cellular automata

    NASA Astrophysics Data System (ADS)

    Sharma, Natasha; Gupta, Arvind Kumar

    2017-04-01

    The delay of an infectious disease is significant when aiming to predict its strength and spreading patterns. In this paper the SEIR ​(susceptible-exposed-infected-recovered) epidemic spread with time delay is analyzed through a two-dimensional cellular automata model. The time delay corresponding to the infectious span, predominantly, includes death during the latency period in due course of infection. The advancement of whole system is described by SEIR transition function complemented with crucial factors like inhomogeneous population distribution, birth and disease independent mortality. Moreover, to reflect more realistic population dynamics some stochastic parameters like population movement and connections at local level are also considered. The existence and stability of disease free equilibrium is investigated. Two prime behavioral patterns of disease dynamics is found depending on delay. The critical value of delay, beyond which there are notable variations in spread patterns, is computed. The influence of important parameters affecting the disease dynamics on basic reproduction number is also examined. The results obtained show that delay plays an affirmative role to control disease progression in an infected host.

  6. Radar wideband digital beamforming based on time delay and phase compensation

    NASA Astrophysics Data System (ADS)

    Fu, Wei; Jiang, Defu

    2018-07-01

    In conventional phased array radars, analogue time delay devices and phase shifters have been used for wideband beamforming. These methods suffer from insertion losses, gain mismatches and delay variations, and they occupy a large chip area. To solve these problems, a compact architecture of digital array antennas based on subarrays was considered. In this study, the receiving beam patterns of wideband linear frequency modulation (LFM) signals were constructed by applying analogue stretch processing via mixing with delayed reference signals at the subarray level. Subsequently, narrowband digital time delaying and phase compensation of the tone signals were implemented with reduced arithmetic complexity. Due to the differences in amplitudes, phases and time delays between channels, severe performance degradation of the beam patterns occurred without corrections. To achieve good beamforming performance, array calibration was performed in each channel to adjust the amplitude, frequency and phase of the tone signal. Using a field-programmable gate array, wideband LFM signals and finite impulse response filters with continuously adjustable time delays were implemented in a polyphase structure. Simulations and experiments verified the feasibility and effectiveness of the proposed digital beamformer.

  7. Limits to Forecasting Precision for Outbreaks of Directly Transmitted Diseases

    PubMed Central

    Drake, John M

    2006-01-01

    Background Early warning systems for outbreaks of infectious diseases are an important application of the ecological theory of epidemics. A key variable predicted by early warning systems is the final outbreak size. However, for directly transmitted diseases, the stochastic contact process by which outbreaks develop entails fundamental limits to the precision with which the final size can be predicted. Methods and Findings I studied how the expected final outbreak size and the coefficient of variation in the final size of outbreaks scale with control effectiveness and the rate of infectious contacts in the simple stochastic epidemic. As examples, I parameterized this model with data on observed ranges for the basic reproductive ratio (R 0) of nine directly transmitted diseases. I also present results from a new model, the simple stochastic epidemic with delayed-onset intervention, in which an initially supercritical outbreak (R 0 > 1) is brought under control after a delay. Conclusion The coefficient of variation of final outbreak size in the subcritical case (R 0 < 1) will be greater than one for any outbreak in which the removal rate is less than approximately 2.41 times the rate of infectious contacts, implying that for many transmissible diseases precise forecasts of the final outbreak size will be unattainable. In the delayed-onset model, the coefficient of variation (CV) was generally large (CV > 1) and increased with the delay between the start of the epidemic and intervention, and with the average outbreak size. These results suggest that early warning systems for infectious diseases should not focus exclusively on predicting outbreak size but should consider other characteristics of outbreaks such as the timing of disease emergence. PMID:16435887

  8. Dynamics of a stochastic cell-to-cell HIV-1 model with distributed delay

    NASA Astrophysics Data System (ADS)

    Ji, Chunyan; Liu, Qun; Jiang, Daqing

    2018-02-01

    In this paper, we consider a stochastic cell-to-cell HIV-1 model with distributed delay. Firstly, we show that there is a global positive solution of this model before exploring its long-time behavior. Then sufficient conditions for extinction of the disease are established. Moreover, we obtain sufficient conditions for the existence of an ergodic stationary distribution of the model by constructing a suitable stochastic Lyapunov function. The stationary distribution implies that the disease is persistent in the mean. Finally, we provide some numerical examples to illustrate theoretical results.

  9. Identification of three signaling molecules required for calcineurin-dependent monopolar growth induced by the DNA replication checkpoint in fission yeast.

    PubMed

    Kume, Kazunori; Hashimoto, Tomoyo; Suzuki, Masashi; Mizunuma, Masaki; Toda, Takashi; Hirata, Dai

    2017-09-30

    Cell polarity is coordinately regulated with the cell cycle. Growth polarity of the fission yeast Schizosaccharomyces pombe transits from monopolar to bipolar during G2 phase, termed NETO (new end take off). Upon perturbation of DNA replication, the checkpoint kinase Cds1/CHK2 induces NETO delay through activation of Ca 2+ /calmodulin-dependent protein phosphatase calcineurin (CN). CN in turn regulates its downstream targets including the microtubule (MT) plus-end tracking CLIP170 homologue Tip1 and the Casein kinase 1γ Cki3. However, whether and which Ca 2+ signaling molecules are involved in the NETO delay remains elusive. Here we show that 3 genes (trp1322, vcx1 and SPAC6c3.06c encoding TRP channel, antiporter and P-type ATPase, respectively) play vital roles in the NETO delay. Upon perturbation of DNA replication, these 3 genes are required for not only the NETO delay but also for the maintenance of cell viability. Trp1322 and Vcx1 act downstream of Cds1 and upstream of CN for the NETO delay, whereas SPAC6c3.06c acts downstream of CN. Consistently, Trp1322 and Vcx1, but not SPAC6c3.06c, are essential for activation of CN. Interestingly, we have found that elevated extracellular Ca 2+ per se induces a NETO delay, which depends on CN and its downstream target genes. These findings imply that Ca 2+ -CN signaling plays a central role in cell polarity control by checkpoint activation. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Temporal Stability of GPS Transmitter Group Delay Variations.

    PubMed

    Beer, Susanne; Wanninger, Lambert

    2018-05-29

    The code observable of global navigation satellite systems (GNSS) is influenced by group delay variations (GDV) of transmitter and receiver antennas. For the Global Positioning System (GPS), the variations can sum up to 1 m in the ionosphere-free linear combination and thus can significantly affect precise code applications. The contribution of the GPS transmitters can amount to 0.8 m peak-to-peak over the entire nadir angle range. To verify the assumption of their time-invariance, we determined daily individual satellite GDV for GPS transmitter antennas over a period of more than two years. Dual-frequency observations of globally distributed reference stations and their multipath combination form the basis for our analysis. The resulting GPS GDV are stable on the level of a few centimeters for C1, P2, and for the ionosphere-free linear combination. Our study reveals that the inconsistencies of the GDV of space vehicle number (SVN) 55 with respect to earlier studies are not caused by temporal instabilities, but are rather related to receiver properties.

  11. High- and low-LET induced chromosome damage in human lymphocytes: a time-course of aberrations in metaphase and interphase

    NASA Technical Reports Server (NTRS)

    George, K.; Wu, H.; Willingham, V.; Furusawa, Y.; Kawata, T.; Cucinotta, F. A.; Dicello, J. F. (Principal Investigator)

    2001-01-01

    PURPOSE: To investigate how cell-cycle delays in human peripheral lymphocytes affect the expression of complex chromosome damage in metaphase following high- and low-LET radiation exposure. MATERIALS AND METHODS: Whole blood was irradiated in vitro with a low and a high dose of 1 GeV u(-1) iron particles, 400MeV u(-1) neon particles or y-rays. Lymphocytes were cultured and metaphase cells were collected at different time points after 48-84h in culture. Interphase chromosomes were prematurely condensed using calyculin-A, either 48 or 72 h after exposure to iron particles or gamma-rays. Cells in first division were analysed using a combination of FISH whole-chromosome painting and DAPI/ Hoechst 33258 harlequin staining. RESULTS: There was a delay in expression of chromosome damage in metaphase that was LET- and dose-dependant. This delay was mostly related to the late emergence of complex-type damage into metaphase. Yields of damage in PCC collected 48 h after irradiation with iron particles were similar to values obtained from cells undergoing mitosis after prolonged incubation. CONCLUSION: The yield of high-LET radiation-induced complex chromosome damage could be underestimated when analysing metaphase cells collected at one time point after irradiation. Chemically induced PCC is a more accurate technique since problems with complicated cell-cycle delays are avoided.

  12. High- and low-LET induced chromosome damage in human lymphocytes: a time-course of aberrations in metaphase and interphase.

    PubMed

    George, K; Wu, H; Willingham, V; Furusawa, Y; Kawata, T; Cucinotta, F A

    2001-02-01

    To investigate how cell-cycle delays in human peripheral lymphocytes affect the expression of complex chromosome damage in metaphase following high- and low-LET radiation exposure. Whole blood was irradiated in vitro with a low and a high dose of 1 GeV u(-1) iron particles, 400MeV u(-1) neon particles or y-rays. Lymphocytes were cultured and metaphase cells were collected at different time points after 48-84h in culture. Interphase chromosomes were prematurely condensed using calyculin-A, either 48 or 72 h after exposure to iron particles or gamma-rays. Cells in first division were analysed using a combination of FISH whole-chromosome painting and DAPI/ Hoechst 33258 harlequin staining. There was a delay in expression of chromosome damage in metaphase that was LET- and dose-dependant. This delay was mostly related to the late emergence of complex-type damage into metaphase. Yields of damage in PCC collected 48 h after irradiation with iron particles were similar to values obtained from cells undergoing mitosis after prolonged incubation. The yield of high-LET radiation-induced complex chromosome damage could be underestimated when analysing metaphase cells collected at one time point after irradiation. Chemically induced PCC is a more accurate technique since problems with complicated cell-cycle delays are avoided.

  13. Enhanced sensitivity of a passive optical cavity by an intracavity dispersive medium

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

    Smith, David D.; Department of Physics, University of Alabama in Huntsville, Huntsville, Alabama 35899; Myneni, Krishna

    2009-07-15

    The pushing of the modes of a Fabry-Perot cavity by an intracavity rubidium cell is measured. The scale factor of the modes is increased by the anomalous dispersion and is inversely proportional to the sum of the effective group index and an additional cavity delay factor that arises from the variation of the Rb absorption over a free spectral range. This additional positive feedback further increases the effect of the anomalous dispersion and goes to zero at the lasing threshold. The mode width does not grow as fast as the scale factor as the intracavity absorption is increased resulting inmore » enhanced measurement sensitivities. For absorptions larger than the scale factor pole, the atom-cavity response is multivalued and mode splitting occurs.« less

  14. Cancer cell uptake behavior of Au nanoring and its localized surface plasmon resonance induced cell inactivation

    NASA Astrophysics Data System (ADS)

    Chu, Che-Kuan; Tu, Yi-Chou; Chang, Yu-Wei; Chu, Chih-Ken; Chen, Shih-Yang; Chi, Ting-Ta; Kiang, Yean-Woei; Yang, Chih-Chung

    2015-02-01

    Au nanorings (NRIs), which have the localized surface plasmon resonance (LSPR) wavelength around 1058 nm, either with or without linked antibodies, are applied to SAS oral cancer cells for cell inactivation through the LSPR-induced photothermal effect when they are illuminated by a laser of 1065 nm in wavelength. Different incubation times of cells with Au NRIs are considered for observing the variations of cell uptake efficiency of Au NRI and the threshold laser intensity for cell inactivation. In each case of incubation time, the cell sample is washed for evaluating the total Au NRI number per cell adsorbed and internalized by the cells based on inductively coupled plasma mass spectrometry measurement. Also, the Au NRIs remaining on cell membrane are etched with KI/I2 solution to evaluate the internalized Au NRI number per cell. The threshold laser intensities for cell inactivation before washout, after washout, and after KI/I2 etching are calibrated from the circular area sizes of inactivated cells around the illuminated laser spot center with various laser power levels. By using Au NRIs with antibodies, the internalized Au NRI number per cell increases monotonically with incubation time up to 24 h. However, the number of Au NRI remaining on cell membrane reaches a maximum at 12 h in incubation time. The cell uptake behavior of an Au NRI without antibodies is similar to that with antibodies except that the uptake NRI number is significantly smaller and the incubation time for the maximum NRI number remaining on cell membrane is delayed to 20 h. By comparing the threshold laser intensities before and after KI/I2 etching, it is found that the Au NRIs remaining on cell membrane cause more effective cancer cell inactivation, when compared with the internalized Au NRIs.

  15. Heterogeneity of residuals from comparison of GNSS and raytracing based troposphere slant total delays, as an indicator of hydrometeors

    NASA Astrophysics Data System (ADS)

    Hordyniec, Paweł; Rohm, Witold; Kapłon, Jan

    2017-04-01

    Post-fit residuals from Precise Point Positioning (PPP) carry the troposphere information except of multipath and residual antenna Phase Centre Variations (PCVs), when precise satellite orbits and clocks were introduced. Slant total delay (STD) of GNSS signal is a sum of a priori slant hydrostatic delay, estimated wet delay, asymetry introduced by the estimated zenith total delay (ZTD) horizontal gradients and a post-fit residual reduced by the systematic (site-dependant) effect. It was revealed, that application of reduced post-fit residuls to the slant total delays obtained from GNSS data processing increases the discrepancy with slant delays from raytracing (RT) through the Numerical Weather Model (NWM). One of the possible sources of that effect is neglected influence of hydrometeors in raytracing procedures. If the assumption of hydrometeor information existence in the PPP post-fit residuals is correct, we expect the diversity of slant delay discrepancies for satellite-receiver rays pointing or not the hydrometeors. Paper presents the spatial and temporal correlation analysis of the slant delay residuals (GNSS - RT) with hydrometeor phenomena recorded during the COST ES1206 GNSS4SWEC benchmark period (May 5th - June 29th, 2013). It presents the discussion of the results from different GNSS PPP slant delay estimation approaches including coordinates unconstraining or heavy constraining, and the calculation of slant delays with and without ZTD horizontal gradients estimation.

  16. Roles for the Histone Modifying and Exchange Complex NuA4 in Cell Cycle Progression in Drosophila melanogaster.

    PubMed

    Flegel, Kerry; Grushko, Olga; Bolin, Kelsey; Griggs, Ellen; Buttitta, Laura

    2016-07-01

    Robust and synchronous repression of E2F-dependent gene expression is critical to the proper timing of cell cycle exit when cells transition to a postmitotic state. Previously NuA4 was suggested to act as a barrier to proliferation in Drosophila by repressing E2F-dependent gene expression. Here we show that NuA4 activity is required for proper cell cycle exit and the repression of cell cycle genes during the transition to a postmitotic state in vivo However, the delay of cell cycle exit caused by compromising NuA4 is not due to additional proliferation or effects on E2F activity. Instead NuA4 inhibition results in slowed cell cycle progression through late S and G2 phases due to aberrant activation of an intrinsic p53-independent DNA damage response. A reduction in NuA4 function ultimately produces a paradoxical cell cycle gene expression program, where certain cell cycle genes become derepressed in cells that are delayed during the G2 phase of the final cell cycle. Bypassing the G2 delay when NuA4 is inhibited leads to abnormal mitoses and results in severe tissue defects. NuA4 physically and genetically interacts with components of the E2F complex termed D: rosophila, R: bf, E: 2F A: nd M: yb/ M: ulti-vulva class B: (DREAM/MMB), and modulates a DREAM/MMB-dependent ectopic neuron phenotype in the posterior wing margin. However, this effect is also likely due to the cell cycle delay, as simply reducing Cdk1 is sufficient to generate a similar phenotype. Our work reveals that the major requirement for NuA4 in the cell cycle in vivo is to suppress an endogenous DNA damage response, which is required to coordinate proper S and G2 cell cycle progression with differentiation and cell cycle gene expression. Copyright © 2016 by the Genetics Society of America.

  17. Roles for the Histone Modifying and Exchange Complex NuA4 in Cell Cycle Progression in Drosophila melanogaster

    PubMed Central

    Flegel, Kerry; Grushko, Olga; Bolin, Kelsey; Griggs, Ellen; Buttitta, Laura

    2016-01-01

    Robust and synchronous repression of E2F-dependent gene expression is critical to the proper timing of cell cycle exit when cells transition to a postmitotic state. Previously NuA4 was suggested to act as a barrier to proliferation in Drosophila by repressing E2F-dependent gene expression. Here we show that NuA4 activity is required for proper cell cycle exit and the repression of cell cycle genes during the transition to a postmitotic state in vivo. However, the delay of cell cycle exit caused by compromising NuA4 is not due to additional proliferation or effects on E2F activity. Instead NuA4 inhibition results in slowed cell cycle progression through late S and G2 phases due to aberrant activation of an intrinsic p53-independent DNA damage response. A reduction in NuA4 function ultimately produces a paradoxical cell cycle gene expression program, where certain cell cycle genes become derepressed in cells that are delayed during the G2 phase of the final cell cycle. Bypassing the G2 delay when NuA4 is inhibited leads to abnormal mitoses and results in severe tissue defects. NuA4 physically and genetically interacts with components of the E2F complex termed Drosophila, Rbf, E2F and Myb/Multi-vulva class B (DREAM/MMB), and modulates a DREAM/MMB-dependent ectopic neuron phenotype in the posterior wing margin. However, this effect is also likely due to the cell cycle delay, as simply reducing Cdk1 is sufficient to generate a similar phenotype. Our work reveals that the major requirement for NuA4 in the cell cycle in vivo is to suppress an endogenous DNA damage response, which is required to coordinate proper S and G2 cell cycle progression with differentiation and cell cycle gene expression. PMID:27184390

  18. Is the Cell Nucleus a Necessary Component in Precise Temporal Patterning?

    PubMed

    Albert, Jaroslav; Rooman, Marianne

    2015-01-01

    One of the functions of the cell nucleus is to help regulate gene expression by controlling molecular traffic across the nuclear envelope. Here we investigate, via stochastic simulation, what effects, if any, does segregation of a system into the nuclear and cytoplasmic compartments have on the stochastic properties of a motif with a negative feedback. One of the effects of the nuclear barrier is to delay the nuclear protein concentration, allowing it to behave in a switch-like manner. We found that this delay, defined as the time for the nuclear protein concentration to reach a certain threshold, has an extremely narrow distribution. To show this, we considered two models. In the first one, the proteins could diffuse freely from cytoplasm to nucleus (simple model); and in the second one, the proteins required assistance from a special class of proteins called importins. For each model, we generated fifty parameter sets, chosen such that the temporal profiles they effectuated were very similar, and whose average threshold time was approximately 150 minutes. The standard deviation of the threshold times computed over one hundred realizations were found to be between 1.8 and 7.16 minutes across both models. To see whether a genetic motif in a prokaryotic cell can achieve this degree of precision, we also simulated five variations on the coherent feed-forward motif (CFFM), three of which contained a negative feedback. We found that the performance of these motifs was nowhere near as impressive as the one found in the eukaryotic cell; the best standard deviation was 6.6 minutes. We argue that the significance of these results, the fact and necessity of spatio-temporal precision in the developmental stages of eukaryotes, and the absence of such a precision in prokaryotes, all suggest that the nucleus has evolved, in part, under the selective pressure to achieve highly predictable phenotypes.

  19. Multilevel linear modelling of the response-contingent learning of young children with significant developmental delays.

    PubMed

    Raab, Melinda; Dunst, Carl J; Hamby, Deborah W

    2018-02-27

    The purpose of the study was to isolate the sources of variations in the rates of response-contingent learning among young children with multiple disabilities and significant developmental delays randomly assigned to contrasting types of early childhood intervention. Multilevel, hierarchical linear growth curve modelling was used to analyze four different measures of child response-contingent learning where repeated child learning measures were nested within individual children (Level-1), children were nested within practitioners (Level-2), and practitioners were nested within the contrasting types of intervention (Level-3). Findings showed that sources of variations in rates of child response-contingent learning were associated almost entirely with type of intervention after the variance associated with differences in practitioners nested within groups were accounted for. Rates of child learning were greater among children whose existing behaviour were used as the building blocks for promoting child competence (asset-based practices) compared to children for whom the focus of intervention was promoting child acquisition of missing skills (needs-based practices). The methods of analysis illustrate a practical approach to clustered data analysis and the presentation of results in ways that highlight sources of variations in the rates of response-contingent learning among young children with multiple developmental disabilities and significant developmental delays. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  20. Crustal origin of trench-parallel shear-wave fast polarizations in the Central Andes

    NASA Astrophysics Data System (ADS)

    Wölbern, I.; Löbl, U.; Rümpker, G.

    2014-04-01

    In this study, SKS and local S phases are analyzed to investigate variations of shear-wave splitting parameters along two dense seismic profiles across the central Andean Altiplano and Puna plateaus. In contrast to previous observations, the vast majority of the measurements reveal fast polarizations sub-parallel to the subduction direction of the Nazca plate with delay times between 0.3 and 1.2 s. Local phases show larger variations of fast polarizations and exhibit delay times ranging between 0.1 and 1.1 s. Two 70 km and 100 km wide sections along the Altiplano profile exhibit larger delay times and are characterized by fast polarizations oriented sub-parallel to major fault zones. Based on finite-difference wavefield calculations for anisotropic subduction zone models we demonstrate that the observations are best explained by fossil slab anisotropy with fast symmetry axes oriented sub-parallel to the slab movement in combination with a significant component of crustal anisotropy of nearly trench-parallel fast-axis orientation. From the modeling we exclude a sub-lithospheric origin of the observed strong anomalies due to the short-scale variations of the fast polarizations. Instead, our results indicate that anisotropy in the Central Andes generally reflects the direction of plate motion while the observed trench-parallel fast polarizations likely originate in the continental crust above the subducting slab.

  1. MECHANISMS IN THE SUPPRESSION OF DELAYED HYPERSENSITIVITY IN THE GUINEA PIG BY 6-MERCAPTOPURINE

    PubMed Central

    Phillips, S. Michael; Zweiman, Burton

    1973-01-01

    The mechanism of suppression, of delayed hypersensitivity to tuberculoprotein by 6-mercaptopurine (6-MP) was studied in guinea pigs. Under the conditions of the protocol, suppression of tuberculin delayed skin test reactivity was not associated with a significantly altered end-organ response to mediators of permeability. No significant alteration of in vivo lymphoid activity, as measured by reconstitution studies, was found. In addition, lymphoid cells from 6-MP-treated animals reacted in a fashion similar to those of placebo-treated animals with respect to (a) antigen-induced lymphocyte proliferation, (b) antigen-induced liberation of macrophage inhibitory factor activity, (c) direct inhibition by antigen of peritoneal exudate cell migration. Conversely, suppression was seen in levels of blood monocytes and in vitro function of macrophages from 6-MP-treated animals in several respects: (a) adherence to glass, (b) migratory rate, (c) phagocytic capacity. Therefore, it would appear that a ma]or mechanism of 6-MP-induced suppression of delayed hypersensitivity is through its action on effector cells. PMID:4196793

  2. Application of Signal Analysis to the Climate

    PubMed Central

    2014-01-01

    The primary ingredient of the Anthropogenic Global Warming hypothesis, namely, the assumption that additional atmospheric carbon dioxide substantially raises the global temperature, is studied. This is done by looking at the data of temperature and CO2, both in the time domain and in the phase domain of periodic data. Bicentenary measurements are analyzed and a relaxation model is introduced in the form of an electronic equivalent circuit. The effects of this relaxation manifest themselves in delays in the time domain and correlated phase shifts in the phase domain. For extremely long relaxation time constants, the delay is maximally one-quarter period, which for the yearly-periodic signal means 3 months. This is not in line with the analyzed data, the latter showing delays of 9 (−3) months. These results indicate a reverse function of cause and effect, with temperature being the cause for atmospheric CO2 changes, rather than their effect. These two hypotheses are discussed on basis of literature, where it was also reported that CO2 variations are lagging behind temperature variations. PMID:27350978

  3. Investigation of a Nonlinear Control System

    NASA Technical Reports Server (NTRS)

    Flugge-Lotz, I; Taylor, C F; Lindberg, H E

    1958-01-01

    A discontinuous variation of coefficients of the differential equation describing the linear control system before nonlinear elements are added is studied in detail. The nonlinear feedback is applied to a second-order system. Simulation techniques are used to study performance of the nonlinear control system and to compare it with the linear system for a wide variety of inputs. A detailed quantitative study of the influence of relay delays and of a transport delay is presented.

  4. Delayed Expansion and Contraction of CD8+ T Cell Response during Infection with Virulent Salmonella typhimurium1

    PubMed Central

    Luu, Rachel A.; Gurnani, Komal; Dudani, Renu; Kammara, Rajagopal; van Faassen, Henk; Sirard, Jean-Claude; Krishnan, Lakshmi; Sad, Subash

    2014-01-01

    Ag presentation to CD8+ T cells often commences immediately after infection, which facilitates their rapid expansion and control of infection. Subsequently, the primed cells undergo rapid contraction. We report that this paradigm is not followed during infection with virulent Salmonella enterica, serovar Typhimurium (ST), an intracellular bacterium that replicates within phagosomes of infected cells. Although susceptible mice die rapidly (~7 days), resistant mice (129×1SvJ) harbor a chronic infection lasting ~60–90 days. Using rOVA-expressing ST (ST-OVA), we show that T cell priming is considerably delayed in the resistant mice. CD8+ T cells that are induced during ST-OVA infection undergo delayed expansion, which peaks around day 21, and is followed by protracted contraction. Initially, ST-OVA induces a small population of cycling central phenotype (CD62LhighIL-7RαhighCD44high) CD8+ T cells. However, by day 14–21, majority of the primed CD8+ T cells display an effector phenotype (CD62LlowIL-7RαlowCD44high). Subsequently, a progressive increase in the numbers of effector memory phenotype cells (CD62LlowIL-7RαhighCD44high) occurs. This differentiation program remained unchanged after accelerated removal of the pathogen with antibiotics, as majority of the primed cells displayed an effector memory phenotype even at 6 mo postinfection. Despite the chronic infection, CD8+ T cells induced by ST-OVA were functional as they exhibited killing ability and cytokine production. Importantly, even memory CD8+ T cells failed to undergo rapid expansion in response to ST-OVA infection, suggesting a delay in T cell priming during infection with virulent ST-OVA. Thus, phagosomal lifestyle may allow escape from host CD8+ T cell recognition, conferring a survival advantage to the pathogen. PMID:16849458

  5. Delay in Apoptosome Formation Attenuates Apoptosis in Mouse Embryonic Stem Cell Differentiation

    PubMed Central

    Akbari-Birgani, Shiva; Hosseinkhani, Saman; Mollamohamadi, Sepideh; Baharvand, Hossein

    2014-01-01

    Differentiation is an inseparable process of development in multicellular organisms. Mouse embryonic stem cells (mESCs) represent a valuable research tool to conduct in vitro studies of cell differentiation. Apoptosis as a well known cell death mechanism shows some common features with cell differentiation, which has caused a number of ambiguities in the field. The research question here is how cells could differentiate these two processes from each other. We have investigated the role of the mitochondrial apoptotic pathway and cell energy level during differentiation of mESCs into the cardiomyocytes and their apoptosis. p53 expression, cytochrome c release, apoptosome formation, and caspase-3/7 activation are observed upon induction of both apoptosis and differentiation. However, remarkable differences are detected in time of cytochrome c appearance, apoptosome formation, and caspase activity upon induction of both processes. In apoptosis, apoptosome formation and caspase activity were observed rapidly following the cytochrome c release. Unlike apoptosis, the release of cytochrome c upon differentiation took more time, and the maximum caspase activity was also postponed for 24 h. This delay suggests that there is a regulatory mechanism during differentiation of mESCs into cardiomyocytes. The highest ATP content of cells was observed immediately after cytochrome c release 6 h after apoptosis induction and then decreased, but it was gradually increased up to 48 h after differentiation. These observations suggest that a delay in the release of cytochrome c or delay in ATP increase attenuate apoptosome formation, and caspase activation thereby discriminates apoptosis from differentiation in mESCs. PMID:24755221

  6. Restoration of Mitochondrial NAD+ Levels Delays Stem Cell Senescence and Facilitates Reprogramming of Aged Somatic Cells.

    PubMed

    Son, Myung Jin; Kwon, Youjeong; Son, Taekwon; Cho, Yee Sook

    2016-12-01

    The fundamental tenet that aging is irreversible has been challenged by the development of reprogramming technology that can restore molecular and cellular age by reversing the progression of aging. The use of cells from aged individuals as sources for reprogramming or transplantation creates a major barrier in stem cell therapy with respect to cell quality and quantity. Here, we investigated the molecular features underlying senescence and rejuvenation during aged cell reprogramming and identified novel factors that can overcome age-associated barriers. Enzymes, such as nicotinamide nucleotide transhydrogenase (NNT) and nicotinamide mononucleotide adenylyltransferase 3 (NMNAT3), that control mitochondrial NAD + levels appear to be susceptible to aging. In aged cells, mitochondrial NAD + levels decrease, accompanied by reduced SIRT3 activity; these changes severely impede cell fate transition. However, in cells collected from aged p16 knockout mice, which exhibit delayed cellular senescence, no changes in NNT or NMNAT3 expression were found. Importantly, restoring mitochondrial NAD + levels by overexpressing NNT and NMNAT3 enhanced reprogramming efficiency of aged somatic cells and extended the lifespan of human mesenchymal stem cells by delaying replicative senescence. These results demonstrate that maintenance of mitochondrial NAD + levels is critical for reversing the mechanisms of aging and ensuring that cells collected from aged individuals are of high quality. Stem Cells 2016;34:2840-2851. © 2016 AlphaMed Press.

  7. Intra-articular Implantation of Mesenchymal Stem Cells, Part 1

    PubMed Central

    Kraeutler, Matthew J.; Mitchell, Justin J.; Chahla, Jorge; McCarty, Eric C.; Pascual-Garrido, Cecilia

    2017-01-01

    Osteoarthritis (OA) after a partial or total meniscectomy procedure is a common pathology. Because of the high incidence of meniscectomy in the general population, as well as the significant burden of knee OA, there is increasing interest in determining methods for delaying postmeniscectomy OA. Biological therapies, including mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and platelet-rich plasma (PRP), have been proposed as possible therapies that could delay OA in this and other settings. Several studies in various animal models have evaluated the effect of injecting MSCs into the knee joints of animals with OA induced either by meniscal excision with or without anterior cruciate ligament transection. When compared with control groups receiving injections without progenitor cells, short-term benefits in the experimental groups have been reported. In human subjects, there are limited data to determine the effect of biological therapies for use in delaying or preventing the onset of OA after a meniscectomy procedure. The purpose of this review is to highlight the findings in the presently available literature on the use of intra-articular implantation of MSCs postmeniscectomy and to offer suggestions for future research with the goal of delaying or treating early OA postmeniscectomy with MSCs. PMID:28203597

  8. Delayed clamping of the umbilical cord after delivery and implications for public cord blood banking.

    PubMed

    Allan, David S; Scrivens, Nicholas; Lawless, Tiffany; Mostert, Karen; Oppenheimer, Lawrence; Walker, Mark; Petraszko, Tanya; Elmoazzen, Heidi

    2016-03-01

    Public banking of umbilical cord blood units (CBUs) containing higher numbers of cells ensures timely engraftment after transplantation for increasing numbers of patients. Delayed clamping of the umbilical cord after birth may benefit some infants by preventing iron deficiency. Implications of delayed cord clamping for public cord blood banking remains unclear. CBUs collected by Canadian Blood Services at one collection site between November 1, 2014, and March 17, 2015, were analyzed. The delay in cord clamping after birth was timed and classified as "no delay," 20 to 60 seconds, more than 60 seconds, or more than 120 seconds. Of 367 collections, 100 reported no delay in clamping while clamping was delayed by 20 to 60 seconds (n = 69), more than 60 seconds (n = 98), or more than 120 seconds (n = 100) in the remaining cases. The mean volume and total nucleated cells (TNCs) in units with no delay in clamping were significantly greater than mean volumes for all categories of delayed clamping (Tukey's test, p < 0.05 for each comparison). The proportion of units with more than 1.5 × 10(9) TNCs was significantly reduced when clamping was delayed (p = 5.5 × 10(-8) ). The difference was most marked for cords that were clamped more than 120 seconds after delivery (6.2% compared with 39%). Delayed cord clamping greatly diminishes the volume and TNC count of units collected for a public cord blood bank. Creating an inventory of CBUs with high TNC content may take more time than expected. © 2015 AABB.

  9. Seafloor age dependence of Rayleigh wave phase velocities in the Indian Ocean

    NASA Astrophysics Data System (ADS)

    Godfrey, Karen E.; Dalton, Colleen A.; Ritsema, Jeroen

    2017-05-01

    Variations in the phase velocity of fundamental-mode Rayleigh waves across the Indian Ocean are determined using two inversion approaches. First, variations in phase velocity as a function of seafloor age are estimated using a pure-path age-dependent inversion method. Second, a two-dimensional parameterization is used to solve for phase velocity within 1.25° × 1.25° grid cells. Rayleigh wave travel time delays have been measured between periods of 38 and 200 s. The number of measurements in the study area ranges between 4139 paths at a period of 200 s and 22,272 paths at a period of 40 s. At periods < 100 s, the phase velocity variations are strongly controlled by seafloor age and shown to be consistent with temperature variations predicted by the half-space-cooling model for a mantle potential temperature of 1400°C. The inferred thermal structure beneath the Indian Ocean is most similar to the structure of the Pacific upper mantle, where phase velocities can also be explained by a half-space-cooling model. The thermal structure is not consistent with that of the Atlantic upper mantle, which is best fit by a plate-cooling model and requires a thin plate. Removing age-dependent phase velocity from the 2-D maps of the Indian Ocean highlights anomalously high velocities at the Rodriguez Triple Junction and the Australian-Antarctic Discordance and anomalously low velocities immediately to the west of the Central Indian Ridge.

  10. Effect of cell therapy on recovery of cognitive functions in rats during the delayed period after brain injury.

    PubMed

    Roshal, L M; Tzyb, A F; Pavlova, L N; Soushkevitch, G N; Semenova, J B; Javoronkov, L P; Kolganova, O I; Konoplyannikov, A G; Shevchuk, A S; Yujakov, V V; Karaseva, O V; Ivanova, T F; Chernyshova, T A; Konoplyannikova, O A; Bandurko, L N; Marey, M V; Sukhikh, G T

    2009-07-01

    We studied the effect of systemic transplantation of human stem cells from various tissues on cognitive functions of the brain in rats during the delayed period after experimental brain injury. Stem cells were shown to increase the efficacy of medical treatment with metabolic and symptomatic drugs for recovery of cognitive functions. They accelerated the formation of the conditioned defense response. Fetal neural stem cells had a stronger effect on some parameters of cognitive function 2 months after brain injury. The efficacy of bone marrow mesenchymal stem cells from adult humans or fetuses was higher 3 months after brain injury.

  11. Effect of caffeine on radiation-induced mitotic delay: delayed expression of G/sub 2/ arrest

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

    Rowley, R.; Zorch, M.; Leeper, D.B.

    1984-01-01

    In the presence of 5 mM caffeine, irradiated (1.5 Gy) S and G/sub 2/ cells progressed to mitosis in register and without arrest in G/sub 2/. Caffeine (5 mM) markedly reduced mitotic delay even after radiation doses up to 20 Gy. When caffeine was removed from irradiated (1.5 Gy) and caffeine-treated cells, a period of G/sub 2/ arrest followed, similar in length to that produced by radiation alone. The arrest expressed was independent of the duration of the caffeine treatment for exposures up to 3 hr. The similarity of the response to the cited effects of caffeine on S-phase delaymore » suggests a common basis for delay induction in S and G/sub 2/ phases.« less

  12. Characterisation of the clinical and activated T cell response to repeat delayed-type hypersensitivity skin challenges in human subjects, with KLH and PPD, as a potential model to test T cell-targeted therapies.

    PubMed

    Belson, Alexandra; Schmidt, Tim; Fernando, Disala; Hardes, Kelly; Scott, Nicola; Brett, Sara; Clark, Deborah; Oliveira, João Joaquim; Davis, Bill; McHugh, Simon; Stone, John

    2016-05-01

    To characterise the delayed-type hypersensitivity (DTH) skin reaction to repeated challenges of keyhole limpet hemocyanin (KLH) and tuberculin purified protein derivative (PPD) in healthy volunteers, as a potential model to test T cell-targeted investigational agents. Forty-nine subjects received either KLH, PPD, or PBS repeat skin challenges, and clinical assessments including induration, erythema and Laser Doppler Imaging. Skin biopsies or suction blisters were taken after challenge to investigate the cellular infiltrate of the challenge site, the T cell activation status, as determined by LAG-3 expression, and, specifically for the blister, the concentrations of inflammatory cytokines. Point estimates, estimates of variation and corresponding 95% confidence intervals were constructed for each type of challenge and timepoint. The DTH response could be measured at 48 and 120 h post-KLH and PPD challenge with induration, erythema and Laser Doppler Imaging, with 48 h post-challenge demonstrating the peak of the response. PPD was well tolerated in subjects after multiple challenges, however, a significant number of KLH-treated subjects demonstrated an injection site reaction 6-7 days following the SC injection. PPD demonstrated a boost effect on the second challenge as measured by increased induration, where as this was not noted consistently for KLH. Compared to unchallenged and PBS control-injected skin, increased T cell numbers were detected in the challenge site by both the skin suction blister and biopsy technique, at either time point following KLH or PPD challenge. Use of the T cell activation marker LAG-3 demonstrated the activated phenotype of these cells. In skin blisters, higher numbers of LAG-3+ T cells were detected at 48 h post-challenge, whereas in the biopsies, similar numbers of LAG-3+ cells were observed at both 48 and 120 h. Analysis of blister T cell subpopulations revealed some differences in phenotypes between the time points and between the CD4 and CD8 T cells. Blister cytokine analysis revealed a pro-inflammatory dominated signature in PPD-challenged skin. In summary, our data support the use of a repeat KLH and PPD DTH challenge in clinical trials and that the clinical measures of induration and to a lesser extent erythema are appropriate to monitor the clinical DTH response. Both the blister and biopsy can be utilised to assess and quantify activated T cells and at the dose used, PPD was better tolerated than KLH and hence may be optimal for future studies.

  13. Piloted simulator study of allowable time delay in pitch flight control system of a transport airplane with negative static stability

    NASA Technical Reports Server (NTRS)

    Grantham, William D.; Smith, Paul M.; Person, Lee H., Jr.; Meyer, Robert T.; Tingas, Stephen A.

    1987-01-01

    A piloted simulation study was conducted to determine the permissible time delay in the flight control system of a 10-percent statically unstable transport airplane during cruise flight conditions. The math model used for the simulation was a derivative Lockheed L-1011 wide-body jet transport. Data were collected and analyzed from a total of 137 cruising flights in both calm- and turbulent-air conditions. Results of this piloted simulation study verify previous findings that show present military specifications for allowable control-system time delay may be too stringent when applied to transport-size airplanes. Also, the degree of handling-qualities degradation due to time delay is shown to be strongly dependent on the source of the time delay in an advanced flight control system. Maximum allowable time delay for each source of time delay in the control system, in addition to a less stringent overall maximum level of time delay, should be considered for large aircraft. Preliminary results also suggest that adverse effects of control-system time delay may be at least partially offset by variations in control gearing. It is recommended that the data base include different airplane baselines, control systems, and piloting tasks with many pilots participating, so that a reasonable set of limits for control-system time delay can be established to replace the military specification limits currently being used.

  14. Mutational screening in patients with profound sensorineural hearing loss and neurodevelopmental delay: Description of a novel m.3861A > C mitochondrial mutation in the MT-ND1 gene.

    PubMed

    Ammar, Marwa; Tabebi, Mouna; Sfaihi, Lamia; Alila-Fersi, Olfa; Maalej, Marwa; Felhi, Rahma; Chabchoub, Imen; Keskes, Leila; Hachicha, Mongia; Fakhfakh, Faiza; Mkaouar-Rebai, Emna

    2016-06-10

    Mitochondrial diseases caused by mitochondrial dysfunction are a clinically and genetically, heterogeneous group of disorders involving multiple organs, particularly tissues with high-energy demand. Hearing loss is a recognized symptom of a number of mitochondrial diseases and can result from neuronal or cochlear dysfunction. The tissue affected in this pathology is most probably the cochlear hair cells, which are essential for hearing function since they are responsible for maintaining the ionic gradients necessary for sound signal transduction. Several mitochondrial DNA mutations have been associated with hearing loss and since mitochondria are crucial for the cellular energy supply in many tissues, most of these mtDNA mutations affect several tissues and will cause syndromic hearing loss. In the present study, we described 2 patients with sensorineural hearing loss and neurodevelopmental delay in whom we tested mitochondrial genes described to be associated with syndromic hearing loss. One of these patients showed a novel heteroplasmic mitochondrial mutation m.3861A > C (W185C) which lead to a loss of stability of the ND1 protein since it created a new hydrogen bund between the unique created cystein C185 and the A182 residue. In the second patient, we detected two novel heteroplasmic variations m.12350C > A (T5N) and m.14351T > C (E108G) respectively in the MT-ND5 and the MT-ND6 genes. The TopPred II prediction for the E108G variation revealed a decrease of the hydrophobicity in the mutated MT-ND6. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Delayed embryonic development in the Indian short-nosed fruit bat, Cynopterus sphinx.

    PubMed

    Meenakumari, Karukayil J; Krishna, Amitabh

    2005-01-01

    The unusual feature of the breeding cycle of Cynopterus sphinx at Varanasi is the significant variation in gestation length of the two successive pregnancies of the year. The aim of this study was to investigate whether the prolongation of the first pregnancy in C. sphinx is due to delayed embryonic development. The first (winter) pregnancy commences in late October and lasts until late March and has a gestation period of about 150 days. The second (summer) pregnancy commences in April and lasts until the end of July or early August with a gestation period of about 125 days. Changes in the size and weight of uterine cornua during the two successive pregnancies suggest retarded embryonic growth during November and December. Histological analysis during the period of retarded embryonic development in November and December showed a slow gastrulation process. The process of amniogenesis was particularly slow. When the embryos attained the early primitive streak stage, their developmental rate suddenly increased considerably. During the summer pregnancy, on the other hand, the process of gastrulation was much faster and proceeded quickly. A comparison of the pattern of embryonic development for 4 consecutive years consistently showed retarded or delayed embryonic development during November and December. The time of parturition and post-partum oestrus showed only a limited variation from 1 year to another. This suggests that delayed embryonic development in C. sphinx may function to synchronize parturition among females. The period of delayed embryonic development in this species clearly coincides with the period of fat deposition. The significance of this correlation warrants further investigation.

  16. Characterization of the Correct Mandibular Premolar Region for Delayed Dental Implantation in Beagle Dogs.

    PubMed

    Xie, Chenxi; Fu, Xiaoming; Xu, Ling; Xu, Sheng

    2018-05-01

    For delayed dental implantation into the mandible, the implant size should be chosen according to the characteristics of that bone. This study investigated anatomic features of the mandible in beagle dogs, to develop recommendations regarding the correct implantation region and available bone area for delayed dental implantation surgery. We used 20 healthy male beagle dogs to create delayed dental implantation models. The dogs' mandibles underwent cone beam CT (CBCT) imaging; the locations of the middle mental foramen and canine root apex were measured on CBCT images. The dogs then were euthanized and their mandibles measured by using a digital vernier caliper. In addition, the correct implantation region and available bone areas were evaluated. The data obtained by using the 2 measuring methods were compared statistically. The results showed that the positions of the middle mental foramen and canine root apex were relatively fixed, with little variation. The implantation and available bone regions showed little variation among dogs and did not differ significantly between the 2 measuring methods. In conclusion, the correct implantation region (mean ± 1 SD) in the beagle mandible for delayed dental implantation surgery was 17.53 ± 0.46 mm in width. The recommended available bone areas (height × width) were 7.22 ± 0.68 mm × 5.32 ± 0.49 mm (P2), 8.21 ± 0.71 mm × 5.81 ± 0.56 mm (P3), and 9.17 ± 0.65 mm × 6.39 ± 0.56 mm (P4) in the premolar region.

  17. The characterization of a full-thickness excision open foot wound model in n5-streptozotocin (STZ)-induced type 2 diabetic rats that mimics diabetic foot ulcer in terms of reduced blood circulation, higher C-reactive protein, elevated inflammation, and reduced cell proliferation.

    PubMed

    Yu, Caroline Oi-Ling; Leung, Kwok-Sui; Fung, Kwok-Pui; Lam, Francis Fu-Yuen; Ng, Ethel Sau-Kuen; Lau, Kit-Man; Chow, Simon Kwoon-Ho; Cheung, Wing-Hoi

    2017-08-05

    Delayed foot wound healing is a major complication attributed to hyperglycemia in type 2 diabetes mellitus (DM) patients, and these wounds may develop into foot ulcers. There are at least two types of DM wound models used in rodents to study delayed wound healing. However, clinically relevant animal models are not common. Most models use type 1 DM rodents or wounds created on the back rather than on the foot. An open full-thickness excision wound on the footpad of type 2 DM rats is more clinically relevant, but such a model has not yet been characterized systematically. The objective of this study was to investigate and characterize how DM affected a full-thickness excision open foot wound in n5-streptozotocin (n5-STZ)-induced type 2 DM rats. We hypothesized that elevated inflammation, reduced blood circulation, and cell proliferation due to hyperglycemia could delay the wound healing of DM rats. The wounds of DM rats were compared with those of non-DM rats (Ctrl) at Days 1 and 8 post wounding. The wound healing process of the DM rats was significantly delayed compared with that of the Ctrl rats. The DM rats also had higher C-reactive protein (CRP) and lower blood circulation and proliferating cell nuclear antigen (PCNA) in DM wounds. This confirmed that elevated inflammation and reduced blood flow and cell proliferation delayed foot wound healing in the n5-STZ rats. Hence, this open foot wound animal model provides a good approach to study the process of delayed wound healing.

  18. The characterization of a full-thickness excision open foot wound model in n5-streptozotocin (STZ)-induced type 2 diabetic rats that mimics diabetic foot ulcer in terms of reduced blood circulation, higher C-reactive protein, elevated inflammation, and reduced cell proliferation

    PubMed Central

    Yu, Caroline Oi-Ling; Leung, Kwok-Sui; Fung, Kwok-Pui; Lam, Francis Fu-Yuen; Ng, Ethel Sau-Kuen; Lau, Kit-Man; Chow, Simon Kwoon-Ho; Cheung, Wing-Hoi

    2017-01-01

    Delayed foot wound healing is a major complication attributed to hyperglycemia in type 2 diabetes mellitus (DM) patients, and these wounds may develop into foot ulcers. There are at least two types of DM wound models used in rodents to study delayed wound healing. However, clinically relevant animal models are not common. Most models use type 1 DM rodents or wounds created on the back rather than on the foot. An open full-thickness excision wound on the footpad of type 2 DM rats is more clinically relevant, but such a model has not yet been characterized systematically. The objective of this study was to investigate and characterize how DM affected a full-thickness excision open foot wound in n5-streptozotocin (n5-STZ)-induced type 2 DM rats. We hypothesized that elevated inflammation, reduced blood circulation, and cell proliferation due to hyperglycemia could delay the wound healing of DM rats. The wounds of DM rats were compared with those of non-DM rats (Ctrl) at Days 1 and 8 post wounding. The wound healing process of the DM rats was significantly delayed compared with that of the Ctrl rats. The DM rats also had higher C-reactive protein (CRP) and lower blood circulation and proliferating cell nuclear antigen (PCNA) in DM wounds. This confirmed that elevated inflammation and reduced blood flow and cell proliferation delayed foot wound healing in the n5-STZ rats. Hence, this open foot wound animal model provides a good approach to study the process of delayed wound healing. PMID:28413186

  19. New insight into the residual inactivation of Microcystis aeruginosa by dielectric barrier discharge

    PubMed Central

    Li, Lamei; Zhang, Hong; Huang, Qing

    2015-01-01

    We report the new insight into the dielectric barrier discharge (DBD) induced inactivation of Microcystis aeruginosa, the dominant algae which caused harmful cyanobacterial blooms in many developing countries. In contrast with the previous work, we employed flow cytometry to examine the algal cells, so that we could assess the dead and living cells with more accuracy, and distinguish an intermediate state of algal cells which were verified as apoptotic. Our results showed that the numbers of both dead and apoptotic cells increased with DBD treatment delay time, and hydrogen peroxide produced by DBD was the main reason for the time-delayed inactivation effect. However, apart from the influence of hydrogen peroxide, the DBD-induced initial injures on the algal cells during the discharge period also played a considerable role in the inactivation of the DBD treated cells, as indicated by the measurement of intracellular reactive oxygen species (ROS) inside the algal cells. We therefore propose an effective approach to utilization of non-thermal plasma technique that makes good use of the residual inactivation effect to optimize the experimental conditions in terms of discharge time and delay time, so that more efficient treatment of cyanobacterial blooms can be achieved. PMID:26347270

  20. On the theory of singular optimal controls in dynamic systems with control delay

    NASA Astrophysics Data System (ADS)

    Mardanov, M. J.; Melikov, T. K.

    2017-05-01

    An optimal control problem with a control delay is considered, and a more broad class of singular (in classical sense) controls is investigated. Various sequences of necessary conditions for the optimality of singular controls in recurrent form are obtained. These optimality conditions include analogues of the Kelley, Kopp-Moyer, R. Gabasov, and equality-type conditions. In the proof of the main results, the variation of the control is defined using Legendre polynomials.

  1. Role of founder cell deficit and delayed neuronogenesis in microencephaly of the trisomy 16 mouse

    NASA Technical Reports Server (NTRS)

    Haydar, T. F.; Nowakowski, R. S.; Yarowsky, P. J.; Krueger, B. K.

    2000-01-01

    Development of the neocortex of the trisomy 16 (Ts16) mouse, an animal model of Down syndrome (DS), is characterized by a transient delay in the radial expansion of the cortical wall and a persistent reduction in cortical volume. Here we show that at each cell cycle during neuronogenesis, a smaller proportion of Ts16 progenitors exit the cell cycle than do control, euploid progenitors. In addition, the cell cycle duration was found to be longer in Ts16 than in euploid progenitors, the Ts16 growth fraction was reduced, and an increase in apoptosis was observed in both proliferative and postmitotic zones of the developing Ts16 neocortical wall. Incorporation of these changes into a model of neuronogenesis indicates that they are sufficient to account for the observed delay in radial expansion. In addition, the number of neocortical founder cells, i.e., precursors present just before neuronogenesis begins, is reduced by 26% in Ts16 mice, leading to a reduction in overall cortical size at the end of Ts16 neuronogenesis. Thus, altered proliferative characteristics during Ts16 neuronogenesis result in a delay in the generation of neocortical neurons, whereas the founder cell deficit leads to a proportional reduction in the overall number of neurons. Such prenatal perturbations in either the timing of neuron generation or the final number of neurons produced may lead to significant neocortical abnormalities such as those found in DS.

  2. Estimates of delays in diagnosis of cervical cancer in Nepal

    PubMed Central

    2014-01-01

    Background Cervical cancer is the leading cause of cancer related deaths among women in Nepal. The long symptom to diagnosis interval means that women have advanced disease at presentation. The aim of this study was to identify, estimate and describe the extent of different delays in diagnosis of cervical cancer in Nepal. Methods A cross-sectional descriptive study was conducted in two tertiary cancer hospitals of Nepal. Face to face interview and medical records review were carried out among 110 cervical cancer patients. Total diagnostic delay was categorized into component delays: patient delay, health care providers delay, referral delay and diagnostic waiting time. Results Total 110 patients recruited in the study represented 40 districts from all three ecological regions of the country. Median total diagnostic delay was 157 days with more than three fourth (77.3%) of the patients having longer total diagnostic delay of >90 days. Out of the total diagnostic delay, median patient delay, median health care provider delay, median referral delay and median diagnostic waiting time were 68.5 days, 40 days, 5 days and 9 days respectively. Majority of the patients had experienced longer delay of each type except referral delay. Fifty seven percent of the patients had experienced longer patient delay of >60 days, 90% had suffered longer health care provider delay of >1 week, 31.8% had longer referral delay of >1 week and 66.2% had waited >1 week at diagnostic center for final diagnosis. Variation in each type of delay was observed among women with different attributes and in context of health care service delivery. Conclusions Longer delays were observed in all the diagnostic pathways except for referral delay and diagnostic waiting time. Among the delays, patient delay is of crucial importance because of its longer span, although health care provider delay is equally important. In the context of limited screening services in Nepal, the efforts should be to reduce the diagnostic delay especially patient and health care provider delay for early detection and reduction of mortality rate of cervical cancer. PMID:24533670

  3. Alterations of mitochondrial DNA in CEM cells selected for resistance toward ddC toxicity.

    PubMed

    Bjerke, M; Franco, M; Johansson, M; Balzarini, J; Karlsson, A

    2006-01-01

    2 ',3 '-dideoxycytidine (ddC) is a nucleoside analog that has been shown to produce a delayed toxicity which may be due to the depletion of mitochondrial DNA (mtDNA). In order to gain further understanding of the events involved in mitochondrial toxicity, two different CEM cell lines were selected for resistance to the delayed ddC toxicity.

  4. Seasonal Variation in Pigeon Body Weight and Delayed Matching-to-sample Performance

    PubMed Central

    Sargisson, Rebecca J; McLean, Ian G; Brown, Glenn S; White, K Geoffrey

    2007-01-01

    The weights of 5 pigeons with free access to food, monitored over 3 calendar years in the laboratory, were found to fluctuate with season. All pigeons were at their heaviest in the winter and were lightest in the summer. Five different pigeons performed a standard delayed matching-to-sample task for 44 weeks from January to November. Their weights were held at 85% of their summer free-feeding weights, making their predicted deprivation level higher in the winter relative to predicted winter free-feeding weights. Slopes of forgetting functions fit to weekly response totals for each pigeon were shallower in winter, showing an improvement in accuracy with longer delays. Thus, delayed matching-to-sample performance may have been affected by the practice of maintaining the pigeons at a constant body weight throughout the calendar year. PMID:18047229

  5. A collection of articles on S/X-band experiment zero delay ranging tests, volume 1

    NASA Technical Reports Server (NTRS)

    Otoshi, T. Y. (Editor)

    1975-01-01

    Articles are presented which are concerned with the development of special test equipment and a dual-frequency zero delay device (ZDD) that were required for range tests and the measurement of ground station delays for the Mariner-Venus-Mercury 1973 S/X-band experiment. Test data obtained at DSS 14 after installation of the ZDD on the 64-m antenna are given. It is shown that large variations of range were observed as a function of antenna elevation angle and were sensitive to antenna location. A ranging calibration configuration that was subsequently developed and a technique for determining the appropriate Z-correction are described. Zero delay test data at DSS 14 during the Mariner 10 Venus-Mercury-Encounter periods (1974 days 12-150) are presented. The theoretical analysis and experimental verifications are included of the effects of multipath and effects of discontinuities on range delay measurements. A movable subreflector technique and the multipath theory were used to isolate principal multipath errors on the 64-m antenna and to enable a more accurate determination of the actual ground station range delay.

  6. Benign, Pathogenic and Copy Number Variations of Unknown Clinical Significance in Patients with Congenital Malformations and Developmental Delay.

    PubMed

    Mihaylova, M; Staneva, R; Toncheva, D; Pancheva, M; Hadjidekova, S

    2017-06-30

    The high frequency (3.0-5.0%) of congenital anomalies (CA) and intellectual disabilities (IDs), make them a serious problem, responsible for a high percentage (33.0%) of neonatal mortality. The genetic cause remains unclear in 40.0% of cases. Recently, molecular karyotyping has become the most powerful method for detection of pathogenic imbalances in patients with multiple CAs and IDs. This method is with high resolution and gives us the opportunity to investigate and identify candidate genes that could explain the genotype-phenotype correlations. This article describes the results from analysis of 81 patients with congenital malformations (CMs), developmental delay (DD) and ID, in which we utilized the CytoChip ISCA oligo microarray, 4 × 44 k, covering the whole genome with a resolution of 70 kb. In the selected group of patients with CAs, 280 copy number variations (CNVs) have been proven, 41 were pathogenic, 118 benign and 121 of unknown clinical significance (average number of variations 3.5). In six patients with established pathogenic variations, our data revealed eight pathogenic aberrations associated with the corresponding phenotype. The interpretation of the other CNVs was made on the basis of their frequency in the investigated group, the size of the variation, content of genes in the region and the type of the CNVs (deletion or duplication).

  7. The behavior of seasonal variations in induced seismicity in the Koyna-Warna region, western India

    NASA Astrophysics Data System (ADS)

    Smirnov, V. B.; Srinagesh, D.; Ponomarev, A. V.; Chadha, R.; Mikhailov, V. O.; Potanina, M. G.; Kartashov, I. M.; Stroganova, S. M.

    2017-07-01

    Based on the earthquake catalog data for the Koyna-Warna region of induced seismicity in western India, the seasonal variations in seismic activity associated with annual fluctuations in the reservoir water level are analyzed over the time span of the entire history of seismological observations in this region. The regularities in the time changes in the structure of seasonal variations are revealed. The seasonal seismic activity is minimal in May-June when the reservoir level is lowest. During the remaining part of the year, the activity has three peaks: the fall peak in September, winter peak in November-December, and spring peak in February-March. The first mentioned peak, which falls in the phase of the water level reaching its maximal seasonal value is considered as the immediate response of the fluid saturated medium to the additional loading under the weight of reservoir water. The two subsequent maxima concur with the decline phase in the reservoir level and are interpreted as the delayed response associated with the changes in the properties of the medium due to water diffusion. It is shown that the intensities of the immediate and delayed responses to the seasonal water level variations both vary with time as does their ratio. The probable factors affecting the variations in the intensity of the seasonal components of the reservoir-induced seismicity are discussed.

  8. Tumour volume response, initial cell kill and cellular repopulation in B16 melanoma treated with cyclophosphamide and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea.

    PubMed Central

    Stephens, T. C.; Peacock, J. H.

    1977-01-01

    The relationship between tumour volume response and cell kill in B16 melanoma following treatment in vivo with cyclophosphamide (CY) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) was investigated. Tumour volume response, expressed as growth delay, was estimated from measurements of tumour dimensions. Depression of in vitro colony-forming ability of cells from treated tumours was used as the measure of tumour cell kill. The relationship between these parameters was clearly different for the two agents studied. CY produced more growth delay (7.5 days) per decade of tumour cell kill than CCNU (2 to 3.5 days). The possibility that this was due to a technical artefact was rejected in favour of an alternative explanation that different rates of cellular repopulation in tumours treated with CY and CCNU might be responsible. Cellular repopulation was measured directly, by performing cell-survival assays at various times after treatment with doses of CY and CCNU which produced about 3 decades of cell kill. The rate of repopulation by clonogenic cells was much slower after treatment with CY than with CCNU, and this appears to account for the longer duration of the growth delay obtained with CY. PMID:921888

  9. Highly precise acoustic calibration method of ring-shaped ultrasound transducer array for plane-wave-based ultrasound tomography

    NASA Astrophysics Data System (ADS)

    Terada, Takahide; Yamanaka, Kazuhiro; Suzuki, Atsuro; Tsubota, Yushi; Wu, Wenjing; Kawabata, Ken-ichi

    2017-07-01

    Ultrasound computed tomography (USCT) is promising for a non-invasive, painless, operator-independent and quantitative system for breast-cancer screening. Assembly error, production tolerance, and aging-degradation variations of the hardwire components, particularly of plane-wave-based USCT systems, may hamper cost effectiveness, precise imaging, and robust operation. The plane wave is transmitted from a ring-shaped transducer array for receiving the signal at a high signal-to-noise-ratio and fast aperture synthesis. There are four signal-delay components: response delays in the transmitters and receivers and propagation delays depending on the positions of the transducer elements and their directivity. We developed a highly precise calibration method for calibrating these delay components and evaluated it with our prototype plane-wave-based USCT system. Our calibration method was found to be effective in reducing delay errors. Gaps and curves were eliminated from the plane wave, and echo images of wires were sharpened in the entire imaging area.

  10. Application of a genetically encoded biosensor for live cell imaging of L-valine production in pyruvate dehydrogenase complex-deficient Corynebacterium glutamicum strains.

    PubMed

    Mustafi, Nurije; Grünberger, Alexander; Mahr, Regina; Helfrich, Stefan; Nöh, Katharina; Blombach, Bastian; Kohlheyer, Dietrich; Frunzke, Julia

    2014-01-01

    The majority of biotechnologically relevant metabolites do not impart a conspicuous phenotype to the producing cell. Consequently, the analysis of microbial metabolite production is still dominated by bulk techniques, which may obscure significant variation at the single-cell level. In this study, we have applied the recently developed Lrp-biosensor for monitoring of amino acid production in single cells of gradually engineered L-valine producing Corynebacterium glutamicum strains based on the pyruvate dehydrogenase complex-deficient (PDHC) strain C. glutamicum ΔaceE. Online monitoring of the sensor output (eYFP fluorescence) during batch cultivation proved the sensor's suitability for visualizing different production levels. In the following, we conducted live cell imaging studies on C. glutamicum sensor strains using microfluidic chip devices. As expected, the sensor output was higher in microcolonies of high-yield producers in comparison to the basic strain C. glutamicum ΔaceE. Microfluidic cultivation in minimal medium revealed a typical Gaussian distribution of single cell fluorescence during the production phase. Remarkably, low amounts of complex nutrients completely changed the observed phenotypic pattern of all strains, resulting in a phenotypic split of the population. Whereas some cells stopped growing and initiated L-valine production, others continued to grow or showed a delayed transition to production. Depending on the cultivation conditions, a considerable fraction of non-fluorescent cells was observed, suggesting a loss of metabolic activity. These studies demonstrate that genetically encoded biosensors are a valuable tool for monitoring single cell productivity and to study the phenotypic pattern of microbial production strains.

  11. Application of a Genetically Encoded Biosensor for Live Cell Imaging of L-Valine Production in Pyruvate Dehydrogenase Complex-Deficient Corynebacterium glutamicum Strains

    PubMed Central

    Mahr, Regina; Helfrich, Stefan; Nöh, Katharina; Blombach, Bastian; Kohlheyer, Dietrich; Frunzke, Julia

    2014-01-01

    The majority of biotechnologically relevant metabolites do not impart a conspicuous phenotype to the producing cell. Consequently, the analysis of microbial metabolite production is still dominated by bulk techniques, which may obscure significant variation at the single-cell level. In this study, we have applied the recently developed Lrp-biosensor for monitoring of amino acid production in single cells of gradually engineered L-valine producing Corynebacterium glutamicum strains based on the pyruvate dehydrogenase complex-deficient (PDHC) strain C. glutamicum ΔaceE. Online monitoring of the sensor output (eYFP fluorescence) during batch cultivation proved the sensor's suitability for visualizing different production levels. In the following, we conducted live cell imaging studies on C. glutamicum sensor strains using microfluidic chip devices. As expected, the sensor output was higher in microcolonies of high-yield producers in comparison to the basic strain C. glutamicum ΔaceE. Microfluidic cultivation in minimal medium revealed a typical Gaussian distribution of single cell fluorescence during the production phase. Remarkably, low amounts of complex nutrients completely changed the observed phenotypic pattern of all strains, resulting in a phenotypic split of the population. Whereas some cells stopped growing and initiated L-valine production, others continued to grow or showed a delayed transition to production. Depending on the cultivation conditions, a considerable fraction of non-fluorescent cells was observed, suggesting a loss of metabolic activity. These studies demonstrate that genetically encoded biosensors are a valuable tool for monitoring single cell productivity and to study the phenotypic pattern of microbial production strains. PMID:24465669

  12. NMDA Receptors Subserve Persistent Neuronal Firing During Working Memory In Dorsolateral Prefrontal Cortex

    PubMed Central

    Wang, Min; Yang, Yang; Wang, Ching-Jung; Gamo, Nao J.; Jin, Lu E.; Mazer, James A.; Morrison, John H.; Wang, Xiao-Jing; Arnsten, Amy F.T.

    2013-01-01

    Summary Neurons in the primate dorsolateral prefrontal cortex (dlPFC) generate persistent firing in the absence of sensory stimulation, the foundation of mental representation. Persistent firing arises from recurrent excitation within a network of pyramidal Delay cells. Here, we examined glutamate receptor influences underlying persistent firing in primate dlPFC during a spatial working memory task. Computational models predicted dependence on NMDA receptor (NMDAR) NR2B stimulation, and Delay cell persistent firing was abolished by local NR2B NMDAR blockade or by systemic ketamine administration. AMPA receptors (AMPAR) contributed background depolarization to sustain network firing. In contrast, many Response cells -which likely predominate in rodent PFC- were sensitive to AMPAR blockade and increased firing following systemic ketamine, indicating that models of ketamine actions should be refined to reflect neuronal heterogeneity. The reliance of Delay cells on NMDAR may explain why insults to NMDARs in schizophrenia or Alzheimer’s Disease profoundly impair cognition. PMID:23439125

  13. Two R7 RGS proteins shape retinal bipolar cell signaling

    PubMed Central

    Mojumder, Deb Kumar; Qian, Yan; Wensel, Theodore G.

    2009-01-01

    RGS7, RGS11, and their binding partner Gβ5 are localized to the dendritic tips of retinal ON bipolar cells (ON-BPC), where mGluR6 responds to glutamate released from photoreceptor terminals by activation of the RGS7/RGS11 substrate, Gαo. To determine their functions in retinal signaling, we investigated cell-specific expression patterns of RGS7 and RGS11 by immunostaining, and measured light responses by electroretinography (ERG) in mice with targeted disruptions of the genes encoding them. RGS7 staining is present in dendritic tips of all rod ON-BPC, but missing in those for subsets of cone ON-BPC, whereas the converse was true for RGS11 staining. Genetic disruption of either RGS7 or RGS11 produced delays in the ON-BPC-derived electroretinogram b-wave, but no changes in the photoreceptor-derived a-wave. Homozygous RGS7 mutant mice had delays in rod-driven b-waves, whereas, RGS11 mutant mice had delays in rod-driven, and especially in cone-driven b-waves. The b-wave delays were further enhanced in mice homozygous for both RGS7 and RGS11 gene disruptions. Thus, RGS7 and RGS11 act in parallel to regulate the kinetics of ON bipolar cell responses, with differential impacts on the rod and cone pathways. PMID:19535587

  14. NF-E2 Overexpression Delays Erythroid Maturation and Increases Erythrocyte Production

    PubMed Central

    Mutschler, Manuel; Magin, Angela S.; Buerge, Martina; Roelz, Roland; Schanne, Daniel H.; Will, Britta; Pilz, Ingo H.; Migliaccio, Anna Rita; Pahl, Heike L.

    2009-01-01

    Summary The transcription factor Nuclear Factor-Erythroid 2 (NF-E2) is overexpressed in the vast majority of patients with polycythaemia vera (PV). In murine models, NF-E2 overexpression increases proliferation and promotes cellular viability in the absence of erythropoietin (EPO). EPO-independent growth is a hallmark of PV. We therefore hypothesized that NF-E2 overexpression contributes to erythrocytosis, the pathognomonic feature of PV. Consequently, we investigated the effect of NF-E2 overexpression in healthy CD34+ cells. NF-E2 overexpression led to a delay in erythroid maturation, manifested by a belated appearance of glycophorin A-positive erythroid precursors. Maturation delay was similarly observed in primary PV patient erythroid cultures compared to healthy controls. Protracted maturation led to a significant increase in the accumulated number of erythroid cells both in PV cultures and in CD34+ cells overexpressing NF-E2. Similarly, NF-E2 overexpression altered erythroid colony formation, leading to an increase in BFU-E formation. These data indicate that NF-E2 overexpression delays the early phase of erythroid maturation, resulting in an expansion of erythroid progenitors, thereby increasing the number of erythrocytes derived from one CD34+ cell. These data propose a role for NF-E2 in mediating the erythrocytosis of PV. PMID:19466964

  15. Concordance of CCR5 genotypes that influence cell-mediated immunity and HIV-1 disease progression rates.

    PubMed

    Catano, Gabriel; Chykarenko, Zoya A; Mangano, Andrea; Anaya, J-M; He, Weijing; Smith, Alison; Bologna, Rosa; Sen, Luisa; Clark, Robert A; Lloyd, Andrew; Shostakovich-Koretskaya, Ludmila; Ahuja, Sunil K

    2011-01-15

    We used cutaneous delayed-type hypersensitivity responses, a powerful in vivo measure of cell-mediated immunity, to evaluate the relationships among cell-mediated immunity, AIDS, and polymorphisms in CCR5, the HIV-1 coreceptor. There was high concordance between CCR5 polymorphisms and haplotype pairs that influenced delayed-type hypersensitivity responses in healthy persons and HIV disease progression. In the cohorts examined, CCR5 genotypes containing -2459G/G (HHA/HHA, HHA/HHC, HHC/HHC) or -2459A/A (HHE/HHE) associated with salutary or detrimental delayed-type hypersensitivity and AIDS phenotypes, respectively. Accordingly, the CCR5-Δ32 allele, when paired with non-Δ32-bearing haplotypes that correlate with low (HHA, HHC) versus high (HHE) CCR5 transcriptional activity, associates with disease retardation or acceleration, respectively. Thus, the associations of CCR5-Δ32 heterozygosity partly reflect the effect of the non-▵32 haplotype in a background of CCR5 haploinsufficiency. The correlations of increased delayed-type hypersensitivity with -2459G/G-containing CCR5 genotypes, reduced CCR5 expression, decreased viral replication, and disease retardation suggest that CCR5 may influence HIV infection and AIDS, at least in part, through effects on cell-mediated immunity.

  16. Steps Toward Determination of the Size and Structure of the Broad-Line Region in Active Galactic Nuclei XVI: A 13 Year Study of Spectral Variability in NGC 5548

    NASA Technical Reports Server (NTRS)

    Peterson, B. M.; Berlind, P.; Bertram, R.; Bischoff, K.; Bochkarev, N. G.; Burenkov, A. N.; Calkins, M.; Carrasco, L.; Chavushyan, V. H.

    2002-01-01

    We present the final installment of an intensive 13 year study of variations of the optical continuum and broad H beta emission line in the Seyfert 1 galaxy NGC 5548. The database consists of 1530 optical continuum measurements and 1248 H beta measurements. The H beta variations follow the continuum variations closely, with a typical time delay of about 20 days. However, a year-by-year analysis shows that the magnitude of emission-line time delay is correlated with the mean continuum flux. We argue that the data are consistent with the simple model prediction between the size of the broad-line region and the ionizing luminosity, r is proportional to L(sup 1/2)(sub ion). Moreover, the apparently linear nature of the correlation between the H beta response time and the nonstellar optical continuum F(sub opt) arises as a consequence of the changing shape of the continuum as it varies, specifically F(sub opt) is proportional to F(sup 0.56)(sub UV).

  17. Inhibition of Bim Enhances Replication of Varicella-Zoster Virus and Delays Plaque Formation in Virus-Infected Cells

    PubMed Central

    Liu, XueQiao

    2014-01-01

    Programmed cell death (apoptosis) is an important host defense mechanism against intracellular pathogens, such as viruses. Accordingly, viruses have evolved multiple mechanisms to modulate apoptosis to enhance replication. Varicella-zoster virus (VZV) induces apoptosis in human fibroblasts and melanoma cells. We found that VZV triggered the phosphorylation of the proapoptotic proteins Bim and BAD but had little or no effect on other Bcl-2 family members. Since phosphorylation of Bim and BAD reduces their proapoptotic activity, this may prevent or delay apoptosis in VZV-infected cells. Phosphorylation of Bim but not BAD in VZV-infected cells was dependent on activation of the MEK/extracellular signal-regulated kinase (ERK) pathway. Cells knocked down for Bim showed delayed VZV plaque formation, resulting in longer survival of VZV-infected cells and increased replication of virus, compared with wild-type cells infected with virus. Conversely, overexpression of Bim resulted in earlier plaque formation, smaller plaques, reduced virus replication, and increased caspase 3 activity. Inhibition of caspase activity in VZV-infected cells overexpressing Bim restored levels of virus production similar to those seen with virus-infected wild-type cells. Previously we showed that VZV ORF12 activates ERK and inhibits apoptosis in virus-infected cells. Here we found that VZV ORF12 contributes to Bim and BAD phosphorylation. In summary, VZV triggers Bim phosphorylation; reduction of Bim levels results in longer survival of VZV-infected cells and increased VZV replication. PMID:24227856

  18. Radiation-induced transmissable chromosomal instability in haemopoietic stem cells

    NASA Astrophysics Data System (ADS)

    Kadhim, M. A.; Wright, E. G.

    Heritable radiation-induced genetic alterations have long been assumed to be ``fixed'' within the first cell division. However, there is a growing body of evidence that a considerable fraction of cells surviving radiation exposure appear normal, but a variety of mutational changes arise in their progeny due to a transmissible genomic instability. In our investigations of G-banded metaphases, non-clonal cytogenetic aberrations, predominantly chromatid-type aberrations, have been observed in the clonal descendants of murine and human haemopoietic stem cells surviving low doses (~1 track per cell) of alpha-particle irradiations. The data are consistent with a transmissible genetic instability induced in a stem cell resulting in a diversity of chromosomal aberrations in its clonal progeny many cell divisions later. Recent studies have demonstrated that the instability phenotype persists in vivo and that the expression of chromosomal instability has a strong dependence on the genetic characteristics of the irradiated cell. At the time when cytogenetic aberrations are detected, an increased incidence of hprt mutations and apoptotic cells have been observed in the clonal descendants of alpha-irradiated murine haemopoietic stem cells. Thus, delayed chromosomal abnormalities, delayed cell death by apoptosis and late-arising specific gene mutations may reflect diverse consequences of radiation-induced genomic instability. The relationship, if any, between these effects is not established. Current studies suggest that expression of these delayed heritable effects is determined by the type of radiation exposure, type of cell and a variety of genetic factors.

  19. Organic solar cells: evaluation of the stability of P3HT using time-delayed degradation

    NASA Astrophysics Data System (ADS)

    Poh, Chung-How; Poh, Chung-Kiak; Bryant, Glenn; Belcher, Warwick; Dastoor, Paul

    2011-12-01

    Despite the fact that the performance of organic solar cells is generally susceptible to degradation by moisture exposure, there has been suggestion that the photoactive layer (P3HT) is surprisingly resilient. This work attempts to confirm the stability of P3HT as an organic solar cell material by deliberately introducing water into the photoactive layer. A dramatic step drop in device performance during cell characterization is observed approximately one day after the device has been fabricated. The time-delayed step drop in output efficiency strongly suggests that moisture has little effect on the P3HT conducting polymer.

  20. Delayed Accumulation of H3K27me3 on Nascent DNA Is Essential for Recruitment of Transcription Factors at Early Stages of Stem Cell Differentiation.

    PubMed

    Petruk, Svetlana; Cai, Jingli; Sussman, Robyn; Sun, Guizhi; Kovermann, Sina K; Mariani, Samanta A; Calabretta, Bruno; McMahon, Steven B; Brock, Hugh W; Iacovitti, Lorraine; Mazo, Alexander

    2017-04-20

    Recruitment of transcription factors (TFs) to repressed genes in euchromatin is essential to activate new transcriptional programs during cell differentiation. However, recruitment of all TFs, including pioneer factors, is impeded by condensed H3K27me3-containing chromatin. Single-cell and gene-specific analyses revealed that, during the first hours of induction of differentiation of mammalian embryonic stem cells (ESCs), accumulation of the repressive histone mark H3K27me3 is delayed after DNA replication, indicative of a decondensed chromatin structure in all regions of the replicating genome. This delay provides a critical "window of opportunity" for recruitment of lineage-specific TFs to DNA. Increasing the levels of post-replicative H3K27me3 or preventing S phase entry inhibited recruitment of new TFs to DNA and significantly blocked cell differentiation. These findings suggest that recruitment of lineage-specifying TFs occurs soon after replication and is facilitated by a decondensed chromatin structure. This insight may explain the developmental plasticity of stem cells and facilitate their exploitation for therapeutic purposes. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Reaction-diffusion systems in natural sciences and new technology transfer

    NASA Astrophysics Data System (ADS)

    Keller, André A.

    2012-12-01

    Diffusion mechanisms in natural sciences and innovation management involve partial differential equations (PDEs). This is due to their spatio-temporal dimensions. Functional semi-discretized PDEs (with lattice spatial structures or time delays) may be even more adapted to real world problems. In the modeling process, PDEs can also formalize behaviors, such as the logistic growth of populations with migration, and the adopters’ dynamics of new products in innovation models. In biology, these events are related to variations in the environment, population densities and overcrowding, migration and spreading of humans, animals, plants and other cells and organisms. In chemical reactions, molecules of different species interact locally and diffuse. In the management of new technologies, the diffusion processes of innovations in the marketplace (e.g., the mobile phone) are a major subject. These innovation diffusion models refer mainly to epidemic models. This contribution introduces that modeling process by using PDEs and reviews the essential features of the dynamics and control in biological, chemical and new technology transfer. This paper is essentially user-oriented with basic nonlinear evolution equations, delay PDEs, several analytical and numerical methods for solving, different solutions, and with the use of mathematical packages, notebooks and codes. The computations are carried out by using the software Wolfram Mathematica®7, and C++ codes.

  2. Judgement on "hit or non-hit" of CHO cells exposed to accelerated heavy-ions (Fe- or Ar-ions) using division delay and CR-39 plastics as an indicator.

    PubMed

    Mehnati, P; Yatagai, F; Tsuzuki, T; Hanaoka, F; Sasaki, H

    2001-03-01

    The cell killing effect of ionizing radiation depends on the degree of linear energy transfer (LET). The relative biological effectiveness (RBE) reaches a maximum at LET of around 100-200 keV/micron and decreases at higher levels. The ion clusters produced by high-LET radiation are not uniformly distributed. The incidence of non-hit cell events is higher in high LET irradiation than in the cases of low-LET irradiation. This fact could explain the decrease in the cell killing effect at higher levels of LET irradiation. Since the cell killing effect may be related to the nuclear traversal of heavy-ions, it is necessary to establish methods to distinguish the hit cells from the non-hit cells, especially in case with high LET irradiation. Using time-lapse photography, we first examined the hit events by observing the division delay in the cells caused by high-LET irradiation. In addition, we explored the use of CR-39 plastics to detect the exact position of heavy-ion traversal on the surface of a flask where cells were growing. When Chinese hamster ovary (CHO-K1) cells were exposed to 4 Gy of accelerated Fe-ions (2000 keV/micron) or Ar (1640 keV/micron)-ions, the surviving fraction decreased to about 30% in both cases of irradiation. Eighty percent of the irradiated cells, suffered a division delay in contrast to the remaining 20% of the cells which showed a normal division time (12-13 hrs). The later 20% of the cells is considered to be a population of cells which were not actually traversed by heavy-ions. The difference between the higher values of the surviving fraction (approximately 30%) and the non-hit cell population (20%) indicates that some hit cells can grow even after being hit by heavy-ions. The fraction of recovered cells determined by the time-lapse photography method was 10%, and this value closely correlated with the difference between the surviving fraction and the non-hit cells. We used the Poisson distribution of the hit-events by heavy-ions among the cell population in order to calculate the fraction of cells receiving at least a single-hit in the cell nucleus (130 micron 2 in average size). From this calculation we determined that 80% of the cells had a single hit to their nuclei by a heavy-ion which induced such early cellular responses as division delay. Our finding in the experiments using CR-39 plastics as a detector for hit-sites further supported the idea that the hit lethality of a cell is related to heavy-ion traversal through its nucleus. This study indicates the possible usefulness of both the division delay and CR-39 plastic methods for evaluating the biological effects of heavy-ions, especially when these two methods are combined.

  3. Insulin, Central Dopamine D2 Receptors, and Monetary Reward Discounting in Obesity

    PubMed Central

    Eisenstein, Sarah A.; Gredysa, Danuta M.; Antenor–Dorsey, Jo Ann; Green, Leonard; Arbeláez, Ana Maria; Koller, Jonathan M.; Black, Kevin J.; Perlmutter, Joel S.; Moerlein, Stephen M.; Hershey, Tamara

    2015-01-01

    Animal research finds that insulin regulates dopamine signaling and reward behavior, but similar research in humans is lacking. We investigated whether individual differences in body mass index, percent body fat, pancreatic β-cell function, and dopamine D2 receptor binding were related to reward discounting in obese and non-obese adult men and women. Obese (n = 27; body mass index>30) and non-obese (n = 20; body mass index<30) adults were assessed for percent body fat with dual-energy X-ray absorptiometry and for β-cell function using disposition index. Choice of larger, but delayed or less certain, monetary rewards relative to immediate, certain smaller monetary rewards was measured using delayed and probabilistic reward discounting tasks. Positron emission tomography using a non-displaceable D2-specific radioligand, [11C](N-methyl)benperidol quantified striatal D2 receptor binding. Groups differed in body mass index, percent body fat, and disposition index, but not in striatal D2 receptor specific binding or reward discounting. Higher percent body fat in non-obese women related to preference for a smaller, certain reward over a larger, less likely one (greater probabilistic discounting). Lower β-cell function in the total sample and lower insulin sensitivity in obese related to stronger preference for an immediate and smaller monetary reward over delayed receipt of a larger one (greater delay discounting). In obese adults, higher striatal D2 receptor binding related to greater delay discounting. Interestingly, striatal D2 receptor binding was not significantly related to body mass index, percent body fat, or β-cell function in either group. Our findings indicate that individual differences in percent body fat, β-cell function, and striatal D2 receptor binding may each contribute to altered reward discounting behavior in non-obese and obese individuals. These results raise interesting questions about whether and how striatal D2 receptor binding and metabolic factors, including β-cell function, interact to affect reward discounting in humans. PMID:26192187

  4. Insulin, Central Dopamine D2 Receptors, and Monetary Reward Discounting in Obesity.

    PubMed

    Eisenstein, Sarah A; Gredysa, Danuta M; Antenor-Dorsey, Jo Ann; Green, Leonard; Arbeláez, Ana Maria; Koller, Jonathan M; Black, Kevin J; Perlmutter, Joel S; Moerlein, Stephen M; Hershey, Tamara

    2015-01-01

    Animal research finds that insulin regulates dopamine signaling and reward behavior, but similar research in humans is lacking. We investigated whether individual differences in body mass index, percent body fat, pancreatic β-cell function, and dopamine D2 receptor binding were related to reward discounting in obese and non-obese adult men and women. Obese (n = 27; body mass index>30) and non-obese (n = 20; body mass index<30) adults were assessed for percent body fat with dual-energy X-ray absorptiometry and for β-cell function using disposition index. Choice of larger, but delayed or less certain, monetary rewards relative to immediate, certain smaller monetary rewards was measured using delayed and probabilistic reward discounting tasks. Positron emission tomography using a non-displaceable D2-specific radioligand, [11C](N-methyl)benperidol quantified striatal D2 receptor binding. Groups differed in body mass index, percent body fat, and disposition index, but not in striatal D2 receptor specific binding or reward discounting. Higher percent body fat in non-obese women related to preference for a smaller, certain reward over a larger, less likely one (greater probabilistic discounting). Lower β-cell function in the total sample and lower insulin sensitivity in obese related to stronger preference for an immediate and smaller monetary reward over delayed receipt of a larger one (greater delay discounting). In obese adults, higher striatal D2 receptor binding related to greater delay discounting. Interestingly, striatal D2 receptor binding was not significantly related to body mass index, percent body fat, or β-cell function in either group. Our findings indicate that individual differences in percent body fat, β-cell function, and striatal D2 receptor binding may each contribute to altered reward discounting behavior in non-obese and obese individuals. These results raise interesting questions about whether and how striatal D2 receptor binding and metabolic factors, including β-cell function, interact to affect reward discounting in humans.

  5. Improving Accuracy in Arrhenius Models of Cell Death: Adding a Temperature-Dependent Time Delay.

    PubMed

    Pearce, John A

    2015-12-01

    The Arrhenius formulation for single-step irreversible unimolecular reactions has been used for many decades to describe the thermal damage and cell death processes. Arrhenius predictions are acceptably accurate for structural proteins, for some cell death assays, and for cell death at higher temperatures in most cell lines, above about 55 °C. However, in many cases--and particularly at hyperthermic temperatures, between about 43 and 55 °C--the particular intrinsic cell death or damage process under study exhibits a significant "shoulder" region that constant-rate Arrhenius models are unable to represent with acceptable accuracy. The primary limitation is that Arrhenius calculations always overestimate the cell death fraction, which leads to severely overoptimistic predictions of heating effectiveness in tumor treatment. Several more sophisticated mathematical model approaches have been suggested and show much-improved performance. But simpler models that have adequate accuracy would provide useful and practical alternatives to intricate biochemical analyses. Typical transient intrinsic cell death processes at hyperthermic temperatures consist of a slowly developing shoulder region followed by an essentially constant-rate region. The shoulder regions have been demonstrated to arise chiefly from complex functional protein signaling cascades that generate delays in the onset of the constant-rate region, but may involve heat shock protein activity as well. This paper shows that acceptably accurate and much-improved predictions in the simpler Arrhenius models can be obtained by adding a temperature-dependent time delay. Kinetic coefficients and the appropriate time delay are obtained from the constant-rate regions of the measured survival curves. The resulting predictions are seen to provide acceptably accurate results while not overestimating cell death. The method can be relatively easily incorporated into numerical models. Additionally, evidence is presented to support the application of compensation law behavior to the cell death processes--that is, the strong correlation between the kinetic coefficients, ln{A} and E(a), is confirmed.

  6. Paclitaxel stimulates chromosomal fusion and instability in cells with dysfunctional telomeres: Implication in multinucleation and chemosensitization

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

    Park, Jeong-Eun; Woo, Seon Rang; Department of Biochemistry, College of Medicine, Korea University, Seoul 136-705

    Research highlights: {yields} Paclitaxel serves as a stimulator of chromosomal fusion in cells in which telomeres are dysfunctional. {yields} Typical fusions involve p-arms, but paclitaxel-induced fusions occur between both q- and p-arms. {yields} Paclitaxel-stimulated fusions in cells in which telomeres are dysfunctional evoke prolonged G2/M cell cycle arrest and delay multinucleation. {yields} Upon telomere erosion, paclitaxel promotes chromosomal instability and subsequent apoptosis. {yields} Chromosomal fusion enhances paclitaxel chemosensitivity under telomere dysfunction. -- Abstract: The anticancer effect of paclitaxel is attributable principally to irreversible promotion of microtubule stabilization and is hampered upon development of chemoresistance by tumor cells. Telomere shortening, andmore » eventual telomere erosion, evoke chromosomal instability, resulting in particular cellular responses. Using telomerase-deficient cells derived from mTREC-/-p53-/- mice, here we show that, upon telomere erosion, paclitaxel propagates chromosomal instability by stimulating chromosomal end-to-end fusions and delaying the development of multinucleation. The end-to-end fusions involve both the p- and q-arms in cells in which telomeres are dysfunctional. Paclitaxel-induced chromosomal fusions were accompanied by prolonged G2/M cell cycle arrest, delayed multinucleation, and apoptosis. Telomere dysfunctional cells with mutlinucleation eventually underwent apoptosis. Thus, as telomere erosion proceeds, paclitaxel stimulates chromosomal fusion and instability, and both apoptosis and chemosensitization eventually develop.« less

  7. Residual delay maps unveil global patterns of atmospheric nonlinearity and produce improved local forecasts

    PubMed Central

    Sugihara, George; Casdagli, Martin; Habjan, Edward; Hess, Dale; Dixon, Paul; Holland, Greg

    1999-01-01

    We use residual-delay maps of observational field data for barometric pressure to demonstrate the structure of latitudinal gradients in nonlinearity in the atmosphere. Nonlinearity is weak and largely lacking in tropical and subtropical sites and increases rapidly into the temperate regions where the time series also appear to be much noisier. The degree of nonlinearity closely follows the meridional variation of midlatitude storm track frequency. We extract the specific functional form of this nonlinearity, a V shape in the lagged residuals that appears to be a basic feature of midlatitude synoptic weather systems associated with frontal passages. We present evidence that this form arises from the relative time scales of high-pressure versus low-pressure events. Finally, we show that this nonlinear feature is weaker in a well regarded numerical forecast model (European Centre for Medium-Range Forecasts) because small-scale temporal and spatial variation is smoothed out in the grided inputs. This is significant, in that it allows us to demonstrate how application of statistical corrections based on the residual-delay map may provide marked increases in local forecast accuracy, especially for severe weather systems. PMID:10588685

  8. Day-to-day variations in the amplitude of the soil temperature cycle and impact on adult eclosion timing of the onion fly.

    PubMed

    Tanaka, Kazuhiro; Watari, Yasuhiko

    2017-06-01

    The onion fly Delia antiqua advances its eclosion timing with decreasing temperature amplitude to compensate for a depth-dependent phase delay of the zeitgeber. To elucidate whether or not naturally occurring day-to-day variations in the amplitude of soil temperature cycle disturb this compensatory response, we monitored daily variations in the temperature amplitude in natural soils and evaluated the impact on adult eclosion timing. Our results indicated that both median and variance of the soil temperature amplitude become smaller as depth increases. Insertion of a larger temperature fluctuation into the thermoperiod with smaller temperature amplitude induced a stronger phase delay, while insertion of a smaller temperature fluctuation into the thermoperiod with larger temperature amplitude had a weaker phase-advancing effect. It is therefore expected that larger diurnal temperature fluctuations disturb the compensatory response, particularly if they occur at deeper locations, while smaller temperature fluctuations do so only at shallower locations. Under natural conditions, however, the probability of occurrence of smaller or larger temperature fluctuations in shallower or deeper soils, respectively, is relatively small. Thus, naturally occurring day-to-day variations in the temperature amplitude rarely disturb the compensatory response, thereby having a subtle or negligible impact on adult eclosion timing.

  9. Defining the Ideal Time Interval Between Planned Induction Therapy and Surgery for Stage IIIA Non-Small Cell Lung Cancer.

    PubMed

    Samson, Pamela; Crabtree, Traves D; Robinson, Cliff G; Morgensztern, Daniel; Broderick, Stephen; Krupnick, A Sasha; Kreisel, Daniel; Patterson, G Alexander; Meyers, Bryan; Puri, Varun

    2017-04-01

    Induction therapy leads to significant improvement in survival for selected patients with stage IIIA non-small cell lung cancer. The ideal time interval between induction therapy and surgery remains unknown. Clinical stage IIIA non-small cell lung cancer patients receiving induction therapy and surgery were identified in the National Cancer Database. Delayed surgery was defined as greater than or equal to 3 months after starting induction therapy. A logistic regression model identified variables associated with delayed surgery. Cox proportional hazards modeling and Kaplan-Meier analysis were performed to evaluate variables independently associated with overall survival. From 2006 to 2010, 1,529 of 2,380 (64.2%) received delayed surgery. Delayed surgery patients were older (61.2 ± 10.0 years versus 60.3 ± 9.2; p = 0.03), more likely to be non-white (12.4% versus 9.7%; p = 0.046), and less likely to have private insurance (50% versus 58.2%; p = 0.002). Delayed surgery patients were also more likely to have a sublobar resection (6.3% versus 2.9%). On multivariate analysis, age greater than 68 years (odds ratio [OR], 1.37; 95% confidence interval [CI], 1.1 to 1.7) was associated with delayed surgery, whereas white race (OR, 0.75; 95% CI, 0.57 to 0.99) and private insurance status (OR, 0.82; 95% CI, 0.68 to 0.99) were associated with early surgery. Delayed surgery was associated with higher risk of long-term mortality (hazard ratio, 1.25; 95% CI, 1.07 to 1.47). Delayed surgery after induction therapy for stage IIIA lung cancer is associated with shorter survival, and is influenced by both social and physiologic factors. Prospective work is needed to further characterize the relationship between patient comorbidities and functional status with receipt of timely surgery. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  10. a Study of Multiplexing Schemes for Voice and Data.

    NASA Astrophysics Data System (ADS)

    Sriram, Kotikalapudi

    Voice traffic variations are characterized by on/off transitions of voice calls, and talkspurt/silence transitions of speakers in conversations. A speaker is known to be in silence for more than half the time during a telephone conversation. In this dissertation, we study some schemes which exploit speaker silences for an efficient utilization of the transmission capacity in integrated voice/data multiplexing and in digital speech interpolation. We study two voice/data multiplexing schemes. In each scheme, any time slots momentarily unutilized by the voice traffic are made available to data. In the first scheme, the multiplexer does not use speech activity detectors (SAD), and hence the voice traffic variations are due to call on/off only. In the second scheme, the multiplexer detects speaker silences using SAD and transmits voice only during talkspurts. The multiplexer with SAD performs digital speech interpolation (DSI) as well as dynamic channel allocation to voice and data. The performance of the two schemes is evaluated using discrete-time modeling and analysis. The data delay performance for the case of English speech is compared with that for the case of Japanese speech. A closed form expression for the mean data message delay is derived for the single-channel single-talker case. In a DSI system, occasional speech losses occur whenever the number of speakers in simultaneous talkspurt exceeds the number of TDM voice channels. In a buffered DSI system, speech loss is further reduced at the cost of delay. We propose a novel fixed-delay buffered DSI scheme. In this scheme, speech fill-in/hangover is not required because there are no variable delays. Hence, all silences that naturally occur in speech are fully utilized. Consequently, a substantial improvement in the DSI performance is made possible. The scheme is modeled and analyzed in discrete -time. Its performance is evaluated in terms of the probability of speech clipping, packet rejection ratio, DSI advantage, and the delay.

  11. Carbidopa abrogates L-dopa decarboxylase coactivation of the androgen receptor and delays prostate tumor progression.

    PubMed

    Wafa, Latif A; Cheng, Helen; Plaa, Nathan; Ghaidi, Fariba; Fukumoto, Takahiro; Fazli, Ladan; Gleave, Martin E; Cox, Michael E; Rennie, Paul S

    2012-06-15

    The androgen receptor (AR) plays a central role in prostate cancer progression to the castration-resistant (CR) lethal state. L-Dopa decarboxylase (DDC) is an AR coactivator that increases in expression with disease progression and is coexpressed with the receptor in prostate adenocarcinoma cells, where it may enhance AR activity. Here, we hypothesize that the DDC enzymatic inhibitor, carbidopa, can suppress DDC-coactivation of AR and retard prostate tumor growth. Treating LNCaP prostate cancer cells with carbidopa in transcriptional assays suppressed the enhanced AR transactivation seen with DDC overexpression and decreased prostate-specific antigen (PSA) mRNA levels. Carbidopa dose-dependently inhibited cell growth and decreased survival in LNCaP cell proliferation and apoptosis assays. The inhibitory effect of carbidopa on DDC-coactivation of AR and cell growth/survival was also observed in PC3 prostate cancer cells (stably expressing AR). In vivo studies demonstrated that serum PSA velocity and tumor growth rates elevated ∼2-fold in LNCaP xenografts, inducibly overexpressing DDC, were reverted to control levels with carbidopa administration. In castrated mice, treating LNCaP tumors, expressing endogenous DDC, with carbidopa delayed progression to the CR state from 6 to 10 weeks, while serum PSA and tumor growth decreased 4.3-fold and 5.4-fold, respectively. Our study is a first time demonstration that carbidopa can abrogate DDC-coactivation of AR in prostate cancer cells and tumors, decrease serum PSA, reduce tumor growth and delay CR progression. Since carbidopa is clinically approved, it may be readily used as a novel therapeutic strategy to suppress aberrant AR activity and delay prostate cancer progression. Copyright © 2011 UICC.

  12. Misregulated progesterone secretion and impaired pregnancy in Cyp11a1 transgenic mice.

    PubMed

    Chien, Yu; Cheng, Wei-Cheng; Wu, Menq-Rong; Jiang, Si-Tse; Shen, Che-Kun James; Chung, Bon-chu

    2013-10-01

    Normal pregnancy is supported by increased levels of progesterone (P4), which is secreted from ovarian luteal cells via enzymatic steps catalyzed by P450scc (CYP11A1) and HSD3B. The development and maintenance of corpora lutea during pregnancy, however, are less well understood. Here we used Cyp11a1 transgenic mice to delineate the steps of luteal cell differentiation during pregnancy. Cyp11a1 in a bacterial artificial chromosome was injected into mouse embryos to generate transgenic mice with transgene expression that recapitulated endogenous Cyp11a1 expression. Cyp11a1 transgenic females displayed reduced pregnancy rate, impaired implantation and placentation, and decreased litter size in utero, although they produced comparable numbers of blastocysts. The differentiation of transgenic luteal cells was delayed during early pregnancy as shown by the delayed activation of genes involved in steroidogenesis and cholesterol availability. Luteal cell mitochondria were elongated, and their numbers were reduced, with morphology and numbers similar to those observed in granulosa cells. Transgenic luteal cells accumulated lipid droplets and secreted less progesterone during early pregnancy. The progesterone level returned to normal on gestation day 9 but was not properly withdrawn at term, leading to delayed stillbirth. P4 supplementation rescued the implantation rates but not the ovarian defects. Thus, overexpression of Cyp11a1 disrupts normal development of the corpus luteum, leading to progesterone insufficiency during early pregnancy. Misregulation of the progesterone production in Cyp11a1 transgenic mice during pregnancy resulted in aberrant implantation, anomalous placentation, and delayed parturition.

  13. SIRT1 deficiency compromises mouse embryonic stem cell hematopoietic differentiation, and embryonic and adult hematopoiesis in the mouse

    PubMed Central

    Ou, Xuan; Chae, Hee-Don; Wang, Rui-Hong; Shelley, William C.; Cooper, Scott; Taylor, Tammi; Kim, Young-June; Deng, Chu-Xia; Yoder, Mervin C.

    2011-01-01

    SIRT1 is a founding member of a sirtuin family of 7 proteins and histone deacetylases. It is involved in cellular resistance to stress, metabolism, differentiation, aging, and tumor suppression. SIRT1−/− mice demonstrate embryonic and postnatal development defects. We examined hematopoietic and endothelial cell differentiation of SIRT1−/− mouse embryonic stem cells (ESCs) in vitro, and hematopoietic progenitors in SIRT1+/++/−, and −/− mice. SIRT1−/− ESCs formed fewer mature blast cell colonies. Replated SIRT1−/− blast colony-forming cells demonstrated defective hematopoietic potential. Endothelial cell production was unaltered, but there were defects in formation of a primitive vascular network from SIRT1−/−-derived embryoid bodies. Development of primitive and definitive progenitors derived from SIRT1−/− ESCs were also delayed and/or defective. Differentiation delay/defects were associated with delayed capacity to switch off Oct4, Nanog and Fgf5 expression, decreased β-H1 globin, β-major globin, and Scl gene expression, and reduced activation of Erk1/2. Ectopic expression of SIRT1 rescued SIRT1−/− ESC differentiation deficiencies. SIRT1−/− yolk sacs manifested fewer primitive erythroid precursors. SIRT1−/− and SIRT1+/− adult marrow had decreased numbers and cycling of hematopoietic progenitors, effects more apparent at 5%, than at 20%, oxygen tension, and these progenitors survived less well in vitro under conditions of delayed growth factor addition. This suggests a role for SIRT1 in ESC differentiation and mouse hematopoiesis. PMID:20966168

  14. Regulation of Cell Cycle and Stress Responses to Hydrostatic Pressure in Fission Yeast

    PubMed Central

    George, Vinoj T.; Brooks, Gavin

    2007-01-01

    We have investigated the cellular responses to hydrostatic pressure by using the fission yeast Schizosaccharomyces pombe as a model system. Exposure to sublethal levels of hydrostatic pressure resulted in G2 cell cycle delay. This delay resulted from Cdc2 tyrosine-15 (Y-15) phosphorylation, and it was abrogated by simultaneous disruption of the Cdc2 kinase regulators Cdc25 and Wee1. However, cell cycle delay was independent of the DNA damage, cytokinesis, and cell size checkpoints, suggesting a novel mechanism of Cdc2-Y15 phosphorylation in response to hydrostatic pressure. Spc1/Sty1 mitogen-activated protein (MAP) kinase, a conserved member of the eukaryotic stress-activated p38, mitogen-activated protein (MAP) kinase family, was rapidly activated after pressure stress, and it was required for cell cycle recovery under these conditions, in part through promoting polo kinase (Plo1) phosphorylation on serine 402. Moreover, the Spc1 MAP kinase pathway played a key role in maintaining cell viability under hydrostatic pressure stress through the bZip transcription factor, Atf1. Further analysis revealed that prestressing cells with heat increased barotolerance, suggesting adaptational cross-talk between these stress responses. These findings provide new insight into eukaryotic homeostasis after exposure to pressure stress. PMID:17699598

  15. Myosin-X functions in polarized epithelial cells

    PubMed Central

    Liu, Katy C.; Jacobs, Damon T.; Dunn, Brian D.; Fanning, Alan S.; Cheney, Richard E.

    2012-01-01

    Myosin-X (Myo10) is an unconventional myosin that localizes to the tips of filopodia and has critical functions in filopodia. Although Myo10 has been studied primarily in nonpolarized, fibroblast-like cells, Myo10 is expressed in vivo in many epithelia-rich tissues, such as kidney. In this study, we investigate the localization and functions of Myo10 in polarized epithelial cells, using Madin-Darby canine kidney II cells as a model system. Calcium-switch experiments demonstrate that, during junction assembly, green fluorescent protein–Myo10 localizes to lateral membrane cell–cell contacts and to filopodia-like structures imaged by total internal reflection fluorescence on the basal surface. Knockdown of Myo10 leads to delayed recruitment of E-cadherin and ZO-1 to junctions, as well as a delay in tight junction barrier formation, as indicated by a delay in the development of peak transepithelial electrical resistance (TER). Although Myo10 knockdown cells eventually mature into monolayers with normal TER, these monolayers do exhibit increased paracellular permeability to fluorescent dextrans. Importantly, knockdown of Myo10 leads to mitotic spindle misorientation, and in three-dimensional culture, Myo10 knockdown cysts exhibit defects in lumen formation. Together these results reveal that Myo10 functions in polarized epithelial cells in junction formation, regulation of paracellular permeability, and epithelial morphogenesis. PMID:22419816

  16. 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.

  17. Mobile technology habits: patterns of association among device usage, intertemporal preference, impulse control, and reward sensitivity.

    PubMed

    Wilmer, Henry H; Chein, Jason M

    2016-10-01

    Mobile electronic devices are playing an increasingly pervasive role in our daily activities. Yet, there has been very little empirical research investigating how mobile technology habits might relate to individual differences in cognition and affect. The research presented in this paper provides evidence that heavier investment in mobile devices is correlated with a relatively weaker tendency to delay gratification (as measured by a delay discounting task) and a greater inclination toward impulsive behavior (i.e., weaker impulse control, assessed behaviorally and through self-report) but is not related to individual differences in sensitivity to reward. Analyses further demonstrated that individual variation in impulse control mediates the relationship between mobile technology usage and delay of gratification. Although based on correlational results, these findings lend some backing to concerns that increased use of portable electronic devices could have negative impacts on impulse control and the ability to appropriately valuate delayed rewards.

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

    D'Huys, Otti, E-mail: otti.dhuys@phy.duke.edu; Haynes, Nicholas D.; Lohmann, Johannes

    Autonomous Boolean networks are commonly used to model the dynamics of gene regulatory networks and allow for the prediction of stable dynamical attractors. However, most models do not account for time delays along the network links and noise, which are crucial features of real biological systems. Concentrating on two paradigmatic motifs, the toggle switch and the repressilator, we develop an experimental testbed that explicitly includes both inter-node time delays and noise using digital logic elements on field-programmable gate arrays. We observe transients that last millions to billions of characteristic time scales and scale exponentially with the amount of time delaysmore » between nodes, a phenomenon known as super-transient scaling. We develop a hybrid model that includes time delays along network links and allows for stochastic variation in the delays. Using this model, we explain the observed super-transient scaling of both motifs and recreate the experimentally measured transient distributions.« less

  19. Propagation effects on radio range and noise in earth-space telecommunications

    NASA Technical Reports Server (NTRS)

    Flock, W. L.; Slobin, S. D.; Smith, E. K.

    1982-01-01

    Attention is given to the propagation effects on radio range and noise in earth-space telecommunications. The use of higher frequencies minimizes ionospheric effects on propagation, but tropospheric effects often increase or dominate. For paths of geostationary satellites, and beyond, the excess range delay caused by the ionosphere and plasmasphere is proportional to the total electron content along the path and inversely proportional to frequency squared. The delay due to dry air is usually of the order of a few meters while the delay due to water vapor (a few tens of centimeters) is responsible for most of the temporal variation in the range delay for clean air. For systems such as that of the Voyager spacecraft, and for attenuation values up to about 10 dB, increased sky noise degrades the received signal-to-noise ratio more than does the reduction in signal level due to attenuation.

  20. Numerical Simulations Studies of the Convective Instability Onset in a Supercritical Fluid

    NASA Technical Reports Server (NTRS)

    Furukawa, A.; Meyer, H.; Onuki, A.

    2004-01-01

    Numerical simulation studies are reported for the convection of a supercritical fluid, He-3, in a Rayleigh-Benard cell. The calculations provide the temporal profile DeltaT(t) of the temperature drop across the fluid layer. In a previous article, systematic delays in the onset of the convective instability in simulations relative to experiments were reported, as seen from the DeltaT(t) profiles. They were attributed to the smallness of the noise which is needed to start the instability. Therefore i) homogeneous temperature noise and ii) spatial lateral periodic temperature variations in the top plate were programmed into the simulations, and DeltaT(t) compared with that of an experiment with the same fluid parameters. An effective speed-up in the instability onset was obtained, with the best results obtained through the spatial temperature variations with a period of 2L, close to the wavelength of a pair of convections rolls. For a small amplitude of 0.5 micro-K, this perturbation gave a semiquantitative agreement with experimental observations. Results for various noise amplitudes are presented and discussed in relation to predictions by El Khouri and Carl es.

  1. Global asymptotic stability and hopf bifurcation for a blood cell production model.

    PubMed

    Crauste, Fabien

    2006-04-01

    We analyze the asymptotic stability of a nonlinear system of two differential equations with delay, describing the dynamics of blood cell produc- tion. This process takes place in the bone marrow, where stem cells differen- tiate throughout division in blood cells. Taking into account an explicit role of the total population of hematopoietic stem cells in the introduction of cells in cycle, we are led to study a characteristic equation with delay-dependent coefficients. We determine a necessary and sufficient condition for the global stability of the first steady state of our model, which describes the popula- tion's dying out, and we obtain the existence of a Hopf bifurcation for the only nontrivial positive steady state, leading to the existence of periodic solutions. These latter are related to dynamical diseases affecting blood cells known for their cyclic nature.

  2. [The effect of 3-aminobenzamide on the mitotic cycle of Chinese hamster cells cultured on a medium with 5-bromodeoxyuridine following ionizing radiation action].

    PubMed

    Kirillova, T V; Rozanov, Iu M; Spivak, I M

    1992-01-01

    A specific inhibitor of poly(ADP-ribose)polymerase-3-aminobenzamide (6 mM) has been shown to: 1) reduce survival of non-irradiated CHO-K1 cells, cultivated in medium containing 5-bromodeoxyuridine (10 mkM, BDU cells), and increase their radiosensitivity; 2) induce G2 delay in BDU cells while progressing through the cell cycle as analysed by the DNA flow cytometry; 3) increase to a great degree G2 delay in X-irradiated BDU cells. 3-Aminobenzamide is primarily effective when it is present during the first or two first cell cycles after the initial addition of BDU. The above data confirm the involvement, presumably an indirect one, of ADP-ribosylation in the DNA repair through affecting the chromatin structure.

  3. Chronic Alcohol Ingestion Delays T Cell Activation and Effector Function in Sepsis.

    PubMed

    Margoles, Lindsay M; Mittal, Rohit; Klingensmith, Nathan J; Lyons, John D; Liang, Zhe; Serbanescu, Mara A; Wagener, Maylene E; Coopersmith, Craig M; Ford, Mandy L

    2016-01-01

    Sepsis is the leading cause of death in intensive care units in the US, and it is known that chronic alcohol use is associated with higher incidence of sepsis, longer ICU stays, and higher mortality from sepsis. Both sepsis and chronic alcohol use are associated with immune deficits such as decreased lymphocyte numbers, impaired innate immunity, delayed-type hypersensitivity reactions, and susceptibility to infections; however, understanding of specific pathways of interaction or synergy between these two states of immune dysregulation is lacking. This study therefore sought to elucidate mechanisms underlying the immune dysregulation observed during sepsis in the setting of chronic alcohol exposure. Using a murine model of chronic ethanol ingestion followed by sepsis induction via cecal ligation and puncture, we determined that while CD4+ and CD8+ T cells isolated from alcohol fed mice eventually expressed the same cellular activation markers (CD44, CD69, and CD43) and effector molecules (IFN-γ, TNF) as their water fed counterparts, there was an overall delay in the acquisition of these phenotypes. This early lag in T cell activation was associated with significantly reduced IL-2 production at a later timepoint in both the CD4+ and CD8+ T cell compartments in alcohol sepsis, as well as with a reduced accumulation of CD8dim activated effectors. Taken together, these data suggest that delayed T cell activation may result in qualitative differences in the immune response to sepsis in the setting of chronic alcohol ingestion.

  4. Delayed reverberation through time windows as a key to cerebellar function.

    PubMed

    Kistler, W M; Leo van Hemmen, J

    1999-11-01

    We present a functional model of the cerebellum comprising cerebellar cortex, inferior olive, deep cerebellar nuclei, and brain stem nuclei. The discerning feature of the model being time coding, we consistently describe the system in terms of postsynaptic potentials, synchronous action potentials, and propagation delays. We show by means of detailed single-neuron modeling that (i) Golgi cells can fulfill a gating task in that they form short and well-defined time windows within which granule cells can reach firing threshold, thus organizing neuronal activity in discrete 'time slices', and that (ii) rebound firing in cerebellar nuclei cells is a robust mechanism leading to a delayed reverberation of Purkinje cell activity through cerebellar-reticular projections back to the cerebellar cortex. Computer simulations of the whole cerebellar network consisting of several thousand neurons reveal that reverberation in conjunction with long-term plasticity at the parallel fiber-Purkinje cell synapses enables the system to learn, store, and recall spatio-temporal patterns of neuronal activity. Climbing fiber spikes act both as a synchronization and as a teacher signal, not as an error signal. They are due to intrinsic oscillatory properties of inferior olivary neurons and to delayed reverberation within the network. In addition to clear experimental predictions the present theory sheds new light on a number of experimental observation such as the synchronicity of climbing fiber spikes and provides a novel explanation of how the cerebellum solves timing tasks on a time scale of several hundreds of milliseconds.

  5. Oxalate exposure provokes HSP 70 response in LLC-PK1 cells, a line of renal epithelial cells: protective role of HSP 70 against oxalate toxicity.

    PubMed

    Koul, Sweaty; Huang, Meiyi; Bhat, Sidarth; Maroni, Paul; Meacham, Randall B; Koul, Hari K

    2008-02-01

    We investigated the effects of oxalate on immediate early genes (IEGs) and stress protein HSP 70, commonly induced genes in response to a variety of stresses. LLC-PK1 cells were exposed to oxalate. Gene transcription and translation were monitored by Northern and Western blot analysis. RNA and DNA synthesis were assessed by [(3)H]-uridine and [(3)H]-thymidine incorporation, respectively. Oxalate exposure selectively increased the levels of mRNA encoding IEGs c-myc and c-jun as well as stress protein HSP 70. While expression of c-myc and c-jun was rapid (within 15 min to 2 h) and transient, HSP 70 expression was delayed (approximately 8 h) and stable. Furthermore, oxalate exposure resulted in delayed induction of generalized transcription by 18 h and reinitiation of the DNA synthesis by 24 h of oxalate exposure. Moreover, we show that prior induction of HSP 70 by mild hypertonic exposure protected the cells from oxalate toxicity. To the best of our knowledge this is the first study to demonstrate rapid IEG response and delayed heat-shock response to oxalate toxicity and protective role of HSP 70 against oxalate toxicity to renal epithelial cells. Oxalate, a metabolic end product, induces IEGs c-myc and c-jun and a delayed HSP 70 expression; While IEG expression may regulate additional genetic responses to oxalate, increased HSP 70 expression would serve an early protective role during oxalate stress.

  6. Generalized binomial τ-leap method for biochemical kinetics incorporating both delay and intrinsic noise

    NASA Astrophysics Data System (ADS)

    Leier, André; Marquez-Lago, Tatiana T.; Burrage, Kevin

    2008-05-01

    The delay stochastic simulation algorithm (DSSA) by Barrio et al. [Plos Comput. Biol. 2, 117(E) (2006)] was developed to simulate delayed processes in cell biology in the presence of intrinsic noise, that is, when there are small-to-moderate numbers of certain key molecules present in a chemical reaction system. These delayed processes can faithfully represent complex interactions and mechanisms that imply a number of spatiotemporal processes often not explicitly modeled such as transcription and translation, basic in the modeling of cell signaling pathways. However, for systems with widely varying reaction rate constants or large numbers of molecules, the simulation time steps of both the stochastic simulation algorithm (SSA) and the DSSA can become very small causing considerable computational overheads. In order to overcome the limit of small step sizes, various τ-leap strategies have been suggested for improving computational performance of the SSA. In this paper, we present a binomial τ-DSSA method that extends the τ-leap idea to the delay setting and avoids drawing insufficient numbers of reactions, a common shortcoming of existing binomial τ-leap methods that becomes evident when dealing with complex chemical interactions. The resulting inaccuracies are most evident in the delayed case, even when considering reaction products as potential reactants within the same time step in which they are produced. Moreover, we extend the framework to account for multicellular systems with different degrees of intercellular communication. We apply these ideas to two important genetic regulatory models, namely, the hes1 gene, implicated as a molecular clock, and a Her1/Her 7 model for coupled oscillating cells.

  7. Highly pathogenic avian influenza H5N1 virus delays apoptotic responses via activation of STAT3

    PubMed Central

    Hui, Kenrie P. Y.; Li, Hung Sing; Cheung, Man Chun; Chan, Renee W. Y.; Yuen, Kit M.; Mok, Chris K. P.; Nicholls, John M.; Peiris, J. S. Malik; Chan, Michael C. W.

    2016-01-01

    Highly pathogenic avian influenza (HPAI) H5N1 virus continues to pose pandemic threat, but there is a lack of understanding of its pathogenesis. We compared the apoptotic responses triggered by HPAI H5N1 and low pathogenic H1N1 viruses using physiologically relevant respiratory epithelial cells. We demonstrated that H5N1 viruses delayed apoptosis in primary human bronchial and alveolar epithelial cells (AECs) compared to H1N1 virus. Both caspase-8 and -9 were activated by H5N1 and H1N1 viruses in AECs, while H5N1 differentially up-regulated TRAIL. H5N1-induced apoptosis was reduced by TRAIL receptor silencing. More importantly, STAT3 knock-down increased apoptosis by H5N1 infection suggesting that H5N1 virus delays apoptosis through activation of STAT3. Taken together, we demonstrate that STAT3 is involved in H5N1-delayed apoptosis compared to H1N1. Since delay in apoptosis prolongs the duration of virus replication and production of pro-inflammatory cytokines and TRAIL from H5N1-infected cells, which contribute to orchestrate cytokine storm and tissue damage, our results suggest that STAT3 may play a previously unsuspected role in H5N1 pathogenesis. PMID:27344974

  8. Ionizing radiation accelerates Drp1-dependent mitochondrial fission, which involves delayed mitochondrial reactive oxygen species production in normal human fibroblast-like cells

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

    Kobashigawa, Shinko, E-mail: kobashin@nagasaki-u.ac.jp; Suzuki, Keiji; Yamashita, Shunichi

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer We report first time that ionizing radiation induces mitochondrial dynamic changes. Black-Right-Pointing-Pointer Radiation-induced mitochondrial fission was caused by Drp1 localization. Black-Right-Pointing-Pointer We found that radiation causes delayed ROS from mitochondria. Black-Right-Pointing-Pointer Down regulation of Drp1 rescued mitochondrial dysfunction after radiation exposure. -- Abstract: Ionizing radiation is known to increase intracellular level of reactive oxygen species (ROS) through mitochondrial dysfunction. Although it has been as a basis of radiation-induced genetic instability, the mechanism involving mitochondrial dysfunction remains unclear. Here we studied the dynamics of mitochondrial structure in normal human fibroblast like cells exposed to ionizing radiation. Delayed mitochondrial O{submore » 2}{sup {center_dot}-} production was peaked 3 days after irradiation, which was coupled with accelerated mitochondrial fission. We found that radiation exposure accumulated dynamin-related protein 1 (Drp1) to mitochondria. Knocking down of Drp1 expression prevented radiation induced acceleration of mitochondrial fission. Furthermore, knockdown of Drp1 significantly suppressed delayed production of mitochondrial O{sub 2}{sup {center_dot}-}. Since the loss of mitochondrial membrane potential, which was induced by radiation was prevented in cells knocking down of Drp1 expression, indicating that the excessive mitochondrial fission was involved in delayed mitochondrial dysfunction after irradiation.« less

  9. Drug Hypersensitivity: How Drugs Stimulate T Cells via Pharmacological Interaction with Immune Receptors.

    PubMed

    Pichler, Werner J; Adam, Jacqueline; Watkins, Stephen; Wuillemin, Natascha; Yun, James; Yerly, Daniel

    2015-01-01

    Small chemicals like drugs tend to bind to proteins via noncovalent bonds, e.g. hydrogen bonds, salt bridges or electrostatic interactions. Some chemicals interact with other molecules than the actual target ligand, representing so-called 'off-target' activities of drugs. Such interactions are a main cause of adverse side effects to drugs and are normally classified as predictable type A reactions. Detailed analysis of drug-induced immune reactions revealed that off-target activities also affect immune receptors, such as highly polymorphic human leukocyte antigens (HLA) or T cell receptors (TCR). Such drug interactions with immune receptors may lead to T cell stimulation, resulting in clinical symptoms of delayed-type hypersensitivity. They are assigned the 'pharmacological interaction with immune receptors' (p-i) concept. Analysis of p-i has revealed that drugs bind preferentially or exclusively to distinct HLA molecules (p-i HLA) or to distinct TCR (p-i TCR). P-i reactions differ from 'conventional' off-target drug reactions as the outcome is not due to the effect on the drug-modified cells themselves, but is the consequence of reactive T cells. Hence, the complex and diverse clinical manifestations of delayed-type hypersensitivity are caused by the functional heterogeneity of T cells. In the abacavir model of p-i HLA, the drug binding to HLA may result in alteration of the presenting peptides. More importantly, the drug binding to HLA generates a drug-modified HLA, which stimulates T cells directly, like an allo-HLA. In the sulfamethoxazole model of p-i TCR, responsive T cells likely require costimulation for full T cell activation. These findings may explain the similarity of delayed-type hypersensitivity reactions to graft-versus-host disease, and how systemic viral infections increase the risk of delayed-type hypersensitivity reactions. © 2015 The Author(s) Published by S. Karger AG, Basel.

  10. Fragile X syndrome and an isodicentric X chromosome in a woman with multiple anomalies, developmental delay, and normal pubertal development.

    PubMed

    Freedenberg, D L; Gane, L W; Richards, C S; Lampe, M; Hills, J; O'Connor, R; Manchester, D; Taylor, A; Tassone, F; Hulseberg, D; Hagerman, R J; Patil, S R

    1999-07-30

    We report on an individual with developmental delays, short stature, skeletal abnormalities, normal pubertal development, expansion of the fragile X triplet repeat, as well as an isodicentric X chromosome. S is a 19-year-old woman who presented for evaluation of developmental delay. Pregnancy was complicated by a threatened miscarriage. She was a healthy child with intellectual impairment noted in infancy. Although she had global delays, speech was noted to be disproportionately delayed with few words until age 3.5 years. Facial appearance was consistent with fragile X syndrome. Age of onset of menses was 11 years with normal breast development. A maternal male second cousin had been identified with fragile X syndrome based on DNA studies. The mother of this child (S's maternal first cousin) and the grandfather (S's maternal uncle) were both intellectually normal but were identified as carrying triplet expansions in the premutation range. S's mother had some school difficulties but was not identified as having global delays. Molecular analysis of S's fragile X alleles noted an expansion of more than 400 CGG repeats in one allele. Routine cytogenetic studies of peripheral blood noted the presence of an isodicentric X in 81of 86 cells scored. Five of 86 cells were noted to be 45,X. Cytogenetic fra(X) studies from peripheral blood showed that the structurally normal chromosome had the fragile site in approximately 16% of the cells. Analysis of maternal fragile X alleles identified an allele with an expansion to approximately 110 repeats. FMRP studies detected the expression of the protein in 24% of cells studied. To our knowledge, this is the first patient reported with an isodicentric X and fragile X syndrome. Whereas her clinical phenotype is suggestive of fragile X syndrome, her skeletal abnormalities may represent the presence of the isodicentric X. Treatment of S with 20 mg/day of Prozac improved her behavior. In the climate of cost con trol, this individual reinforces the recommendation of obtaining chromosomes on individuals with developmental delay even with a family history of fragile X syndrome. Copyright 1999 Wiley-Liss, Inc.

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

    Chen, Ying; Li, Cuiying; Weng, Dong

    Silica exposure can cause lung inflammation and fibrosis, known as silicosis. Interleukin-17A (IL-17A) and Th17 cells play a pivotal role in controlling inflammatory diseases. However, the roles of IL-17A and Th17 cells in the progress of silica-induced inflammation and fibrosis are poorly understood. This study explored the effects of IL-17A on silica-induced inflammation and fibrosis. We used an anti-mouse IL-17A antibody to establish an IL-17A-neutralized mice model, and mice were exposed to silica to establish an experimental silicosis model. We showed that IL-17A neutralization delayed neutrophil accumulation and progression of silica-induced lung inflammation and fibrosis. IL-17A neutralization reduced the percentagemore » of Th17 in CD4 + T cells, decreased IL-6 and IL-1β expression, and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A delayed silica-induced Th1/Th2 immune and autoimmune responses. These results suggest that IL-17A neutralization alleviates early stage silica-induced lung inflammation and delays progression of silica-induced lung inflammation and fibrosis. Neutralization of IL-17A suppressed Th17 cell development by decreasing IL-6 and/or IL-1β and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A also delayed the Th1/Th2 immune response during silica-induced lung inflammation and fibrosis. IL-17A may play a pivotal role in the early phase of silica-induced inflammation and may mediate the Th immune response to influence silica-induced lung inflammation and fibrosis in mice. - Highlights: • Neutralization of IL-17A alleviated silica-induced lung inflammation of early stage. • Neutralization of IL-17A decreased Th17 cells and increased Tregs. • IL-17A mediated the reciprocal relationship of Th17/Tregs by IL-6 and/or IL-1β. • Neutralization of IL-17A delayed silica-induced Th1/Th2 immune response. • Neutralization of IL-17A delayed silica-induced lung inflammation and fibrosis.« less

  12. De novo alloreactive memory CD8+ T cells develop following allogeneic challenge when CNI immunosuppression is delayed.

    PubMed

    Hart-Matyas, M; Gareau, A J; Hirsch, G M; Lee, T D G

    2015-01-01

    Allospecific memory T cells are a recognized threat to the maintenance of solid-organ transplants. Limited information exists regarding the development of alloreactive memory T cells when post-transplant immunosuppression is present. The clinical practice of delaying calcineurin inhibitor (CNI) initiation post-transplant may permit the development of a de novo allospecific memory population. We investigated the development of de novo allospecific memory CD8+ T cells following the introduction of CNI immunosuppression in a murine model using allogeneic cell priming. Recipient mice alloprimed with splenocytes from fully mismatched donors received cyclosporine (CyA), initiated at 0, 2, 6, or 10days post-prime. Splenocytes from recipients were analyzed by flow cytometry or enzyme-linked immunosorbent assay for evidence of memory cell formation. Memory and effector CD8+ T cell development was prevented when CyA was initiated at 0day or 2days post-prime (p<0.001), but not 6days post-prime. Following a boost challenge, these memory CD8+ T cells were capable of producing a similarly sized population of secondary effectors as recipients not treated with CyA (p>0.05). Delaying CyA up to 6days or later post-prime permits the development of functional de novo allospecific memory CD8+ T cells. The development of this potentially detrimental T cell population in patients could be prevented by starting CNI immunosuppression early post-transplant. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Bifurcation analysis of delay-induced resonances of the El-Niño Southern Oscillation

    PubMed Central

    Krauskopf, Bernd; Sieber, Jan

    2014-01-01

    Models of global climate phenomena of low to intermediate complexity are very useful for providing an understanding at a conceptual level. An important aspect of such models is the presence of a number of feedback loops that feature considerable delay times, usually due to the time it takes to transport energy (for example, in the form of hot/cold air or water) around the globe. In this paper, we demonstrate how one can perform a bifurcation analysis of the behaviour of a periodically forced system with delay in dependence on key parameters. As an example, we consider the El-Niño Southern Oscillation (ENSO), which is a sea-surface temperature (SST) oscillation on a multi-year scale in the basin of the Pacific Ocean. One can think of ENSO as being generated by an interplay between two feedback effects, one positive and one negative, which act only after some delay that is determined by the speed of transport of SST anomalies across the Pacific. We perform here a case study of a simple delayed-feedback oscillator model for ENSO, which is parametrically forced by annual variation. More specifically, we use numerical bifurcation analysis tools to explore directly regions of delay-induced resonances and other stability boundaries in this delay-differential equation model for ENSO. PMID:25197254

  14. Novel RF Interrogation of a Fiber Bragg Grating Sensor Using Bidirectional Modulation of a Mach-Zehnder Electro-Optical Modulator

    PubMed Central

    Choi, Sang-Jin; Mao, Wankai; Pan, Jae-Kyung

    2013-01-01

    We propose and experimentally demonstrate the novel radio-frequency (RF) interrogation of a fiber Bragg grating (FBG) sensor using bidirectional modulation of a Mach-Zehnder electro-optical modulator (MZ-EOM). Based on the microwave photonic technique and active detection, the transfer function of the proposed system was obtained, and the time delay was calculated from the change in the free spectral range (FSR) at different wavelengths over the optimal measuring range. The results show that the time delay and the wavelength variation have a good linear relationship, with a gradient of 9.31 ps/nm. An actual measurement taken with a sensing FBG for temperature variation shows the relationship with a gradient of 0.93 ps/10 °C. The developed system could be used for FBG temperature or strain sensing and other multiplexed sensor applications. PMID:23820744

  15. ITG: A New Global GNSS Tropospheric Correction Model

    PubMed Central

    Yao, Yibin; Xu, Chaoqian; Shi, Junbo; Cao, Na; Zhang, Bao; Yang, Junjian

    2015-01-01

    Tropospheric correction models are receiving increasing attentions, as they play a crucial role in Global Navigation Satellite System (GNSS). Most commonly used models to date include the GPT2 series and the TropGrid2. In this study, we analyzed the advantages and disadvantages of existing models and developed a new model called the Improved Tropospheric Grid (ITG). ITG considers annual, semi-annual and diurnal variations, and includes multiple tropospheric parameters. The amplitude and initial phase of diurnal variation are estimated as a periodic function. ITG provides temperature, pressure, the weighted mean temperature (Tm) and Zenith Wet Delay (ZWD). We conducted a performance comparison among the proposed ITG model and previous ones, in terms of meteorological measurements from 698 observation stations, Zenith Total Delay (ZTD) products from 280 International GNSS Service (IGS) station and Tm from Global Geodetic Observing System (GGOS) products. Results indicate that ITG offers the best performance on the whole. PMID:26196963

  16. RESPIRATION AND INTENSITY DEPENDENCE OF PHOTOSYNTHESIS IN CHLORELLA

    PubMed Central

    Brackett, Frederick S.; Olson, Rodney A.; Crickard, Robert G.

    1953-01-01

    1. Respiration changes as a result of illumination. 2. In the absence of glucose or other supply of substrate, respiration decays in the dark showing at least two types—a fast decay in a few minutes and a slow decay lasting hours. 3. Respiratory response to illumination is delayed. 4. Intermittent illumination (in the absence of glucose, etc.) produces a periodic variation in respiration with a delay or phase lag. 5. Periodic variation of respiration may produce a higher average value in the dark than in the light due to the lag and depending upon the period of intermittent illumination. 6. Based upon average respiration values our data confirm the Kok effect. 7. Interpolated values of respiration, however, result in photosynthetic rates which are linearly dependent upon intensity of illumination. 8. Thus the quantum efficiency is found to be independent of intensity, over the wide range of intensities investigated. PMID:13035068

  17. Immediate versus delayed primary nerve repair in the rabbit sciatic nerve

    PubMed Central

    Piskin, Ahmet; Altunkaynak, Berrin Zühal; Çιtlak, Atilla; Sezgin, Hicabi; Yazιcι, Ozgür; Kaplan, Süleyman

    2013-01-01

    It is well known that peripheral nerve injury should be treated immediately in the clinic, but in some instances, repair can be delayed. This study investigated the effects of immediate versus delayed (3 days after injury) neurorrhaphy on repair of transected sciatic nerve in New Zealand rabbits using stereological, histomorphological and biomechanical methods. At 8 weeks after immediate and delayed neurorrhaphy, axon number and area in the sciatic nerve, myelin sheath and epineurium thickness, Schwann cell morphology, and the mechanical property of nerve fibers did not differ obviously. These results indicate that delayed neurorrhaphy do not produce any deleterious effect on sciatic nerve repair. PMID:25206663

  18. Delayed luminescence in a multiparameter approach to evaluation and reduction of radiobiological risks

    NASA Astrophysics Data System (ADS)

    Grasso, Rosaria; Cammarata, Francesco Paolo; Minafra, Luigi; Marchese, Valentina; Russo, Giorgio; Manti, Lorenzo; Musumeci, Francesco; Scordino, Agata

    2017-07-01

    In the framework of the research project ETHICS "Pre-clinical experimental and theoretical studies to improve treatment and protection by charged particles" funded by the National Nuclear Physics Institute, Italy, we studied the phenomenon called delayed luminescence emitted by non-tumorigenic breast epithelial MCF10A cell line after proton irradiation at different doses (0.5, 2, 6, 9 Gy). The aim is to found possible correlations between delayed luminescence and in vitro damaging induced by ion irradiation. The first results of this research show that the delayed luminescence kinetics is proton dose dependent. An interesting correlation between delayed luminescence and clonogenic potential was observed.

  19. Break-before-make CMOS inverter for power-efficient delay implementation.

    PubMed

    Puhan, Janez; Raič, Dušan; Tuma, Tadej; Bűrmen, Árpád

    2014-01-01

    A modified static CMOS inverter with two inputs and two outputs is proposed to reduce short-circuit current in order to increment delay and reduce power overhead where slow operation is required. The circuit is based on bidirectional delay element connected in series with the PMOS and NMOS switching transistors. It provides differences in the dynamic response so that the direct-path current in the next stage is reduced. The switching transistors are never ON at the same time. Characteristics of various delay element implementations are presented and verified by circuit simulations. Global optimization procedure is used to obtain the most power-efficient transistor sizing. The performance of the modified CMOS inverter chain is compared to standard implementation for various delays. The energy (charge) per delay is reduced up to 40%. The use of the proposed delay element is demonstrated by implementing a low-power delay line and a leading-edge detector cell.

  20. Break-before-Make CMOS Inverter for Power-Efficient Delay Implementation

    PubMed Central

    Raič, Dušan

    2014-01-01

    A modified static CMOS inverter with two inputs and two outputs is proposed to reduce short-circuit current in order to increment delay and reduce power overhead where slow operation is required. The circuit is based on bidirectional delay element connected in series with the PMOS and NMOS switching transistors. It provides differences in the dynamic response so that the direct-path current in the next stage is reduced. The switching transistors are never ON at the same time. Characteristics of various delay element implementations are presented and verified by circuit simulations. Global optimization procedure is used to obtain the most power-efficient transistor sizing. The performance of the modified CMOS inverter chain is compared to standard implementation for various delays. The energy (charge) per delay is reduced up to 40%. The use of the proposed delay element is demonstrated by implementing a low-power delay line and a leading-edge detector cell. PMID:25538951

  1. High speed capacitor-inverter based carbon nanotube full adder.

    PubMed

    Navi, K; Rashtian, M; Khatir, A; Keshavarzian, P; Hashemipour, O

    2010-03-18

    Carbon Nanotube filed-effect transistor (CNFET) is one of the promising alternatives to the MOS transistors. The geometry-dependent threshold voltage is one of the CNFET characteristics, which is used in the proposed Full Adder cell. In this paper, we present a high speed Full Adder cell using CNFETs based on majority-not (Minority) function. Presented design uses eight transistors and eight capacitors. Simulation results show significant improvement in terms of delay and power-delay product in comparison to contemporary CNFET Adder Cells. Simulations were carried out using HSPICE based on CNFET model with 0.6 V VDD.

  2. Implications for Ophthalmic Formulations: Ocular Buffers Show Varied Cytotoxic Impact on Human Corneal-Limbal and Human Conjunctival Epithelial Cells.

    PubMed

    Schuerer, Nadine; Stein, Elisabeth; Inic-Kanada, Aleksandra; Pucher, Marion; Hohenadl, Christine; Bintner, Nora; Ghasemian, Ehsan; Montanaro, Jacqueline; Barisani-Asenbauer, Talin

    2017-06-01

    To investigate toxicity associated with buffers commonly used in topical ocular drug formulations using a human corneal-limbal epithelial (HCLE) and a human conjunctival epithelial (HCjE) cell model. HCLE and HCjE cells were incubated for 10, 30, or 60 minutes with 4 different buffers based on borate, citrate, phosphate, and Tris-HCl at 10, 50, and 100 mM concentrations. To detect possible delayed effects on cell viability, after 60 minutes of buffer incubation, cells were further incubated for 24 hours with a cell medium. Cell viability was determined using a colorimetric XTT-based assay. The morphology of cells was also investigated. HCjE cells showed more sensitivity to buffer incubation than HCLE cells. The 100 mM phosphate buffer displayed significant delayed effects on cell viability of HCLE 16.8 ± 4.8% and HCjE 39.2 ± 6.1% cells after 60 minutes of exposure (P < 0.05). HCjE cell viability was reduced after 60 minutes incubations with 50 and 100 mM citrate buffer to 42.8 ± 6.5% and 39.3 ± 7.9%, respectively, and even lower percentages at the delayed time point (both P < 0.05). HCLE cell morphology was distinctly altered by 100 mM phosphate and Tris buffers after 30 minutes, whereas HCjE cells already showed marked changes after 10 minutes of exposure to 100 mM citrate and phosphate buffers. We observed a time-dependent decrease of viability in both HCLE and HCjE cells exposed to higher buffer concentrations. Therefore, we propose further in vivo studies to translate these finding to humans to discern the real effects of the buffer concentration in eye drops on the ocular surface.

  3. Implications for Ophthalmic Formulations: Ocular Buffers Show Varied Cytotoxic Impact on Human Corneal–Limbal and Human Conjunctival Epithelial Cells

    PubMed Central

    Schuerer, Nadine; Stein, Elisabeth; Inic-Kanada, Aleksandra; Pucher, Marion; Hohenadl, Christine; Bintner, Nora; Ghasemian, Ehsan; Montanaro, Jacqueline

    2017-01-01

    Purpose: To investigate toxicity associated with buffers commonly used in topical ocular drug formulations using a human corneal–limbal epithelial (HCLE) and a human conjunctival epithelial (HCjE) cell model. Methods: HCLE and HCjE cells were incubated for 10, 30, or 60 minutes with 4 different buffers based on borate, citrate, phosphate, and Tris-HCl at 10, 50, and 100 mM concentrations. To detect possible delayed effects on cell viability, after 60 minutes of buffer incubation, cells were further incubated for 24 hours with a cell medium. Cell viability was determined using a colorimetric XTT–based assay. The morphology of cells was also investigated. Results: HCjE cells showed more sensitivity to buffer incubation than HCLE cells. The 100 mM phosphate buffer displayed significant delayed effects on cell viability of HCLE 16.8 ± 4.8% and HCjE 39.2 ± 6.1% cells after 60 minutes of exposure (P < 0.05). HCjE cell viability was reduced after 60 minutes incubations with 50 and 100 mM citrate buffer to 42.8 ± 6.5% and 39.3 ± 7.9%, respectively, and even lower percentages at the delayed time point (both P < 0.05). HCLE cell morphology was distinctly altered by 100 mM phosphate and Tris buffers after 30 minutes, whereas HCjE cells already showed marked changes after 10 minutes of exposure to 100 mM citrate and phosphate buffers. Conclusions: We observed a time-dependent decrease of viability in both HCLE and HCjE cells exposed to higher buffer concentrations. Therefore, we propose further in vivo studies to translate these finding to humans to discern the real effects of the buffer concentration in eye drops on the ocular surface. PMID:28399036

  4. Expression of orphan G-protein coupled receptor GPR174 in CHO cells induced morphological changes and proliferation delay via increasing intracellular cAMP

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

    Sugita, Kazuya; Yamamura, Chiaki; Tabata, Ken-ichi

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer Expression of GPR174 in CHO cells induces morphological changes and proliferation delay. Black-Right-Pointing-Pointer These are due to increase in intracellular cAMP concentration. Black-Right-Pointing-Pointer Lysophosphatidylserine was identified to stimulate GPR174 leading to activate ACase. Black-Right-Pointing-Pointer The potencies of fatty acid moiety on LysoPS were oleoyl Greater-Than-Or-Slanted-Equal-To stearoyl > palmitoyl. Black-Right-Pointing-Pointer We propose that GPR174 is a lysophosphatidylserine receptor. -- Abstract: We established cell lines that stably express orphan GPCR GPR174 using CHO cells, and studied physiological and pharmacological features of the receptor. GPR174-expressing cells showed cell-cell adhesion with localization of actin filaments to cell membrane, and revealed significant delaymore » of cell proliferation. Since the morphological changes of GPR174-cells were very similar to mock CHO cells treated with cholera toxin, we measured the concentration of intracellular cAMP. The results showed the concentration was significantly elevated in GPR174-cells. By measuring intracellular cAMP concentration in GPR174-cells, we screened lipids and nucleotides to identify ligands for GPR174. We found that lysophosphatidylserine (LysoPS) stimulated increase in intracellular cAMP in a dose-dependent manner. Moreover, phosphorylation of Erk was elevated by LysoPS in GPR174 cells. These LysoPS responses were inhibited by NF449, an inhibitor of G{alpha}{sub s} protein. These results suggested that GPR174 was a putative LysoPS receptor conjugating with G{alpha}{sub s}, and its expression induced morphological changes in CHO cells by constitutively activating adenylyl cycles accompanied with cell conjunctions and delay of proliferation.« less

  5. InSAR atmospheric correction using Himawari-8 Geostationary Meteorological Satellite

    NASA Astrophysics Data System (ADS)

    Kinoshita, Y.; Nimura, T.; Furuta, R.

    2017-12-01

    The atmospheric delay effect is one of the limitations for the accurate surface displacement detection by Synthetic Aperture Radar Interferometry (InSAR). Many previous studies have attempted to mitigate the neutral atmospheric delay in InSAR (e.g. Jolivet et al. 2014; Foster et al. 2006; Kinoshita et al. 2013). Hanssen et al. (2001) investigated the relationship between the 27 hourly observations of GNSS precipitable water vapor (PWV) and the infrared brightness temperature derived from visible satellite imagery, and showed a good correlation. Here we showed a preliminary result of the newly developed method for the neutral atmospheric delay correction using the Himawari-8 Japanese geostationary meteorological satellite data. The Himawari-8 satellite is the Japanese state-of-the-art geostationary meteorological satellite that has 16 observation channels and has spatial resolutions of 0.5 km (visible) and 2.0 km (near-infrared and infrared) with an time interval of 2.5 minutes around Japan. To estimate the relationship between the satellite brightness temperature and the atmospheric delay amount. Since the InSAR atmospheric delay is principally the same as that in GNSS, we at first compared the Himawari-8 data with the GNSS zenith tropospheric delay data derived from the Japanese dense GNSS network. The comparison of them showed that the band with the wavelength of 6.9 μm had the highest correlation to the GNSS observation. Based on this result, we developed an InSAR atmospheric delay model that uses the Himawari-8 6.9 μm band data. For the model validation, we generated InSAR images from the ESA's C-band Sentinel-1 SLC data with the GAMMA SAR software. We selected two regions around Tokyo and Sapporo (both in Japan) as the test sites because of the less temporal decorrelation. The validation result showed that the delay model reasonably estimate large scale phase variation whose spatial scale was on the order of over 20 km. On the other hand, phase variations of a few km scale were not estimated by the model. This would be due to the horizontal resolution of the input data (2 km in the 6.9 μm band). In the presentation we will show these results and the progress after the abstract submission, and discuss the limitation of our method and the future research plan.

  6. Delayed Hospital Discharges of Older Patients: A Systematic Review on Prevalence and Costs.

    PubMed

    Landeiro, Filipa; Roberts, Kenny; Gray, Alastair Mcintosh; Leal, José

    2017-05-23

    To determine the prevalence of delayed discharges of elderly inpatients and associated costs. We searched Medline, Embase, Global Health, CAB Abstracts, Econlit, Web of Knowledge, EBSCO - CINAHL, The Cochrane Library, Health Management Information Consortium, and SCIE - Social Care Online for evidence published between 1990 and 2015 on number of days or proportion of delayed discharges for elderly inpatients in acute hospitals. Descriptive and regression analyses were conducted. Data on proportions of delayed discharges were pooled using a random effects logistic model and the association of relevant factors was assessed. Mean costs of delayed discharge were calculated in USD adjusted for Purchasing Power Parity (PPP). Of 64 studies included, 52 (81.3%) reported delayed discharges as proportions of total hospital stay and 9 (14.1%) estimated the respective costs for these delays. Proportions of delayed discharges varied widely, from 1.6% to 91.3% with a weighted mean of 22.8%. This variation was also seen in studies from the same country, for example, in the United Kingdom, they ranged between 1.6% and 60.0%. No factor was found to be significantly associated with delays. The mean costs of delayed discharge also varied widely (between 142 and 31,935 USD PPP adjusted), reflecting the variability in mean days of delay per patient. Delayed discharges occur in most countries and the associated costs are significant. However, the variability in prevalence of delayed discharges and available data on costs limit our knowledge of the full impact of delayed discharges. A standardization of methods is necessary to allow comparisons to be made, and additional studies are required-preferably by disease area-to determine the postdischarge needs of specific patient groups and the estimated costs of delays. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Managing variation in demand: lessons from the UK National Health Service.

    PubMed

    Walley, Paul; Silvester, Kate; Steyn, Richard

    2006-01-01

    Managers within the U.S. healthcare system are becoming more aware of the impact of variation in demand on healthcare processes. The UK National Health Service provides a prime example of a system that has experienced the consequences when the issue is not dealt with satisfactorily, having suffered from excessive queues for a prolonged period. These delays are mostly caused by a lack of attention to variation and inappropriate responses to the queues, rather than a capacity shortage. A number of collaborative programs recently have come to grips with many of the causes of the queues in both elective care and emergency care. Although there are still areas that need large-scale improvement, good progress has been made, especially within emergency care. The authors of this article have acted as technical advisors to a number of these improvement programs and have been able to document many of the practices that have helped to reduce or eliminate unnecessary queues and delays across the 200 sites in England that have 24-hour emergency care facilities. Local program managers at these sites continuously reported progress for a period of 18 months. A number of important lessons for both the design and control of healthcare processes have emerged from the collaborative work. These lessons focus on understanding and measurement of demand, capacity planning, reduction of introduced variation, segmentation and streaming of work, process design, capacity yield management, and measurement of variation.

  8. Consistency of metabolic tumor volume of non-small-cell lung cancer primary tumor measured using 18F-FDG PET/CT at two different tracer uptake times.

    PubMed

    Liu, Haiping; Chen, Ping; Wroblewski, Kristen; Hou, Peng; Zhang, Chen-Peng; Jiang, Yulei; Pu, Yonglin

    2016-01-01

    The objective of this study was to test the hypothesis that the metabolic tumor volume (MTV) of primary non-small-cell lung cancer is not sensitive to differences in F-fluorodeoxyglucose (F-FDG) uptake time, and to compare this consistency of MTV measurements with that of standardized uptake value (SUV) and total lesion glycolysis (TLG). Under Institutional Review Board approval, 134 consecutive patients with histologically proven non-small-cell lung cancer underwent F-FDG PET/computed tomography scanning at about 1 h (early) and 2 h (delayed) after intravenous injection of F-FDG. MTV, SUV, and TLG of the primary tumor were all measured. Student's t-test and Wilcoxon's signed-rank test for paired data were used to compare MTV, SUV, and TLG between the two scans. The intraclass correlation coefficient (ICC) was used to assess agreement in PET parameters between the two scans and between the measurements made by two observers. MTV was not significantly different (P=0.17) between the two scans. However, SUVmax, SUVmean, SUVpeak, and TLG increased significantly from the early to the delayed scans (P<0.0001 for all). The median percentage change between the two scans in MTV (1.65%) was smaller than in SUVmax (11.76%), SUVmean(10.57%), SUVpeak(13.51%), and TLG (14.34%); the ICC of MTV (0.996) was greater than that of SUVmax (0.933), SUVmean (0.952), SUVpeak (0.928), and TLG (0.982). Interobserver agreement between the two radiologists was excellent for MTV, SUV, and TLG on both scans (ICC: 0.934-0.999). MTV is not sensitive to common clinical variations in F-FDG uptake time, its consistency is greater than that of SUVmax, SUVmean, SUVpeak, and TLG, and it has excellent interobserver agreement.

  9. UV-C irradiation delays mitotic progression by recruiting Mps1 to kinetochores.

    PubMed

    Zhang, Xiaojuan; Ling, Youguo; Wang, Wenjun; Zhang, Yanhong; Ma, Qingjun; Tan, Pingping; Song, Ting; Wei, Congwen; Li, Ping; Liu, Xuedong; Ma, Runlin Z; Zhong, Hui; Cao, Cheng; Xu, Quanbin

    2013-04-15

    The effect of UV irradiation on replicating cells during interphase has been studied extensively. However, how the mitotic cell responds to UV irradiation is less well defined. Herein, we found that UV-C irradiation (254 nm) increases recruitment of the spindle checkpoint proteins Mps1 and Mad2 to the kinetochore during metaphase, suggesting that the spindle assembly checkpoint (SAC) is reactivated. In accordance with this, cells exposed to UV-C showed delayed mitotic progression, characterized by a prolonged chromosomal alignment during metaphase. UV-C irradiation also induced the DNA damage response and caused a significant accumulation of γ-H2AX on mitotic chromosomes. Unexpectedly, the mitotic delay upon UV-C irradiation is not due to the DNA damage response but to the relocation of Mps1 to the kinetochore. Further, we found that UV-C irradiation activates Aurora B kinase. Importantly, the kinase activity of Aurora B is indispensable for full recruitment of Mps1 to the kinetochore during both prometaphase and metaphase. Taking these findings together, we propose that UV irradiation delays mitotic progression by evoking the Aurora B-Mps1 signaling cascade, which exerts its role through promoting the association of Mps1 with the kinetochore in metaphase.

  10. STAT3 signaling in CD4+ T cells is critical for the pathogenesis of chronic sclerodermatous graft-versus-host disease in a murine model.

    PubMed

    Radojcic, Vedran; Pletneva, Maria A; Yen, Hung-Rong; Ivcevic, Sanja; Panoskaltsis-Mortari, Angela; Gilliam, Anita C; Drake, Charles G; Blazar, Bruce R; Luznik, Leo

    2010-01-15

    Donor CD4+ T cells are thought to be essential for inducing delayed host tissue injury in chronic graft-versus-host disease (GVHD). However, the relative contributions of distinct effector CD4+ T cell subpopulations and the molecular pathways influencing their generation are not known. We investigated the role of the STAT3 pathway in a murine model of chronic sclerodermatous GVHD. This pathway integrates multiple signaling events during the differentiation of naive CD4+ T cells and impacts their homeostasis. We report that chimeras receiving an allograft containing STAT3-ablated donor CD4+ T cells do not develop classic clinical and pathological manifestations of alloimmune tissue injury. Analysis of chimeras showed that abrogation of STAT3 signaling reduced the in vivo expansion of donor-derived CD4+ T cells and their accumulation in GVHD target tissues without abolishing antihost alloreactivity. STAT3 ablation did not significantly affect Th1 differentiation while enhancing CD4+CD25+Foxp3+ T cell reconstitution through thymus-dependent and -independent pathways. Transient depletion of CD25+ T cells in chimeras receiving STAT3-deficient T cells resulted in delayed development of alloimmune gut and liver injury. This delayed de novo GVHD was associated with the emergence of donor hematopoietic stem cell-derived Th1 and Th17 cells. These results suggest that STAT3 signaling in graft CD4+ T cells links the alloimmune tissue injury of donor graft T cells and the emergence of donor hematopoietic stem cell-derived pathogenic effector cells and that both populations contribute, albeit in different ways, to the genesis of chronic GVHD after allogenic bone marrow transplantation in a murine model.

  11. Detection of IL28B SNP DNA from Buccal Epithelial Cells, Small Amounts of Serum, and Dried Blood Spots

    PubMed Central

    Halfon, Philippe; Ouzan, Denis; Khiri, Hacène; Pénaranda, Guillaume; Castellani, Paul; Oulès, Valerie; Kahloun, Asma; Amrani, Nolwenn; Fanteria, Lise; Martineau, Agnès; Naldi, Lou; Bourlière, Marc

    2012-01-01

    Background & Aims Point mutations in the coding region of the interleukin 28 gene (rs12979860) have recently been identified for predicting the outcome of treatment of hepatitis C virus infection. This polymorphism detection was based on whole blood DNA extraction. Alternatively, DNA for genetic diagnosis has been derived from buccal epithelial cells (BEC), dried blood spots (DBS), and genomic DNA from serum. The aim of the study was to investigate the reliability and accuracy of alternative routes of testing for single nucleotide polymorphism allele rs12979860CC. Methods Blood, plasma, and sera samples from 200 patients were extracted (400 µL). Buccal smears were tested using an FTA card. To simulate postal delay, we tested the influence of storage at ambient temperature on the different sources of DNA at five time points (baseline, 48 h, 6 days, 9 days, and 12 days) Results There was 100% concordance between blood, plasma, sera, and BEC, validating the use of DNA extracted from BEC collected on cytology brushes for genetic testing. Genetic variations in HPTR1 gene were detected using smear technique in blood smear (3620 copies) as well as in buccal smears (5870 copies). These results are similar to those for whole blood diluted at 1/10. A minimum of 0.04 µL, 4 µL, and 40 µL was necessary to obtain exploitable results respectively for whole blood, sera, and plasma. No significant variation between each time point was observed for the different sources of DNA. IL28B SNPs analysis at these different time points showed the same results using the four sources of DNA. Conclusion We demonstrated that genomic DNA extraction from buccal cells, small amounts of serum, and dried blood spots is an alternative to DNA extracted from peripheral blood cells and is helpful in retrospective and prospective studies for multiple genetic markers, specifically in hard-to-reach individuals. PMID:22412970

  12. Chloromethyl chlorosulfate as a voltage delay inhibitor in lithium cells

    DOEpatents

    Delnick, F.M.

    1993-04-13

    Chloromethyl chlorosulfate (CMCS) is used as a passive film growth inhibitor in electrochemical cells to minimize voltage delay and low-voltage discharge. Film growth on lithium anodes is significantly diminished when CMCS is added to SOCl[sub 2] and SO[sub 2]Cl[sub 2] electrolytes of lithium batteries. The CMCS also has the effect of extending the shelf-life of Li/SOCl[sub 2] and Li/SO[sub 2]Cl[sub 2] batteries.

  13. Chloromethyl chlorosulfate as a voltage delay inhibitor in lithium cells

    DOEpatents

    Delnick, Frank M.

    1993-01-01

    Chloromethyl chlorosulfate (CMCS) is used as a passive film growth inhibitor in electrochemical cells to minimize voltage delay and low-voltage discharge. Film growth on lithium anodes is significantly diminished when CMCS is added to SOCl.sub.2 and SO.sub.2 Cl.sub.2 electrolytes of lithium batteries. The CMCS also has the effect of extending the shelf-life of Li/SOCl.sub.2 and Li/SO.sub.2 Cl.sub.2 batteries.

  14. Distributed delays in a hybrid model of tumor-immune system interplay.

    PubMed

    Caravagna, Giulio; Graudenzi, Alex; d'Onofrio, Alberto

    2013-02-01

    A tumor is kinetically characterized by the presence of multiple spatio-temporal scales in which its cells interplay with, for instance, endothelial cells or Immune system effectors, exchanging various chemical signals. By its nature, tumor growth is an ideal object of hybrid modeling where discrete stochastic processes model low-numbers entities, and mean-field equations model abundant chemical signals. Thus, we follow this approach to model tumor cells, effector cells and Interleukin-2, in order to capture the Immune surveillance effect. We here present a hybrid model with a generic delay kernel accounting that, due to many complex phenomena such as chemical transportation and cellular differentiation, the tumor-induced recruitment of effectors exhibits a lag period. This model is a Stochastic Hybrid Automata and its semantics is a Piecewise Deterministic Markov process where a two-dimensional stochastic process is interlinked to a multi-dimensional mean-field system. We instantiate the model with two well-known weak and strong delay kernels and perform simulations by using an algorithm to generate trajectories of this process. Via simulations and parametric sensitivity analysis techniques we (i) relate tumor mass growth with the two kernels, we (ii) measure the strength of the Immune surveillance in terms of probability distribution of the eradication times, and (iii) we prove, in the oscillatory regime, the existence of a stochastic bifurcation resulting in delay-induced tumor eradication.

  15. BOLD delay times using group delay in sickle cell disease

    NASA Astrophysics Data System (ADS)

    Coloigner, Julie; Vu, Chau; Bush, Adam; Borzage, Matt; Rajagopalan, Vidya; Lepore, Natasha; Wood, John

    2016-03-01

    Sickle cell disease (SCD) is an inherited blood disorder that effects red blood cells, which can lead to vasoocclusion, ischemia and infarct. This disease often results in neurological damage and strokes, leading to morbidity and mortality. Functional Magnetic Resonance Imaging (fMRI) is a non-invasive technique for measuring and mapping the brain activity. Blood Oxygenation Level-Dependent (BOLD) signals contain also information about the neurovascular coupling, vascular reactivity, oxygenation and blood propagation. Temporal relationship between BOLD fluctuations in different parts of the brain provides also a mean to investigate the blood delay information. We used the induced desaturation as a label to profile transit times through different brain areas, reflecting oxygen utilization of tissue. In this study, we aimed to compare blood flow propagation delay times between these patients and healthy subjects in areas vascularized by anterior, middle and posterior cerebral arteries. In a group comparison analysis with control subjects, BOLD changes in these areas were found to be almost simultaneous and shorter in the SCD patients, because of their increased brain blood flow. Secondly, the analysis of a patient with a stenosis on the anterior cerebral artery indicated that signal of the area vascularized by this artery lagged the MCA signal. These findings suggest that sickle cell disease causes blood propagation modifications, and that these changes could be used as a biomarker of vascular damage.

  16. The actin cytoskeleton of chemotactic amoebae operates close to the onset of oscillations

    NASA Astrophysics Data System (ADS)

    Westendorf, Christian; Negrete, Jose, Jr.; Bae, Albert; Sandmann, Rabea; Bodenschatz, Eberhard; Beta, Carsten

    2013-03-01

    We report evidence that the actin machinery of chemotactic Dictyostelium cells operates close to an oscillatory instability. The averaged F-actin response of many cells to a short-time pulse of cAMP is reminiscent of a damped oscillation. At the single-cell level, however, the response dynamics ranged from short, strongly damped responses to slowly decaying, weakly damped oscillations. Furthermore, in a small subpopulation, we observed self-sustained oscillations in the cortical F-actin concentration. We systematically exposed a large number of cells to periodic pulse trains. The results indicate a resonance peak at periodic inputs of around 20 s. We propose a delayed feedback model that explains our experimental findings based on a time-delay in the actin regulatory network. To quantitatively test the model, we performed stimulation experiments with cells that express GFP-tagged fusion proteins of Coronin and Aip1. These served as markers of the F-actin disassembly process and thus allow us to estimate the delay time. Based on this independent estimate, our model predicts an intrinsic period of 20 s, which agrees with the resonance observed experimentally. Financial support by the Max-Planck Society and the DFG (SFB 937).

  17. Anti-FcεR1 antibody injections activate basophils and mast cells and delay Type I diabetes onset in NOD mice

    PubMed Central

    Larson, David; Torrero, Marina N.; Mueller, Ellen; Shi, Yinghui; Killoran, Kristin

    2012-01-01

    Mounting evidence suggests that helminth infections protect against autoimmune diseases. As helminths cause chronic IgE-mediated activation of basophils and mast cells we hypothesized that continuous activation of these cells could prevents diabetes onset in nonobese diabetic (NOD) mice in the absence of infection. Anti-FcεR1 activated basophils and mast cells and resulted in the release of IL-4 and histamine into the bloodstream. Anti-FcεR1-treated NOD mice showed a type 2 shift in insulin-specific antibody production and exhibited significant delays in diabetes onset. IL-4 responses played a partial role as the protective effect of anti-FcεR1 therapy was diminished in IL-4-deficient NOD mice. In contrast, histamine signaling was not required as anti-FcεR1-mediated protection was not reduced in mice treated with histamine receptor blockers. These results demonstrate that anti-FcεR1 therapy delays diabetes onset in NOD mice and suggest that chronic basophil and mast cell activation may represent a new avenue of therapy for Th1-associated autoimmune diseases. PMID:21920822

  18. Deep sequencing reveals cell-type-specific patterns of single-cell transcriptome variation.

    PubMed

    Dueck, Hannah; Khaladkar, Mugdha; Kim, Tae Kyung; Spaethling, Jennifer M; Francis, Chantal; Suresh, Sangita; Fisher, Stephen A; Seale, Patrick; Beck, Sheryl G; Bartfai, Tamas; Kuhn, Bernhard; Eberwine, James; Kim, Junhyong

    2015-06-09

    Differentiation of metazoan cells requires execution of different gene expression programs but recent single-cell transcriptome profiling has revealed considerable variation within cells of seeming identical phenotype. This brings into question the relationship between transcriptome states and cell phenotypes. Additionally, single-cell transcriptomics presents unique analysis challenges that need to be addressed to answer this question. We present high quality deep read-depth single-cell RNA sequencing for 91 cells from five mouse tissues and 18 cells from two rat tissues, along with 30 control samples of bulk RNA diluted to single-cell levels. We find that transcriptomes differ globally across tissues with regard to the number of genes expressed, the average expression patterns, and within-cell-type variation patterns. We develop methods to filter genes for reliable quantification and to calibrate biological variation. All cell types include genes with high variability in expression, in a tissue-specific manner. We also find evidence that single-cell variability of neuronal genes in mice is correlated with that in rats consistent with the hypothesis that levels of variation may be conserved. Single-cell RNA-sequencing data provide a unique view of transcriptome function; however, careful analysis is required in order to use single-cell RNA-sequencing measurements for this purpose. Technical variation must be considered in single-cell RNA-sequencing studies of expression variation. For a subset of genes, biological variability within each cell type appears to be regulated in order to perform dynamic functions, rather than solely molecular noise.

  19. Systems for controlling the intensity variations in a laser beam and for frequency conversion thereof

    DOEpatents

    Skupsky, S.; Craxton, R.S.; Soures, J.

    1990-10-02

    In order to control the intensity of a laser beam so that its intensity varies uniformly and provides uniform illumination of a target, such as a laser fusion target, a broad bandwidth laser pulse is spectrally dispersed spatially so that the frequency components thereof are spread apart. A disperser (grating) provides an output beam which varies spatially in wavelength in at least one direction transverse to the direction of propagation of the beam. Temporal spread (time delay) across the beam is corrected by using a phase delay device (a time delay compensation echelon). The dispersed beam may be amplified with laser amplifiers and frequency converted (doubled, tripled or quadrupled in frequency) with nonlinear optical elements (birefringent crystals). The spectral variation across the beam is compensated by varying the angle of incidence on one of the crystals with respect to the crystal optical axis utilizing a lens which diverges the beam. Another lens after the frequency converter may be used to recollimate the beam. The frequency converted beam is recombined so that portions of different frequency interfere and, unlike interference between waves of the same wavelength, there results an intensity pattern with rapid temporal oscillations which average out rapidly in time thereby producing uniform illumination on target. A distributed phase plate (also known as a random phase mask), through which the spectrally dispersed beam is passed and then focused on a target, is used to provide the interference pattern which becomes nearly modulation free and uniform in intensity in the direction of the spectral variation. 16 figs.

  20. Systems for controlling the intensity variations in a laser beam and for frequency conversion thereof

    DOEpatents

    Skupsky, Stanley; Craxton, R. Stephen; Soures, John

    1990-01-01

    In order to control the intensity of a laser beam so that its intensity varies uniformly and provides uniform illumination of a target, such as a laser fusion target, a broad bandwidth laser pulse is spectrally dispersed spatially so that the frequency components thereof are spread apart. A disperser (grating) provides an output beam which varies spatially in wavelength in at least one direction transverse to the direction of propagation of the beam. Temporal spread (time delay) across the beam is corrected by using a phase delay device (a time delay compensation echelon). The dispersed beam may be amplified with laser amplifiers and frequency converted (doubled, tripled or quadrupled in frequency) with nonlinear optical elements (birefringent crystals). The spectral variation across the beam is compensated by varying the angle of incidence on one of the crystals with respect to the crystal optical axis utilizing a lens which diverges the beam. Another lens after the frequency converter may be used to recollimate the beam. The frequency converted beam is recombined so that portions of different frequency interfere and, unlike interference between waves of the same wavelength, there results an intensity pattern with rapid temoral oscillations which average out rapidly in time thereby producing uniform illumination on target. A distributed phase plate (also known as a random phase mask), through which the spectrally dispersed beam is passed and then focused on a target, is used to provide the interference pattern which becomes nearly modulation free and uniform in intensity in the direction of the spectral variation.

  1. Seismic anisotropy and its precursory change before eruptions at Piton de la Fournaise volcano, La Réunion

    NASA Astrophysics Data System (ADS)

    Savage, M. K.; Ferrazzini, V.; Peltier, A.; Rivemale, E.; Mayor, J.; Schmid, A.; Brenguier, F.; Massin, F.; Got, J.-L.; Battaglia, J.; DiMuro, A.; Staudacher, T.; Rivet, D.; Taisne, B.; Shelley, A.

    2015-05-01

    The Piton de la Fournaise volcano exhibits frequent eruptions preceded by seismic swarms and is a good target to test hypotheses about magmatically induced variations in seismic wave properties. We use a permanent station network and a portable broadband network to compare seismic anisotropy measured via shear wave splitting with geodetic displacements, ratios of compressional to shear velocity (Vp/Vs), earthquake focal mechanisms, and ambient noise correlation analysis of surface wave velocities and to examine velocity and stress changes from 2000 through 2012. Fast directions align radially to the central cone and parallel to surface cracks and fissures, suggesting stress-controlled cracks. High Vp/Vs ratios under the summit compared with low ratios under the flank suggest spatial variations in the proportion of fluid-filled versus gas-filled cracks. Secular variations of fast directions (ϕ) and delay times (dt) between split shear waves are interpreted to sense changing crack densities and pressure. Delay times tend to increase while surface wave velocity decreases before eruptions. Rotations of ϕ may be caused by changes in either stress direction or fluid pressure. These changes usually correlate with GPS baseline changes. Changes in shear wave splitting measurements made on multiplets yield several populations with characteristic delay times, measured incoming polarizations, and fast directions, which change their proportion as a function of time. An eruption sequence on 14 October 2010 yielded over 2000 shear wave splitting measurements in a 14 h period, allowing high time resolution measurements to characterize the sequence. Stress directions from a propagating dike model qualitatively fit the temporal change in splitting.

  2. Encoding of Spatio-Temporal Input Characteristics by a CA1 Pyramidal Neuron Model

    PubMed Central

    Pissadaki, Eleftheria Kyriaki; Sidiropoulou, Kyriaki; Reczko, Martin; Poirazi, Panayiota

    2010-01-01

    The in vivo activity of CA1 pyramidal neurons alternates between regular spiking and bursting, but how these changes affect information processing remains unclear. Using a detailed CA1 pyramidal neuron model, we investigate how timing and spatial arrangement variations in synaptic inputs to the distal and proximal dendritic layers influence the information content of model responses. We find that the temporal delay between activation of the two layers acts as a switch between excitability modes: short delays induce bursting while long delays decrease firing. For long delays, the average firing frequency of the model response discriminates spatially clustered from diffused inputs to the distal dendritic tree. For short delays, the onset latency and inter-spike-interval succession of model responses can accurately classify input signals as temporally close or distant and spatially clustered or diffused across different stimulation protocols. These findings suggest that a CA1 pyramidal neuron may be capable of encoding and transmitting presynaptic spatiotemporal information about the activity of the entorhinal cortex-hippocampal network to higher brain regions via the selective use of either a temporal or a rate code. PMID:21187899

  3. Backscatter and attenuation characterization of ventricular myocardium

    NASA Astrophysics Data System (ADS)

    Gibson, Allyson Ann

    2009-12-01

    This Dissertation presents quantitative ultrasonic measurements of the myocardium in fetal hearts and adult human hearts with the goal of studying the physics of sound waves incident upon anisotropic and inhomogeneous materials. Ultrasound has been used as a clinical tool to assess heart structure and function for several decades. The clinical usefulness of this noninvasive approach has grown with our understanding of the physical mechanisms underlying the interaction of ultrasonic waves with the myocardium. In this Dissertation, integrated backscatter and attenuation analyses were performed on midgestational fetal hearts to assess potential differences in the left and right ventricular myocardium. The hearts were interrogated using a 50 MHz transducer that enabled finer spatial resolution than could be achieved at more typical clinical frequencies. Ultrasonic data analyses demonstrated different patterns and relative levels of backscatter and attenuation from the myocardium of the left ventricle and the right ventricle. Ultrasonic data of adult human hearts were acquired with a clinical imaging system and quantified by their magnitude and time delay of cyclic variation of myocardial backscatter. The results were analyzing using Bayes Classification and ROC analysis to quantify potential advantages of using a combination of two features of cyclic variation of myocardial backscatter over using only one or the other feature to distinguish between groups of subjects. When the subjects were classified based on hemoglobin A1c, the homeostasis model assessment of insulin resistance, and the ratio of triglyceride to high-density lipoprotein-cholesterol, differences in the magnitude and normalized time delay of cyclic variation of myocardial backscatter were observed. The cyclic variation results also suggested a trend toward a larger area under the ROC curve when information from magnitude and time delay of cyclic variation is combined using Bayes classification than when each feature is analyzed individually. Ultrasound continues to be a powerful tool that enables noninvasive quantification of material properties. The studies in this Dissertation show that understanding the physical mechanisms behind the interaction of sound waves with myocardium can reveal new information about the structure, composition and overall state of the heart.

  4. Delayed BCG vaccination results in minimal alterations in T cell immunogenicity of acellular pertussis and tetanus immunizations in HIV-exposed infants.

    PubMed

    Blakney, Anna K; Tchakoute, Christophe Toukam; Hesseling, Anneke C; Kidzeru, Elvis B; Jones, Christine E; Passmore, Jo-Ann S; Sodora, Donald L; Gray, Clive M; Jaspan, Heather B

    2015-09-11

    Bacille Calmette-Guerin (BCG) is effective in preventing disseminated tuberculosis (TB) in children but may also have non-specific benefits, and is thought to improve immunity to unrelated antigens through trained innate immunity. In HIV-infected infants, there is a risk of BCG-associated adverse events. We aimed to explore whether delaying BCG vaccination by 8 weeks, in utero or perinatal HIV infection is excluded, affected T-cell responses to B. pertussis (BP) and tetanus toxoid (TT), in HIV-exposed, uninfected infants. Infants were randomized to receive BCG vaccination at birth or 8 weeks of age. At 8 and 14 weeks, T cell proliferation and intracellular cytokine (IL-2, IL-13, IL-17, and IFN-γ) expression was analyzed in response to BP, TT and Staphylococcal enterotoxin B (SEB) antigens. Delaying BCG vaccination did not alter T-cell proliferation to BP or TT antigens. Infants immunized with BCG at birth had higher CD4+ T cell proliferation to SEB at 14 weeks of age (p=0.018). Birth-vaccinated infants had increased CD8+ IL-2 expression in response to BP, but not TT or SEB, at 8 weeks. Infants vaccinated with BCG at 8 weeks had significantly lower IL-13 expression by BP-specific CD4+ and CD8+ T cells at 14 weeks (p=0.032 and p=0.0035, respectively). There were no observed differences in multifunctional cytokine response to TT, BP or SEB between infants vaccinated with BCG at birth versus 8 weeks of age. Delaying BCG vaccination until 8 weeks of age results in robust T-cellular responses to BP and TT in HIV-exposed infants. NCT02062580. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. mei-41 and bub1 block mitosis at two distinct steps in response to incomplete DNA replication in Drosophila embryos.

    PubMed

    Garner, M; van Kreeveld, S; Su, T T

    2001-10-16

    Drosophila double park encodes a homolog of Cdt1 that functions in initiation of DNA replication in fission yeast and Xenopus. dup mutants complete the first 15 embryonic cell cycles, presumably via maternal dup products, and show defects in the 16(th) S phase (S16). Cells carrying dup(a1) allele forgo S16 altogether but enter mitosis 16 (M16). We find that the timing of entry into M16 is similar in dup(a1) and heterozygous or wild-type (wt) controls. In contrast, we find that mutant cells carrying another allele, dup(a3), undergo a partial S16 and delay the entry into M16. Thus, initiation of S16 appears necessary for delaying M16. This delay is absent in double mutants of dup(a3) and mei-41 (Drosophila ATR), indicating that a mei-41-dependent checkpoint acts to delay the entry into mitosis in response to incomplete DNA replication. dup(a3) and dup(a1) mutant cells that enter M16 become arrested in M16. We find that mitotic cyclins are stabilized and that a spindle checkpoint protein, Bub1, localizes onto chromosomes during mitotic arrest in dup mutants. These features suggest an arrest prior to metaphase-anaphase transition. dup(a3) bub1 double mutant cells exit M16, indicating that a bub1-mediated checkpoint acts to block mitotic exit in dup mutants. To our knowledge, this is the first report of (1) incomplete DNA replication affecting both the entry into and the exit from mitosis in a single cell cycle via different mechanisms and (2) the role of bub1 in regulating mitotic exit in response to incomplete DNA replication.

  6. Delayed pituitary adenylate cyclase-activating polypeptide delivery after brain stroke improves functional recovery by inducing m2 microglia/macrophage polarization.

    PubMed

    Brifault, Coralie; Gras, Marjorie; Liot, Donovan; May, Victor; Vaudry, David; Wurtz, Olivier

    2015-02-01

    Until now, except thrombolysis, the therapeutical strategies targeting the acute phase of cerebral ischemia have been proven ineffective, and no approach is available to attenuate the delayed cell death mechanisms and the resulting functional deficits in the late phase. Then, we investigated whether a targeted and delayed delivery of pituitary adenylate cyclase-activating polypeptide (PACAP), a peptide known to exert neuroprotective activities, may dampen delayed pathophysiological processes improving functional recovery. Three days after permanent focal ischemia, PACAP-producing stem cells were transplanted intracerebro ventricularly in nonimmunosuppressed mice. At 7 and 14 days post ischemia, the effects of this stem cell-based targeted delivery of PACAP on functional recovery, volume lesions, and inflammatory processes were analyzed. The delivery of PACAP in the vicinity of the infarct zone 3 days post stroke promotes fast, stable, and efficient functional recovery. This was correlated with a modulation of the postischemic inflammatory response. Transcriptomic and Ingenuity Pathway Analysis-based bioinformatic analyses identified several gene networks, functions, and key transcriptional factors, such as nuclear factor-κB, C/EBP-β, and Notch/RBP-J as PACAP's potential targets. Such PACAP-dependent immunomodulation was further confirmed by morphometric and phenotypic analyses of microglial cells showing increased number of Arginase-1(+) cells in mice treated with PACAP-expressing cells specifically, demonstrating the redirection of the microglial response toward a neuroprotective M2 phenotype. Our results demonstrated that immunomodulatory strategies capable of redirecting the microglial response toward a neuroprotective M2 phenotype in the late phase of brain ischemia could represent attractive options for stroke treatment in a new and unexploited therapeutical window. © 2014 American Heart Association, Inc.

  7. Time-resolved delayed luminescence image microscopy using an europium ion chelate complex.

    PubMed Central

    Marriott, G.; Heidecker, M.; Diamandis, E. P.; Yan-Marriott, Y.

    1994-01-01

    Improvements and extended applications of time-resolved delayed luminescence imaging microscopy (TR-DLIM) in cell biology are described. The emission properties of europium ion complexed to a fluorescent chelating group capable of labeling proteins are exploited to provide high contrast images of biotin labeled ligands through detection of the delayed emission. The streptavidin-based macromolecular complex (SBMC) employs streptavidin cross-linked to thyroglobulin multiply labeled with the europium-fluorescent chelate. The fluorescent chelate is efficiently excited with 340-nm light, after which it sensitizes europium ion emission at 612 nm hundreds of microseconds later. The SBMC complex has a high quantum yield orders of magnitude higher than that of eosin, a commonly used delayed luminescent probe, and can be readily seen by the naked eye, even in specimens double-labeled with prompt fluorescent probes. Unlike triplet-state phosphorescent probes, sensitized europium ion emission is insensitive to photobleaching and quenching by molecular oxygen; these properties have been exploited to obtain delayed luminescence images of living cells in aerated medium thus complementing imaging studies using prompt fluorescent probes. Since TR-DLIM has the unique property of rejecting enormous signals that originate from scattered light, autofluorescence, and prompt fluorescence it has been possible to resolve double emission images of living amoeba cells containing an intensely stained lucifer yellow in pinocytosed vesicles and membrane surface-bound SBMC-labeled biotinylated concanavalin A. Images of fixed cells represented in terms of the time decay of the sensitized emission show the lifetime of the europium ion emission is sensitive to the environment in which it is found. Through the coupling of SBMC to streptavidin,a plethora of biotin-based tracer molecules are available for immunocytochemical studies. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 PMID:7811952

  8. PPARα autocrine regulation of Ca²⁺-regulated exocytosis in guinea pig antral mucous cells: NO and cGMP accumulation.

    PubMed

    Tanaka, Saori; Sugiyama, Nanae; Takahashi, Yuko; Mantoku, Daiki; Sawabe, Yukinori; Kuwabara, Hiroko; Nakano, Takashi; Shimamoto, Chikao; Matsumura, Hitoshi; Marunaka, Yoshinori; Nakahari, Takashi

    2014-12-15

    In antral mucous cells, acetylcholine (ACh, 1 μM) activates Ca(2+)-regulated exocytosis, consisting of a peak in exocytotic events that declines rapidly (initial phase) followed by a second slower decline (late phase) lasting during ACh stimulation. GW7647 [a peroxisome proliferation activation receptor α (PPARα) agonist] enhanced the ACh-stimulated initial phase, and GW6471 (a PPARα antagonist) abolished the GW7647-induced enhancement. However, GW6471 produced the delayed, but transient, increase in the ACh-stimulated late phase, and it also decreased the initial phase and produced the delayed increase in the late phase during stimulation with ACh alone. A similar delayed increase in the ACh-stimulated late phase is induced by an inhibitor of the PKG, Rp8BrPETcGMPS, suggesting that GW6471 inhibits cGMP accumulation. An inhibitor of nitric oxide synthase 1 (NOS1), N(5)-[imino(propylamino)methyl]-L-ornithine hydrochloride (N-PLA), also abolished the GW7647-induced-enhancement of ACh-stimulated initial phase but produced the delayed increase in the late phase. However, in the presence of N-PLA, an NO donor or 8BrcGMP enhanced the ACh-stimulated initial phase and abolished the delayed increase in the late phase. Moreover, GW7647 and ACh stimulated NO production and cGMP accumulation in antral mucosae, which was inhibited by GW6471 or N-PLA. Western blotting and immunohistochemistry revealed that NOS1 and PPARα colocalize in antral mucous cells. In conclusion, during ACh stimulation, a PPARα autocrine mechanism, which accumulates NO via NOS1 leading to cGMP accumulation, modulates the Ca(2+)-regulated exocytosis in antral mucous cells. Copyright © 2014 the American Physiological Society.

  9. Acoustical Measurement of Nonlinear Internal Waves Using the Inverted Echo Sounder

    DTIC Science & Technology

    2009-05-05

    showed that the vertical round-trip travel time of an acoustic pulse allowed measurement of the variation of thermal stratification caused by internal...translate from distance to time , note that reflection from a position 56 m from zenith to a PIES at 1024-m depth would have a delay time of 2 ms. Note that...approximation of the travel time scatter, the delay to the arrival of the dis- tribution peak tp is directly related to the width b: t p 5 t 0 1 b. (24) The

  10. A study on parameter variation effects on battery packs for electric vehicles

    NASA Astrophysics Data System (ADS)

    Zhou, Long; Zheng, Yuejiu; Ouyang, Minggao; Lu, Languang

    2017-10-01

    As one single cell cannot meet power and driving range requirement in an electric vehicle, the battery packs with hundreds of single cells connected in parallel and series should be constructed. The most significant difference between a single cell and a battery pack is cell variation. Not only does cell variation affect pack energy density and power density, but also it causes early degradation of battery and potential safety issues. The cell variation effects on battery packs are studied, which are of great significant to battery pack screening and management scheme. In this study, the description for the consistency characteristics of battery packs was first proposed and a pack model with 96 cells connected in series was established. A set of parameters are introduced to study the cell variation and their impacts on battery packs are analyzed through the battery pack capacity loss simulation and experiments. Meanwhile, the capacity loss composition of the battery pack is obtained and verified by the temperature variation experiment. The results from this research can demonstrate that the temperature, self-discharge rate and coulombic efficiency are the major affecting parameters of cell variation and indicate the dissipative cell equalization is sufficient for the battery pack.

  11. Plerixafor Improves Primary Tumor Response and Reduces Metastases in Cervical Cancer Treated with Radio-Chemotherapy.

    PubMed

    Chaudary, Naz; Pintilie, Melania; Jelveh, Salomeh; Lindsay, Patricia; Hill, Richard P; Milosevic, Michael

    2017-03-01

    Purpose: There is an important need to improve the effectiveness of radio-chemotherapy (RTCT) for cervical cancer. The CXCL12/CXCR4 pathway can influence RT response by recruiting normal myeloid cells to the tumor microenvironment that in turn can exert radioprotective effects, and may promote metastases. The objective of this study was to explore the efficacy and toxicity of combining RTCT with CXCL12/CXCR4 inhibition in cervical cancer. Experimental Design: CXCR4 expression was measured in 115 patients with cervical cancer. Two primary orthotopic cervical cancer xenografts (OCICx) with different levels of CXCR4 expression were treated with RT (30 Gy: 15 daily fractions) and weekly cisplatin (4 mg/kg), with or without the CXCR4 inhibitor Plerixafor (5 mg/kg/day). The endpoints were tumor growth delay and lymph node metastases. Acute intestinal toxicity was assessed using a crypt cell assay. Results: There was a fivefold variation in CXCR4 mRNA expression in the patient samples, and good correlation between the expression in patients and in the xenografts. The combination of RTCT and Plerixafor produced substantial tumor growth delay and reduced lymph node metastases compared with RTCT alone in both of the xenograft models. There was a trend toward reduced acute intestinal toxicity with the addition of Plerixafor to RTCT. There were no changes in normal organ morphology to suggest increased late toxicity. Conclusions: This study demonstrates that the addition of Plerixafor to standard RTCT improves primary tumor response and reduces metastases in cervical cancer with no increase in toxicity. This combination warrants further investigation in phase I/II clinical trials. Clin Cancer Res; 23(5); 1242-9. ©2016 AACR . ©2016 American Association for Cancer Research.

  12. Effect of metrology time delay on overlay APC

    NASA Astrophysics Data System (ADS)

    Carlson, Alan; DiBiase, Debra

    2002-07-01

    The run-to-run control strategy of lithography APC is primarily composed of a feedback loop as shown in the diagram below. It is known that the insertion of a time delay in a feedback loop can cause degradation in control performance and could even cause a stable system to become unstable, if the time delay becomes sufficiently large. Many proponents of integrated metrology methods have cited the damage caused by metrology time delays as the primary justification for moving from a stand-alone to integrated metrology. While there is little dispute over the qualitative form of this argument, there has been very light published about the quantitative effects under real fab conditions - precisely how much control is lost due to these time delays. Another issue regarding time delays is that the length of these delays is not typically fixed - they vary from lot to lot and in some cases this variance can be large - from one hour on the short side to over 32 hours on the long side. Concern has been expressed that the variability in metrology time delays can cause undesirable dynamics in feedback loops that make it difficult to optimize feedback filters and gains and at worst could drive a system unstable. By using data from numerous fabs, spanning many sizes and styles of operation, we have conducted a quantitative study of the time delay effect on overlay run- to-run control. Our analysis resulted in the following conclusions: (1) There is a significant and material relationship between metrology time delay and overlay control under a variety of real world production conditions. (2) The run-to-run controller can be configured to minimize sensitivity to time delay variations. (3) The value of moving to integrated metrology can be quantified.

  13. Variation is function: Are single cell differences functionally important?: Testing the hypothesis that single cell variation is required for aggregate function.

    PubMed

    Dueck, Hannah; Eberwine, James; Kim, Junhyong

    2016-02-01

    There is a growing appreciation of the extent of transcriptome variation across individual cells of the same cell type. While expression variation may be a byproduct of, for example, dynamic or homeostatic processes, here we consider whether single-cell molecular variation per se might be crucial for population-level function. Under this hypothesis, molecular variation indicates a diversity of hidden functional capacities within an ensemble of identical cells, and this functional diversity facilitates collective behavior that would be inaccessible to a homogenous population. In reviewing this topic, we explore possible functions that might be carried by a heterogeneous ensemble of cells; however, this question has proven difficult to test, both because methods to manipulate molecular variation are limited and because it is complicated to define, and measure, population-level function. We consider several possible methods to further pursue the hypothesis that variation is function through the use of comparative analysis and novel experimental techniques. © 2015 The Authors. BioEssays published by WILEY Periodicals, Inc.

  14. Gamma Oscillations and Visual Binding

    NASA Astrophysics Data System (ADS)

    Robinson, Peter A.; Kim, Jong Won

    2006-03-01

    At the root of visual perception is the mechanism the brain uses to analyze features in a scene and bind related ones together. Experiments show this process is linked to oscillations of brain activity in the 30-100 Hz gamma band. Oscillations at different sites have correlation functions (CFs) that often peak at zero lag, implying simultaneous firing, even when conduction delays are large. CFs are strongest between cells stimulated by related features. Gamma oscillations are studied here by modeling mm-scale patchy interconnections in the visual cortex. Resulting predictions for gamma responses to stimuli account for numerous experimental findings, including why oscillations and zero-lag synchrony are associated, observed connections with feature preferences, the shape of the zero-lag peak, and variations of CFs with attention. Gamma waves are found to obey the Schroedinger equation, opening the possibility of cortical analogs of quantum phenomena. Gamma instabilities are tied to observations of gamma activity linked to seizures and hallucinations.

  15. [Microbiological diagnosis of viral respiratory infections].

    PubMed

    Eiros, José M; Ortiz de Lejarazu, Raúl; Tenorio, Alberto; Casas, Inmaculada; Pozo, Francisco; Ruiz, Guillermo; Pérez-Breña, Pilar

    2009-03-01

    Acute respiratory infection is the most common disease occurring over a person's lifetime, with etiological variations determined mainly by age, environmental circumstances, the healthcare setting, and the underlying pathology. More than 200 different viruses distributed in six viral families have been implicated in the pathogenesis of respiratory tract infection. These facts are generating an increasing diagnostic demand that should be incorporated into the healthcare setting without delay. To meet this demand, the Spanish Society of Infectious Diseases and Clinical Microbiology has updated its Standard Procedure for the microbiological diagnosis of viral respiratory infection. This document contains an update primarily of infections caused by influenza viruses, and secondarily, infections due to other conventional and emerging respiratory viruses. In all cases, the methods for direct virological diagnosis (cell culture, and detection of antigens and nucleic acid) are reviewed, with special reference to techniques for molecular detection and genetic characterization.

  16. Light-induced biophotonic emission from plant tissues.

    PubMed

    Bajpai, R P; Bajpai, P K

    1992-07-01

    The emission of biophotons in the visible range, following a delay time of 2-200 seconds after exposure to light, has been measured in germinating seeds, roots, flowers, leaves, and cells. It was found that the biophotonic signals are reproducible and light-induced. The observed signals from germinating seeds of Phaseolus aures and decaying leaves of Eucalyptus are presented to show that the signals have characteristic kinetics and intensity. The kinetics of the signal was found to be independent of the stage of growth or decay, though its intensity varied with biological factors. The kinetics in the first minute is characterized by a single exponential decay term while that in the region t less than or equal to 200 s is characterized by two exponentials. The variation in the intensity of the signal with mass, state of hydration, and growth, and the effect of inhibitors in various systems (e.g. leaves, lichen, Chlorella) are reported.

  17. Cellular responses to a prolonged delay in mitosis are determined by a DNA damage response controlled by Bcl-2 family proteins.

    PubMed

    Colin, Didier J; Hain, Karolina O; Allan, Lindsey A; Clarke, Paul R

    2015-03-01

    Anti-cancer drugs that disrupt mitosis inhibit cell proliferation and induce apoptosis, although the mechanisms of these responses are poorly understood. Here, we characterize a mitotic stress response that determines cell fate in response to microtubule poisons. We show that mitotic arrest induced by these drugs produces a temporally controlled DNA damage response (DDR) characterized by the caspase-dependent formation of γH2AX foci in non-apoptotic cells. Following exit from a delayed mitosis, this initial response results in activation of DDR protein kinases, phosphorylation of the tumour suppressor p53 and a delay in subsequent cell cycle progression. We show that this response is controlled by Mcl-1, a regulator of caspase activation that becomes degraded during mitotic arrest. Chemical inhibition of Mcl-1 and the related proteins Bcl-2 and Bcl-xL by a BH3 mimetic enhances the mitotic DDR, promotes p53 activation and inhibits subsequent cell cycle progression. We also show that inhibitors of DDR protein kinases as well as BH3 mimetics promote apoptosis synergistically with taxol (paclitaxel) in a variety of cancer cell lines. Our work demonstrates the role of mitotic DNA damage responses in determining cell fate in response to microtubule poisons and BH3 mimetics, providing a rationale for anti-cancer combination chemotherapies.

  18. Cellular responses to a prolonged delay in mitosis are determined by a DNA damage response controlled by Bcl-2 family proteins

    PubMed Central

    Colin, Didier J.; Hain, Karolina O.; Allan, Lindsey A.; Clarke, Paul R.

    2015-01-01

    Anti-cancer drugs that disrupt mitosis inhibit cell proliferation and induce apoptosis, although the mechanisms of these responses are poorly understood. Here, we characterize a mitotic stress response that determines cell fate in response to microtubule poisons. We show that mitotic arrest induced by these drugs produces a temporally controlled DNA damage response (DDR) characterized by the caspase-dependent formation of γH2AX foci in non-apoptotic cells. Following exit from a delayed mitosis, this initial response results in activation of DDR protein kinases, phosphorylation of the tumour suppressor p53 and a delay in subsequent cell cycle progression. We show that this response is controlled by Mcl-1, a regulator of caspase activation that becomes degraded during mitotic arrest. Chemical inhibition of Mcl-1 and the related proteins Bcl-2 and Bcl-xL by a BH3 mimetic enhances the mitotic DDR, promotes p53 activation and inhibits subsequent cell cycle progression. We also show that inhibitors of DDR protein kinases as well as BH3 mimetics promote apoptosis synergistically with taxol (paclitaxel) in a variety of cancer cell lines. Our work demonstrates the role of mitotic DNA damage responses in determining cell fate in response to microtubule poisons and BH3 mimetics, providing a rationale for anti-cancer combination chemotherapies. PMID:25761368

  19. The Rts1 Regulatory Subunit of Protein Phosphatase 2A Is Required for Control of G1 Cyclin Transcription and Nutrient Modulation of Cell Size

    PubMed Central

    Artiles, Karen; Anastasia, Stephanie; McCusker, Derek; Kellogg, Douglas R.

    2009-01-01

    The key molecular event that marks entry into the cell cycle is transcription of G1 cyclins, which bind and activate cyclin-dependent kinases. In yeast cells, initiation of G1 cyclin transcription is linked to achievement of a critical cell size, which contributes to cell-size homeostasis. The critical cell size is modulated by nutrients, such that cells growing in poor nutrients are smaller than cells growing in rich nutrients. Nutrient modulation of cell size does not work through known critical regulators of G1 cyclin transcription and is therefore thought to work through a distinct pathway. Here, we report that Rts1, a highly conserved regulatory subunit of protein phosphatase 2A (PP2A), is required for normal control of G1 cyclin transcription. Loss of Rts1 caused delayed initiation of bud growth and delayed and reduced accumulation of G1 cyclins. Expression of the G1 cyclin CLN2 from an inducible promoter rescued the delayed bud growth in rts1Δ cells, indicating that Rts1 acts at the level of transcription. Moreover, loss of Rts1 caused altered regulation of Swi6, a key component of the SBF transcription factor that controls G1 cyclin transcription. Epistasis analysis revealed that Rts1 does not work solely through several known critical upstream regulators of G1 cyclin transcription. Cells lacking Rts1 failed to undergo nutrient modulation of cell size. Together, these observations demonstrate that Rts1 is a key player in pathways that link nutrient availability, cell size, and G1 cyclin transcription. Since Rts1 is highly conserved, it may function in similar pathways in vertebrates. PMID:19911052

  20. Reproducibility of Digital PCR Assays for Circulating Tumor DNA Analysis in Advanced Breast Cancer

    PubMed Central

    Hrebien, Sarah; O’Leary, Ben; Beaney, Matthew; Schiavon, Gaia; Fribbens, Charlotte; Bhambra, Amarjit; Johnson, Richard; Turner, Nicholas

    2016-01-01

    Circulating tumor DNA (ctDNA) analysis has the potential to allow non-invasive analysis of tumor mutations in advanced cancer. In this study we assessed the reproducibility of digital PCR (dPCR) assays of circulating tumor DNA in a cohort of patients with advanced breast cancer and assessed delayed plasma processing using cell free DNA preservative tubes. We recruited a cohort of 96 paired samples from 71 women with advanced breast cancer who had paired blood samples processed either immediately or delayed in preservative tubes with processing 48–72 hours after collection. Plasma DNA was analysed with multiplex digital PCR (mdPCR) assays for hotspot mutations in PIK3CA, ESR1 and ERBB2, and for AKT1 E17K. There was 94.8% (91/96) agreement in mutation calling between immediate and delayed processed tubes, kappa 0.88 95% CI 0.77–0.98). Discordance in mutation calling resulted from low allele frequency and likely stochastic effects. In concordant samples there was high correlation in mutant copies per ml plasma (r2 = 0.98; p<0.0001). There was elevation of total cell free plasma DNA concentrations in 10.3% of delayed processed tubes, although overall quantification of total cell free plasma DNA had similar prognostic effects in immediate (HR 3.6) and delayed (HR 3.0) tubes. There was moderate agreement in changes in allele fraction between sequential samples in quantitative mutation tracking (r = 0.84, p = 0.0002). Delayed processing of samples using preservative tubes allows for centralized ctDNA digital PCR mutation screening in advanced breast cancer. The potential of preservative tubes in quantitative mutation tracking requires further research. PMID:27760227

  1. Reproducibility of Digital PCR Assays for Circulating Tumor DNA Analysis in Advanced Breast Cancer.

    PubMed

    Hrebien, Sarah; O'Leary, Ben; Beaney, Matthew; Schiavon, Gaia; Fribbens, Charlotte; Bhambra, Amarjit; Johnson, Richard; Garcia-Murillas, Isaac; Turner, Nicholas

    2016-01-01

    Circulating tumor DNA (ctDNA) analysis has the potential to allow non-invasive analysis of tumor mutations in advanced cancer. In this study we assessed the reproducibility of digital PCR (dPCR) assays of circulating tumor DNA in a cohort of patients with advanced breast cancer and assessed delayed plasma processing using cell free DNA preservative tubes. We recruited a cohort of 96 paired samples from 71 women with advanced breast cancer who had paired blood samples processed either immediately or delayed in preservative tubes with processing 48-72 hours after collection. Plasma DNA was analysed with multiplex digital PCR (mdPCR) assays for hotspot mutations in PIK3CA, ESR1 and ERBB2, and for AKT1 E17K. There was 94.8% (91/96) agreement in mutation calling between immediate and delayed processed tubes, kappa 0.88 95% CI 0.77-0.98). Discordance in mutation calling resulted from low allele frequency and likely stochastic effects. In concordant samples there was high correlation in mutant copies per ml plasma (r2 = 0.98; p<0.0001). There was elevation of total cell free plasma DNA concentrations in 10.3% of delayed processed tubes, although overall quantification of total cell free plasma DNA had similar prognostic effects in immediate (HR 3.6) and delayed (HR 3.0) tubes. There was moderate agreement in changes in allele fraction between sequential samples in quantitative mutation tracking (r = 0.84, p = 0.0002). Delayed processing of samples using preservative tubes allows for centralized ctDNA digital PCR mutation screening in advanced breast cancer. The potential of preservative tubes in quantitative mutation tracking requires further research.

  2. Haem oxygenase delays programmed cell death in wheat aleurone layers by modulation of hydrogen peroxide metabolism

    PubMed Central

    Wu, Mingzhu; Huang, Jingjing; Xu, Sheng; Ling, Tengfang; Xie, Yanjie; Shen, Wenbiao

    2011-01-01

    Haem oxygenase-1 (HO-1) confers protection against a variety of oxidant-induced cell and tissue injury in animals and plants. In this report, it is confirmed that programmed cell death (PCD) in wheat aleurone layers is stimulated by GA and prevented by ABA. Meanwhile, HO activity and HO-1 protein expression exhibited lower levels in GA-treated layers, whereas the hydrogen peroxide (H2O2) content was apparently increased. The pharmacology approach illustrated that scavenging or accumulating H2O2 either delayed or accelerated GA-induced PCD. Furthermore, pretreatment with the HO-1 specific inhibitor, zinc protoporphyrin IX (ZnPPIX), before exposure to GA, not only decreased HO activity but also accelerated GA-induced PCD significantly. The application of the HO-1 inducer, haematin, and the enzymatic reaction product of HO, carbon monoxide (CO) aqueous solution, both of which brought about a noticeable induction of HO expression, substantially prevented GA-induced PCD. These effects were reversed when ZnPPIX was added, suggesting that HO in vivo played a role in delaying PCD. Meanwhile, catalase (CAT) and ascorbate peroxidase (APX) activities or transcripts were enhanced by haematin, CO, or bilirubin (BR), the catalytic by-product of HO. This enhancement resulted in a decrease in H2O2 production and a delay in PCD. In addition, the antioxidants butylated hydroxytoluene (BHT), dithiothreitol (DTT), and ascorbic acid (AsA) were able not only to delay PCD but also to mimic the effects of haematin and CO on HO up-regulation. Overall, the above results suggested that up-regulation of HO expression delays PCD through the down-regulation of H2O2 production. PMID:20797999

  3. Computational Stimulation of the Basal Ganglia Neurons with Cost Effective Delayed Gaussian Waveforms

    PubMed Central

    Daneshzand, Mohammad; Faezipour, Miad; Barkana, Buket D.

    2017-01-01

    Deep brain stimulation (DBS) has compelling results in the desynchronization of the basal ganglia neuronal activities and thus, is used in treating the motor symptoms of Parkinson's disease (PD). Accurate definition of DBS waveform parameters could avert tissue or electrode damage, increase the neuronal activity and reduce energy cost which will prolong the battery life, hence avoiding device replacement surgeries. This study considers the use of a charge balanced Gaussian waveform pattern as a method to disrupt the firing patterns of neuronal cell activity. A computational model was created to simulate ganglia cells and their interactions with thalamic neurons. From the model, we investigated the effects of modified DBS pulse shapes and proposed a delay period between the cathodic and anodic parts of the charge balanced Gaussian waveform to desynchronize the firing patterns of the GPe and GPi cells. The results of the proposed Gaussian waveform with delay outperformed that of rectangular DBS waveforms used in in-vivo experiments. The Gaussian Delay Gaussian (GDG) waveforms achieved lower number of misses in eliciting action potential while having a lower amplitude and shorter length of delay compared to numerous different pulse shapes. The amount of energy consumed in the basal ganglia network due to GDG waveforms was dropped by 22% in comparison with charge balanced Gaussian waveforms without any delay between the cathodic and anodic parts and was also 60% lower than a rectangular charged balanced pulse with a delay between the cathodic and anodic parts of the waveform. Furthermore, by defining a Synchronization Level metric, we observed that the GDG waveform was able to reduce the synchronization of GPi neurons more effectively than any other waveform. The promising results of GDG waveforms in terms of eliciting action potential, desynchronization of the basal ganglia neurons and reduction of energy consumption can potentially enhance the performance of DBS devices. PMID:28848417

  4. Computational Stimulation of the Basal Ganglia Neurons with Cost Effective Delayed Gaussian Waveforms.

    PubMed

    Daneshzand, Mohammad; Faezipour, Miad; Barkana, Buket D

    2017-01-01

    Deep brain stimulation (DBS) has compelling results in the desynchronization of the basal ganglia neuronal activities and thus, is used in treating the motor symptoms of Parkinson's disease (PD). Accurate definition of DBS waveform parameters could avert tissue or electrode damage, increase the neuronal activity and reduce energy cost which will prolong the battery life, hence avoiding device replacement surgeries. This study considers the use of a charge balanced Gaussian waveform pattern as a method to disrupt the firing patterns of neuronal cell activity. A computational model was created to simulate ganglia cells and their interactions with thalamic neurons. From the model, we investigated the effects of modified DBS pulse shapes and proposed a delay period between the cathodic and anodic parts of the charge balanced Gaussian waveform to desynchronize the firing patterns of the GPe and GPi cells. The results of the proposed Gaussian waveform with delay outperformed that of rectangular DBS waveforms used in in-vivo experiments. The Gaussian Delay Gaussian (GDG) waveforms achieved lower number of misses in eliciting action potential while having a lower amplitude and shorter length of delay compared to numerous different pulse shapes. The amount of energy consumed in the basal ganglia network due to GDG waveforms was dropped by 22% in comparison with charge balanced Gaussian waveforms without any delay between the cathodic and anodic parts and was also 60% lower than a rectangular charged balanced pulse with a delay between the cathodic and anodic parts of the waveform. Furthermore, by defining a Synchronization Level metric, we observed that the GDG waveform was able to reduce the synchronization of GPi neurons more effectively than any other waveform. The promising results of GDG waveforms in terms of eliciting action potential, desynchronization of the basal ganglia neurons and reduction of energy consumption can potentially enhance the performance of DBS devices.

  5. Role of adiponectin in delayed embryonic development of the short-nosed fruit bat, Cynopterus sphinx.

    PubMed

    Anuradha; Krishna, Amitabh

    2014-12-01

    The aim of this study was to evaluate the role of adiponectin in the delayed embryonic development of Cynopterus sphinx. Adiponectin receptor (ADIPOR1) abundance was first observed to be lower during the delayed versus non-delayed periods of utero-embryonic unit development. The effects of adiponectin treatment on embryonic development were then evaluated during the period of delayed development. Exogenous treatment increased the in vivo rate of embryonic development, as indicated by an increase in weight, ADIPOR1 levels in the utero-embryonic unit, and histological changes in embryonic development. Treatment with adiponectin during embryonic diapause showed a significant increase in circulating progesterone and estradiol concentrations, and in production of their receptors in the utero-embryonic unit. The adiponectin-induced increase in estradiol synthesis was correlated with increased cell survival (BCL2 protein levels) and cell proliferation (PCNA protein levels) in the utero-embryonic unit, suggesting an indirect effect of adiponectin via estradiol synthesis by the ovary. An in vitro study further confirmed the in vivo findings that adiponectin treatment increases PCNA levels together with increased uptake of glucose by increasing the abundance of glucose transporter 8 (GLUT8) in the utero-embryonic unit. The in vitro study also revealed that adiponectin, together with estradiol but not alone, significantly increased ADIPOR1 protein levels. Thus, adiponectin works in concert with estradiol to increase glucose transport to the utero-embryonic unit and promote cell proliferation, which together accelerate embryonic development. © 2014 Wiley Periodicals, Inc.

  6. Inverse Problems for Nonlinear Delay Systems

    DTIC Science & Technology

    2011-03-15

    population dynamics. We consider the delay between birth and adulthood for neonate pea aphids and present a mathematical model that treats this delay as...which there is currently no known cure. For HIV, the core of the virus is composed of single-stranded viral RNA and protein components. As depicted in...at a CD4 receptor site and the viral core is injected into the cell. Once inside, the protein components enable transcription and integration of the

  7. Chromosome damage evolution after low and high LET irradiation

    NASA Astrophysics Data System (ADS)

    Andreev, Sergey; Eidelman, Yuri

    Ionizing radiation induces DNA and chromatin lesions which are converted to chromosome lesions detected in the first post-irradiation mitosis by classic cytogenetic techniques as chromosomal aberrations (CAs). These techniques allow to monitor also delayed aberrations observed after many cell generations post-irradiation - the manifestation of chromosomal instability phenotype (CIN). The problem discussed is how to predict time evolution from initial to delayed DNA/chromosome damage. To address this question, in the present work a mechanistic model of CIN is elaborated which integrates pathways of (*) DNA damage induction and its conversion to chromosome lesions (aberrations), (**) lesion transmission and generation through cell cycles. Delayed aberrations in subsequent cycles are formed in the model owing to two pathways, DNA damage generation de novo as well as CA transmission from previous cycles. DNA damage generation rate is assumed to consist of bystander and non-bystander components. Bystander signals impact all cells roughly equally, whereas non-bystander DSB generation rate differs for the descendants of unirradiated and irradiated cells. Monte Carlo simulation of processes underlying CIN allows to predict the time evolution of initial radiation-induced damage - kinetics curve for delayed unstable aberrations (dicentrics) together with dose response and RBE as a function of time after high vs low LET irradiation. The experimental data for radiation-induced CIN in TK6 lymphoblastoid cells and human lymphocytes irradiated with low (gamma) and high (Fe, C) LET radiation are analyzed on the basis of the proposed model. One of the conclusions is that without bystander signaling, just taking into account the initial DNA damage and non-bystander DSB generation, it is impossible to describe the available experimental data for high-LET-induced CIN. The exact contribution of bystander effects for high vs low LET remains unknown, but the relative contribution may be assessed at large times after initial acute irradiation. RBE for delayed aberrations depends on LET, time and cell line, which probably reflects a genetic background for bystander component. The proposed modeling approach creates a basis for integration of complex network of bystander/inflammatory signaling in systems-level platform for quantification of radiation induced CIN.

  8. Endogenous T cell responses to antigens expressed in lung adenocarcinomas delay malignant tumor progression

    PubMed Central

    DuPage, Michel; Cheung, Ann; Mazumdar, Claire; Winslow, Monte M.; Bronson, Roderick; Schmidt, Leah M.; Crowley, Denise; Chen, Jianzhu; Jacks, Tyler

    2010-01-01

    SUMMARY Neoantigens derived from somatic mutations in tumors may provide a critical link between the adaptive immune system and cancer. Here we describe a system to introduce exogenous antigens into genetically engineered mouse lung cancers to mimic tumor neoantigens. We show that endogenous T cells respond to and infiltrate tumors, significantly delaying malignant progression. Despite continued antigen expression, T cell infiltration does not persist and tumors ultimately escape immune attack. Transplantation of cell lines derived from these lung tumors or prophylactic vaccination against the autochthonous tumors, however, results in rapid tumor eradication or selection of tumors that lose antigen expression. These results provide insight into the dynamic nature of the immune response to naturally arising tumors. PMID:21251614

  9. Nanosecond monolithic CMOS readout cell

    DOEpatents

    Souchkov, Vitali V.

    2004-08-24

    A pulse shaper is implemented in monolithic CMOS with a delay unit formed of a unity gain buffer. The shaper is formed of a difference amplifier having one input connected directly to an input signal and a second input connected to a delayed input signal through the buffer. An elementary cell is based on the pulse shaper and a timing circuit which gates the output of an integrator connected to the pulse shaper output. A detector readout system is formed of a plurality of elementary cells, each connected to a pixel of a pixel array, or to a microstrip of a plurality of microstrips, or to a detector segment.

  10. Gain-scheduling multivariable LPV control of an irrigation canal system.

    PubMed

    Bolea, Yolanda; Puig, Vicenç

    2016-07-01

    The purpose of this paper is to present a multivariable linear parameter varying (LPV) controller with a gain scheduling Smith Predictor (SP) scheme applicable to open-flow canal systems. This LPV controller based on SP is designed taking into account the uncertainty in the estimation of delay and the variation of plant parameters according to the operating point. This new methodology can be applied to a class of delay systems that can be represented by a set of models that can be factorized into a rational multivariable model in series with left/right diagonal (multiple) delays, such as, the case of irrigation canals. A multiple pool canal system is used to test and validate the proposed control approach. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

  11. Estimation of network path segment delays

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

    Nichols, Kathleen Marie

    A method for estimation of a network path segment delay includes determining a scaled time stamp for each packet of a plurality of packets by scaling a time stamp for each respective packet to minimize a difference of at least one of a frequency and a frequency drift between a transport protocol clock of a host and a monitoring point. The time stamp for each packet is provided by the transport protocol clock of the host. A corrected time stamp for each packet is determined by removing from the scaled time stamp for each respective packet, a temporal offset betweenmore » the transport protocol clock and the monitoring clock by minimizing a temporal delay variation of the plurality of packets traversing a segment between the host and the monitoring point.« less

  12. Comparison of in-situ delay monitors for use in Adaptive Voltage Scaling

    NASA Astrophysics Data System (ADS)

    Pour Aryan, N.; Heiß, L.; Schmitt-Landsiedel, D.; Georgakos, G.; Wirnshofer, M.

    2012-09-01

    In Adaptive Voltage Scaling (AVS) the supply voltage of digital circuits is tuned according to the circuit's actual operating condition, which enables dynamic compensation to PVTA variations. By exploiting the excessive safety margins added in state-of-the-art worst-case designs considerable power saving is achieved. In our approach, the operating condition of the circuit is monitored by in-situ delay monitors. This paper presents different designs to implement the in-situ delay monitors capable of detecting late but still non-erroneous transitions, called Pre-Errors. The developed Pre-Error monitors are integrated in a 16 bit multiplier test circuit and the resulting Pre-Error AVS system is modeled by a Markov chain in order to determine the power saving potential of each Pre-Error detection approach.

  13. Study of radiation effects on mammalian cells in vitro

    NASA Technical Reports Server (NTRS)

    Sinclair, W. K.

    1968-01-01

    Radiation effect on single cells and cell populations of Chinese hamster lung tissue is studied in vitro. The rate and position as the cell progresses through the generation cycle shows division delay, changes in some biochemical processes in the cell, chromosomal changes, colony size changes, and loss of reproductive capacity.

  14. Delayed Cell Cycle Progression and Apoptosis Induced by Hemicellulase-Treated Agaricus blazei

    PubMed Central

    Kasai, Hirotake

    2007-01-01

    We examined the effects of hemicellulase-treated Agaricus blazei (AB fraction H, ABH) on growth of several tumor cell lines. ABH inhibited the proliferation of some cell lines without cytotoxic effects. It markedly prolonged the S phase of the cell cycle. ABH also induced mitochondria-mediated apoptosis in different cell lines. However, it had no impact on the growth of other cell lines. ABH induced strong activation of p38 mitogen-activated protein kinase (MAPK) in the cells in which it evoked apoptosis. On the other hand, ABH showed only a weak p38 activation effect in those cell lines in which it delayed cell cycle progression with little induction of apoptosis. However, p38 MAPK-specific inhibitor inhibited both ABH-induced effects, and ABH also caused apoptosis in the latter cells under conditions of high p38 MAPK activity induced by combined treatment with TNF-α. These results indicate that the responsiveness of p38 MAPK to ABH, which differs between cell lines, determines subsequent cellular responses on cell growth. PMID:17342245

  15. Pressure Monitoring Using Hybrid fs/ps Rotational CARS

    NASA Technical Reports Server (NTRS)

    Kearney, Sean P.; Danehy, Paul M.

    2015-01-01

    We investigate the feasibility of gas-phase pressure measurements at kHz-rates using fs/ps rotational CARS. Femtosecond pump and Stokes pulses impulsively prepare a rotational Raman coherence, which is then probed by a high-energy 6-ps pulse introduced at a time delay from the Raman preparation. Rotational CARS spectra were recorded in N2 contained in a room-temperature gas cell for pressures from 0.1 to 3 atm and probe delays ranging from 10-330 ps. Using published self-broadened collisional linewidth data for N2, both the spectrally integrated coherence decay rate and the spectrally resolved decay were investigated as means for detecting pressure. Shot-averaged and single-laser-shot spectra were interrogated for pressure and the accuracy and precision as a function of probe delay and cell pressure are discussed. Single-shot measurement accuracies were within 0.1 to 6.5% when compared to a transducer values, while the precision was generally between 1% and 6% of measured pressure for probe delays of 200 ps or more, and better than 2% as the delay approached 300 ps. A byproduct of the pressure measurement is an independent but simultaneous measurement of the gas temperature.

  16. Data analysis of a dense GPS network operated during the ESCOMPTE campaign: first results

    NASA Astrophysics Data System (ADS)

    Walpersdorf, A.; Bock, O.; Doerflinger, E.; Masson, F.; van Baelen, J.; Somieski, A.; Bürki, B.

    The experiment GPS/H 2O involving 17 GPS receivers has been operated for two weeks in June 2001 in a dense network around Marseille. This project was integrated into the ESCOMPTE campaign. This paper will focus on the GPS analysis in preparation of the tomographic inversion of GPS slant delays. As first results, GPS tropospheric parameters zenith delays and horizontal gradients have been extracted. For a first visualization of the humidity field overlying the network, zenith delays have been transformed into precipitable water. Successive humidity fields are presented for a period of sudden drop in humidity, indicating some spatial resolution in the small network. The time series of horizontal gradients evaluated at individual sites are compared to correlated zenith delay variations over the whole network (horizontal gradient of zenith delays), showing that in the small size network horizontal atmospheric structure is reflected by both types of parameters. To compare these two quantities, scaling of zenith delays due to different station altitudes was necessary. In this way, a GPS internal validation of the individual gradients by comparison with the horizontal gradient of zenith delays has been established. Differential features along transects across the network indicate a good spatial resolution of tropospheric phenomena, encouraging for the further tomographic exploitation of the data. Moreover, individual and zenith delay gradients weight differently atmospheric horizontal gradients occurring at different heights. This different sensitivity has been used for a first identification of a vertical atmospheric structure from GPS tropospheric delays, by observing an inclined frontal zone crossing the network.

  17. Temporal variations of electron density and temperature in Kr/Ne/H2 photoionized plasma induced by nanosecond pulses from extreme ultraviolet source

    NASA Astrophysics Data System (ADS)

    Saber, I.; Bartnik, A.; Wachulak, P.; Skrzeczanowski, W.; Jarocki, R.; Fiedorowicz, H.

    2017-06-01

    Spectral investigations of low-temperature photoionized plasmas created in a Kr/Ne/H2 gas mixture were performed. The low-temperature plasmas were generated by gas mixture irradiation using extreme ultraviolet pulses from a laser-plasma source. Emission spectra in the ultraviolet/visible range from the photoionized plasmas contained lines that mainly corresponded to neutral atoms and singly charged ions. Temporal variations in the plasma electron temperature and electron density were studied using different characteristic emission lines at various delay times. Results, based on Kr II lines, showed that the electron temperature decreased from 1.7 to 0.9 eV. The electron densities were estimated using different spectral lines at each delay time. In general, except for the Hβ line, in which the electron density decreased from 3.78 × 1016 cm-3 at 200 ns to 5.77 × 1015 cm-3 at 2000 ns, most of the electron density values measured from the different lines were of the order of 1015 cm-3 and decreased slightly while maintaining the same order when the delay time increased. The time dependences of the measured and simulated intensities of a spectral line of interest were also investigated. The validity of the partial or full local thermodynamic equilibrium (LTE) conditions in plasma was explained based on time-resolved electron density measurements. The partial LTE condition was satisfied for delay times in the 200 ns to 1500 ns range. The results are summarized, and the dominant basic atomic processes in the gas mixture photoionized plasma are discussed.

  18. Increased Arf/p53 activity in stem cells, aging and cancer.

    PubMed

    Carrasco-Garcia, Estefania; Moreno, Manuel; Moreno-Cugnon, Leire; Matheu, Ander

    2017-04-01

    Arf/p53 pathway protects the cells against DNA damage induced by acute stress. This characteristic is the responsible for its tumor suppressor activity. Moreover, it regulates the chronic type of stress associated with aging. This is the basis of its anti-aging activity. Indeed, increased gene dosage of Arf/p53 displays elongated longevity and delayed aging. At a cellular level, it has been recently shown that increased dosage of Arf/p53 delays age-associated stem cell exhaustion and the subsequent decline in tissue homeostasis and regeneration. However, p53 can also promote aging if constitutively activated. In this context, p53 reduces tissue regeneration, which correlates with premature exhaustion of stem cells. We discuss here the current evidence linking the Arf/p53 pathway to the processes of aging and cancer through stem cell regulation. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  19. [Effect of inhibitors serine/threonine protein kinases and protein phosphatases on mitosis progression of synchronized tobacco by-2 cells].

    PubMed

    Sheremet, Ia A; Emets, A I; Azmi, A; Vissenberg, K; Verbelen, J-P; Blium, Ia B

    2012-01-01

    In order to investigate the role of various serine/ threonine protein kinases and protein phosphatases in the regulation of mitosis progression in plant cells the influence of cyclin-dependent (olomoucine) and Ca2+ -calmodulin-dependent (W7) protein kinases inhibitors, as well as protein kinase C inhibitors (H7 and staurosporine) and protein phosphatases inhibitor (okadaic acid) on mitosis progression in synchronized tobacco BY-2 cells has been studied. It was found that BY-2 culture treatment with inhibitors of cyclin dependent protein kinases and protein kinase C causes prophase delay, reduces the mitotic index and displaces of mitotic peak as compare with control cells. Inhibition of Ca2+ -calmodulin dependent protein kinases enhances the cell entry into prophase and delays their exit from mitosis. Meanwhile inhibition of serine/threonine protein phosphatases insignificantly enhances of synchronized BY-2 cells entering into all phases of mitosis.

  20. MC1R and cAMP signaling inhibit cdc25B activity and delay cell cycle progression in melanoma cells

    PubMed Central

    Lyons, Jesse; Bastian, Boris C.; McCormick, Frank

    2013-01-01

    The melanocortin 1 receptor (MC1R) mediates the tanning response through induction of cAMP and downstream pigmentary enzymes. Diminished function alleles of MC1R are associated with decreased tanning and increased melanoma risk, which has been attributed to increased rates of mutation. We have found that MC1R or cAMP signaling also directly decreases proliferation in melanoma cell lines. MC1R overexpression, treatment with the MC1R ligand, or treatment with small-molecule activators of cAMP signaling causes delayed progression from G2 into mitosis. This delay is caused by phosphorylation and inhibition of cdc25B, a cyclin dependent kinase 1-activating phosphatase, and is rescued by expression of a cdc25B mutant that cannot be phosphorylated at the serine 323 residue. These results show that MC1R and cAMP signaling can directly inhibit melanoma growth through regulation of the G2/M checkpoint. PMID:23908401

  1. Reduced virus replication, proinflammatory cytokine production, and delayed macrophage cell death in human PBMCs infected with the newly discovered Bundibugyo ebolavirus relative to Zaire ebolavirus.

    PubMed

    Gupta, Manisha; Goldsmith, Cynthia S; Metcalfe, Maureen G; Spiropoulou, Christina F; Spipopoulou, Christina F; Rollin, Pierre E

    2010-06-20

    Bundibugyo ebolavirus is a newly identified Ebolavirus species. The virus was responsible for a recent hemorrhagic fever outbreak in Uganda with an approximate 30% case fatality rate. In this study, we compared the pathogenesis of Bundibugyo with highly lethal Zaire Ebolavirus by using in vitro human PBMCs. We found that PBMCs infected with Bundibugyo ebolaviruses resulted in 1 to 2 log lower virus yields compared to Zaire ebolavirus and produced 2- to 10-fold lower levels of TNF-alpha, MCP-1, IL-1beta, MIP1-alpha and IL-10 than PBMCs infected with Zaire ebolavirus. In addition, flow cytometric studies have shown lower levels and delay of the macrophage cell death in Bundibugyo ebolavirus compared to Zaire ebolavirus infection. The findings of slower Bundibugyo ebolavirus replication, lower production of proinflammatory cytokines and delay in macrophage cell death provide insight into the basis of the lower case fatality observed with Bundibugyo ebolavirus. Published by Elsevier Inc.

  2. Relationships between processing delay and microbial load of broiler neck skin samples.

    PubMed

    Lucianez, A; Holmes, M A; Tucker, A W

    2010-01-01

    The measurable microbial load on poultry carcasses during processing is determined by a number of factors including farm or origin, processing hygiene, and external temperature. This study investigated associations between carcass microbial load and progressive delays to processing. A total of 30 carcasses were delayed immediately after defeathering and before evisceration in a commercial abattoir in groups of five, and were held at ambient temperature for 1, 2, 3, 4, 6, and 8 h. Delayed carcasses were reintroduced to the processing line, and quantitative assessment of total viable count, coliforms, Staphylococcus aureus, and Pseudomonas spp. was undertaken on neck skin flap samples collected after carcass chilling and then pooled for each group. Sampling was repeated on 5 separate days, and the data were combined. Significant increases in total viable count (P = 0.001) and coliforms (P = 0.004), but not for S. aureus or Pseudomonas loads, were observed across the 8-h period of delay. In line with previous studies, there was significant variation in microbiological data according to sampling day. In conclusion, there is a significant and measurable decline in microbiological status of uneviscerated but defeathered poultry carcasses after an 8-h delay, but the variability of sampling results, reflecting the wide range of factors that impact microbial load, means that it is not possible to determine maximum or minimum acceptable periods of processing delay based on this criterion alone.

  3. From single-cell to cell-pool transcriptomes: stochasticity in gene expression and RNA splicing.

    PubMed

    Marinov, Georgi K; Williams, Brian A; McCue, Ken; Schroth, Gary P; Gertz, Jason; Myers, Richard M; Wold, Barbara J

    2014-03-01

    Single-cell RNA-seq mammalian transcriptome studies are at an early stage in uncovering cell-to-cell variation in gene expression, transcript processing and editing, and regulatory module activity. Despite great progress recently, substantial challenges remain, including discriminating biological variation from technical noise. Here we apply the SMART-seq single-cell RNA-seq protocol to study the reference lymphoblastoid cell line GM12878. By using spike-in quantification standards, we estimate the absolute number of RNA molecules per cell for each gene and find significant variation in total mRNA content: between 50,000 and 300,000 transcripts per cell. We directly measure technical stochasticity by a pool/split design and find that there are significant differences in expression between individual cells, over and above technical variation. Specific gene coexpression modules were preferentially expressed in subsets of individual cells, including one enriched for mRNA processing and splicing factors. We assess cell-to-cell variation in alternative splicing and allelic bias and report evidence of significant differences in splice site usage that exceed splice variation in the pool/split comparison. Finally, we show that transcriptomes from small pools of 30-100 cells approach the information content and reproducibility of contemporary RNA-seq from large amounts of input material. Together, our results define an experimental and computational path forward for analyzing gene expression in rare cell types and cell states.

  4. Vγ4 T Cells Inhibit the Pro-healing Functions of Dendritic Epidermal T Cells to Delay Skin Wound Closure Through IL-17A

    PubMed Central

    Li, Yashu; Wang, Yangping; Zhou, Lina; Liu, Meixi; Liang, Guangping; Yan, Rongshuai; Jiang, Yufeng; Hao, Jianlei; Zhang, Xiaorong; Hu, Xiaohong; Huang, Yong; Wang, Rupeng; Yin, Zhinan; Wu, Jun; Luo, Gaoxing; He, Weifeng

    2018-01-01

    Dendritic epidermal T cells (DETCs) and dermal Vγ4 T cells engage in wound re-epithelialization and skin inflammation. However, it remains unknown whether a functional link between Vγ4 T cell pro-inflammation and DETC pro-healing exists to affect the outcome of skin wound closure. Here, we revealed that Vγ4 T cell-derived IL-17A inhibited IGF-1 production by DETCs to delay skin wound healing. Epidermal IL-1β and IL-23 were required for Vγ4 T cells to suppress IGF-1 production by DETCs after skin injury. Moreover, we clarified that IL-1β rather than IL-23 played a more important role in inhibiting IGF-1 production by DETCs in an NF-κB-dependent manner. Together, these findings suggested a mechanistic link between Vγ4 T cell-derived IL-17A, epidermal IL-1β/IL-23, DETC-derived IGF-1, and wound-healing responses in the skin. PMID:29483920

  5. Patterns of Early Skill Attainment and Loss in Young Children with Autism

    PubMed Central

    Thurm, Audrey; Manwaring, Stacy S.; Luckenbaugh, David A.; Lord, Catherine; Swedo, Susan E.

    2015-01-01

    The purpose of this study was to extend the literature on the ontogeny of autism spectrum disorder (ASD) by examining early attainment and loss of specific sociocommunicative skills in children with autism (AUT; n = 125), pervasive developmental disorder not otherwise specified (PDD-NOS; n = 42), nonspectrum developmental delays (n = 46), and typical development (n = 31). The ages of skill attainment and loss were obtained from a caregiver interview. The findings indicated that children with AUT, PDD-NOS, and developmental delays diverged from typically developing children in attainment of sociocommunicative skills early in the first year of life. Loss of at least one skill was reported in a majority of children with AUT and PDD-NOS. Significant delays in attainment of skills were also reported in children who lost skills. The wide variation in skill attainment and loss reported across children indicates that symptom onset and regression may be best represented continuously, with at least some early delay and loss present for a great majority of children with ASD. PMID:24274034

  6. Patterns of skill attainment and loss in young children with autism.

    PubMed

    Thurm, Audrey; Manwaring, Stacy S; Luckenbaugh, David A; Lord, Catherine; Swedo, Susan E

    2014-02-01

    The purpose of this study was to extend the literature on the ontogeny of autism spectrum disorder (ASD) by examining early attainment and loss of specific sociocommunicative skills in children with autism (AUT; n = 125), pervasive developmental disorder not otherwise specified (PDD-NOS; n = 42), nonspectrum developmental delays (n = 46), and typical development (n = 31). The ages of skill attainment and loss were obtained from a caregiver interview. The findings indicated that children with AUT, PDD-NOS, and developmental delays diverged from typically developing children in attainment of sociocommunicative skills early in the first year of life. Loss of at least one skill was reported in a majority of children with AUT and PDD-NOS. Significant delays in attainment of skills were also reported in children who lost skills. The wide variation in skill attainment and loss reported across children indicates that symptom onset and regression may be best represented continuously, with at least some early delay and loss present for a great majority of children with ASD.

  7. [Ischemic Changes in the Electrocardiogram and Circulatory Collapse Accompanied by Severe Anemia Owing to the Delay of Red Blood Cell Concentrate Transfusion in Two Patients with Intraoperative Massive Bleeding].

    PubMed

    Horiuchi, Toshinori; Noguchi, Teruo; Kurita, Naoko; Yamaguchi, Ayako; Takeda, Masafumi; Sha, Keiichi; Nagahata, Toshihiro

    2016-01-01

    We present two patients developing intraoperative massive bleeding and showed ischemic changes in the electrocardiogram and circulatory collapse accompanied by severe anemia owing to the delay of red blood cell concentrate transfusion. One patient underwent hepatectomy and the other pancreaticoduodenectomy. Their lowest hemoglobin concentration was around 2 g x dl(-1), and they showed ischemic changes in the electrocardiogram and severe decreases in blood pressure. The former received compatible red blood cell concentrate and the latter received uncrossmatched same blood group red blood cell concentrate immediately, and their electrocardiogram and blood pressure quickly improved. To avoid life-threatening anemia, emergency red blood cell concentrate transfusion including compatible different blood group transfusion should be applied for intraoperative massive bleeding.

  8. Influence of distributed delays on the dynamics of a generalized immune system cancerous cells interactions model

    NASA Astrophysics Data System (ADS)

    Piotrowska, M. J.; Bodnar, M.

    2018-01-01

    We present a generalisation of the mathematical models describing the interactions between the immune system and tumour cells which takes into account distributed time delays. For the analytical study we do not assume any particular form of the stimulus function describing the immune system reaction to presence of tumour cells but we only postulate its general properties. We analyse basic mathematical properties of the considered model such as existence and uniqueness of the solutions. Next, we discuss the existence of the stationary solutions and analytically investigate their stability depending on the forms of considered probability densities that is: Erlang, triangular and uniform probability densities separated or not from zero. Particular instability results are obtained for a general type of probability densities. Our results are compared with those for the model with discrete delays know from the literature. In addition, for each considered type of probability density, the model is fitted to the experimental data for the mice B-cell lymphoma showing mean square errors at the same comparable level. For estimated sets of parameters we discuss possibility of stabilisation of the tumour dormant steady state. Instability of this steady state results in uncontrolled tumour growth. In order to perform numerical simulation, following the idea of linear chain trick, we derive numerical procedures that allow us to solve systems with considered probability densities using standard algorithm for ordinary differential equations or differential equations with discrete delays.

  9. Contribution of methylglyoxal to delayed healing of bone injury in diabetes.

    PubMed

    Aikawa, Takao; Matsubara, Hidenori; Ugaji, Shuhei; Shirakawa, Junichi; Nagai, Ryoji; Munesue, Seiichi; Harashima, Ai; Yamamoto, Yasuhiko; Tsuchiya, Hiroyuki

    2017-07-01

    Patients with diabetes are vulnerable to delayed bone fracture healing or pseudoarthrosis. Chronic sustained hyperglycemia, reactive intermediate derivatives of glucose metabolism, such as methylglyoxal (MGO), and advanced glycation end‑products (AGEs) are implicated in diabetic complications. In the present study, it was examined whether MGO is able to cause disturbed bone healing in diabetes. Diabetes was induced in male mice by injection of streptozotocin (50 mg/kg) for 5 days. A bone defect (1.0‑mm diameter) was created in the left distal femur, and bone repair was assessed from an examination of computed tomography scans. ST2 cells were exposed to MGO (0‑400 µM) to investigate osteoblastic differentiation, cell viability, and damage. Consequently, blood glucose and hemoglobin A1c levels in diabetic mice were determined to be 493±14.1 mg/dl and 8.0±0.05%, respectively. Compared with non‑diabetic control mice, diabetic mice exhibited markedly delayed bone healing, with increased levels of the MGO‑derived AGEs, Nε‑(carboxymethyl)‑lysine and Nδ‑(5‑hydro‑5‑methyl‑4‑imidazolone‑2‑yl)‑ornithine, in the sera and femurs. MGO inhibited the osteoblastic differentiation of ST2 cells in a dose‑dependent manner, and markedly decreased cell proliferation through cytotoxicity. In conclusion, MGO has been demonstrated to cause impaired osteoblastic differentiation and delayed bone repair in diabetes. Therefore, detoxification of MGO may be a potentially useful strategy against bone problems in patients with diabetes.

  10. Mitochondrial respiratory complex I probed by delayed luminescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Baran, Irina; Ionescu, Diana; Privitera, Simona; Scordino, Agata; Mocanu, Maria Magdalena; Musumeci, Francesco; Grasso, Rosaria; Gulino, Marisa; Iftime, Adrian; Tofolean, Ioana Teodora; Garaiman, Alexandru; Goicea, Alexandru; Irimia, Ruxandra; Dimancea, Alexandru; Ganea, Constanta

    2013-12-01

    The role of mitochondrial complex I in ultraweak photon-induced delayed photon emission [delayed luminescence (DL)] of human leukemia Jurkat T cells was probed by using complex I targeting agents like rotenone, menadione, and quercetin. Rotenone, a complex I-specific inhibitor, dose-dependently increased the mitochondrial level of reduced nicotinamide adenine dinucleotide (NADH), decreased clonogenic survival, and induced apoptosis. A strong correlation was found between the mitochondrial levels of NADH and oxidized flavin mononucleotide (FMNox) in rotenone-, menadione- and quercetin-treated cells. Rotenone enhanced DL dose-dependently, whereas quercetin and menadione inhibited DL as well as NADH or FMNox. Collectively, the data suggest that DL of Jurkat cells originates mainly from mitochondrial complex I, which functions predominantly as a dimer and less frequently as a tetramer. In individual monomers, both pairs of pyridine nucleotide (NADH/reduced nicotinamide adenine dinucleotide phosphate) sites and flavin (FMN-a/FMN-b) sites appear to bind cooperatively their specific ligands. Enhancement of delayed red-light emission by rotenone suggests that the mean time for one-electron reduction of ubiquinone or FMN-a by the terminal Fe/S center (N2) is 20 or 284 μs, respectively. All these findings suggest that DL spectroscopy could be used as a reliable, sensitive, and robust technique to probe electron flow within complex I in situ.

  11. UV-C irradiation delays mitotic progression by recruiting Mps1 to kinetochores

    PubMed Central

    Zhang, Xiaojuan; Ling, Youguo; Wang, Wenjun; Zhang, Yanhong; Ma, Qingjun; Tan, Pingping; Song, Ting; Wei, Congwen; Li, Ping; Liu, Xuedong; Ma, Runlin Z.; Zhong, Hui; Cao, Cheng; Xu, Quanbin

    2013-01-01

    The effect of UV irradiation on replicating cells during interphase has been studied extensively. However, how the mitotic cell responds to UV irradiation is less well defined. Herein, we found that UV-C irradiation (254 nm) increases recruitment of the spindle checkpoint proteins Mps1 and Mad2 to the kinetochore during metaphase, suggesting that the spindle assembly checkpoint (SAC) is reactivated. In accordance with this, cells exposed to UV-C showed delayed mitotic progression, characterized by a prolonged chromosomal alignment during metaphase. UV-C irradiation also induced the DNA damage response and caused a significant accumulation of γ-H2AX on mitotic chromosomes. Unexpectedly, the mitotic delay upon UV-C irradiation is not due to the DNA damage response but to the relocation of Mps1 to the kinetochore. Further, we found that UV-C irradiation activates Aurora B kinase. Importantly, the kinase activity of Aurora B is indispensable for full recruitment of Mps1 to the kinetochore during both prometaphase and metaphase. Taking these findings together, we propose that UV irradiation delays mitotic progression by evoking the Aurora B-Mps1 signaling cascade, which exerts its role through promoting the association of Mps1 with the kinetochore in metaphase. PMID:23531678

  12. Delayed Dermal Hypersensitivity in Mice to Spherule and Mycelial Extracts of Coccidioides immitis

    PubMed Central

    Kong, Yi-Chi M.; Savage, D. C.; Kong, Leighton N. L.

    1966-01-01

    Kong, Yi-chi M. (University of California, Berkeley), D. C. Savage, and Leighton N. L. Kong. Delayed dermal hypersensitivity in mice to spherule and mycelial extracts of Coccidioides immitis. J. Bacteriol. 91:876–883. 1966.—A delayed hypersensitivity reaction to spherule and mycelial extracts of Coccidioides immitis was elicited in the footpads of mice vaccinated with killed spherules. Emulsification of the spherules with Freund's adjuvants was unnecessary, but a high concentration of antigen was required to elicit the reaction. Injection of the extracts produced, initially, a swelling which subsided within 4 hr, and then induration, which began at 6 to 8 hr and reached a maximum at 24 hr. The time course of the reaction corresponded to that of the tuberculin reaction in BCG-vaccinated mice. The histological response to coccidioidal extracts was characterized by the early infiltration of both polymorphonuclear and mononuclear cells, and the subsequent predominance of mononuclear cells at 24 to 48 hr. By 72 hr, the mononuclear cells comprised >90% of the cellular infiltrate. Animals infected intranasally with arthrospores (1 to 5 ld50) reacted negatively before and during the crisis period; thereafter (by 28 to 31 days after infection), up to 50% of the survivors showed a delayed reaction. Images PMID:5894227

  13. Mesoporous silica nanoparticle-based substrates for cell directed delivery of Notch signalling modulators to control myoblast differentiation

    NASA Astrophysics Data System (ADS)

    Böcking, Dominique; Wiltschka, Oliver; Niinimäki, Jenni; Shokry, Hussein; Brenner, Rolf; Lindén, Mika; Sahlgren, Cecilia

    2014-01-01

    Biochemical cues are critical to control stem cell function and can be utilized to develop smart biomaterials for stem cell engineering. The challenge is to deliver these cues in a restricted manner with spatial and temporal control. Here we have developed bilayer films of mesoporous silica nanoparticles for delayed cellular delivery of Notch modulators to promote muscle stem cell differentiation. We demonstrate that drug-loaded particles are internalized from the particle-covered surface, which allows for direct delivery of the drug into the cell and a delayed and confined drug release. Substrates of particles loaded with γ-secretase-inhibitors, which block the Notch signalling pathway, promoted efficient differentiation of myoblasts. The particle substrates were fully biocompatible and did not interfere with the inherent differentiation process. We further demonstrate that impregnating commercially available, biocompatible polymer scaffolds with MSNs allows for a free standing substrate for cell directed drug delivery.Biochemical cues are critical to control stem cell function and can be utilized to develop smart biomaterials for stem cell engineering. The challenge is to deliver these cues in a restricted manner with spatial and temporal control. Here we have developed bilayer films of mesoporous silica nanoparticles for delayed cellular delivery of Notch modulators to promote muscle stem cell differentiation. We demonstrate that drug-loaded particles are internalized from the particle-covered surface, which allows for direct delivery of the drug into the cell and a delayed and confined drug release. Substrates of particles loaded with γ-secretase-inhibitors, which block the Notch signalling pathway, promoted efficient differentiation of myoblasts. The particle substrates were fully biocompatible and did not interfere with the inherent differentiation process. We further demonstrate that impregnating commercially available, biocompatible polymer scaffolds with MSNs allows for a free standing substrate for cell directed drug delivery. Electronic supplementary information (ESI) available: (1) Particle characterization. (2) Immunohistochemistry and SEM analyses of C2C12 cells grown on films for 3, 6, 24 and 72 h. Light microscopy and WST1 analyses of cells grown on cover slips and films for 6, 24 and 72 h (3) Quantification of protein levels of C2C12 cells differentiating on cover slips versus MSN films. (4) Stability of MSN films in biological solution and the influence on cell viability. (5) Cell internalization of particles from MSN films and intracellular drug release at 12 and 24 h (6) Cell internalization and intracellular DiI release of MSNs from (3Dtro®) fiber scaffolds impregnated with MSNs. See DOI: 10.1039/c3nr04022d

  14. Orientation-specific responses to sustained uniaxial stretching in focal adhesion growth and turnover

    PubMed Central

    Chen, Yun; Pasapera, Ana M.; Koretsky, Alan P.; Waterman, Clare M.

    2013-01-01

    Cells are mechanosensitive to extracellular matrix (ECM) deformation, which can be caused by muscle contraction or changes in hydrostatic pressure. Focal adhesions (FAs) mediate the linkage between the cell and the ECM and initiate mechanically stimulated signaling events. We developed a stretching apparatus in which cells grown on fibronectin-coated elastic substrates can be stretched and imaged live to study how FAs dynamically respond to ECM deformation. Human bone osteosarcoma epithelial cell line U2OS was transfected with GFP-paxillin as an FA marker and subjected to sustained uniaxial stretching. Two responses at different timescales were observed: rapid FA growth within seconds after stretching, and delayed FA disassembly and loss of cell polarity that occurred over tens of minutes. Rapid FA growth occurred in all cells; however, delayed responses to stretch occurred in an orientation-specific manner, specifically in cells with their long axes perpendicular to the stretching direction, but not in cells with their long axes parallel to stretch. Pharmacological treatments demonstrated that FA kinase (FAK) promotes but Src inhibits rapid FA growth, whereas FAK, Src, and calpain 2 all contribute to delayed FA disassembly and loss of polarity in cells perpendicular to stretching. Immunostaining for phospho-FAK after stretching revealed that FAK activation was maximal at 5 s after stretching, specifically in FAs oriented perpendicular to stretch. We hypothesize that orientation-specific activation of strain/stress-sensitive proteins in FAs upstream to FAK and Src promote orientation-specific responses in FA growth and disassembly that mediate polarity rearrangement in response to sustained stretch. PMID:23754369

  15. Further characterization of the circulating cell in chronic lymphocytic leukemia

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

    Schutz, E.F.; Davis, S.; Rubin, A.D.

    Peripheral lymphocytes from normal individuals and from patients with chronic lymphocytic leukemia (CLL) were cultured in vitro for 1-7 days. The growth response to phytohemagglutinin (PHA) was quantitated by the incorporation of tritiated uridine into RNA nucleotide during a 2-hr pulse with the radioisotope. While the maximum response in PHA-stimulated normal cultures appeared at 2-3 days, CLL cultures required 5-7 days to develop their maximal response, which was 50 percent-60 percent of the normal magnitude. Dilution of the number of normally reactive lymphocytes by culturing them with totally unreactive, mitomycin-treated cells produced a normal 72-hr maximal response, no matter whatmore » proportion of unreactive cells was included in the PHA-stimulated cultures. In addition, the response of peripheral lymphocytes from patients with myeloblastic leukemia, where large numbers of unreactive myeloblasts diluted the normal small lymphocytes, a depressed reaction occurred at the anticipated 2-3 days. Nylon fiber-adherent lymphocytes consisting of 85 percent immunoglobulin (Ig)-bearing cells responded minimally to PHA, but showed no evidence of a delay. When isolated from CLL patients, both fiber-adherent cells (ig-bearing) as well as non-fiber-adherent (sheep erythrocyte-rosetting) cells responded to PHA in a delayed fashion. Similarly, a case of CLL, in which 93.5 percent of the circulating lymphocytes bore sheep red blood cell receptors, showed its peak response to PHA at 7 days. Therefore, using surface marker criteria considered characteristic of normal T cells and B cells, the delayed response to PHA on the part of CLL lymphocytes was independent of thymic or nonthymic origin.« less

  16. Understanding neural system dynamics through task modulation and measurement of functional MRI amplitude, latency, and width

    PubMed Central

    Bellgowan, P. S. F.; Saad, Z. S.; Bandettini, P. A.

    2003-01-01

    Estimates of hemodynamic amplitude, delay, and width were combined to investigate system dynamics involved in lexical decision making. Subjects performed a lexical decision task using word and nonword stimuli rotated 0°, 60°, or 120°. Averaged hemodynamic responses to repeated stimulation were fit to a Gamma-variate function convolved with a heavyside function of varying onset and duration to estimate each voxel's activation delay and width. Consistent with prolonged reaction times for the rotated stimuli and nonwords, the motor cortex showed delayed hemodynamic onset for both conditions. Language areas such as the lingual gyrus, middle temporal gyrus, fusiform gyrus, and precuneus all showed delayed hemodynamic onsets to rotated stimuli but not to nonword stimuli. The inferior frontal gyrus showed both increased onset latency for rotated stimuli and a wider hemodynamic response to nonwords, consistent with prolonged processing in this area during the lexical decision task. Phonological processing areas such as superior temporal and angular gyrus showed no delay or width difference for rotated stimuli. These results suggest that phonological routes but not semantic routes to the lexicon can proceed regardless of stimulus orientation. This study demonstrates the utility of estimating hemodynamic delay and width in addition to amplitude allowing for more quantitative measures of brain function such as mental chronometry. PMID:12552093

  17. Preventing delayed diagnosis of cancer: clinicians’ views on main problems and solutions

    PubMed Central

    Car, Lorainne Tudor; Papachristou, Nikolaos; Urch, Catherine; Majeed, Azeem; El–Khatib, Mona; Aylin, Paul; Atun, Rifat; Car, Josip; Vincent, Charles

    2016-01-01

    Background Delayed diagnosis is a major contributing factor to the UK’s lower cancer survival compared to many European countries. In the UK, there is a significant national variation in early cancer diagnosis. Healthcare providers can offer an insight into local priorities for timely cancer diagnosis. In this study, we aimed to identify the main problems and solutions relating to delay cancer diagnosis according to cancer care clinicians. Methods We developed and implemented a new priority–setting approach called PRIORITIZE and invited North West London cancer care clinicians to identify and prioritize main causes for and solutions to delayed diagnosis of cancer care. Results Clinicians identified a number of concrete problems and solutions relating to delayed diagnosis of cancer. Raising public awareness, patient education as well as better access to specialist care and diagnostic testing were seen as the highest priorities. The identified suggestions focused mostly on the delays during referrals from primary to secondary care. Conclusions Many identified priorities were feasible, affordable and converged around common themes such as public awareness, care continuity and length of consultation. As a timely, proactive and scalable priority–setting approach, PRIORITZE could be implemented as a routine preventative system for determining patient safety issues by frontline staff. PMID:28028437

  18. Obtaining reliable phase-gradient delays from otoacoustic emission data.

    PubMed

    Shera, Christopher A; Bergevin, Christopher

    2012-08-01

    Reflection-source otoacoustic emission phase-gradient delays are widely used to obtain noninvasive estimates of cochlear function and properties, such as the sharpness of mechanical tuning and its variation along the length of the cochlear partition. Although different data-processing strategies are known to yield different delay estimates and trends, their relative reliability has not been established. This paper uses in silico experiments to evaluate six methods for extracting delay trends from reflection-source otoacoustic emissions (OAEs). The six methods include both previously published procedures (e.g., phase smoothing, energy-weighting, data exclusion based on signal-to-noise ratio) and novel strategies (e.g., peak-picking, all-pass factorization). Although some of the methods perform well (e.g., peak-picking), others introduce substantial bias (e.g., phase smoothing) and are not recommended. In addition, since standing waves caused by multiple internal reflection can complicate the interpretation and compromise the application of OAE delays, this paper develops and evaluates two promising signal-processing strategies, the first based on time-frequency filtering using the continuous wavelet transform and the second on cepstral analysis, for separating the direct emission from its subsequent reflections. Altogether, the results help to resolve previous disagreements about the frequency dependence of human OAE delays and the sharpness of cochlear tuning while providing useful analysis methods for future studies.

  19. Fibrin glue inhibits migration of ocular surface epithelial cells

    PubMed Central

    Yeung, A M; Faraj, L A; McIntosh, O D; Dhillon, V K; Dua, H S

    2016-01-01

    Purpose Fibrin glue has been used successfully in numerous ophthalmic surgical procedures. Recently, fibrin glue has been used in limbal stem cell transplantation to reduce both operative time and to negate the need for sutures. The aim of this study was to determine the effects of fibrin glue on epithelial cell migration in vitro. Methods Corneoscleral rims were split to retain the epithelial layer, Bowman's layer, and anterior stroma. Rims were cut into eight equal-sized pieces and were placed directly on culture plates or affixed with fibrin glue. Rims were maintained in culture for 25 days and epithelial cell growth was monitored. Cells were photographed to measure area or growth and immunofluorescence staining of explants for fibrin was performed. Results Explants that were glued demonstrated significantly delayed epithelial cell growth and migration as compared with explants without glue. By day 16, all fibrin glue had dissolved and coincided with onset of cell growth from glued explants. Cell growth commenced between days 3 and 4 for control explants without glue and around days 14–16 for explants with fibrin glue. Conclusions Fibrin glue delays epithelial cell migration by acting as a physical barrier and can potentially interfere with explant-derived limbal epithelial cell migration on to the corneal surface. We propose that glue should be used to attach the conjunctival frill of the limbal explant but care should be taken to ensure that the glue does not wrap around the explant if used to secure the explant as well. Strategic use of glue, to attach the recessed conjunctiva, can be advantageous in delaying conjunctival cell migration and reducing the need for sequential sector conjunctival epitheliectomy. PMID:27367746

  20. Stochastic resonance in a tumor-immune system subject to bounded noises and time delay

    NASA Astrophysics Data System (ADS)

    Guo, Wei; Mei, Dong-Cheng

    2014-12-01

    Immunotherapy is one of the most recent approaches in cancer therapy. A mathematical model of tumor-immune interaction, subject to a periodic immunotherapy treatment (imitated by a periodic signal), correlative and bounded stochastic fluctuations and time delays, is investigated by numerical simulations for its signal power amplification (SPA). Within the tailored parameter regime, the synchronous response of tumor growth to the immunotherapy, stochastic resonance (SR), versus both the noises and delays is obtained. The details are as follows (i) the peak values of SPA versus the noise intensity (A) in the proliferation term of tumor cells decrease as the frequency of periodic signal increases, i.e. an increase of the frequency restrains the SR; (ii) an increase of the amplitude of periodic signal restrains the SR versus A, but boosts up the SR versus the noise intensity B in the immune term; (iii) there is an optimum cross-correlated degree between the two bounded noises, at which the system exhibits the strongest SR versus the delay time τα(the reaction time of tumor cell population to their surrounding environment constraints); (iv) upon increasing the delay time τα, double SR versus the delay time τβ (the time taken by both the tumor antigen identification and tumor-stimulated proliferation of effectors) emerges. These results may be helpful for an immunotherapy treatment for the sufferer.

  1. Lithium delays the radiation-induced apoptotic process in external granule cells of mouse cerebellum.

    PubMed

    Inouye, M; Yamamura, H; Nakano, A

    1995-09-01

    Proliferating cells of the external granular layer (EGL) in the developing cerebellum are highly sensitive to ionizing radiation. We examined the effect of lithium, an inhibitor of intracellular signaling, on the manifestation of radiation-induced apoptosis. Newborn mice were exposed to 0.5 Gy gamma-irradiation alone, or first were treated with lithium (10 mumol/g, SC) then given 0.5 Gy irradiation 2 hr later. The EGL was examined histologically for apoptosis at various times after treatment. Apoptotic cells increased rapidly, peaked (about 14%) 6 hr after irradiation, then decreased gradually to the control level by 24 hr. Prior treatment with lithium delayed the manifestation of apoptosis, the peak appearing at 12 hr. The disappearance of dead cells was delayed for about one day. The lithium concentration in the whole brain increased rapidly, being 30 micrograms/g at the time of irradiation and remaining at more than 40 micrograms/g for 40 hr. Lithium is reported to inhibit guanine-nucleotide binding to G proteins as well as phosphoinositide turnover. Of the variety of lesions induced by radiation, DNA double strand breaks are the most important source of cell lethality. The present findings, however, suggest that cyclic AMP-mediated and/or phosphoinositidemediated signaling systems regulate radiation-induced apoptosis.

  2. Automated and manual patch clamp data of human induced pluripotent stem cell-derived dopaminergic neurons.

    PubMed

    Franz, Denise; Olsen, Hervør Lykke; Klink, Oliver; Gimsa, Jan

    2017-04-25

    Human induced pluripotent stem cells can be differentiated into dopaminergic neurons (Dopa.4U). Dopa.4U neurons expressed voltage-gated Na V and K V channels and showed neuron-like spontaneous electrical activity. In automated patch clamp measurements with suspended Dopa.4U neurons, delayed rectifier K + current (delayed K V ) and rapidly inactivating A-type K + current (fast K V ) were identified. Examination of the fast K V current with inhibitors yielded IC 50 values of 0.4 mM (4-aminopyridine) and 0.1 mM (tetraethylammonium). In manual patch clamp measurements with adherent Dopa.4U neurons, fast K V current could not be detected, while the delayed K V current showed an IC 50 of 2 mM for 4-aminopyridine. The Na V channels in adherent and suspended Dopa.4U neurons showed IC 50 values for tetrodotoxin of 27 and 2.9 nM, respectively. GABA-induced currents that could be observed in adherent Dopa.4U neurons could not be detected in suspended cells. Application of current pulses induced action potentials in approx. 70 % of the cells. Our results proved the feasibility of automated electrophysiological characterization of neuronal cells.

  3. An efficient hybrid method for stochastic reaction-diffusion biochemical systems with delay

    NASA Astrophysics Data System (ADS)

    Sayyidmousavi, Alireza; Ilie, Silvana

    2017-12-01

    Many chemical reactions, such as gene transcription and translation in living cells, need a certain time to finish once they are initiated. Simulating stochastic models of reaction-diffusion systems with delay can be computationally expensive. In the present paper, a novel hybrid algorithm is proposed to accelerate the stochastic simulation of delayed reaction-diffusion systems. The delayed reactions may be of consuming or non-consuming delay type. The algorithm is designed for moderately stiff systems in which the events can be partitioned into slow and fast subsets according to their propensities. The proposed algorithm is applied to three benchmark problems and the results are compared with those of the delayed Inhomogeneous Stochastic Simulation Algorithm. The numerical results show that the new hybrid algorithm achieves considerable speed-up in the run time and very good accuracy.

  4. A Novel Double Subculture Method and Its Theory for the Enumeration of Injured Cells in Stressed Microbial Population.

    PubMed

    Tsuchido, Tetsuaki

    2017-01-01

    　A novel double subculture method, termed DiVSaL (Differential Viabilities between Solid and Liquid media) method, for the enumeration of injured cell population of a microorganism, which occurs after some sublethal to lethal treatment, was proposed. In this method injured cells were enumerated as the differential value between viabilities determined with two different techniques, the conventional plate counting using a solid agar medium and the growth delay analysis using a liquid medium. In the former technique, the viable cell number is obtained as colony forming unit (CFU) formed on an agar medium where sublethally injured cells are as much rescued as possible. In the latter technique, on the other hand," the integrated viability" defined by Takano and Tsuchido (1982) is introduced and is calculated from the growth delay of a stressed population, referred to unstressed one. For the growth delay analysis, in this paper, not only the original theoretical model, where the specific growth rate (and therefore the defined G 10 value) does not change after the exposure to a stress treatment, but also a novel modified theory, where the parameter changes, is proposed. On the theoretical background, this DiVSaL method as a double subculture method can be used to enumerate the injured cells without selection by addition of some inhibitor or by nutritional shortage.

  5. Tumor-environment biomimetics delay peritoneal metastasis formation by deceiving and redirecting disseminated cancer cells.

    PubMed

    De Vlieghere, Elly; Gremonprez, Félix; Verset, Laurine; Mariën, Lore; Jones, Christopher J; De Craene, Bram; Berx, Geert; Descamps, Benedicte; Vanhove, Christian; Remon, Jean-Paul; Ceelen, Wim; Demetter, Pieter; Bracke, Marc; De Geest, Bruno G; De Wever, Olivier

    2015-06-01

    Peritoneal metastasis is life threatening and is the result of an extensive communication between disseminated cancer cells, mesothelial cells and cancer-associated fibroblasts (CAF). CAFs secrete extracellular matrix (ECM) proteins creating a receptive environment for peritoneal implantation. Considering cancer as an ecosystem may provide opportunities to exploit CAFs to create biomimetic traps to deceive and redirect cancer cells. We have designed microparticles (MP) containing a CAF-derived ECM-surface that is intended to compete with natural niches. CAFs were encapsulated in alginate/gelatine beads (500-750 μm in diameter) functionalised with a polyelectrolyte coating (MP[CAF]). The encapsulated CAFs remain viable and metabolically active (≥35 days), when permanently encapsulated. CAF-derived ECM proteins are retained by the non-biodegradable coating. Adhesion experiments mimicking the environment of the peritoneal cavity show the selective capture of floating cancer cells from different tumor origins by MP[CAF] compared to control MP. MP[CAF] are distributed throughout the abdominal cavity without attachment to intestinal organs and without signs of inflammatory reaction. Intraperitoneal delivery of MP[CAF] and sequential removal redirects cancer cell adhesion from the surgical wound to the MP[CAF], delays peritoneal metastasis formation and prolongs animal survival. Our experiments suggest the use of a biomimetic trap based on tumor-environment interactions to delay peritoneal metastasis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. The combination of Hsp90 inhibitor 17AAG and heavy-ion irradiation provides effective tumor control in human lung cancer cells.

    PubMed

    Hirakawa, Hirokazu; Fujisawa, Hiroshi; Masaoka, Aya; Noguchi, Miho; Hirayama, Ryoichi; Takahashi, Momoko; Fujimori, Akira; Okayasu, Ryuichi

    2015-03-01

    Hsp90 inhibitors have become well-studied antitumor agents for their selective property against tumors versus normal cells. The combined treatment of Hsp90 inhibitor and conventional photon radiation also showed more effective tumor growth delay than radiation alone. However, little is known regarding the combined treatment of Hsp90 inhibitor and heavy-ion irradiation. In this study, SQ5 human lung tumor cells were used in vitro for clonogenic cell survival and in vivo for tumor growth delay measurement using a mouse xenograft model after 17-allylamino-17-demethoxygeldanamycin (17AAG) pretreatment and carbon ion irradiation. Repair of DNA double strand breaks (DSBs) was also assessed along with expressions of DSB repair-related proteins. Cell cycle analysis after the combined treatment was also performed. The combined treatment of 17AAG and carbon ions revealed a promising treatment option in both in vitro and in vivo studies. One likely cause of this effectiveness was shown to be the inhibition of homologous recombination repair by 17AAG. The more intensified G2 cell cycle delay was also associated with the combined treatment when compared with carbon ion treatment alone. Our findings indicate that the combination of Hsp90 inhibition and heavy-ion irradiation provides a new effective therapeutic alternative for treatment of solid tumors. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  7. Caloric restriction delays yeast chronological aging by remodeling carbohydrate and lipid metabolism, altering peroxisomal and mitochondrial functionalities, and postponing the onsets of apoptotic and liponecrotic modes of regulated cell death

    PubMed Central

    Arlia-Ciommo, Anthony; Leonov, Anna; Beach, Adam; Richard, Vincent R.; Bourque, Simon D.; Burstein, Michelle T.; Kyryakov, Pavlo; Gomez-Perez, Alejandra; Koupaki, Olivia; Feldman, Rachel; Titorenko, Vladimir I.

    2018-01-01

    A dietary regimen of caloric restriction delays aging in evolutionarily distant eukaryotes, including the budding yeast Saccharomyces cerevisiae. Here, we assessed how caloric restriction influences morphological, biochemical and cell biological properties of chronologically aging yeast advancing through different stages of the aging process. Our findings revealed that this low-calorie diet slows yeast chronological aging by mechanisms that coordinate the spatiotemporal dynamics of various cellular processes before entry into a non-proliferative state and after such entry. Caloric restriction causes a stepwise establishment of an aging-delaying cellular pattern by tuning a network that assimilates the following: 1) pathways of carbohydrate and lipid metabolism; 2) communications between the endoplasmic reticulum, lipid droplets, peroxisomes, mitochondria and the cytosol; and 3) a balance between the processes of mitochondrial fusion and fission. Through different phases of the aging process, the caloric restriction-dependent remodeling of this intricate network 1) postpones the age-related onsets of apoptotic and liponecrotic modes of regulated cell death; and 2) actively increases the chance of cell survival by supporting the maintenance of cellular proteostasis. Because caloric restriction decreases the risk of cell death and actively increases the chance of cell survival throughout chronological lifespan, this dietary intervention extends longevity of chronologically aging yeast. PMID:29662634

  8. A modelling tool for capacity planning in acute and community stroke services.

    PubMed

    Monks, Thomas; Worthington, David; Allen, Michael; Pitt, Martin; Stein, Ken; James, Martin A

    2016-09-29

    Mathematical capacity planning methods that can take account of variations in patient complexity, admission rates and delayed discharges have long been available, but their implementation in complex pathways such as stroke care remains limited. Instead simple average based estimates are commonplace. These methods often substantially underestimate capacity requirements. We analyse the capacity requirements for acute and community stroke services in a pathway with over 630 admissions per year. We sought to identify current capacity bottlenecks affecting patient flow, future capacity requirements in the presence of increased admissions, the impact of co-location and pooling of the acute and rehabilitation units and the impact of patient subgroups on capacity requirements. We contrast these results to the often used method of planning by average occupancy, often with arbitrary uplifts to cater for variability. We developed a discrete-event simulation model using aggregate parameter values derived from routine administrative data on over 2000 anonymised admission and discharge timestamps. The model mimicked the flow of stroke, high risk TIA and complex neurological patients from admission to an acute ward through to community rehab and early supported discharge, and predicted the probability of admission delays. An increase from 10 to 14 acute beds reduces the number of patients experiencing a delay to the acute stroke unit from 1 in every 7 to 1 in 50. Co-location of the acute and rehabilitation units and pooling eight beds out of a total bed stock of 26 reduce the number of delayed acute admissions to 1 in every 29 and the number of delayed rehabilitation admissions to 1 in every 20. Planning by average occupancy would resulted in delays for one in every five patients in the acute stroke unit. Planning by average occupancy fails to provide appropriate reserve capacity to manage the variations seen in stroke pathways to desired service levels. An appropriate uplift from the average cannot be based simply on occupancy figures. Our method draws on long available, intuitive, but underused mathematical techniques for capacity planning. Implementation via simulation at our study hospital provided valuable decision support for planners to assess future bed numbers and organisation of the acute and rehabilitation services.

  9. Prolactin modulates luteal activity in the short-nosed fruit bat, Cynopterus sphinx during delayed embryonic development.

    PubMed

    Anuradha; Krishna, Amitabh

    2017-07-01

    The aim of this study was to evaluate the role of prolactin as a modulator of luteal steroidogenesis during the period of delayed embryonic development in Cynopterus sphinx. A marked decline in circulating prolactin levels was noted during the months of November through December coinciding with the period of decreased serum progesterone and delayed embryonic development. The seasonal changes in serum prolactin levels correlated positively with circulating progesterone (P) level, but inversely with circulating melatonin level during first pregnancy showing delayed development in Cynopterus sphinx. The results also showed decreased expression of prolactin receptor-short form (PRL-RS) both in the corpus luteum and in the utero-embryonic unit during the period of delayed embryonic development. Bats treated in vivo with prolactin during the period of delayed development showed significant increase in serum progesterone and estradiol levels together with significant increase in the expression of PRL-RS, luteinizing hormone receptor (LH-R), steroidogenic acute receptor protein (STAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD) in the ovary. Prolactin stimulated ovarian angiogenesis (vascular endothelial growth factor) and cell survival (B-cell lymphoma 2) in vivo. Significant increases in ovarian progesterone production and the expression of prolactin-receptor, LH-R, STAR and 3β-HSD proteins were noted following the exposure of LH or prolactin in vitro during the delayed period. In conclusion, short-day associated increased melatonin level may be responsible for decreased prolactin release during November-December. The decline in prolactin level might play a role in suppressing P and estradiol-17β (E2) estradiol levels thereby causing delayed embryonic development in C. sphinx. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Generation of optimum vertical profiles for an advanced flight management system

    NASA Technical Reports Server (NTRS)

    Sorensen, J. A.; Waters, M. H.

    1981-01-01

    Algorithms for generating minimum fuel or minimum cost vertical profiles are derived and examined. The option for fixing the time of flight is included in the concepts developed. These algorithms form the basis for the design of an advanced on-board flight management system. The variations in the optimum vertical profiles (resulting from these concepts) due to variations in wind, takeoff mass, and range-to-destination are presented. Fuel savings due to optimum climb, free cruise altitude, and absorbing delays enroute are examined.

  11. Tolerable hearing-aid delays: IV. effects on subjective disturbance during speech production by hearing-impaired subjects.

    PubMed

    Stone, Michael A; Moore, Brian C J

    2005-04-01

    We assessed the effects of time delay in a hearing aid on subjective disturbance and reading rates while the user of the aid was speaking, using hearing-impaired subjects and real-time processing. The time delay was constant across frequency. A digital signal processor was programmed as a four-channel, fast-acting, wide-dynamic-range compression hearing aid. One of four delays could be selected on the aid to produce a total delay of 13, 21, 30, or 40 msec between microphone and receiver. Twenty-five subjects, mostly with near-symmetric hearing impairment of cochlear origin, were fitted bilaterally with behind-the-ear aids connected to the processor. The aids were programmed with insertion gains prescribed by the CAMEQ loudness equalization procedure for each subject and ear. Subjects were asked to read aloud from scripts: speech production rates were measured and subjective ratings of the disturbance of the delay were obtained. Subjects required some training to recognize the effects of the delay to rate it consistently. Subjective disturbance increased progressively with increasing delay and was a nonmonotonic function of low-frequency hearing loss. Subjects with mild or severe low-frequency hearing loss were generally less disturbed by the delay than those with moderate loss. Disturbance ratings tended to decrease over successive tests. Word production rates were not significantly affected by delay over the range of delays tested. The results follow a pattern similar to those presented in , obtained using a simulation of hearing loss and normally hearing subjects, except for the nonmonotonic variation of disturbance with low-frequency hearing loss. We hypothesize that disturbance is maximal when the levels in the ear canal of the low-frequency components are similar for the unaided and aided sounds. A rating of 3, which is probably just acceptable, was obtained for delays ranging from 14 to 30 msec, depending on the hearing loss. Some acclimatization to the subjective disturbance occurred over a time scale of about 1 hour.

  12. Delayed luminescence to monitor programmed cell death induced by berberine on thyroid cancer cells

    NASA Astrophysics Data System (ADS)

    Scordino, Agata; Campisi, Agata; Grasso, Rosaria; Bonfanti, Roberta; Gulino, Marisa; Iauk, Liliana; Parenti, Rosalba; Musumeci, Francesco

    2014-11-01

    Correlation between apoptosis and UVA-induced ultraweak photon emission delayed luminescence (DL) from tumor thyroid cell lines was investigated. In particular, the effects of berberine, an alkaloid that has been reported to have anticancer activities, on two cancer cell lines were studied. The FTC-133 and 8305C cell lines, as representative of follicular and anaplastic thyroid human cancer, respectively, were chosen. The results show that berberine is able to arrest cell cycle and activate apoptotic pathway as shown in both cell lines by deoxyribonucleic acid fragmentation, caspase-3 cleavage, p53 and p27 protein overexpression. In parallel, changes in DL spectral components after berberine treatment support the hypothesis that DL from human cells originates mainly from mitochondria, since berberine acts especially at the mitochondrial level. The decrease of DL blue component for both cell lines could be related to the decrease of intra-mitochondrial nicotinamide adenine dinucleotide and may be a hallmark of induced apoptosis. In contrast, the response in the red spectral range is different for the two cell lines and may be ascribed to a different iron homeostasis.

  13. Performance characteristics of lithium primary cells after controlled storage. [on-orbit for energy power supply

    NASA Technical Reports Server (NTRS)

    Deligiannis, F.; Shen, D. H.; Halpert, G.; Ang, V.; Donley, S.

    1991-01-01

    A program was initiated to investigate the effects of storage on the performance of lithium primary cells. Two types of liquid cathode cells were chosen to investigate these effects. The cell types included Li-SOCl2/BCX cells, Li-SO2 cells from two different manufacturers, and a small sample size of 8-year-old Li-SO2 cells. The following measurements are performed at each test interval: open circuit voltage, resistance and weight, microcalorimetry, ac impedance, capacity, and voltage delay. The authors examine the performance characteristics of these cells after one year of controlled storage at two temperatures (10 and 30 C). The Li-SO2 cells experienced little to no voltage and capacity degradation after one year storage. The Li-SOCl2/BCX cells exhibited significant voltage and capacity degradation after 30 C storage. Predischarging shortly prior to use appears to be an effective method of reducing the initial voltage drop. Studies are in progress to correlate ac impedance and microcalorimetry measurements with capacity losses and voltage delay.

  14. Systematic Analysis of Cell Cycle Effects of Common Drugs Leads to the Discovery of a Suppressive Interaction between Gemfibrozil and Fluoxetine

    PubMed Central

    Hoose, Scott A.; Duran, Camille; Malik, Indranil; Eslamfam, Shabnam; Shasserre, Samantha C.; Downing, S. Sabina; Hoover, Evelyn M.; Dowd, Katherine E.; Smith, Roger; Polymenis, Michael

    2012-01-01

    Screening chemical libraries to identify compounds that affect overall cell proliferation is common. However, in most cases, it is not known whether the compounds tested alter the timing of particular cell cycle transitions. Here, we evaluated an FDA-approved drug library to identify pharmaceuticals that alter cell cycle progression in yeast, using DNA content measurements by flow cytometry. This approach revealed strong cell cycle effects of several commonly used pharmaceuticals. We show that the antilipemic gemfibrozil delays initiation of DNA replication, while cells treated with the antidepressant fluoxetine severely delay progression through mitosis. Based on their effects on cell cycle progression, we also examined cell proliferation in the presence of both compounds. We discovered a strong suppressive interaction between gemfibrozil and fluoxetine. Combinations of interest among diverse pharmaceuticals are difficult to identify, due to the daunting number of possible combinations that must be evaluated. The novel interaction between gemfibrozil and fluoxetine suggests that identifying and combining drugs that show cell cycle effects might streamline identification of drug combinations with a pronounced impact on cell proliferation. PMID:22567160

  15. Systematic analysis of cell cycle effects of common drugs leads to the discovery of a suppressive interaction between gemfibrozil and fluoxetine.

    PubMed

    Hoose, Scott A; Duran, Camille; Malik, Indranil; Eslamfam, Shabnam; Shasserre, Samantha C; Downing, S Sabina; Hoover, Evelyn M; Dowd, Katherine E; Smith, Roger; Polymenis, Michael

    2012-01-01

    Screening chemical libraries to identify compounds that affect overall cell proliferation is common. However, in most cases, it is not known whether the compounds tested alter the timing of particular cell cycle transitions. Here, we evaluated an FDA-approved drug library to identify pharmaceuticals that alter cell cycle progression in yeast, using DNA content measurements by flow cytometry. This approach revealed strong cell cycle effects of several commonly used pharmaceuticals. We show that the antilipemic gemfibrozil delays initiation of DNA replication, while cells treated with the antidepressant fluoxetine severely delay progression through mitosis. Based on their effects on cell cycle progression, we also examined cell proliferation in the presence of both compounds. We discovered a strong suppressive interaction between gemfibrozil and fluoxetine. Combinations of interest among diverse pharmaceuticals are difficult to identify, due to the daunting number of possible combinations that must be evaluated. The novel interaction between gemfibrozil and fluoxetine suggests that identifying and combining drugs that show cell cycle effects might streamline identification of drug combinations with a pronounced impact on cell proliferation.

  16. KinD is a checkpoint protein linking spore formation to extracellular-matrix production in Bacillus subtilis biofilms.

    PubMed

    Aguilar, Claudio; Vlamakis, Hera; Guzman, Alejandra; Losick, Richard; Kolter, Roberto

    2010-05-18

    Bacillus subtilis cells form multicellular biofilm communities in which spatiotemporal regulation of gene expression occurs, leading to differentiation of multiple coexisting cell types. These cell types include matrix-producing and sporulating cells. Extracellular matrix production and sporulation are linked in that a mutant unable to produce matrix is delayed for sporulation. Here, we show that the delay in sporulation is not due to a growth advantage of the matrix-deficient mutant under these conditions. Instead, we show that the link between matrix production and sporulation is through the Spo0A signaling pathway. Both processes are regulated by the phosphorylated form of the master transcriptional regulator Spo0A. When cells have low levels of phosphorylated Spo0A (Spo0A~P), matrix genes are expressed; however, at higher levels of Spo0A~P, sporulation commences. We have found that Spo0A~P levels are maintained at low levels in the matrix-deficient mutant, thereby delaying expression of sporulation-specific genes. This is due to the activity of one of the components of the Spo0A phosphotransfer network, KinD. A deletion of kinD suppresses the sporulation defect of matrix mutants, while its overproduction delays sporulation. Our data indicate that KinD displays a dual role as a phosphatase or a kinase and that its activity is linked to the presence of extracellular matrix in the biofilms. We propose a novel role for KinD in biofilms as a checkpoint protein that regulates the onset of sporulation by inhibiting the activity of Spo0A until matrix, or a component therein, is sensed.

  17. KinD Is a Checkpoint Protein Linking Spore Formation to Extracellular-Matrix Production in Bacillus subtilis Biofilms

    PubMed Central

    Aguilar, Claudio; Vlamakis, Hera; Guzman, Alejandra; Losick, Richard; Kolter, Roberto

    2010-01-01

    ABSTRACT Bacillus subtilis cells form multicellular biofilm communities in which spatiotemporal regulation of gene expression occurs, leading to differentiation of multiple coexisting cell types. These cell types include matrix-producing and sporulating cells. Extracellular matrix production and sporulation are linked in that a mutant unable to produce matrix is delayed for sporulation. Here, we show that the delay in sporulation is not due to a growth advantage of the matrix-deficient mutant under these conditions. Instead, we show that the link between matrix production and sporulation is through the Spo0A signaling pathway. Both processes are regulated by the phosphorylated form of the master transcriptional regulator Spo0A. When cells have low levels of phosphorylated Spo0A (Spo0A~P), matrix genes are expressed; however, at higher levels of Spo0A~P, sporulation commences. We have found that Spo0A~P levels are maintained at low levels in the matrix-deficient mutant, thereby delaying expression of sporulation-specific genes. This is due to the activity of one of the components of the Spo0A phosphotransfer network, KinD. A deletion of kinD suppresses the sporulation defect of matrix mutants, while its overproduction delays sporulation. Our data indicate that KinD displays a dual role as a phosphatase or a kinase and that its activity is linked to the presence of extracellular matrix in the biofilms. We propose a novel role for KinD in biofilms as a checkpoint protein that regulates the onset of sporulation by inhibiting the activity of Spo0A until matrix, or a component therein, is sensed. PMID:20689749

  18. Estimation of physical activity levels using cell phone questionnaires: a comparison with accelerometry for evaluation of between-subject and within-subject variations.

    PubMed

    Bexelius, Christin; Sandin, Sven; Trolle Lagerros, Ylva; Litton, Jan-Eric; Löf, Marie

    2011-09-25

    Physical activity promotes health and longevity. Further elaboration of the role of physical activity for human health in epidemiological studies on large samples requires accurate methods that are easy to use, cheap, and possible to repeat. The use of telecommunication technologies such as cell phones is highly interesting in this respect. In an earlier report, we showed that physical activity level (PAL) assessed using a cell phone procedure agreed well with corresponding estimates obtained using the doubly labeled water method. However, our earlier study indicated high within-subject variation in relation to between-subject variations in PAL using cell phones, but we could not assess if this was a true variation of PAL or an artifact of the cell phone technique. Our objective was to compare within- and between-subject variations in PAL by means of cell phones with corresponding estimates using an accelerometer. In addition, we compared the agreement of daily PAL values obtained using the cell phone questionnaire with corresponding data obtained using an accelerometer. PAL was measured both with the cell phone questionnaire and with a triaxial accelerometer daily during a 2-week study period in 21 healthy Swedish women (20 to 45 years of age and BMI from 17.7 kg/m² to 33.6 kg/m²). The results were evaluated by fitting linear mixed effect models and descriptive statistics and graphs. With the accelerometer, 57% (95% confidence interval [CI] 40%-66%) of the variation was within subjects, while with the cell phone, within-subject variation was 76% (95% CI 59%-83%). The day-to-day variations in PAL observed using the cell phone questions agreed well with the corresponding accelerometer results. Both the cell phone questionnaire and the accelerometer showed high within-subject variations. Furthermore, day-to-day variations in PAL within subjects assessed using the cell phone agreed well with corresponding accelerometer values. Consequently, our cell phone questionnaire is a promising tool for assessing levels of physical activity. The tool may be useful for large-scale prospective studies.

  19. Delayed brain radiation necrosis: pathological review and new molecular targets for treatment.

    PubMed

    Furuse, Motomasa; Nonoguchi, Naosuke; Kawabata, Shinji; Miyatake, Shin-Ichi; Kuroiwa, Toshihiko

    2015-12-01

    Delayed radiation necrosis is a well-known adverse event following radiotherapy for brain diseases and has been studied since the 1930s. The primary pathogenesis is thought to be the direct damage to endothelial and glial cells, particularly oligodendrocytes, which causes vascular hyalinization and demyelination. This primary pathology leads to tissue inflammation and ischemia, inducing various tissue protective responses including angiogenesis. Macrophages and lymphocytes then infiltrate the surrounding areas of necrosis, releasing inflammatory cytokines such as interleukin (IL)-1α, IL-6, and tumor necrosis factor (TNF)-α. Microglia also express these inflammatory cytokines. Reactive astrocytes play an important role in angiogenesis, expressing vascular endothelial growth factor (VEGF). Some chemokine networks, like the CXCL12/CXCR4 axis, are upregulated by tissue inflammation. Hypoxia may mediate the cell-cell interactions among reactive astrocytes, macrophages, and microglial cells around the necrotic core. Recently, bevacizumab, an anti-VEGF antibody, has demonstrated promising results as an alternative treatment for radiation necrosis. The importance of VEGF in the pathophysiology of brain radiation necrosis is being recognized. The discovery of new molecular targets could facilitate novel treatments for radiation necrosis. This literature review will focus on recent work characterizing delayed radiation necrosis in the brain.

  20. Naturally Inspired Firefly Controller For Stabilization Of Double Inverted Pendulum

    NASA Astrophysics Data System (ADS)

    Srikanth, Kavirayani; Nagesh, Gundavarapu

    2015-12-01

    A double inverted pendulum plant as an established model that is analyzed as part of this work was tested under the influence of time delay, where the controller was fine tuned using a firefly algorithm taking into considering the fitness function of variation of the cart position and to minimize the cart position displacement and still stabilize it effectively. The naturally inspired algorithm which imitates the fireflies definitely is an energy efficient method owing to the inherent logic of the way the fireflies respond collectively and has shown that critical time delays makes the system healthy.

  1. Red cell exchange to mitigate a delayed hemolytic transfusion reaction in a patient transfused with incompatible red blood cells.

    PubMed

    Irani, Mehraboon S; Karafin, Matthew S; Ernster, Luke

    2017-02-01

    A red cell exchange was performed to prevent a potentially fatal hemolytic transfusion reaction in a patient with anti-e who was transfused with e-antigen unscreened red blood cells during liver transplant surgery. A 64-year-old woman with cirrhosis due to hepatitis C was scheduled to receive a liver transplant. She had a previously documented anti-e, an antibody to the Rh(e)-antigen that is known to cause delayed hemolytic transfusion reactions. Pre-operatively and intra-operatively, she had massive hemorrhage which required transfusion of 34 e-antigen unscreened red blood cells (RBCs) most of which were incompatible. The hemoglobin dropped from 9.1 g/dL on post-operative day (POD)1 to 6.6 g/dL on POD6, with no evidence of blood loss. The bilirubin also increased from 5.0 mg/dL on POD 1 to 11.0 mg/dL on POD 6. As she was also becoming more hemodynamically unstable, a red cell exchange with 10 units of e-negative RBCs was performed on POD 6. She improved clinically and was extubated the following day. A few residual transfused e-positive red cells were detected after the red cell exchange until POD 13. This case illustrates how a red cell exchange can mitigate the potentially harmful effects of a delayed hemolytic transfusion reaction caused by red cell antibodies. With massive intraoperative blood loss it may not be possible to have antigen-negative RBCs immediately available, particularly for the e-antigen, which is present in 98% of the donor population. The ability to perform such a procedure may be life-saving in such patients. J. Clin. Apheresis 32:59-61, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels

    NASA Astrophysics Data System (ADS)

    Khetan, Sudhir; Guvendiren, Murat; Legant, Wesley R.; Cohen, Daniel M.; Chen, Christopher S.; Burdick, Jason A.

    2013-05-01

    Although cell-matrix adhesive interactions are known to regulate stem cell differentiation, the underlying mechanisms, in particular for direct three-dimensional encapsulation within hydrogels, are poorly understood. Here, we demonstrate that in covalently crosslinked hyaluronic acid (HA) hydrogels, the differentiation of human mesenchymal stem cells (hMSCs) is directed by the generation of degradation-mediated cellular traction, independently of cell morphology or matrix mechanics. hMSCs within HA hydrogels of equivalent elastic moduli that permit (restrict) cell-mediated degradation exhibited high (low) degrees of cell spreading and high (low) tractions, and favoured osteogenesis (adipogenesis). Moreover, switching the permissive hydrogel to a restrictive state through delayed secondary crosslinking reduced further hydrogel degradation, suppressed traction, and caused a switch from osteogenesis to adipogenesis in the absence of changes to the extended cellular morphology. Furthermore, inhibiting tension-mediated signalling in the permissive environment mirrored the effects of delayed secondary crosslinking, whereas upregulating tension induced osteogenesis even in the restrictive environment.

  3. Cannibalism enhances biofilm development in Bacillus subtilis.

    PubMed

    López, Daniel; Vlamakis, Hera; Losick, Richard; Kolter, Roberto

    2009-11-01

    Cannibalism is a mechanism to delay sporulation in Bacillus subtilis. Cannibal cells express the skf and sdp toxin systems to lyse a fraction of their sensitive siblings. The lysed cells release nutrients that serve to feed the community, effectively delaying spore formation. Here we provide evidence that the subpopulation of cells that differentiates into cannibals is the same subpopulation that produces the extracellular matrix that holds cells together in biofilms. Cannibalism and matrix formation are both triggered in response to the signalling molecule surfactin. Nutrients released by the cannibalized cells are preferentially used by matrix-producing cells, as they are the only cells expressing resistance to the Skf and Sdp toxins. As a result this subpopulation increases in number and matrix production is enhanced when cannibalism toxins are produced. The cannibal/matrix-producing subpopulation is also generated in response to antimicrobials produced by other microorganisms and may thus constitute a defense mechanism to protect B. subtilis from the action of antibiotics in natural settings.

  4. Multiple lesion track structure model

    NASA Technical Reports Server (NTRS)

    Wilson, John W.; Cucinotta, Francis A.; Shinn, Judy L.

    1992-01-01

    A multilesion cell kinetic model is derived, and radiation kinetic coefficients are related to the Katz track structure model. The repair-related coefficients are determined from the delayed plating experiments of Yang et al. for the C3H10T1/2 cell system. The model agrees well with the x ray and heavy ion experiments of Yang et al. for the immediate plating, delaying plating, and fractionated exposure protocols employed by Yang. A study is made of the effects of target fragments in energetic proton exposures and of the repair-deficient target-fragment-induced lesions.

  5. [Effect of indolylacetic acid on formation of bacteroid forms of Rhizobium leguminosarum].

    PubMed

    Lobanok, E V; Bakanchikova, T I

    1979-01-01

    The purpose of this work was to study the effect of indolylacetic acid (IAA) on the strains of Rhizobium leguminosarum, effective and noneffective with respect to symbiotic nitrogen fixation (L4 and 245a, and 14--73, respectively). IAA at a concentration of 50 mcg/ml and higher inhibited the growth of the bacterium, temporarily delayed celular division, and induced intensive formation of elongated bacteroid-like cells, predominantly Y-shaped or having a clavate shape. Many bacteroid-like cells were capable of division after a certain delay.

  6. Cell-mediated immunity in herpes simplex virus-infected mice: H-2 mapping of the delayed-type hypersensitivity response and the antiviral T cell response.

    PubMed

    Nash, A A; Phelan, J; Wildy, P

    1981-04-01

    An adoptive transfer system was used to investigate the H-2 restriction of delayed-type hypersensitivity (DTH) to herpes simplex virus. A successful DTH transfer was achieved when donor and recipient were compatible at the I-A region, with K and D region compatibility unnecessary. However, the rapid clearance of infectious virus from the inoculation site was found only when the donor and recipients were compatible at H-2K (and presumably D) and I-A regions.

  7. Constitutional pericentric inversion of chromosome 9 and hematopoietic recovery after allogeneic stem cell transplantation.

    PubMed

    Manola, K N; Harhalakis, N; Symeonidis, A; Rigana, H; Stavropoulou, C; Karakasis, D; Tiniakou, M; Baltathakis, I; Stamouli, M I; Zoumbos, N; Pantelias, G E; Sambani, C

    2006-09-01

    Recent reports suggest that hemopoietic stem cells with constitutional pericentric inversion of chromosome 9 [inv(9)] may be related to delayed engraftment or hemopoietic defect after stem cell transplantation (SCT). We conducted a retrospective study on five allogeneic SCT in which constitutional inv(9) was detected either in the donor or the recipient. The results showed that hematologic recovery was within the expected time range for all our patients. However, one patient exhibited decreasing blood counts between day +45 and +272 after transplantation, possibly due to protracted cytomegalovirus (CMV) infection and gansiclovir and imatinib treatment. Our findings suggest that constitutional inv(9) may not be associated with delayed hemopoietic recovery after SCT.

  8. Granulocyte-colony stimulating factor (G-CSF)-primed, delayed marrow harvests as a source of hematopoietic stem and progenitor cells for allogeneic transplantation.

    PubMed

    Phillips, G L; Davey, D D; Hale, G A; Marshall, K W; Munn, R K; Nath, R; Reece, D E; Van Zant, G

    1999-10-01

    We evaluated the ability of G-CSF to increase the number of hematopoietic stem cells obtained by "delayed" BM harvest for allogeneic transplantation. Five normal donors received G-CSF @ 10 mcg/kg/day x 5 followed by repeat PB and BM assays at day 6 and 16, and BM harvest at day 16. Stem cells were not increased in the BM at day 16. Five patients underwent BMT and engrafted at +10 to +19 days. While the tested strategy offers no intrinsic advantages, its potential cannot be evaluated fully without alternative timing and/or additional, "early acting" growth factors.

  9. Optical Path Difference Fluctations at the CHARA Interferometric Array

    NASA Astrophysics Data System (ADS)

    Merand, A.; ten Brummelaar, T. A.; McAlister, H. A.; Ridgway, S. T.; Sturmann, J.; Sturmann, L.; Turner, N. H.; Bagnuolo, W. G.; Hrynevych, M.; Shure, M. A.

    2001-05-01

    Commissioning observations at the CHARA Array have been carried out with the two south telescopes, with a telescope separation of 34 meters. Due to the size of the array (>340 meters across) and the optical delay geometry, the beams travel horizontal distances of approximately 200 meters, with a number of reflections in the telescope coude area and the optical delay and beam combination areas. Stellar and laboratory observations have been analyzed to determine the variations of the optical path, as revealed by shifts in the interference pattern. The power spectra of the OPD variations are diagnostic of the atmospheric turbulence characteristics, and of any internal vibrations in the laboratory. Results of the OPD analysis will be compared to similar studies at other interferometric facilities. The CHARA Array, a six-telescope O/IR interferometric array operated by Georgia State University on Mt. Wilson, Calfornia, was funded by the National Science Foundation, the W.M. Keck Foundation, the David and Lucile Packard Foundation, and Georgia State University.

  10. Global characteristics of stream flow seasonality and variability

    USGS Publications Warehouse

    Dettinger, M.D.; Diaz, Henry F.

    2000-01-01

    Monthly stream flow series from 1345 sites around the world are used to characterize geographic differences in the seasonality and year-to-year variability of stream flow. Stream flow seasonality varies regionally, depending on the timing of maximum precipitation, evapotranspiration, and contributions from snow and ice. Lags between peaks of precipitation and stream flow vary smoothly from long delays in high-latitude and mountainous regions to short delays in the warmest sectors. Stream flow is most variable from year to year in dry regions of the southwest United States and Mexico, the Sahel, and southern continents, and it varies more (relatively) than precipitation in the same regions. Tropical rivers have the steadiest flows. El Nin??o variations are correlated with stream flow in many parts of the Americas, Europe, and Australia. Many stream flow series from North America, Europe, and the Tropics reflect North Pacific climate, whereas series from the eastern United States, Europe, and tropical South America and Africa reflect North Atlantic climate variations.

  11. Global asymptotic stability for HIV-1 dynamics with two distributed delays.

    PubMed

    Wang, Jinliang; Huang, Gang; Takeuchi, Yasuhiro

    2012-09-01

    Based on the drugs treatment to control HIV-1 infection and viral replication, we express the intracellular eclipse phase of virions in host cell as distributed delays because of pharmacological actions. In present paper, we investigate a class of HIV-1 infection dynamical model with two distributed delays. One of them describes the period between the time that HIV virion enters (infects) target cell and the time that the infected cell starts to produce new viral particles. The other describes the time for the virion maturation process. They are both allowed to tend to be infinite because of drugs resistent strains. By the Lyapunov direct method of and utilizing the technology of constructing Lyapunov functionals, we identify the basic reproduction number R(0) as a threshold quantity for the stability of equilibria. More precisely, if R(0) ≤ 1, the infection-free equilibrium is globally asymptotically stable; on the contrary, if R(0) > 1, then an infected equilibrium appears which is globally asymptotically stable. The dynamical results indicate that time delays have effect on the global stability of two equilibria through threshold value R(0), which is a decreasing function of delays. The biological meanings imply that any drugs that can prolong the time of viral reproduction through slowing down the reverse transcription of HIV in host and virus maturation process may also help control the HIV-1 infection and virus loads. Another way to increase the efficacy of the protease inhibitor and the reverse transcriptase inhibitor (i.e. increasing n(p) and n(rt)) is also desirable treatment strategies.

  12. Lipid overloading during liver regeneration causes delayed hepatocyte DNA replication by increasing ER stress in mice with simple hepatic steatosis.

    PubMed

    Hamano, Mina; Ezaki, Hisao; Kiso, Shinichi; Furuta, Kunimaro; Egawa, Mayumi; Kizu, Takashi; Chatani, Norihiro; Kamada, Yoshihiro; Yoshida, Yuichi; Takehara, Tetsuo

    2014-02-01

    Impaired fatty liver regeneration has already been reported in many genetic modification models. However, in diet-induced simple hepatic steatosis, which showed similar phenotype with clinical pathology, whether liver regeneration is impaired or not remains unclear. In this study, we evaluated liver regeneration in mice with diet-induced simple hepatic steatosis, and focused on excess lipid accumulation occurring during liver regeneration. Mice were fed high fat diet (HFD) or control diet for 9-10 weeks. We analyzed intrahepatic lipid accumulation, DNA replication, and various signaling pathways including cell proliferation and ER stress during liver regeneration after partial hepatectomy. In addition, some of mice were pretreated with tauroursodeoxycholic acid (TUDCA), a chemical chaperone which alleviates ER stress, and then we estimated TUDCA effects on liver regeneration. The peak of hepatocyte BrdU incorporation, the expression of proliferation cell nuclear antigen (PCNA) protein, and the expressions of cell cycle-related genes were observed in delayed time in HFD mice. The expression of phosphorylated Erk1/2 was also delayed in HFD mice. The amounts of liver triglyceride were at least twofold higher in HFD mice at each time point. Intrahepatic palmitic acid was increased especially in HFD mice. ER stress induced during liver regeneration was significantly higher in HFD mice. In HFD mice, pretreatment with TUDCA reduced ER stress and resulted in improvement of delayed liver regeneration. In simple hepatic steatosis, lipid overloading occurring during liver regeneration might be caused ER stress and results in delayed hepatocyte DNA replication.

  13. Implications of delayed initiation of radiotherapy: accelerated repopulation after induction chemotherapy for stage III non-small cell lung cancer.

    PubMed

    Chen, Chien P; Weinberg, Vivian K; Jahan, Thierry M; Jablons, David M; Yom, Sue S

    2011-11-01

    For patients with stage III non-small cell lung cancer treated with induction chemotherapy (ICT), delayed initiation of subsequent radiotherapy (RT) may allow for repopulation in the interval between treatment modalities and during the early phase of RT. We quantified the impact of postinduction RT timing by evaluating the pace of tumor regrowth. Institutionally approved retrospective review identified 21 analyzable patients with stage III non-small cell lung cancer who had platinum-based ICT followed by RT+/- chemotherapy from 2002 to 2009. Radiographic response was determined by RECIST criteria and the volume of the single largest tumor mass on the pre-ICT, post-ICT, and RT-planning computed tomography scans. After ICT, the median percent volume change from pre-ICT baseline was -41% (range -86 to +86%). By the RT-planning computed tomography scan, the median percent volume change from the post-ICT timepoint was +40% (range -11 to +311%) and the median volume change was +20 ml (range -4 to 102 ml); these changes were significant (p = 0.0002). Similar results were seen for tumor diameter. A correlation was observed between the amount of delay and degree of regrowth for percent volume (p = 0.0006) and percent diameter change (p = 0.003). A delay greater than 21 days produced greater increases in percent volume change (p = 0.002) and percent diameter (p = 0.055) than lesser delays. After ICT, tumor regrowth can occur within a few weeks. Radiation treatment planning should begin as soon as possible after the administration of ICT to maximize the benefits of cytoreduction.

  14. Transition from Target to Gaze Coding in Primate Frontal Eye Field during Memory Delay and Memory-Motor Transformation.

    PubMed

    Sajad, Amirsaman; Sadeh, Morteza; Yan, Xiaogang; Wang, Hongying; Crawford, John Douglas

    2016-01-01

    The frontal eye fields (FEFs) participate in both working memory and sensorimotor transformations for saccades, but their role in integrating these functions through time remains unclear. Here, we tracked FEF spatial codes through time using a novel analytic method applied to the classic memory-delay saccade task. Three-dimensional recordings of head-unrestrained gaze shifts were made in two monkeys trained to make gaze shifts toward briefly flashed targets after a variable delay (450-1500 ms). A preliminary analysis of visual and motor response fields in 74 FEF neurons eliminated most potential models for spatial coding at the neuron population level, as in our previous study (Sajad et al., 2015). We then focused on the spatiotemporal transition from an eye-centered target code (T; preferred in the visual response) to an eye-centered intended gaze position code (G; preferred in the movement response) during the memory delay interval. We treated neural population codes as a continuous spatiotemporal variable by dividing the space spanning T and G into intermediate T-G models and dividing the task into discrete steps through time. We found that FEF delay activity, especially in visuomovement cells, progressively transitions from T through intermediate T-G codes that approach, but do not reach, G. This was followed by a final discrete transition from these intermediate T-G delay codes to a "pure" G code in movement cells without delay activity. These results demonstrate that FEF activity undergoes a series of sensory-memory-motor transformations, including a dynamically evolving spatial memory signal and an imperfect memory-to-motor transformation.

  15. High speed CMOS/SOS standard cell notebook

    NASA Technical Reports Server (NTRS)

    1978-01-01

    The NASA/MSFC high speed CMOS/SOS standard cell family, designed to be compatible with the PR2D (Place, Route in 2-Dimensions) automatic layout program, is described. Standard cell data sheets show the logic diagram, the schematic, the truth table, and propagation delays for each logic cell.

  16. Depletion of mRNA export regulator DBP5/DDX19, GLE1 or IPPK that is a key enzyme for the production of IP6, resulting in differentially altered cytoplasmic mRNA expression and specific cell defect

    PubMed Central

    Okamura, Masumi; Yamanaka, Yasutaka; Shigemoto, Maki; Kitadani, Yuya; Kobayashi, Yuhko; Kambe, Taiho; Nagao, Masaya; Kobayashi, Issei; Okumura, Katsuzumi

    2018-01-01

    DBP5, also known as DDX19, GLE1 and inositol hexakisphosphate (IP6) function in messenger RNA (mRNA) export at the cytoplasmic surface of the nuclear pore complex in eukaryotic cells. DBP5 is a DEAD-box RNA helicase, and its activity is stimulated by interactions with GLE1 and IP6. In addition, these three factors also have unique role(s). To investigate how these factors influenced the cytoplasmic mRNA expression and cell phenotype change, we performed RNA microarray analysis to detect the effect and function of DBP5, GLE1 and IP6 on the cytoplasmic mRNA expression. The expression of some cytoplasmic mRNA subsets (e.g. cell cycle, DNA replication) was commonly suppressed by the knock-down of DBP5, GLE1 and IPPK (IP6 synthetic enzyme). The GLE1 knock-down selectively reduced the cytoplasmic mRNA expression required for mitotic progression, results in an abnormal spindle phenotype and caused the delay of mitotic process. Meanwhile, G1/S cell cycle arrest was observed in DBP5 and IPPK knock-down cells. Several factors that function in immune response were also down-regulated in DBP5 or IPPK knock-down cells. Thereby, IFNβ-1 mRNA transcription evoked by poly(I:C) treatment was suppressed. These results imply that DBP5, GLE1 and IP6 have a conserved and individual function in the cytoplasmic mRNA expression. Variations in phenotype are due to the difference in each function of DBP5, GLE1 and IPPK in intracellular mRNA metabolism. PMID:29746542

  17. Data-Gathering Scheme Using AUVs in Large-Scale Underwater Sensor Networks: A Multihop Approach

    PubMed Central

    Khan, Jawaad Ullah; Cho, Ho-Shin

    2016-01-01

    In this paper, we propose a data-gathering scheme for hierarchical underwater sensor networks, where multiple Autonomous Underwater Vehicles (AUVs) are deployed over large-scale coverage areas. The deployed AUVs constitute an intermittently connected multihop network through inter-AUV synchronization (in this paper, synchronization means an interconnection between nodes for communication) for forwarding data to the designated sink. In such a scenario, the performance of the multihop communication depends upon the synchronization among the vehicles. The mobility parameters of the vehicles vary continuously because of the constantly changing underwater currents. The variations in the AUV mobility parameters reduce the inter-AUV synchronization frequency contributing to delays in the multihop communication. The proposed scheme improves the AUV synchronization frequency by permitting neighboring AUVs to share their status information via a pre-selected node called an agent-node at the static layer of the network. We evaluate the proposed scheme in terms of the AUV synchronization frequency, vertical delay (node→AUV), horizontal delay (AUV→AUV), end-to-end delay, and the packet loss ratio. Simulation results show that the proposed scheme significantly reduces the aforementioned delays without the synchronization time-out process employed in conventional works. PMID:27706042

  18. Data-Gathering Scheme Using AUVs in Large-Scale Underwater Sensor Networks: A Multihop Approach.

    PubMed

    Khan, Jawaad Ullah; Cho, Ho-Shin

    2016-09-30

    In this paper, we propose a data-gathering scheme for hierarchical underwater sensor networks, where multiple Autonomous Underwater Vehicles (AUVs) are deployed over large-scale coverage areas. The deployed AUVs constitute an intermittently connected multihop network through inter-AUV synchronization (in this paper, synchronization means an interconnection between nodes for communication) for forwarding data to the designated sink. In such a scenario, the performance of the multihop communication depends upon the synchronization among the vehicles. The mobility parameters of the vehicles vary continuously because of the constantly changing underwater currents. The variations in the AUV mobility parameters reduce the inter-AUV synchronization frequency contributing to delays in the multihop communication. The proposed scheme improves the AUV synchronization frequency by permitting neighboring AUVs to share their status information via a pre-selected node called an agent-node at the static layer of the network. We evaluate the proposed scheme in terms of the AUV synchronization frequency, vertical delay (node→AUV), horizontal delay (AUV→AUV), end-to-end delay, and the packet loss ratio. Simulation results show that the proposed scheme significantly reduces the aforementioned delays without the synchronization time-out process employed in conventional works.

  19. Variation in seed dormancy quantitative trait loci in Arabidopsis thaliana originating from one site.

    PubMed

    Silady, Rebecca A; Effgen, Sigi; Koornneef, Maarten; Reymond, Matthieu

    2011-01-01

    A Quantitative Trait Locus (QTL) analysis was performed using two novel Recombinant Inbred Line (RIL) populations, derived from the progeny between two Arabidopsis thaliana genotypes collected at the same site in Kyoto (Japan) crossed with the reference laboratory strain Landsberg erecta (Ler). We used these two RIL populations to determine the genetic basis of seed dormancy and flowering time, which are assumed to be the main traits controlling life history variation in Arabidopsis. The analysis revealed quantitative variation for seed dormancy that is associated with allelic variation at the seed dormancy QTL DOG1 (for Delay Of Germination 1) in one population and at DOG6 in both. These DOG QTL have been previously identified using mapping populations derived from accessions collected at different sites around the world. Genetic variation within a population may enhance its ability to respond accurately to variation within and between seasons. In contrast, variation for flowering time, which also segregated within each mapping population, is mainly governed by the same QTL.

  20. Action of caffeine on x-irradiated HeLa cells. IV. Progression delays and enhanced cell killing at high caffeine concentrations

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

    Tolmach, L.J.; Busse, P.M.

    1980-05-01

    The response of x-irradiated and unirradiated HeLa S3 cells to treatment with caffeine at concentrations between 1 and 10 nM has been examined with respect to both delay in progression through the cell generation cycle and enhancement of the expression of potentially lethal x-ray damage. Progression is delayed in a concentration-dependent fashion: the generation time is doubled at about 4 mM. The duration of G/sub 1/ is lengthened, and the rate of DNA synthesis is reduced, although the kinetics are different in the two phases; the rate of DNA synthesis is usually unaffected at 1 or 2 mM, while theremore » is no concentration threshold for the slowing of progression through G/sub 1/. Progression through G/sub 2/ appears to be unaffected by concentrations up to at least 10 mM. Killing of irradiated cells in G/sub 2/ is somewhat greater after treatment with the higher caffeine concentrations than reported previously for 1 mM. Moreover, an additional mode of killing is observed in irradiated G/sub 1/ cells which had been found previously to be only slightly affected by 1 mM caffeine; they suffer extensive killing at concentrations above 5 mM. The time-survival curves for irradiated, caffeine-treated G/sub 1/ and G/sub 2/ cells have characteristically different shapes. The dose-survival curves for cells treated with the higher caffeine concentrations display steeper terminal slopes and narrower shoulders.« less

  1. Impaired wound healing in mice deficient in a matricellular protein SPARC (osteonectin, BM-40)

    PubMed Central

    Basu, Amitabha; Kligman, Lorraine H; Samulewicz, Stefan J; Howe, Chin C

    2001-01-01

    Background SPARC is a matricellular protein involved in cell-matrix interactions. From expression patterns at the wound site and in vitro studies, SPARC has been implicated in the control of wound healing. Here we examined the function of SPARC in cutaneous wound healing using SPARC-null mice and dermal fibroblasts derived from them. Results In large (25 mm) wounds, SPARC-null mice showed a significant delay in healing as compared to wild-type mice (31 days versus 24 days). Granulation tissue formation and extracellular matrix protein production were delayed in small 6 mm SPARC-null wounds initially but were resolved by day 6. In in vitro wound-healing assays, while wild-type primary dermal fibroblasts showed essentially complete wound closure at 11 hours, wound closure of SPARC-null cells was incomplete even at 31 hours. Addition of purified SPARC restored the normal time course of wound closure. Treatment of SPARC-null cells with mitomycin C to analyze cell migration without cell proliferation showed that wound repair remained incomplete after 31 hours. Cell proliferation as measured by 3H-thymidine incorporation and collagen gel contraction by SPARC-null cells were not compromised. Conclusions A significant delay in healing large excisional wounds and setback in granulation tissue formation and extracellular matrix protein production in small wounds establish that SPARC is required for granulation tissue formation during normal repair of skin wounds in mice. A defect in wound closure in vitro indicates that SPARC regulates cell migration. We conclude that SPARC plays a role in wound repair by promoting fibroblast migration and thus granulation tissue formation. PMID:11532190

  2. Spontaneous ignition delay characteristics of hydrocarbon fuel-air mixtures

    NASA Technical Reports Server (NTRS)

    Lefebvre, A. H.; Freeman, W. G.; Cowell, L. H.

    1986-01-01

    The influence of pressure on the autoignition characteristics of homogeneous mixtures of hydrocarbon fuels in air is examined. Autoignition delay times are measured for propane, ethylene, methane, and acetylene in a continuous flow apparatus featuring a multi-point fuel injector. Results are presented for mixture temperatures from 670K to 1020K, pressures from 1 to 10 atmospheres, equivalence ratios from 0.2 to 0.7, and velocities from 5 to 30 m/s. Delay time is related to pressure, temperature, and fuel concentration by global reaction theory. The results show variations in global activation energy from 25 to 38 kcal/kg-mol, pressure exponents from 0.66 to 1.21, and fuel concentration exponents from 0.19 to 0.75 for the fuels studied. These results are generally in good agreement with previous studies carried out under similar conditions.

  3. Effects of caffeine on radiation-induced phenomena associated with cell- cycle traverse of mammalian cells

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

    Walters, R.A.; Gurley, L.R.; Tobby, R.A.

    1974-02-01

    Caffeine induced a state of G/sub 1/ arrest when added to an exponentially growing culture of Chinese hamster cells (line CHO). In addition to its effect on cell-cycle traverse, caffeine ameliorated a number of the responses of cells to ionizing radiation. The duration of the division delay period following x-irradiation of caffeine-treated cells was reduced, and the magnitude of reduction was dependent on caffeine concentration. Cells irradiated during the DNA synthetic phase in the presence of caffeine were delayed less in their exit from S, measured autoradiographically, and the radiation-induced reduction of radioactive thymidine incorporation into DNA was lessened. Cellsmore » synchronized by isoleucine deprivation, while being generally less sensitive to the effects of ionizing radiation than mitotically synchronized cells, were equally responsive to the effects of caffeine. The x-rayinduced reduction of phosphorylation of lysine-rich histone F1 was less in caffeine-treated cells than in untreated cells. Finally, survival after irradiation was only slightly reduced in caffeinetreated cells. A possible role of cyclic AMP in cell-cycle traverse of irradiated cells is discussed. (auth)« less

  4. A Presumptive Developmental Role for a Sea Urchin Cyclin B Splice Variant

    PubMed Central

    Lozano, Jean-Claude; Schatt, Philippe; Marquès, François; Peaucellier, Gérard; Fort, Philippe; Féral, Jean-Pierre; Genevière, Anne-Marie; Picard, André

    1998-01-01

    We show that a splice variant–derived cyclin B is produced in sea urchin oocytes and embryos. This splice variant protein lacks highly conserved sequences in the COOH terminus of the protein. It is found strikingly abundant in growing oocytes and cells committed to differentiation during embryogenesis. Cyclin B splice variant (CBsv) protein associates weakly in the cell with Xenopus cdc2 and with budding yeast CDC28p. In contrast to classical cyclin B, CBsv very poorly complements a triple CLN deletion in budding yeast, and its microinjection prevents an initial step in MPF activation, leading to an important delay in oocyte meiosis reinitiation. CBsv microinjection in fertilized eggs induces cell cycle delay and abnormal development. We assume that CBsv is produced in growing oocytes to keep them in prophase, and during embryogenesis to slow down cell cycle in cells that will be committed to differentiation. PMID:9442104

  5. Infectious Complications after Umbilical Cord-Blood Transplantation from Unrelated Donors

    PubMed Central

    Montoro, Juan; Piñana, José Luis; Moscardó, Federico; Sanz, Jaime

    2016-01-01

    Umbilical cord-blood (UCB) is a well-recognized alternative source of stem cells for unrelated donor hematopoietic stem cell transplantation (HSCT). As compared with other stem cell sources from adult donors, it has the advantages of immediate availability of cells, absence of risk to the donor and reduced risk of graft-versus-host disease despite donor-recipient HLA disparity. However, the use of UCB is limited by the delayed post-transplant hematologic recovery due, at least in part, to the reduced number of hematopoietic cells in the graft and the delayed or incomplete immune reconstitution. As a result, severe infectious complications continue to be a leading cause of morbidity and mortality following UCB transplantation (UCBT). We will address the complex differences in the immune properties of UCB and review the incidence, characteristics, risk factors, and severity of bacterial, fungal and viral infectious complications in patients undergoing UCBT. PMID:27872731

  6. Corrections of stratified tropospheric delays in SAR interferometry: Validation with global atmospheric models

    NASA Astrophysics Data System (ADS)

    Doin, Marie-Pierre; Lasserre, Cécile; Peltzer, Gilles; Cavalié, Olivier; Doubre, Cécile

    2010-05-01

    The main limiting factor on the accuracy of Interferometric SAR measurements (InSAR) comes from phase propagation delays through the troposphere. The delay can be divided into a stratified component, which correlates with the topography and often dominates the tropospheric signal, and a turbulent component. We use Global Atmospheric Models (GAM) to estimate the stratified phase delay and delay-elevation ratio at epochs of SAR acquisitions, and compare them to observed phase delay derived from SAR interferograms. Three test areas are selected with different geographic and climatic environments and with large SAR archive available. The Lake Mead, Nevada, USA is covered by 79 ERS1/2 and ENVISAT acquisitions, the Haiyuan Fault area, Gansu, China, by 24 ERS1/2 acquisitions, and the Afar region, Republic of Djibouti, by 91 Radarsat acquisitions. The hydrostatic and wet stratified delays are computed from GAM as a function of atmospheric pressure P, temperature T, and water vapor partial pressure e vertical profiles. The hydrostatic delay, which depends on ratio P/T, varies significantly at low elevation and cannot be neglected. The wet component of the delay depends mostly on the near surface specific humidity. GAM predicted delay-elevation ratios are in good agreement with the ratios derived from InSAR data away from deforming zones. Both estimations of the delay-elevation ratio can thus be used to perform a first order correction of the observed interferometric phase to retrieve a ground motion signal of low amplitude. We also demonstrate that aliasing of daily and seasonal variations in the stratified delay due to uneven sampling of SAR data significantly bias InSAR data stacks or time series produced after temporal smoothing. In all three test cases, the InSAR data stacks or smoothed time series present a residual stratified delay of the order of the expected deformation signal. In all cases, correcting interferograms from the stratified delay removes all these biases. We quantify the standard error associated with the correction of the stratified atmospheric delay. It varies from one site to another depending on the prevailing atmospheric conditions, but remains bounded by the standard deviation of the daily fluctuations of the stratified delay around the seasonal average. Finally we suggest that the phase delay correction can potentially be improved by introducing a non-linear dependence to the elevation derived from GAM.

  7. Corrections of stratified tropospheric delays in SAR interferometry: Validation with global atmospheric models

    NASA Astrophysics Data System (ADS)

    Doin, M.-P.; Lasserre, C.; Peltzer, G.; Cavalié, O.; Doubre, C.

    2009-09-01

    The main limiting factor on the accuracy of Interferometric SAR measurements (InSAR) comes from phase propagation delays through the troposphere. The delay can be divided into a stratified component, which correlates with the topography and often dominates the tropospheric signal, and a turbulent component. We use Global Atmospheric Models (GAM) to estimate the stratified phase delay and delay-elevation ratio at epochs of SAR acquisitions, and compare them to observed phase delay derived from SAR interferograms. Three test areas are selected with different geographic and climatic environments and with large SAR archive available. The Lake Mead, Nevada, USA is covered by 79 ERS1/2 and ENVISAT acquisitions, the Haiyuan Fault area, Gansu, China, by 24 ERS1/2 acquisitions, and the Afar region, Republic of Djibouti, by 91 Radarsat acquisitions. The hydrostatic and wet stratified delays are computed from GAM as a function of atmospheric pressure P, temperature T, and water vapor partial pressure e vertical profiles. The hydrostatic delay, which depends on ratio P/ T, varies significantly at low elevation and cannot be neglected. The wet component of the delay depends mostly on the near surface specific humidity. GAM predicted delay-elevation ratios are in good agreement with the ratios derived from InSAR data away from deforming zones. Both estimations of the delay-elevation ratio can thus be used to perform a first order correction of the observed interferometric phase to retrieve a ground motion signal of low amplitude. We also demonstrate that aliasing of daily and seasonal variations in the stratified delay due to uneven sampling of SAR data significantly bias InSAR data stacks or time series produced after temporal smoothing. In all three test cases, the InSAR data stacks or smoothed time series present a residual stratified delay of the order of the expected deformation signal. In all cases, correcting interferograms from the stratified delay removes all these biases. We quantify the standard error associated with the correction of the stratified atmospheric delay. It varies from one site to another depending on the prevailing atmospheric conditions, but remains bounded by the standard deviation of the daily fluctuations of the stratified delay around the seasonal average. Finally we suggest that the phase delay correction can potentially be improved by introducing a non-linear dependence to the elevation derived from GAM.

  8. Nicotine alters MicroRNA expression and hinders human adult stem cell regenerative potential.

    PubMed

    Ng, Tsz Kin; Carballosa, Carlos M; Pelaez, Daniel; Wong, Hoi Kin; Choy, Kwong Wai; Pang, Chi Pui; Cheung, Herman S

    2013-03-01

    Adult stem cells are critical for the healing process in regenerative medicine. However, cigarette smoking inhibits stem cell recruitment to tissues and delays the wound-healing process. This study investigated the effect of nicotine, a major constituent in the cigarette smoke, on the regenerative potentials of human mesenchymal stem cells (MSC) and periodontal ligament-derived stem cells (PDLSC). The cell proliferation of 1.0 μM nicotine-treated MSC and PDLSC was significantly reduced when compared to the untreated control. Moreover, nicotine also retarded the locomotion of these adult stem cells. Furthermore, their osteogenic differentiation capabilities were reduced in the presence of nicotine as evidenced by gene expression (RUNX2, ALPL, BGLAP, COL1A1, and COL1A2), calcium deposition, and alkaline phosphatase activity analyses. In addition, the microRNA (miRNA) profile of nicotine-treated PDLSC was altered; suggesting miRNAs might play an important role in the nicotine effects on stem cells. This study provided the possible mechanistic explanations on stem cell-associated healing delay in cigarette smoking.

  9. Genetic basis of delay discounting in frequent gamblers: examination of a priori candidates and exploration of a panel of dopamine-related loci

    PubMed Central

    Gray, Joshua C; MacKillop, James

    2014-01-01

    Introduction Delay discounting is a behavioral economic index of impulsivity that reflects preferences for small immediate rewards relative to larger delayed rewards. It has been consistently linked to pathological gambling and other forms of addictive behavior, and has been proposed to be a behavioral characteristic that may link genetic variation and risk of developing addictive disorders (i.e., an endophenotype). Studies to date have revealed significant associations with polymorphisms associated with dopamine neurotransmission. The current study examined associations between delay discounting and both previously linked variants and a novel panel of dopamine-related variants in a sample of frequent gamblers. Methods Participants were 175 weekly gamblers of European ancestry who completed the Monetary Choice Questionnaire to assess delay discounting preferences and provided a DNA via saliva. Results In a priori tests, two loci previously associated with delayed reward discounting (rs1800497 and rs4680) were not replicated, however, the long form of DRD4 VNTR was significantly associated with lower discounting of delayed rewards. Exploratory analysis of the dopamine-related panel revealed 11 additional significant associations in genes associated with dopamine synthesis, breakdown, reuptake, and receptor function (DRD3, SLC6A3, DDC, DBH, and SLC18A2). An aggregate genetic risk score from the nominally significant loci accounted for 17% of the variance in discounting. Mediational analyses largely supported the presence of indirect effects between the associated loci, delay discounting, and pathological gambling severity. Conclusions These findings do not replicate previously reported associations but identify several novel candidates and provide preliminary support for a systems biology approach to understand the genetic basis of delay discounting. PMID:25365808

  10. De novo variants in EBF3 are associated with hypotonia, developmental delay, intellectual disability, and autism

    PubMed Central

    Tanaka, Akemi J.; Cho, Megan T.; Willaert, Rebecca; Retterer, Kyle; Zarate, Yuri A.; Bosanko, Katie; Stefans, Vikki; Oishi, Kimihiko; Williamson, Amy; Wilson, Golder N.; Basinger, Alice; Barbaro-Dieber, Tina; Ortega, Lucia; Sorrentino, Susanna; Gabriel, Melissa K.; Anderson, Ilse J.; Sacoto, Maria J. Guillen; Schnur, Rhonda E.; Chung, Wendy K.

    2017-01-01

    Using whole-exome sequencing, we identified seven unrelated individuals with global developmental delay, hypotonia, dysmorphic facial features, and an increased frequency of short stature, ataxia, and autism with de novo heterozygous frameshift, nonsense, splice, and missense variants in the Early B-cell Transcription Factor Family Member 3 (EBF3) gene. EBF3 is a member of the collier/olfactory-1/early B-cell factor (COE) family of proteins, which are required for central nervous system (CNS) development. COE proteins are highly evolutionarily conserved and regulate neuronal specification, migration, axon guidance, and dendritogenesis during development and are essential for maintaining neuronal identity in adult neurons. Haploinsufficiency of EBF3 may affect brain development and function, resulting in developmental delay, intellectual disability, and behavioral differences observed in individuals with a deleterious variant in EBF3. PMID:29162653

  11. Stability and Hopf Bifurcation in a HIV-1 System with Multitime Delays

    NASA Astrophysics Data System (ADS)

    Zhao, Lingyan; Liu, Haihong; Yan, Fang

    In this paper, we propose a mathematical model for HIV-1 infection with three time delays. The model examines a viral-therapy for controlling infections by using an engineered virus to selectively eliminate infected cells. In our model, three time delays represent the latent period of pathogen virus, pathogen virus production period and recombinant (genetically modified) virus production period, respectively. Detailed theoretical analysis have demonstrated that the values of three delays can affect the stability of equilibrium solutions, can also lead to Hopf bifurcation and oscillated solutions of the system. Moreover, we give the conditions for the existence of stable positive equilibrium solution and Hopf bifurcation. Further, the properties of Hopf bifurcation are discussed. These theoretical results indicate that the delays play an important role in determining the dynamic behavior quantitatively. Therefore, it is a fact that delays are very important, which should not be missed in controlling HIV-1 infections.

  12. Trastuzumab emtansine delays and overcomes resistance to the third-generation EGFR-TKI osimertinib in NSCLC EGFR mutated cell lines.

    PubMed

    La Monica, Silvia; Cretella, Daniele; Bonelli, Mara; Fumarola, Claudia; Cavazzoni, Andrea; Digiacomo, Graziana; Flammini, Lisa; Barocelli, Elisabetta; Minari, Roberta; Naldi, Nadia; Petronini, Pier Giorgio; Tiseo, Marcello; Alfieri, Roberta

    2017-12-04

    Osimertinib is a third-generation EGFR-TKI with a high selective potency against T790M-mutant NSCLC patients. Considering that osimertinib can lead to enhanced HER-2 expression on cell surface and HER-2 overexpression is a mechanism of resistance to osimertinib, this study was addressed to investigate the potential of combining osimertinib with trastuzumab emtansine (T-DM1) in order to improve the efficacy of osimertinib and delay or overcome resistance in NSCLC cell lines with EGFR activating mutation and with T790M mutation or HER-2 amplification. The effects of osimertinib combined with T-DM1 on cell proliferation, cell cycle, cell death, antibody-dependent cell-mediated cytotoxicity (ADCC), and acquisition of osimertinib resistance was investigated in PC9, PC9-T790M and H1975 cell lines. The potential of overcoming osimertinib resistance with T-DM1 was tested in a PC9/HER2c1 xenograft model. T-DM1 exerted an additive effect when combined with osimertinib in terms of inhibition of cell proliferation, cell death and ADCC induction in PC9, PC9-T790M and H1975 cell lines. Combining osimertinib and T-DM1 using different schedules in long-term growth experiments revealed that the appearance of osimertinib-resistance was prevented in PC9-T790M and delayed in H1975 cells when the two drugs were given together. By contrast, when osimertinib was followed by T-DM1 an antagonistic effect was observed on cell proliferation, cell death and resistance acquisition. In xenograft models, we demonstrated that HER-2 amplification was associated with osimertinib-resistance and that T-DM1 co-administration is a potential strategy to overcome this resistance. Our data suggest that concomitant treatment with osimertinib and T-DM1 may be a promising therapeutic strategy for EGFR-mutant NSCLC.

  13. Mast cells play no role in the pathogenesis of postoperative ileus induced by intestinal manipulation.

    PubMed

    Gomez-Pinilla, Pedro J; Farro, Giovanna; Di Giovangiulio, Martina; Stakenborg, Nathalie; Némethova, Andrea; de Vries, Annick; Liston, Adrian; Feyerabend, Thorsten B; Rodewald, Hans-Reimer; Rodewald, Hans-Reimwer; Boeckxstaens, Guy E; Matteoli, Gianluca

    2014-01-01

    Intestinal manipulation (IM) during abdominal surgery results in intestinal inflammation leading to hypomotility or ileus. Mast cell activation is thought to play a crucial role in the pathophysiology of postoperative ileus (POI). However, this conclusion was mainly drawn using mast cell-deficient mouse models with abnormal Kit signaling. These mice also lack interstitial cells of Cajal (ICC) resulting in aberrant gastrointestinal motility even prior to surgery, compromising their use as model to study POI. To avoid these experimental weaknesses we took advantage of a newly developed knock-in mouse model, Cpa3(Cre/+) , devoid of mast cells but with intact Kit signaling. The role of mast cells in the development of POI and intestinal inflammation was evaluated assessing gastrointestinal transit and muscularis externa inflammation after IM in two strains of mice lacking mast cells, i.e. Kit(W-sh/W-sh) and Cpa3(Cre/+) mice, and by use of the mast cell stabilizer cromolyn. Kit(W-sh/W-sh) mice lack ICC networks and already revealed significantly delayed gastrointestinal transit even before surgery. IM did not further delay intestinal transit, but induced infiltration of myeloperoxidase positive cells, expression of inflammatory cytokines and recruitment of monocytes and neutrophils into the muscularis externa. On the contrary, Cpa3(Cre/+) mice have a normal network of ICC and normal gastrointestinal. Surprisingly, IM in Cpa3(Cre/+) mice caused delay in gut motility and intestinal inflammation as in wild type littermates mice (Cpa3(+/+) ). Furthermore, treatment with the mast cell inhibitor cromolyn resulted in an inhibition of mast cells without preventing POI. Here, we confirm that IM induced mast cell degranulation. However, our data demonstrate that mast cells are not required for the pathogenesis of POI in mice. Although there might be species differences between mouse and human, our results argue against mast cell inhibitors as a therapeutic approach to shorten POI.

  14. Mast Cells Play No Role in the Pathogenesis of Postoperative Ileus Induced by Intestinal Manipulation

    PubMed Central

    Gomez-Pinilla, Pedro J.; Farro, Giovanna; Di Giovangiulio, Martina; Stakenborg, Nathalie; Némethova, Andrea; de Vries, Annick; Liston, Adrian; Feyerabend, Thorsten B.; Rodewald, Hans-Reimwer; Boeckxstaens, Guy E.; Matteoli, Gianluca

    2014-01-01

    Introduction Intestinal manipulation (IM) during abdominal surgery results in intestinal inflammation leading to hypomotility or ileus. Mast cell activation is thought to play a crucial role in the pathophysiology of postoperative ileus (POI). However, this conclusion was mainly drawn using mast cell-deficient mouse models with abnormal Kit signaling. These mice also lack interstitial cells of Cajal (ICC) resulting in aberrant gastrointestinal motility even prior to surgery, compromising their use as model to study POI. To avoid these experimental weaknesses we took advantage of a newly developed knock-in mouse model, Cpa3Cre/+, devoid of mast cells but with intact Kit signaling. Design The role of mast cells in the development of POI and intestinal inflammation was evaluated assessing gastrointestinal transit and muscularis externa inflammation after IM in two strains of mice lacking mast cells, i.e. KitW-sh/W-sh and Cpa3Cre/+ mice, and by use of the mast cell stabilizer cromolyn. Results KitW-sh/W-sh mice lack ICC networks and already revealed significantly delayed gastrointestinal transit even before surgery. IM did not further delay intestinal transit, but induced infiltration of myeloperoxidase positive cells, expression of inflammatory cytokines and recruitment of monocytes and neutrophils into the muscularis externa. On the contrary, Cpa3Cre/+ mice have a normal network of ICC and normal gastrointestinal. Surprisingly, IM in Cpa3Cre/+ mice caused delay in gut motility and intestinal inflammation as in wild type littermates mice (Cpa3+/+). Furthermore, treatment with the mast cell inhibitor cromolyn resulted in an inhibition of mast cells without preventing POI. Conclusions Here, we confirm that IM induced mast cell degranulation. However, our data demonstrate that mast cells are not required for the pathogenesis of POI in mice. Although there might be species differences between mouse and human, our results argue against mast cell inhibitors as a therapeutic approach to shorten POI. PMID:24416383

  15. Interrogating the variation of element masses and distribution patterns in single cells using ICP-MS with a high efficiency cell introduction system.

    PubMed

    Wang, Hailong; Wang, Meng; Wang, Bing; Zheng, Lingna; Chen, Hanqing; Chai, Zhifang; Feng, Weiyue

    2017-02-01

    Cellular heterogeneity is an inherent condition of cell populations, which results from stochastic expression of genes, proteins, and metabolites. The heterogeneity of individual cells can dramatically influence cellular decision-making and cell fate. So far, our knowledge about how the variation of endogenous metals and non-metals in individual eukaryotic cells is limited. In this study, ICP-MS equipped with a high efficiency cell introduction system (HECIS) was developed as a method of single-cell ICP-MS (SC-ICP-MS). The method was applied to the single-cell analysis of Mn, Fe, Co, Cu, Zn, P, and S in human cancer cell lines (HeLa and A549) and normal human bronchial epithelial cell line (16HBE). The analysis showed obvious variation of the masses of Cu, Fe, Zn, and P in individual HeLa cells, and variation of Fe, Zn, and P in individual A549 cells. On the basis of the single-cell data, a multimodal distribution of the elements in the cell population was fitted, which showed marked differences among the various cell lines. Importantly, subpopulations of the elements were found in the cell populations, especially in the HeLa cancer cells. This study demonstrates that SC-ICP-MS is able to unravel the extent of variation of endogenous elements in individual cells, which will help to improve our fundamental understanding of cellular biology and reveal novel insights into human biology and medicine. Graphical abstract The variations of masses and distribution patterns of elements Mn, Fe, Co, Cu, Zn, P, and S in single cells were successfully detected by ICP-MS coupled with a high efficiency cell introduction system (HECIS).

  16. Mnemonic neuronal activity in somatosensory cortex.

    PubMed Central

    Zhou, Y D; Fuster, J M

    1996-01-01

    Single-unit activity was recorded from the hand areas of the somatosensory cortex of monkeys trained to perform a haptic delayed matching to sample task with objects of identical dimensions but different surface features. During the memory retention period of the task (delay), many units showed sustained firing frequency change, either excitation or inhibition. In some cases, firing during that period was significantly higher after one sample object than after another. These observations indicate the participation of somatosensory neurons not only in the perception but in the short-term memory of tactile stimuli. Neurons most directly implicated in tactile memory are (i) those with object-selective delay activity, (ii) those with nondifferential delay activity but without activity related to preparation for movement, and (iii) those with delay activity in the haptic-haptic delayed matching task but no such activity in a control visuo-haptic delayed matching task. The results indicate that cells in early stages of cortical somatosensory processing participate in haptic short-term memory. PMID:8927629

  17. Spectral models for early time SN 2011fe observations

    NASA Astrophysics Data System (ADS)

    Baron, E.; Hoeflich, P.; Friesen, Brian; Sullivan, M.; Hsiao, E.; Ellis, R. S.; Gal-Yam, A.; Howell, D. A.; Nugent, P. E.; Dominguez, I.; Krisciunas, K.; Phillips, M. M.; Suntzeff, N.; Wang, L.; Thomas, R. C.

    2015-12-01

    We use observed UV through near-IR spectra to examine whether SN 2011fe can be understood in the framework of Branch-normal Type Ia supernovae (SNe Ia) and to examine its individual peculiarities. As a benchmark, we use a delayed-detonation model with a progenitor metallicity of Z⊙/20. We study the sensitivity of features to variations in progenitor metallicity, the outer density profile, and the distribution of radioactive nickel. The effect of metallicity variations in the progenitor have a relatively small effect on the synthetic spectra. We also find that the abundance stratification of SN 2011fe resembles closely that of a delayed-detonation model with a transition density that has been fit to other Branch-normal SNe Ia. At early times, the model photosphere is formed in material with velocities that are too high, indicating that the photosphere recedes too slowly or that SN 2011fe has a lower specific energy in the outer ≈0.1 M⊙ than does the model. We discuss several explanations for the discrepancies. Finally, we examine variations in both the spectral energy distribution and in the colours due to variations in the progenitor metallicity, which suggests that colours are only weak indicators for the progenitor metallicity, in the particular explosion model that we have studied. We do find that the flux in the U band is significantly higher at maximum light in the solar metallicity model than in the lower metallicity model and the lower metallicity model much better matches the observed spectrum.

  18. Differential roles of two delayed rectifier potassium currents in regulation of ventricular action potential duration and arrhythmia susceptibility.

    PubMed

    Devenyi, Ryan A; Ortega, Francis A; Groenendaal, Willemijn; Krogh-Madsen, Trine; Christini, David J; Sobie, Eric A

    2017-04-01

    Arrhythmias result from disruptions to cardiac electrical activity, although the factors that control cellular action potentials are incompletely understood. We combined mathematical modelling with experiments in heart cells from guinea pigs to determine how cellular electrical activity is regulated. A mismatch between modelling predictions and the experimental results allowed us to construct an improved, more predictive mathematical model. The balance between two particular potassium currents dictates how heart cells respond to perturbations and their susceptibility to arrhythmias. Imbalances of ionic currents can destabilize the cardiac action potential and potentially trigger lethal cardiac arrhythmias. In the present study, we combined mathematical modelling with information-rich dynamic clamp experiments to determine the regulation of action potential morphology in guinea pig ventricular myocytes. Parameter sensitivity analysis was used to predict how changes in ionic currents alter action potential duration, and these were tested experimentally using dynamic clamp, a technique that allows for multiple perturbations to be tested in each cell. Surprisingly, we found that a leading mathematical model, developed with traditional approaches, systematically underestimated experimental responses to dynamic clamp perturbations. We then re-parameterized the model using a genetic algorithm, which allowed us to estimate ionic current levels in each of the cells studied. This unbiased model adjustment consistently predicted an increase in the rapid delayed rectifier K + current and a drastic decrease in the slow delayed rectifier K + current, and this prediction was validated experimentally. Subsequent simulations with the adjusted model generated the clinically relevant prediction that the slow delayed rectifier is better able to stabilize the action potential and suppress pro-arrhythmic events than the rapid delayed rectifier. In summary, iterative coupling of simulations and experiments enabled novel insight into how the balance between cardiac K + currents influences ventricular arrhythmia susceptibility. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  19. Ultra-low-power and robust digital-signal-processing hardware for implantable neural interface microsystems.

    PubMed

    Narasimhan, S; Chiel, H J; Bhunia, S

    2011-04-01

    Implantable microsystems for monitoring or manipulating brain activity typically require on-chip real-time processing of multichannel neural data using ultra low-power, miniaturized electronics. In this paper, we propose an integrated-circuit/architecture-level hardware design framework for neural signal processing that exploits the nature of the signal-processing algorithm. First, we consider different power reduction techniques and compare the energy efficiency between the ultra-low frequency subthreshold and conventional superthreshold design. We show that the superthreshold design operating at a much higher frequency can achieve comparable energy dissipation by taking advantage of extensive power gating. It also provides significantly higher robustness of operation and yield under large process variations. Next, we propose an architecture level preferential design approach for further energy reduction by isolating the critical computation blocks (with respect to the quality of the output signal) and assigning them higher delay margins compared to the noncritical ones. Possible delay failures under parameter variations are confined to the noncritical components, allowing graceful degradation in quality under voltage scaling. Simulation results using prerecorded neural data from the sea-slug (Aplysia californica) show that the application of the proposed design approach can lead to significant improvement in total energy, without compromising the output signal quality under process variations, compared to conventional design approaches.

  20. Individual variation in the neural processes of motor decisions in the stop signal task: the influence of novelty seeking and harm avoidance personality traits.

    PubMed

    Hu, Jianping; Lee, Dianne; Hu, Sien; Zhang, Sheng; Chao, Herta; Li, Chiang-Shan R

    2016-06-01

    Personality traits contribute to variation in human behavior, including the propensity to take risk. Extant work targeted risk-taking processes with an explicit manipulation of reward, but it remains unclear whether personality traits influence simple decisions such as speeded versus delayed responses during cognitive control. We explored this issue in an fMRI study of the stop signal task, in which participants varied in response time trial by trial, speeding up and risking a stop error or slowing down to avoid errors. Regional brain activations to speeded versus delayed motor responses (risk-taking) were correlated to novelty seeking (NS), harm avoidance (HA) and reward dependence (RD), with age and gender as covariates, in a whole brain regression. At a corrected threshold, the results showed a positive correlation between NS and risk-taking responses in the dorsomedial prefrontal, bilateral orbitofrontal, and frontopolar cortex, and between HA and risk-taking responses in the parahippocampal gyrus and putamen. No regional activations varied with RD. These findings demonstrate that personality traits influence the neural processes of executive control beyond behavioral tasks that involve explicit monetary reward. The results also speak broadly to the importance of characterizing inter-subject variation in studies of cognition and brain functions.

  1. Local equilibrium and the second law of thermodynamics for irreversible systems with thermodynamic inertia.

    PubMed

    Glavatskiy, K S

    2015-10-28

    Validity of local equilibrium has been questioned for non-equilibrium systems which are characterized by delayed response. In particular, for systems with non-zero thermodynamic inertia, the assumption of local equilibrium leads to negative values of the entropy production, which is in contradiction with the second law of thermodynamics. In this paper, we address this question by suggesting a variational formulation of irreversible evolution of a system with non-zero thermodynamic inertia. We introduce the Lagrangian, which depends on the properties of the normal and the so-called "mirror-image" systems. We show that the standard evolution equations, in particular, the Maxwell-Cattaneo-Vernotte equation, can be derived from the variational procedure without going beyond the assumption of local equilibrium. We also argue that the second law of thermodynamics in non-equilibrium should be understood as a consequence of the variational procedure and the property of local equilibrium. For systems with instantaneous response this leads to the standard requirement of the local instantaneous entropy production being always positive. However, if a system is characterized by delayed response, the formulation of the second law of thermodynamics should be altered. In particular, the quantity, which is always positive, is not the instantaneous entropy production, but the entropy production averaged over a proper time interval.

  2. Effects of delayed treatment with combined GDNF and continuous electrical stimulation on spiral ganglion cell survival in deafened guinea pigs.

    PubMed

    Scheper, Verena; Paasche, Gerrit; Miller, Josef M; Warnecke, Athanasia; Berkingali, Nurdanat; Lenarz, Thomas; Stöver, Timo

    2009-05-01

    Electrical stimulation (ES) of spiral ganglion cells (SGC) via a cochlear implant is the standard treatment for profound sensor neural hearing loss. However, loss of hair cells as the morphological correlate of sensor neural hearing loss leads to deafferentation and death of SGC. Although immediate treatment with ES or glial cell line-derived neurotrophic factor (GDNF) can prevent degeneration of SGC, only few studies address the effectiveness of delayed treatment. We hypothesize that both interventions have a synergistic effect and that even delayed treatment would protect SGC. Therefore, an electrode connected to a pump was implanted into the left cochlea of guinea pigs 3 weeks after deafening. The contralateral untreated cochleae served as deafened intraindividual controls. Four groups were set up. Control animals received intracochlear infusion of artificial perilymph (AP/-). The experimental groups consisted of animals treated with AP in addition to continuous ES (AP/ES) or treated with GDNF alone (GDNF/-) or GDNF combined with continuous ES (GDNF/ES). Acoustically and electrically evoked auditory brain stem responses were recorded. All animals were killed 48 days after deafening; their cochleae were histologically evaluated. Survival of SGC increased significantly in the GDNF/- and AP/ES group compared with the AP/- group. A highly significant increase in SGC density was observed in the GDNF/ES group compared with the control group. Additionally, animals in the GDNF/ES group showed reduced EABR thresholds. Thus, delayed treatment with GDNF and ES can protect SGC from degeneration and may improve the benefits of cochlear implants.

  3. Serotonin Transporter Promoter Region (5-HTTLPR) Polymorphism Is Not Associated With Paroxetine-Induced Ejaculation Delay in Dutch Men With Lifelong Premature Ejaculation

    PubMed Central

    Janssen, Paddy K.C.; Zwinderman, Aeilko H.; Olivier, Berend

    2014-01-01

    Purpose To investigate the association between the 5-HT-transporter-gene-linked promoter region (5-HTTLPR) polymorphism and 20-mg paroxetine-induced ejaculation delay in men with lifelong premature ejaculation (LPE). Materials and Methods This was a prospective study of 10 weeks of paroxetine treatment in 54 men with LPE. Intravaginal ejaculation latency time (IELT) was measured by stopwatch. Controls consisted of 92 Caucasian men. All men with LPE were genotyped for the 5-HTTLPR polymorphism. Allele frequencies and genotypes of short (S) and long (L) variants of the polymorphism were compared between patients and controls. Associations between the LL, SL, and SS genotypes and fold increase of mean IELT were investigated. Results Of the 54 patients, 43 (79.6%) responded to 20-mg paroxetine treatment with an ejaculation delay, whereas 11 patients (20.4%) did not respond; 44%, 18%, and 18% of the patients showed a fold increase in mean IELT of 2-10, 10-20, and more than 20, respectively. Of the 54 men, 14 (25.9%) had the LL genotype, 29 (53.7%) had the SL genotype, and 11 (20.4%) had the SS genotype. In the 92 controls, the LL, SL, and SS genotypes were present in 27 (29.3%), 41 (44.6%), and 24 (26.1%), respectively. No statistically significant differences were found in 5-HTTLPR allelic variations or in 5-HTTLPR gene variations. In all men treated with 20 mg paroxetine, analysis of variance of the natural logarithm of fold increase in the IELT showed no statistically significant difference according to genotype (p=0.83). Conclusions The 5-HTTLPR polymorphism is not associated with daily 20-mg paroxetine treatment-induced ejaculation delay in men with LPE. PMID:24578810

  4. The Genetic Control of Reproductive Development under High Ambient Temperature.

    PubMed

    Ejaz, Mahwish; von Korff, Maria

    2017-01-01

    Ambient temperature has a large impact on reproductive development and grain yield in temperate cereals. However, little is known about the genetic control of development under different ambient temperatures. Here, we demonstrate that in barley (Hordeum vulgare), high ambient temperatures accelerate or delay reproductive development depending on the photoperiod response gene PHOTOPERIOD1 (Ppd-H1) and its upstream regulator EARLY FLOWERING3 (HvELF3). A natural mutation in Ppd-H1 prevalent in spring barley delayed floral development and reduced the number of florets and seeds per spike, while the wild-type Ppd-H1 or a mutant Hvelf3 allele accelerated floral development and maintained the seed number under high ambient temperatures. High ambient temperature delayed the expression phase and reduced the amplitude of clock genes and repressed the floral integrator gene FLOWERING LOCUS T1 independently of the genotype. Ppd-H1-dependent variation in flowering time under different ambient temperatures correlated with relative expression levels of the BARLEY MADS-box genes VERNALIZATION1 (HvVRN1), HvBM3, and HvBM8 in the leaf. Finally, we show that Ppd-H1 interacts with regulatory variation at HvVRN1. Ppd-H1 only accelerated floral development in the background of a spring HvVRN1 allele with a deletion in the regulatory intron. The full-length winter Hvvrn1 allele was strongly down-regulated, and flowering was delayed by high temperatures irrespective of Ppd-H1 Our findings demonstrate that the photoperiodic and vernalization pathways interact to control flowering time and floret fertility in response to ambient temperature in barley. © 2017 American Society of Plant Biologists. All Rights Reserved.

  5. The Genetic Control of Reproductive Development under High Ambient Temperature1[OPEN

    PubMed Central

    2017-01-01

    Ambient temperature has a large impact on reproductive development and grain yield in temperate cereals. However, little is known about the genetic control of development under different ambient temperatures. Here, we demonstrate that in barley (Hordeum vulgare), high ambient temperatures accelerate or delay reproductive development depending on the photoperiod response gene PHOTOPERIOD1 (Ppd-H1) and its upstream regulator EARLY FLOWERING3 (HvELF3). A natural mutation in Ppd-H1 prevalent in spring barley delayed floral development and reduced the number of florets and seeds per spike, while the wild-type Ppd-H1 or a mutant Hvelf3 allele accelerated floral development and maintained the seed number under high ambient temperatures. High ambient temperature delayed the expression phase and reduced the amplitude of clock genes and repressed the floral integrator gene FLOWERING LOCUS T1 independently of the genotype. Ppd-H1-dependent variation in flowering time under different ambient temperatures correlated with relative expression levels of the BARLEY MADS-box genes VERNALIZATION1 (HvVRN1), HvBM3, and HvBM8 in the leaf. Finally, we show that Ppd-H1 interacts with regulatory variation at HvVRN1. Ppd-H1 only accelerated floral development in the background of a spring HvVRN1 allele with a deletion in the regulatory intron. The full-length winter Hvvrn1 allele was strongly down-regulated, and flowering was delayed by high temperatures irrespective of Ppd-H1. Our findings demonstrate that the photoperiodic and vernalization pathways interact to control flowering time and floret fertility in response to ambient temperature in barley. PMID:28049855

  6. Delayed CO2 emissions from mid-ocean ridge volcanism as a possible cause of late-Pleistocene glacial cycles

    NASA Astrophysics Data System (ADS)

    Huybers, P. J.

    2016-12-01

    The coupled variations in ice volume, temperature, and atmospheric CO2 during the late Pleistocene are most often represented as involving some combination of orbital forcing, ice dynamics, and ocean circulation. Also previously argued is that changes in glaciation influence atmospheric CO2 concentrations through modifying subaerial volcanic eruptions and CO2 emissions. Building on recent evidence that ocean ridge volcanism responds to changes in sea level, a conceptual model is presented wherein ocean ridges play an important role in generating late-Pleistocene 100 ky glacial cycles on account of an inherent delay in their feedback response. If all volcanic CO2 emissions responded immediately to changes in pressure, subaerial and ocean-ridge volcanic emissions anomalies would merely oppose one another. At ocean ridges, however, the egress of CO2 from the mantle is delayed by tens-of-thousands of years, or longer, owing to ascent time. The simple model involves temperature, ice, and CO2 and is shown to oscillates at 100 ky time scales when incorporating a delayed CO2 contribution from ocean ridge volcanism, even if the feedback accounts for only a small fraction of total changes in CO2. Features of the model that are consistent with observations include that it readily become phase-locked with insolation forcing associated with changes in Earth's orbit, and that temperature variations lead changes in CO2 by several centuries during deglaciation. Under certain parameterizations, a transition from 41 ky to larger 100 ky oscillations occurs during the middle Pleistocene in response to modulations in orbital forcing. This novel description of Pleistocene glaciation should be testable through ongoing advances in understanding the circulation of carbon through the solid earth.

  7. Changes in autumn vegetation dormancy onset date and the climate controls across temperate ecosystems in China from 1982 to 2010.

    PubMed

    Yang, Yuting; Guan, Huade; Shen, Miaogen; Liang, Wei; Jiang, Lei

    2015-02-01

    Vegetation phenology is a sensitive indicator of the dynamic response of terrestrial ecosystems to climate change. In this study, the spatiotemporal pattern of vegetation dormancy onset date (DOD) and its climate controls over temperate China were examined by analysing the satellite-derived normalized difference vegetation index and concurrent climate data from 1982 to 2010. Results show that preseason (May through October) air temperature is the primary climatic control of the DOD spatial pattern across temperate China, whereas preseason cumulative precipitation is dominantly associated with the DOD spatial pattern in relatively cold regions. Temporally, the average DOD over China's temperate ecosystems has delayed by 0.13 days per year during the past three decades. However, the delay trends are not continuous throughout the 29-year period. The DOD experienced the largest delay during the 1980s, but the delay trend slowed down or even reversed during the 1990s and 2000s. Our results also show that interannual variations in DOD are most significantly related with preseason mean temperature in most ecosystems, except for the desert ecosystem for which the variations in DOD are mainly regulated by preseason cumulative precipitation. Moreover, temperature also determines the spatial pattern of temperature sensitivity of DOD, which became significantly lower as temperature increased. On the other hand, the temperature sensitivity of DOD increases with increasing precipitation, especially in relatively dry areas (e.g. temperate grassland). This finding stresses the importance of hydrological control on the response of autumn phenology to changes in temperature, which must be accounted in current temperature-driven phenological models. © 2014 John Wiley & Sons Ltd.

  8. The use of a prospective audit proforma to improve door-to-mask times for acute exacerbations chronic obstructive pulmonary disease (COPD) requiring non-invasive ventilation (NIV).

    PubMed

    Mandal, S; Howes, T Q; Parker, M; Roberts, C M

    2014-12-01

    Non-invasive ventilation (NIV) is an evidence based management of acidotic, hypercapnic exacerbations of COPD. Previous national and international audits of clinical practice have shown variation against guideline standards with significant delays in initiating NIV. We aimed to map the clinical pathway to better understand delays and reduce the door-to-NIV time to less than 3 hours for all patients with acidotic, hypercapnic exacerbations of COPD requiring this intervention, by mandating the use of a guideline based educational management proforma.The proforma was introduced at 7 acute hospitals in North London and Essex and initiated at admission of the patient. It was used to record the clinical pathway and patient outcomes until the point of discharge or death. Data for 138 patients were collected. 48% of patients commenced NIV within 3 hours with no reduction in door-to-mask time during the study period. Delays in starting NIV were due to: time taken for review by the medical team (101 minutes) and time taken for NIV to be started once a decision had been made (49 minutes). There were significant differences in door-to-NIV decision and mask times between differing respiratory on-call systems, p < 0.05). The introduction of the proforma had no effect on door-to-mask times over the study period. Main reasons for delay were related to timely access to medical staff and to NIV equipment; however, a marked variation in practice within these hospitals was been noted, with a 9-5 respiratory on-call system associated with shorter NIV initiation times.

  9. High-temperature langatate elastic constants and experimental validation up to 900 degrees C.

    PubMed

    Davulis, Peter M; da Cunha, Mauricio Pereira

    2010-01-01

    This paper reports on a set of langatate (LGT) elastic constants extracted from room temperature to 1100 degrees C using resonant ultrasound spectroscopy techniques and an accompanying assessment of these constants at high temperature. The evaluation of the constants employed SAW device measurements from room temperature to 900 degrees C along 6 different LGT wafer orientations. Langatate parallelepipeds and wafers were aligned, cut, ground, and polished, and acoustic wave devices were fabricated at the University of Maine facilities along specific orientations for elastic constant extraction and validation. SAW delay lines were fabricated on LGT wafers prepared at the University of Maine using 100-nm platinumrhodium- zirconia electrodes capable of withstanding temperatures up to 1000 degrees C. The numerical predictions based on the resonant ultrasound spectroscopy high-temperature constants were compared with SAW phase velocity, fractional frequency variation, and temperature coefficients of delay extracted from SAW delay line frequency response measurements. In particular, the difference between measured and predicted fractional frequency variation is less than 2% over the 25 degrees C to 900 degrees C temperature range and within the calculated and measured discrepancies. Multiple temperature-compensated orientations at high temperature were predicted and verified in this paper: 4 of the measured orientations had turnover temperatures (temperature coefficient of delay = 0) between 200 and 420 degrees C, and 2 had turnover temperatures below 100 degrees C. In summary, this work reports on extracted high-temperature elastic constants for LGT up to 1100 degrees C, confirmed the validity of those constants by high-temperature SAW device measurements up to 900 degrees C, and predicted and identified temperature-compensated LGT orientations at high temperature.

  10. Effects of adenosine 5'-monophosphate on epidermal turnover.

    PubMed

    Furukawa, Fukumi; Kanehara, Shoko; Harano, Fumiki; Shinohara, Shigeo; Kamimura, Junko; Kawabata, Shigekatsu; Igarashi, Sachiyo; Kawamura, Mitsuaki; Yamamoto, Yuki; Miyachi, Yoshiki

    2008-10-01

    The structure and function of the epidermis is maintained by cell renewal based on epidermal turnover. Epidermal turnover is delayed by aging, and it is thought that the delay of the epidermal turnover is a cause of aging alternation of skin. The epidermal turnover is related to the energy metabolism of epidermal basal cells. Adenosine 5'-triphosphate (ATP) is needed for cell renewal: cell division, and adenosine 5'-monophosphate (AMP) increases the amount of intracellular ATP. These findings suggest that AMP accelerates the epidermal turnover delayed by aging. This study investigated whether AMP and adenosine 5'-monophosphate disodium salt (AMP2Na) accelerates the epidermal turnover. An effect of AMP2Na on cell proliferation was examined by our counting of keratinocytes. An effect of AMP2Na on cell cycle was examined by our counting of basal cells in DNA synthetic period of hairless rats. The effects of AMP2Na (or AMP) on the epidermal turnover were examined by our measuring stratum corneum transit time by use of guinea pigs, and by our measuring stratum corneum surface area by use of hairless rats and in a clinical pharmacological study. The AMP2Na showed two different profiles on the proliferation of primary cultured keratinocytes. At a low concentration it induced cell growth, whereas at a high concentration it inhibited cell growth. The number of basal cells in the DNA synthetic period of AMP2Na was significantly higher than that of the vehicle in hairless rats. The stratum corneum transit time of AMP2Na was significantly shorter than that of the vehicle in guinea pigs. The corneocyte surface area of emulsion containing AMP2Na was significantly smaller than that of the vehicle in volunteers. We conclude that AMP promotes the cell proliferation and the cell cycle progression of epidermal basal cells and accelerates epidermal turnover safely. In addition, AMP is useful for skin rejuvenation in dermatology and aesthetic dermatology.

  11. Solar generated quasi-biennial geomagnetic variation

    NASA Technical Reports Server (NTRS)

    Sugiura, M.; Poros, D. J.

    1977-01-01

    The existence of highly correlated quasi-biennial variations in the geomagnetic field and in solar activity is demonstrated. The analysis uses a numerical filter technique applied to monthly averages of the geomagnetic horizontal component and of the Zurich relative sunspot number. Striking correlations are found between the quasi-biennial geomagnetic variations determined from several magnetic observatories located at widely different longitudes, indicating a worldwide nature of the obtained variation. The correlation coefficient between the filtered Dst index and the filtered relative sunspot number is found to be -0.79 at confidence level greater than 99% with a time-lag of 4 months, with solar activity preceding the Dst variation. The correlation between the unfiltered data of Dst and of the sunspot number is also high with a similar time-lag. Such a timelag has not been discussed in the literature, and a further study is required to establish the mode of sun-earth relationship that gives this time delay.

  12. Influence of hatch time and access to feed on intramuscular adipose tissue deposition in broilers.

    PubMed

    Powell, D J; Velleman, S G; Cowieson, A J; Singh, M; Muir, W I

    2016-06-01

    The effect of hatch time and subsequent access to feed on intramuscular adipose tissue deposition was studied in the pectoralis major muscle of male Ross 308 broiler chickens. Based on their hatch time chicks were classified as early (EH), midterm (MH), or late (LH) hatchers, with an average incubation duration of 497.7 h for EH, 508.8 h for MH, and 514.5 h for LH birds. Chicks were provided access to feed either immediately at hatch, or 24 h after the conclusion of the hatch window. Expression of the adipogenic regulatory genes peroxisome proliferator-activated receptor gamma (PPARγ), and stearoyl-CoA desaturase (SCD), were measured at the time of hatch, and zero, one, 4, 7, 28, and 40 d. Intramuscular adipocyte cell width and visualization of adipose tissue deposition was observed at 28 and 40 d. Expression of PPARγ was increased in the pectoralis major of LH birds at the time of hatch, zero, and one d. The expression of PPARγ at one and 7 d, and SCD at 7 d were increased in all birds that received delayed access to feed. At 28 d, adipocyte cell width was increased in LH birds with delayed access to feed, compared to EH and MH birds with delayed access to feed and LH birds with immediate access to feed. At 40 d, adipocyte cell width was increased in all birds that received delayed access to feed. Also at 40 d, there was a trend (P = 0.078) for more extensive intramuscular adipose tissue deposition in LH than EH birds, and in birds with delayed access to feed (P = 0.075). These data indicate delayed access to feed increases intramuscular adipose tissue deposition in the pectoralis major muscle, and suggest that hatch time influences this regulation. © 2016 Poultry Science Association Inc.

  13. Cytotoxic effects of ultra-diluted remedies on breast cancer cells.

    PubMed

    Frenkel, Moshe; Mishra, Bal Mukund; Sen, Subrata; Yang, Peiying; Pawlus, Alison; Vence, Luis; Leblanc, Aimee; Cohen, Lorenzo; Banerji, Pratip; Banerji, Prasanta

    2010-02-01

    The use of ultra-diluted natural products in the management of disease and treatment of cancer has generated a lot of interest and controversy. We conducted an in vitro study to determine if products prescribed by a clinic in India have any effect on breast cancer cell lines. We studied four ultra-diluted remedies (Carcinosin, Phytolacca, Conium and Thuja) against two human breast adenocarcinoma cell lines (MCF-7 and MDA-MB-231) and a cell line derived from immortalized normal human mammary epithelial cells (HMLE). The remedies exerted preferential cytotoxic effects against the two breast cancer cell lines, causing cell cycle delay/arrest and apoptosis. These effects were accompanied by altered expression of the cell cycle regulatory proteins, including downregulation of phosphorylated Rb and upregulation of the CDK inhibitor p27, which were likely responsible for the cell cycle delay/arrest as well as induction of the apoptotic cascade that manifested in the activation of caspase 7 and cleavage of PARP in the treated cells. The findings demonstrate biological activity of these natural products when presented at ultra-diluted doses. Further in-depth studies with additional cell lines and animal models are warranted to explore the clinical applicability of these agents.

  14. DELAY OF CLEAVAGE OF THE ARBACIA EGG BY ULTRAVIOLET RADIATION

    PubMed Central

    Blum, Harold F.; Price, Judith P.

    1950-01-01

    While our data do not permit us to state the exact locus or mode of action of ultraviolet radiation in the Arbacia egg, certain general conclusions may be reached. The amount of delay of cleavage of these eggs is determined by two principal factors: (1) The extent of an effect, resulting from photochemical action induced by ultraviolet radiation, which is reversible in a biological sense, the reversibility not being directly dependent upon the process of cell division. (2) The sensitivity of the cell division process to the effects of the ultraviolet-induced photochemical reaction. This factor varies with the stage of cell division, the cell being insensitive during a period corresponding to most of mitosis. It seems likely that these findings may apply to cell division in general, but, since the quantitative relationships observed must, in this case, reflect the integration of two semi-independent factors, the over-all picture may appear quite different for different kinds of cells. PMID:15410486

  15. Enhanced clonal burst size corrects an otherwise defective memory response by CD8+ recent thymic emigrants

    PubMed Central

    Deets, Katherine A.; Berkley, Amy M.; Bergsbaken, Tessa; Fink, Pamela J.

    2016-01-01

    The youngest peripheral T cells (recent thymic emigrants or RTEs) are functionally distinct from naïve T cells that have completed post-thymic maturation. We now assess the RTE memory response, and find that RTEs produced less granzyme B than their mature counterparts during infection, but proliferated more and therefore generated equivalent target killing in vivo. After infection, RTE numbers contracted less dramatically than those of mature T cells, but RTEs were delayed in their transition to central memory, displaying impaired expression of CD62L, IL-2, Eomesodermin, and CXCR4, which resulted in impaired bone marrow localization. RTE-derived and mature memory cells expanded equivalently during rechallenge, indicating the robust proliferative capacity of RTEs was maintained independently of central memory phenotype. Thus, the diminished effector function and delayed central memory differentiation of RTE-derived memory cells are counterbalanced by their increased proliferative capacity, driving the efficacy of the RTE response to that of mature T cells. PMID:26873989

  16. Cutting Edge: Enhanced Clonal Burst Size Corrects an Otherwise Defective Memory Response by CD8+ Recent Thymic Emigrants.

    PubMed

    Deets, Katherine A; Berkley, Amy M; Bergsbaken, Tessa; Fink, Pamela J

    2016-03-15

    The youngest peripheral T cells (recent thymic emigrants [RTEs]) are functionally distinct from naive T cells that have completed postthymic maturation. We assessed the RTE memory response and found that RTEs produced less granzyme B than their mature counterparts during infection but proliferated more and, therefore, generated equivalent target killing in vivo. Postinfection, RTE numbers contracted less dramatically than those of mature T cells, but RTEs were delayed in their transition to central memory, displaying impaired expression of CD62L, IL-2, Eomesodermin, and CXCR4, which resulted in impaired bone marrow localization. RTE-derived and mature memory cells expanded equivalently during rechallenge, indicating that the robust proliferative capacity of RTEs was maintained independently of central memory phenotype. Thus, the diminished effector function and delayed central memory differentiation of RTE-derived memory cells are counterbalanced by their increased proliferative capacity, driving the efficacy of the RTE response to that of mature T cells. Copyright © 2016 by The American Association of Immunologists, Inc.

  17. The acoustic sensor for rapid analysis of bacterial cells in the conductive suspensions.

    PubMed

    Borodina, I A; Zaitsev, B D; Guliy, O; Teplykh, A A; Shikhabudinov, A M

    2017-11-01

    The possibility of using the acoustic sensor on the basis of a two-channel delay line for rapid analysis of bacterial cells in the conductive suspensions was investigated. The dependencies of change in phase and insertion loss of output signal of the sensor on conductivity of buffer solution with various concentrations of cells due to a specific interaction "bacterial cells - mini-antibodies" for electrically open and electrically shorted channels of delay line were measured. It has been found that these changes have the most values for the electrically open channel. It has been also shown that the sensor rapidly responds to the specific interaction and the time stabilization of the phase and insertion loss of output signal is less than 10min. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Impaired activity of CCA-adding enzyme TRNT1 impacts OXPHOS complexes and cellular respiration in SIFD patient-derived fibroblasts.

    PubMed

    Liwak-Muir, Urszula; Mamady, Hapsatou; Naas, Turaya; Wylie, Quinlan; McBride, Skye; Lines, Matthew; Michaud, Jean; Baird, Stephen D; Chakraborty, Pranesh K; Holcik, Martin

    2016-06-18

    SIFD (Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay) is a novel form of congenital sideroblastic anemia associated with B-cell immunodeficiency, periodic fevers, and developmental delay caused by mutations in the CCA-adding enzyme TRNT1, but the precise molecular pathophysiology is not known. We show that the disease causing mutations in patient-derived fibroblasts do not affect subcellular localization of TRNT1 and show no gross morphological differences when compared to control cells. Analysis of cellular respiration and oxidative phosphorylation (OXPHOS) complexes demonstrates that both basal and maximal respiration rates are decreased in patient cells, which may be attributed to an observed decrease in the abundance of select proteins of the OXPHOS complexes. Our data provides further insight into cellular pathophysiology of SIFD.

  19. Graphene quantum dots for cancer targeted drug delivery.

    PubMed

    Iannazzo, Daniela; Pistone, Alessandro; Salamò, Marina; Galvagno, Signorino; Romeo, Roberto; Giofré, Salvatore V; Branca, Caterina; Visalli, Giuseppa; Di Pietro, Angela

    2017-02-25

    A biocompatible and cell traceable drug delivery system Graphene Quantum Dots (GQD) based, for the targeted delivery of the DNA intercalating drug doxorubicin (DOX) to cancer cells, is here reported. Highly dispersible and water soluble GQD, synthesized by acidic oxidation and exfoliation of multi-walled carbon nanotubes (MWCNT), were covalently linked to the tumor targeting module biotin (BTN), able to efficiently recognize biotin receptors over-expressed on cancer cells and loaded with DOX. Biological test performed on A549 cells reported a very low toxicity of the synthesized carrier (GQD and GQD-BTN). In GQD-BTN-DOX treated cancer cells, the cytotoxicity was strongly dependent from cell uptake which was greater and delayed after treatment with GQD-BTN-DOX system with respect to what observed for cells treated with the same system lacking of the targeting module BTN (GQD-DOX) or with the free drug alone. A delayed nuclear internalization of the drug is reported, due to the drug detachment from the nanosystem, triggered by the acidic environment of cancer cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Photonic modulation of EGFR: 280nm low level light arrests cancer cell activation and migration

    NASA Astrophysics Data System (ADS)

    Botelho, Cláudia M.; Marques, Rogério; Viruthachalam, Thiagarajan; Gonçalves, Odete; Vorum, Henrik; Gomes, Andreia C.; Neves-Petersen, Maria Teresa

    2017-02-01

    Overexpression of the Epidermal Growth Factor Receptor (EGFR) by cancer cells is associated with a poor prognosis for the patient. For several decades, therapies targeting EGFR have been designed, including the use of monoclonal antibodies and small molecule tyrosine kinase inhibitors. The use of these molecules had good clinical results, although its efficiency (and specificity) is still far from being optimal. In this paper, we present a new approach for a possible new cancer therapy targeting EGFR and using low intensity 280nm light. The influence of 280nm UVB illumination on cancer cells stimulated with 2nM of EGF was followed by time-lapse confocal microscopy. The 280nm illumination of the cancer cells blocks EGFR activation, inhibiting EGFR internalization and cell migration thus inhibiting the transition to the metastatic phenotype. Exposure time is a very important factor. The higher the illumination time the more significant differences were observed: 280nm light delayed or completely halted EGFR activation in the cell membrane, mainly at the cell junction level, and delayed or halted EGFR endocytic internalization, filopodia formation and cell migration.

  1. Loss of BID Delays FASL-Induced Cell Death of Mouse Neutrophils and Aggravates DSS-Induced Weight Loss.

    PubMed

    Wicki, Simone; Gurzeler, Ursina; Corazza, Nadia; Genitsch, Vera; Wong, Wendy Wei-Lynn; Kaufmann, Thomas

    2018-02-28

    Neutrophils are key players in the early defense against invading pathogens. Due to their potent effector functions, programmed cell death of activated neutrophils has to be tightly controlled; however, its underlying mechanisms remain unclear. Fas ligand (FASL/CD95L) has been shown to induce neutrophil apoptosis, which is accelerated by the processing of the BH3-only protein BH3 interacting domain death agonist (BID) to trigger mitochondrial apoptotic events, and been attributed a regulatory role during viral and bacterial infections. Here, we show that, in accordance with previous works, mouse neutrophils underwent caspase-dependent apoptosis in response to FASL, and that this cell death was significantly delayed upon loss of BID. However, pan-caspase inhibition failed to protect mouse neutrophils from FASL-induced apoptosis and caused a switch to RIPK3-dependent necroptotic cell death. Intriguingly, such a switch was less evident in the absence of BID, particularly under inflammatory conditions. Delayed neutrophil apoptosis has been implicated in several auto-inflammatory diseases, including inflammatory bowel disease. We show that neutrophil and macrophage driven acute dextran sulfate sodium (DSS) induced colitis was slightly more aggravated in BID-deficient mice, based on significantly increased weight loss compared to wild-type controls. Taken together, our data support a central role for FASL > FAS and BID in mouse neutrophil cell death and further underline the anti-inflammatory role of BID.

  2. Loss of BID Delays FASL-Induced Cell Death of Mouse Neutrophils and Aggravates DSS-Induced Weight Loss

    PubMed Central

    Wicki, Simone; Gurzeler, Ursina; Corazza, Nadia; Genitsch, Vera

    2018-01-01

    Neutrophils are key players in the early defense against invading pathogens. Due to their potent effector functions, programmed cell death of activated neutrophils has to be tightly controlled; however, its underlying mechanisms remain unclear. Fas ligand (FASL/CD95L) has been shown to induce neutrophil apoptosis, which is accelerated by the processing of the BH3-only protein BH3 interacting domain death agonist (BID) to trigger mitochondrial apoptotic events, and been attributed a regulatory role during viral and bacterial infections. Here, we show that, in accordance with previous works, mouse neutrophils underwent caspase-dependent apoptosis in response to FASL, and that this cell death was significantly delayed upon loss of BID. However, pan-caspase inhibition failed to protect mouse neutrophils from FASL-induced apoptosis and caused a switch to RIPK3-dependent necroptotic cell death. Intriguingly, such a switch was less evident in the absence of BID, particularly under inflammatory conditions. Delayed neutrophil apoptosis has been implicated in several auto-inflammatory diseases, including inflammatory bowel disease. We show that neutrophil and macrophage driven acute dextran sulfate sodium (DSS) induced colitis was slightly more aggravated in BID-deficient mice, based on significantly increased weight loss compared to wild-type controls. Taken together, our data support a central role for FASL > FAS and BID in mouse neutrophil cell death and further underline the anti-inflammatory role of BID. PMID:29495595

  3. Suppression of the PI3K subunit p85α delays embryoid body development and inhibits cell adhesion.

    PubMed

    Gurney, Susan M R; Forster, Peter; Just, Ursula; Schwanbeck, Ralf

    2011-12-01

    Phosphatidylinositol-3-kinases (PI3Ks) exert a variety of signaling functions in eukaryotes. We suppressed the PI3K regulatory subunit p85α using a small interfering RNA (Pik3r1 siRNA) and examined the effects on embryoid body (EB) development in hanging drop culture. We observed a 150% increase in the volume of the treated EBs within 24 h, compared to the negative controls. Fluorescence Activated Cell Sorting (FACS) assays showed that this increase in volume is not due to increased cellular proliferation. Instead, the increase in volume appears to be due to reduced cellular aggregation and adherence. This is further shown by our observation that 40% of treated EBs form twin instead of single EBs, and that they have a significantly reduced ability to adhere to culture dishes when plated. A time course over the first 96 h reveals that the impaired adherence is transient and explained by an initial 12-hour delay in EB development. Quantitative PCR expression analysis suggests that the adhesion molecule integrin-β1 (ITGB1) is transiently downregulated by the p85α suppression. In conclusion we found that suppressing p85α leads to a delay in forming compact EBs, accompanied by a transient inability of the EBs to undergo normal cell-cell and cell-substrate adhesion. Copyright © 2011 Wiley Periodicals, Inc.

  4. Biophysical modelling of early and delayed radiation damage at chromosome level

    NASA Astrophysics Data System (ADS)

    Andreev, S.; Eidelman, Y.

    Exposure by ionising radiation increases cancer risk in human population Cancer is thought to originate from an altered expression of certain number of specific genes It is now widely recognised that chromosome aberrations CA are involved in stable change in expression of genes by gain or loss of their functions Thus CA can contribute to initiation or progression of cancer Therefore understanding mechanisms of CA formation in the course of cancer development might be valuable tool for quantification and prognosis of different stages of radiation carcinogenesis Early CA are defined as aberrations induced in first post-irradiation mitotic cycle The present work describes the original biophysical technique for early CA modelling It includes the following simulation steps the ionising particle track structure the structural organisation of all chromosomes in G 0 G 1 cell nucleus spatial distribution of radiation induced DNA double-strand breaks dsb within chromosomes dsb rejoining and misrejoining modelling cell cycle taking into account mitotic delay which results in complex time dependence of aberrant cells in first mitosis The results on prediction of dose-response curves for simple and complex CA measured in cells undergoing first division cycle are presented in comparison with recent experimental data There is increasing evidence that CA are also observed in descendents of irradiated cells many generations after direct DNA damage These delayed CA or chromosome instability CI are thought to be a manifestation of genome

  5. Glucose metabolism during rotational shift-work in healthcare workers.

    PubMed

    Sharma, Anu; Laurenti, Marcello C; Dalla Man, Chiara; Varghese, Ron T; Cobelli, Claudio; Rizza, Robert A; Matveyenko, Aleksey; Vella, Adrian

    2017-08-01

    Shift-work is associated with circadian rhythm disruption and an increased risk of obesity and type 2 diabetes. We sought to determine the effect of rotational shift-work on glucose metabolism in humans. We studied 12 otherwise healthy nurses performing rotational shift-work using a randomised crossover study design. On each occasion, participants underwent an isotope-labelled mixed meal test during a simulated day shift and a simulated night shift, enabling simultaneous measurement of glucose flux and beta cell function using the oral minimal model. We sought to determine differences in fasting and postprandial glucose metabolism during the day shift vs the night shift. Postprandial glycaemic excursion was higher during the night shift (381±33 vs 580±48 mmol/l per 5 h, p<0.01). The time to peak insulin and C-peptide and nadir glucagon suppression in response to meal ingestion was also delayed during the night shift. While insulin action did not differ between study days, the beta cell responsivity to glucose (59±5 vs 44±4 × 10 -9  min -1 ; p<0.001) and disposition index were decreased during the night shift. Impaired beta cell function during the night shift may result from normal circadian variation, the effect of rotational shift-work or a combination of both. As a consequence, higher postprandial glucose concentrations are observed during the night shift.

  6. Manufacturing of biodrugs: need for harmonization in regulatory standards.

    PubMed

    Sahoo, Niharika; Choudhury, Koel; Manchikanti, Padmavati

    2009-01-01

    Biodrugs (biologics) are much more complex than chemically synthesized drugs because of their structural heterogeneity and interactions within a given biologic system. The manufacturing process in the biodrug industry varies with each type of molecule and is far more elaborate and stringent due to the use of living organisms and complex substrates. Product purity and altered structural characteristics leading to potential immunogenicity have often been of concern when establishing quality and safety in the use of biodrugs. Regulatory compliance in manufacturing and commercialization of biodrugs involves quality control, quality assurance, and batch documentation. Many factors such as host cell development, cell bank establishment, cell culture, protein production, purification, analysis, formulation, storage, and handling are critical for ensuring the purity, activity, and safety of the finished product. Good Manufacturing Practice (GMP) for biodrugs has been developed in certain regions such as the EU, US, and Japan. Due to differences in manufacturing methods and systems, product-specific GMP guidelines are evolving. In general, there are variations in GMP guidelines between countries, which lead to difficulty for the manufacturers in conforming to different standards, thus entailing delays in the commercialization of biodrugs. There is a need to develop a unified regulatory guideline for biodrug manufacturing across various countries, which would be helpful in the marketing of products and trade. This review deals with the comparative framework and analysis of GMP regulation of biodrugs.

  7. Active flutter suppression using optical output feedback digital controllers

    NASA Technical Reports Server (NTRS)

    1982-01-01

    A method for synthesizing digital active flutter suppression controllers using the concept of optimal output feedback is presented. A convergent algorithm is employed to determine constrained control law parameters that minimize an infinite time discrete quadratic performance index. Low order compensator dynamics are included in the control law and the compensator parameters are computed along with the output feedback gain as part of the optimization process. An input noise adjustment procedure is used to improve the stability margins of the digital active flutter controller. Sample rate variation, prefilter pole variation, control structure variation and gain scheduling are discussed. A digital control law which accommodates computation delay can stabilize the wing with reasonable rms performance and adequate stability margins.

  8. Autoignition characteristics of aircraft-type fuels

    NASA Technical Reports Server (NTRS)

    Spadaccini, L. J.; Tevelde, J. A.

    1980-01-01

    The ignition delay characteristics of Jet A, JP 4, no. 2 diesel, cetane and an experimental referee broad specification (ERBS) fuel in air at inlet temperatures up to 1000 K, pressures of 10, 15, 20, 25 and 30 atm, and fuel air equivalence ratios of 0.3, 0.5, 0.7 and 1.0 were mapped. Ignition delay times in the range of 1 to 50 msec at freestream flow velocities ranging from 20 to 100 m/sec were obtained using a continuous flow test apparatus which permitted independent variation and evaluation of the effect of temperature, pressure, flow rate, and fuel/air ratio. The ignition delay times for all fuels tested appeared to correlate with the inverse of pressure and the inverse exponent of temperature. With the exception of pure cetane, which had the shortest ignition delay times, the differences between the fuels tested did not appear to be significant. The apparent global activation energies for the typical gas turbine fuels ranged from 38 to 40 kcal/mole, while the activation energy determined for cetane was 50 kcal/mole. In addition, the data indicate that for lean mixtures, ignition delay times decrease with increasing equivalence ratio. It was also noted that physical (apparatus dependent) phenomena, such as mixing (i.e., length and number of injection sites) and airstream cooling (due to fuel heating, vaporization and convective heat loss) can have an important effect on the ignition delay.

  9. Effects of additional food in a delayed predator-prey model.

    PubMed

    Sahoo, Banshidhar; Poria, Swarup

    2015-03-01

    We examine the effects of supplying additional food to predator in a gestation delay induced predator-prey system with habitat complexity. Additional food works in favor of predator growth in our model. Presence of additional food reduces the predatory attack rate to prey in the model. Supplying additional food we can control predator population. Taking time delay as bifurcation parameter the stability of the coexisting equilibrium point is analyzed. Hopf bifurcation analysis is done with respect to time delay in presence of additional food. The direction of Hopf bifurcations and the stability of bifurcated periodic solutions are determined by applying the normal form theory and the center manifold theorem. The qualitative dynamical behavior of the model is simulated using experimental parameter values. It is observed that fluctuations of the population size can be controlled either by supplying additional food suitably or by increasing the degree of habitat complexity. It is pointed out that Hopf bifurcation occurs in the system when the delay crosses some critical value. This critical value of delay strongly depends on quality and quantity of supplied additional food. Therefore, the variation of predator population significantly effects the dynamics of the model. Model results are compared with experimental results and biological implications of the analytical findings are discussed in the conclusion section. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Amplitude death and synchronized states in nonlinear time-delay systems coupled through mean-field diffusion

    NASA Astrophysics Data System (ADS)

    Banerjee, Tanmoy; Biswas, Debabrata

    2013-12-01

    We explore and experimentally demonstrate the phenomena of amplitude death (AD) and the corresponding transitions through synchronized states that lead to AD in coupled intrinsic time-delayed hyperchaotic oscillators interacting through mean-field diffusion. We identify a novel synchronization transition scenario leading to AD, namely transitions among AD, generalized anticipatory synchronization (GAS), complete synchronization (CS), and generalized lag synchronization (GLS). This transition is mediated by variation of the difference of intrinsic time-delays associated with the individual systems and has no analogue in non-delayed systems or coupled oscillators with coupling time-delay. We further show that, for equal intrinsic time-delays, increasing coupling strength results in a transition from the unsynchronized state to AD state via in-phase (complete) synchronized states. Using Krasovskii-Lyapunov theory, we derive the stability conditions that predict the parametric region of occurrence of GAS, GLS, and CS; also, using a linear stability analysis, we derive the condition of occurrence of AD. We use the error function of proper synchronization manifold and a modified form of the similarity function to provide the quantitative support to GLS and GAS. We demonstrate all the scenarios in an electronic circuit experiment; the experimental time-series, phase-plane plots, and generalized autocorrelation function computed from the experimental time series data are used to confirm the occurrence of all the phenomena in the coupled oscillators.

  11. Spin-dependent delay time in ferromagnet/insulator/ferromagnet heterostructures

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

    Xie, ZhengWei; Zheng Shi, De; Lv, HouXiang

    2014-07-07

    We study theoretically spin-dependent group delay and dwell time in ferromagnet/insulator/ferromagnet (FM/I/FM) heterostructure. The results indicate that, when the electrons with different spin orientations tunnel through the FM/I/FM junction, the spin-up process and the spin-down process are separated on the time scales. As the self-interference delay has the spin-dependent features, the variations of spin-dependent dwell-time and spin-dependent group-delay time with the structure parameters appear different features, especially, in low incident energy range. These different features show up as that the group delay times for the spin-up electrons are always longer than those for spin-down electrons when the barrier height ormore » incident energy increase. In contrast, the dwell times for the spin-up electrons are longer (shorter) than those for spin-down electrons when the barrier heights (the incident energy) are under a certain value. When the barrier heights (the incident energy) exceed a certain value, the dwell times for the spin-up electrons turn out to be shorter (longer) than those for spin-down electrons. In addition, the group delay time and the dwell time for spin-up and down electrons also relies on the comparative direction of magnetization in two FM layers and tends to saturation with the thickness of the barrier.« less

  12. CD4+CD25+ regulatory T cells suppress allograft rejection mediated by memory CD8+ T cells via a CD30-dependent mechanism.

    PubMed

    Dai, Zhenhua; Li, Qi; Wang, Yinong; Gao, Ge; Diggs, Lonnette S; Tellides, George; Lakkis, Fadi G

    2004-01-01

    CD4(+)CD25(+) regulatory T (Treg) cells suppress naive T cell responses, prevent autoimmunity, and delay allograft rejection. It is not known, however, whether Treg cells suppress allograft rejection mediated by memory T cells, as the latter mount faster and stronger immune responses than their naive counterparts. Here we show that antigen-induced, but not naive, Treg cells suppress allograft rejection mediated by memory CD8(+) T cells. Suppression was allospecific, as Treg cells induced by third-party antigens did not delay allograft rejection. In vivo and in vitro analyses revealed that the apoptosis of allospecific memory CD8(+) T cells is significantly increased in the presence of antigen-induced Treg cells, while their proliferation remains unaffected. Importantly, neither suppression of allograft rejection nor enhanced apoptosis of memory CD8(+) T cells was observed when Treg cells lacked CD30 or when CD30 ligand-CD30 interaction was blocked with anti-CD30 ligand Ab. This study therefore provides direct evidence that pathogenic memory T cells are amenable to suppression in an antigen-specific manner and identifies CD30 as a molecule that is critical for the regulation of memory T cell responses.

  13. CD4+CD25+ regulatory T cells suppress allograft rejection mediated by memory CD8+ T cells via a CD30-dependent mechanism

    PubMed Central

    Dai, Zhenhua; Li, Qi; Wang, Yinong; Gao, Ge; Diggs, Lonnette S.; Tellides, George; Lakkis, Fadi G.

    2004-01-01

    CD4+CD25+ regulatory T (Treg) cells suppress naive T cell responses, prevent autoimmunity, and delay allograft rejection. It is not known, however, whether Treg cells suppress allograft rejection mediated by memory T cells, as the latter mount faster and stronger immune responses than their naive counterparts. Here we show that antigen-induced, but not naive, Treg cells suppress allograft rejection mediated by memory CD8+ T cells. Suppression was allospecific, as Treg cells induced by third-party antigens did not delay allograft rejection. In vivo and in vitro analyses revealed that the apoptosis of allospecific memory CD8+ T cells is significantly increased in the presence of antigen-induced Treg cells, while their proliferation remains unaffected. Importantly, neither suppression of allograft rejection nor enhanced apoptosis of memory CD8+ T cells was observed when Treg cells lacked CD30 or when CD30 ligand–CD30 interaction was blocked with anti–CD30 ligand Ab. This study therefore provides direct evidence that pathogenic memory T cells are amenable to suppression in an antigen-specific manner and identifies CD30 as a molecule that is critical for the regulation of memory T cell responses. PMID:14722622

  14. Delayed seroconversion and rapid onset of lymphoproliferative disease after transmission of human T-cell lymphotropic virus type 1 from a multiorgan donor.

    PubMed

    Glowacka, Ilona; Korn, Klaus; Potthoff, Sebastian A; Lehmann, Ulrich; Kreipe, Hans H; Ivens, Katrin; Barg-Hock, Hannelore; Schulz, Thomas F; Heim, Albert

    2013-11-01

    Human T-cell lymphotropic virus type 1 (HTLV-1) screening of blood and organ donors is not mandatory in Germany because of its low prevalence (about 7/100 000). An HTLV-1 transmission event caused by a multiple organ donor was investigated. Validity of diagnostic procedures and HTLV-1 disease association in immunosuppressed organ recipients were analyzed. Two screening immunoassays and an immunoblot (confirmatory assay) were used for detection of HLTV-1/2 antibodies. Proviral DNA was quantified in blood and biopsies of organ recipients by HTLV-1 real-time polymerase chain reaction (PCR). Proviral HTLV-1-DNA was detected in all blood samples of 3 organ recipients (1-100 copies/10(2) cells), but seroconversion was delayed for up to 2 years in screening assays and >6 years in the confirmatory assay. In 2 of 3 organ recipients, a cutaneous T-cell lymphoma was diagnosed 2 and 3 years after infection, respectively. Proviral HTLV-1 DNA concentration was almost 100 copies/10(2) cells in cutaneous lymphoma biopsies whereas in biopsies of other tissues ≤3.0 copies/10(2) cells were found. The third organ recipient did not suffer from lymphoma, but detailed clinical data on this patient were not available to us. Biopsy results support an etiological role for HTLV-1 in these cases of primary cutaneous T-cell lymphoma after solid organ transplant. HTLV-1-associated lymphoma can arise quickly in immunocompromised transplant recipients. The diagnosis of potentially HTLV-1-associated disease in organ recipients may require PCR because of delayed seroconversion.

  15. Intracellular population genetics: evidence for random drift of mitochondrial allele frequencies in Saccharomyces cerevisiae and Schizosaccharomyces pombe.

    PubMed

    Thrailkill, K M; Birky, C W

    1980-09-01

    We report evidence for random drift of mitochondrial allele frequencies in zygote clones of Saccharomyces cerevisiae and Schizosaccharomyces pombe. Monofactorial and bifactorial crosses were done, using strains resistant or sensitive to erythromycin (alleles Er, Es), oligomycin (Or, Os), or diuron (Dr, Ds). The frequencies of resistant and sensitive cells (and thus the frequencies of the resistant and sensitive alleles) were determined for each of a number of clones of diploid cells arising from individual zygotes. Allele frequencies were extremely variable among these zygote clones; some clones were "uniparental," with mitochondrial alleles from only one parent present. These observations suggest random drift of the allele frequencies in the population of mitochondrial genes within an individual zygote and its diploid progeny. Drift would cease when all the cells in a clone become homoplasmic, due to segregation of the mitochondrial genomes during vegetative cell divisions. To test this, we delayed cell division (and hence segregation) for varying times by starving zygotes in order to give drift more time to operate. As predicted, delaying cell division resulted in an increase in the variance of allele frequencies among the zygote clones and an increase in the proportion of uniparental zygote clones. The changes in form of the allele frequency distributions resembled those seen during random drift in finite Mendelian populations. In bifactorial crosses, genotypes as well as individual alleles were fixed or lost in some zygote clones. However, the mean recombination frequency for a large number of clones did not increase when cell division was delayed. Several possible molecular mechanisms for intracellular random drift are discussed.

  16. Actin cytoskeleton of chemotactic amoebae operates close to the onset of oscillations

    PubMed Central

    Westendorf, Christian; Negrete, Jose; Bae, Albert J.; Sandmann, Rabea; Bodenschatz, Eberhard; Beta, Carsten

    2013-01-01

    The rapid reorganization of the actin cytoskeleton in response to external stimuli is an essential property of many motile eukaryotic cells. Here, we report evidence that the actin machinery of chemotactic Dictyostelium cells operates close to an oscillatory instability. When averaging the actin response of many cells to a short pulse of the chemoattractant cAMP, we observed a transient accumulation of cortical actin reminiscent of a damped oscillation. At the single-cell level, however, the response dynamics ranged from short, strongly damped responses to slowly decaying, weakly damped oscillations. Furthermore, in a small subpopulation, we observed self-sustained oscillations in the cortical F-actin concentration. To substantiate that an oscillatory mechanism governs the actin dynamics in these cells, we systematically exposed a large number of cells to periodic pulse trains of different frequencies. Our results indicate a resonance peak at a stimulation period of around 20 s. We propose a delayed feedback model that explains our experimental findings based on a time-delay in the regulatory network of the actin system. To test the model, we performed stimulation experiments with cells that express GFP-tagged fusion proteins of Coronin and actin-interacting protein 1, as well as knockout mutants that lack Coronin and actin-interacting protein 1. These actin-binding proteins enhance the disassembly of actin filaments and thus allow us to estimate the delay time in the regulatory feedback loop. Based on this independent estimate, our model predicts an intrinsic period of 20 s, which agrees with the resonance observed in our periodic stimulation experiments. PMID:23431176

  17. 75 FR 67901 - National Diabetes Month, 2010

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-04

    ... more complicated or dangerous delivery, and can contribute to their child's obesity later in life. With... together to better prevent, manage, and treat this disease in all its variations. Obesity is one of the... delay or prevent complications. We must also do more to reverse the climbing rates of childhood obesity...

  18. Dysgraphia in Children: Lasting Psychomotor Deficiency or Transient Developmental Delay?

    ERIC Educational Resources Information Center

    Smits-Engelsman, Bouwien C. M.; Van Galen, Gerard P.

    1997-01-01

    Used writing tasks recorded on a computer-monitored XY tablet to differentiate between normal variations in psychomotor development and dysgraphia in 16 young children. Found that control of spatial accuracy, not allograph retrieval or size control, discriminated dysgraphic children from others. Poor writers were less accurate than proficient…

  19. Transition from Target to Gaze Coding in Primate Frontal Eye Field during Memory Delay and Memory–Motor Transformation123

    PubMed Central

    Sajad, Amirsaman; Sadeh, Morteza; Yan, Xiaogang; Wang, Hongying

    2016-01-01

    Abstract The frontal eye fields (FEFs) participate in both working memory and sensorimotor transformations for saccades, but their role in integrating these functions through time remains unclear. Here, we tracked FEF spatial codes through time using a novel analytic method applied to the classic memory-delay saccade task. Three-dimensional recordings of head-unrestrained gaze shifts were made in two monkeys trained to make gaze shifts toward briefly flashed targets after a variable delay (450-1500 ms). A preliminary analysis of visual and motor response fields in 74 FEF neurons eliminated most potential models for spatial coding at the neuron population level, as in our previous study (Sajad et al., 2015). We then focused on the spatiotemporal transition from an eye-centered target code (T; preferred in the visual response) to an eye-centered intended gaze position code (G; preferred in the movement response) during the memory delay interval. We treated neural population codes as a continuous spatiotemporal variable by dividing the space spanning T and G into intermediate T–G models and dividing the task into discrete steps through time. We found that FEF delay activity, especially in visuomovement cells, progressively transitions from T through intermediate T–G codes that approach, but do not reach, G. This was followed by a final discrete transition from these intermediate T–G delay codes to a “pure” G code in movement cells without delay activity. These results demonstrate that FEF activity undergoes a series of sensory–memory–motor transformations, including a dynamically evolving spatial memory signal and an imperfect memory-to-motor transformation. PMID:27092335

  20. Increased proliferation of late-born retinal progenitor cells by gestational lead exposure delays rod and bipolar cell differentiation.

    PubMed

    Chaney, Shawnta Y; Mukherjee, Shradha; Giddabasappa, Anand; Rueda, Elda M; Hamilton, W Ryan; Johnson, Jerry E; Fox, Donald A

    2016-01-01

    Studies of neuronal development in the retina often examine the stages of proliferation, differentiation, and synaptic development, albeit independently. Our goal was to determine if a known neurotoxicant insult to a population of retinal progenitor cells (RPCs) would affect their eventual differentiation and synaptic development. To that end, we used our previously published human equivalent murine model of low-level gestational lead exposure (GLE). Children and animals with GLE exhibit increased scotopic electroretinogram a- and b-waves. Adult mice with GLE exhibit an increased number of late-born RPCs, a prolonged period of RPC proliferation, and an increased number of late-born rod photoreceptors and rod and cone bipolar cells (BCs), with no change in the number of late-born Müller glial cells or early-born neurons. The specific aims of this study were to determine whether increased and prolonged RPC proliferation alters the spatiotemporal differentiation and synaptic development of rods and BCs in early postnatal GLE retinas compared to control retinas. C57BL/6N mouse pups were exposed to lead acetate via drinking water throughout gestation and until postnatal day 10, which is equivalent to the human gestation period for retinal neurogenesis. RT-qPCR, immunohistochemical analysis, and western blots of well-characterized, cell-specific genes and proteins were performed at embryonic and early postnatal ages to assess rod and cone photoreceptor differentiation, rod and BC differentiation and synaptic development, and Müller glial cell differentiation. Real-time quantitative PCR (RT-qPCR) with the rod-specific transcription factors Nrl , Nr2e3 , and Crx and the rod-specific functional gene Rho , along with central retinal confocal studies with anti-recoverin and anti-rhodopsin antibodies, revealed a two-day delay in the differentiation of rod photoreceptors in GLE retinas. Rhodopsin immunoblots supported this conclusion. No changes in glutamine synthetase gene or protein expression, a marker for late-born Müller glial cells, were observed in the developing retinas. In the retinas from the GLE mice, anti-PKCα, - Chx10 (Vsx2) and -secretagogin antibodies revealed a two- to three-day delay in the differentiation of rod and cone BCs, whereas the expression of the proneural and BC genes Otx2 and Chx10 , respectively, increased. In addition, confocal studies of proteins associated with functional synapses (e.g., vesicular glutamate transporter 1 [VGluT1], plasma membrane calcium ATPase [PMCA], transient receptor potential channel M1 [TRPM1], and synaptic vesicle glycoprotein 2B [SV2B]) revealed a two-day delay in the formation of the outer and inner plexiform layers of the GLE retinas. Moreover, several markers revealed that the initiation of the differentiation and intensity of the labeling of early-born cells in the retinal ganglion cell and inner plexiform layers were not different in the control retinas. Our combined gene, confocal, and immunoblot findings revealed that the onset of rod and BC differentiation and their subsequent synaptic development is delayed by two to three days in GLE retinas. These results suggest that perturbations during the early proliferative stages of late-born RPCs fated to be rods and BCs ultimately alter the coordinated time-dependent progression of rod and BC differentiation and synaptic development. These GLE effects were selective for late-born neurons. Although the molecular mechanisms are unknown, alterations in soluble neurotrophic factors and/or their receptors are likely to play a role. Since neurodevelopmental delays and altered synaptic connectivity are associated with neuropsychiatric and behavioral disorders as well as cognitive deficits, future work is needed to determine if similar effects occur in the brains of GLE mice and whether children with GLE experience similar delays in retinal and brain neuronal differentiation and synaptic development.

  1. Hypoxia Response Element-Regulated MMP-9 Promotes Neurological Recovery via Glial Scar Degradation and Angiogenesis in Delayed Stroke.

    PubMed

    Cai, Hongxia; Ma, Yuanyuan; Jiang, Lu; Mu, Zhihao; Jiang, Zhen; Chen, Xiaoyan; Wang, Yongting; Yang, Guo-Yuan; Zhang, Zhijun

    2017-06-07

    Matrix metalloproteinase 9 (MMP-9) plays a beneficial role in the delayed phase of middle cerebral artery occlusion (MCAO). However, the mechanism is obscure. Here, we constructed hypoxia response element (HRE)-regulated MMP-9 to explore its effect on glial scars and neurogenesis in delayed ischemic stroke. Adult male Institute of Cancer Research (ICR) mice underwent MCAO and received a stereotactic injection of lentivirus carrying HRE-MMP-9 or normal saline (NS)/lentivirus-GFP 7 days after ischemia. We found that HRE-MMP-9 improved neurological outcomes, reduced ischemia-induced brain atrophy, and degraded glial scars (p < 0.05). Furthermore, HRE-MMP-9 increased the number of microvessels in the peri-infarct area (p < 0.001), which may have been due to the accumulation of endogenous endothelial progenitor cells (EPCs) in the peri-infarct area after glial scar degradation. Finally, HRE-MMP-9 increased the number of bromodeoxyuridine-positive (BrdU + )/NeuN + cells and the expression of PSD-95 in the peri-infarct area (p < 0.01). These changes could be blocked by vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor SU5416 and MMP-9 inhibitor 2-[[(4-phenoxyphenyl)sulfonyl]methyl]-thiirane (SB-3CT). Our results provided a novel mechanism by which glial scar degradation and vascular endothelial growth factor (VEGF)/VEGFR2-dependent angiogenesis may be key procedures for neurological recovery in delayed ischemic stroke after HRE-MMP-9 treatment. Therefore, HRE-MMP-9 overexpression in the delayed ischemic brain is a promising approach for neurological recovery. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  2. High quality cord blood banking is feasible with delayed clamping practices. The eight-year experience and current status of the national Swedish Cord Blood Bank.

    PubMed

    Frändberg, Sofia; Waldner, Berit; Konar, Jan; Rydberg, Lennart; Fasth, Anders; Holgersson, Jan

    2016-09-01

    The National Swedish Cord Blood Bank (NS-CBB) is altruistic and publicly funded. Herein we describe the status of the bank and the impact of delayed versus early clamping on cell number and volume. Cord Blood Units (CBUs) were collected at two University Hospitals in Sweden. Collected volume and nucleated cell content (TNC) were investigated in 146 consecutive Cord Blood (CB) collections sampled during the first quarter of 2012 and in 162 consecutive CB collections done in the first quarter of 2013, before and after clamping practices were changed from immediate to late (60 s) clamping. NS-CBB now holds close to 5000 units whereof 30 % are from non-Caucasian or mixed origins. Delayed clamping had no major effect on collection efficiency. The volume collected was slightly reduced (mean difference, 8.1 ml; 95 % CI, 1.3-15.0 ml; p = 0.02), while cell recovery was not (p = 0.1). The proportion of CBUs that met initial total TNC banking criteria was 60 % using a TNC threshold of 12.5 × 10(8), and 47 % using a threshold of 15 × 10(8) for the early clamping group and 52 and 37 % in the late clamping group. Following implementation of delayed clamping practices at NS-CBB; close to 40 % of the collections in the late clamping group still met the high TNC banking threshold and were eligible for banking, implicating that that cord blood banking is feasible with delayed clamping practices.

  3. Protein degradation rate is the dominant mechanism accounting for the differences in protein abundance of basal p53 in a human breast and colorectal cancer cell line.

    PubMed

    Lakatos, Eszter; Salehi-Reyhani, Ali; Barclay, Michael; Stumpf, Michael P H; Klug, David R

    2017-01-01

    We determine p53 protein abundances and cell to cell variation in two human cancer cell lines with single cell resolution, and show that the fractional width of the distributions is the same in both cases despite a large difference in average protein copy number. We developed a computational framework to identify dominant mechanisms controlling the variation of protein abundance in a simple model of gene expression from the summary statistics of single cell steady state protein expression distributions. Our results, based on single cell data analysed in a Bayesian framework, lends strong support to a model in which variation in the basal p53 protein abundance may be best explained by variations in the rate of p53 protein degradation. This is supported by measurements of the relative average levels of mRNA which are very similar despite large variation in the level of protein.

  4. Single-cell profiling of peanut-responsive T cells in patients with peanut allergy reveals heterogeneous effector TH2 subsets.

    PubMed

    Chiang, David; Chen, Xintong; Jones, Stacie M; Wood, Robert A; Sicherer, Scott H; Burks, A Wesley; Leung, Donald Y M; Agashe, Charuta; Grishin, Alexander; Dawson, Peter; Davidson, Wendy F; Newman, Leah; Sebra, Robert; Merad, Miriam; Sampson, Hugh A; Losic, Bojan; Berin, M Cecilia

    2018-06-01

    The contribution of phenotypic variation of peanut-specific T cells to clinical allergy or tolerance to peanut is not well understood. Our objective was to comprehensively phenotype peanut-specific T cells in the peripheral blood of subjects with and without peanut allergy (PA). We obtained samples from patients with PA, including a cohort undergoing baseline peanut challenges for an immunotherapy trial (Consortium of Food Allergy Research [CoFAR] 6). Subjects were confirmed as having PA, or if they passed a 1-g peanut challenge, they were termed high-threshold subjects. Healthy control (HC) subjects were also recruited. Peanut-responsive T cells were identified based on CD154 expression after 6 to 18 hours of stimulation with peanut extract. Cells were analyzed by using flow cytometry and single-cell RNA sequencing. Patients with PA had tissue- and follicle-homing peanut-responsive CD4 + T cells with a heterogeneous pattern of T H 2 differentiation, whereas control subjects had undetectable T-cell responses to peanut. The PA group had a delayed and IL-2-dependent upregulation of CD154 on cells expressing regulatory T (Treg) cell markers, which was absent in HC or high-threshold subjects. Depletion of Treg cells enhanced cytokine production in HC subjects and patients with PA in vitro, but cytokines associated with highly differentiated T H 2 cells were more resistant to Treg cell suppression in patients with PA. Analysis of gene expression by means of single-cell RNA sequencing identified T cells with highly correlated expression of IL4, IL5, IL9, IL13, and the IL-25 receptor IL17RB. These results demonstrate the presence of highly differentiated T H 2 cells producing T H 2-associated cytokines with functions beyond IgE class-switching in patients with PA. A multifunctional T H 2 response was more evident than a Treg cell deficit among peanut-responsive T cells. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. All rights reserved.

  5. Cytogenetic effects of space-relevant hze-particles in human blood lymphocytes

    NASA Astrophysics Data System (ADS)

    Lee, R.; Nasonova, E.; Ritter, S.

    The analysis of aberrations in human lymphocytes collected 48 h after exposure is used since the 1960s to estimate the radiation risk. However, evidence is increasing that this protocol is not reliable in the case of high LET exposure, because particle induced cell cycle delays influence the aberration yield. To contribute to this issue lymphocytes obtained from a healthy donor were irradiated with Fe-ions (200 MeV/n, 440 keV/μ m), iron-like particles (˜ 4 MeV/n Ni- and Cr-ions, ˜ 4000 keV/μ m) and X-rays. Directly after irradiation PHA and BrdU was added to the cell culture medium. Aberrations were measured in first mitoses collected at 48, 60 and 72 h post-irradiation following colcemid treatment and in prematurely condensed G2-cells (PCCs) at 48 h using calyculin A. Samples were stained with the FPG-technique to allow cell cycle discrimination. Additionally, the mitotic index, the BrdU-labelling index and the number of apoptotic cells were determined at several time-points. Analysis of the BrdU-labelling indices and the mitotic indices revealed a dose- and LET-dependent delay in the cell cycle progression. Cells that reached the first mitosis 48 h after high LET exposure carried only a few aberrations. However, cells that entered the first mitosis 60 to 72 h after high LET exposure carried at least five times more aberrations than those collected at 48 h. The analysis of chromosomal damage in G2-PCCs showed that the delayed entry of severely damaged cells into mitosis results from a prolonged arrest in G2. Conversely, after X-ray exposure a stable aberration-yield was observed in lymphocytes collected at different time-points post-irradiation and the number of aberrations measured in G2-PCCs was only slightly higher than in metaphase cells. Furthermore, only in samples exposed to stopping heavy charged particles a high frequency of apoptotic cells was detected indicating that under this exposure conditions a large proportion of heavily damaged cells is rapidly removed from the cell population. In summary, our data demonstrate that the genetic risk of high energy Fe-ions will be considerably underestimated, when metaphase cells are only analysed at 48 h post-treatment, because of a selective delay of heavily damaged lymphocytes. Similarly, stopping heavy particles affect the time-course of aberrations. However, due to the low mitotic indices and the high apoptotic rates observed in samples exposed to stopping particles, it is reasonable to assume that most aberrant cells are rapidly eliminated from the cell population. Thus, the neoplastic risk of low energy, high LET particles is expected to be low. Supported by BMBF (Bonn), grant 02S8203.

  6. Peripolesis followed by cytotoxicity in chronic idiopathic inflammatory bowel disease.

    PubMed Central

    Wilders, M M; Drexhage, H A; Kokjé, M; Verspaget, H W; Meuwissen, S G

    1984-01-01

    Antigen presenting veiled cells have recently been described in cell suspensions prepared from the gut wall of patients with chronic idiopathic inflammatory bowel disease (CIBD). The normal gut wall is virtually devoid of these cells. In this report we describe a phenomenon known as peripolesis studied by phase contrast cinematography. This is a process in which lymphocytes are seen to wander around larger target cells. These could be identified ultrastructurally as Ia positive veiled cells. In most cases peripolesis was followed by lysis of the target cell. Peripolesis was recorded in cell suspensions of three out of seven patients with ulcerative colitis and in three out of nine patients with Crohn's disease; furthermore peripolesis was observed in one out of two patients with non-classifiable CIBD. In four cell suspensions showing peripolesis, cell lysis could be recorded and was especially striking in ulcerative colitis. Peripolesis involving veiled cells was previously described in delayed hypersensitivity reactions. This study lends support to the concept that delayed allergic reactivity plays a part in chronic inflammatory bowel disease. The antigens involved are, however, completely unknown. Images Fig. 1 Fig. 2 Fig. 3 PMID:6380839

  7. The effect of modifying response and performance feedback parameters on the CNV in humans

    NASA Technical Reports Server (NTRS)

    Otto, D. A.; Leifer, L. J.

    1972-01-01

    The effect on the CNV of sustained and delayed motor response with the dominant and nondominant hand in the presence and absence of visual performance feedback, was studied in 15 male adults. Monopolar scalp recordings were obtained at Fz, Cz, Pz, and bilaterally over the motor hand area. Results indicated that the magnitude of the CNV was greater in the delayed than sustained response task, greater in the presence than absence of feedback, and greater over the motor hand area contralateral to movement. Frontal CNV habituated in the sustained, but not the delayed response task, suggested that frontal negative variations in the former case signify an orienting response to novelty or uncertainty. The absence of habituation in the delay condition was interpreted in terms of the motor inhibitory function of frontal association cortex. Performance feedback appeared to enhance CNV indirectly by increasing the motivation of subjects. A multiprocess conception of CNV was proposed in which vortex-negative slow potentials reflect a multiplicity of psychophysiological processes occurring at a variety of cortical and subcortical locations in the brain preparatory to a motor or mental action.

  8. Dynamical Behaviors in Complex-Valued Love Model With or Without Time Delays

    NASA Astrophysics Data System (ADS)

    Deng, Wei; Liao, Xiaofeng; Dong, Tao

    2017-12-01

    In this paper, a novel version of nonlinear model, i.e. a complex-valued love model with two time delays between two individuals in a love affair, has been proposed. A notable feature in this model is that we separate the emotion of one individual into real and imaginary parts to represent the variation and complexity of psychophysiological emotion in romantic relationship instead of just real domain, and make our model much closer to reality. This is because love is a complicated cognitive and social phenomenon, full of complexity, diversity and unpredictability, which refers to the coexistence of different aspects of feelings, states and attitudes ranging from joy and trust to sadness and disgust. By analyzing associated characteristic equation of linearized equations for our model, it is found that the Hopf bifurcation occurs when the sum of time delays passes through a sequence of critical value. Stability of bifurcating cyclic love dynamics is also derived by applying the normal form theory and the center manifold theorem. In addition, it is also shown that, for some appropriate chosen parameters, chaotic behaviors can appear even without time delay.

  9. The character of pulse delays during radio bursts in the pulsar B0943+10

    NASA Astrophysics Data System (ADS)

    Suleymanova, S. A.; Pugachev, V. D.

    2017-05-01

    Results of a new series of observations of the anomalous pulsar B0943+10 carried out on the Large Scanning Antenna and DKR-1000 radio telescope of the Pushchino Radio Astronomy Observatory at 112 and 62 MHz, respectively, are presented. Several hundred pulse-arrival times (PATs) obtained on various days in 2013-2016 that correspond to the burst (B) mode emission are analyzed. A method for establishing the many-hour pulse shift in the emission window from 3.5-minute fragments is proposed. The delay of the mean pulse relative to the pre-calculated value follows an exponential law with a relaxation time of about 47 minutes. The pulse delay grows by 6 ms during the five hours following the onset of a burst. The random scatter of the residual PAT deviations is comparable to the amplitude of the systematic variations in these times over the lifetime of the B mode. These observations show that the character of the pulse delay as a function of time is the same at 112 and 62 MHz.

  10. De novo variants in EBF3 are associated with hypotonia, developmental delay, intellectual disability, and autism.

    PubMed

    Tanaka, Akemi J; Cho, Megan T; Willaert, Rebecca; Retterer, Kyle; Zarate, Yuri A; Bosanko, Katie; Stefans, Vikki; Oishi, Kimihiko; Williamson, Amy; Wilson, Golder N; Basinger, Alice; Barbaro-Dieber, Tina; Ortega, Lucia; Sorrentino, Susanna; Gabriel, Melissa K; Anderson, Ilse J; Sacoto, Maria J Guillen; Schnur, Rhonda E; Chung, Wendy K

    2017-11-01

    Using whole-exome sequencing, we identified seven unrelated individuals with global developmental delay, hypotonia, dysmorphic facial features, and an increased frequency of short stature, ataxia, and autism with de novo heterozygous frameshift, nonsense, splice, and missense variants in the Early B-cell Transcription Factor Family Member 3 ( EBF3 ) gene. EBF3 is a member of the collier/olfactory-1/early B-cell factor (COE) family of proteins, which are required for central nervous system (CNS) development. COE proteins are highly evolutionarily conserved and regulate neuronal specification, migration, axon guidance, and dendritogenesis during development and are essential for maintaining neuronal identity in adult neurons. Haploinsufficiency of EBF3 may affect brain development and function, resulting in developmental delay, intellectual disability, and behavioral differences observed in individuals with a deleterious variant in EBF3 . © 2017 Tanaka et al.; Published by Cold Spring Harbor Laboratory Press.

  11. Endothelial NOS-deficient mice reveal dual roles for nitric oxide during experimental autoimmune encephalomyelitis.

    PubMed

    Wu, Muzhou; Tsirka, Stella E

    2009-08-15

    Multiple sclerosis (MS) is a demyelinating autoimmune disease characterized by infiltration of T cells into the central nervous system (CNS) after compromise of the blood-brain barrier. A model used to mimic the disease in mice is experimental autoimmune encephalomyelitis (EAE). In this report, we examine the clinical and histopathological course of EAE in eNOS-deficient (eNOS-/-) mice to determine the role of nitric oxide (NO) derived from this enzyme in the disease progression. We find that eNOS-/- mice exhibit a delayed onset of EAE that correlates with delayed BBB breakdown, thus suggesting that NO production by eNOS underlies the T cell infiltration into the CNS. However, the eNOS-/- mice also eventually exhibit more severe EAE and delayed recovery, indicating that NO undertakes dual roles in MS/EAE, one proinflammatory that triggers disease onset, and the other neuroprotective that promotes recovery from disease exacerbation events.

  12. Radiation-Induced Epigenetic Alterations after Low and High LET Irradiations

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

    Aypar, Umut; Morgan, William F.; Baulch, Janet E.

    Epigenetics, including DNA methylation and microRNA (miRNA) expression, could be the missing link in understanding the delayed, non-targeted effects of radiation including radiationinduced genomic instability (RIGI). This study tests the hypothesis that irradiation induces epigenetic aberrations, which could eventually lead to RIGI, and that the epigenetic aberrations induced by low linear energy transfer (LET) irradiation are different than those induced by high LET irradiations. GM10115 cells were irradiated with low LET x-rays and high LET iron (Fe) ions and evaluated for DNA damage, cell survival and chromosomal instability. The cells were also evaluated for specific locus methylation of nuclear factor-kappamore » B (NFκB), tumor suppressor in lung cancer 1 (TSLC1) and cadherin 1 (CDH1) gene promoter regions, long interspersed nuclear element 1 (LINE-1) and Alu repeat element methylation, CpG and non-CpG global methylation and miRNA expression levels. Irradiated cells showed increased micronucleus induction and cell killing immediately following exposure, but were chromosomally stable at delayed times post-irradiation. At this same delayed time, alterations in repeat element and global DNA methylation and miRNA expression were observed. Analyses of DNA methylation predominantly showed hypomethylation, however hypermethylation was also observed. MiRNA shown to be altered in expression level after x-ray irradiation are involved in chromatin remodeling and DNA methylation. Different and higher incidence of epigenetic changes were observed after exposure to low LET x-rays than high LET Fe ions even though Fe ions elicited more chromosomal damage and cell killing. This study also shows that the irradiated cells acquire epigenetic changes even though they are chromosomally stable suggesting that epigenetic aberrations may arise in the cell without initiating RIGI.« less

  13. Cell killing and chromatid damage in primary human bronchial epithelial cells irradiated with accelerated 56Fe ions

    NASA Technical Reports Server (NTRS)

    Suzuki, M.; Piao, C.; Hall, E. J.; Hei, T. K.

    2001-01-01

    We examined cell killing and chromatid damage in primary human bronchial epithelial cells irradiated with high-energy 56Fe ions. Cells were irradiated with graded doses of 56Fe ions (1 GeV/nucleon) accelerated with the Alternating Gradient Synchrotron at Brookhaven National Laboratory. The survival curves for cells plated 1 h after irradiation (immediate plating) showed little or no shoulder. However, the survival curves for cells plated 24 h after irradiation (delayed plating) had a small initial shoulder. The RBE for 56Fe ions compared to 137Cs gamma rays was 1.99 for immediate plating and 2.73 for delayed plating at the D10. The repair ratio (delayed plating/immediate plating) was 1.67 for 137Cs gamma rays and 1.22 for 56Fe ions. The dose-response curves for initially measured and residual chromatid fragments detected by the Calyculin A-mediated premature chromosome condensation technique showed a linear response. The results indicated that the induction frequency for initially measured fragments was the same for 137Cs gamma rays and 56Fe ions. On the other hand, approximately 85% of the fragments induced by 137Cs gamma rays had rejoined after 24 h of postirradiation incubation; the corresponding amount for 56Fe ions was 37%. Furthermore, the frequency of chromatid exchanges induced by gamma rays measured 24 h after irradiation was higher than that induced by 56Fe ions. No difference in the amount of chromatid damage induced by the two types of radiations was detected when assayed 1 h after irradiation. The results suggest that high-energy 56Fe ions induce a higher frequency of complex, unrepairable damage at both the cellular and chromosomal levels than 137Cs gamma rays in the target cells for radiation-induced lung cancers.

  14. Cenozoic tectonic subsidence in the Southern Continental Margin, South China Sea

    NASA Astrophysics Data System (ADS)

    Fang, Penggao; Ding, Weiwei; Fang, Yinxia; Zhao, Zhongxian; Feng, Zhibing

    2017-06-01

    We analyzed two recently acquired multichannel seismic profiles across the Dangerous Grounds and the Reed Bank area in the South China Sea. Reconstruction of the tectonic subsidence shows that the southern continental margin can be divided into three stages with variable subsidence rate. A delay of tectonic subsidence existed in both areas after a break-up, which was likely related to the major mantle convection during seafloor spreading, that was triggered by the secondary mantle convection below the continental margin, in addition to the variation in lithospheric thickness. Meanwhile, the stage with delayed subsidence rate differed along strikes. In the Reed Bank area, this stage is between 32-23.8 Ma, while in the Dangerous Grounds, it was much later (between 19-15.5 Ma). We believe the propagated rifting in the South China Sea dominated the changes of this delayed subsidence rate stage.

  15. Impulsive Effects on Quasi-Synchronization of Neural Networks With Parameter Mismatches and Time-Varying Delay.

    PubMed

    Tang, Ze; Park, Ju H; Feng, Jianwen

    2018-04-01

    This paper is concerned with the exponential synchronization issue of nonidentically coupled neural networks with time-varying delay. Due to the parameter mismatch phenomena existed in neural networks, the problem of quasi-synchronization is thus discussed by applying some impulsive control strategies. Based on the definition of average impulsive interval and the extended comparison principle for impulsive systems, some criteria for achieving the quasi-synchronization of neural networks are derived. More extensive ranges of impulsive effects are discussed so that impulse could either play an effective role or play an adverse role in the final network synchronization. In addition, according to the extended formula for the variation of parameters with time-varying delay, precisely exponential convergence rates and quasi-synchronization errors are obtained, respectively, in view of different types impulsive effects. Finally, some numerical simulations with different types of impulsive effects are presented to illustrate the effectiveness of theoretical analysis.

  16. Model Predictive Optimal Control of a Time-Delay Distributed-Parameter Systems

    NASA Technical Reports Server (NTRS)

    Nguyen, Nhan

    2006-01-01

    This paper presents an optimal control method for a class of distributed-parameter systems governed by first order, quasilinear hyperbolic partial differential equations that arise in many physical systems. Such systems are characterized by time delays since information is transported from one state to another by wave propagation. A general closed-loop hyperbolic transport model is controlled by a boundary control embedded in a periodic boundary condition. The boundary control is subject to a nonlinear differential equation constraint that models actuator dynamics of the system. The hyperbolic equation is thus coupled with the ordinary differential equation via the boundary condition. Optimality of this coupled system is investigated using variational principles to seek an adjoint formulation of the optimal control problem. The results are then applied to implement a model predictive control design for a wind tunnel to eliminate a transport delay effect that causes a poor Mach number regulation.

  17. Traffic Management in ATM Networks Over Satellite Links

    NASA Technical Reports Server (NTRS)

    Goyal, Rohit; Jain, Raj; Goyal, Mukul; Fahmy, Sonia; Vandalore, Bobby; vonDeak, Thomas

    1999-01-01

    This report presents a survey of the traffic management Issues in the design and implementation of satellite Asynchronous Transfer Mode (ATM) networks. The report focuses on the efficient transport of Transmission Control Protocol (TCP) traffic over satellite ATM. First, a reference satellite ATM network architecture is presented along with an overview of the service categories available in ATM networks. A delay model for satellite networks and the major components of delay and delay variation are described. A survey of design options for TCP over Unspecified Bit Rate (UBR), Guaranteed Frame Rate (GFR) and Available Bit Rate (ABR) services in ATM is presented. The main focus is on traffic management issues. Several recommendations on the design options for efficiently carrying data services over satellite ATM networks are presented. Most of the results are based on experiments performed on Geosynchronous (GEO) latencies. Some results for Low Earth Orbits (LEO) and Medium Earth Orbit (MEO) latencies are also provided.

  18. Revisiting the Marshmallow Test: A Conceptual Replication Investigating Links Between Early Delay of Gratification and Later Outcomes.

    PubMed

    Watts, Tyler W; Duncan, Greg J; Quan, Haonan

    2018-05-01

    We replicated and extended Shoda, Mischel, and Peake's (1990) famous marshmallow study, which showed strong bivariate correlations between a child's ability to delay gratification just before entering school and both adolescent achievement and socioemotional behaviors. Concentrating on children whose mothers had not completed college, we found that an additional minute waited at age 4 predicted a gain of approximately one tenth of a standard deviation in achievement at age 15. But this bivariate correlation was only half the size of those reported in the original studies and was reduced by two thirds in the presence of controls for family background, early cognitive ability, and the home environment. Most of the variation in adolescent achievement came from being able to wait at least 20 s. Associations between delay time and measures of behavioral outcomes at age 15 were much smaller and rarely statistically significant.

  19. Controlling periodic ripple microstructure formation on 4H-SiC crystal with three time-delayed femtosecond laser beams of different linear polarizations.

    PubMed

    He, Wanlin; Yang, Jianjun; Guo, Chunlei

    2017-03-06

    The control of laser-induced periodic ripple microstructures on 4H-SiC crystal surface is studied using temporally delayed collinear three femtosecond laser pulse trains linearly polarized in different directions. The ripple orientation appears to develop independent of the individual laser polarizations and exhibits non-monotonical change with variable time delays, whose variation tendency is also affected by the polarization intersection angles. Remarkably, the ripple period is observed to transfer from high- to low-spatial-frequency regions, accompanied by distinctly improved morphological uniformity and clearness. The results are satisfactorily interpreted based on a physical model of the surface wave excitation on a transient index metasurface, which is confirmed by further experiments. Our investigations indicate that transient noneqilibrium dynamics of the material surface provides an effective way to manipulate the laser-induced microstructures.

  20. Influence of cell temperature on sulfur dioxide contamination in proton exchange membrane fuel cells

    NASA Astrophysics Data System (ADS)

    Zhai, Y.; Bender, G.; Bethune, K.; Rocheleau, R.

    2014-02-01

    The effects of temperature on sulfur dioxide (SO2) contamination in PEMFCs are investigated by operating single cells with 2 ppm SO2 in the cathode at different temperatures. Cell performance response shows that voltage degradation was delayed and appears a transition of multiple processes at low temperatures; a similar performance loss is observed when performances reached steady state. The restored performance from the reversible and the irreversible degradations highly depends on temperature. At low temperature, the performance recovery is only negligible with neat air operation (self-recovery), while full recovery is observed after cyclic voltammetry (CV) scanning. As temperature increased, so did the self-recovery performance. However, the total recovery performance decreased. Electrochemical impedance spectroscopy analysis indicates that the potential-dependent poisoning process was delayed at low temperature, and the removal of the sulfur species from Pt/C was inhibited during the self-recovery. Water balance analysis implies that the delay could be attributed to the effect of liquid water scavenging and the mass transport of SO2 in the membrane electrode assemblies. The CV analysis confirms that the decomposition/desorption of the sulfur adsorbates was inhibited and indicates that the SO2 crossover from the cathode to the anode side was also mitigated at low temperature.

Some links on this page may take you to non-federal websites. Their policies may differ from this site.
Top