The oncogenic transforming potential of the passage of single α particles through mammalian cell nuclei

PubMed Central

Miller, Richard C.; Randers-Pehrson, Gerhard; Geard, Charles R.; Hall, Eric J.; Brenner, David J.

1999-01-01

Domestic, low-level exposure to radon gas is considered a major environmental lung-cancer hazard involving DNA damage to bronchial cells by α particles from radon progeny. At domestic exposure levels, the relevant bronchial cells are very rarely traversed by more than one α particle, whereas at higher radon levels—at which epidemiological studies in uranium miners allow lung-cancer risks to be quantified with reasonable precision—these bronchial cells are frequently exposed to multiple α-particle traversals. Measuring the oncogenic transforming effects of exactly one α particle without the confounding effects of multiple traversals has hitherto been unfeasible, resulting in uncertainty in extrapolations of risk from high to domestic radon levels. A technique to assess the effects of single α particles uses a charged-particle microbeam, which irradiates individual cells or cell nuclei with predefined exact numbers of particles. Although previously too slow to assess the relevant small oncogenic risks, recent improvements in throughput now permit microbeam irradiation of large cell numbers, allowing the first oncogenic risk measurements for the traversal of exactly one α particle through a cell nucleus. Given positive controls to ensure that the dosimetry and biological controls were comparable, the measured oncogenicity from exactly one α particle was significantly lower than for a Poisson-distributed mean of one α particle, implying that cells traversed by multiple α particles contribute most of the risk. If this result applies generally, extrapolation from high-level radon risks (involving cellular traversal by multiple α particles) may overestimate low-level (involving only single α particles) radon risks. PMID:9874764

MTR FAST NEUTRON FLUX MEASUREMENTS FOR CYCLE 146

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

Weber, L D; Hogg, C H

1962-03-20

The fast neutron fluxes in selected positions of the MTR were measured for Cycle 146. The measurements were made at the beginning, throughout, and at the end of the cycle (564 Mwd). Vertical traverses for each position monitors are shown. (auth)

The effects of delta rays on the number of particle-track traversals per cell in laboratory and space exposures

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; Nikjoo, H.; Goodhead, D. T.; Wilson, J. W. (Principal Investigator)

1998-01-01

It is a common practice to estimate the number of particle-track traversals per cell or cell nucleus as the product of the ion's linear energy transfer (LET) and cell area. This practice ignores the effects of track width due to the lateral extension of delta rays. We make estimates of the number of particle-track traversals per cell, which includes the effects of delta rays using radial cutoffs in the ionization density about an ion's track of 1 mGy and 1 cGy. Calculations for laboratory and space radiation exposures are discussed, and show that the LET approximation provides a large underestimate of the actual number of particle-track traversals per cell from high-charge and energy (HZE) ions. In light of the current interest in the mechanisms of radiation action, including signal transduction and cytoplasmic damage, these results should be of interest for radiobiology studies with HZE ions.

Histone H2A is required for normal centromere function in Saccharomyces cerevisiae

PubMed Central

Pinto, Inés; Winston, Fred

2000-01-01

Histones are structural and functional components of the eukaryotic chromosome, and their function is essential for normal cell cycle progression. In this work, we describe the characterization of two Saccharomyces cerevisiae cold-sensitive histone H2A mutants. Both mutants contain single amino acid replacements of residues predicted to be on the surface of the nucleosome and in close contact with DNA. We show that these H2A mutations cause an increase-in-ploidy phenotype, an increased rate of chromosome loss, and a defect in traversing the G2–M phase of the cell cycle. Moreover, these H2A mutations show genetic interactions with mutations in genes encoding kinetochore components. Finally, chromatin analysis of these H2A mutants has revealed an altered centromeric chromatin structure. Taken together, these results strongly suggest that histone H2A is required for proper centromere–kinetochore function during chromosome segregation. PMID:10747028

The relationship of fibroblast translocations to cell morphology and stress fibre density.

PubMed

Lewis, L; Verna, J M; Levinstone, D; Sher, S; Marek, L; Bell, E

1982-02-01

Translocation of human fibroblasts in culture was studied using techniques of time-lapse cinemicrography, indirect immunofluorescence, and computer analysis. An inverse relationship between the velocity of cells during the last hour of life and the density of stress fibers seen by immune staining was demonstrated. Translocating cells generally assumed one of two interconvertible morphologies: a triangular tailed shape or tailed fibroblast (TF), and a tailless form that resembled a half-moon, which we call a half-moon fibroblast (HMF). The tail of TFs formed only on regions of substrate that had been previously traversed by cells. The half-moon morphology developed either on previously used or on virgin substrate. Cells adopted the HMF rather than the TF morphology with a four-fold greater frequency. HMFs translocated slightly faster than TFs. The foregoing observation suggest that the fibroblast tail is not an organelle essential for translocation. Since our technique allowed us to distinguish between cells which were cycling and those which had left cycle, we compared their velocities and found them to be similar. Also the average velocities of cells of different population-doubling levels (10th, 30th, 40th) were approximately equal.

Enforced expression of the c-myc oncogene inhibits cell differentiation by precluding entry into a distinct predifferentiation state in G/sub 0//G/sub 1/

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

Freytag, S.O.

1988-04-01

A broad base of data has implicated a role for the c-myc proto-oncogene in the control of the cell cycle and cell differentiation. To further define the role of myc in these processes, the authors examined the effect of enforced myc expression on several events that are thought to be important steps leading to the terminally differentiated state: (i) the ability to arrest growth in G/sub 0//G/sub 1/, (ii) the ability to replicate the genome upon initiation of the differentiation program, and (iii) the ability to loose responsiveness to mitogens and withdraw from the cell cycle. 3T3-L1 preadipocyte cell linesmore » expressing various levels of myc mRNA were established by transfection with a recombinant myc gene under the transcriptional control of the Rous sarcoma virus (RSV) promoter. Cells that expressed high constitutive levels of pRSV myc mRNA arrested in G/sub 0//G/sub 1/ at densities similar to those of normal cells at confluence. Upon initiation of the differentiation program, such cells traversed the cell cycle with kinetics similar to those of normal cells and subsequently arrested in G/sub 0//G/sub 1/. Thus, enforced expression of myc had no effect on the ability of cells to arrest growth in G/sub 0//G/sub 1/ or to replicate the genome upon initiation of the differentiation program. Cells were then tested for their ability to reenter the cell cycle upon exposure to high concentrations of serum and for their capacity to differentiate. In contrast to normal cells, cells expressing high constitutive levels of myc RNA reentered the cell cycle when challenged with 30% serum and failed to terminally differentiate.« less

Repetitive Supra-Physiological Shear Stress Impairs Red Blood Cell Deformability and Induces Hemolysis.

PubMed

Horobin, Jarod T; Sabapathy, Surendran; Simmonds, Michael J

2017-11-01

The supra-physiological shear stress that blood is exposed to while traversing mechanical circulatory assist devices affects the physical properties of red blood cells (RBCs), impairs RBC deformability, and may induce hemolysis. Previous studies exploring RBC damage following exposure to supra-physiological shear stress have employed durations exceeding clinical instrumentation, thus we explored changes in RBC deformability following exposure to shear stress below the reported "hemolytic threshold" using shear exposure durations per minute (i.e., duty-cycles) reflective of that employed by circulatory assist devices. Blood collected from 20 male donors, aged 18-38 years, was suspended in a viscous medium and exposed to an intermittent shear stress protocol of 1 s at 100 Pa, every 60 s for 60 duty-cycles. During the remaining 59 s/min, the cells were left at stasis until the subsequent duty-cycle commenced. At discrete time points (15/30/45/60 duty-cycles), an ektacytometer measured RBC deformability immediately after shear exposure at 100 Pa. Plasma-free hemoglobin, a measurement of hemolysis, was quantified via spectrophotometry. Supra-physiological shear stress impaired RBC properties, as indicated by: (1) decreased maximal elongation of RBCs at infinite shear stress following 15 duty-cycles (P <0.05); (2) increased real-time RBC deformability during application of the supra-physiological shear stress protocol (100 Pa) following exposure to 1 duty-cycle (F (1.891, 32.15) = 12.21, P = 0.0001); and (3) increased plasma-free hemoglobin following 60 duty-cycles (P < 0.01). The present study indicates that exposure of RBCs to short-term, repeated supra-physiological shear stress, impairs RBC deformability, with the extent of impairment exacerbated with each duty-cycle, and ultimately precipitates hemolysis. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Cellular and molecular alterations in human epithelial cells transformed by high let radiation

NASA Astrophysics Data System (ADS)

Hei, T. K.; Piao, C. Q.; Sutter, T.; Willey, J. C.; Suzuki, K.

An understanding of the radiobiological effects of high LET radiation is essential for human risk estimation and radiation protection. In the present study, we show that a single, 30 cGy dose of 150 keV/mum ^4He ions can malignantly transform human papillomavirus immortalized human bronchial epithelial [BEP2D] cells. Transformed cells produce progressively growing tumors in nude mice. The transformation frequency by the single dose of alpha particles is estimated to be approximately 4 x 10^-7. Based on the average cross-sectional area of BEP2D cells, it can be calculated that a mean traversal of 1.4 particles per cell is sufficient to induce tumorigenic conversion of these cells 3 to 4 months post-irradiation. Tumorigenic BEP2D cells overexpress mutated p53 tumor suppressor oncoproteins in addition to the cell cycle control gene cyclin D1 and D2. This model provides an opportunity to study the cellular and molecular changes at the various stages in radiation carcinogenesis involving human cells.

Plant WEE1 kinase is cell cycle regulated and removed at mitosis via the 26S proteasome machinery

PubMed Central

Cook, Gemma S.; Grønlund, Anne Lentz; Siciliano, Ilario; Spadafora, Natasha; Amini, Maryam; Herbert, Robert J.; Bitonti, M. Beatrice; Graumann, Katja; Francis, Dennis; Rogers, Hilary J.

2013-01-01

In yeasts and animals, premature entry into mitosis is prevented by the inhibitory phosphorylation of cyclin-dependent kinase (CDK) by WEE1 kinase, and, at mitosis, WEE1 protein is removed through the action of the 26S proteasome. Although in higher plants WEE1 function has been confirmed in the DNA replication checkpoint, Arabidopsis wee1 insertion mutants grow normally, and a role for the protein in the G2/M transition during an unperturbed plant cell cycle is yet to be confirmed. Here data are presented showing that the inhibitory effect of WEE1 on CDK activity in tobacco BY-2 cell cultures is cell cycle regulated independently of the DNA replication checkpoint: it is high during S-phase but drops as cells traverse G2 and enter mitosis. To investigate this mechanism further, a yeast two-hybrid screen was undertaken to identify proteins interacting with Arabidopsis WEE1. Three F-box proteins and a subunit of the proteasome complex were identified, and bimolecular fluorescence complementation confirmed an interaction between AtWEE1 and the F-box protein SKP1 INTERACTING PARTNER 1 (SKIP1). Furthermore, the AtWEE1–green fluorescent protein (GFP) signal in Arabidopsis primary roots treated with the proteasome inhibitor MG132 was significantly increased compared with mock-treated controls. Expression of AtWEE1–YFPC (C-terminal portion of yellow fluorescent protein) or AtWEE1 per se in tobacco BY-2 cells resulted in a premature increase in the mitotic index compared with controls, whereas co-expression of AtSKIP1–YFPN negated this effect. These data support a role for WEE1 in a normal plant cell cycle and its removal at mitosis via the 26S proteasome. PMID:23536609

Space charge tune shift, fast resonance traversal, and current limits in circular accelerators

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

Rees, G.H.

1996-06-01

Space charge tune shifts, fast resonance traversals, and current limits are important design issues for low energy, high power circular accelerators. Areas of interest are accumulator rings and fast cycling synchrotrons, and typical applications are for pulsed spallation neutron sources, heavy ion fusion storage ring drivers, and booster injectors for high energy proton and ion facilities. Aspects of the three topics are discussed in the paper. {copyright} {ital 1996 American Institute of Physics.}

Fuel cell water transport

DOEpatents

Vanderborgh, Nicholas E.; Hedstrom, James C.

1990-01-01

The moisture content and temperature of hydrogen and oxygen gases is regulated throughout traverse of the gases in a fuel cell incorporating a solid polymer membrane. At least one of the gases traverses a first flow field adjacent the solid polymer membrane, where chemical reactions occur to generate an electrical current. A second flow field is located sequential with the first flow field and incorporates a membrane for effective water transport. A control fluid is then circulated adjacent the second membrane on the face opposite the fuel cell gas wherein moisture is either transported from the control fluid to humidify a fuel gas, e.g., hydrogen, or to the control fluid to prevent excess water buildup in the oxidizer gas, e.g., oxygen. Evaporation of water into the control gas and the control gas temperature act to control the fuel cell gas temperatures throughout the traverse of the fuel cell by the gases.

The Expression Pattern of the Cell Cycle Inhibitor p19INK4d by Progenitor Cells of the Rat Embryonic Telencephalon and Neonatal Anterior Subventricular Zone

PubMed Central

Coskun, Volkan; Luskin, Marla B.

2014-01-01

In this study we investigated whether the pattern of expression of the cyclin-dependent kinase inhibitor p19INK4d by the unique progenitor cells of the neonatal anterior subventricular zone (SVZa) can account for their ability to divide even though they express phenotypic characteristics of differentiated neurons. p19INK4d was chosen for analysis because it usually acts to block permanently the cell cycle at the G1 phase. p19INK4d immunoreactivity and the incorporation of bromodeoxyuridine (BrdU) by SVZa cells were compared with that of the more typical progenitor cells of the prenatal telencephalic ventricular zone. In the developing telencephalon, p19INK4d is expressed by postmitotic cells and has a characteristic perinuclear distribution depending on the laminar position and state of differentiation of a cell. Moreover, the laminar-specific staining of the developing cerebral cortex revealed that the ventricular zone (VZ) is divided into p19INK4d(+) and p19INK4d(−) sublaminae, indicating that the VZ has a previously unrecognized level of functional organization. Furthermore, the rostral migratory stream, traversed by the SVZa-derived cells, exhibits an anteriorhigh–posteriorlow gradient of p19INK4d expression. On the basis of the p19INK4d immunoreactivity and BrdU incorporation, SVZa-derived cells appear to exit and reenter the cell cycle successively. Thus, in contrast to telencephalic VZ cells, SVZa cells continue to undergo multiple rounds of division and differentiation before becoming postmitotic. PMID:11312294

Calcium-responsive contractility during fertilization in sea urchin eggs.

PubMed

Stack, Christianna; Lucero, Amy J; Shuster, Charles B

2006-04-01

Fertilization triggers a reorganization of oocyte cytoskeleton, and in sea urchins, there is a dramatic increase in cortical F-actin. However, the role that myosin II plays during fertilization remains largely unexplored. Myosin II is localized to the cortical cytoskeleton both before and after fertilization and to examine myosin II contractility in living cells, Lytechinus pictus eggs were observed by time-lapse microscopy. Upon sperm binding, a cell surface deflection traversed the egg that was followed by and dependent on the calcium wave. The calcium-dependence of surface contractility could be reproduced in unfertilized eggs, where mobilization of intracellular calcium in unfertilized eggs under compression resulted in a marked contractile response. Lastly, inhibition of myosin II delayed absorption of the fertilization cone, suggesting that myosin II not only responds to the same signals that activate eggs but also participates in the remodeling of the cortical actomyosin cytoskeleton during the first zygotic cell cycle. (c) 2006 Wiley-Liss, Inc.

Calcium-Responsive Contractility During Fertilization in Sea Urchin Eggs

PubMed Central

Stack, Christianna; Lucero, Amy J.; Shuster, Charles B.

2008-01-01

Fertilization triggers a reorganization of oocyte cytoskeleton, and in sea urchins there is a dramatic increase in cortical F-actin. However, the role that myosin II plays during fertilization remains largely unexplored. Myosin II is localized to the cortical cytoskeleton both prior to- and following fertilization, and to examine myosin II contractility in living cells, Lytechinus pictus eggs were observed by time-lapse microscopy. Upon sperm binding, a cell surface deflection traversed the egg that was followed- and dependent on the calcium wave. The calcium-dependence of surface contractility could be reproduced in unfertilized eggs, where mobilization of intracellular calcium in unfertilized eggs under compression resulted in a marked contractile response. Lastly, inhibition of myosin II delayed absorption of the fertilization cone, suggesting that myosin II not only responds to the same signals that activate eggs, but also participates in the remodeling of the cortical actomyosin cytoskeleton during the first zygotic cell cycle. PMID:16470603

Ray tracing a three dimensional scene using a grid

DOEpatents

Wald, Ingo; Ize, Santiago; Parker, Steven G; Knoll, Aaron

2013-02-26

Ray tracing a three-dimensional scene using a grid. One example embodiment is a method for ray tracing a three-dimensional scene using a grid. In this example method, the three-dimensional scene is made up of objects that are spatially partitioned into a plurality of cells that make up the grid. The method includes a first act of computing a bounding frustum of a packet of rays, and a second act of traversing the grid slice by slice along a major traversal axis. Each slice traversal includes a first act of determining one or more cells in the slice that are overlapped by the frustum and a second act of testing the rays in the packet for intersection with any objects at least partially bounded by the one or more cells overlapped by the frustum.

Rotaviruses induce an early membrane permeabilization of MA104 cells and do not require a low intracellular Ca2+ concentration to initiate their replication cycle.

PubMed Central

Cuadras, M A; Arias, C F; López, S

1997-01-01

In this work, we found that rotavirus infection induces an early membrane permeabilization of MA104 cells and promotes the coentry of toxins, such as alpha-sarcin, into the cell. This cell permeability was shown to depend on infectious virus and was also shown to be virus dose dependent, with 10 infectious particles per cell being sufficient to achieve maximum permeability; transient, lasting no more than 15 min after virus entry and probably occurring concomitantly with virus penetration; and specific, since cells that are poorly permissive for rotavirus were not permeabilized. The rotavirus-mediated coentry of toxins was not blocked by the endocytosis inhibitors dansylcadaverine and cytochalasin D or by the vacuolar proton-ATPase inhibitor bafilomycin A1, suggesting that neither endocytocis nor an intraendosomal acidic pH or a proton gradient is required for permeabilization of the cells. Compounds that raise the intracellular concentration of calcium ([Ca2+]i) by different mechanisms, such as the calcium ionophores A23187 and ionomycin and the endoplasmic reticulum calcium-ATPase inhibitor thapsigargin, did not block the coentry of alpha-sarcin or affect the onset of viral protein synthesis, suggesting that a low [Ca2+]i is not essential for the initial steps of the virus life cycle. Since the entry of alpha-sarcin correlates with virus penetration in all parameters tested, the assay for permeabilization to toxins might be a useful tool for studying and characterizing the route of entry and the mechanism used by rotaviruses to traverse the cell membrane and initiate a productive replication cycle. PMID:9371563

Autonomous Science Analyses of Digital Images for Mars Sample Return and Beyond

NASA Technical Reports Server (NTRS)

Gulick, V. C.; Morris, R. L.; Ruzon, M.; Roush, T. L.

1999-01-01

To adequately explore high priority landing sites, scientists require rovers with greater mobility. Therefore, future Mars missions will involve rovers capable of traversing tens of kilometers (vs. tens of meters traversed by Mars Pathfinder's Sojourner). However, the current process by which scientists interact with a rover does not scale to such distances. A single science objective is achieved through many iterations of a basic command cycle: (1) all data must be transmitted to Earth and analyzed; (2) from this data, new targets are selected and the necessary information from the appropriate instruments are requested; (3) new commands are then uplinked and executed by the spacecraft and (4) the resulting data are returned to Earth, starting the process again. Experience with rover tests on Earth shows that this time intensive process cannot be substantially shortened given the limited data downlink bandwidth and command cycle opportunities of real missions. Sending complete multicolor panoramas at several waypoints, for example, is out of the question for a single downlink opportunity. As a result, long traverses requiring many science command cycles would likely require many weeks, months or even years, perhaps exceeding rover design life or other constraints. Autonomous onboard science analyses can address these problems in two ways. First, it will allow the rover to transmit only "interesting" images, defined as those likely to have higher science content. Second, the rover will be able to anticipate future commands, for example acquiring and returning spectra of "interesting" rocks along with the images in which they were detected. Such approaches, coupled with appropriate navigational software, address both the data volume and command cycle bottlenecks that limit both rover mobility and science yield. We are developing algorithms to enable such intelligent decision making by autonomous spacecraft. Reflecting the ultimate level of ability we aim for, this program has been dubbed the "Grad Student on Mars Project". We envision, for example, an appropriately intelligent Athena-like rover at the Pathfinder landing site might be able to traverse over the ridge towards "Twin Peaks" to obtain better information on the stratigraphy of these "streamlined islands" or of the size, composition and morphology of boulders located on them. Along the traverse, the intelligent rover would collect and analyze images and obtain spectra of geologically interesting features or regions. The intelligent rover might also traverse further up Arcs Vallis, and find additional paleoflood stage indicators such as slackwater deposits. Recognizing additional regions where boulders are imbricated, noting changes in their size, distribution, morphology, composition and the associated changes in channel geometry would yield important information on the outflow channel's paleoflood history, Representative images and associated supporting data from these locations could be downlinked to Earth along with the data requested by scientists from the previous uplink opportunity. Our initial work has focused on recognizing geologically interesting portions of images. Here we summarize some of the algorithms to date.

Mutagenic effects of a single and an exact number of alpha particles in mammalian cells

NASA Technical Reports Server (NTRS)

Hei, T. K.; Wu, L. J.; Liu, S. X.; Vannais, D.; Waldren, C. A.; Randers-Pehrson, G.

1997-01-01

One of the main uncertainties in risk estimation for environmental radon exposure using lung cancer data from underground miners is the extrapolation from high- to low-dose exposure where multiple traversal is extremely rare. The biological effects of a single alpha particle are currently unknown. Using the recently available microbeam source at the Radiological Research Accelerator Facility at Columbia University, we examined the frequencies and molecular spectrum of S1- mutants induced in human-hamster hybrid (A(L)) cells by either a single or an exact number of alpha particles. Exponentially growing cells were stained briefly with a nontoxic concentration of Hoechst dye for image analysis, and the location of individual cells was computer-monitored. The nucleus of each cell was irradiated with either 1,2,4, or 8 alpha particles at a linear energy transfer of 90 keV/microm consistent with the energy spectrum of domestic radon exposure. Although single-particle traversal was only slightly cytotoxic to A(L) cells (survival fraction approximately 0.82), it was highly mutagenic, and the induced mutant fraction averaged 110 mutants per 10(5) survivors. In addition, both toxicity and mutant induction were dose-dependent. Multiplex PCR analysis of mutant DNA showed that the proportion of mutants with multilocus deletions increased with the number of particle traversals. These data provide direct evidence that a single a particle traversing a nucleus will have a high probability of resulting in a mutation and highlight the need for radiation protection at low doses.

Mutagenic effects of a single and an exact number of alpha particles in mammalian cells.

PubMed

Hei, T K; Wu, L J; Liu, S X; Vannais, D; Waldren, C A; Randers-Pehrson, G

1997-04-15

One of the main uncertainties in risk estimation for environmental radon exposure using lung cancer data from underground miners is the extrapolation from high- to low-dose exposure where multiple traversal is extremely rare. The biological effects of a single alpha particle are currently unknown. Using the recently available microbeam source at the Radiological Research Accelerator Facility at Columbia University, we examined the frequencies and molecular spectrum of S1- mutants induced in human-hamster hybrid (A(L)) cells by either a single or an exact number of alpha particles. Exponentially growing cells were stained briefly with a nontoxic concentration of Hoechst dye for image analysis, and the location of individual cells was computer-monitored. The nucleus of each cell was irradiated with either 1,2,4, or 8 alpha particles at a linear energy transfer of 90 keV/microm consistent with the energy spectrum of domestic radon exposure. Although single-particle traversal was only slightly cytotoxic to A(L) cells (survival fraction approximately 0.82), it was highly mutagenic, and the induced mutant fraction averaged 110 mutants per 10(5) survivors. In addition, both toxicity and mutant induction were dose-dependent. Multiplex PCR analysis of mutant DNA showed that the proportion of mutants with multilocus deletions increased with the number of particle traversals. These data provide direct evidence that a single a particle traversing a nucleus will have a high probability of resulting in a mutation and highlight the need for radiation protection at low doses.

Intercellular adhesion molecules (ICAMs) and spermatogenesis

PubMed Central

Xiao, Xiang; Mruk, Dolores D.; Cheng, C. Yan

2013-01-01

BACKGROUND During the seminiferous epithelial cycle, restructuring takes places at the Sertoli–Sertoli and Sertoli–germ cell interface to accommodate spermatogonia/spermatogonial stem cell renewal via mitosis, cell cycle progression and meiosis, spermiogenesis and spermiation since developing germ cells, in particular spermatids, move ‘up and down’ the seminiferous epithelium. Furthermore, preleptotene spermatocytes differentiated from type B spermatogonia residing at the basal compartment must traverse the blood–testis barrier (BTB) to enter the adluminal compartment to prepare for meiosis at Stage VIII of the epithelial cycle, a process also accompanied by the release of sperm at spermiation. These cellular events that take place at the opposite ends of the epithelium are co-ordinated by a functional axis designated the apical ectoplasmic specialization (ES)—BTB—basement membrane. However, the regulatory molecules that co-ordinate cellular events in this axis are not known. METHODS Literature was searched at http://www.pubmed.org and http://scholar.google.com to identify published findings regarding intercellular adhesion molecules (ICAMs) and the regulation of this axis. RESULTS Members of the ICAM family, namely ICAM-1 and ICAM-2, and the biologically active soluble ICAM-1 (sICAM-1) are the likely regulatory molecules that co-ordinate these events. sICAM-1 and ICAM-1 have antagonistic effects on the Sertoli cell tight junction-permeability barrier, involved in Sertoli cell BTB restructuring, whereas ICAM-2 is restricted to the apical ES, regulating spermatid adhesion during the epithelial cycle. Studies in other epithelia/endothelia on the role of the ICAM family in regulating cell movement are discussed and this information has been evaluated and integrated into studies of these proteins in the testis to create a hypothetical model, depicting how ICAMs regulate junction restructuring events during spermatogenesis. CONCLUSIONS ICAMs are crucial regulatory molecules of spermatogenesis. The proposed hypothetical model serves as a framework in designing functional experiments for future studies. PMID:23287428

Complex Chemical Reaction Networks from Heuristics-Aided Quantum Chemistry.

PubMed

Rappoport, Dmitrij; Galvin, Cooper J; Zubarev, Dmitry Yu; Aspuru-Guzik, Alán

2014-03-11

While structures and reactivities of many small molecules can be computed efficiently and accurately using quantum chemical methods, heuristic approaches remain essential for modeling complex structures and large-scale chemical systems. Here, we present a heuristics-aided quantum chemical methodology applicable to complex chemical reaction networks such as those arising in cell metabolism and prebiotic chemistry. Chemical heuristics offer an expedient way of traversing high-dimensional reactive potential energy surfaces and are combined here with quantum chemical structure optimizations, which yield the structures and energies of the reaction intermediates and products. Application of heuristics-aided quantum chemical methodology to the formose reaction reproduces the experimentally observed reaction products, major reaction pathways, and autocatalytic cycles.

Pigeons trade efficiency for stability in response to level of challenge during confined flight.

PubMed

Williams, C David; Biewener, Andrew A

2015-03-17

Individuals traversing challenging obstacles are faced with a decision: they can adopt traversal strategies that minimally disrupt their normal locomotion patterns or they can adopt strategies that substantially alter their gait, conferring new advantages and disadvantages. We flew pigeons (Columba livia) through an array of vertical obstacles in a flight arena, presenting them with this choice. The pigeons selected either a strategy involving only a slight pause in the normal wing beat cycle, or a wings-folded posture granting reduced efficiency but greater stability should a misjudgment lead to collision. The more stable but less efficient flight strategy was not used to traverse easy obstacles with wide gaps for passage but came to dominate the postures used as obstacle challenge increased with narrower gaps and there was a greater chance of a collision. These results indicate that birds weigh potential obstacle negotiation strategies and estimate task difficulty during locomotor pattern selection.

Pigeons trade efficiency for stability in response to level of challenge during confined flight

PubMed Central

Williams, C. David; Biewener, Andrew A.

2015-01-01

Individuals traversing challenging obstacles are faced with a decision: they can adopt traversal strategies that minimally disrupt their normal locomotion patterns or they can adopt strategies that substantially alter their gait, conferring new advantages and disadvantages. We flew pigeons (Columba livia) through an array of vertical obstacles in a flight arena, presenting them with this choice. The pigeons selected either a strategy involving only a slight pause in the normal wing beat cycle, or a wings-folded posture granting reduced efficiency but greater stability should a misjudgment lead to collision. The more stable but less efficient flight strategy was not used to traverse easy obstacles with wide gaps for passage but came to dominate the postures used as obstacle challenge increased with narrower gaps and there was a greater chance of a collision. These results indicate that birds weigh potential obstacle negotiation strategies and estimate task difficulty during locomotor pattern selection. PMID:25733863

Effects of altered gravity on the cell cycle, actin cytoskeleton and proteome in Physarum polycephalum

NASA Astrophysics Data System (ADS)

He, Jie; Zhang, Xiaoxian; Gao, Yong; Li, Shuijie; Sun, Yeqing

Some researchers suggest that the changes of cell cycle under the effect of microgravity may be associated with many serious adverse physiological changes. In the search for underlying mechanisms and possible new countermeasures, we used the slime mold Physarum polycephalum in which all the nuclei traverse the cell cycle in natural synchrony to study the effects of altered gravity on the cell cycle, actin cytoskeleton and proteome. In parallel, the cell cycle was analyzed in Physarum incubated (1) in altered gravity for 20 h, (2) in altered gravity for 40 h, (3) in altered gravity for 80 h, and (4) in ground controls. The cell cycle, the actin cytoskeleton, and proteome in the altered gravity and ground controls were examined. The results indicated that the duration of the G2 phase was lengthened 20 min in high aspect ratio vessel (HARV) for 20 h, and prolonged 2 h in altered gravity either for 40 h or for 80 h, whereas the duration of other phases in the cell cycle was unchanged with respect to the control. The microfilaments in G2 phase had a reduced number of fibers and a unique abnormal morphology in altered gravity for 40 h, whereas the microfilaments in other phases of cell cycle were unchanged when compared to controls. Employing classical two-dimensional electrophoresis (2-DE), we examined the effect of the altered gravity on P. polycephalum proteins. The increase in the duration of G2 phase in altered gravity for 40 h was accompanied by changes in the 2-DE protein profiles, over controls. Out of a total of 200 protein spots investigated in G2 phase, which were reproducible in repeated experiments, 72 protein spots were visually identified as specially expressed, and 11 proteins were up-regulated by 2-fold and 28 proteins were down-regulated by 2-fold over controls. Out of a total of three low-expressed proteins in G2 phase in altered gravity for 40 h, two proteins were unknown proteins, and one protein was spherulin 3b by MALDI-TOF mass spectrometry (MS). Our results suggest that a low level of spherulin 3b in G2 phase, which may lead to a reduction of Poly(b-L-malate) (PMLA), may contribute to the lengthened duration of G2 phase in altered gravity for 40 h. Present results indicate that altered gravity results in the prolongation of G2 phase with significantly altered actin cytoskeleton and proteome in P. polycephalum.

Effects of cholera toxin and isobutylmethylxanthine on growth of human fibroblasts

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

Espinoza, B.; Wharton, W.

1986-08-01

Cholera toxin produced a dose-dependent decrease in the restimulation of G0/G1 traverse in density-arrested human fibroblasts but did not inhibit the stimulation of cells arrested in G0 after serum starvation at low density. In addition, cholera toxin did not inhibit the proliferation of sparse logarithmically growing human fibroblasts, even when low concentrations of the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) were also present. However, the final density to which sparse cells grew was limited by cholera toxin, when added either alone or together with low concentrations of IBMX. In contrast, high concentrations of the phosphodiesterase inhibitor alone produced a profound inhibition inmore » the growth of sparse human fibrobasts. IBMX produced an inhibition both in the G1 and in the G2 phases of the cell cycle by a mechanism(s) that was not related to the magnitude of the increases in adenosine 3,5-cyclic monophosphate concentrations.« less

Robotic Exploration: The Role of Science Autonomy

NASA Technical Reports Server (NTRS)

Roush, Ted L.; DeVincenzi, D. (Technical Monitor)

2002-01-01

Historical mission operations have involved: (1) commands transmitted to the craft; (2) execution of commands; (3) return of scientific data; (4) evaluation of these data by scientists; and (5) recommendations for future mission activity by scientists. This cycle is repeated throughout the mission with command opportunities once or twice per day. For a rover, this historical cycle is not amenable to rapid long range traverses or rapid response to any novel or unexpected situations.

Propagation Distance of the α-Particle-Induced Bystander Effect: The Role of Nuclear Traversal and Gap Junction Communication

PubMed Central

Gaillard, Sylvain; Pusset, David; de Toledo, Sonia M.; Fromm, Michel; Azzam, Edouard I.

2009-01-01

When cell populations are exposed to low-dose α-particle radiation, a significant fraction of the cells will not be traversed by a radiation track. However, stressful effects occur in both irradiated and bystander cells in the population. Characterizing these effects, and investigating their underlying mechanism(s), is critical to understanding human health risks associated with exposure to α particles. To this end, confluent normal human fibroblast cultures were grown on polyethylene terephthalate foil grafted to an ultrathin solid-state nuclear track detector and exposed under non-perturbing conditions to low-fluence α particles from a broadbeam irradiator. Irradiated and affected bystander cells were localized with micrometer precision. The stress-responsive protein p21Waf1 (also known as CDKN1A) was induced in bystander cells within a 100-µm radius from an irradiated cell. The mean propagation distance ranged from 20 to 40 µm around the intranuclear α-particle impact point, which corresponds to a set of ∼30 cells. Nuclear traversal, induced DNA damage, and gap junction communication were critical contributors to propagation of this stressful effect The strategy described here may be ideal to investigate the size of radiation-affected target and the relative contribution of different cellular organelles to bystander effects induced by energetic particles, which is relevant to radioprotection and cancer radiotherapy. PMID:19580486

Evaluation of the ability of arsenic species to traverse cell membranes by simple diffusion using octanol-water and liposome-water partition coefficients.

PubMed

Chávez-Capilla, Teresa; Maher, William; Kelly, Tamsin; Foster, Simon

2016-11-01

Arsenic metabolism in living organisms is dependent on the ability of different arsenic species to traverse biological membranes. Simple diffusion provides an alternative influx and efflux route to mediated transport mechanisms that can increase the amount of arsenic available for metabolism in cells. Using octanol-water and liposome-water partition coefficients, the ability of arsenous acid, arsenate, methylarsonate, dimethylarsinate, thio-methylarsonate, thio-dimethylarsinic acid, arsenotriglutathione and monomethylarsonic diglutathione to diffuse through the lipid bilayer of cell membranes was investigated. Molecular modelling of arsenic species was used to explain the results. All arsenic species with the exception of arsenate, methylarsonate and thio-methylarsonate were able to diffuse through the lipid bilayer of liposomes, with liposome-water partition coefficients between 0.04 and 0.13. Trivalent arsenic species and thio-pentavalent arsenic species showed higher partition coefficients, suggesting that they can easily traverse cell membranes by passive simple diffusion. Given the higher toxicity of these species compared to oxo-pentavalent arsenic species, this study provides evidence supporting the risk associated with human exposure to trivalent and thio-arsenic species. Copyright © 2016. Published by Elsevier B.V.

Investigation of the Rocket Induced Flow Field in a Rectangular Duct

NASA Technical Reports Server (NTRS)

Landrum, D. Brian; Thames, Mignon; Parkinson, Doug; Gautney, Serena; Hawk, Clark

1999-01-01

Several tests were performed on a one-sixth scale Rocket Based Combined Cycle (RBCC) engine model at the University of Alabama in Huntsville. The UAH RBCC facility consists of a rectangular duct with a vertical strut mounted in the center. The scaled strut consists of two supersonic rocket nozzles with an embedded vertical turbine between the rocket nozzles. The tests included mass flow, flow visualization and horizontal pressure traverses. The mass flow test indicated a c:hoked condition when the rocket chamber pressure is between 200 psi and 300 psi. The flow visualization tests narrowed the rocket chamber pressure range from, 250 psi to 300 psi. Also, from this t.est, an assumption of a minimum

Streptomyces Exploration: Competition, Volatile Communication and New Bacterial Behaviours.

PubMed

Jones, Stephanie E; Elliot, Marie A

2017-07-01

Streptomyces bacteria are prolific producers of specialized metabolites, and have a well studied, complex life cycle. Recent work has revealed a new type of Streptomyces growth termed 'exploration' - so named for the ability of explorer cells to rapidly traverse solid surfaces. Streptomyces exploration is stimulated by fungal interactions, and is associated with the production of an alkaline volatile organic compound (VOC) capable of inducing exploration by other streptomycetes. Here, we examine Streptomyces exploration from the perspectives of interkingdom interactions, pH-induced morphological switches, and VOC-mediated communication. The phenotypic diversity that can be revealed through microbial interactions and VOC exposure is providing us with insight into novel modes of microbial development, and an opportunity to exploit VOCs to stimulate desired microbial behaviours. Copyright © 2017 Elsevier Ltd. All rights reserved.

The mechanism of nucleosome traversal by RNA polymerase II

PubMed Central

2011-01-01

RNA polymerase II traverses nucleosomes rapidly and efficiently in the cell but it has not been possible to duplicate this process in the test tube. A single nucleosome has generally been found to provide a strong barrier to transcript elongation in vitro. Recent studies have shown that effective transcript elongation can occur on nucleosomal templates in vitro, but this depends on both facilitated uncoiling of DNA from the octamer surface and the presence of transcription factors that maintain polymerase in the transcriptionally competent state. These findings indicate that the efficiency and rate of transcription through chromatin could be regulated through controlled DNA uncoiling. These studies also demonstrate that nucleosome traversal need not result in nucleosome displacement. PMID:21519186

Induction of chromatin damage and distribution of isochromatid breaks in human fibroblast cells exposed to heavy ions

NASA Technical Reports Server (NTRS)

Kawata, Tetsuya; Ito, Hisao; Motoori, Ken; Ueda, Takuya; Shigematsu, Naoyuki; Furusawa, Yoshiya; Durante, Marco; George, Kerry; Wu, Honglu; Cucinotta, Francis A.

2002-01-01

The frequency of chromatid breaks and the distribution of isochromatid breaks were measured in G2-phase normal human fibroblasts prematurely condensed a short time after exposure to low- or high-LET radiations. The average number of isochromatid breaks from a single particle traversal increased with increasing LET values, while the average number of chromatid-type breaks appeared to reach a plateau. The distribution of isochromatid breaks after high-LET iron particles exposure was overdispersed compared to gamma-rays, indicating that a single iron particle traversal through a cell nucleus can produce multiple isochromatid breaks.

Induction of chromatin damage and distribution of isochromatid breaks in human fibroblast cells exposed to heavy ions.

PubMed

Kawata, Tetsuya; Ito, Hisao; Motoori, Ken; Ueda, Takuya; Shigematsu, Naoyuki; Furusawa, Yoshiya; Durante, Marco; George, Kerry; Wu, Honglu; Cucinotta, Francis A

2002-12-01

The frequency of chromatid breaks and the distribution of isochromatid breaks were measured in G2-phase normal human fibroblasts prematurely condensed a short time after exposure to low- or high-LET radiations. The average number of isochromatid breaks from a single particle traversal increased with increasing LET values, while the average number of chromatid-type breaks appeared to reach a plateau. The distribution of isochromatid breaks after high-LET iron particles exposure was overdispersed compared to gamma-rays, indicating that a single iron particle traversal through a cell nucleus can produce multiple isochromatid breaks.

LR: Compact connectivity representation for triangle meshes

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

Gurung, T; Luffel, M; Lindstrom, P

2011-01-28

We propose LR (Laced Ring) - a simple data structure for representing the connectivity of manifold triangle meshes. LR provides the option to store on average either 1.08 references per triangle or 26.2 bits per triangle. Its construction, from an input mesh that supports constant-time adjacency queries, has linear space and time complexity, and involves ordering most vertices along a nearly-Hamiltonian cycle. LR is best suited for applications that process meshes with fixed connectivity, as any changes to the connectivity require the data structure to be rebuilt. We provide an implementation of the set of standard random-access, constant-time operators formore » traversing a mesh, and show that LR often saves both space and traversal time over competing representations.« less

Stereo-vision-based terrain mapping for off-road autonomous navigation

NASA Astrophysics Data System (ADS)

Rankin, Arturo L.; Huertas, Andres; Matthies, Larry H.

2009-05-01

Successful off-road autonomous navigation by an unmanned ground vehicle (UGV) requires reliable perception and representation of natural terrain. While perception algorithms are used to detect driving hazards, terrain mapping algorithms are used to represent the detected hazards in a world model a UGV can use to plan safe paths. There are two primary ways to detect driving hazards with perception sensors mounted to a UGV: binary obstacle detection and traversability cost analysis. Binary obstacle detectors label terrain as either traversable or non-traversable, whereas, traversability cost analysis assigns a cost to driving over a discrete patch of terrain. In uncluttered environments where the non-obstacle terrain is equally traversable, binary obstacle detection is sufficient. However, in cluttered environments, some form of traversability cost analysis is necessary. The Jet Propulsion Laboratory (JPL) has explored both approaches using stereo vision systems. A set of binary detectors has been implemented that detect positive obstacles, negative obstacles, tree trunks, tree lines, excessive slope, low overhangs, and water bodies. A compact terrain map is built from each frame of stereo images. The mapping algorithm labels cells that contain obstacles as nogo regions, and encodes terrain elevation, terrain classification, terrain roughness, traversability cost, and a confidence value. The single frame maps are merged into a world map where temporal filtering is applied. In previous papers, we have described our perception algorithms that perform binary obstacle detection. In this paper, we summarize the terrain mapping capabilities that JPL has implemented during several UGV programs over the last decade and discuss some challenges to building terrain maps with stereo range data.

Stereo Vision Based Terrain Mapping for Off-Road Autonomous Navigation

NASA Technical Reports Server (NTRS)

Rankin, Arturo L.; Huertas, Andres; Matthies, Larry H.

2009-01-01

Successful off-road autonomous navigation by an unmanned ground vehicle (UGV) requires reliable perception and representation of natural terrain. While perception algorithms are used to detect driving hazards, terrain mapping algorithms are used to represent the detected hazards in a world model a UGV can use to plan safe paths. There are two primary ways to detect driving hazards with perception sensors mounted to a UGV: binary obstacle detection and traversability cost analysis. Binary obstacle detectors label terrain as either traversable or non-traversable, whereas, traversability cost analysis assigns a cost to driving over a discrete patch of terrain. In uncluttered environments where the non-obstacle terrain is equally traversable, binary obstacle detection is sufficient. However, in cluttered environments, some form of traversability cost analysis is necessary. The Jet Propulsion Laboratory (JPL) has explored both approaches using stereo vision systems. A set of binary detectors has been implemented that detect positive obstacles, negative obstacles, tree trunks, tree lines, excessive slope, low overhangs, and water bodies. A compact terrain map is built from each frame of stereo images. The mapping algorithm labels cells that contain obstacles as no-go regions, and encodes terrain elevation, terrain classification, terrain roughness, traversability cost, and a confidence value. The single frame maps are merged into a world map where temporal filtering is applied. In previous papers, we have described our perception algorithms that perform binary obstacle detection. In this paper, we summarize the terrain mapping capabilities that JPL has implemented during several UGV programs over the last decade and discuss some challenges to building terrain maps with stereo range data.

Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts After Exposure to Very Low Dose of High Let Radiation

NASA Technical Reports Server (NTRS)

Hada, M.; George, K.; Chappell, L.; Cucinotta, F. A.

2011-01-01

The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (0.01 - 0.20 Gy) of 170 MeV/u Si-28 ions or 600 MeV/u Fe-56 ions, including doses where on average less than one direct ion traversal per cell nucleus occurs. Chromosomes were analyzed using the whole-chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The responses for doses above 0.1 Gy (more than one ion traverses a cell) showed linear dose responses. However, for doses less than 0.1 Gy, both Si-28 ions and Fe-56 ions showed a dose independent response above background chromosome aberrations frequencies. Possible explanations for our results are non-targeted effects due to aberrant cell signaling [1], or delta-ray dose fluctuations [2] where a fraction of cells receive significant delta-ray doses due to the contributions of multiple ion tracks that do not directly traverse cell nuclei where chromosome aberrations are scored.

Constant volume gas cell optical phase-shifter

DOEpatents

Phillion, Donald W.

2002-01-01

A constant volume gas cell optical phase-shifter, particularly applicable for phase-shifting interferometry, contains a sealed volume of atmospheric gas at a pressure somewhat different than atmospheric. An optical window is present at each end of the cell, and as the length of the cell is changed, the optical path length of a laser beam traversing the cell changes. The cell comprises movable coaxial tubes with seals and a volume equalizing opening. Because the cell is constant volume, the pressure, temperature, and density of the contained gas do not change as the cell changes length. This produces an exactly linear relationship between the change in the length of the gas cell and the change in optical phase of the laser beam traversing it. Because the refractive index difference between the gas inside and the atmosphere outside is very much the same, a large motion must be made to change the optical phase by the small fraction of a wavelength that is required by phase-shifting interferometry for its phase step. This motion can be made to great fractional accuracy.

Cell junction dynamics in the testis: Sertoli-germ cell interactions and male contraceptive development.

PubMed

Cheng, C Yan; Mruk, Dolores D

2002-10-01

Spermatogenesis is an intriguing but complicated biological process. However, many studies since the 1960s have focused either on the hormonal events of the hypothalamus-pituitary-testicular axis or morphological events that take place in the seminiferous epithelium. Recent advances in biochemistry, cell biology, and molecular biology have shifted attention to understanding some of the key events that regulate spermatogenesis, such as germ cell apoptosis, cell cycle regulation, Sertoli-germ cell communication, and junction dynamics. In this review, we discuss the physiology and biology of junction dynamics in the testis, in particular how these events affect interactions of Sertoli and germ cells in the seminiferous epithelium behind the blood-testis barrier. We also discuss how these events regulate the opening and closing of the blood-testis barrier to permit the timely passage of preleptotene and leptotene spermatocytes across the blood-testis barrier. This is physiologically important since developing germ cells must translocate across the blood-testis barrier as well as traverse the seminiferous epithelium during their development. We also discuss several available in vitro and in vivo models that can be used to study Sertoli-germ cell anchoring junctions and Sertoli-Sertoli tight junctions. An in-depth survey in this subject has also identified several potential targets to be tackled to perturb spermatogenesis, which will likely lead to the development of novel male contraceptives.

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.

Heritable non-lethal damage to cultured human cells irradiated with heavy ions.

PubMed

Walker, James T; Todd, Paul; Walker, Olivia A

2002-12-01

During interplanetary flights the nuclei of all of a crew member's cells could be traversed by at least one high-LET (Linear Energy Transfer) cosmic-ray particle. In mammalian cells irradiated in vitro about 1 in 10,000 of the surviving cells traversed by heavy particles is transformed to malignancy or mutated. What, if anything, happens to the remaining >99% of surviving cells? A retrospective analysis of archived data and samples from heavy-ion irradiation experiments with cultured human cells in vitro indicated that heavy ions caused a dose- and LET-dependent reduction in growth rates of progeny of irradiated cells, based on colony-size distributions. The maximum action cross section for this effect is between 100 and 300 microm2, at least as large as the cell nuclear area and up to 3 times the cross section for cell killing. Thus, heritable slow growth is the most prevalent effect of high-LET radiations on cultured animal cells, which may have implications for crew health during deep space travel. The views expressed in this article are those of the author(s) and do not necessarily reflect the views or policies of the USEPA.

Correlation of Particle Traversals with Clonogenic Survival Using Cell-Fluorescent Ion Track Hybrid Detector.

PubMed

Dokic, Ivana; Niklas, Martin; Zimmermann, Ferdinand; Mairani, Andrea; Seidel, Philipp; Krunic, Damir; Jäkel, Oliver; Debus, Jürgen; Greilich, Steffen; Abdollahi, Amir

2015-01-01

Development of novel approaches linking the physical characteristics of particles with biological responses are of high relevance for the field of particle therapy. In radiobiology, the clonogenic survival of cells is considered the gold standard assay for the assessment of cellular sensitivity to ionizing radiation. Toward further development of next generation biodosimeters in particle therapy, cell-fluorescent ion track hybrid detector (Cell-FIT-HD) was recently engineered by our group and successfully employed to study physical particle track information in correlation with irradiation-induced DNA damage in cell nuclei. In this work, we investigated the feasibility of Cell-FIT-HD as a tool to study the effects of clinical beams on cellular clonogenic survival. Tumor cells were grown on the fluorescent nuclear track detector as cell culture, mimicking the standard procedures for clonogenic assay. Cell-FIT-HD was used to detect the spatial distribution of particle tracks within colony-initiating cells. The physical data were associated with radiation-induced foci as surrogates for DNA double-strand breaks, the hallmark of radiation-induced cell lethality. Long-term cell fate was monitored to determine the ability of cells to form colonies. We report the first successful detection of particle traversal within colony-initiating cells at subcellular resolution using Cell-FIT-HD.

Identification of GAPDH on the surface of Plasmodium sporozoites as a new candidate for targeting malaria liver invasion

PubMed Central

Kim, Min-Sik

2016-01-01

Malaria transmission begins when an infected mosquito delivers Plasmodium sporozoites into the skin. The sporozoite subsequently enters the circulation and infects the liver by preferentially traversing Kupffer cells, a macrophage-like component of the liver sinusoidal lining. By screening a phage display library, we previously identified a peptide designated P39 that binds to CD68 on the surface of Kupffer cells and blocks sporozoite traversal. In this study, we show that the P39 peptide is a structural mimic of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) on the sporozoite surface and that GAPDH directly interacts with CD68 on the Kupffer cell surface. Importantly, an anti-P39 antibody significantly inhibits sporozoite liver invasion without cross-reacting with mammalian GAPDH. Therefore, Plasmodium-specific GAPDH epitopes may provide novel antigens for the development of a prehepatic vaccine. PMID:27551151

Identification of GAPDH on the surface of Plasmodium sporozoites as a new candidate for targeting malaria liver invasion.

PubMed

Cha, Sung-Jae; Kim, Min-Sik; Pandey, Akhilesh; Jacobs-Lorena, Marcelo

2016-09-19

Malaria transmission begins when an infected mosquito delivers Plasmodium sporozoites into the skin. The sporozoite subsequently enters the circulation and infects the liver by preferentially traversing Kupffer cells, a macrophage-like component of the liver sinusoidal lining. By screening a phage display library, we previously identified a peptide designated P39 that binds to CD68 on the surface of Kupffer cells and blocks sporozoite traversal. In this study, we show that the P39 peptide is a structural mimic of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) on the sporozoite surface and that GAPDH directly interacts with CD68 on the Kupffer cell surface. Importantly, an anti-P39 antibody significantly inhibits sporozoite liver invasion without cross-reacting with mammalian GAPDH. Therefore, Plasmodium-specific GAPDH epitopes may provide novel antigens for the development of a prehepatic vaccine. © 2016 Cha et al.

Experimental investigation of shock-cell noise reduction for single-stream nozzles in simulated flight, comprehensive data report. Volume 2: Laser velocimeter data

NASA Technical Reports Server (NTRS)

Yamamoto, K.; Brausch, J. F.; Janardan, B. A.; Hoerst, D. J.; Price, A. O.; Knott, P. R.

1984-01-01

Mean velocity (axial component) and turbulent velocity (axial component) measurements for thirty one selected flow conditions of six models were performed employing the Laser Doppler Velocimeter Aerodynamic conditions which define the test points are given. Tabulations which explain the scope of mean velocity traverses and turbulence histogram measurements are also presented. The actual LV position, the type of traverse, and measured mean and turbulent velocities along copies of the LV mean velocity traces are contained.

Capturing a flavivirus pre-fusion intermediate.

PubMed

Kaufmann, Bärbel; Chipman, Paul R; Holdaway, Heather A; Johnson, Syd; Fremont, Daved H; Kuhn, Richard J; Diamond, Michael S; Rossmann, Michael G

2009-11-01

During cell entry of flaviviruses, low endosomal pH triggers the rearrangement of the viral surface glycoproteins to a fusion-active state that allows the release of the infectious RNA into the cytoplasm. In this work, West Nile virus was complexed with Fab fragments of the neutralizing mAb E16 and was subsequently exposed to low pH, trapping the virions in a pre-fusion intermediate state. The structure of the complex was studied by cryo-electron microscopy and provides the first structural glimpse of a flavivirus fusion intermediate near physiological conditions. A radial expansion of the outer protein layer of the virion was observed compared to the structure at pH 8. The resulting approximately 60 A-wide shell of low density between lipid bilayer and outer protein layer is likely traversed by the stem region of the E glycoprotein. By using antibody fragments, we have captured a structural intermediate of a virus that likely occurs during cell entry. The trapping of structural transition states by antibody fragments will be applicable for other processes in the flavivirus life cycle and delineating other cellular events that involve conformational rearrangements.

Experimentally induced metamorphosis in axolotls reduces regenerative rate and fidelity

PubMed Central

Stier, Adrian C.; Michonneau, François; Smith, Matthew D.; Pasch, Bret; Maden, Malcolm

2014-01-01

Abstract While most tetrapods are unable to regenerate severed body parts, amphibians display a remarkable ability to regenerate an array of structures. Frogs can regenerate appendages as larva, but they lose this ability around metamorphosis. In contrast, salamanders regenerate appendages as larva, juveniles, and adults. However, the extent to which fundamental traits (e.g., metamorphosis, body size, aging, etc.) restrict regenerative ability remains contentious. Here we utilize the ability of normally paedomorphic adult axolotls (Ambystoma mexicanum) to undergo induced metamorphosis by thyroxine exposure to test how metamorphosis and body size affects regeneration in age‐matched paedomorphic and metamorphic individuals. We show that body size does not affect regeneration in adult axolotls, but metamorphosis causes a twofold reduction in regeneration rate, and lead to carpal and digit malformations. Furthermore, we find evidence that metamorphic blastemal cells may take longer to traverse the cell cycle and display a lower proliferative rate. This study identifies the axolotl as a powerful system to study how metamorphosis restricts regeneration independently of developmental stage, body size, and age; and more broadly how metamorphosis affects tissue‐specific changes. PMID:27499857

Clusters of circulating tumor cells traverse capillary-sized vessels

PubMed Central

Au, Sam H.; Storey, Brian D.; Moore, John C.; Tang, Qin; Chen, Yeng-Long; Javaid, Sarah; Sarioglu, A. Fatih; Sullivan, Ryan; Madden, Marissa W.; O’Keefe, Ryan; Haber, Daniel A.; Maheswaran, Shyamala; Langenau, David M.; Stott, Shannon L.; Toner, Mehmet

2016-01-01

Multicellular aggregates of circulating tumor cells (CTC clusters) are potent initiators of distant organ metastasis. However, it is currently assumed that CTC clusters are too large to pass through narrow vessels to reach these organs. Here, we present evidence that challenges this assumption through the use of microfluidic devices designed to mimic human capillary constrictions and CTC clusters obtained from patient and cancer cell origins. Over 90% of clusters containing up to 20 cells successfully traversed 5- to 10-μm constrictions even in whole blood. Clusters rapidly and reversibly reorganized into single-file chain-like geometries that substantially reduced their hydrodynamic resistances. Xenotransplantation of human CTC clusters into zebrafish showed similar reorganization and transit through capillary-sized vessels in vivo. Preliminary experiments demonstrated that clusters could be disrupted during transit using drugs that affected cellular interaction energies. These findings suggest that CTC clusters may contribute a greater role to tumor dissemination than previously believed and may point to strategies for combating CTC cluster-initiated metastasis. PMID:27091969

Network and intrinsic cellular mechanisms underlying theta phase precession of hippocampal neurons.

PubMed

Maurer, Andrew P; McNaughton, Bruce L

2007-07-01

Hippocampal 'place cells' systematically shift their phase of firing in relation to the theta rhythm as an animal traverses the 'place field'. These dynamics imply that the neural ensemble begins each theta cycle at a point in its state-space that might 'represent' the current location of the rat, but that the ensemble 'looks ahead' during the rest of the cycle. Phase precession could result from intrinsic cellular dynamics involving interference of two oscillators of different frequencies, or from network interactions, similar to Hebb's 'phase sequence' concept, involving asymmetric synaptic connections. Both models have difficulties accounting for all of the available experimental data, however. A hybrid model, in which the look-ahead phenomenon implied by phase precession originates in superficial entorhinal cortex by some form of interference mechanism and is enhanced in the hippocampus proper by asymmetric synaptic plasticity during sequence encoding, seems to be consistent with available data, but as yet there is no fully satisfactory theoretical account of this phenomenon. This review is part of the INMED/TINS special issue Physiogenic and pathogenic oscillations: the beauty and the beast, based on presentations at the annual INMED/TINS symposium (http://inmednet.com).

Cockroaches traverse crevices, crawl rapidly in confined spaces, and inspire a soft, legged robot

PubMed Central

Jayaram, Kaushik; Full, Robert J.

2016-01-01

Jointed exoskeletons permit rapid appendage-driven locomotion but retain the soft-bodied, shape-changing ability to explore confined environments. We challenged cockroaches with horizontal crevices smaller than a quarter of their standing body height. Cockroaches rapidly traversed crevices in 300–800 ms by compressing their body 40–60%. High-speed videography revealed crevice negotiation to be a complex, discontinuous maneuver. After traversing horizontal crevices to enter a vertically confined space, cockroaches crawled at velocities approaching 60 cm⋅s−1, despite body compression and postural changes. Running velocity, stride length, and stride period only decreased at the smallest crevice height (4 mm), whereas slipping and the probability of zigzag paths increased. To explain confined-space running performance limits, we altered ceiling and ground friction. Increased ceiling friction decreased velocity by decreasing stride length and increasing slipping. Increased ground friction resulted in velocity and stride length attaining a maximum at intermediate friction levels. These data support a model of an unexplored mode of locomotion—“body-friction legged crawling” with body drag, friction-dominated leg thrust, but no media flow as in air, water, or sand. To define the limits of body compression in confined spaces, we conducted dynamic compressive cycle tests on living animals. Exoskeletal strength allowed cockroaches to withstand forces 300 times body weight when traversing the smallest crevices and up to nearly 900 times body weight without injury. Cockroach exoskeletons provided biological inspiration for the manufacture of an origami-style, soft, legged robot that can locomote rapidly in both open and confined spaces. PMID:26858443

Cockroaches traverse crevices, crawl rapidly in confined spaces, and inspire a soft, legged robot.

PubMed

Jayaram, Kaushik; Full, Robert J

2016-02-23

Jointed exoskeletons permit rapid appendage-driven locomotion but retain the soft-bodied, shape-changing ability to explore confined environments. We challenged cockroaches with horizontal crevices smaller than a quarter of their standing body height. Cockroaches rapidly traversed crevices in 300-800 ms by compressing their body 40-60%. High-speed videography revealed crevice negotiation to be a complex, discontinuous maneuver. After traversing horizontal crevices to enter a vertically confined space, cockroaches crawled at velocities approaching 60 cm⋅s(-1), despite body compression and postural changes. Running velocity, stride length, and stride period only decreased at the smallest crevice height (4 mm), whereas slipping and the probability of zigzag paths increased. To explain confined-space running performance limits, we altered ceiling and ground friction. Increased ceiling friction decreased velocity by decreasing stride length and increasing slipping. Increased ground friction resulted in velocity and stride length attaining a maximum at intermediate friction levels. These data support a model of an unexplored mode of locomotion--"body-friction legged crawling" with body drag, friction-dominated leg thrust, but no media flow as in air, water, or sand. To define the limits of body compression in confined spaces, we conducted dynamic compressive cycle tests on living animals. Exoskeletal strength allowed cockroaches to withstand forces 300 times body weight when traversing the smallest crevices and up to nearly 900 times body weight without injury. Cockroach exoskeletons provided biological inspiration for the manufacture of an origami-style, soft, legged robot that can locomote rapidly in both open and confined spaces.

Fungal cell gigantism during mammalian infection.

PubMed

Zaragoza, Oscar; García-Rodas, Rocío; Nosanchuk, Joshua D; Cuenca-Estrella, Manuel; Rodríguez-Tudela, Juan Luis; Casadevall, Arturo

2010-06-17

The interaction between fungal pathogens with the host frequently results in morphological changes, such as hyphae formation. The encapsulated pathogenic fungus Cryptococcus neoformans is not considered a dimorphic fungus, and is predominantly found in host tissues as round yeast cells. However, there is a specific morphological change associated with cryptococcal infection that involves an increase in capsule volume. We now report another morphological change whereby gigantic cells are formed in tissue. The paper reports the phenotypic characterization of giant cells isolated from infected mice and the cellular changes associated with giant cell formation. C. neoformans infection in mice resulted in the appearance of giant cells with cell bodies up to 30 microm in diameter and capsules resistant to stripping with gamma-radiation and organic solvents. The proportion of giant cells ranged from 10 to 80% of the total lung fungal burden, depending on infection time, individual mice, and correlated with the type of immune response. When placed on agar, giant cells budded to produce small daughter cells that traversed the capsule of the mother cell at the speed of 20-50 m/h. Giant cells with dimensions that approximated those in vivo were observed in vitro after prolonged culture in minimal media, and were the oldest in the culture, suggesting that giant cell formation is an aging-dependent phenomenon. Giant cells recovered from mice displayed polyploidy, suggesting a mechanism by which gigantism results from cell cycle progression without cell fission. Giant cell formation was dependent on cAMP, but not on Ras1. Real-time imaging showed that giant cells were engaged, but not engulfed by phagocytic cells. We describe a remarkable new strategy for C. neoformans to evade the immune response by enlarging cell size, and suggest that gigantism results from replication without fission, a phenomenon that may also occur with other fungal pathogens.

Low-Temperature Flex Durability of Fabrics for Polar Sleds

DTIC Science & Technology

2014-10-06

friction owing to solar gain, so SPoT is systematically replacing older tan bladders with black ones constructed from similar polyurethane -coated...specimens of the existing bladder material (single-layer polyurethane - coated fabric) within a few cycles. Remarkably, the specimens could with- stand...fabrics: • Antarctic traverses should continue to use fuel bladders constructed from ATL-853C (black) polyurethane -coated fabric as supplied by Aero Tec

Improved cell for water-vapor electrolysis

NASA Technical Reports Server (NTRS)

Aylward, J. R.

1981-01-01

Continuous-flow electrolytic cells decompose water vapor in steam and room air into hydrogen and oxygen. Sintered iridium oxide catalytic anode coating yields dissociation rates hundredfold greater than those obtained using platinum black. Cell consists of two mirror-image cells, with dual cathode sandwiched between two anodes. Gas traverses serpentine channels within cell and is dissociated at anode. Oxygen mingles with gas stream, while hydrogen migrates through porous matrix and is liberated as gas at cathode.

Isolated few-cycle radiation from chirped-pulse compression of a superradiant free-electron laser

DOE PAGES

Huang, Yen -Chieh; Zhang, Zhen; Chen, Chia -Hsiang; ...

2015-08-31

When a short electron bunch traverses an undulator to radiate a wavelength longer than the bunch length, intense superradiance from the electron bunch can quickly deplete the electron’s kinetic energy and lead to generation of an isolated chirped radiation pulse. Here, we develop a theory to describe this novel chirped pulse radiation in a superradiant free-electron laser and show the opportunity to generate isolated few-cycle high-power radiation through chirped-pulse compression after the undulator. The theory is completely characterized by how fast the electron energy is depleted for a given length of an undulator. We further present two design examples atmore » the THz and extreme-ultraviolet wavelengths and numerically generate isolated three- and nine-cycle radiation pulses, respectively.« less

Identification of early indicators of altered metabolism in normal development using a rodent model system.

PubMed

Prabakaran, Ashok Daniel; Karakkat, Jimsheena Valiyakath; Vijayan, Ranjit; Chalissery, Jisha; Ibrahim, Marwa F; Kaimala, Suneesh; Adeghate, Ernest A; Al-Marzouqi, Ahmed Hassan; Ansari, Suraiya Anjum; Mensah-Brown, Eric; Emerald, Bright Starling

2018-03-01

Although the existence of a close relationship between the early maternal developmental environment, fetal size at birth and the risk of developing disease in adulthood has been suggested, most studies, however, employed experimentally induced intrauterine growth restriction as a model to link this with later adult disease. Because embryonic size variation also occurs under normal growth and differentiation, elucidating the molecular mechanisms underlying these changes and their relevance to later adult disease risk becomes important. The birth weight of rat pups vary according to the uterine horn positions. Using birth weight as a marker, we compared two groups of rat pups - lower birth weight (LBW, 5th to 25th percentile) and average birth weight (ABW, 50th to 75th percentile) - using morphological, biochemical and molecular biology, and genetic techniques. Our results show that insulin metabolism, Pi3k/Akt and Pparγ signaling and the genes regulating growth and metabolism are significantly different in these groups. Methylation at the promoter of the InsII ( Ins2 ) gene and DNA methyltransferase 1 in LBW pups are both increased. Additionally, the Dnmt1 repressor complex, which includes Hdac1, Rb (Rb1) and E2f1, was also upregulated in LBW pups. We conclude that the Dnmt1 repressor complex, which regulates the restriction point of the cell cycle, retards the rate at which cells traverse the G1 or G0 phase of the cell cycle in LBW pups, thereby slowing down growth. This regulatory mechanism mediated by Dnmt1 might contribute to the production of small-size pups and altered physiology and pathology in adult life. © 2018. Published by The Company of Biologists Ltd.

Identification of early indicators of altered metabolism in normal development using a rodent model system

PubMed Central

Prabakaran, Ashok Daniel; Karakkat, Jimsheena Valiyakath; Chalissery, Jisha; Ibrahim, Marwa F.; Kaimala, Suneesh; Adeghate, Ernest A.; Al-Marzouqi, Ahmed Hassan; Ansari, Suraiya Anjum

2018-01-01

ABSTRACT Although the existence of a close relationship between the early maternal developmental environment, fetal size at birth and the risk of developing disease in adulthood has been suggested, most studies, however, employed experimentally induced intrauterine growth restriction as a model to link this with later adult disease. Because embryonic size variation also occurs under normal growth and differentiation, elucidating the molecular mechanisms underlying these changes and their relevance to later adult disease risk becomes important. The birth weight of rat pups vary according to the uterine horn positions. Using birth weight as a marker, we compared two groups of rat pups – lower birth weight (LBW, 5th to 25th percentile) and average birth weight (ABW, 50th to 75th percentile) – using morphological, biochemical and molecular biology, and genetic techniques. Our results show that insulin metabolism, Pi3k/Akt and Pparγ signaling and the genes regulating growth and metabolism are significantly different in these groups. Methylation at the promoter of the InsII (Ins2) gene and DNA methyltransferase 1 in LBW pups are both increased. Additionally, the Dnmt1 repressor complex, which includes Hdac1, Rb (Rb1) and E2f1, was also upregulated in LBW pups. We conclude that the Dnmt1 repressor complex, which regulates the restriction point of the cell cycle, retards the rate at which cells traverse the G1 or G0 phase of the cell cycle in LBW pups, thereby slowing down growth. This regulatory mechanism mediated by Dnmt1 might contribute to the production of small-size pups and altered physiology and pathology in adult life. PMID:29434026

Cyber-physical experiments on the efficiency of swimming protocols

NASA Astrophysics Data System (ADS)

Wei, Nathaniel; Floryan, Daniel; van Buren, Tyler; Smits, Alexander

2016-11-01

We present results from experiments on a biologically inspired cyber-physical system, composed of a two-dimensional heaving and pitching rigid airfoil attached to a six component load cell, mounted to a traverse that can move along a water channel. A feedback controller, influenced by the apparatus of Mackowski and Williamson, introduces the effects of a fictional drag force specified by a virtual body profile and drives the traverse accordingly. Free-swimming protocols using the force-feedback system are compared with similar motions on a motionless traverse. The propulsive efficiency of burst-and-coast kinematics is also considered. Of particular interest are (1) the implementation of the cyber-physical control system with respect to the accessible experimental parameter space, (2) the impact of force-based streamwise actuation on experimental data, and (3) the effects of burst-and-coast motions on propulsive efficiency. The work was supported by the Office of Naval Research (ONR) under MURI Grant N00014-14-1-0533.

Protein O-fucosylation in Plasmodium falciparum ensures efficient infection of mosquito and vertebrate hosts.

PubMed

Lopaticki, Sash; Yang, Annie S P; John, Alan; Scott, Nichollas E; Lingford, James P; O'Neill, Matthew T; Erickson, Sara M; McKenzie, Nicole C; Jennison, Charlie; Whitehead, Lachlan W; Douglas, Donna N; Kneteman, Norman M; Goddard-Borger, Ethan D; Boddey, Justin A

2017-09-15

O-glycosylation of the Plasmodium sporozoite surface proteins CSP and TRAP was recently identified, but the role of this modification in the parasite life cycle and its relevance to vaccine design remain unclear. Here, we identify the Plasmodium protein O-fucosyltransferase (POFUT2) responsible for O-glycosylating CSP and TRAP. Genetic disruption of POFUT2 in Plasmodium falciparum results in ookinetes that are attenuated for colonizing the mosquito midgut, an essential step in malaria transmission. Some POFUT2-deficient parasites mature into salivary gland sporozoites although they are impaired for gliding motility, cell traversal, hepatocyte invasion, and production of exoerythrocytic forms in humanized chimeric liver mice. These defects can be attributed to destabilization and incorrect trafficking of proteins bearing thrombospondin repeats (TSRs). Therefore, POFUT2 plays a similar role in malaria parasites to that in metazoans: it ensures the trafficking of Plasmodium TSR proteins as part of a non-canonical glycosylation-dependent endoplasmic reticulum protein quality control mechanism.The role of O-glycosylation in the malaria life cycle is largely unknown. Here, the authors identify a Plasmodium protein O-fucosyltransferase and show that it is important for normal trafficking of a subset of surface proteins, particularly CSP and TRAP, and efficient infection of mosquito and vertebrate hosts.

How Cryptococcus interacts with the blood-brain barrier.

PubMed

Tseng, Hsiang-Kuang; Huang, Tseng-Yu; Wu, Alice Ying-Jung; Chen, Hsin-Hong; Liu, Chang-Pan; Jong, Ambrose

2015-01-01

Cryptococcus demonstrates predilection for invasion of the brain, but the mechanism by which Cryptococcus crosses the blood-brain barrier (BBB) to cause brain invasion is largely unknown. In order for Cryptococcus to cross the BBB, there must be a way to either cross human brain microvascular endothelial cells, which are the main constitute of the BBB, or go in between tight junctions. Recent evidence of human brain microvascular endothelial cell responses to transcellular brain invasions includes membrane rearrangements, intracellular signaling pathways and cytoskeletal activations. Several Cryptococcal genes related to the traversal of BBB have been identified, including CPS1, ITR1a, ITR3c, PLB1, MPR1, FNX1 and RUB1. In addition, Cryptococcus neoformans-derived microvesicles may contribute to cryptococcal brain invasion. Paracellularly, Cryptococcus may traverse across BBB using either routes utilizing plasmin, ammonia or macrophages in a Trojan horse mechanism.

Autonomous Science Decision Making for Mars Sample Return

NASA Technical Reports Server (NTRS)

Roush, Ted L.; Gulick, V.; Morris, R.; Gazis, P.; Benedix, G.; Glymour, C.; Ramsey, J.; Pedersen, L.; Ruzon, M.; Buntine, W.;

Subcellular Spatial Correlation of Particle Traversal and Biological Response in Clinical Ion Beams

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

Niklas, Martin, E-mail: m.niklas@dkfz.de; German Cancer Consortium, National Center for Radiation Research in Oncology, Heidelberg Institute of Radiation Oncology, Heidelberg; Abdollahi, Amir

2013-12-01

Purpose: To report on the spatial correlation of physical track information (fluorescent nuclear track detectors, FNTDs) and cellular DNA damage response by using a novel hybrid detector (Cell-Fit-HD). Methods and Materials: The FNTDs were coated with a monolayer of human non-small cell lung carcinoma (A549) cells and irradiated with carbon ions (270.55 MeV u{sup −1}, rising flank of the Bragg peak). Phosphorylated histone variant H2AX accumulating at the irradiation-induced double-strand break site was labeled (RIF). The position and direction of ion tracks in the FNTD were registered with the location of the RIF sequence as an ion track surrogate inmore » the cell layer. Results: All RIF sequences could be related to their corresponding ion tracks, with mean deviations of 1.09 μm and −1.72 μm in position and of 2.38° in slope. The mean perpendicular between ion track and RIF sequence was 1.58 μm. The mean spacing of neighboring RIFs exhibited a regular rather than random spacing. Conclusions: Cell-Fit-HD allows for unambiguous spatial correlation studies of cell damage with respect to the intracellular ion traversal under therapeutic beam conditions.« less

Intravital Observation of Plasmodium berghei Sporozoite Infection of the Liver

PubMed Central

Engelmann, Sabine; Zougbédé, Sergine; Stange, Jörg; Ng, Bruce; Matuschewski, Kai; Liebes, Leonard; Yee, Herman

2005-01-01

Plasmodium sporozoite invasion of liver cells has been an extremely elusive event to study. In the prevailing model, sporozoites enter the liver by passing through Kupffer cells, but this model was based solely on incidental observations in fixed specimens and on biochemical and physiological data. To obtain direct information on the dynamics of sporozoite infection of the liver, we infected live mice with red or green fluorescent Plasmodium berghei sporozoites and monitored their behavior using intravital microscopy. Digital recordings show that sporozoites entering a liver lobule abruptly adhere to the sinusoidal cell layer, suggesting a high-affinity interaction. They glide along the sinusoid, with or against the bloodstream, to a Kupffer cell, and, by slowly pushing through a constriction, traverse across the space of Disse. Once inside the liver parenchyma, sporozoites move rapidly for many minutes, traversing several hepatocytes, until ultimately settling within a final one. Migration damage to hepatocytes was confirmed in liver sections, revealing clusters of necrotic hepatocytes adjacent to structurally intact, sporozoite-infected hepatocytes, and by elevated serum alanine aminotransferase activity. In summary, malaria sporozoites bind tightly to the sinusoidal cell layer, cross Kupffer cells, and leave behind a trail of dead hepatocytes when migrating to their final destination in the liver. PMID:15901208

p53-dependent p21-mediated growth arrest pre-empts and protects HCT116 cells from PUMA-mediated apoptosis induced by EGCG

PubMed Central

Thakur, Vijay S; Amin, A.R.M. Ruhul; Paul, Rajib K; Gupta, Kalpana; Hastak, Kedar; Agarwal, Mukesh K; Jackson, Mark W; Wald, David N; Mukhtar, Hasan; Agarwal, Munna L

2010-01-01

The tumor suppressor protein p53 plays a key role in regulation of negative cellular growth in response to EGCG. To further explore the role of p53 signaling and elucidate the molecular mechanism, we employed colon cancer HCT116 cell line and its derivatives in which a specific transcriptional target of p53 is knocked down by homologous recombination. Cells expressing p53 and p21 accumulate in G1 upon treatment with EGCG. In contrast, same cells lacking p21 traverse through the cell cycle and eventually undergo apoptosis as revealed by TUNEL staining. Treatment with EGCG leads to induction of p53, p21 and PUMA in p21 wild-type, and p53 and PUMA in p21−/− cells. Ablation of p53 by RNAi protects p21−/− cells, thus indicating a p53-dependent apoptosis by EGCG. Furthermore, analysis of cells lacking PUMA or Bax with or without p21 but with p53 reveals that all the cells expressing p53 and p21 survived after EGCG treatment. More interestingly, cells lacking both PUMA and p21 survived ECGC treatment whereas those lacking p21 and Bax did not. Taken together, our results present a novel concept wherein p21-dependent growth arrest pre-empts and protects cells from otherwise, in its absence, apoptosis which is mediated by activation of pro-apoptotic protein PUMA. Furthermore, we find that p53-dependent activation of PUMA in response to EGCG directly leads to apoptosis with out requiring Bax as is the case in response to agents that induce DNA damage. p21, thus can be used as a molecular switch for therapeutic intervention of colon cancer. PMID:20444544

Method for measuring the rate of cell reproduction by analysis of nanoliter cell samples

DOEpatents

Gourley, Paul L.

2005-04-26

A method of detecting cancer using a laser biocavity having a semiconductor laser including a microchannel through which cells in fluid traverse, comprising determining the laser wavelength of the laser biocavity with only fluid in the microchannel; determining the wavelength shift of the biocavity when each cell passes through the microchannel; and determining the percentage of cells in G2 phase from the wavelength shift of the cells; wherein an increased percentage of G2 phase cells is an indication of cancer.

Single-Frame Terrain Mapping Software for Robotic Vehicles

NASA Technical Reports Server (NTRS)

Rankin, Arturo L.

2011-01-01

This software is a component in an unmanned ground vehicle (UGV) perception system that builds compact, single-frame terrain maps for distribution to other systems, such as a world model or an operator control unit, over a local area network (LAN). Each cell in the map encodes an elevation value, terrain classification, object classification, terrain traversability, terrain roughness, and a confidence value into four bytes of memory. The input to this software component is a range image (from a lidar or stereo vision system), and optionally a terrain classification image and an object classification image, both registered to the range image. The single-frame terrain map generates estimates of the support surface elevation, ground cover elevation, and minimum canopy elevation; generates terrain traversability cost; detects low overhangs and high-density obstacles; and can perform geometry-based terrain classification (ground, ground cover, unknown). A new origin is automatically selected for each single-frame terrain map in global coordinates such that it coincides with the corner of a world map cell. That way, single-frame terrain maps correctly line up with the world map, facilitating the merging of map data into the world map. Instead of using 32 bits to store the floating-point elevation for a map cell, the vehicle elevation is assigned to the map origin elevation and reports the change in elevation (from the origin elevation) in terms of the number of discrete steps. The single-frame terrain map elevation resolution is 2 cm. At that resolution, terrain elevation from 20.5 to 20.5 m (with respect to the vehicle's elevation) is encoded into 11 bits. For each four-byte map cell, bits are assigned to encode elevation, terrain roughness, terrain classification, object classification, terrain traversability cost, and a confidence value. The vehicle s current position and orientation, the map origin, and the map cell resolution are all included in a header for each map. The map is compressed into a vector prior to delivery to another system.

Antarctic Exploration Parallels for Future Human Planetary Exploration: The Role and Utility of Long Range, Long Duration Traverses

NASA Technical Reports Server (NTRS)

Hoffman, Stephen J. (Editor); Voels, Stephen A. (Editor)

2012-01-01

Topics covered include: Antarctic Exploration Parallels for Future Human Planetary Exploration: Science Operations Lessons Learned, Planning, and Equipment Capabilities for Long Range, Long Duration Traverses; Parallels Between Antarctic Travel in 1950 and Planetary Travel in 2050 (to Accompany Notes on "The Norwegian British-Swedish Antarctic Expedition 1949-52"); My IGY in Antarctica; Short Trips and a Traverse; Geologic Traverse Planning for Apollo Missions; Desert Research and Technology Studies (DRATS) Traverse Planning; Science Traverses in the Canadian High Arctic; NOR-USA Scientific Traverse of East Antarctica: Science and Logistics on a Three-Month Expedition Across Antarctica's Farthest Frontier; A Notional Example of Understanding Human Exploration Traverses on the Lunar Surface; and The Princess Elisabeth Station.

Differential Transmission of HIV Traversing Fetal Oral/Intestinal Epithelia and Adult Oral Epithelia

PubMed Central

Herrera, Rossana; Veluppillai, Piri; Greenspan, Deborah; Soros, Vanessa; Greene, Warner C.; Levy, Jay A.; Palefsky, Joel M.

2012-01-01

While human immunodeficiency virus (HIV) transmission through the adult oral route is rare, mother-to-child transmission (MTCT) through the neonatal/infant oral and/or gastrointestinal route is common. To study the mechanisms of cell-free and cell-associated HIV transmission across adult oral and neonatal/infant oral/intestinal epithelia, we established ex vivo organ tissue model systems of adult and fetal origin. Given the similarity of neonatal and fetal oral epithelia with respect to epithelial stratification and density of HIV-susceptible immune cells, we used fetal oral the epithelium as a model for neonatal/infant oral epithelium. We found that cell-free HIV traversed fetal oral and intestinal epithelia and infected HIV-susceptible CD4+ T lymphocytes, Langerhans/dendritic cells, and macrophages. To study the penetration of cell-associated virus into fetal oral and intestinal epithelia, HIV-infected macrophages and lymphocytes were added to the surfaces of fetal oral and intestinal epithelia. HIV-infected macrophages, but not lymphocytes, transmigrated across fetal oral epithelia. HIV-infected macrophages and, to a lesser extent, lymphocytes transmigrated across fetal intestinal epithelia. In contrast to the fetal oral/intestinal epithelia, cell-free HIV transmigration through adult oral epithelia was inefficient and virions did not infect intraepithelial and subepithelial HIV-susceptible cells. In addition, HIV-infected macrophages and lymphocytes did not transmigrate through intact adult oral epithelia. Transmigration of cell-free and cell-associated HIV across the fetal oral/intestinal mucosal epithelium may serve as an initial mechanism for HIV MTCT. PMID:22205732

Theta phase precession of grid and place cell firing in open environments

PubMed Central

Jeewajee, A.; Barry, C.; Douchamps, V.; Manson, D.; Lever, C.; Burgess, N.

2014-01-01

Place and grid cells in the rodent hippocampal formation tend to fire spikes at successively earlier phases relative to the local field potential theta rhythm as the animal runs through the cell's firing field on a linear track. However, this ‘phase precession’ effect is less well characterized during foraging in two-dimensional open field environments. Here, we mapped runs through the firing fields onto a unit circle to pool data from multiple runs. We asked which of seven behavioural and physiological variables show the best circular–linear correlation with the theta phase of spikes from place cells in hippocampal area CA1 and from grid cells from superficial layers of medial entorhinal cortex. The best correlate was the distance to the firing field peak projected onto the animal's current running direction. This was significantly stronger than other correlates, such as instantaneous firing rate and time-in-field, but similar in strength to correlates with other measures of distance travelled through the firing field. Phase precession was stronger in place cells than grid cells overall, and robust phase precession was seen in traversals through firing field peripheries (although somewhat less than in traversals through the centre), consistent with phase coding of displacement along the current direction. This type of phase coding, of place field distance ahead of or behind the animal, may be useful for allowing calculation of goal directions during navigation. PMID:24366140

An asynchronous traversal engine for graph-based rich metadata management

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

Dai, Dong; Carns, Philip; Ross, Robert B.

Rich metadata in high-performance computing (HPC) systems contains extended information about users, jobs, data files, and their relationships. Property graphs are a promising data model to represent heterogeneous rich metadata flexibly. Specifically, a property graph can use vertices to represent different entities and edges to record the relationships between vertices with unique annotations. The high-volume HPC use case, with millions of entities and relationships, naturally requires an out-of-core distributed property graph database, which must support live updates (to ingest production information in real time), low-latency point queries (for frequent metadata operations such as permission checking), and large-scale traversals (for provenancemore » data mining). Among these needs, large-scale property graph traversals are particularly challenging for distributed graph storage systems. Most existing graph systems implement a "level synchronous" breadth-first search algorithm that relies on global synchronization in each traversal step. This performs well in many problem domains; but a rich metadata management system is characterized by imbalanced graphs, long traversal lengths, and concurrent workloads, each of which has the potential to introduce or exacerbate stragglers (i.e., abnormally slow steps or servers in a graph traversal) that lead to low overall throughput for synchronous traversal algorithms. Previous research indicated that the straggler problem can be mitigated by using asynchronous traversal algorithms, and many graph-processing frameworks have successfully demonstrated this approach. Such systems require the graph to be loaded into a separate batch-processing framework instead of being iteratively accessed, however. In this work, we investigate a general asynchronous graph traversal engine that can operate atop a rich metadata graph in its native format. We outline a traversal-aware query language and key optimizations (traversal-affiliate caching and execution merging) necessary for efficient performance. We further explore the effect of different graph partitioning strategies on the traversal performance for both synchronous and asynchronous traversal engines. Our experiments show that the asynchronous graph traversal engine is more efficient than its synchronous counterpart in the case of HPC rich metadata processing, where more servers are involved and larger traversals are needed. Furthermore, the asynchronous traversal engine is more adaptive to different graph partitioning strategies.« less

An asynchronous traversal engine for graph-based rich metadata management

DOE PAGES

Dai, Dong; Carns, Philip; Ross, Robert B.; ...

2016-06-23

Rich metadata in high-performance computing (HPC) systems contains extended information about users, jobs, data files, and their relationships. Property graphs are a promising data model to represent heterogeneous rich metadata flexibly. Specifically, a property graph can use vertices to represent different entities and edges to record the relationships between vertices with unique annotations. The high-volume HPC use case, with millions of entities and relationships, naturally requires an out-of-core distributed property graph database, which must support live updates (to ingest production information in real time), low-latency point queries (for frequent metadata operations such as permission checking), and large-scale traversals (for provenancemore » data mining). Among these needs, large-scale property graph traversals are particularly challenging for distributed graph storage systems. Most existing graph systems implement a "level synchronous" breadth-first search algorithm that relies on global synchronization in each traversal step. This performs well in many problem domains; but a rich metadata management system is characterized by imbalanced graphs, long traversal lengths, and concurrent workloads, each of which has the potential to introduce or exacerbate stragglers (i.e., abnormally slow steps or servers in a graph traversal) that lead to low overall throughput for synchronous traversal algorithms. Previous research indicated that the straggler problem can be mitigated by using asynchronous traversal algorithms, and many graph-processing frameworks have successfully demonstrated this approach. Such systems require the graph to be loaded into a separate batch-processing framework instead of being iteratively accessed, however. In this work, we investigate a general asynchronous graph traversal engine that can operate atop a rich metadata graph in its native format. We outline a traversal-aware query language and key optimizations (traversal-affiliate caching and execution merging) necessary for efficient performance. We further explore the effect of different graph partitioning strategies on the traversal performance for both synchronous and asynchronous traversal engines. Our experiments show that the asynchronous graph traversal engine is more efficient than its synchronous counterpart in the case of HPC rich metadata processing, where more servers are involved and larger traversals are needed. Furthermore, the asynchronous traversal engine is more adaptive to different graph partitioning strategies.« less

Robust Control Techniques Enabling Duty Cycle Experiments Utilizing a 6-DOF Crewstation Motion Base, a Full Scale Combat Hybrid Electric Power System, and Long Distance Internet Communications

DTIC Science & Technology

2006-11-10

Electric Power System, and Long Distance Internet Communications Marc Compere , Jarrett Goodell, Miguel Simon, Wilford Smith Science Applications...System, and Long Distance Internet Communication 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Marc Compere ...Systems Symposium, NDIA, Traverse City, MI, June 2006. 3. Miguel Simon, Marc Compere , Thomas Connolly, Charles Lars, Wilford Smith, Mark Brudnak, "Hybrid

Fungal Cell Gigantism during Mammalian Infection

PubMed Central

Zaragoza, Oscar; García-Rodas, Rocío; Nosanchuk, Joshua D.; Cuenca-Estrella, Manuel; Rodríguez-Tudela, Juan Luis; Casadevall, Arturo

2010-01-01

The interaction between fungal pathogens with the host frequently results in morphological changes, such as hyphae formation. The encapsulated pathogenic fungus Cryptococcus neoformans is not considered a dimorphic fungus, and is predominantly found in host tissues as round yeast cells. However, there is a specific morphological change associated with cryptococcal infection that involves an increase in capsule volume. We now report another morphological change whereby gigantic cells are formed in tissue. The paper reports the phenotypic characterization of giant cells isolated from infected mice and the cellular changes associated with giant cell formation. C. neoformans infection in mice resulted in the appearance of giant cells with cell bodies up to 30 µm in diameter and capsules resistant to stripping with γ-radiation and organic solvents. The proportion of giant cells ranged from 10 to 80% of the total lung fungal burden, depending on infection time, individual mice, and correlated with the type of immune response. When placed on agar, giant cells budded to produce small daughter cells that traversed the capsule of the mother cell at the speed of 20–50 m/h. Giant cells with dimensions that approximated those in vivo were observed in vitro after prolonged culture in minimal media, and were the oldest in the culture, suggesting that giant cell formation is an aging-dependent phenomenon. Giant cells recovered from mice displayed polyploidy, suggesting a mechanism by which gigantism results from cell cycle progression without cell fission. Giant cell formation was dependent on cAMP, but not on Ras1. Real-time imaging showed that giant cells were engaged, but not engulfed by phagocytic cells. We describe a remarkable new strategy for C. neoformans to evade the immune response by enlarging cell size, and suggest that gigantism results from replication without fission, a phenomenon that may also occur with other fungal pathogens. PMID:20585557

Body-terrain interaction affects large bump traversal of insects and legged robots.

PubMed

Gart, Sean W; Li, Chen

2018-02-02

Small animals and robots must often rapidly traverse large bump-like obstacles when moving through complex 3D terrains, during which, in addition to leg-ground contact, their body inevitably comes into physical contact with the obstacles. However, we know little about the performance limits of large bump traversal and how body-terrain interaction affects traversal. To address these, we challenged the discoid cockroach and an open-loop six-legged robot to dynamically run into a large bump of varying height to discover the maximal traversal performance, and studied how locomotor modes and traversal performance are affected by body-terrain interaction. Remarkably, during rapid running, both the animal and the robot were capable of dynamically traversing a bump much higher than its hip height (up to 4 times the hip height for the animal and 3 times for the robot, respectively) at traversal speeds typical of running, with decreasing traversal probability with increasing bump height. A stability analysis using a novel locomotion energy landscape model explained why traversal was more likely when the animal or robot approached the bump with a low initial body yaw and a high initial body pitch, and why deflection was more likely otherwise. Inspired by these principles, we demonstrated a novel control strategy of active body pitching that increased the robot's maximal traversable bump height by 75%. Our study is a major step in establishing the framework of locomotion energy landscapes to understand locomotion in complex 3D terrains.

Ultrasound-induced cavitation enhances the delivery and therapeutic efficacy of an oncolytic virus in an in vitro model.

PubMed

Bazan-Peregrino, Miriam; Arvanitis, Costas D; Rifai, Bassel; Seymour, Leonard W; Coussios, Constantin-C

2012-01-30

We investigated whether ultrasound-induced cavitation at 0.5 MHz could improve the extravasation and distribution of a potent breast cancer-selective oncolytic adenovirus, AdEHE2F-Luc, to tumour regions that are remote from blood vessels. We developed a novel tumour-mimicking model consisting of a gel matrix containing human breast cancer cells traversed by a fluid channel simulating a tumour blood vessel, through which the virus and microbubbles could be made to flow. Ultrasonic pressures were chosen to maximize either broadband emissions, associated with inertial cavitation, or ultraharmonic emissions, associated with stable cavitation, while varying duty cycle to keep the total acoustic energy delivered constant for comparison across exposures. None of the exposure conditions tested affected cell viability in the absence of the adenovirus. When AdEHE2F-Luc was delivered via the vessel, inertial cavitation increased transgene expression in tumour cells by up to 200 times. This increase was not observed in the absence of Coxsackie and Adenovirus Receptor cell expression, discounting sonoporation as the mechanism of action. In the presence of inertial cavitation, AdEHE2F-Luc distribution was greatly improved in the matrix surrounding the vessel, particularly in the direction of the ultrasound beam; this enabled AdEHE2F-Luc to kill up to 80% of cancer cells within the ultrasound focal volume in the gel 24 hours after delivery, compared to 0% in the absence of cavitation. Copyright © 2011 Elsevier B.V. All rights reserved.

Pseudogynecomastia due to neurofibromatosis--a light microscopic and ultrastructural study.

PubMed

Lipper, S; Willson, C F; Copeland, K C

1981-08-01

A six year old boy with bilateral breast enlargement was found to have a normal endocrine status. Resected tissue revealed the features of pseudogynecomastia due to a proliferation of fibrous tissue traversed by neuroid structures. Multinucleated giant cells were present within the fibrous tissue. Ultrastructural study revealed organized nerve elements in a collagenous stroma. The multinucleated giant cells appeared to be variants of the predominant stromal fibroblasts.

Extracellular Hsp70 Enhances Mesoangioblast Migration via an Autocrine Signaling Pathway.

PubMed

Barreca, Maria M; Spinello, Walter; Cavalieri, Vincenzo; Turturici, Giuseppina; Sconzo, Gabriella; Kaur, Punit; Tinnirello, Rosaria; Asea, Alexzander A A; Geraci, Fabiana

2017-07-01

Mouse mesoangioblasts are vessel-associated progenitor stem cells endowed with the ability of multipotent mesoderm differentiation. Therefore, they represent a promising tool in the regeneration of injured tissues. Several studies have demonstrated that homing of mesoangioblasts into blood and injured tissues are mainly controlled by cytokines/chemokines and other inflammatory factors. However, little is known about the molecular mechanisms regulating their ability to traverse the extracellular matrix (ECM). Here, we demonstrate that membrane vesicles released by mesoangioblasts contain Hsp70, and that the released Hsp70 is able to interact by an autocrine mechanism with Toll-like receptor 4 (TLR4) and CD91 to stimulate migration. We further demonstrate that Hsp70 has a positive role in regulating matrix metalloproteinase 2 (MMP2) and MMP9 expression and that MMP2 has a more pronounced effect on cell migration, as compared to MMP9. In addition, the analysis of the intracellular pathways implicated in Hsp70 regulated signal transduction showed the involvement of both PI3K/AKT and NF-κB. Taken together, our findings present a paradigm shift in our understanding of the molecular mechanisms that regulate mesoangioblast stem cells ability to traverse the extracellular matrix (ECM). J. Cell. Physiol. 232: 1845-1861, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Non-Target Effect for Chromosome Aberrations in Human Lymphocytes and Fibroblasts After Exposure to Very Low Doses of High LET Radiation

NASA Technical Reports Server (NTRS)

Hada, Megumi; George, Kerry A.; Cucinotta, F. A.

2011-01-01

The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (.01 - 0.2 Gy) of 170 MeV/u Si-28-ions or 600 MeV/u Fe-56-ions. Chromosomes were analyzed using the whole chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The curves for doses above 0.1 Gy were more than one ion traverses a cell showed linear dose responses. However, for doses less than 0.1 Gy, Si-28-ions showed no dose response, suggesting a non-targeted effect when less than one ion traversal occurs. Additional findings for Fe-56 will be discussed.

Environmental Assessment Lake Traverse Master Plan for Public-Use Development and Resource Management Lake Traverse Minnesota - South Dakota.

DTIC Science & Technology

1978-09-01

classified as wet meadow. k. Tame Grassland Community (limited) - This community is of minor extent and importance in the vicinity of Lake Traverse...purposes of flood control and water conservation, the Lake Traverse-lois de Sioux flood control project began operation in 1941. It con- sists of two...reservoir pools--Lake Traverse and Mud Lake--plus 24 miles of channel improvement. Several consepts are recoiended for future development of the

Quantifying Traversability of Terrain for a Mobile Robot

NASA Technical Reports Server (NTRS)

Howard, Ayanna; Seraji, Homayoun; Werger, Barry

2005-01-01

A document presents an updated discussion on a method of autonomous navigation for a robotic vehicle navigating across rough terrain. The method involves, among other things, the use of a measure of traversability, denoted the fuzzy traversability index, which embodies the information about the slope and roughness of terrain obtained from analysis of images acquired by cameras mounted on the robot. The improvements presented in the report focus on the use of the fuzzy traversability index to generate a traversability map and a grid map for planning the safest path for the robot. Once grid traversability values have been computed, they are utilized for rejecting unsafe path segments and for computing a traversalcost function for ranking candidate paths, selected by a search algorithm, from a specified initial position to a specified final position. The output of the algorithm is a set of waypoints designating a path having a minimal-traversal cost.

"Birds of passage" or "career" women? Thoughts on the life cycle of the eighteenth-century European servant.

PubMed

Simonton, Deborah

2011-01-01

Frequently eighteenth-century service is described as a life-cycle stage used to build up the financial wherewithal to set up house. As such it was central to the way youth or girlhood was traversed, and studies of adolescent years rightly emphasise the importance of service. However, this narrative, while largely accurate, is also problematic. What happened when service did not end with marriage, or when a woman remained single well into adulthood? In practice, servants were found among both the married and single, and among the young and the old. Concentrating on the eighteenth century, and incorporating material from Nordic Europe, this article teases out some of the nuances in the context and experience of service that partially disrupt the established narrative.

Predicting First Traversal Times for Virions and Nanoparticles in Mucus with Slowed Diffusion

PubMed Central

Erickson, Austen M.; Henry, Bruce I.; Murray, John M.; Klasse, Per Johan; Angstmann, Christopher N.

2015-01-01

Particle-tracking experiments focusing on virions or nanoparticles in mucus have measured mean-square displacements and reported diffusion coefficients that are orders of magnitude smaller than the diffusion coefficients of such particles in water. Accurate description of this subdiffusion is important to properly estimate the likelihood of virions traversing the mucus boundary layer and infecting cells in the epithelium. However, there are several candidate models for diffusion that can fit experimental measurements of mean-square displacements. We show that these models yield very different estimates for the time taken for subdiffusive virions to traverse through a mucus layer. We explain why fits of subdiffusive mean-square displacements to standard diffusion models may be misleading. Relevant to human immunodeficiency virus infection, using computational methods for fractional subdiffusion, we show that subdiffusion in normal acidic mucus provides a more effective barrier against infection than previously thought. By contrast, the neutralization of the mucus by alkaline semen, after sexual intercourse, allows virions to cross the mucus layer and reach the epithelium in a short timeframe. The computed barrier protection from fractional subdiffusion is some orders of magnitude greater than that derived by fitting standard models of diffusion to subdiffusive data. PMID:26153713

Archaeal viruses at the cell envelope: entry and egress

PubMed Central

Quemin, Emmanuelle R. J.; Quax, Tessa E. F.

2015-01-01

The cell envelope represents the main line of host defense that viruses encounter on their way from one cell to another. The cytoplasmic membrane in general is a physical barrier that needs to be crossed both upon viral entry and exit. Therefore, viruses from the three domains of life employ a wide range of strategies for perforation of the cell membrane, each adapted to the cell surface environment of their host. Here, we review recent insights on entry and egress mechanisms of viruses infecting archaea. Due to the unique nature of the archaeal cell envelope, these particular viruses exhibit novel and unexpected mechanisms to traverse the cellular membrane. PMID:26097469

Impact of the track structure of heavy charged particles on cytogenetic damage in human blood lymphocytes

NASA Astrophysics Data System (ADS)

Lee, Ryonfa; Nasonova, Elena; Sommer, Sylwetster; Hartel, Carola; Durante, Marco; Ritter, Sylvia

In space, astronauts are unavoidably exposed to charged particles from protons to irons. For a better estimate of the health risks of astronauts, further knowledge on the biological effects of charged particles, in particular the induction of cytogenetic damage is required. One im-portant factor that determines the biological response is the track structure of particles, i.e. their microscopic dose deposition in cells. The aim of the present study was to assess the influence of track structure of heavy ions on the yield and the quality of cytogenetic damage in human peripheral blood lymphocytes representing normal tissue. Cells were irradiated with 9.5 MeV/u C-ions or 990 MeV/u Fe-ions which have a comparable LET (175 keV/µm and 155 keV/µm, respectively) but a different track radius (2.3 and 6200 µm, respectively). When aberrations were analyzed in first cycle metaphases collected at different post-irradiation times (48-84 h) following fluorescence plus Giemsa staining, an increase in the aberration yield with sampling time was observed for both radiation qualities reflecting a damage dependent cell cycle progression delay to mitosis. The pronounced differences in the aberration frequency per cell are attributable to the stochastic distribution of particle traversals per cell nucleus (radius: 2.8 µm). Following C-ion exposure we found a high fraction of non-aberrant cells in samples collected at 48 h which represent cells not directly hit by a particle and slightly damaged cells that successfully repaired the induced lesions. In addition, at higher C-ion fluences the aberra-tion yield saturated, suggesting that a fraction of lymphocytes receiving multiple particle hits is not able to reach mitosis. On the other hand, at 48 h after Fe-ion exposure the proportion of non-aberrant cells is lower than after C-ion irradiation clearly reflecting the track structure of high energy particles (i.e. more homogeneous dose deposition compared to low energy C-ions). Furthermore, the aberration yield increased linearly with Fe-ion fluence. When aberrations were analyzed in first cycle G2 -PCC cells to account for the prolonged G2 arrest of damaged cells, the same trend was detected. However, the increase in the aberration yield with time and the saturation effect were less pronounced compared to metaphase samples. Altogether, these data show that the aberration analysis with multiple samplings is necessary for a reliable estimate of cytogenetic damage induced by charged particles. In particular, when damage is measured at one early time-point the effectiveness of low energy particles will be considerably underestimated. When the aberration spectrum induced by low energy C-ions and high en-ergy Fe-ions was compared, we did not find a difference. Preliminary data obtained with the high resolution mFISH-technique confirm this observation. (Work supported by BMBF, Bonn, under contract 02S8497)

78 FR 25407 - Safety Zones; National Cherry Festival Air Show and Fireworks Display; West Grand Traverse Bay...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-01

...-AA00 Safety Zones; National Cherry Festival Air Show and Fireworks Display; West Grand Traverse Bay... National Cherry Festival in Traverse City, MI will host an air show over the West Arm of Grand Traverse Bay. At the conclusion of the National Cherry Festival on July 6, 2013, fireworks will be launched in...

Autonomous Onboard Science Image Analysis for Future Mars Rover Missions

NASA Technical Reports Server (NTRS)

Gulick, V. C.; Morris, R. L.; Ruzon, M. A.; Roush, T. L.

1999-01-01

To explore high priority landing sites and to prepare for eventual human exploration, future Mars missions will involve rovers capable of traversing tens of kilometers. However, the current process by which scientists interact with a rover does not scale to such distances. Specifically, numerous command cycles are required to complete even simple tasks, such as, pointing the spectrometer at a variety of nearby rocks. In addition, the time required by scientists to interpret image data before new commands can be given and the limited amount of data that can be downlinked during a given command cycle constrain rover mobility and achievement of science goals. Experience with rover tests on Earth supports these concerns. As a result, traverses to science sites as identified in orbital images would require numerous science command cycles over a period of many weeks, months or even years, perhaps exceeding rover design life and other constraints. Autonomous onboard science analysis can address these problems in two ways. First, it will allow the rover to transmit only "interesting" images, defined as those likely to have higher science content. Second, the rover will be able to anticipate future commands. For example, a rover might autonomously acquire and return spectra of "interesting" rocks along with a high resolution image of those rocks in addition to returning the context images in which they were detected. Such approaches, coupled with appropriate navigational software, help to address both the data volume and command cycle bottlenecks that limit both rover mobility and science yield. We are developing fast, autonomous algorithms to enable such intelligent on-board decision making by spacecraft. Autonomous algorithms developed to date have the ability to identify rocks and layers in a scene, locate the horizon, and compress multi-spectral image data. Output from these algorithms could be used to autonomously obtain rock spectra, determine which images should be transmitted to the ground, or to aid in image compression. We will discuss these and other algorithms and demonstrate their performance during a recent rover field test.

The Blood-Testis Barrier and Its Implications for Male Contraception

PubMed Central

Mruk, Dolores D.

2012-01-01

The blood-testis barrier (BTB) is one of the tightest blood-tissue barriers in the mammalian body. It divides the seminiferous epithelium into the basal and the apical (adluminal) compartments. Meiosis I and II, spermiogenesis, and spermiation all take place in a specialized microenvironment behind the BTB in the apical compartment, but spermatogonial renewal and differentiation and cell cycle progression up to the preleptotene spermatocyte stage take place outside of the BTB in the basal compartment of the epithelium. However, the BTB is not a static ultrastructure. Instead, it undergoes extensive restructuring during the seminiferous epithelial cycle of spermatogenesis at stage VIII to allow the transit of preleptotene spermatocytes at the BTB. Yet the immunological barrier conferred by the BTB cannot be compromised, even transiently, during the epithelial cycle to avoid the production of antibodies against meiotic and postmeiotic germ cells. Studies have demonstrated that some unlikely partners, namely adhesion protein complexes (e.g., occludin-ZO-1, N-cadherin-β-catenin, claudin-5-ZO-1), steroids (e.g., testosterone, estradiol-17β), nonreceptor protein kinases (e.g., focal adhesion kinase, c-Src, c-Yes), polarity proteins (e.g., PAR6, Cdc42, 14-3-3), endocytic vesicle proteins (e.g., clathrin, caveolin, dynamin 2), and actin regulatory proteins (e.g., Eps8, Arp2/3 complex), are working together, apparently under the overall influence of cytokines (e.g., transforming growth factor-β3, tumor necrosis factor-α, interleukin-1α). In short, a “new” BTB is created behind spermatocytes in transit while the “old” BTB above transiting cells undergoes timely degeneration, so that the immunological barrier can be maintained while spermatocytes are traversing the BTB. We also discuss recent findings regarding the molecular mechanisms by which environmental toxicants (e.g., cadmium, bisphenol A) induce testicular injury via their initial actions at the BTB to elicit subsequent damage to germ-cell adhesion, thereby leading to germ-cell loss, reduced sperm count, and male infertility or subfertility. Moreover, we also critically evaluate findings in the field regarding studies on drug transporters in the testis and discuss how these influx and efflux pumps regulate the entry of potential nonhormonal male contraceptives to the apical compartment to exert their effects. Collectively, these findings illustrate multiple potential targets are present at the BTB for innovative contraceptive development and for better delivery of drugs to alleviate toxicant-induced reproductive dysfunction in men. PMID:22039149

A quantum Otto engine with finite heat baths: energy, correlations, and degradation

NASA Astrophysics Data System (ADS)

Pozas-Kerstjens, Alejandro; Brown, Eric G.; Hovhannisyan, Karen V.

2018-04-01

We study a driven harmonic oscillator operating an Otto cycle by strongly interacting with two thermal baths of finite size. Using the tools of Gaussian quantum mechanics, we directly simulate the dynamics of the engine as a whole, without the need to make any approximations. This allows us to understand the non-equilibrium thermodynamics of the engine not only from the perspective of the working medium, but also as it is seen from the thermal baths’ standpoint. For sufficiently large baths, our engine is capable of running a number of perfect cycles, delivering finite power while operating very close to maximal efficiency. Thereafter, having traversed the baths, the perturbations created by the interaction abruptly deteriorate the engine’s performance. We additionally study the correlations generated in the system, and, in particular, we find a direct connection between the build up of bath–bath correlations and the degradation of the engine’s performance over the course of many cycles.

PCNA-dependent accumulation of CDKN1A into nuclear foci after ionizing irradiation

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

Wiese, Claudia; Rudolph, Jeanette Heede; Jakob, Burkhard

2012-03-26

The cyclin-dependent kinase inhibitor CDKN1A/p21 confers cell-cycle arrest in response to DNA damage and inhibits DNA replication through its direct interaction with the proliferating cell nuclear antigen (PCNA) and cyclin/cyclin-dependent kinase complexes. Previously, we reported that in response to densely ionizing radiation CDKN1A rapidly is recruited to the sites of particle traversal, and that CDKN1A foci formation in response to heavy ions is independent of its transactivation by TP53. In this paper, we show that exposure of normal human fibroblasts to X-rays or to H 2O 2 also induces nuclear accumulations of CDKN1A. We find that CDKN1A foci formation inmore » response to radiation damage is dependent on its dephosphorylation and on its direct physical interaction with PCNA. Live cell imaging analyses of ectopically expressed EGFP-CDKN1A and dsRed-PCNA show rapid recruitment of both proteins into foci after radiation damage. Detailed dynamic measurements reveal a slightly delayed recruitment of CDKN1A compared to PCNA, which is best described by bi-exponential curve fitting, taking the preceding binding of PCNA to DNA into account. Finally, we propose a regulatory role for CDKN1A in mediating PCNA function after radiation damage, and provide evidence that this role is distinct from its involvement in nucleotide excision repair and unrelated to double-strand break repair.« less

Truly Incomplete and Complex Chromosomal Exchanges in Human Fibroblast Cells Exposed In Situ to Energetic Heavy Ions

NASA Technical Reports Server (NTRS)

Wu, Honglu; Durante, marco; Furusawa, Yoshiya; George, Kerry; Kawata, Tetsuya; Cucinotta, Francis A.

2003-01-01

Confluent human fibroblast cells (AG 1522) were irradiated with gamma rays, 490 MeV/nucleon Si, or with Fe ions at either 200 or 500 MeV/nucleon. The cells were allowed to repair at 37 C for 24 hours after exposure, and a chemically induced premature chromosome condensation (PCC) technique was used to condense chromosomes in the G2 phase of the cell cycle. Incomplete and complex exchanges were analyzed in the irradiated samples. In order to verify that chromosomal breaks were truly unrejoined, chromosome aberrations were analyzed using a combination of whole chromosome specific probes and probes specific for the telomere region of the chromosome. Results showed that the frequency of unrejoined chromosome breaks was higher after high-LET radiation, and consequently, the ratio of incomplete to complete exchanges increased steadily with LET up to 440 keV/micron, the highest LET value in the present study. For samples exposed to 200 MeV/nucleon Fe ions, chromosome aberrations were analyzed using the multicolor FISH (mFISH) technique that allow identification of both complex and truly incomplete exchanges. Results of the mFISH study showed that 0.7 and 3 Gy dose of the Fe ions produced similar ratios of complex to simple exchanges and incomplete to complete exchanges, values for which were higher than those obtained after a 6 Gy gamma exposure. After 0.7 Gy of Fe ions, most complex aberrations were found to involve three or four chromosomes, which is a likely indication of the maximum number of chromosome domains traversed by a single Fe ion track.

Analysis of Heavy Ion-Induced Chromosome Aberrations in Human Fibroblast Cells Using In Situ Hybridization

NASA Technical Reports Server (NTRS)

Wu, Honglu; Durante, Marco; Furusawa, Yoshiya; George, Kerry; Kawata, Tetsuya; Cucinotta, Francis A.

2003-01-01

Confluent human fibroblast cells (AG1522) were irradiated with gamma rays, 490 MeV/nucleon Si, or with Fe ions at either 200 or 500 MeV/nucleon. The cells were allowed to repair at 37 0 C for 24 hours after exposure, and a chemically induced premature chromosome condensation (PCC) technique was used to condense chromosomes in the G2 phase of the cell cycle. Unrejoined chromosomal breaks and complex exchanges were analyzed in the irradiated samples. In order to verify that chromosomal breaks were truly unrejoined, chromosome aberrations were analyzed using a combination of whole chromosome specific probes and probes specific for the telomere region of the chromosome. Results showed that the frequency of unrejoined chromosome breaks was higher after high-LET radiation, and consequently, the ratio of incomplete to complete exchanges increased steadily with LET up to 440 keV/micron, the highest LET value in the present study. For samples exposed to 200 MeV/nucleon Fe ions, chromosome aberrations were analyzed using the multicolor FISH (mFISH) technique that allows identification of both complex and truly incomplete exchanges. Results of the mFISH study showed that 0.7 and 3 Gy dose of the Fe ions produced similar ratios of complex to simple exchanges and incomplete to complete exchanges, values for which were higher than those obtained after a 6 Gy gamma exposure. After 0.7 Gy of Fe ions, most complex aberrations were found to involve three or four chromosomes, indicating the maximum number of chromosome domains traversed by a single Fe ion track. 2

Three-dimensional low Reynolds number flows with a free surface

NASA Technical Reports Server (NTRS)

Degani, D.; Gutfinger, C.

1977-01-01

The two-dimensional leveling problem (Degani, Gutfinger, 1976) is extended to three dimensions in the case where the flow Re number is very low and attention is paid to the free surface boundary condition with surface tension effects included. The no-slip boundary condition on the wall is observed. The numerical solution falls back on the Marker and Cell (MAC) method (Harlow and Welch, 1965) with the computation region divided into a finite number of stationary rectangular cells (or boxes in the 3-D case) and fluid flow traverses the cells (or boxes).

Terradynamically streamlined shapes in animals and robots enhance traversability through densely cluttered terrain.

PubMed

Li, Chen; Pullin, Andrew O; Haldane, Duncan W; Lam, Han K; Fearing, Ronald S; Full, Robert J

2015-06-22

Many animals, modern aircraft, and underwater vehicles use fusiform, streamlined body shapes that reduce fluid dynamic drag to achieve fast and effective locomotion in air and water. Similarly, numerous small terrestrial animals move through cluttered terrain where three-dimensional, multi-component obstacles like grass, shrubs, vines, and leaf litter also resist motion, but it is unknown whether their body shape plays a major role in traversal. Few ground vehicles or terrestrial robots have used body shape to more effectively traverse environments such as cluttered terrain. Here, we challenged forest-floor-dwelling discoid cockroaches (Blaberus discoidalis) possessing a thin, rounded body to traverse tall, narrowly spaced, vertical, grass-like compliant beams. Animals displayed high traversal performance (79 ± 12% probability and 3.4 ± 0.7 s time). Although we observed diverse obstacle traversal strategies, cockroaches primarily (48 ± 9% probability) used a novel roll maneuver, a form of natural parkour, allowing them to rapidly traverse obstacle gaps narrower than half their body width (2.0 ± 0.5 s traversal time). Reduction of body roundness by addition of artificial shells nearly inhibited roll maneuvers and decreased traversal performance. Inspired by this discovery, we added a thin, rounded exoskeletal shell to a legged robot with a nearly cuboidal body, common to many existing terrestrial robots. Without adding sensory feedback or changing the open-loop control, the rounded shell enabled the robot to traverse beam obstacles with gaps narrower than shell width via body roll. Such terradynamically 'streamlined' shapes can reduce terrain resistance and enhance traversability by assisting effective body reorientation via distributed mechanical feedback. Our findings highlight the need to consider body shape to improve robot mobility in real-world terrain often filled with clutter, and to develop better locomotor-ground contact models to understand interaction with 3D, multi-component terrain.

Traverse Planning Experiments for Future Planetary Surface Exploration

NASA Technical Reports Server (NTRS)

Hoffman, S. J.; Voels, S. A.; Mueller, R. P.; Lee, P. C.

2011-01-01

This paper describes the results of a recent (July-August 2010 and July 2011) planetary surface traverse planning experiment. The purpose of this experiment was to gather data relevant to robotically repositioning surface assets used for planetary surface exploration. This is a scenario currently being considered for future human exploration missions to the Moon and Mars. The specific scenario selected was a robotic traverse on the lunar surface from an outpost at Shackleton Crater to the Malapert Massif. As these are exploration scenarios, the route will not have been previously traversed and the only pre-traverse data sets available will be remote (orbital) observations. Devon Island was selected as an analog location where a traverse route of significant length could be planned and then traveled. During the first half of 2010, a team of engineers and scientists who had never been to Devon Island used remote sensing data comparable to that which is likely to be available for the Malapert region (eg., 2-meter/pixel imagery, 10-meter interval topographic maps and associated digital elevation models, etc.) to plan a 17-kilometer (km) traverse. Surface-level imagery data was then gathered on-site that was provided to the planning team. This team then assessed whether the route was actually traversable or not. Lessons learned during the 2010 experiment were then used in a second experiment in 2011 for which a much longer traverse (85 km) was planned and additional surface-level imagery different from that gathered in 2010 was obtained for a comparative analysis. This paper will describe the route planning techniques used, the data sets available to the route planners and the lessons learned from the two traverses planned and carried out on Devon Island.

Pertussis toxin permeabilization enhances the traversal of Escherichia coli K1, macrophages, and monocytes in a cerebral endothelial barrier model in vitro.

PubMed

Seidel, Gabriela; Böcker, Kathrin; Schulte, Jessica; Wewer, Corinna; Greune, Lilo; Humberg, Verena; Schmidt, M Alexander

2011-03-01

The occasionally severe neurological complications following the human respiratory tract infection 'whooping cough' have been attributed to pertussis toxin (PT) expressed by the causative agent Bordetella pertussis. Disruption of the endothelial blood-brain barrier (BBB) by PT might facilitate the translocation of immune cells and of hematogenous microbial pathogens. To test this hypothesis, we investigated whether PT enhances the traversal of bacteria employing human brain microvascular endothelial cells (HBMEC) as an in vitro endothelial barrier model. PT incubation significantly increased the translocation of Escherichia coli K1 across the HBMEC barrier. Only intercellular E. coli K1 bacteria could be identified by electron microscopy suggesting paracellular translocation. In addition, the migration of differentiated HL60-derived macrophages and of human monocytic U937 cells through PT-treated HBMEC barriers was also enhanced. In comparison to E. coli C600, E. coli K1 showed prolonged survival in translocated HL60-derived and J774 macrophages as well as in U937 monocytes which suggested a contribution of the 'Trojan horse' mechanism. In summary, our findings demonstrate that the PT-induced permeabilization of endothelial barriers enhances the paracellular transmigration of microbes and immune cells. In vivo, this activity might lower the threshold of bacteremia facilitating secondary cerebral infections and the subsequent development of brain pathologies. Copyright © 2010 Elsevier GmbH. All rights reserved.

Aerodynamic/acoustic performance of YJ101/double bypass VCE with coannular plug nozzle

NASA Technical Reports Server (NTRS)

Vdoviak, J. W.; Knott, P. R.; Ebacker, J. J.

1981-01-01

Results of a forward Variable Area Bypass Injector test and a Coannular Nozzle test performed on a YJ101 Double Bypass Variable Cycle Engine are reported. These components are intended for use on a Variable Cycle Engine. The forward Variable Area Bypass Injector test demonstrated the mode shifting capability between single and double bypass operation with less than predicted aerodynamic losses in the bypass duct. The acoustic nozzle test demonstrated that coannular noise suppression was between 4 and 6 PNdB in the aft quadrant. The YJ101 VCE equipped with the forward VABI and the coannular exhaust nozzle performed as predicted with exhaust system aerodynamic losses lower than predicted both in single and double bypass modes. Extensive acoustic data were collected including far field, near field, sound separation/ internal probe measurements as Laser Velocimeter traverses.

Results of Gravity Fieldwork Conducted in March 2008 in the Moapa Valley Region of Clark County, Nevada

USGS Publications Warehouse

Scheirer, Daniel S.; Andreasen, Arne Dossing

2008-01-01

In March 2008, we collected gravity data along 12 traverses across newly-mapped faults in the Moapa Valley region of Clark County, Nevada. In areas crossed by these faults, the traverses provide better definition of the gravity field and, thus, the density structure, than prior gravity observations. Access problems prohibited complete gravity coverage along all of the planned gravity traverses, and we added and adjusted the locations of traverses to maximize our data collection. Most of the traverses exhibit isostatic gravity anomalies that have gradients characteristic of exposed or buried faults, including several of the newly-mapped faults.

Time for pulse traversal through slabs of dispersive and negative ({epsilon}, {mu}) materials

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

Nanda, Lipsa; Ramakrishna, S. Anantha

2007-12-15

The traversal times for an electromagnetic pulse traversing a slab of dispersive and dissipative material with negative dielectric permittivity ({epsilon}) and magnetic permeability ({mu}) have been calculated by using the average flow of electromagnetic energy in the medium. The effects of bandwidth of the pulse and dissipation in the medium have been investigated. While both large bandwidth and large dissipation have similar effects in smoothening out the resonant features that appear due to Fabry-Perot resonances, large dissipation can result in very small or even negative traversal times near the resonant frequencies. We have also investigated the traversal times and Wignermore » delay times for obliquely incident pulses and evanescent pulses. The coupling to slab plasmon-polariton modes in frequency ranges with negative {epsilon} or {mu} is shown to result in large traversal times at the resonant conditions. We also find that the group velocity mainly contributes to the delay times for pulses propagating across a slab with n=-1. We have checked that the traversal times are positive and subluminal for pulses with sufficiently large bandwidths.« less

Menstrual Cycle Hormone Changes in Women Traversing Menopause: Study of Women’s Health Across the Nation

PubMed Central

Crawford, Sybil L.; El Khoudary, Samar R.; Allshouse, Amanda A.; Burnett-Bowie, Sherri-Ann; Finkelstein, Joel; Derby, Carol; Matthews, Karen; Kravitz, Howard M.; Harlow, Sioban D.; Greendale, Gail A.; Gold, Ellen B.; Kazlauskaite, Rasa; McConnell, Dan; Neal-Perry, Genevieve; Pavlovic, Jelena; Randolph, John; Weiss, Gerson; Chen, Hsiang-Yu; Lasley, Bill

2017-01-01

Context: Menstrual cycle hormone patterns in women approaching menopause are inadequately studied. Objective: To describe day-to-day menstrual cycle hormones in women as they approach menopause from the Study of Women's Health Across the Nation Daily Hormone Study (DHS). Design: DHS enrollees collected daily urine for one entire menstrual cycle or up to 50 days, whichever came first, annually, up to the final menstrual period (FMP) or for up to 10 years. Setting: Seven sites across the United States. Participants: A total of 511 premenopausal or early perimenopausal women at enrollment, within 10 years before menopause. Intervention: Time-to-FMP measurement. Main Outcome Measures: Evidence of luteal activity (ELA), determined using objective algorithms. Menstrual cycle/segment length; whole cycle, and segment integrated urinary luteinizing hormone, follicle-stimulating hormone, estrone conjugates, and pregnanediol glucuronide (Pdg) for each year, organized around the FMP. Results: Mean menstrual cycle length was remarkably preserved at 26 to 27 days in ELA cycles; non-ELA cycles had greater variability. The percentage of cycles that were ELA remained high until 5 years before the FMP (87.9%); only 22.8% of cycles within 1 year of the FMP were ELA. Whole cycle hormones remained relatively stable up to 3 years before the FMP, when gonadotropins began to increase. Pdg excretion declined slowly with progress to the FMP, but Pdg patterns of ELA cycles remained distinguishable from non-ELA. Conclusions: Menstrual cycle hormone patterns in perimenopausal women resemble those of midreproductive-aged women until 5 years before menopause, and presumably ovulatory cycles retain a potentially fertile pattern up to the end of reproductive life. PMID:28368525

High-Performance Plastic Sled Design for Polar Traversing

DTIC Science & Technology

2015-06-01

snow resupply traverses in Antarctica and Greenland tow high- efficiency fuel sleds that consist of flexible fuel bladders strapped to flexi- ble sheets...Foundation, Division of Polar Programs (NSF-PLR), operates over-snow traverses in Antarctica and Greenland to resupply their science stations. The 1030...mile (one way) South Pole Traverse (SPoT) begins at McMurdo Station on Ross Island, travels across the Ross Ice Shelf, up the Leverett Glacier, and

Traverse Planning Experiments for Future Planetary Surface Exploration

NASA Technical Reports Server (NTRS)

Hoffman, Stephen J.; Voels, Stephen A.; Mueller, Robert P.; Lee, Pascal C.

2012-01-01

The purpose of the investigation is to evaluate methodology and data requirements for remotely-assisted robotic traverse of extraterrestrial planetary surface to support human exploration program, assess opportunities for in-transit science operations, and validate landing site survey and selection techniques during planetary surface exploration mission analog demonstration at Haughton Crater on Devon Island, Nunavut, Canada. Additionally, 1) identify quality of remote observation data sets (i.e., surface imagery from orbit) required for effective pre-traverse route planning and determine if surface level data (i.e., onboard robotic imagery or other sensor data) is required for a successful traverse, and if additional surface level data can improve traverse efficiency or probability of success (TRPF Experiment). 2) Evaluate feasibility and techniques for conducting opportunistic science investigations during this type of traverse. (OSP Experiment). 3) Assess utility of remotely-assisted robotic vehicle for landing site validation survey. (LSV Experiment).

Biological effect of food additive titanium dioxide nanoparticles on intestine: an in vitro study.

PubMed

Song, Zheng-Mei; Chen, Ni; Liu, Jia-Hui; Tang, Huan; Deng, Xiaoyong; Xi, Wen-Song; Han, Kai; Cao, Aoneng; Liu, Yuanfang; Wang, Haifang

2015-10-01

Titanium dioxide nanoparticles (TiO2 NPs) are widely found in food-related consumer products. Understanding the effect of TiO2 NPs on the intestinal barrier and absorption is essential and vital for the safety assessment of orally administrated TiO2 NPs. In this study, the cytotoxicity and translocation of two native TiO2 NPs, and these two TiO2 NPs pretreated with the digestion simulation fluid or bovine serum albumin were investigated in undifferentiated Caco-2 cells, differentiated Caco-2 cells and Caco-2 monolayer. TiO2 NPs with a concentration less than 200 µg ml(-1) did not induce any toxicity in differentiated cells and Caco-2 monolayer after 24 h exposure. However, TiO2 NPs pretreated with digestion simulation fluids at 200 µg ml(-1) inhibited the growth of undifferentiated Caco-2 cells. Undifferentiated Caco-2 cells swallowed native TiO2 NPs easily, but not pretreated NPs, implying the protein coating on NPs impeded the cellular uptake. Compared with undifferentiated cells, differentiated ones possessed much lower uptake ability of these TiO2 NPs. Similarly, the traverse of TiO2 NPs through the Caco-2 monolayer was also negligible. Therefore, we infer the possibility of TiO2 NPs traversing through the intestine of animal or human after oral intake is quite low. This study provides valuable information for the risk assessment of TiO2 NPs in food. Copyright © 2015 John Wiley & Sons, Ltd.

A novel microfluidics-based method for probing weak protein-protein interactions.

PubMed

Tan, Darren Cherng-wen; Wijaya, I Putu Mahendra; Andreasson-Ochsner, Mirjam; Vasina, Elena Nikolaevna; Nallani, Madhavan; Hunziker, Walter; Sinner, Eva-Kathrin

2012-08-07

We report the use of a novel microfluidics-based method to detect weak protein-protein interactions between membrane proteins. The tight junction protein, claudin-2, synthesised in vitro using a cell-free expression system in the presence of polymer vesicles as membrane scaffolds, was used as a model membrane protein. Individual claudin-2 molecules interact weakly, although the cumulative effect of these interactions is significant. This effect results in a transient decrease of average vesicle dispersivity and reduction in transport speed of claudin-2-functionalised vesicles. Polymer vesicles functionalised with claudin-2 were perfused through a microfluidic channel and the time taken to traverse a defined distance within the channel was measured. Functionalised vesicles took 1.19 to 1.69 times longer to traverse this distance than unfunctionalised ones. Coating the channel walls with protein A and incubating the vesicles with anti-claudin-2 antibodies prior to perfusion resulted in the functionalised vesicles taking 1.75 to 2.5 times longer to traverse this distance compared to the controls. The data show that our system is able to detect weak as well as strong protein-protein interactions. This system offers researchers a portable, easily operated and customizable platform for the study of weak protein-protein interactions, particularly between membrane proteins.

Photograph of Apollo 17 Lunar Roving Vehicle traverses

NASA Image and Video Library

1972-10-01

S72-03145 (October 1972) --- A vertical view of the Apollo 17 Taurus-Littrow site with an overlay to illustrate the three planned Apollo 17 traverses using the Lunar Roving Vehicle (LRV). The EVA-1 traverse has a single station (1); the EVA-2 traverse has four stations (2,3,4,5); and the EVA-3 traverse has five stations (6,7,8,9,10). Stations 10-A and 10-B are alternate locations for Station 10. In addition to the major stations mentioned above, brief stops are planned for sampling between stations using the LRV sampler tool (note diamond-shaped figures), and for deploying explosive charges associated with the Lunar Seismic Profiling Experiment (LSPE - note black x-marks).

Application of the LI-COR CO2 analyzer to volcanic plumes: a case study, volcán Popocatépetl, Mexico, June 7 and 10, 1995

USGS Publications Warehouse

Gerlach, T.M.; Delgado, H.; McGee, K.A.; Doukas, M.P.; Venegas, J.J.; Cardenas, L.

1997-01-01

Volcanic CO2 emission rate data are sparse despite their potential importance for constraining the role of magma degassing in the biogeochemical cycle of carbon and for assessing volcanic hazards. We used a LI-COR CO2 analyzer to determine volcanic CO2 emission rates by airborne measurements in volcanic plumes at Popocatépetl volcano on June 7 and 10, 1995. LI-COR sample paths of ∼72 m, compared with ∼1 km for the analyzer customarily used, together with fast Fourier transforms to remove instrument noise from raw data greatly improve resolution of volcanic CO2 anomalies. Parametric models fit to background CO2 provide a statistical tool for distinguishing volcanic from ambient CO2. Global Positioning System referenced flight traverses provide vastly improved data on the shape, coherence, and spatial distribution of volcanic CO2 in plume cross sections and contrast markedly with previous results based on traverse stacking. The continuous escape of CO2 and SO2 from Popocatépetl was fundamentally noneruptive and represented quiescent magma degassing from the top of a magma chamber ∼5 km deep. The average CO2 emission rate for January-June 1995 is estimated to be at least 6400 t d−1, one of the highest determined for a quiescently degassing volcano, although correction for downwind dispersion effects on volcanic CO2 indicates a higher rate of ∼9000 t d−1. Analysis of random errors indicates emission rates have 95% confidence intervals of ∼±20%, with uncertainty contributed mostly by wind speed variance, although the variance of plume cross-sectional areas during traversing is poorly constrained and possibly significant.

Induced vibrations facilitate traversal of cluttered obstacles

NASA Astrophysics Data System (ADS)

Thoms, George; Yu, Siyuan; Kang, Yucheng; Li, Chen

When negotiating cluttered terrains such as grass-like beams, cockroaches and legged robots with rounded body shapes most often rolled their bodies to traverse narrow gaps between beams. Recent locomotion energy landscape modeling suggests that this locomotor pathway overcomes the lowest potential energy barriers. Here, we tested the hypothesis that body vibrations induced by intermittent leg-ground contact facilitate obstacle traversal by allowing exploration of locomotion energy landscape to find this lowest barrier pathway. To mimic a cockroach / legged robot pushing against two adjacent blades of grass, we developed an automated robotic system to move an ellipsoidal body into two adjacent beams, and varied body vibrations by controlling an oscillation actuator. A novel gyroscope mechanism allowed the body to freely rotate in response to interaction with the beams, and an IMU and cameras recorded the motion of the body and beams. We discovered that body vibrations facilitated body rolling, significantly increasing traversal probability and reducing traversal time (P <0.0001, ANOVA). Traversal probability increased with and traversal time decreased with beam separation. These results confirmed our hypothesis and support the plausibility of locomotion energy landscapes for understanding the formation of locomotor pathways in complex 3-D terrains.

Chaotic Traversal (CHAT): Very Large Graphs Traversal Using Chaotic Dynamics

NASA Astrophysics Data System (ADS)

Changaival, Boonyarit; Rosalie, Martin; Danoy, Grégoire; Lavangnananda, Kittichai; Bouvry, Pascal

2017-12-01

Graph Traversal algorithms can find their applications in various fields such as routing problems, natural language processing or even database querying. The exploration can be considered as a first stepping stone into knowledge extraction from the graph which is now a popular topic. Classical solutions such as Breadth First Search (BFS) and Depth First Search (DFS) require huge amounts of memory for exploring very large graphs. In this research, we present a novel memoryless graph traversal algorithm, Chaotic Traversal (CHAT) which integrates chaotic dynamics to traverse large unknown graphs via the Lozi map and the Rössler system. To compare various dynamics effects on our algorithm, we present an original way to perform the exploration of a parameter space using a bifurcation diagram with respect to the topological structure of attractors. The resulting algorithm is an efficient and nonresource demanding algorithm, and is therefore very suitable for partial traversal of very large and/or unknown environment graphs. CHAT performance using Lozi map is proven superior than the, commonly known, Random Walk, in terms of number of nodes visited (coverage percentage) and computation time where the environment is unknown and memory usage is restricted.

Terrain Traversing Device Having a Wheel with Microhooks

NASA Technical Reports Server (NTRS)

Parness, Aaron (Inventor); McKenzie, Clifford F. (Inventor)

2014-01-01

A terrain traversing device includes an annular rotor element with a plurality of co-planar microspine hooks arranged on the periphery of the annular rotor element. Each microspine hook has an independently flexible suspension configuration that permits the microspine hook to initially engage an irregularity in a terrain surface at a preset initial engagement angle and subsequently engage the irregularity with a continuously varying engagement angle when the annular rotor element is rotated for urging the terrain traversing device to traverse a terrain surface.

Geologic Traverse Planning for Apollo Missions

NASA Technical Reports Server (NTRS)

Lofgren, Gary

2012-01-01

The science on Apollo missions was overseen by the Science Working Panel (SWP), but done by multiple PIs. There were two types of science, packages like the Apollo Lunar Surface Experiment Package (ALSEP) and traverse science. Traverses were designed on Earth for the astronauts to execute. These were under direction of the Lunar Surface PI, but the agreed traverse was a cooperation between the PI and SWP. The landing sites were selected by a different designated committee, not the SWP, and were based on science and safety.

Comparison of pitot traverses taken at varying distances downstream of obstructions.

PubMed

Guffey, S E; Booth, D W

1999-01-01

This study determined the deviations between pitot traverses taken under "ideal" conditions--at least seven duct diameter's lengths (i.e., distance = 7D) from obstructions, elbows, junction fittings, and other disturbances to flows--with those taken downstream from commonplace disturbances. Two perpendicular 10-point, log-linear velocity pressure traverses were taken at various distances downstream of tested upstream conditions. Upstream conditions included a plain duct opening, a junction fitting, a single 90 degrees elbow, and two elbows rotated 90 degrees from each other into two orthogonal planes. Airflows determined from those values were compared with the values measured more than 40D downstream of the same obstructions under ideal conditions. The ideal measurements were taken on three traverse diameters in the same plane separated by 120 degrees in honed drawn-over-mandrel tubing. In all cases the pitot tubes were held in place by devices that effectively eliminated alignment errors and insertion depth errors. Duct velocities ranged from 1500 to 4500 ft/min. Results were surprisingly good if one employed two perpendicular traverses. When the averages of two perpendicular traverses was taken, deviations from ideal value were 6% or less even for traverses taken as close as 2D distance from the upstream disturbances. At 3D distance, deviations seldom exceeded 5%. With single diameter traverses, errors seldom exceeded 5% at 6D or more downstream from the disturbance. Interestingly, percentage deviations were about the same at high and low velocities. This study demonstrated that two perpendicular pitot traverses can be taken as close as 3D from these disturbances with acceptable (< or = 5%) deviations from measurements taken under ideal conditions.

Results of gamma activity traverses made in process tube channels and VSR channels at 105-KW

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

Greene, M.C. Jr.

1955-02-03

Activity traverses were made at Hanford reactor 105-KW in VSR channels 23, 29, 37, 46, 55, 63 and 69 and in process channels 4669, 4569, 4668, 4670 and 4769. These traverses were made during cleaning operations to assist in the location of any contaminated material in these channels and again after completion of the cleaning operations to determine if all of the contaminated material was removed. Upon completion of the cleaning of the VSR channels and process channels activity traverses were made in all of the channels. The results of these traverses show that no detectable amounts of contaminated materialmore » were present in any of these channels. The traverses made in the VSR channels all show a large peak in the lower part of the pile indicating that the metal in the lower part of the pile received as much as five times the integrated exposure received by the metal in the upper half of the pile. 15 figs.« less

Dynamic traversal of large gaps by insects and legged robots reveals a template.

PubMed

Gart, Sean W; Yan, Changxin; Othayoth, Ratan; Ren, Zhiyi; Li, Chen

2018-02-02

It is well known that animals can use neural and sensory feedback via vision, tactile sensing, and echolocation to negotiate obstacles. Similarly, most robots use deliberate or reactive planning to avoid obstacles, which relies on prior knowledge or high-fidelity sensing of the environment. However, during dynamic locomotion in complex, novel, 3D terrains, such as a forest floor and building rubble, sensing and planning suffer bandwidth limitation and large noise and are sometimes even impossible. Here, we study rapid locomotion over a large gap-a simple, ubiquitous obstacle-to begin to discover the general principles of the dynamic traversal of large 3D obstacles. We challenged the discoid cockroach and an open-loop six-legged robot to traverse a large gap of varying length. Both the animal and the robot could dynamically traverse a gap as large as one body length by bridging the gap with its head, but traversal probability decreased with gap length. Based on these observations, we developed a template that accurately captured body dynamics and quantitatively predicted traversal performance. Our template revealed that a high approach speed, initial body pitch, and initial body pitch angular velocity facilitated dynamic traversal, and successfully predicted a new strategy for using body pitch control that increased the robot's maximal traversal gap length by 50%. Our study established the first template of dynamic locomotion beyond planar surfaces, and is an important step in expanding terradynamics into complex 3D terrains.

Modification of Salmonella Lipopolysaccharides Prevents the Outer Membrane Penetration of Novobiocin

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

Nobre, Thatyane M.; Martynowycz, Michael W.; Andreev, Konstantin

Small hydrophilic antibiotics traverse the outer membrane of Gram-negative bacteria through porin channels. Large lipophilic agents traverse the outer membrane through its bilayer, containing a majority of lipopolysaccharides in its outer leaflet. Genes controlled by the two-component regulatory system PhoPQ modify lipopolysaccharides. We isolate lipopolysaccharides from isogenic mutants of Salmonella sp., one lacking the modification, the other fully modified. These lipopolysaccharides were reconstituted asmonolayers at the air-water interface, and their properties, aswell as their interaction with a large lipophilic drug, novobiocin, was studied. X-ray reflectivity showed that the drug penetrated the monolayer of the unmodified lipopolysaccharides reaching the hydrophobic region,butwasmore » prevented fromthis penetration intothemodified lipopolysaccharides.Results correlatewith behavior of bacterial cells, which become resistant to antibiotics after PhoPQ-regulated modifications. Grazing incidence x-ray diffraction showed that novobiocin produced a striking increase in crystalline coherence length, and the size of the near-crystalline domains.« less

Traversable highways report 2002 : a report on the status of prospective State Highway Routes over traversable facilities maintained by other agencies.

DOT National Transportation Integrated Search

2002-10-01

Traversable Highways are routes that have been approved by the Legislation as future State : Highway Routes. These routes when constructed to the Department of Transportation (Caltrans) : standards, the California Transportation Commission (CTC) shal...

Science Autonomy in Robotic Exploration

NASA Technical Reports Server (NTRS)

Roush, Ted L.; DeVincenzi, Donald (Technical Monitor)

2001-01-01

Historical mission operations have involved: (1) return of scientific data; (2) evaluation of these data by scientists; (3) recommendations for future mission activity by scientists; (4) commands for these transmitted to the craft; and (5) the activity being undertaken. This cycle is repeated throughout the mission with command opportunities once or twice per day. For a rover, this historical cycle is not amenable to rapid long range traverses or rapid response to any novel or unexpected situations. In addition to real-time response issues, imaging and/or spectroscopic devices can produce tremendous data volumes during a traverse. However, such data volumes can rapidly exceed on-board memory capabilities prior to the ability to transmit it to Earth. Additionally, the necessary communication band-widths are restrictive enough so that only a small portion of these data can actually be returned to Earth. Such scenarios suggest enabling some science decisions to be made on-board the robots. These decisions involve automating various aspects of scientific discovery instead of the electromechanical control, health, and navigation issues associated with robotic operations. The robot retains access to the full data fidelity obtained by its scientific sensors, and is in the best position to implement actions based upon these data. Such an approach would eventually enable the robot to alter observations and assure only the highest quality data is obtained for analysis. Additionally, the robot can begin to understand what is scientifically interesting and implement alternative observing sequences, because the observed data deviate from expectations based upon current theories/models of planetary processes. Such interesting data and/or conclusions can then be prioritized and selectively transmitted to Earth; reducing memory and communications demands. Results of Ames' current work in this area will be presented.

Robotic Exploration: The Role of Science Autonomy

NASA Technical Reports Server (NTRS)

Roush, Ted L.; DeVincenzi, Donald (Technical Monitor)

2001-01-01

Historical mission operations have involved: (1) return of scientific data; (2) evaluation of these data by scientists; (3) recommendations for future mission activity by scientists; (4) commands for these transmitted to the craft; and (5) the activity being, undertaken. This cycle is repeated throughout the mission with command opportunities once or twice per day. For a rover, this historical cycle is not amenable to rapid long range traverses or rapid response to any novel or unexpected situations. In addition to real-time response issues, imaging and/or spectroscopic devices can produce tremendous data volumes during a traverse. However, such data volumes can rapidly exceed on-board memory capabilities prior to the ability to transmit it to Earth. Additionally, the necessary communication band-widths are restrictive enough so that only a small portion of these data can actually be returned to Earth. Such scenarios suggest enabling some science decisions to be made on-board the robots. These decisions involve automating various aspects of scientific discovery instead of the electromechanical control, health, and navigation issues associated with robotic operations. The robot retains access to the full data fidelity obtained by its scientific sensors, and is in the best position to implement actions based upon these data. Such an approach would eventually enable the robot to alter observations and assure only the highest quality data is obtained for analysis. Additionally, the robot can begin to understand what is scientifically interesting and implement alternative observing sequences, because the observed data deviate from expectations based upon current theories/models of planetary processes. Such interesting data and/or conclusions can then be prioritized and selectively transmitted to Earth; reducing memory and communications demands. Results of Ames' current work in this area will be presented.

Septal Junctions in Filamentous Heterocyst-Forming Cyanobacteria.

PubMed

Flores, Enrique; Herrero, Antonia; Forchhammer, Karl; Maldener, Iris

2016-02-01

In the filaments of heterocyst-forming cyanobacteria, septal junctions that traverse the septal peptidoglycan join adjacent cells, allowing intercellular communication. Perforations in the septal peptidoglycan have been observed, and proteins involved in the formation of such perforations and putative protein components of the septal junctions have been identified, but their relationships are debated. Copyright © 2015 Elsevier Ltd. All rights reserved.

Elucidation of the new generation fluorescent protein tdTomato for space related radiobiological research

NASA Astrophysics Data System (ADS)

Chishti, Arif Ali; Baumstark-Khan, Christa; Hellweg, Christine; Reitz, Guenther

Astronauts in space are exposed to a potentially harmful radiation field, which does not exist in its quality and quantity on earth. Radiation exposure in space can lead to delayed or acute health effects. A successful long-term space mission requires better risk estimation and development of appropriate countermeasures, therefore study of the cellular radiation response is necessary. Ionizing radiation can provoke active cellular responses (cell cycle arrest, DNA repair, apoptosis or other forms of cell type). Exposure to ionizing radiation also activates various signaling pathways in human cells. In the cellular radiation-response, two pivotal signal transduction pathways have to be comprehensively studied i.e. the p53-pathway and NF-κB-pathway. Discovery of fluorescent proteins has revolutionized biological research by making it possible to carry out functional studies in living cells and understanding complex signaling pathways. Previously the green fluorescent proteins EGFP and d2EGFP were used for signaling pathway studies. In this work the new red fluorescent protein tdTomato will be used for comprehensive investigation of NF-κB and other transcription factor activation after exposure of human cells to ionizing radiation (X-rays, heavy ions; space conditions). tdTomato has many advantages over EGFP because of its high fluorescence signals and a better signal/noise ratio in human cells. The previously constructed reporter system with d2EGFP was used to evaluate NF-kB activation after exposure to heavy ion particles of different biological effectiveness. The sensitivity threshold of this system was determined to be 2 particle traversals per cell nucleus. In the current study a more sensitive reporter assay will be constructed using a GAL4-VP16 turbo system that comprises a receptor plasmid and a reporter plasmid. This reporter assay will be designed and constructed with tdTomato and evaluation will be done with different molecular techniques.

Induction of micronuclei in human fibroblasts across the Bragg curve of energetic heavy ions

NASA Technical Reports Server (NTRS)

Hada, Megumi; Rusek, Adam; Cucinotta, Francis A.; Wu, Honglu

2006-01-01

The space environment consists of a varying field of radiation particles including high energy ions, with spacecraft shielding material providing the major protection to astronauts from harmful exposure. Unlike low-L or X-rays, the presence of shielding does not always reduce the radiation risks for energetic charged particle exposure. Although the dose delivered by the charged particle increases sharply as the particle approaches the Bragg peak, the Bragg curve does not necessarily represent the biological damage along the particle traversal. The "biological Bragg curve" is dependent on the energy and the type of the primary particle, and may vary for different biological endpoints. To investigate "biological Bragg curves", we analyzed micronuclei (MN) induction along the particle traversal of Si and Fe ions at incident energies of 300 MeV/nucleon and 1 GeV/nucleon. A quantitative biological response curve did not reveal an increased yield of MN at the location of the Bragg peak. However, the ratio of mono-to bi-nucleated cells, which indicates inhibition in cell progression, increased at the Bragg peak location. These results confirm the hypothesis that "over kill" at the Bragg peak will affect the outcome of other biological endpoints.

Vertical and lateral forces when a permanent magnet above a superconductor traverses in arbitrary directions

NASA Astrophysics Data System (ADS)

Yang, Yong

2008-12-01

In an actual levitation system composed of high temperature superconductors (HTSs) and permanent magnets (PMs), the levitating bodies may traverse in arbitrary directions. Many previous researchers assumed that the levitating bodies moved in a vertical direction or a lateral direction in order to simplify the problem. In this paper, the vertical and lateral forces acting on the PM are calculated by the modified frozen-image method when a PM above an HTS traverses in arbitrary directions. In order to study the effects of the movement directions on the vertical and lateral forces, comparisons of the forces that act on a PM traversing in a tilted direction with those that act on a PM traversing in a vertical direction or a lateral direction have been presented.

Dynamic traversal of high bumps and large gaps by a small legged robot

NASA Astrophysics Data System (ADS)

Gart, Sean; Winey, Nastasia; de La Tijera Obert, Rafael; Li, Chen

Small animals encounter and negotiate diverse obstacles comparable in size or larger than themselves. In recent experiments, we found that cockroaches can dynamically traverse bumps up to 4 times hip height and gaps up to 1 body length. To better understand the physics that governs these locomotor transitions, we studied a small six-legged robot negotiating high bumps and large gaps and compared it to animal observations. We found that the robot was able to traverse bumps as large as 1 hip height and gaps as wide as 0.5 body length. For the bump, the robot often climbed over to traverse when initial body yaw was small, but was often deflected laterally and failed to traverse when initial body yaw was large. A simple locomotion energy landscape model explained these observations. For the gap, traversal probability decreased with gap width, which was well explained by a simple Lagrangian model of a forward-moving rigid body falling over the gap edge. For both the bump and the gap, animal performance far exceeded that of the robot, likely due to their relatively higher running speeds and larger rotational oscillations prior to and during obstacle traversal. Differences between animal and robot obstacle negotiation behaviors revealed that animals used active strategies to overcome potential energy barriers.

Autonomous Image Analysis for Future Mars Missions

NASA Technical Reports Server (NTRS)

Gulick, V. C.; Morris, R. L.; Ruzon, M. A.; Bandari, E.; Roush, T. L.

1999-01-01

To explore high priority landing sites and to prepare for eventual human exploration, future Mars missions will involve rovers capable of traversing tens of kilometers. However, the current process by which scientists interact with a rover does not scale to such distances. Specifically, numerous command cycles are required to complete even simple tasks, such as, pointing the spectrometer at a variety of nearby rocks. In addition, the time required by scientists to interpret image data before new commands can be given and the limited amount of data that can be downlinked during a given command cycle constrain rover mobility and achievement of science goals. Experience with rover tests on Earth supports these concerns. As a result, traverses to science sites as identified in orbital images would require numerous science command cycles over a period of many weeks, months or even years, perhaps exceeding rover design life and other constraints. Autonomous onboard science analysis can address these problems in two ways. First, it will allow the rover to preferentially transmit "interesting" images, defined as those likely to have higher science content. Second, the rover will be able to anticipate future commands. For example, a rover might autonomously acquire and return spectra of "interesting" rocks along with a high-resolution image of those rocks in addition to returning the context images in which they were detected. Such approaches, coupled with appropriate navigational software, help to address both the data volume and command cycle bottlenecks that limit both rover mobility and science yield. We are developing fast, autonomous algorithms to enable such intelligent on-board decision making by spacecraft. Autonomous algorithms developed to date have the ability to identify rocks and layers in a scene, locate the horizon, and compress multi-spectral image data. We are currently investigating the possibility of reconstructing a 3D surface from a sequence of images acquired by a robotic arm camera. This would then allow the return of a single completely in focus image constructed only from those portions of individual images that lie within the camera's depth of field. Output from these algorithms could be used to autonomously obtain rock spectra, determine which images should be transmitted to the ground, or to aid in image compression. We will discuss these algorithms and their performance during a recent rover field test.

27 CFR 9.114 - Old Mission Peninsula.

Code of Federal Regulations, 2011 CFR

2011-04-01

... boundary in Grand Traverse County, Michigan, consists of all of Peninsula Township, excluding Marion and Bassett Islands. In addition, the viticultural area takes in a small portion of Traverse City Township. (1... Grand Traverse Bay at Section 1, Township 27 North, Range 11 West (T27N, R11W), approximately 500 feet...

27 CFR 9.114 - Old Mission Peninsula.

Code of Federal Regulations, 2010 CFR

2010-04-01

... boundary in Grand Traverse County, Michigan, consists of all of Peninsula Township, excluding Marion and Bassett Islands. In addition, the viticultural area takes in a small portion of Traverse City Township. (1... Grand Traverse Bay at Section 1, Township 27 North, Range 11 West (T27N, R11W), approximately 500 feet...

76 FR 9597 - Notice of Inventory Completion: Denver Museum of Nature & Science, Denver, CO

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-18

... the Duck Valley Reservation, Nevada; Sisseton-Wahpeton Oyate of the Lake Traverse Reservation, South...; Shoshone-Paiute Tribes of the Duck Valley Reservation, Nevada; Sisseton-Wahpeton Oyate of the Lake Traverse...; Shoshone-Paiute Tribes of the Duck Valley Reservation, Nevada; Sisseton-Wahpeton Oyate of the Lake Traverse...

New Modeling Approaches to Investigate Cell Signaling in Radiation Response

NASA Technical Reports Server (NTRS)

Plante, Ianik; Cucinotta, Francis A.; Ponomarev, Artem L.

2011-01-01

Ionizing radiation damages individual cells and tissues leading to harmful biological effects. Among many radiation-induced lesions, DNA double-strand breaks (DSB) are considered the key precursors of most early and late effects [1] leading to direct mutation or aberrant signal transduction processes. In response to damage, a flow of information is communicated to cells not directly hit by the radiation through signal transduction pathways [2]. Non-targeted effects (NTE), which includes bystander effects and genomic instability in the progeny of irradiated cells and tissues, may be particularly important for space radiation risk assessment [1], because astronauts are exposed to a low fluence of heavy ions and only a small fraction of cells are traversed by an ion. NTE may also have important consequences clinical radiotherapy [3]. In the recent years, new simulation tools and modeling approaches have become available to study the tissue response to radiation. The simulation of signal transduction pathways require many elements such as detailed track structure calculations, a tissue or cell culture model, knowledge of biochemical pathways and Brownian Dynamics (BD) propagators of the signaling molecules in their micro-environment. Recently, the Monte-Carlo simulation code of radiation track structure RITRACKS was used for micro and nano-dosimetry calculations [4]. RITRACKS will be used to calculate the fraction of cells traversed by an ion and delta-rays and the energy deposited in cells in a tissue model. RITRACKS also simulates the formation of chemical species by the radiolysis of water [5], notably the .OH radical. This molecule is implicated in DNA damage and in the activation of the transforming growth factor beta (TGF), a signaling molecule involved in NTE. BD algorithms for a particle near a membrane comprising receptors were also developed and will be used to simulate trajectories of signaling molecules in the micro-environment and characterize autocrine and paracrine cell communication and signal transduction.

Astronauts Lovell and Haise during simulation of lunar traverse at Hawaii

NASA Image and Video Library

1969-12-01

S70-20253 (December 1969) --- Astronauts James A. Lovell Jr. (left) commander, and Fred W. Haise Jr., lunar module pilot, carry out a simulation of a lunar traverse at Kilauea, Hawaii, site. Both crew members of NASA's third team of moon explorers were carrying cameras and communications equipment during the simulated traverse. They maintained contact with men in the roles of spacecraft throughout the traverse. Lovell holds a scoop for the Apollo Lunar Hand Tools (ALHT) and a gnomon, also for the ALHT is deployed in front of Haise. The ALHT carrier is at left background, (almost obscured by Lovell).

Study of journal bearing dynamics using 3-dimensional motion picture graphics

NASA Technical Reports Server (NTRS)

Brewe, D. E.; Sosoka, D. J.

1985-01-01

Computer generated motion pictures of three dimensional graphics are being used to analyze journal bearings under dynamically loaded conditions. The motion pictures simultaneously present the motion of the journal and the pressures predicted within the fluid film of the bearing as they evolve in time. The correct prediction of these fluid film pressures can be complicated by the development of cavitation within the fluid. The numerical model that is used predicts the formation of the cavitation bubble and its growth, downstream movement, and subsequent collapse. A complete physical picture is created in the motion picture as the journal traverses through the entire dynamic cycle.

75 FR 9015 - Notice of Availability of a Final Environmental Assessment (Final EA) and a Finding of No...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-26

... the New Airport Traffic Control Tower and Base Building at Cherry Capital Airport, Traverse City, MI... the New Airport Traffic Control Tower and Base Building at Cherry Capital Airport, Traverse City... Control Tower (ATCT) and Base Building at Cherry Capital Airport (TVC) in Traverse City, Michigan. The FAA...

Phantom energy traversable wormholes

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

Lobo, Francisco S.N.; Campo Grande, Ed. C8 1749-016 Lisbon

2005-04-15

It has been suggested that a possible candidate for the present accelerated expansion of the Universe is 'phantom energy'. The latter possesses an equation of state of the form {omega}{identical_to}p/{rho}<-1, consequently violating the null energy condition. As this is the fundamental ingredient to sustain traversable wormholes, this cosmic fluid presents us with a natural scenario for the existence of these exotic geometries. 'Note, however, that the notion of phantom energy is that of a homogeneously distributed fluid. Nevertheless, it can be extended to inhomogeneous spherically symmetric spacetimes, and it is shown that traversable wormholes may be supported by phantom energy.more » Because of the fact of the accelerating Universe, macroscopic wormholes could naturally be grown from the submicroscopic constructions that originally pervaded the quantum foam. One could also imagine an advanced civilization mining the cosmic fluid for phantom energy necessary to construct and sustain a traversable wormhole. In this context, we investigate the physical properties and characteristics of traversable wormholes constructed using the equation of state p={omega}{rho}, with {omega}<-1. We analyze specific wormhole geometries, considering asymptotically flat spacetimes and imposing an isotropic pressure. We also construct a thin shell around the interior wormhole solution, by imposing the phantom energy equation of state on the surface stresses. Using the 'volume integral quantifier' we verify that it is theoretically possible to construct these geometries with vanishing amounts of averaged null energy condition violating phantom energy. Specific wormhole dimensions and the traversal velocity and time are also deduced from the traversability conditions for a particular wormhole geometry. These phantom energy traversable wormholes have far-reaching physical and cosmological implications. For instance, an advanced civilization may use these geometries to induce closed timelike curves, consequently violating causality.« less

Vision-Based Real-Time Traversable Region Detection for Mobile Robot in the Outdoors.

PubMed

Deng, Fucheng; Zhu, Xiaorui; He, Chao

2017-09-13

Environment perception is essential for autonomous mobile robots in human-robot coexisting outdoor environments. One of the important tasks for such intelligent robots is to autonomously detect the traversable region in an unstructured 3D real world. The main drawback of most existing methods is that of high computational complexity. Hence, this paper proposes a binocular vision-based, real-time solution for detecting traversable region in the outdoors. In the proposed method, an appearance model based on multivariate Gaussian is quickly constructed from a sample region in the left image adaptively determined by the vanishing point and dominant borders. Then, a fast, self-supervised segmentation scheme is proposed to classify the traversable and non-traversable regions. The proposed method is evaluated on public datasets as well as a real mobile robot. Implementation on the mobile robot has shown its ability in the real-time navigation applications.

US/USSR cooperative program in open-cycle MHD electrical power generation: joint test report No. 4. Tests in the U-25B facility: MHD generator tests No. 6 and 7

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

Picologlou, B F; Batenin, V M

1981-01-01

A description of the main results obtained during Tests No. 6 and 7 at the U-25B Facility using the new channel No. 2 is presented. The purpose of these tests was to operate the MHD generator at its design parameters. Described here are new plasma diagnostic devices: a traversing dual electrical probe for determining distribution of electron concentrations, and a traversing probe that includes a pitot tube for measuring total and static pressure, and a light detector for measuring plasma luminescence. Data are presented on heat flux distribution along the channel, the first data of this type obtained for anmore » MHD facility of such size. Results are given of experimental studies of plasma characteristics, gasdynamic, thermal, and electrical MHD channel performance, and temporal and spatial nonuniformities. Typical modes of operation are analyzed by means of local electrical analyses. Computer models are used to obtain predictions for both localized and overall generator characteristics. These theoretical predictions agree closely with the results of the local analyses, as well as with measurements of the overall gasdynamic and electrical characteristics of the generator.« less

Blood-testis barrier dynamics are regulated by testosterone and cytokines via their differential effects on the kinetics of protein endocytosis and recycling in Sertoli cells

PubMed Central

Yan, Helen H. N.; Mruk, Dolores D.; Lee, Will M.; Cheng, C. Yan

2009-01-01

During spermatogenesis in the mammalian testis, preleptotene/leptotene spermatocytes differentiate from type B spermatogonia and traverse the blood-testis barrier (BTB) at stage VIII of the seminiferous epithelial cycle for further development. This timely movement of germ cells involves extensive junction restructuring at the BTB. Previous studies have shown that these events are regulated by testosterone (T) and cytokines [e.g., the transforming growth factor (TGF) -βs], which promote and disrupt the BTB assembly, respectively. However, the mechanisms underlying the “opening” of the BTB above a migrating preleptotene/leptotene spermatocyte and the “resealing” of the barrier underneath this cell remain obscure. We now report findings on a novel mechanism utilized by the testes to regulate these events. Using cell surface protein biotinylation coupled with immunoblotting and immunofluorescent microscopy, we assessed the kinetics of endocytosis and recycling of BTB-associated integral membrane proteins: occludin, JAM-A, and N-cadherin. It was shown that these proteins were continuously endocytosed and recycled back to the Sertoli cell surface via the clathrin-mediated but not the caveolin-mediated pathway. When T or TGF-β2 was added to Sertoli cell cultures with established functional BTB, both factors accelerated the kinetics of internalization of BTB proteins from the cell surface, perhaps above the migrating preleptotene spermatocyte, thereby opening the BTB. Likewise, T also enhanced the kinetics of recycling of internalized biotinylated proteins back to the cell surface, plausibly relocating these proteins beneath the migrating spermatocyte to reassemble the BTB. In contrast, TGF-β2 targeted internalized biotinylated proteins to late endosomes for degradation, destabilizing the BTB. In summary, the transient opening of the BTB that facilitates germ cell movement is mediated via the differential effects of T and cytokines on the kinetics of endocytosis and recycling of integral membrane proteins at the BTB. The net result of these interactions, in turn, determines the steady-state protein levels at the Sertoli-Sertoli cell interface at the BTB. PMID:18192323

Time-Lapse Monitoring of DNA Damage Colocalized With Particle Tracks in Single Living Cells

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

McFadden, Conor H.; Hallacy, Timothy M.; Department of Physics and Astronomy, Rice University, Houston, Texas

2016-09-01

Purpose: Understanding the DNA damage and repair induced by hadron therapy (HT) beams is crucial for developing novel strategies to maximize the use of HT beams to treat cancer patients. However, spatiotemporal studies of DNA damage and repair for beam energies relevant to HT have been challenging. We report a technique that enables spatiotemporal measurement of radiation-induced damage in live cells and colocalization of this damage with charged particle tracks over a broad range of clinically relevant beam energies. The technique uses novel fluorescence nuclear track detectors with fluorescence confocal laser scanning microscopy in the beam line to visualize particlemore » track traversals within the subcellular compartments of live cells within seconds after injury. Methods and Materials: We designed and built a portable fluorescence confocal laser scanning microscope for use in the beam path, coated fluorescence nuclear track detectors with fluorescent-tagged live cells (HT1080 expressing enhanced green fluorescent protein tagged to XRCC1, a single-strand break repair protein), placed the entire assembly into a proton therapy beam line, and irradiated the cells with a fluence of ∼1 × 10{sup 6} protons/cm{sup 2}. Results: We successfully obtained confocal images of proton tracks and foci of DNA single-strand breaks immediately after irradiation. Conclusions: This technique represents an innovative method for analyzing biological responses in any HT beam line at energies and dose rates relevant to therapy. It allows precise determination of the number of tracks traversing a subcellular compartment and monitoring the cellular damage therein, and has the potential to measure the linear energy transfer of each track from therapeutic beams.« less

33 CFR 110.82a - Little Traverse Bay, Lake Michigan, Harbor Springs, Mich.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Little Traverse Bay, Lake Michigan, Harbor Springs, Mich. 110.82a Section 110.82a Navigation and Navigable Waters COAST GUARD... Traverse Bay, Lake Michigan, Harbor Springs, Mich. (a) Area 1. Beginning at latitude 45°25′42.2″ N...

33 CFR 110.82a - Little Traverse Bay, Lake Michigan, Harbor Springs, Mich.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Little Traverse Bay, Lake Michigan, Harbor Springs, Mich. 110.82a Section 110.82a Navigation and Navigable Waters COAST GUARD... Traverse Bay, Lake Michigan, Harbor Springs, Mich. (a) Area 1. Beginning at latitude 45°25′42.2″ N...

33 CFR 110.82a - Little Traverse Bay, Lake Michigan, Harbor Springs, Mich.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Little Traverse Bay, Lake Michigan, Harbor Springs, Mich. 110.82a Section 110.82a Navigation and Navigable Waters COAST GUARD... Traverse Bay, Lake Michigan, Harbor Springs, Mich. (a) Area 1. Beginning at latitude 45°25′42.2″ N...

33 CFR 110.82a - Little Traverse Bay, Lake Michigan, Harbor Springs, Mich.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Little Traverse Bay, Lake Michigan, Harbor Springs, Mich. 110.82a Section 110.82a Navigation and Navigable Waters COAST GUARD... Traverse Bay, Lake Michigan, Harbor Springs, Mich. (a) Area 1. Beginning at latitude 45°25′42.2″ N...

33 CFR 110.82a - Little Traverse Bay, Lake Michigan, Harbor Springs, Mich.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Little Traverse Bay, Lake Michigan, Harbor Springs, Mich. 110.82a Section 110.82a Navigation and Navigable Waters COAST GUARD... Traverse Bay, Lake Michigan, Harbor Springs, Mich. (a) Area 1. Beginning at latitude 45°25′42.2″ N...

Terrain Traversing Device Having a Wheel with Microhooks

NASA Technical Reports Server (NTRS)

Wiltsie, Nicholas (Inventor); Carpenter, Kalind C. (Inventor); Parness, Aaron (Inventor)

2015-01-01

A terrain traversing device is described. The device includes an annular rotor element with a plurality of co-planar microspine hooks arranged on the periphery of the annular rotor element. Each microspine hook has an independently flexible suspension configuration that permits the microspine hook to initially engage an irregularity in a terrain surface at a preset initial engagement angle and subsequently engage the irregularity with a continuously varying engagement angle when the annular rotor element is rotated for urging the terrain traversing device to traverse a terrain surface. Improvements related to the design, fabrication and use of the microspine hooks in the device are also described.

Practopoiesis: or how life fosters a mind.

PubMed

Nikolić, Danko

2015-05-21

The mind is a biological phenomenon. Thus, biological principles of organization should also be the principles underlying mental operations. Practopoiesis states that the key for achieving intelligence through adaptation is an arrangement in which mechanisms laying at a lower level of organization, by their operations and interaction with the environment, enable creation of mechanisms laying at a higher level of organization. When such an organizational advance of a system occurs, it is called a traverse. A case of traverse is when plasticity mechanisms (at a lower level of organization), by their operations, create a neural network anatomy (at a higher level of organization). Another case is the actual production of behavior by that network, whereby the mechanisms of neuronal activity operate to create motor actions. Practopoietic theory explains why the adaptability of a system increases with each increase in the number of traverses. With a larger number of traverses, a system can be relatively small and yet, produce a higher degree of adaptive/intelligent behavior than a system with a lower number of traverses. The present analyses indicate that the two well-known traverses - neural plasticity and neural activity - are not sufficient to explain human mental capabilities. At least one additional traverse is needed, which is named anapoiesis for its contribution in reconstructing knowledge e.g., from long-term memory into working memory. The conclusions bear implications for brain theory, the mind-body explanatory gap, and developments of artificial intelligence technologies. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

The traverse planning process for D-RATS 2010

NASA Astrophysics Data System (ADS)

Hörz, Friedrich; Lofgren, Gary E.; Gruener, John E.; Eppler, Dean B.; Skinner, James A.; Fortezzo, Corey M.; Graf, Jodi S.; Bluethmann, William J.; Seibert, Marc A.; Bell, Ernest R.

2013-10-01

This report describes the traverse planning process for the Desert Research and Technology Studies (D-RATS) 2010 field simulation of a conceptual 14-day planetary mission. This activity took place between August 23 and September 17, 2010 in the San Francisco Volcanic Field, Arizona. It focused on the utilization of two pressurized rovers and a ground-based communication system, as well as on the development of mission operation concepts for long duration, dual-rover missions. The early planning process began some 12 months prior to the actual field tests and defined the first order engineering-, flight operations, and science objectives. The detailed implementation and refinement of these objectives took place over the ensuing 10 months, resulting in a large number of technical and operational constraints that affected the actual traverse route or the cumulative Extravehicular Activity (EVA) time available for detailed field observations. The science planning proceeded from the generation of photogeologic maps of the test area, to the establishment of prioritized science objectives and associated candidate sites for detailed field exploration. The combination of operational constraints and science objectives resulted in the final design of traverse routes and time lines for each of the 24 traverses needed to support 12 field days by two rovers. Examples of daily traverses will be given that will hopefully illustrate that the design of long duration, long distance planetary traverses is a highly interdisciplinary and time-consuming collaboration between diverse engineers, flight operations personnel, human factors interests, and planetary scientists.

Differential Radiosensitivity Phenotypes of DNA-PKcs Mutations Affecting NHEJ and HRR Systems following Irradiation with Gamma-Rays or Very Low Fluences of Alpha Particles

PubMed Central

Little, John B.; Kato, Takamitsu A.; Shih, Hung-Ying; Xie, Xian-Jin; Wilson Jr., Paul F.; Brogan, John R.; Kurimasa, Akihiro; Chen, David J.; Bedford, Joel S.; Chen, Benjamin P. C.

2014-01-01

We have examined cell-cycle dependence of chromosomal aberration induction and cell killing after high or low dose-rate γ irradiation in cells bearing DNA-PKcs mutations in the S2056 cluster, the T2609 cluster, or the kinase domain. We also compared sister chromatid exchanges (SCE) production by very low fluences of α-particles in DNA-PKcs mutant cells, and in homologous recombination repair (HRR) mutant cells including Rad51C, Rad51D, and Fancg/xrcc9. Generally, chromosomal aberrations and cell killing by γ-rays were similarly affected by mutations in DNA-PKcs, and these mutant cells were more sensitive in G1 than in S/G2 phase. In G1-irradiated DNA-PKcs mutant cells, both chromosome- and chromatid-type breaks and exchanges were in excess than wild-type cells. For cells irradiated in late S/G2 phase, mutant cells showed very high yields of chromatid breaks compared to wild-type cells. Few exchanges were seen in DNA-PKcs-null, Ku80-null, or DNA-PKcs kinase dead mutants, but exchanges in excess were detected in the S2506 or T2609 cluster mutants. SCE induction by very low doses of α-particles is resulted from bystander effects in cells not traversed by α-particles. SCE seen in wild-type cells was completely abolished in Rad51C- or Rad51D-deficient cells, but near normal in Fancg/xrcc9 cells. In marked contrast, very high levels of SCEs were observed in DNA-PKcs-null, DNA-PKcs kinase-dead and Ku80-null mutants. SCE induction was also abolished in T2609 cluster mutant cells, but was only slightly reduced in the S2056 cluster mutant cells. Since both non-homologous end-joining (NHEJ) and HRR systems utilize initial DNA lesions as a substrate, these results suggest the possibility of a competitive interference phenomenon operating between NHEJ and at least the Rad51C/D components of HRR; the level of interaction between damaged DNA and a particular DNA-PK component may determine the level of interaction of such DNA with a relevant HRR component. PMID:24714417

Glial cell biology in the Great Lakes region.

PubMed

Feinstein, Douglas L; Skoff, Robert P

2016-03-31

We report on the tenth bi-annual Great Lakes Glial meeting, held in Traverse City, Michigan, USA, September 27-29 2015. The GLG meeting is a small conference that focuses on current research in glial cell biology. The array of functions that glial cells (astrocytes, microglia, oligodendrocytes, Schwann cells) play in health and disease is constantly increasing. Despite this diversity, GLG meetings bring together scientists with common interests, leading to a better understanding of these cells. This year's meeting included two keynote speakers who presented talks on the regulation of CNS myelination and the consequences of stress on Schwann cell biology. Twenty-two other talks were presented along with two poster sessions. Sessions covered recent findings in the areas of microglial and astrocyte activation; age-dependent changes to glial cells, Schwann cell development and pathology, and the role of stem cells in glioma and neural regeneration.

Adjudin disrupts spermatogenesis by targeting drug transporters

PubMed Central

Qian, Xiaojing; Cheng, Yan-ho; Jenardhanan, Pranitha; Mruk, Dolores D.; Mathur, Premendu P.; Xia, Weiliang; Silvestrini, Bruno; Cheng, C. Yan

2013-01-01

For non-hormonal male contraceptives that exert their effects in the testis locally instead of via the hypothalamic-pituitary-testicular axis, such as adjudin that disrupts germ cell adhesion, a major hurdle in their development is to improve their bioavailability so that they can be efficiently delivered to the seminiferous epithelium by transporting across the blood-testis barrier (BTB). If this can be done, it would widen the gap between their efficacy and general toxicity. However, Sertoli cells that constitute the BTB, peritubular myoid cells in the tunica propria, germ cells at different stages of their development, as well as endothelial cells that constitute the microvessels in the interstitium are all equipped with multiple drug transporters, most notably efflux drug transporters, such as P-glycoprotein, multidrug resistance-related protein 1 (MRP1) and breast cancer resistance protein (BCRP) that can actively prevent drugs (e.g., adjudin) from entering the seminiferous epithelium to exert their effects. Recent studies have shown that BCRP is highly expressed by endothelial cells of the microvessels in the interstitium in the testis and also peritubular myoid cells in tunica propria even though it is absent from Sertoli cells at the site of the BTB. Furthermore, BCRP is also expressed spatiotemporally by Sertoli cells and step 19 spermatids in the rat testis and stage-specifically, limiting to stage VII‒VIII of the epithelial cycle, and restricted to the apical ectoplasmic specialization [apical ES, a testis-specific F-actin-rich adherens junction (AJ)]. Interestingly, adjudin was recently shown to be capable of downregulating BCRP expression at the apical ES. In this Opinion article, we critically discuss the latest findings on BCRP; in particular, we provide some findings utilizing molecular modeling to define the interacting domains of BCRP with adjudin. Based on this information, it is hoped that the next generation of adjudin analogs to be synthesized can improve their efficacy in downregulating BCRP and perhaps other drug efflux transporters in the testis to improve their efficacy to traverse the BTB by modifying their interacting domains. PMID:23885306

Development of Intelligent Unmanned Systems

DTIC Science & Technology

2011-05-01

statistical analysis on the terrain map. The data points are stored in the corresponding cells of the Traversability Grid as a linked list of 3-D Cartesian...allowed for multiple configurations of specified data to be as flexible as possible. For example, when an object is being created the knowledge store ...library was also used for querying and storing spatial data . It provided many geometric abstractions necessary such as overlap and intersects

Large Tunable Delays in Fiber and On-Chip Via Conversion/Dispersion

DTIC Science & Technology

2013-05-01

Venkataraman , Pablo Londero, and Alexander L. Gaeta School of Applied and Engineering Physics, Cornell University, Ithaca, New York 14853, USA (Received...BHAGWAT, VENKATARAMAN , LONDERO, AND GAETA PHYSICAL REVIEW A 81, 053825 (2010) broadening occurs when fast-moving particles rapidly traverse the light...experiments conducted in bulk vapor cells 053825-3 SLEPKOV, BHAGWAT, VENKATARAMAN , LONDERO, AND GAETA PHYSICAL REVIEW A 81, 053825 (2010) require the two

Modeling Parkinson's disease falls associated with brainstem cholinergic systems decline.

PubMed

Kucinski, Aaron; Sarter, Martin

2015-04-01

In addition to the primary disease-defining symptoms, approximately half of patients with Parkinson's disease (PD) suffer from postural instability, impairments in gait control and a propensity for falls. Consistent with evidence from patients, we previously demonstrated that combined striatal dopamine (DA) and basal forebrain (BF) cholinergic cell loss causes falls in rats traversing dynamic surfaces. Because evidence suggests that degeneration of brainstem cholinergic neurons arising from the pedunculopontine nucleus (PPN) also contributes to impaired gait and falls, here we assessed the effects of selective cholinergic PPN lesions in combination with striatal DA loss or BF cholinergic cells loss as well as losses in all 3 regions. Results indicate that all combination losses that included the BF cholinergic system slowed traversal and increased slips and falls. However, the performance of rats with losses in all 3 regions (PPN, BF, and DA) was not more severely impaired than following combined BF cholinergic and striatal DA lesions. These results confirm the hypothesis that BF cholinergic-striatal disruption of attentional-motor interactions is a primary source of falls. Additional losses of PPN cholinergic neurons may worsen posture and gait control in situations not captured by the current testing conditions. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

EAST93: Geophysical traverse from the Transantarctic Mountains to the Wilkes Basin, East Antarctica

USGS Publications Warehouse

ten Brink, Uri S.; Bannister, Stephen

1995-01-01

The East Antarctic Seismic Traverse (EAST93) was a geophysical traverse designed to image the bedrock under the East Antarctic ice cap. The traverse started 10 km west of the Taylor Dome drill site and 25 km west of the exposed bedrock of the Transantarctic Mountains at Lashly Mt. and ended 323 km west of the drill site over the Wilkes subglacial basin (Fig. 1). The traverse was located subparallel to latitude 78° S starting 30-50 km north of the Victoria Land Traverse (1958-1959). It was carried out jointly by the U.S. Geological Survey and Stanford University, U.S.A., together with the Institute of Geological and Nuclear Sciences, and Victoria University, New Zealand, during December 1993 and January 1994. The geophysical traverse included 236 km of multichannel seismic reflection data at 150 m shot intervals, 312.5 km of gravity data collected at intervals of 2.1 km, 312.5 km of magnetic data (total field intensity) collected at average intervals of 0.5 km, and 205 km of ground penetrating radar at intervals of 77 m. Relative locations and elevations of the entire traverse were measured at intervals of 150 m by traditional surveying methods, and tied to three absolute locations measured by the Global Positioning System (GPS). EAST93 is the first large-scale geophysical traverse on the polar plateau to our knowledge since the early 1960s. As such, the experiment presented several logistical challenges: (1) how to collect regional seismic profiles during the short Antarctic summer; (2) how to keep the scientific instruments running with minimal protection in harsh conditions; and (3) how to combine daily moves of camp with full days of work. The scientific and logistical aspects of the project proceeded, in general, according to plan despite the harsh conditions and our lack of previous experience on the polar plateau. Two unanticipated problems affected the progress of the work: the strong wind which slowed seismic acquisition, and the break-down of one of the large traverse vehicles. The major operational lessons of this project are. (1) Primacord laid close to the surface is not an adequate seismic source for imaging under the thick East Antarctic ice sheet, despite positive prior tests on the Ross Ice Shelf. (2) It is necessary to reduce the 6-7 hours spent daily on camp move and other chores by integrating the living quarters into the working teams, and by improving vehicle warming methods and generator housing. The following report details the operational and logistical aspects of the work, the weather and ground conditions, the technical aspects of acquisition of geophysical data, and lessons and recommendations for future geophysical traverses.

CD68 acts as a major gateway for malaria sporozoite liver infection

PubMed Central

Cha, Sung-Jae; Park, Kiwon; Srinivasan, Prakash; Schindler, Christian W.; van Rooijen, Nico; Stins, Monique

2015-01-01

After being delivered by the bite from an infected mosquito, Plasmodium sporozoites enter the blood circulation and infect the liver. Previous evidence suggests that Kupffer cells, a macrophage-like component of the liver blood vessel lining, are traversed by sporozoites to initiate liver invasion. However, the molecular determinants of sporozoite–Kupffer cell interactions are unknown. Understanding the molecular basis for this specific recognition may lead to novel therapeutic strategies to control malaria. Using a phage display library screen, we identified a peptide, P39, that strongly binds to the Kupffer cell surface and, importantly, inhibits sporozoite Kupffer cell entry. Furthermore, we determined that P39 binds to CD68, a putative receptor for sporozoite invasion of Kupffer cells that acts as a gateway for malaria infection of the liver. PMID:26216124

Software Tool for Computing Maximum Von Mises Stress

NASA Technical Reports Server (NTRS)

Chen, Long Y.; Knutson, Kurt; Martin, Eric

2007-01-01

The maximum Van Mises stress and stress direction are of interest far analyzing launch accelerations such as with the Mass Acceleration Curves developed by JPL. Maximum launch stresses can be combined with appropriate load cases at consistent locations with resulting stress tensors. Maximum Van Mises stress is also of interest for understanding maximum operational loading such as traverse events. - For example, planetary traversing simulations may prescribe bounding acceleration values during traverse for a rover such as Mars Science Lab (MSL) in (X,Y,Z) of the rover. - Such accelerations can be really in any directions for many parts such as a mast or head mounted components which can be in numerous configurations and orientations when traversing a planet surface.

Defined lipid analogues induce transient channels to facilitate drug-membrane traversal and circumvent cancer therapy resistance

PubMed Central

van Hell, Albert J.; Melo, Manuel N.; van Blitterswijk, Wim J.; Gueth, Dayana M.; Braumuller, Tanya M.; Pedrosa, Lilia R. C.; Song, Ji-Ying; Marrink, Siewert J.; Koning, Gerben A.; Jonkers, Jos; Verheij, Marcel

2013-01-01

Design and efficacy of bioactive drugs is restricted by their (in)ability to traverse cellular membranes. Therapy resistance, a major cause of ineffective cancer treatment, is frequently due to suboptimal intracellular accumulation of the drug. We report a molecular mechanism that promotes trans-membrane movement of a stereotypical, widely used anti-cancer agent to counteract resistance. Well-defined lipid analogues adapt to the amphiphilic drug doxorubicin, when co-inserted into the cell membrane, and assemble a transient channel that rapidly facilitates the translocation of the drug onto the intracellular membrane leaflet. Molecular dynamic simulations unveiled the structure and dynamics of membrane channel assembly. We demonstrate that this principle successfully addresses multi-drug resistance of genetically engineered mouse breast cancer models. Our results illuminate the role of the plasma membrane in restricting the efficacy of established therapies and drug resistance - and provide a mechanism to overcome ineffectiveness of existing and candidate drugs. PMID:23739489

Traverse Planning with Temporal-Spatial Constraints

NASA Technical Reports Server (NTRS)

Bresina, John L.; Morris, Paul H.; Deans, Mathew C.; Cohen, Tamar E.; Lees, David S.

2017-01-01

We present an approach to planning rover traverses in a domain that includes temporal-spatial constraints. We are using the NASA Resource Prospector mission as a reference mission in our research. The objective of this mission is to explore permanently shadowed regions at a Lunar pole. Most of the time the rover is required to avoid being in shadow. This requirement depends on where the rover is located and when it is at that location. Such a temporal-spatial constraint makes traverse planning more challenging for both humans and machines. We present a mixed-initiative traverse planner which addresses this challenge. This traverse planner is part of the Exploration Ground Data Systems (xGDS), which we have enhanced with new visualization features, new analysis tools, and new automation for path planning, in order to be applicable to the Re-source Prospector mission. The key concept that is the basis of the analysis tools and that supports the automated path planning is reachability in this dynamic environment due to the temporal-spatial constraints.

Characterization and functional analysis of a slow-cycling subpopulation in colorectal cancer enriched by cell cycle inducer combined chemotherapy.

PubMed

Wu, Feng-Hua; Mu, Lei; Li, Xiao-Lan; Hu, Yi-Bing; Liu, Hui; Han, Lin-Tao; Gong, Jian-Ping

2017-10-03

The concept of cancer stem cells has been proposed in various malignancies including colorectal cancer. Recent studies show direct evidence for quiescence slow-cycling cells playing a role in cancer stem cells. There exists an urgent need to isolate and better characterize these slow-cycling cells. In this study, we developed a new model to enrich slow-cycling tumor cells using cell-cycle inducer combined with cell cycle-dependent chemotherapy in vitro and in vivo . Our results show that Short-term exposure of colorectal cancer cells to chemotherapy combined with cell-cycle inducer enriches for a cell-cycle quiescent tumor cell population. Specifically, these slow-cycling tumor cells exhibit increased chemotherapy resistance in vitro and tumorigenicity in vivo . Notably, these cells are stem-cell like and participate in metastatic dormancy. Further exploration indicates that slow-cycling colorectal cancer cells in our model are less sensitive to cytokine-induced-killer cell mediated cytotoxic killing in vivo and in vitro . Collectively, our cell cycle inducer combined chemotherapy exposure model enriches for a slow-cycling, dormant, chemo-resistant tumor cell sub-population that are resistant to cytokine induced killer cell based immunotherapy. Studying unique signaling pathways in dormant tumor cells enriched by cell cycle inducer combined chemotherapy treatment is expected to identify novel therapeutic targets for preventing tumor recurrence.

Characterization and functional analysis of a slow-cycling subpopulation in colorectal cancer enriched by cell cycle inducer combined chemotherapy

PubMed Central

Wu, Feng-Hua; Mu, Lei; Li, Xiao-Lan; Hu, Yi-Bing; Liu, Hui; Han, Lin-Tao; Gong, Jian-Ping

2017-01-01

The concept of cancer stem cells has been proposed in various malignancies including colorectal cancer. Recent studies show direct evidence for quiescence slow-cycling cells playing a role in cancer stem cells. There exists an urgent need to isolate and better characterize these slow-cycling cells. In this study, we developed a new model to enrich slow-cycling tumor cells using cell-cycle inducer combined with cell cycle-dependent chemotherapy in vitro and in vivo. Our results show that Short-term exposure of colorectal cancer cells to chemotherapy combined with cell-cycle inducer enriches for a cell-cycle quiescent tumor cell population. Specifically, these slow-cycling tumor cells exhibit increased chemotherapy resistance in vitro and tumorigenicity in vivo. Notably, these cells are stem-cell like and participate in metastatic dormancy. Further exploration indicates that slow-cycling colorectal cancer cells in our model are less sensitive to cytokine-induced-killer cell mediated cytotoxic killing in vivo and in vitro. Collectively, our cell cycle inducer combined chemotherapy exposure model enriches for a slow-cycling, dormant, chemo-resistant tumor cell sub-population that are resistant to cytokine induced killer cell based immunotherapy. Studying unique signaling pathways in dormant tumor cells enriched by cell cycle inducer combined chemotherapy treatment is expected to identify novel therapeutic targets for preventing tumor recurrence. PMID:29108242

Determination of Slope Safety Factor with Analytical Solution and Searching Critical Slip Surface with Genetic-Traversal Random Method

PubMed Central

2014-01-01

In the current practice, to determine the safety factor of a slope with two-dimensional circular potential failure surface, one of the searching methods for the critical slip surface is Genetic Algorithm (GA), while the method to calculate the slope safety factor is Fellenius' slices method. However GA needs to be validated with more numeric tests, while Fellenius' slices method is just an approximate method like finite element method. This paper proposed a new method to determine the minimum slope safety factor which is the determination of slope safety factor with analytical solution and searching critical slip surface with Genetic-Traversal Random Method. The analytical solution is more accurate than Fellenius' slices method. The Genetic-Traversal Random Method uses random pick to utilize mutation. A computer automatic search program is developed for the Genetic-Traversal Random Method. After comparison with other methods like slope/w software, results indicate that the Genetic-Traversal Random Search Method can give very low safety factor which is about half of the other methods. However the obtained minimum safety factor with Genetic-Traversal Random Search Method is very close to the lower bound solutions of slope safety factor given by the Ansys software. PMID:24782679

Autonomous Rover Traverse and Precise Arm Placement on Remotely Designated Targets

NASA Technical Reports Server (NTRS)

Felder, Michael; Nesnas, Issa A.; Pivtoraiko, Mihail; Kelly, Alonzo; Volpe, Richard

2011-01-01

Exploring planetary surfaces typically involves traversing challenging and unknown terrain and acquiring in-situ measurements at designated locations using arm-mounted instruments. We present field results for a new implementation of an autonomous capability that enables a rover to traverse and precisely place an arm-mounted instrument on remote targets. Using point-and-click mouse commands, a scientist designates targets in the initial imagery acquired from the rover's mast cameras. The rover then autonomously traverse the rocky terrain for a distance of 10 - 15 m, tracks the target(s) of interest during the traverse, positions itself for approaching the target, and then precisely places an arm-mounted instrument within 2-3 cm from the originally designated target. The rover proceeds to acquire science measurements with the instrument. This work advances what has been previously developed and integrated on the Mars Exploration Rovers by using algorithms that are capable of traversing more rock-dense terrains, enabling tight thread-the-needle maneuvers. We integrated these algorithms on the newly refurbished Athena Mars research rover and fielded them in the JPL Mars Yard. We conducted 43 runs with targets at distances ranging from 5 m to 15 m and achieved a success rate of 93% for placement of the instrument within 2-3 cm.

Restraining reactive oxygen species in Listeria monocytogenes promotes the apoptosis of glial cells.

PubMed

Li, Sen; Li, Yixuan; Chen, Guowei; Zhang, Jingchen; Xu, Fei; Wu, Man

2017-07-01

Listeria monocytogenes is a facultative anaerobic foodborne pathogen that can traverse the blood-brain barrier and cause brain infection. L. monocytogenes infection induces host cell apoptosis in several cell types. In this study, we investigated the apoptosis of human glioma cell line U251 invaded by L. monocytogenes and evaluated the function of bacterial reactive oxygen species (ROS) during infection. Bacterial ROS level was reduced by carrying out treatment with N-acetyl cysteine (NAC) and diphenyleneiodonium chloride (DPI). After infection, the apoptosis of U251 cells was examined by flow cytometry assay and propidium iodide staining. DPI and NAC efficiently decreased ROS level in L. monocytogenes without affecting bacterial growth. Moreover, the apoptosis of glial cells was enhanced upon invasion of DPI- and NAC-pretreated L. monocytogenes. Results indicate that the apoptosis of glial cells can be induced by L. monocytogenes, and that the inhibition of bacterial ROS increases the apoptosis of host cells.

Truly incomplete and complex exchanges in prematurely condensed chromosomes of human fibroblasts exposed in vitro to energetic heavy ions

NASA Technical Reports Server (NTRS)

Wu, Honglu; Durante, Marco; Furusawa, Yoshiya; George, Kerry; Kawata, Tetsuya; Cucinotta, Francis A.

2003-01-01

Confluent human fibroblast cells (AG1522) were irradiated with gamma rays, 490 MeV/nucleon silicon ions, or iron ions at either 200 or 500 MeV/nucleon. The cells were allowed to repair at 37 degrees C for 24 h after exposure, and a chemically induced premature chromosome condensation (PCC) technique was used to condense chromosomes in the G2 phase of the cell cycle. Incomplete and complex exchanges were analyzed in the irradiated samples. To verify that chromosomal breaks were truly unrejoined, chromosome aberrations were analyzed using a combination of whole-chromosome specific probes and probes specific for the telomere region of the chromosome. Results showed that the frequency of unrejoined chromosome breaks was higher after irradiation with the heavy ions of high LET, and consequently the ratio of incomplete to complete exchanges increased steadily with LET up to 440 keV/microm, the highest LET included in the present study. For samples exposed to 200 MeV/nucleon iron ions, chromosome aberrations were analyzed using the multicolor FISH (mFISH) technique, which allows identification of both complex and truly incomplete exchanges. Results of the mFISH study showed that 0.7 and 3 Gy iron ions produced similar ratios of complex to simple exchanges and incomplete to complete exchanges; these ratios were higher than those obtained after exposure to 6 Gy gamma rays. After 0.7 Gy of iron ions, most complex aberrations were found to involve three or four chromosomes, which is a likely indication of the maximum number of chromosome domains traversed by a single iron-ion track.

Arctic Circle Traverse 2010 (ACT-10): South East Greenland snow accumulation variability from firn coring and ice sounding radar

NASA Astrophysics Data System (ADS)

Forster, R. R.; Miege, C.; Box, J. E.; McConnell, J.; Spikes, V. B.; Burgess, E. W.

2010-12-01

The Greenland Ice Sheet plays an important role in Earth’s climate system evolution. The snow accumulation rate is the largest single mass budget term. With only 14% of the ice sheet area, Southeast Greenland contains the highest accumulation rates, accounting for one third of the total snow accumulation and annual variability. The high accumulation rates have made the region less desirable for long climate record ice cores and therefore, contain relatively very few in situ measurements to constrain the ice sheet mass budget. We present annual snow accumulation rates from the Arctic Circle Traverse 2010 (ACT-10). During April and May 2010 we acquired three 50 m firn cores connected by surface-based 400 MHz ground penetrating radar (GPR) in Southeast Greenland. The traverse repeated and extended the original Arctic Circle Traverse in 2004 (Spikes et al., 2004). Dating is achieved using geochemical analysis of the cores to identify isochronal layers detected by the GPR yielding annual accumulation estimates along the traverse between the core sites. The 300 km ACT-10 GPR snowmobile traverse extended the ACT-04 path 80 km to the lowest elevation core site at 1776 m. Meanwhile, airborne radars, operating as part of NASA’s Operation IceBridge also acquired data over the full length of the ACT-10 path, simultaneously with a portion of the traverse and within days for the remaining segments. The IceBridge and ACT-10 data are to be combined in a calibration effort such that snow accumulation rates may be mapped elsewhere in Greenland and even in Antarctica.

Long range geoid control through the European GPS traverse: Final results

NASA Technical Reports Server (NTRS)

Torge, W.; Basic, T.; Denker, H.; Doliff, J.; Wenzel, H.-G.

1989-01-01

The European north-south Global Positioning System (GPS)-traverse proposed by IAG SSG 3.88, should control and improve the European geoid. This traverse follows first order leveling lines, included in the United European Leveling Network. From May to August 1986 and in July 1987, the central and northern part of this traverse (approx. 3000 km) was observed using up to four TI 4100 receivers, covering Austria, Federal Republic of Germany, Denmark, Sweden and Norway. Both traverse parts contain 71 stations with distances of about 50 km. In addition, 8 stations have been occupied for overlapping connections, and traverse links were established for connecting the fundamental stations Wettzell (VLBI and SLR) and Onsala (VLBI). Final results show a GPS observation precision of a few cm for loops of some 100 km circumference. After transformation of the GPS results to geoid heights using the leveled heights, comparisons with different existing gravimetric geoid determinations including geopotential models were performed. In addition, new geopotential models complete to degree and order 360 tailored to gravity data in Europe, and gravimetric geoid solutions using 6 x 10' mean gravity anomalies were investigated. The comparison with GPS and leveling yields rms discrepancies of + or - 0.1...0.2 m over 1000 km traverse sections for the best solutions, but a strong slope is existing in Sweden and southern Norway in almost all solutions, which is probably caused by systematic errors in the available gravity data for Scandinavia. This is confirmed by a new geoid computation at the Danish Geodetic Institute where the slope has disappeared. If this new solution is taken for the northern traverse section and the best solution for the central part, the rms discrepancy reduces to approximately + or - 0.2 m over 3000 km. Thus, a + or - 10 (exp 7) relative height accuracy seems to be achievable over long distances with the GPS/leveling and the gravimetric geoid calculation techniques, applied in this experiment.

Laser characterization of electric field oscillations in the Hall thruster breathing mode

NASA Astrophysics Data System (ADS)

Young, Christopher; Lucca Fabris, Andrea; MacDonald-Tenenbaum, Natalia; Hargus, William, Jr.; Cappelli, Mark

2016-10-01

Hall thrusters are a mature technology for space propulsion applications that exhibit a wide array of dynamic behavior, including plasma waves, instabilities and turbulence. One common low frequency (10-50 kHz) discharge current oscillation is the breathing mode, a cycle of neutral propellant injection, strong ionization, and ion acceleration by a steep potential gradient. A time-resolved laser-induced fluorescence diagnostic non-intrusively captures this propagating ionization front in the channel of a commercial BHT-600 Hall thruster manufactured by Busek Co. Measurements of ion velocity and relative ion density (using the 5 d[ 4 ] 7 / 2 - 6 p[ 3 ] 5 / 2 Xe II transition at 834.95 nm, vacuum) reveal a dynamic electric field structure traversing the channel throughout the breathing mode cycle. This work is sponsored by the U.S. Air Force Office of Scientific Research, with Dr. M. Birkan as program manager. C.Y. acknowledges support from the DOE NSSA Stewardship Science Graduate Fellowship under contract DE-FC52-08NA28752.

Verification tests of the US Electricar Corporation Lectric Leopard

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

Dowgiallo, E.J. Jr.; Snellings, I.R.; Chapman, R.D.

1982-04-01

The Lectric Leopard, manufactured by US Electricar Corporation, was tested during the period 3 August 1981 to 25 September 1981. Part of the verification results are summarized below (complete tests results are contained in Section V): Acceleration: 0-50 km/h (31.1 mi/h) in 9.9 s. Range: SAE J227a cycle ''C'' on level (+-1-percent grade) terrain yielded 66.2 km (41.2 mi) and 120 cycles. Forward Speed Capability: Forward speed of 80 km/h (50 mi/h) was maintained for more than 5 min on the level (+-1-percent grade) portion of the MERADCOM Test Track. Gradeability at Speed: At 25 km/h (15.5 mi/h) the vehiclemore » can traverse a 15.5-percent grade based on calculations from acceleration tests. Gradeability Limit: Calculations based on drawbar-pull test indicate a 35.2-percent forward and a 36.4-percent gradeability for at least 20 s.« less

Development of balloon-borne reel-down and -up winch system

NASA Astrophysics Data System (ADS)

Matsuzaka, Y.; Yamagami, T.; Yamanaka, M. D.; Nishimura, J.

Balloon-borne winches, which can reel down and up scientific instruments repeatedly, have been developed since 1981 in order to observe stratospheric vertical microstuctures. The instrument is suspended by a kevler wire through a traverse-cum ropeguide, and its depth is accurately measured by counting numbers of spool rotations and ropeguide turns. Battery consumption is minimized by utilizing an efficient deccelerator and a hysteresis brake. In 1983 we have successfully performed to reel up and down a 12 kg payload through 1 km for three cycles at 24 km altitude. We are improving the capability of the winch, and have succeeded (May 1984) to reel down a 22 kg payload up to 3 km from a balloon.

Light pollution is greatest within migration passage areas for nocturnally-migrating birds around the world.

PubMed

Cabrera-Cruz, Sergio A; Smolinsky, Jaclyn A; Buler, Jeffrey J

2018-02-19

Excessive or misdirected artificial light at night (ALAN) produces light pollution that influences several aspects of the biology and ecology of birds, including disruption of circadian rhythms and disorientation during flight. Many migrating birds traverse large expanses of land twice every year at night when ALAN illuminates the sky. Considering the extensive and increasing encroachment of light pollution around the world, we evaluated the association of the annual mean ALAN intensity over land within the geographic ranges of 298 nocturnally migrating bird species with five factors: phase of annual cycle, mean distance between breeding and non-breeding ranges, range size, global hemisphere of range, and IUCN category of conservation concern. Light pollution within geographic ranges was relatively greater during the migration season, for shorter-distance migrants, for species with smaller ranges, and for species in the western hemisphere. Our results suggest that migratory birds may be subject to the effects of light pollution particularly during migration, the most critical stage in their annual cycle. We hope these results will spur further research on how light pollution affects not only migrating birds, but also other highly mobile animals throughout their annual cycle.

Traversing psychological distance.

PubMed

Liberman, Nira; Trope, Yaacov

2014-07-01

Traversing psychological distance involves going beyond direct experience, and includes planning, perspective taking, and contemplating counterfactuals. Consistent with this view, temporal, spatial, and social distances as well as hypotheticality are associated, affect each other, and are inferred from one another. Moreover, traversing all distances involves the use of abstraction, which we define as forming a belief about the substitutability for a specific purpose of subjectively distinct objects. Indeed, across many instances of both abstraction and psychological distancing, more abstract constructs are used for more distal objects. Here, we describe the implications of this relation for prediction, choice, communication, negotiation, and self-control. We ask whether traversing distance is a general mental ability and whether distance should replace expectancy in expected-utility theories. Copyright © 2014 Elsevier Ltd. All rights reserved.

Membrane potential dynamics of grid cells

PubMed Central

Domnisoru, Cristina; Kinkhabwala, Amina A.; Tank, David W.

2014-01-01

During navigation, grid cells increase their spike rates in firing fields arranged on a strikingly regular triangular lattice, while their spike timing is often modulated by theta oscillations. Oscillatory interference models of grid cells predict theta amplitude modulations of membrane potential during firing field traversals, while competing attractor network models predict slow depolarizing ramps. Here, using in-vivo whole-cell recordings, we tested these models by directly measuring grid cell intracellular potentials in mice running along linear tracks in virtual reality. Grid cells had large and reproducible ramps of membrane potential depolarization that were the characteristic signature tightly correlated with firing fields. Grid cells also exhibited intracellular theta oscillations that influenced their spike timing. However, the properties of theta amplitude modulations were not consistent with the view that they determine firing field locations. Our results support cellular and network mechanisms in which grid fields are produced by slow ramps, as in attractor models, while theta oscillations control spike timing. PMID:23395984

Polarization squeezing of light by single passage through an atomic vapor

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

Barreiro, S.; Valente, P.; Failache, H.

We have studied relative-intensity fluctuations for a variable set of orthogonal elliptic polarization components of a linearly polarized laser beam traversing a resonant {sup 87}Rb vapor cell. Significant polarization squeezing at the threshold level (-3dB) required for the implementation of several continuous-variable quantum protocols was observed. The extreme simplicity of the setup, which is based on standard polarization components, makes it particularly convenient for quantum information applications.

Bragg Curve, Biological Bragg Curve and Biological Issues in Space Radiation Protection with Shielding

NASA Technical Reports Server (NTRS)

Honglu, Wu; Cucinotta, F.A.; Durante, M.; Lin, Z.; Rusek, A.

2006-01-01

The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the major protection to astronauts from harmful exposure. Unlike low-LET gamma or X-rays, the presence of shielding does not always reduce the radiation risks for energetic charged particle exposure. Since the dose delivered by the charged particle increases sharply as the particle approaches the end of its range, a position known as the Bragg peak, the Bragg curve does not necessarily represent the biological damage along the particle traversal since biological effects are influenced by the track structure of both primary and secondary particles. Therefore, the biological Bragg curve is dependent on the energy and the type of the primary particle, and may vary for different biological endpoints. To achieve a Bragg curve distribution, we exposed cells to energetic heavy ions with the beam geometry parallel to a monolayer of fibroblasts. Qualitative analyses of gamma-H2AX fluorescence, a known marker of DSBs, indicated increased clustering of DNA damage before the Bragg peak, enhanced homogenous distribution at the peak, and provided visual evidence of high linear energy transfer (LET) particle traversal of cells beyond the Bragg peak. A quantitative biological response curve generated for micronuclei (MN) induction across the Bragg curve did not reveal an increased yield of MN at the location of the Bragg peak. However, the ratio of mono-to bi-nucleated cells, which indicates inhibition in cell progression, increased at the Bragg peak location. These results, along with other biological concerns, show that space radiation protection with shielding can be a complicated issue.

Circadian Clock Synchronization of the Cell Cycle in Zebrafish Occurs through a Gating Mechanism Rather Than a Period-phase Locking Process.

PubMed

Laranjeiro, Ricardo; Tamai, T Katherine; Letton, William; Hamilton, Noémie; Whitmore, David

2018-04-01

Studies from a number of model systems have shown that the circadian clock controls expression of key cell cycle checkpoints, thus providing permissive or inhibitory windows in which specific cell cycle events can occur. However, a major question remains: Is the clock actually regulating the cell cycle through such a gating mechanism or, alternatively, is there a coupling process that controls the speed of cell cycle progression? Using our light-responsive zebrafish cell lines, we address this issue directly by synchronizing the cell cycle in culture simply by changing the entraining light-dark (LD) cycle in the incubator without the need for pharmacological intervention. Our results show that the cell cycle rapidly reentrains to a shifted LD cycle within 36 h, with changes in p21 expression and subsequent S phase timing occurring within the first few hours of resetting. Reentrainment of mitosis appears to lag S phase resetting by 1 circadian cycle. The range of entrainment of the zebrafish clock to differing LD cycles is large, from 16 to 32 hour periods. We exploited this feature to explore cell cycle entrainment at both the population and single cell levels. At the population level, cell cycle length is shortened or lengthened under corresponding T-cycles, suggesting that a 1:1 coupling mechanism is capable of either speeding up or slowing down the cell cycle. However, analysis at the single cell level reveals that this, in fact, is not true and that a gating mechanism is the fundamental method of timed cell cycle regulation in zebrafish. Cell cycle length at the single cell level is virtually unaltered with varying T-cycles.

Circadian Clock Synchronization of the Cell Cycle in Zebrafish Occurs through a Gating Mechanism Rather Than a Period-phase Locking Process

PubMed Central

Tamai, T. Katherine; Letton, William; Hamilton, Noémie; Whitmore, David

2018-01-01

Studies from a number of model systems have shown that the circadian clock controls expression of key cell cycle checkpoints, thus providing permissive or inhibitory windows in which specific cell cycle events can occur. However, a major question remains: Is the clock actually regulating the cell cycle through such a gating mechanism or, alternatively, is there a coupling process that controls the speed of cell cycle progression? Using our light-responsive zebrafish cell lines, we address this issue directly by synchronizing the cell cycle in culture simply by changing the entraining light-dark (LD) cycle in the incubator without the need for pharmacological intervention. Our results show that the cell cycle rapidly reentrains to a shifted LD cycle within 36 h, with changes in p21 expression and subsequent S phase timing occurring within the first few hours of resetting. Reentrainment of mitosis appears to lag S phase resetting by 1 circadian cycle. The range of entrainment of the zebrafish clock to differing LD cycles is large, from 16 to 32 hour periods. We exploited this feature to explore cell cycle entrainment at both the population and single cell levels. At the population level, cell cycle length is shortened or lengthened under corresponding T-cycles, suggesting that a 1:1 coupling mechanism is capable of either speeding up or slowing down the cell cycle. However, analysis at the single cell level reveals that this, in fact, is not true and that a gating mechanism is the fundamental method of timed cell cycle regulation in zebrafish. Cell cycle length at the single cell level is virtually unaltered with varying T-cycles. PMID:29444612

The Potential Risks and Future Impact of a Large Leverett Glacier Crevasse along the South Pole Traverse (SPoT)

DTIC Science & Technology

2017-10-01

agricultural tractors used on SPoT (Case Corporation and Caterpillar). (Adapted from Lever and Thur 2014.) ................. 2 2 Map showing the 1600...traversed for the first time in 2005 as a proof-of-concept, using a combination of several commercial rubber-tracked agricultural tractors (Caterpillar...traverse route. Inset shows two rubber-tracked, agricultural tractors used on SPoT (Case Corporation and Caterpillar). (Adapted from Lever and Thur 2014

Automatic detection of sweep-meshable volumes

DOEpatents

Tautges,; Timothy J. , White; David, R [Pittsburgh, PA

2006-05-23

A method of and software for automatically determining whether a mesh can be generated by sweeping for a representation of a geometric solid comprising: classifying surface mesh schemes for surfaces of the representation locally using surface vertex types; grouping mappable and submappable surfaces of the representation into chains; computing volume edge types for the representation; recursively traversing surfaces of the representation and grouping the surfaces into source, target, and linking surface lists; and checking traversal direction when traversing onto linking surfaces.

Life cycle of Renylaima capensis, a brachylaimid trematode of shrews and slugs in South Africa: two-host and three-host transmission modalities suggested by epizootiology and DNA sequencing

PubMed Central

2012-01-01

Background The life cycle of the brachylaimid trematode species Renylaima capensis, infecting the urinary system of the shrew Myosorex varius (Mammalia: Soricidae: Crocidosoricinae) in the Hottentots Holland Nature Reserve, South Africa, has been elucidated by a study of its larval stages, epizootiological data in local snails and mammals during a 34-year period, and its verification with mtDNA sequencing. Methods Parasites obtained from dissected animals were mounted in microscope slides for the parasitological study and measured according to standardized methods. The mitochondrial DNA cox1 gene was sequenced by the dideoxy chain-termination method. Results The slugs Ariostralis nebulosa and Ariopelta capensis (Gastropoda: Arionidae) act as specific first and second intermediate hosts, respectively. Branched sporocysts massively develop in A. nebulosa. Intrasporocystic mature cercariae show differentiated gonads, male terminal duct, ventral genital pore, and usually no tail, opposite to Brachylaimidae in which mature cercariae show a germinal primordium and small tail. Unencysted metacercariae, usually brevicaudate, infect the kidney of A. capensis and differ from mature cercariae by only a slightly greater size. The final microhabitats are the kidneys and ureters of the shrews, kidney pelvis and calyces in light infections and also kidney medulla and cortex in heavy infections. Sporocysts, cercariae, metacercariae and adults proved to belong to R. capensis by analysis of a 437-bp-long cox1 fragment, which was identical except for three mutations in metacercariae, of which only one silent. Epizootiological studies showed usual sporocyst infection in A. nebulosa and very rare metacercarial infection in A. capensis, which does not agree with high prevalences and intensities in the shrews. Conclusions The presence of monotesticular adult forms and larval prevalences and intensities observed suggest that R. capensis may use two transmission strategies, a two-host life cycle by predation of A. nebulosa harbouring intrasporocystic cercariae may be the normal pattern, whereas a second mollusc host is just starting to be introduced. In shrews, a tissue-traversing, intraorganic migration followed by an interorganic migration to reach and penetrate the outer surface of either of both kidneys should occur. For first slug infection, the fluke takes advantage of the phenomenon that M. varius always urinate during defaecation. Consequently, in Brachylaimidae, the second intermediate mollusc host should evolutionarily be seen as a last addition to the cycle and their present adult stage microhabitat restricted to digestive tract and related organs as a loss of the tissue-traversing capacity of the metacercaria. PMID:22889081

Radiation-induced bystander effect and adaptive response in mammalian cells

NASA Technical Reports Server (NTRS)

Zhou, H.; Randers-Pehrson, G.; Waldren, C. A.; Hei, T. K.

2004-01-01

Two conflicting phenomena, bystander effect and adaptive response, are important in determining the biological responses at low doses of radiation and have the potential to impact the shape of the dose-response relationship. Using the Columbia University charged-particle microbeam and the highly sensitive AL cell mutagenic assay, we show here that non-irradiated cells acquire mutagenesis through direct contact with cells whose nuclei have been traversed with a single alpha particle each. Pretreatment of cells with a low dose of X-rays four hours before alpha particle irradiation significantly decreased this bystander mutagenic response. Results from the present study address some of the fundamental issues regarding both the actual target and radiation dose effect and can contribute to our current understanding in radiation risk assessment. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

CD68 acts as a major gateway for malaria sporozoite liver infection.

PubMed

Cha, Sung-Jae; Park, Kiwon; Srinivasan, Prakash; Schindler, Christian W; van Rooijen, Nico; Stins, Monique; Jacobs-Lorena, Marcelo

2015-08-24

After being delivered by the bite from an infected mosquito, Plasmodium sporozoites enter the blood circulation and infect the liver. Previous evidence suggests that Kupffer cells, a macrophage-like component of the liver blood vessel lining, are traversed by sporozoites to initiate liver invasion. However, the molecular determinants of sporozoite-Kupffer cell interactions are unknown. Understanding the molecular basis for this specific recognition may lead to novel therapeutic strategies to control malaria. Using a phage display library screen, we identified a peptide, P39, that strongly binds to the Kupffer cell surface and, importantly, inhibits sporozoite Kupffer cell entry. Furthermore, we determined that P39 binds to CD68, a putative receptor for sporozoite invasion of Kupffer cells that acts as a gateway for malaria infection of the liver. © 2015 Cha et al.

Cell cycle regulation in human embryonic stem cells: links to adaptation to cell culture.

PubMed

Barta, Tomas; Dolezalova, Dasa; Holubcova, Zuzana; Hampl, Ales

2013-03-01

Cell cycle represents not only a tightly orchestrated mechanism of cell replication and cell division but it also plays an important role in regulation of cell fate decision. Particularly in the context of pluripotent stem cells or multipotent progenitor cells, regulation of cell fate decision is of paramount importance. It has been shown that human embryonic stem cells (hESCs) show unique cell cycle characteristics, such as short doubling time due to abbreviated G1 phase; these properties change with the onset of differentiation. This review summarizes the current understanding of cell cycle regulation in hESCs. We discuss cell cycle properties as well as regulatory machinery governing cell cycle progression of undifferentiated hESCs. Additionally, we provide evidence that long-term culture of hESCs is accompanied by changes in cell cycle properties as well as configuration of several cell cycle regulatory molecules.

Validity of a device designed to measure braking power in bicycle disc brakes.

PubMed

Miller, Matthew C; Fink, Philip W; Macdermid, Paul William; Perry, Blake G; Stannard, Stephen R

2017-07-21

Real-world cycling performance depends not only on exercise capacities, but also on efficiently traversing the bicycle through the terrain. The aim of this study was to determine if it was possible to quantify the braking done by a cyclist in the field. One cyclist performed 408 braking trials (348 on a flat road; 60 on a flat dirt path) over 5 days on a bicycle fitted with brake torque and angular velocity sensors to measure brake power. Based on Newtonian physics, the sum of brake work, aerodynamic drag and rolling resistance was compared with the change in kinetic energy in each braking event. Strong linear relationships between the total energy removed from the bicycle-rider system through braking and the change in kinetic energy were observed on the tar-sealed road (r 2  = 0.989; p < 0.0001) and the dirt path (r 2  = 0.952; p < 0.0001). T-tests revealed no difference between the total energy removed and the change in kinetic energy on the road (p = 0.715) or dirt (p = 0.128). This study highlights that brake torque and angular velocity sensors are valid for calculating brake power on the disc brakes of a bicycle in field conditions. Such a device may be useful for investigating cyclists' ability to traverse through various terrains.

Antitumor effect of the selective COX-2 inhibitor celecoxib on endometrial adenocarcinoma in vitro and in vivo

PubMed Central

XIAO, YITAO; TENG, YINCHENG; ZHANG, RUI; LUO, LAIMIN

2012-01-01

The aim of this study was to investigate the antitumor effect of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib on endometrial adenocarcinoma in mice. Various amounts of celecoxib were added to HEC-1B cells in vitro for different durations. Cell cycle and apoptosis were analyzed using flow cytometry. HEC-1B cytostasis, invasiveness and COX-2 expression were examined by MTT, transwell cabin and western blot assays, respectively. An in vivo human endometrial adenocarcinoma model was established in BALB/c nude mice using HEC-1B cells. For two weeks, the celecoxib groups were treated with celecoxib 2 or 4 mg/day via oral administration and the control group was treated with saline. Tumor volume, growth curves and the inhibition rate (IR) were recorded. COX-2 expression levels and microvessel density (MVD) were investigated using an immunohistochemical technique. In the celecoxib groups, cell proliferation was significantly inhibited in a concentration- and time-dependent manner. The proportion of cells in the G0/G1 phase increased within 24 h after the addition of celecoxib whereas those in the S and G2/M phases decreased with an increasing apoptosis peak (sub-G1) and apoptosis rate. The microporous Matrigel-coated polycarbonate membrane of the Transwell cabin was traversable for the HEC-1B cells. The invasiveness was attenuated when the celecoxib concentration was increased. The tumor growth was also greatly inhibited when the celecoxib concentration was increased. The tumor IRs were 32.4 and 48.6% following treatment with 2 and 4 mg/day celecoxib, respectively. COX-2 was mainly expressed in the cytoplasm of the tumor cells. In the celecoxib groups, the COX-2 expression levels were concentration-dependent. The COX-2 expression level and MVD decreased when the celecoxib concentration was increased. The results of dependability analysis revealed that the COX-2 expression level was positively correlated with MVD (r=0.921; P<0.01). The antitumor effect of celecoxib on endometrial adenocarcinoma in nude mice may be related to the inhibition of COX-2 expression and microangiogenesis. PMID:23226798

Magnetic resonance imaging (MRI) of PEM dehydration and gas manifold flooding during continuous fuel cell operation

NASA Astrophysics Data System (ADS)

Minard, Kevin R.; Viswanathan, Vilayanur V.; Majors, Paul D.; Wang, Li-Qiong; Rieke, Peter C.

Magnetic resonance imaging (MRI) was employed for visualizing water inside a proton exchange membrane (PEM) fuel cell during 11.4 h of continuous operation with a constant load. Two-dimensional images acquired every 128 s revealed the formation of a dehydration front that propagated slowly over the surface of the fuel cell membrane-starting from gas inlets and progressing toward gas outlets. After traversing the entire PEM surface, channels in the gas manifold began to flood on the cathode side. To establish a qualitative understanding of these observations, acquired images were correlated to the current output and the operating characteristics of the fuel cell. Results demonstrate the power of MRI for visualizing changing water distributions during PEM fuel cell operation, and highlight its potential utility for studying the causes of cell failure and/or strategies of water management.

A map of protein dynamics during cell-cycle progression and cell-cycle exit

PubMed Central

Gookin, Sara; Min, Mingwei; Phadke, Harsha; Chung, Mingyu; Moser, Justin; Miller, Iain; Carter, Dylan

2017-01-01

The cell-cycle field has identified the core regulators that drive the cell cycle, but we do not have a clear map of the dynamics of these regulators during cell-cycle progression versus cell-cycle exit. Here we use single-cell time-lapse microscopy of Cyclin-Dependent Kinase 2 (CDK2) activity followed by endpoint immunofluorescence and computational cell synchronization to determine the temporal dynamics of key cell-cycle proteins in asynchronously cycling human cells. We identify several unexpected patterns for core cell-cycle proteins in actively proliferating (CDK2-increasing) versus spontaneously quiescent (CDK2-low) cells, including Cyclin D1, the levels of which we find to be higher in spontaneously quiescent versus proliferating cells. We also identify proteins with concentrations that steadily increase or decrease the longer cells are in quiescence, suggesting the existence of a continuum of quiescence depths. Our single-cell measurements thus provide a rich resource for the field by characterizing protein dynamics during proliferation versus quiescence. PMID:28892491

Infantry Weapons Test Methodology Study. Volume 3. Light Machine Gun Test Methodology

DTIC Science & Technology

1972-06-01

Trajjectnry and marionim ordiwate. to the target increases beyond 500 meters, the beaten zone will become shorter and wider. When fires are de - livered into...traversing amount of elevation change is de - handwheel. To insure adequate tar- termined by the slope of the terrain get coverage, a burst is fired after and...to the traversing handwheel. The 6-mii increments on the traversing amount of elevation change Is de - handwheel. To insure adequate tar- termined by

Anchoring Junctions As Drug Targets: Role in Contraceptive Development

PubMed Central

Mruk, Dolores D.; Silvestrini, Bruno; Cheng, C. Yan

2010-01-01

In multicellular organisms, cell-cell interactions are mediated in part by cell junctions, which underlie tissue architecture. Throughout spermatogenesis, for instance, preleptotene leptotene spermatocytes residing in the basal compartment of the seminiferous epithelium must traverse the blood-testis barrier to enter the adluminal compartment for continued development. At the same time, germ cells must also remain attached to Sertoli cells, and numerous studies have reported extensive restructuring at the Sertoli-Sertoli and Sertoli-germ cell interface during germ cell movement across the seminiferous epithelium. Furthermore, the proteins and signaling cascades that regulate adhesion between testicular cells have been largely delineated. These findings have unveiled a number of potential “druggable” targets that can be used to induce premature release of germ cells from the seminiferous epithelium, resulting in transient infertility. Herein, we discuss a novel approach with the aim of developing a nonhormonal male contraceptive for future human use, one that involves perturbing adhesion between Sertoli and germ cells in the testis. PMID:18483144

Cell division cycle 45 promotes papillary thyroid cancer progression via regulating cell cycle.

PubMed

Sun, Jing; Shi, Run; Zhao, Sha; Li, Xiaona; Lu, Shan; Bu, Hemei; Ma, Xianghua

2017-05-01

Cell division cycle 45 was reported to be overexpressed in some cancer-derived cell lines and was predicted to be a candidate oncogene in cervical cancer. However, the clinical and biological significance of cell division cycle 45 in papillary thyroid cancer has never been investigated. We determined the expression level and clinical significance of cell division cycle 45 using The Cancer Genome Atlas, quantitative real-time polymerase chain reaction, and immunohistochemistry. A great upregulation of cell division cycle 45 was observed in papillary thyroid cancer tissues compared with adjacent normal tissues. Furthermore, overexpression of cell division cycle 45 positively correlates with more advanced clinical characteristics. Silence of cell division cycle 45 suppressed proliferation of papillary thyroid cancer cells via G1-phase arrest and inducing apoptosis. The oncogenic activity of cell division cycle 45 was also confirmed in vivo. In conclusion, cell division cycle 45 may serve as a novel biomarker and a potential therapeutic target for papillary thyroid cancer.

Landscape and flux reveal a new global view and physical quantification of mammalian cell cycle

PubMed Central

Li, Chunhe; Wang, Jin

2014-01-01

Cell cycles, essential for biological function, have been investigated extensively. However, enabling a global understanding and defining a physical quantification of the stability and function of the cell cycle remains challenging. Based upon a mammalian cell cycle gene network, we uncovered the underlying Mexican hat landscape of the cell cycle. We found the emergence of three local basins of attraction and two major potential barriers along the cell cycle trajectory. The three local basins of attraction characterize the G1, S/G2, and M phases. The barriers characterize the G1 and S/G2 checkpoints, respectively, of the cell cycle, thus providing an explanation of the checkpoint mechanism for the cell cycle from the physical perspective. We found that the progression of a cell cycle is determined by two driving forces: curl flux for acceleration and potential barriers for deceleration along the cycle path. Therefore, the cell cycle can be promoted (suppressed), either by enhancing (suppressing) the flux (representing the energy input) or by lowering (increasing) the barrier along the cell cycle path. We found that both the entropy production rate and energy per cell cycle increase as the growth factor increases. This reflects that cell growth and division are driven by energy or nutrition supply. More energy input increases flux and decreases barrier along the cell cycle path, leading to faster oscillations. We also identified certain key genes and regulations for stability and progression of the cell cycle. Some of these findings were evidenced from experiments whereas others lead to predictions and potential anticancer strategies. PMID:25228772

Identification of Cell Cycle-Regulated Genes by Convolutional Neural Network.

PubMed

Liu, Chenglin; Cui, Peng; Huang, Tao

2017-01-01

The cell cycle-regulated genes express periodically with the cell cycle stages, and the identification and study of these genes can provide a deep understanding of the cell cycle process. Large false positives and low overlaps are big problems in cell cycle-regulated gene detection. Here, a computational framework called DLGene was proposed for cell cycle-regulated gene detection. It is based on the convolutional neural network, a deep learning algorithm representing raw form of data pattern without assumption of their distribution. First, the expression data was transformed to categorical state data to denote the changing state of gene expression, and four different expression patterns were revealed for the reported cell cycle-regulated genes. Then, DLGene was applied to discriminate the non-cell cycle gene and the four subtypes of cell cycle genes. Its performances were compared with six traditional machine learning methods. At last, the biological functions of representative cell cycle genes for each subtype are analyzed. Our method showed better and more balanced performance of sensitivity and specificity comparing to other machine learning algorithms. The cell cycle genes had very different expression pattern with non-cell cycle genes and among the cell-cycle genes, there were four subtypes. Our method not only detects the cell cycle genes, but also describes its expression pattern, such as when its highest expression level is reached and how it changes with time. For each type, we analyzed the biological functions of the representative genes and such results provided novel insight to the cell cycle mechanisms. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effect of atomic noise on optical squeezing via polarization self-rotation in a thermal vapor cell

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

Hsu, M. T. L.; Hetet, G.; Peng, A.

2006-02-15

The traversal of an elliptically polarized optical field through a thermal vapor cell can give rise to a rotation of its polarization axis. This process, known as polarization self-rotation (PSR), has been suggested as a mechanism for producing squeezed light at atomic transition wavelengths. We show results of the characterization of PSR in isotopically enhanced rubidium-87 cells, performed in two independent laboratories. We observed that, contrary to earlier work, the presence of atomic noise in the thermal vapor overwhelms the observation of squeezing. We present a theory that contains atomic noise terms and show that a null result in squeezingmore » is consistent with this theory.« less

[Multi-channel in vivo recording techniques: analysis of phase coupling between spikes and rhythmic oscillations of local field potentials].

PubMed

Wang, Ce-Qun; Chen, Qiang; Zhang, Lu; Xu, Jia-Min; Lin, Long-Nian

2014-12-25

The purpose of this article is to introduce the measurements of phase coupling between spikes and rhythmic oscillations of local field potentials (LFPs). Multi-channel in vivo recording techniques allow us to record ensemble neuronal activity and LFPs simultaneously from the same sites in the brain. Neuronal activity is generally characterized by temporal spike sequences, while LFPs contain oscillatory rhythms in different frequency ranges. Phase coupling analysis can reveal the temporal relationships between neuronal firing and LFP rhythms. As the first step, the instantaneous phase of LFP rhythms can be calculated using Hilbert transform, and then for each time-stamped spike occurred during an oscillatory epoch, we marked instantaneous phase of the LFP at that time stamp. Finally, the phase relationships between the neuronal firing and LFP rhythms were determined by examining the distribution of the firing phase. Phase-locked spikes are revealed by the non-random distribution of spike phase. Theta phase precession is a unique phase relationship between neuronal firing and LFPs, which is one of the basic features of hippocampal place cells. Place cells show rhythmic burst firing following theta oscillation within a place field. And phase precession refers to that rhythmic burst firing shifted in a systematic way during traversal of the field, moving progressively forward on each theta cycle. This relation between phase and position can be described by a linear model, and phase precession is commonly quantified with a circular-linear coefficient. Phase coupling analysis helps us to better understand the temporal information coding between neuronal firing and LFPs.

Battery Capacity Fading Estimation Using a Force-Based Incremental Capacity Analysis

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

Samad, Nassim A.; Kim, Youngki; Siegel, Jason B.

Traditionally health monitoring techniques in lithium-ion batteries rely on voltage and current measurements. A novel method of using a mechanical rather than electrical signal in the incremental capacity analysis (ICA) method is introduced in this paper. This method derives the incremental capacity curves based onmeasured force (ICF) instead of voltage (ICV). The force ismeasured on the surface of a cell under compression in a fixture that replicates a battery pack assembly and preloading. The analysis is performed on data collected from cycling encased prismatic Lithium-ion Nickel-Manganese-Cobalt Oxide (NMC) cells. For the NMC chemistry, the ICF method can complement or replacemore » the ICV method for the following reasons. The identified ICV peaks are centered around 40% of state of charge (SOC) while the peaks of the ICF method are centered around 70% of SOC indicating that the ICF can be used more often because it is more likely that an electric vehicle (EV) or a plug-in hybrid electric vehicle (PHEV) will traverse the 70% SOC range than the 40% SOC. In addition the Signal to Noise ratio (SNR) of the force signal is four times larger than the voltage signal using laboratory grade sensors. The proposed ICF method is shown to achieve 0.42% accuracy in capacity estimation during a low C-rate constant current discharge. Future work will investigate the application of the capacity estimation technique under charging and operation under high C-rates by addressing the transient behavior of force so that an online methodology for capacity estimation is developed.« less

Battery Capacity Fading Estimation Using a Force-Based Incremental Capacity Analysis

DOE PAGES

Samad, Nassim A.; Kim, Youngki; Siegel, Jason B.; ...

2016-05-27

Traditionally health monitoring techniques in lithium-ion batteries rely on voltage and current measurements. A novel method of using a mechanical rather than electrical signal in the incremental capacity analysis (ICA) method is introduced in this paper. This method derives the incremental capacity curves based onmeasured force (ICF) instead of voltage (ICV). The force ismeasured on the surface of a cell under compression in a fixture that replicates a battery pack assembly and preloading. The analysis is performed on data collected from cycling encased prismatic Lithium-ion Nickel-Manganese-Cobalt Oxide (NMC) cells. For the NMC chemistry, the ICF method can complement or replacemore » the ICV method for the following reasons. The identified ICV peaks are centered around 40% of state of charge (SOC) while the peaks of the ICF method are centered around 70% of SOC indicating that the ICF can be used more often because it is more likely that an electric vehicle (EV) or a plug-in hybrid electric vehicle (PHEV) will traverse the 70% SOC range than the 40% SOC. In addition the Signal to Noise ratio (SNR) of the force signal is four times larger than the voltage signal using laboratory grade sensors. The proposed ICF method is shown to achieve 0.42% accuracy in capacity estimation during a low C-rate constant current discharge. Future work will investigate the application of the capacity estimation technique under charging and operation under high C-rates by addressing the transient behavior of force so that an online methodology for capacity estimation is developed.« less

Cell cycle phases in the unequal mother/daughter cell cycles of Saccharomyces cerevisiae.

PubMed

Brewer, B J; Chlebowicz-Sledziewska, E; Fangman, W L

1984-11-01

During cell division in the yeast Saccharomyces cerevisiae mother cells produce buds (daughter cells) which are smaller and have longer cell cycles. We performed experiments to compare the lengths of cell cycle phases in mothers and daughters. As anticipated from earlier indirect observations, the longer cell cycle time of daughter cells is accounted for by a longer G1 interval. The S-phase and the G2-phase are of the same duration in mother and daughter cells. An analysis of five isogenic strains shows that cell cycle phase lengths are independent of cell ploidy and mating type.

Factors Controlling the Formation of Oxidized Root Channels: A Review and Annotated Bibliography

DTIC Science & Technology

1993-08-01

professor at the Wetland Bio - geochemistry Institute and the Department of Oceanography and Coastal Science at LoLisiana State University. The work was...accumulated in the cells of the epidermis, exodermis, endodermis, and marginal layers of the stele . Zinc and phosphorus appeared to be associated possibly...intercellular spaces. Iron was also found on the tissue diaphragms that traverse the cortex of the root, connecting its outer cortex with the stele . Electron

The Global Regulatory Architecture of Transcription during the Caulobacter Cell Cycle

PubMed Central

Zhou, Bo; Schrader, Jared M.; Kalogeraki, Virginia S.; Abeliuk, Eduardo; Dinh, Cong B.; Pham, James Q.; Cui, Zhongying Z.; Dill, David L.; McAdams, Harley H.; Shapiro, Lucy

2015-01-01

Each Caulobacter cell cycle involves differentiation and an asymmetric cell division driven by a cyclical regulatory circuit comprised of four transcription factors (TFs) and a DNA methyltransferase. Using a modified global 5′ RACE protocol, we globally mapped transcription start sites (TSSs) at base-pair resolution, measured their transcription levels at multiple times in the cell cycle, and identified their transcription factor binding sites. Out of 2726 TSSs, 586 were shown to be cell cycle-regulated and we identified 529 binding sites for the cell cycle master regulators. Twenty-three percent of the cell cycle-regulated promoters were found to be under the combinatorial control of two or more of the global regulators. Previously unknown features of the core cell cycle circuit were identified, including 107 antisense TSSs which exhibit cell cycle-control, and 241 genes with multiple TSSs whose transcription levels often exhibited different cell cycle timing. Cumulatively, this study uncovered novel new layers of transcriptional regulation mediating the bacterial cell cycle. PMID:25569173

Indirect-fired gas turbine dual fuel cell power cycle

DOEpatents

Micheli, Paul L.; Williams, Mark C.; Sudhoff, Frederick A.

1996-01-01

A fuel cell and gas turbine combined cycle system which includes dual fuel cell cycles combined with a gas turbine cycle wherein a solid oxide fuel cell cycle operated at a pressure of between 6 to 15 atms tops the turbine cycle and is used to produce CO.sub.2 for a molten carbonate fuel cell cycle which bottoms the turbine and is operated at essentially atmospheric pressure. A high pressure combustor is used to combust the excess fuel from the topping fuel cell cycle to further heat the pressurized gas driving the turbine. A low pressure combustor is used to combust the excess fuel from the bottoming fuel cell to reheat the gas stream passing out of the turbine which is used to preheat the pressurized air stream entering the topping fuel cell before passing into the bottoming fuel cell cathode. The CO.sub.2 generated in the solid oxide fuel cell cycle cascades through the system to the molten carbonate fuel cell cycle cathode.

The global regulatory architecture of transcription during the Caulobacter cell cycle.

PubMed

Zhou, Bo; Schrader, Jared M; Kalogeraki, Virginia S; Abeliuk, Eduardo; Dinh, Cong B; Pham, James Q; Cui, Zhongying Z; Dill, David L; McAdams, Harley H; Shapiro, Lucy

2015-01-01

Each Caulobacter cell cycle involves differentiation and an asymmetric cell division driven by a cyclical regulatory circuit comprised of four transcription factors (TFs) and a DNA methyltransferase. Using a modified global 5' RACE protocol, we globally mapped transcription start sites (TSSs) at base-pair resolution, measured their transcription levels at multiple times in the cell cycle, and identified their transcription factor binding sites. Out of 2726 TSSs, 586 were shown to be cell cycle-regulated and we identified 529 binding sites for the cell cycle master regulators. Twenty-three percent of the cell cycle-regulated promoters were found to be under the combinatorial control of two or more of the global regulators. Previously unknown features of the core cell cycle circuit were identified, including 107 antisense TSSs which exhibit cell cycle-control, and 241 genes with multiple TSSs whose transcription levels often exhibited different cell cycle timing. Cumulatively, this study uncovered novel new layers of transcriptional regulation mediating the bacterial cell cycle.

Measuring cell cycle progression kinetics with metabolic labeling and flow cytometry.

PubMed

Fleisig, Helen; Wong, Judy

2012-05-22

Precise control of the initiation and subsequent progression through the various phases of the cell cycle are of paramount importance in proliferating cells. Cell cycle division is an integral part of growth and reproduction and deregulation of key cell cycle components have been implicated in the precipitating events of carcinogenesis. Molecular agents in anti-cancer therapies frequently target biological pathways responsible for the regulation and coordination of cell cycle division. Although cell cycle kinetics tend to vary according to cell type, the distribution of cells amongst the four stages of the cell cycle is rather consistent within a particular cell line due to the consistent pattern of mitogen and growth factor expression. Genotoxic events and other cellular stressors can result in a temporary block of cell cycle progression, resulting in arrest or a temporary pause in a particular cell cycle phase to allow for instigation of the appropriate response mechanism. The ability to experimentally observe the behavior of a cell population with reference to their cell cycle progression stage is an important advance in cell biology. Common procedures such as mitotic shake off, differential centrifugation or flow cytometry-based sorting are used to isolate cells at specific stages of the cell cycle. These fractionated, cell cycle phase-enriched populations are then subjected to experimental treatments. Yield, purity and viability of the separated fractions can often be compromised using these physical separation methods. As well, the time lapse between separation of the cell populations and the start of experimental treatment, whereby the fractionated cells can progress from the selected cell cycle stage, can pose significant challenges in the successful implementation and interpretation of these experiments. Other approaches to study cell cycle stages include the use of chemicals to synchronize cells. Treatment of cells with chemical inhibitors of key metabolic processes for each cell cycle stage are useful in blocking the progression of the cell cycle to the next stage. For example, the ribonucleotide reductase inhibitor hydroxyurea halts cells at the G1/S juncture by limiting the supply of deoxynucleotides, the building blocks of DNA. Other notable chemicals include treatment with aphidicolin, a polymerase alpha inhibitor for G1 arrest, treatment with colchicine and nocodazole, both of which interfere with mitotic spindle formation to halt cells in M phase and finally, treatment with the DNA chain terminator 5-fluorodeoxyridine to initiate S phase arrest. Treatment with these chemicals is an effective means of synchronizing an entire population of cells at a particular phase. With removal of the chemical, cells rejoin the cell cycle in unison. Treatment of the test agent following release from the cell cycle blocking chemical ensures that the drug response elicited is from a uniform, cell cycle stage-specific population. However, since many of the chemical synchronizers are known genotoxic compounds, teasing apart the participation of various response pathways (to the synchronizers vs. the test agents) is challenging. Here we describe a metabolic labeling method for following a subpopulation of actively cycling cells through their progression from the DNA replication phase, through to the division and separation of their daughter cells. Coupled with flow cytometry quantification, this protocol enables for measurement of kinetic progression of the cell cycle in the absence of either mechanically- or chemically- induced cellular stresses commonly associated with other cell cycle synchronization methodologies. In the following sections we will discuss the methodology, as well as some of its applications in biomedical research.

The cell cycle as a brake for β-cell regeneration from embryonic stem cells.

PubMed

El-Badawy, Ahmed; El-Badri, Nagwa

2016-01-13

The generation of insulin-producing β cells from stem cells in vitro provides a promising source of cells for cell transplantation therapy in diabetes. However, insulin-producing cells generated from human stem cells show deficiency in many functional characteristics compared with pancreatic β cells. Recent reports have shown molecular ties between the cell cycle and the differentiation mechanism of embryonic stem (ES) cells, assuming that cell fate decisions are controlled by the cell cycle machinery. Both β cells and ES cells possess unique cell cycle machinery yet with significant contrasts. In this review, we compare the cell cycle control mechanisms in both ES cells and β cells, and highlight the fundamental differences between pluripotent cells of embryonic origin and differentiated β cells. Through critical analysis of the differences of the cell cycle between these two cell types, we propose that the cell cycle of ES cells may act as a brake for β-cell regeneration. Based on these differences, we discuss the potential of modulating the cell cycle of ES cells for the large-scale generation of functionally mature β cells in vitro. Further understanding of the factors that modulate the ES cell cycle will lead to new approaches to enhance the production of functional mature insulin-producing cells, and yield a reliable system to generate bona fide β cells in vitro.

Opportunity Mars Rover mission: Overview and selected results from Purgatory ripple to traverses to Endeavour crater

USGS Publications Warehouse

Arvidson, R. E.; Ashley, James W.; Bell, J.F.; Chojnacki, M.; Cohen, J.; Economou, T.E.; Farrand, W. H.; Fergason, R.; Fleischer, I.; Geissler, P.; Gellert, Ralf; Golombek, M.P.; Grotzinger, J.P.; Guinness, E.A.; Haberle, R.M.; Herkenhoff, K. E.; Herman, J.A.; Iagnemma, K.D.; Jolliff, B.L.; Johnson, J. R.; Klingelhofer, G.; Knoll, A.H.; Knudson, A.T.; Li, R.; McLennan, S.M.; Mittlefehldt, D. W.; Morris, R.V.; Parker, T.J.; Rice, M.S.; Schroder, C.; Soderblom, L.A.; Squyres, S. W.; Sullivan, R.J.; Wolff, M.J.

2011-01-01

Opportunity has been traversing the Meridiani plains since 25 January 2004 (sol 1), acquiring numerous observations of the atmosphere, soils, and rocks. This paper provides an overview of key discoveries between sols 511 and 2300, complementing earlier papers covering results from the initial phases of the mission. Key new results include (1) atmospheric argon measurements that demonstrate the importance of atmospheric transport to and from the winter carbon dioxide polar ice caps; (2) observations showing that aeolian ripples covering the plains were generated by easterly winds during an epoch with enhanced Hadley cell circulation; (3) the discovery and characterization of cobbles and boulders that include iron and stony-iron meteorites and Martian impact ejecta; (4) measurements of wall rock strata within Erebus and Victoria craters that provide compelling evidence of formation by aeolian sand deposition, with local reworking within ephemeral lakes; (5) determination that the stratigraphy exposed in the walls of Victoria and Endurance craters show an enrichment of chlorine and depletion of magnesium and sulfur with increasing depth. This result implies that regional-scale aqueous alteration took place before formation of these craters. Most recently, Opportunity has been traversing toward the ancient Endeavour crater. Orbital data show that clay minerals are exposed on its rim. Hydrated sulfate minerals are exposed in plains rocks adjacent to the rim, unlike the surfaces of plains outcrops observed thus far by Opportunity. With continued mechanical health, Opportunity will reach terrains on and around Endeavour's rim that will be markedly different from anything examined to date.

Opportunity Mars Rover mission: Overview and selected results from Purgatory ripple to traverses to Endeavour crater

USGS Publications Warehouse

Arvidson, R. E.; Ashley, James W.; Bell, J.F.; Chojnacki, M.; Cohen, J.; Economou, T.E.; Farrand, W. H.; Fergason, R.; Fleischer, I.; Geissler, P.; Gellert, Ralf; Golombek, M.P.; Grotzinger, J.P.; Guinness, E.A.; Haberle, R.M.; Herkenhoff, K. E.; Herman, J.A.; Iagnemma, K.D.; Jolliff, B.L.; Johnson, J. R.; Klingelhofer, G.; Knoll, A.H.; Knudson, A.T.; Li, R.; McLennan, S.M.; Mittlefehldt, D. W.; Morris, R.V.; Parker, T.J.; Rice, M.S.; Schroder, C.; Soderblom, L.A.; Squyres, S. W.; Sullivan, R.J.; Wolff, M.J.

2011-01-01

Opportunity has been traversing the Meridiani plains since 25 January 2004 (sol 1), acquiring numerous observations of the atmosphere, soils, and rocks. This paper provides an overview of key discoveries between sols 511 and 2300, complementing earlier papers covering results from the initial phases of the mission. Key new results include (1) atmospheric argon measurements that demonstrate the importance of atmospheric transport to and from the winter carbon dioxide polar ice caps; (2) observations showing that aeolian ripples covering the plains were generated by easterly winds during an epoch with enhanced Hadley cell circulation; (3) the discovery and characterization of cobbles and boulders that include iron and stony-iron meteorites and Martian impact ejecta; (4) measurements of wall rock strata within Erebus and Victoria craters that provide compelling evidence of formation by aeolian sand deposition, with local reworking within ephemeral lakes; (5) determination that the stratigraphy exposed in the walls of Victoria and Endurance craters show an enrichment of chlorine and depletion of magnesium and sulfur with increasing depth. This result implies that regional-scale aqueous alteration took place before formation of these craters. Most recently, Opportunity has been traversing toward the ancient Endeavour crater. Orbital data show that clay minerals are exposed on its rim. Hydrated sulfate minerals are exposed in plains rocks adjacent to the rim, unlike the surfaces of plains outcrops observed thus far by Opportunity. With continued mechanical health, Opportunity will reach terrains on and around Endeavour's rim that will be markedly different from anything examined to date. Copyright 2011 by the American Geophysical Union.

Alantolactone, a natural sesquiterpene lactone, has potent antitumor activity against glioblastoma by targeting IKKβ kinase activity and interrupting NF-κB/COX-2-mediated signaling cascades.

PubMed

Wang, Xun; Yu, Zhenlong; Wang, Chao; Cheng, Wei; Tian, Xiangge; Huo, Xiaokui; Wang, Yan; Sun, Chengpeng; Feng, Lei; Xing, Jinshan; Lan, Yulong; Sun, Dongdong; Hou, Qingjuan; Zhang, Baojing; Ma, Xiaochi; Zhang, Bo

2017-07-12

Glioblastoma multiforme (GBM) is one of the most refractory and palindromic central nervous system (CNS) neoplasms, and current treatments have poor effects in GBM patients. Hence, the identification of novel therapeutic targets and the development of effective treatment strategies are essential. Alantolactone (ATL) has a wide range of pharmacological activities, and its anti-tumor effect is receiving increasing attention. However, the molecular mechanism underlying the anti-GBM activity of ATL remains poorly understood. The biological functions of ATL in GBM cells were investigated using migration/invasion, colony formation and cell cycle/apoptosis assays. The localization of nuclear factor kappa B (NF-κB) p50/p65 and its binding to the cyclooxygenase 2 (COX-2) promoter were determined using confocal immunofluorescence, a streptavidin-agarose pulldown assay and a chromatin immunoprecipitation (ChIP) assay. IKKβ kinase activity was determined using a cell IKKβ kinase activity spectrophotometry quantitative detection kit and a molecular docking study. LC-MS/MS analysis was performed to determine the ability of ATL to traverse the blood-brain barrier (BBB). The in vivo anti-tumor efficacy of ATL was also analyzed in xenografted nude mice. Western blot analysis was performed to detect the protein expression levels. ATL significantly suppressed the growth of GBM in vivo and in vitro. ATL significantly reduced the expression of COX-2 by inhibiting the kinase activity of IKKβ by targeting the ATP-binding site and then attenuating the binding of NF-κB to the COX-2 promoter region. Furthermore, ATL induced apoptosis by activating the cytochrome c (cyt c)/caspase cascade signaling pathway. Moreover, ATL could penetrate the BBB. ATL exerts its anti-tumor effects in human GBM cells at least in part via NF-κB/COX-2-mediated signaling cascades by inhibiting IKKβ kinase activity. ATL, which is a natural small molecule inhibitor, is a promising candidate for clinical applications in the treatment of CNS tumors.

Comparative cell cycle transcriptomics reveals synchronization of developmental transcription factor networks in cancer cells

PubMed Central

Johard, Helena; Mahdessian, Diana; Fedr, Radek; Marks, Carolyn; Medalová, Jiřina; Souček, Karel; Lundberg, Emma; Linnarsson, Sten; Bryja, Vítězslav; Sekyrova, Petra; Altun, Mikael; Andäng, Michael

2017-01-01

The cell cycle coordinates core functions such as replication and cell division. However, cell-cycle-regulated transcription in the control of non-core functions, such as cell identity maintenance through specific transcription factors (TFs) and signalling pathways remains unclear. Here, we provide a resource consisting of mapped transcriptomes in unsynchronized HeLa and U2OS cancer cells sorted for cell cycle phase by Fucci reporter expression. We developed a novel algorithm for data analysis that enables efficient visualization and data comparisons and identified cell cycle synchronization of Notch signalling and TFs associated with development. Furthermore, the cell cycle synchronizes with the circadian clock, providing a possible link between developmental transcriptional networks and the cell cycle. In conclusion we find that cell cycle synchronized transcriptional patterns are temporally compartmentalized and more complex than previously anticipated, involving genes, which control cell identity and development. PMID:29228002

Curiosity Traverse into Different Terrain

NASA Image and Video Library

2013-01-15

This image maps the traverse of NASA Mars rover Curiosity from Bradbury Landing to Yellowknife Bay, with an inset documenting a change in the ground thermal properties with arrival at a different type of terrain.

Effect of KOH concentration on LEO cycle life of IPV nickel-hydrogen flight cell - Update II

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Hall, Stephen W.

1992-01-01

An update of validation test results confirming the breakthrough in LEO cycle life of nickel-hydrogen cells containing 26 percent KOH electrolyte is presented. A breakthrough in the LEO cycle life of individual pressure vessel (IPV) nickel-hydrogen cells has been previously reported. The cycle life of boiler plate cells containing 26 percent potassium hydroxide (KOH) electrolyte was about 40,000 LEO cycles, compared to 3500 cycles for cells containing 31 percent KOH. The cycle regime was a stressful accelerated LEO, which consisted of a 27.5 min charge followed by a 17.5 min discharge (2X normal rate). The depth-of-discharge was 80 percent. Six 48-Ah Hughes recirculation design IPV nickel-hydrogen flight battery cells are being evaluated. Three of the cells contain 26 percent KOH (test cells), and three contain 31 percent KOH (control cells). They are undergoing real time LEO cycle life testing. The cycle regime is a 90-min LEO orbit consisting of a 54-min charge followed by a 36-min discharge. The depth-of-discharge is 80 percent. The cell temperature is maintained at 10 C. The three 31 percent KOH cells failed (cycles 3729, 4165, and 11355). One of the 26 percent KOH cells failed at cycle 15314. The other two 26 percent KOH cells were cycled for over 16,000 cycles during the continuing test.

The cell cycle.

PubMed

Singh, N; Lim, R B; Sawyer, M A

2000-07-01

The cell cycle and the cell cycle control system are the engines that drive life. They allow for the processes of cell renewal and the growth of organisms, under controlled conditions. The control system is essential for the monitoring of normal cell growth and replication of genetic material and to ensure that normal, functional daughter cells are produced at completion of each cell cycle. Although certain clinical applications exist which take advantage of the events of the cell cycle, our understanding of its mechanisms and how to manipulate them is infantile. The next decades will continue to see the effort of many researchers focused upon unlocking the mysteries of the cell cycle and the cell cycle control system.

Pathological implications of cell cycle re-entry in Alzheimer disease.

PubMed

Bonda, David J; Lee, Hyun-pil; Kudo, Wataru; Zhu, Xiongwei; Smith, Mark A; Lee, Hyoung-gon

2010-06-29

The complex neurodegeneration underlying Alzheimer disease (AD), although incompletely understood, is characterised by an aberrant re-entry into the cell cycle in neurons. Pathological evidence, in the form of cell cycle markers and regulatory proteins, suggests that cell cycle re-entry is an early event in AD, which precedes the formation of amyloid-beta plaques and neurofibrillary tangles (NFTs). Although the exact mechanisms that induce and mediate these cell cycle events in AD are not clear, significant advances have been made in further understanding the pathological role of cell cycle re-entry in AD. Importantly, recent studies indicate that cell cycle re-entry is not a consequence, but rather a cause, of neurodegeneration, suggesting that targeting of cell cycle re-entry may provide an opportunity for therapeutic intervention. Moreover, multiple inducers of cell cycle re-entry and their interactions in AD have been proposed. Here, we review the most recent advances in understanding the pathological implications of cell cycle re-entry in AD.

Functionally Graded Aluminum Foam Fabricated by Friction Powder Sintering Process with Traversing Tool

NASA Astrophysics Data System (ADS)

Hangai, Yoshihiko; Morita, Tomoaki; Koyama, Shinji; Kuwazuru, Osamu; Yoshikawa, Nobuhiro

2016-09-01

Functionally graded aluminum foam (FG Al foam) is a new class of Al foam in which the pore structure varies over the foam, resulting in corresponding variations in the mechanical properties of the foam. In this study, FG Al foam plates were fabricated by a friction powder sintering (FPS) process with a traversing tool that is based on a previously developed sintering and dissolution process. The variation of the mechanical properties was realized by setting the volume fraction φ of NaCl in the mixture to 60, 70, and 80%. Long FG Al foam plates were fabricated with a length equal to the tool traversing length with φ varying in the tool traversing direction. From x-ray computed tomography observation, it was shown that the density of the Al foam decreased with increasing φ. In contrast, almost uniform pore structures were obtained in each area. According to the results of compression tests on each area, the plateau stress and energy absorption tended to decrease with increasing φ. Therefore, it was shown that FG Al foam plates with varying mechanical properties can be fabricated by the FPS process with the traversing tool.

Cell-cycle synchronisation of bloodstream forms of Trypanosoma brucei using Vybrant DyeCycle Violet-based sorting.

PubMed

Kabani, Sarah; Waterfall, Martin; Matthews, Keith R

2010-01-01

Studies on the cell-cycle of Trypanosoma brucei have revealed several unusual characteristics that differ from the model eukaryotic organisms. However, the inability to isolate homogenous populations of parasites in distinct cell-cycle stages has limited the analysis of trypanosome cell division and complicated the understanding of mutant phenotypes with possible impact on cell-cycle related events. Although hydroxyurea-induced cell-cycle arrest in procyclic and bloodstream forms has been applied recently with success, such block-release protocols can complicate the analysis of cell-cycle regulated events and have the potential to disrupt important cell-cycle checkpoints. An alternative approach based on flow cytometry of parasites stained with Vybrant DyeCycle Orange circumvents this problem, but is restricted to procyclic form parasites. Here, we apply Vybrant Dyecycle Violet staining coupled with flow cytometry to effectively select different cell-cycle stages of bloodstream form trypanosomes. Moreover, the sorted parasites remain viable, although synchrony is rapidly lost. This method enables cell-cycle enrichment of populations of trypanosomes in their mammal infective stage, particularly at the G1 phase.

Cell-cycle synchronisation of bloodstream forms of Trypanosoma brucei using Vybrant DyeCycle Violet-based sorting

PubMed Central

Kabani, Sarah; Waterfall, Martin; Matthews, Keith R.

2010-01-01

Studies on the cell-cycle of Trypanosoma brucei have revealed several unusual characteristics that differ from the model eukaryotic organisms. However, the inability to isolate homogenous populations of parasites in distinct cell-cycle stages has limited the analysis of trypanosome cell division and complicated the understanding of mutant phenotypes with possible impact on cell-cycle related events. Although hydroxyurea-induced cell-cycle arrest in procyclic and bloodstream forms has been applied recently with success, such block-release protocols can complicate the analysis of cell-cycle regulated events and have the potential to disrupt important cell-cycle checkpoints. An alternative approach based on flow cytometry of parasites stained with Vybrant DyeCycle Orange circumvents this problem, but is restricted to procyclic form parasites. Here, we apply Vybrant Dyecycle Violet staining coupled with flow cytometry to effectively select different cell-cycle stages of bloodstream form trypanosomes. Moreover, the sorted parasites remain viable, although synchrony is rapidly lost. This method enables cell-cycle enrichment of populations of trypanosomes in their mammal infective stage, particularly at the G1 phase. PMID:19729042

Machine learning challenges in Mars rover traverse science

NASA Technical Reports Server (NTRS)

Castano, R.; Judd, M.; Anderson, R. C.; Estlin, T.

2003-01-01

The successful implementation of machine learning in autonomous rover traverse science requires addressing challenges that range from the analytical technical realm, to the fuzzy, philosophical domain of entrenched belief systems within scientists and mission managers.

Tortuous Pore Path Through the Glaucomatous Lamina Cribrosa.

PubMed

Wang, Bo; Lucy, Katie A; Schuman, Joel S; Sigal, Ian A; Bilonick, Richard A; Lu, Chen; Liu, Jonathan; Grulkowski, Ireneusz; Nadler, Zachary; Ishikawa, Hiroshi; Kagemann, Larry; Fujimoto, James G; Wollstein, Gadi

2018-05-08

The lamina cribrosa is a primary site of damage in glaucoma. While mechanical distortion is hypothesized to cause reduction of axoplasmic flow, little is known about how the pores, which contains the retinal ganglion cell axons, traverse the lamina cribrosa. We investigated lamina cribrosa pore paths in vivo to quantify differences in tortuosity of pore paths between healthy and glaucomatous eyes. We imaged 16 healthy, 23 glaucoma suspect and 48 glaucomatous eyes from 70 subjects using a swept source optical coherence tomography system. The lamina cribrosa pores were automatically segmented using a previously described segmentation algorithm. Individual pore paths were automatically tracked through the depth of the lamina cribrosa using custom software. Pore path convergence to the optic nerve center and tortuosity was quantified for each eye. We found that lamina cribrosa pore pathways traverse the lamina cribrosa closer to the optic nerve center along the depth of the lamina cribrosa regardless of disease severity or diagnostic category. In addition, pores of glaucoma eyes take a more tortuous path through the lamina cribrosa compared to those of healthy eyes, suggesting a potential mechanism for reduction of axoplasmic flow in glaucoma.

Tunneling and traversal of ultracold three-level atoms through vacuum-induced potentials

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

Badshah, Fazal; Irfan, Muhammad; Qamar, Shahid

2011-09-15

The passage of ultracold three-level atoms through the potential induced by the vacuum cavity mode is discussed using cascade atomic configuration. We study the tunneling or traversal time of the ultracold atoms via a bimodal high-Q cavity. It is found that the phase time, which may be considered as a measure for the time required to traverse the cavity, exhibits superclassical and subclassical behaviors. Further, the dark states and interference effects in cascade atomic configuration may influence the passage time of the atom through the cavity.

Importance of dose-rate and cell proliferation in the evaluation of biological experimental results

NASA Technical Reports Server (NTRS)

Curtis, S. B.

1994-01-01

The nuclei of cells within the bodies of astronauts traveling on extended missions outside the geomagnetosphere will experience single traversals of particles with high Linear Energy Transfer (LET) (e.g., one iron ion per one hundred years, on average) superimposed on a background of tracks with low LET (approximately one proton every two to three days, and one helium ion per month). In addition, some cell populations within the body will be proliferating, thus possibly providing increasing numbers of cells with 'initiated' targets for subsequent radiation hits. These temporal characteristics are not generally reproduced in laboratory experimental protocols. Implications of the differences in the temporal patterns of radiation delivery between conventionally designed radiation biology experiments and the pattern to be experienced in space are examined and the importance of dose-rate and cell proliferation are pointed out in the context of radiation risk assessment on long mission in space.

Method for delivery of small molecules and proteins across the cell wall of algae using molecular transporters

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

Geihe, Erika; Trantow, Brian; Wender, Paul

The introduction of tools to study, control or expand the inner-workings of algae has been slow to develop. Provided are embodiments of a molecular method based on guanidinium-rich molecular transporters (GR-MoTrs) for bringing molecular cargos into algal cells. The methods of the disclosure have been shown to work in wild-type algae that have an intact cell wall. Developed using Chlamydomonas reinhardtii, this method is also successful with less studied algae, including Neochloris oleoabundans and Scenedesmus dimorphus, thus providing a new and versatile tool for algal research and modification. The method of delivering a cargo compound to an algal cell comprisesmore » contacting an algal cell with a guanidinium-rich delivery vehicle comprising a guanidinium-rich molecular transporter (GR-MoTr) linked to a cargo compound desired to be delivered to the algal cell, whereby the guanidinium-rich molecular transporter can traverse the algal cell wall, thereby delivering the cargo compound to the algal cell.« less

Cell-to-cell communication via plasmodesmata in vascular plants

PubMed Central

Sevilem, Iris; Miyashima, Shunsuke; Helariutta, Ykä

2013-01-01

In plant development, cell-to-cell signaling is mediated by mobile signals, including transcription factors and small RNA molecules. This communication is essential for growth and patterning. Short-range movement of signals occurs in the extracellular space via the apoplastic pathway or directly from cell-to-cell via the symplastic pathway. Symplastic transport is mediated by plant specific structures called plasmodesmata, which are plasma membrane-lined pores that traverse the cell walls of adjacent cells thus connecting their cytoplasms. However, a thorough understanding of molecules moving via plasmodesmata and regulatory networks relying on symplastic signaling is lacking. Traffic via plasmodesmata is highly regulated, and callose turnover is known to be one mechanism. In Arabidopsis, plasmodesmata apertures can be regulated in a spatially and temporally specific manner with the icals3m, an inducible vector system expressing the mutated CalS3 gene encoding a plasmodesmata localized callose synthase that increases callose deposition at plasmodesmata. We discuss strategies to use the icals3m system for global analyses on symplastic signaling in plants. PMID:23076211

Alteration of cell cycle progression by Sindbis virus infection

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

Yi, Ruirong; Saito, Kengo; Isegawa, Naohisa

We examined the impact of Sindbis virus (SINV) infection on cell cycle progression in a cancer cell line, HeLa, and a non-cancerous cell line, Vero. Cell cycle analyses showed that SINV infection is able to alter the cell cycle progression in both HeLa and Vero cells, but differently, especially during the early stage of infection. SINV infection affected the expression of several cell cycle regulators (CDK4, CDK6, cyclin E, p21, cyclin A and cyclin B) in HeLa cells and caused HeLa cells to accumulate in S phase during the early stage of infection. Monitoring SINV replication in HeLa and Veromore » cells expressing cell cycle indicators revealed that SINV which infected HeLa cells during G{sub 1} phase preferred to proliferate during S/G{sub 2} phase, and the average time interval for viral replication was significantly shorter in both HeLa and Vero cells infected during G{sub 1} phase than in cells infected during S/G{sub 2} phase. - Highlights: • SINV infection was able to alter the cell cycle progression of infected cancer cells. • SINV infection can affect the expression of cell cycle regulators. • SINV infection exhibited a preference for the timing of viral replication among the cell cycle phases.« less

Autonomous Rover Traverse and Precise Arm Placement on Remotely Designated Targets

NASA Technical Reports Server (NTRS)

Nesnas, Issa A.; Pivtoraiko, Mihail N.; Kelly, Alonzo; Fleder, Michael

2012-01-01

This software controls a rover platform to traverse rocky terrain autonomously, plan paths, and avoid obstacles using its stereo hazard and navigation cameras. It does so while continuously tracking a target of interest selected from 10 20 m away. The rover drives and tracks the target until it reaches the vicinity of the target. The rover then positions itself to approach the target, deploys its robotic arm, and places the end effector instrument on the designated target to within 2-3-cm accuracy of the originally selected target. This software features continuous navigation in a fairly rocky field in an outdoor environment and the ability to enable the rover to avoid large rocks and traverse over smaller ones. Using point-and-click mouse commands, a scientist designates targets in the initial imagery acquired from the rover s mast cameras. The navigation software uses stereo imaging, traversability analysis, path planning, trajectory generation, and trajectory execution. It also includes visual target tracking of a designated target selected from 10 m away while continuously navigating the rocky terrain. Improvements in this design include steering while driving, which uses continuous curvature paths. There are also several improvements to the traversability analyzer, including improved data fusion of traversability maps that result from pose estimation uncertainties, dealing with boundary effects to enable tighter maneuvers, and handling a wider range of obstacles. This work advances what has been previously developed and integrated on the Mars Exploration Rovers by using algorithms that are capable of traversing more rock-dense terrains, enabling tight, thread-the-needle maneuvers. These algorithms were integrated on the newly refurbished Athena Mars research rover, and were fielded in the JPL Mars Yard. Forty-three runs were conducted with targets at distances ranging from 5 to 15 m, and a success rate of 93% was achieved for placement of the instrument within 2-3 cm of the target.

Enhancing fuzzy robot navigation systems by mimicking human visual perception of natural terrain traversibility

NASA Technical Reports Server (NTRS)

Tunstel, E.; Howard, A.; Edwards, D.; Carlson, A.

2001-01-01

This paper presents a technique for learning to assess terrain traversability for outdoor mobile robot navigation using human-embedded logic and real-time perception of terrain features extracted from image data.

Time of travel of the Flint River, Utah Dam to highway M-13, Michigan, August 4-8, 1981

USGS Publications Warehouse

Cummings, T. Ray; Miller, John B.

1982-01-01

Tracing of rhodamine WT dye has provided time-of-travel data for waste-load allocation studies of a 42.8-mile reach of the Flint River at low flow. A discharge equaled or exceeded about 90 percent of the time was measured at Grand Traverse Street in Flint before dye injection. Dye was injected at two locations in Flint--at Utah Dam and at Grand Traverse Street, From Utah Dam to Grand Traverse Street, the mean velocity of flow was about 0.1 foot per second; time-of-travel was 35.3 hours. From Grand Traverse Street to Highway M-13, mean velocity was about 0.7 foot per second; time-of-travel was 78.8 hours. Time-of-travel for the reach between Utah Dam and Highway M-13 was thus 114 hours.

My IGY in Antarctica

NASA Technical Reports Server (NTRS)

Bentley, Charles

2012-01-01

Dr Charles Bentley is the A.P. Crary Professor Emeritus of Geophysics, Department of Geology and Geophysics, University of Wisconsin-Madison. Dr. Bentley joined the Arctic Institute of North America in 1956 to participate in International Geophysical Year (IGY)-related activities in the Antarctic. He wintered over consecutively in 1957 and 1958 at Byrd Station, a station in the interior of West Antarctica that housed 24 men each winter - 12 Navy support people and 12 civilian scientists/technicians. During the austral summers, he also participated in over-snow traverses, first as co-leader, then leader (the other coleader went home after the first year). These traverses consisted of six men and three vehicles, and lasted several months. These traverses covered more than 1609 kilometers (1000 miles) of largely unmapped and unphotographed terrain. During these traverses, connections to Byrd Station were by radio (daily, when the transmission conditions were good enough) and roughly every 2 weeks by resupply flight.

Quantitative imaging with Fucci and mathematics to uncover temporal dynamics of cell cycle progression.

PubMed

Saitou, Takashi; Imamura, Takeshi

2016-01-01

Cell cycle progression is strictly coordinated to ensure proper tissue growth, development, and regeneration of multicellular organisms. Spatiotemporal visualization of cell cycle phases directly helps us to obtain a deeper understanding of controlled, multicellular, cell cycle progression. The fluorescent ubiquitination-based cell cycle indicator (Fucci) system allows us to monitor, in living cells, the G1 and the S/G2/M phases of the cell cycle in red and green fluorescent colors, respectively. Since the discovery of Fucci technology, it has found numerous applications in the characterization of the timing of cell cycle phase transitions under diverse conditions and various biological processes. However, due to the complexity of cell cycle dynamics, understanding of specific patterns of cell cycle progression is still far from complete. In order to tackle this issue, quantitative approaches combined with mathematical modeling seem to be essential. Here, we review several studies that attempted to integrate Fucci technology and mathematical models to obtain quantitative information regarding cell cycle regulatory patterns. Focusing on the technological development of utilizing mathematics to retrieve meaningful information from the Fucci producing data, we discuss how the combined methods advance a quantitative understanding of cell cycle regulation. © 2015 Japanese Society of Developmental Biologists.

Cell Cycle Control in the Early Embryonic Development of Aquatic Animal Species

PubMed Central

Siefert, Joseph C.; Clowdus, Emily A.; Sansam, Christopher L.

2016-01-01

The cell cycle is integrated with many aspects of embryonic development. Not only is proper control over the pace of cell proliferation important, but also the timing of cell cycle progression is coordinated with transcription, cell migration, and cell differentiation. Due to the ease with which the embryos of aquatic organisms can be observed and manipulated, they have been a popular choice for embryologists throughout history. In the cell cycle field, aquatic organisms have been extremely important because they have played a major role in the discovery and analysis of key regulators of the cell cycle. In particular, the frog Xenopus laevis has been instrumental for understanding how the basic embryonic cell cycle is regulated. More recently, the zebrafish has been used to understand how the cell cycle is remodeled during vertebrate development and how it is regulated during morphogenesis. This review describes how some of the unique strengths of aquatic species have been leveraged for cell cycle research and suggests how species such as Xenopus and zebrafish will continue to reveal the roles of the cell cycle in human biology and disease. PMID:26475527

Cell cycle arrest in the jewel wasp Nasonia vitripennis in larval diapause.

PubMed

Shimizu, Yuta; Mukai, Ayumu; Goto, Shin G

2018-04-01

Insects enter diapause to synchronise their life cycle with biotic and abiotic environmental conditions favourable for their development, reproduction, and survival. One of the most noticeable characteristics of diapause is the blockage of ontogeny. Although this blockage should occur with the cessation of cellular proliferation, i.e. cell cycle arrest, it was confirmed only in a few insect species and information on the molecular pathways involved in cell cycle arrest is limited. In the present study, we investigated developmental and cell cycle arrest in diapause larvae of the jewel wasp Nasonia vitripennis. Developmental and cell cycle arrest occur in the early fourth instar larval stage of N. vitripennis under short days. By entering diapause, the S fraction of the cell cycle disappears and approximately 80% and 20% of cells arrest their cell cycle in the G0/G1 and G2 phases, respectively. We further investigated expression of cell cycle regulatory genes and some housekeeping genes to dissect molecular mechanisms underlying the cell cycle arrest. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modelling cell cycle synchronisation in networks of coupled radial glial cells.

PubMed

Barrack, Duncan S; Thul, Rüdiger; Owen, Markus R

2015-07-21

Radial glial cells play a crucial role in the embryonic mammalian brain. Their proliferation is thought to be controlled, in part, by ATP mediated calcium signals. It has been hypothesised that these signals act to locally synchronise cell cycles, so that clusters of cells proliferate together, shedding daughter cells in uniform sheets. In this paper we investigate this cell cycle synchronisation by taking an ordinary differential equation model that couples the dynamics of intracellular calcium and the cell cycle and extend it to populations of cells coupled via extracellular ATP signals. Through bifurcation analysis we show that although ATP mediated calcium release can lead to cell cycle synchronisation, a number of other asynchronous oscillatory solutions including torus solutions dominate the parameter space and cell cycle synchronisation is far from guaranteed. Despite this, numerical results indicate that the transient and not the asymptotic behaviour of the system is important in accounting for cell cycle synchronisation. In particular, quiescent cells can be entrained on to the cell cycle via ATP mediated calcium signals initiated by a driving cell and crucially will cycle in near synchrony with the driving cell for the duration of neurogenesis. This behaviour is highly sensitive to the timing of ATP release, with release at the G1/S phase transition of the cell cycle far more likely to lead to near synchrony than release during mid G1 phase. This result, which suggests that ATP release timing is critical to radial glia cell cycle synchronisation, may help us to understand normal and pathological brain development. Copyright © 2015 Elsevier Ltd. All rights reserved.

Unraveling Interfaces between Energy Metabolism and Cell Cycle in Plants.

PubMed

Siqueira, João Antonio; Hardoim, Pablo; Ferreira, Paulo C G; Nunes-Nesi, Adriano; Hemerly, Adriana S

2018-06-19

Oscillation in energy levels is widely variable in dividing and differentiated cells. To synchronize cell proliferation and energy fluctuations, cell cycle-related proteins have been implicated in the regulation of mitochondrial energy-generating pathways in yeasts and animals. Plants have chloroplasts and mitochondria, coordinating the cell energy flow. Recent findings suggest an integrated regulation of these organelles and the nuclear cell cycle. Furthermore, reports indicate a set of interactions between the cell cycle and energy metabolism, coordinating the turnover of proteins in plants. Here, we discuss how cell cycle-related proteins directly interact with energy metabolism-related proteins to modulate energy homeostasis and cell cycle progression. We provide interfaces between cell cycle and energy metabolism-related proteins that could be explored to maximize plant yield. Copyright © 2018 Elsevier Ltd. All rights reserved.

Coordination of Myeloid Differentiation with Reduced Cell Cycle Progression by PU.1 Induction of MicroRNAs Targeting Cell Cycle Regulators and Lipid Anabolism.

PubMed

Solomon, Lauren A; Podder, Shreya; He, Jessica; Jackson-Chornenki, Nicholas L; Gibson, Kristen; Ziliotto, Rachel G; Rhee, Jess; DeKoter, Rodney P

2017-05-15

During macrophage development, myeloid progenitor cells undergo terminal differentiation coordinated with reduced cell cycle progression. Differentiation of macrophages from myeloid progenitors is accompanied by increased expression of the E26 transformation-specific transcription factor PU.1. Reduced PU.1 expression leads to increased proliferation and impaired differentiation of myeloid progenitor cells. It is not understood how PU.1 coordinates macrophage differentiation with reduced cell cycle progression. In this study, we utilized cultured PU.1-inducible myeloid cells to perform genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) analysis coupled with gene expression analysis to determine targets of PU.1 that may be involved in regulating cell cycle progression. We found that genes encoding cell cycle regulators and enzymes involved in lipid anabolism were directly and inducibly bound by PU.1 although their steady-state mRNA transcript levels were reduced. Inhibition of lipid anabolism was sufficient to reduce cell cycle progression in these cells. Induction of PU.1 reduced expression of E2f1 , an important activator of genes involved in cell cycle and lipid anabolism, indirectly through microRNA 223. Next-generation sequencing identified microRNAs validated as targeting cell cycle and lipid anabolism for downregulation. These results suggest that PU.1 coordinates cell cycle progression with differentiation through induction of microRNAs targeting cell cycle regulators and lipid anabolism. Copyright © 2017 American Society for Microbiology.

Cell cycle-related metabolism and mitochondrial dynamics in a replication-competent pancreatic beta-cell line.

PubMed

Montemurro, Chiara; Vadrevu, Suryakiran; Gurlo, Tatyana; Butler, Alexandra E; Vongbunyong, Kenny E; Petcherski, Anton; Shirihai, Orian S; Satin, Leslie S; Braas, Daniel; Butler, Peter C; Tudzarova, Slavica

2017-01-01

Cell replication is a fundamental attribute of growth and repair in multicellular organisms. Pancreatic beta-cells in adults rarely enter cell cycle, hindering the capacity for regeneration in diabetes. Efforts to drive beta-cells into cell cycle have so far largely focused on regulatory molecules such as cyclins and cyclin-dependent kinases (CDKs). Investigations in cancer biology have uncovered that adaptive changes in metabolism, the mitochondrial network, and cellular Ca 2+ are critical for permitting cells to progress through the cell cycle. Here, we investigated these parameters in the replication-competent beta-cell line INS 832/13. Cell cycle synchronization of this line permitted evaluation of cell metabolism, mitochondrial network, and cellular Ca 2+ compartmentalization at key cell cycle stages. The mitochondrial network is interconnected and filamentous at G1/S but fragments during the S and G2/M phases, presumably to permit sorting to daughter cells. Pyruvate anaplerosis peaks at G1/S, consistent with generation of biomass for daughter cells, whereas mitochondrial Ca 2+ and respiration increase during S and G2/M, consistent with increased energy requirements for DNA and lipid synthesis. This synchronization approach may be of value to investigators performing live cell imaging of Ca 2+ or mitochondrial dynamics commonly undertaken in INS cell lines because without synchrony widely disparate data from cell to cell would be expected depending on position within cell cycle. Our findings also offer insight into why replicating beta-cells are relatively nonfunctional secreting insulin in response to glucose. They also provide guidance on metabolic requirements of beta-cells for the transition through the cell cycle that may complement the efforts currently restricted to manipulating cell cycle to drive beta-cells through cell cycle.

A Short-Term Advantage for Syngamy in the Origin of Eukaryotic Sex: Effects of Cell Fusion on Cell Cycle Duration and Other Effects Related to the Duration of the Cell Cycle-Relationship between Cell Growth Curve and the Optimal Size of the Species, and Circadian Cell Cycle in Photosynthetic Unicellular Organisms.

PubMed

Mancebo Quintana, J M; Mancebo Quintana, S

2012-01-01

The origin of sex is becoming a vexatious issue for Evolutionary Biology. Numerous hypotheses have been proposed, based on the genetic effects of sex, on trophic effects or on the formation of cysts and syncytia. Our approach addresses the change in cell cycle duration which would cause cell fusion. Several results are obtained through graphical and mathematical analysis and computer simulations. (1) In poor environments, cell fusion would be an advantageous strategy, as fusion between cells of different size shortens the cycle of the smaller cell (relative to the asexual cycle), and the majority of mergers would occur between cells of different sizes. (2) The easiest-to-evolve regulation of cell proliferation (sexual/asexual) would be by modifying the checkpoints of the cell cycle. (3) A regulation of this kind would have required the existence of the G2 phase, and sex could thus be the cause of the appearance of this phase. Regarding cell cycle, (4) the exponential curve is the only cell growth curve that has no effect on the optimal cell size in unicellular species; (5) the existence of a plateau with no growth at the end of the cell cycle explains the circadian cell cycle observed in unicellular algae.

A balance of FGF and BMP signals regulates cell cycle exit and Equarin expression in lens cells

PubMed Central

Jarrin, Miguel; Pandit, Tanushree; Gunhaga, Lena

2012-01-01

In embryonic and adult lenses, a balance of cell proliferation, cell cycle exit, and differentiation is necessary to maintain physical function. The molecular mechanisms regulating the transition of proliferating lens epithelial cells to differentiated primary lens fiber cells are poorly characterized. To investigate this question, we used gain- and loss-of-function analyses to modulate fibroblast growth factor (FGF) and/or bone morphogenetic protein (BMP) signals in chick lens/retina explants. Here we show that FGF activity plays a key role for proliferation independent of BMP signals. Moreover, a balance of FGF and BMP signals regulates cell cycle exit and the expression of Ccdc80 (also called Equarin), which is expressed at sites where differentiation of lens fiber cells occurs. BMP activity promotes cell cycle exit and induces Equarin expression in an FGF-dependent manner. In contrast, FGF activity is required but not sufficient to induce cell cycle exit or Equarin expression. Furthermore, our results show that in the absence of BMP activity, lens cells have increased cell cycle length or are arrested in the cell cycle, which leads to decreased cell cycle exit. Taken together, these findings suggest that proliferation, cell cycle exit, and early differentiation of primary lens fiber cells are regulated by counterbalancing BMP and FGF signals. PMID:22718906

Transcription Factor Binding Profiles Reveal Cyclic Expression of Human Protein-coding Genes and Non-coding RNAs

PubMed Central

Cheng, Chao; Ung, Matthew; Grant, Gavin D.; Whitfield, Michael L.

2013-01-01

Cell cycle is a complex and highly supervised process that must proceed with regulatory precision to achieve successful cellular division. Despite the wide application, microarray time course experiments have several limitations in identifying cell cycle genes. We thus propose a computational model to predict human cell cycle genes based on transcription factor (TF) binding and regulatory motif information in their promoters. We utilize ENCODE ChIP-seq data and motif information as predictors to discriminate cell cycle against non-cell cycle genes. Our results show that both the trans- TF features and the cis- motif features are predictive of cell cycle genes, and a combination of the two types of features can further improve prediction accuracy. We apply our model to a complete list of GENCODE promoters to predict novel cell cycle driving promoters for both protein-coding genes and non-coding RNAs such as lincRNAs. We find that a similar percentage of lincRNAs are cell cycle regulated as protein-coding genes, suggesting the importance of non-coding RNAs in cell cycle division. The model we propose here provides not only a practical tool for identifying novel cell cycle genes with high accuracy, but also new insights on cell cycle regulation by TFs and cis-regulatory elements. PMID:23874175

Cycle life test and failure model of nickel-hydrogen cells

NASA Technical Reports Server (NTRS)

Smithrick, J. J.

1983-01-01

Six ampere hour individual pressure vessel nickel hydrogen cells were charge/discharge cycled to failure. Failure as used here is defined to occur when the end of discharge voltage degraded to 0.9 volts. They were cycled under a low earth orbit cycle regime to a deep depth of discharge (80 percent of rated ampere hour capacity). Both cell designs were fabricated by the same manufacturer and represent current state of the art. A failure model was advanced which suggests both cell designs have inadequate volume tolerance characteristics. The limited existing data base at a deep depth of discharge (DOD) was expanded. Two cells of each design were cycled. One COMSAT cell failed at cycle 1712 and the other failed at cycle 1875. For the Air Force/Hughes cells, one cell failed at cycle 2250 and the other failed at cycle 2638. All cells, of both designs, failed due to low end of discharge voltage (0.9 volts). No cell failed due to electrical shorts. After cell failure, three different reconditioning tests (deep discharge, physical reorientation, and open circuit voltage stand) were conducted on all cells of each design. A fourth reconditioning test (electrolyte addition) was conducted on one cell of each design. In addition post cycle cell teardown and failure analysis were performed on the one cell of each design which did not have electrolyte added after failure.

Laser amplifier and method

DOEpatents

Backus, S.; Kapteyn, H.C.; Murnane, M.M.

1997-07-01

Laser amplifiers and methods for amplifying a laser beam are disclosed. A representative embodiment of the amplifier comprises first and second curved mirrors, a gain medium, a third mirror, and a mask. The gain medium is situated between the first and second curved mirrors at the focal point of each curved mirror. The first curved mirror directs and focuses a laser beam to pass through the gain medium to the second curved mirror which reflects and recollimates the laser beam. The gain medium amplifies and shapes the laser beam as the laser beam passes therethrough. The third mirror reflects the laser beam, reflected from the second curved mirror, so that the laser beam bypasses the gain medium and return to the first curved mirror, thereby completing a cycle of a ring traversed by the laser beam. The mask defines at least one beam-clipping aperture through which the laser beam passes during a cycle. The gain medium is pumped, preferably using a suitable pumping laser. The laser amplifier can be used to increase the energy of continuous-wave or, especially, pulsed laser beams including pulses of femtosecond duration and relatively high pulse rate. 7 figs.

Laser amplifier and method

DOEpatents

Backus, Sterling; Kapteyn, Henry C.; Murnane, Margaret M.

1997-01-01

Laser amplifiers and methods for amplifying a laser beam are disclosed. A representative embodiment of the amplifier comprises first and second curved mirrors, a gain medium, a third mirror, and a mask. The gain medium is situated between the first and second curved mirrors at the focal point of each curved mirror. The first curved mirror directs and focuses a laser beam to pass through the gain medium to the second curved mirror which reflects and recollimates the laser beam. The gain medium amplifies and shapes the laser beam as the laser beam passes therethough. The third mirror reflects the laser beam, reflected from the second curved mirror, so that the laser beam bypasses the gain medium and return to the first curved mirror, thereby completing a cycle of a ring traversed by the laser beam. The mask defines at least one beam-clipping aperture through which the laser beam passes during a cycle. The gain medium is pumped, preferably using a suitable pumping laser. The laser amplifier can be used to increase the energy of continuous-wave or, especially, pulsed laser beams including pulses of femtosecond duration and relatively high pulse rate.

Verification test of the Battronic Truck Volta Electric Pickup, July 1980-January 1981

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

Dowgiallo, E.J. Jr.; Snellings, I.R.; Chapman, R.D.

1982-04-01

The Volta pickup truck is an electric, multipurpose utility vehicle manufactured by the Battronic Truck Corporation of Boyertown, Pennsylvania. The vehicle was teted from July 1980 to September 1981. Complete test results are contained in Section V of this report. Part of the verification test results are summarized below: (1) Acceleration: 0 to 50 km/h (31.1 mi/h) in 10.0 s. (2) Range: SAE J227a ''B'' cycle on level (+-1-percent grade) terrain yielded 55.2 km (34.3 mi) and 162 cycles. (3) Forward Speed Capability: The vehicle maintained 70 km/h (43.5 mi/h) for more than 5 min on the level (+-1-percent) portionmore » of the MERADCOM test track. (4) Gradeability at Speed: At 25 km/h (15.5 mi/h) the vehicle can traverse a 13-percent grade based on calculations from acceleration tests. (5) Gradeability Limit: Calculations based on drawbar-pull tests indicate a 11.5-percent forward and 12.4-percent reverse gradeability for at least 20 s.« less

Representations of the language recognition problem for a theorem prover

NASA Technical Reports Server (NTRS)

Minker, J.; Vanderbrug, G. J.

1972-01-01

Two representations of the language recognition problem for a theorem prover in first order logic are presented and contrasted. One of the representations is based on the familiar method of generating sentential forms of the language, and the other is based on the Cocke parsing algorithm. An augmented theorem prover is described which permits recognition of recursive languages. The state-transformation method developed by Cordell Green to construct problem solutions in resolution-based systems can be used to obtain the parse tree. In particular, the end-order traversal of the parse tree is derived in one of the representations. An inference system, termed the cycle inference system, is defined which makes it possible for the theorem prover to model the method on which the representation is based. The general applicability of the cycle inference system to state space problems is discussed. Given an unsatisfiable set S, where each clause has at most one positive literal, it is shown that there exists an input proof. The clauses for the two representations satisfy these conditions, as do many state space problems.

An additional step in the transmission of Yersinia pestis?

PubMed Central

Easterday, W Ryan; Kausrud, Kyrre L; Star, Bastiaan; Heier, Lise; Haley, Bradd J; Ageyev, Vladimir; Colwell, Rita R; Stenseth, Nils Chr

2012-01-01

Plague, caused by the bacterium Yersinia pestis, is a mammalian vector-borne disease, transmitted by fleas that serve as the vector between rodent hosts. For many pathogens, including Y. pestis, there are strong evolutionary pressures that lead to a reduction in ‘useless genes', with only those retained that reflect function in the specific environment inhabited by the pathogen. Genetic traits critical for survival and transmission between two environments, the rodent and the flea, are conserved in epizootic/epidemic plague strains. However, there are genes that remain conserved for which no function in the flea–rodent cycle has yet been observed, indicating an additional environment may exist in the transmission cycle of plague. Here, we present evidence for highly conserved genes that suggests a role in the persistence of Y. pestis after death of its host. Furthermore, maintenance of these genes points to Y. pestis traversing a post-mortem path between, and possibly within, epizootic periods and offering insight into mechanisms that may allow Y. pestis an alternative route of transmission in the natural environment. PMID:21833036

Cell Cycle Control by PTEN.

PubMed

Brandmaier, Andrew; Hou, Sheng-Qi; Shen, Wen H

2017-07-21

Continuous and error-free chromosome inheritance through the cell cycle is essential for genomic stability and tumor suppression. However, accumulation of aberrant genetic materials often causes the cell cycle to go awry, leading to malignant transformation. In response to genotoxic stress, cells employ diverse adaptive mechanisms to halt or exit the cell cycle temporarily or permanently. The intrinsic machinery of cycling, resting, and exiting shapes the cellular response to extrinsic stimuli, whereas prevalent disruption of the cell cycle machinery in tumor cells often confers resistance to anticancer therapy. Phosphatase and tensin homolog (PTEN) is a tumor suppressor and a guardian of the genome that is frequently mutated or deleted in human cancer. Moreover, it is increasingly evident that PTEN deficiency disrupts the fundamental processes of genetic transmission. Cells lacking PTEN exhibit cell cycle deregulation and cell fate reprogramming. Here, we review the role of PTEN in regulating the key processes in and out of cell cycle to optimize genomic integrity. Copyright © 2017 Elsevier Ltd. All rights reserved.

The therapeutic potential of cell cycle targeting in multiple myeloma.

PubMed

Maes, Anke; Menu, Eline; Veirman, Kim De; Maes, Ken; Vand Erkerken, Karin; De Bruyne, Elke

2017-10-27

Proper cell cycle progression through the interphase and mitosis is regulated by coordinated activation of important cell cycle proteins (including cyclin-dependent kinases and mitotic kinases) and several checkpoint pathways. Aberrant activity of these cell cycle proteins and checkpoint pathways results in deregulation of cell cycle progression, which is one of the key hallmarks of cancer. Consequently, intensive research on targeting these cell cycle regulatory proteins identified several candidate small molecule inhibitors that are able to induce cell cycle arrest and even apoptosis in cancer cells. Importantly, several of these cell cycle regulatory proteins have also been proposed as therapeutic targets in the plasma cell malignancy multiple myeloma (MM). Despite the enormous progress in the treatment of MM the past 5 years, MM still remains most often incurable due to the development of drug resistance. Deregulated expression of the cyclins D is observed in virtually all myeloma patients, emphasizing the potential therapeutic interest of cyclin-dependent kinase inhibitors in MM. Furthermore, other targets have also been identified in MM, such as microtubules, kinesin motor proteins, aurora kinases, polo-like kinases and the anaphase promoting complex/cyclosome. This review will provide an overview of the cell cycle proteins and checkpoint pathways deregulated in MM and discuss the therapeutic potential of targeting proteins or protein complexes involved in cell cycle control in MM.

NASA Lewis advanced IPV nickel-hydrogen technology

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Britton, Doris L.

1993-01-01

Individual pressure vessel (IPV) nickel-hydrogen technology was advanced at NASA Lewis and under Lewis contracts. Some of the advancements are as follows: to use 26 percent potassium hydroxide electrolyte to improve cycle life and performance, to modify the state of the art cell design to eliminate identified failure modes and further improve cycle life, and to develop a lightweight nickel electrode to reduce battery mass, hence reduce launch and/or increase satellite payload. A breakthrough in the LEO cycle life of individual pressure vessel nickel-hydrogen battery cells was reported. The cycle life of boiler plate cells containing 26 percent KOH electrolyte was about 40,000 accelerated LEO cycles at 80 percent DOD compared to 3,500 cycles for cells containing 31 percent KOH. Results of the boiler plate cell tests have been validated at NWSC, Crane, Indiana. Forty-eight ampere-hour flight cells containing 26 and 31 percent KOH have undergone real time LEO cycle life testing at an 80 percent DOD, 10 C. The three cells containing 26 percent KOH failed on the average at cycle 19,500. The three cells containing 31 percent KOH failed on the average at cycle 6,400. Validation testing of NASA Lewis 125 Ah advanced design IPV nickel-hydrogen flight cells is also being conducted at NWSC, Crane, Indiana under a NASA Lewis contract. This consists of characterization, storage, and cycle life testing. There was no capacity degradation after 52 days of storage with the cells in the discharged state, on open circuit, 0 C, and a hydrogen pressure of 14.5 psia. The catalyzed wall wick cells have been cycled for over 22,694 cycles with no cell failures in the continuing test. All three of the non-catalyzed wall wick cells failed (cycles 9,588; 13,900; and 20,575). Cycle life test results of the Fibrex nickel electrode has demonstrated the feasibility of an improved nickel electrode giving a higher specific energy nickel-hydrogen cell. A nickel-hydrogen boiler plate cell using an 80 mil thick, 90 percent porous Fibrex nickel electrode has been cycled for 10,000 cycles at 40 percent DOD.

Lunar map showing traverse plans for Apollo 14 lunar landing mission

NASA Image and Video Library

1970-09-01

This lunar map shows the traverse plans for the Apollo 14 lunar landing mission. Areas marked include Lunar module landing site, areas for the Apollo Lunar Surface Experiment Package (ALSEP) and areas for gathering of core samples.

Message passing with parallel queue traversal

DOEpatents

Underwood, Keith D [Albuquerque, NM; Brightwell, Ronald B [Albuquerque, NM; Hemmert, K Scott [Albuquerque, NM

2012-05-01

In message passing implementations, associative matching structures are used to permit list entries to be searched in parallel fashion, thereby avoiding the delay of linear list traversal. List management capabilities are provided to support list entry turnover semantics and priority ordering semantics.

Expanding the Detection of Traversable Area with RealSense for the Visually Impaired

PubMed Central

Yang, Kailun; Wang, Kaiwei; Hu, Weijian; Bai, Jian

2016-01-01

The introduction of RGB-Depth (RGB-D) sensors into the visually impaired people (VIP)-assisting area has stirred great interest of many researchers. However, the detection range of RGB-D sensors is limited by narrow depth field angle and sparse depth map in the distance, which hampers broader and longer traversability awareness. This paper proposes an effective approach to expand the detection of traversable area based on a RGB-D sensor, the Intel RealSense R200, which is compatible with both indoor and outdoor environments. The depth image of RealSense is enhanced with IR image large-scale matching and RGB image-guided filtering. Traversable area is obtained with RANdom SAmple Consensus (RANSAC) segmentation and surface normal vector estimation, preliminarily. A seeded growing region algorithm, combining the depth image and RGB image, enlarges the preliminary traversable area greatly. This is critical not only for avoiding close obstacles, but also for allowing superior path planning on navigation. The proposed approach has been tested on a score of indoor and outdoor scenarios. Moreover, the approach has been integrated into an assistance system, which consists of a wearable prototype and an audio interface. Furthermore, the presented approach has been proved to be useful and reliable by a field test with eight visually impaired volunteers. PMID:27879634

Numerical investigation of the relationship between magnetic stiffness and minor loop size in the HTS levitation system

NASA Astrophysics Data System (ADS)

Yang, Yong; Li, Chengshan

2017-10-01

The effect of minor loop size on the magnetic stiffness has not been paid attention to by most researchers in experimental and theoretical studies about the high temperature superconductor (HTS) magnetic levitation system. In this work, we numerically investigate the average magnetic stiffness obtained by the minor loop traverses Δz (or Δx) varying from 0.1 mm to 2 mm in zero field cooling and field cooling regimes, respectively. The approximate values of the magnetic stiffness with zero traverse are obtained using the method of linear extrapolation. Compared with the average magnetic stiffness gained by any minor loop traverse, these approximate values are Not always close to the average magnetic stiffness produced by the smallest size of minor loops. The relative deviation ranges of average magnetic stiffness gained by the usually minor loop traverse (1 or 2 mm) are presented by the ratios of approximate values to average stiffness for different moving processes and two typical cooling conditions. The results show that most of average magnetic stiffness are remarkably influenced by the sizes of minor loop, which indicates that the magnetic stiffness obtained by a single minor loop traverse Δ z or Δ x, for example, 1 or 2 mm, can be generally caused a large deviation.

Wear-Induced Changes in FSW Tool Pin Profile: Effect of Process Parameters

NASA Astrophysics Data System (ADS)

Sahlot, Pankaj; Jha, Kaushal; Dey, G. K.; Arora, Amit

2018-06-01

Friction stir welding (FSW) of high melting point metallic (HMPM) materials has limited application due to tool wear and relatively short tool life. Tool wear changes the profile of the tool pin and adversely affects weld properties. A quantitative understanding of tool wear and tool pin profile is crucial to develop the process for joining of HMPM materials. Here we present a quantitative wear study of H13 steel tool pin profile for FSW of CuCrZr alloy. The tool pin profile is analyzed at multiple traverse distances for welding with various tool rotational and traverse speeds. The results indicate that measured wear depth is small near the pin root and significantly increases towards the tip. Near the pin tip, wear depth increases with increase in tool rotational speed. However, change in wear depth near the pin root is minimal. Wear depth also increases with decrease in tool traverse speeds. Tool pin wear from the bottom results in pin length reduction, which is greater for higher tool rotational speeds, and longer traverse distances. The pin profile changes due to wear and result in root defect for long traverse distance. This quantitative understanding of tool wear would be helpful to estimate tool wear, optimize process parameters, and tool pin shape during FSW of HMPM materials.

Effect of cycling on the lithium/electrolyte interface in organic electrolytes

NASA Technical Reports Server (NTRS)

Surampudi, S.; Shen, D. H.; Huang, C.-K.; Narayanan, S. R.; Attia, A.; Halpert, G.; Peled, E.

1993-01-01

Nondestructive methods such as ac impedance spectroscopy and microcalorimetry are used to study the effect of cell cycling on the lithium/electrolyte interface. The reactivity of both uncycled and cycled lithium towards various electrolytes is examined by measuring the heat evolved from the cells under open-circuit conditions at 25 C by microcalorimetry. Cycled cells at the end of charge/discharge exhibited considerably higher heat output compared with the uncycled cells. After 30 d of storage, the heat output of the cycled cells is similar to that of the uncycled cells. The cell internal resistance increases with cycling, and this is attributed to the degradation of the electrolyte with cycling.

Cycle for Science: An informal outreach program connecting K-12 students with renewable energy and physics through miniature 3D-printed, solar-powered bicycles

NASA Astrophysics Data System (ADS)

Woods-Robinson, R.; Case, E.

2017-12-01

Engaging communities with renewable energy is key to fighting climate change. Cycle for Science, an innovative STEM outreach organization, has reached more than 3,000 K-12 students across the United States by bringing early-career female scientists into classrooms to teach basic physics and solar energy engineering through hands-on, DIY science activities. We designed a fleet of miniature, 3D-printed, solar-powered bicycles called "Sol Cycles" to use as teaching tools. Traveling by bicycle, Cycle for Science has brought them to rural and urban communities across the U.S. in two major efforts so far: one traversing the country (2015), and one through central California (2017). The program involves (1) introducing the scientists and why they value science, (2) running a skit to demonstrate how electrons and photons interact inside the solar panel, (3) assembling the Sol Cycles, (4) taking students outdoors to test the effects of variables (e.g. light intensity) on the Sol Cycles' movement, (5) and debriefing about the importance of renewable energy. In addition to physics and solar energy, the lessons teach the scientific process, provide tactile engagement with science, and introduce a platform to engage students with climate change impacts. By cycling to classrooms, we provide positive examples of low-impact transportation and a unique avenue for discussing climate action. It was important that this program extend beyond the trips, so the lesson and Sol Cycle design are open source to encourage teachers and students to play, change and improve the design, as well as incorporate new exercises (e.g. could you power the bicycle by wind?). Additionally, it has been permanently added to the XRaise Lending Library at Cornell University, so teachers across the world can implement the lesson. By sharing our project at AGU, we aim to connect with other scientists, educators, and concerned citizens about how to continue to bring renewable energy lessons into classrooms.

Temporal fluxomics reveals oscillations in TCA cycle flux throughout the mammalian cell cycle.

PubMed

Ahn, Eunyong; Kumar, Praveen; Mukha, Dzmitry; Tzur, Amit; Shlomi, Tomer

2017-11-06

Cellular metabolic demands change throughout the cell cycle. Nevertheless, a characterization of how metabolic fluxes adapt to the changing demands throughout the cell cycle is lacking. Here, we developed a temporal-fluxomics approach to derive a comprehensive and quantitative view of alterations in metabolic fluxes throughout the mammalian cell cycle. This is achieved by combining pulse-chase LC-MS-based isotope tracing in synchronized cell populations with computational deconvolution and metabolic flux modeling. We find that TCA cycle fluxes are rewired as cells progress through the cell cycle with complementary oscillations of glucose versus glutamine-derived fluxes: Oxidation of glucose-derived flux peaks in late G1 phase, while oxidative and reductive glutamine metabolism dominates S phase. These complementary flux oscillations maintain a constant production rate of reducing equivalents and oxidative phosphorylation flux throughout the cell cycle. The shift from glucose to glutamine oxidation in S phase plays an important role in cell cycle progression and cell proliferation. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Playing with the cell cycle to build the spinal cord.

PubMed

Molina, Angie; Pituello, Fabienne

2017-12-01

A fundamental issue in nervous system development and homeostasis is to understand the mechanisms governing the balance between the maintenance of proliferating progenitors versus their differentiation into post-mitotic neurons. Accumulating data suggest that the cell cycle and core regulators of the cell cycle machinery play a major role in regulating this fine balance. Here, we focus on the interplay between the cell cycle and cellular and molecular events governing spinal cord development. We describe the existing links between the cell cycle and interkinetic nuclear migration (INM). We show how the different morphogens patterning the neural tube also regulate the cell cycle machinery to coordinate proliferation and patterning. We give examples of how cell cycle core regulators regulate transcriptionally, or post-transcriptionally, genes involved in controlling the maintenance versus the differentiation of neural progenitors. Finally, we describe the changes in cell cycle kinetics occurring during neural tube patterning and at the time of neuronal differentiation, and we discuss future research directions to better understand the role of the cell cycle in cell fate decisions. Copyright © 2017 Elsevier Inc. All rights reserved.

Cell cycle proteins as promising targets in cancer therapy.

PubMed

Otto, Tobias; Sicinski, Piotr

2017-01-27

Cancer is characterized by uncontrolled tumour cell proliferation resulting from aberrant activity of various cell cycle proteins. Therefore, cell cycle regulators are considered attractive targets in cancer therapy. Intriguingly, animal models demonstrate that some of these proteins are not essential for proliferation of non-transformed cells and development of most tissues. By contrast, many cancers are uniquely dependent on these proteins and hence are selectively sensitive to their inhibition. After decades of research on the physiological functions of cell cycle proteins and their relevance for cancer, this knowledge recently translated into the first approved cancer therapeutic targeting of a direct regulator of the cell cycle. In this Review, we focus on proteins that directly regulate cell cycle progression (such as cyclin-dependent kinases (CDKs)), as well as checkpoint kinases, Aurora kinases and Polo-like kinases (PLKs). We discuss the role of cell cycle proteins in cancer, the rationale for targeting them in cancer treatment and results of clinical trials, as well as the future therapeutic potential of various cell cycle inhibitors.

Cell cycle nucleic acids, polypeptides and uses thereof

DOEpatents

Gordon-Kamm, William J [Urbandale, IA; Lowe, Keith S [Johnston, IA; Larkins, Brian A [Tucson, AZ; Dilkes, Brian R [Tucson, AZ; Sun, Yuejin [Westfield, IN

2007-08-14

The invention provides isolated nucleic acids and their encoded proteins that are involved in cell cycle regulation. The invention further provides recombinant expression cassettes, host cells, transgenic plants, and antibody compositions. The present invention provides methods and compositions relating to altering cell cycle protein content, cell cycle progression, cell number and/or composition of plants.

Quantitative Cell Cycle Analysis Based on an Endogenous All-in-One Reporter for Cell Tracking and Classification.

PubMed

Zerjatke, Thomas; Gak, Igor A; Kirova, Dilyana; Fuhrmann, Markus; Daniel, Katrin; Gonciarz, Magdalena; Müller, Doris; Glauche, Ingmar; Mansfeld, Jörg

2017-05-30

Cell cycle kinetics are crucial to cell fate decisions. Although live imaging has provided extensive insights into this relationship at the single-cell level, the limited number of fluorescent markers that can be used in a single experiment has hindered efforts to link the dynamics of individual proteins responsible for decision making directly to cell cycle progression. Here, we present fluorescently tagged endogenous proliferating cell nuclear antigen (PCNA) as an all-in-one cell cycle reporter that allows simultaneous analysis of cell cycle progression, including the transition into quiescence, and the dynamics of individual fate determinants. We also provide an image analysis pipeline for automated segmentation, tracking, and classification of all cell cycle phases. Combining the all-in-one reporter with labeled endogenous cyclin D1 and p21 as prime examples of cell-cycle-regulated fate determinants, we show how cell cycle and quantitative protein dynamics can be simultaneously extracted to gain insights into G1 phase regulation and responses to perturbations. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Interplay between cancer cell cycle and metabolism: Challenges, targets and therapeutic opportunities.

PubMed

Roy, Debmalya; Sheng, Gao Ying; Herve, Semukunzi; Carvalho, Evandro; Mahanty, Arpan; Yuan, Shengtao; Sun, Li

2017-05-01

A growing interest has emerged in the field of studying the cross-talk between cancer cell cycle and metabolism. In this review, we aimed to present how metabolism and cell cycle are correlated and how cancer cells get energy to drive cell cycle. Cell proliferation and cell death largely depend on the metabolic activity of the cell. Cell cycle proteins, e.g. cyclin D, cyclin dependent kinase (CDK), some pro-apoptotic and anti-apoptotic proteins, and P53 have been shown to be regulated by metabolic crosstalk. Dysregulation of this cross-talk between metabolism and cell cycle leads to degenerative disorder(s) and cancer. It is not fully understood the actual reason of aberration between metabolism and cell cycle, but it is a hallmark of cancer research. Herein, we discussed the role of some regulatory molecules relative of cell cycle and metabolism and highlight how they control the function of each other. We also pointed out, current therapeutic opportunities and some additional crucial therapeutic targets on these fields that could be a breakthrough in cancer research. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effect of KOH concentration on LEO cycle life of IPV nickel-hydrogen flight cells. An update

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Hall, Stephen W.

1991-01-01

An update of validation test results confirming the breakthrough in LEO cycle life of nickel-hydrogen cells containing 26 percent potassium hydroxide (KOH) electrolyte is presented. A breakthrough in the LEO cycle life of individual pressure vessel nickel-hydrogen cells is reported. The cycle life of boiler plate cells containing 26 percent KOH electrolyte was about 40,000 LEO cycles compared to 3500 cycles for cells containing 31 percent KOH.

Effect of KOH concentration on LEO cycle life of IPV nickel-hydrogen flight cells - An update

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Hall, Stephen W.

1991-01-01

An update of validation test results confirming the breakthrough in LEO cycle life of nickel-hydrogen cells containing 26 percent potassium hydroxide (KOH) electrolyte is presented. A breakthrough in the LEO cycle life of individual pressure vessel nickel-hydrogen cells is reported. The cycle life of boiler plate cells containing 26 percent KOH electrolyte was about 40,000 LEO cycles compared to 3500 cycles for cells containing 31 percent KOH.

Effect of LEO cycling on 125 Ah advanced design IPV nickel-hydrogen flight cells - An update

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Hall, Stephen W.

1991-01-01

An update of validation test results confirming the breakthrough in LEO cycle life of nickel-hydrogen cells containing 26 percent potassium hydroxide (KOH) electrolyte is presented. A breakthrough in the LEO cycle life of individual pressure vessel nickel-hydrogen cells is reported. The cycle life of boiler plate cells containing 26 percent KOH electrolyte was about 40,000 LEO cycles compared to 3500 cycles for cells containing 31 percent KOH.

Exploring the Underlying Mechanisms of the Xenopus laevis Embryonic Cell Cycle.

PubMed

Zhang, Kun; Wang, Jin

2018-05-31

The cell cycle is an indispensable process in proliferation and development. Despite significant efforts, global quantification and physical understanding are still challenging. In this study, we explored the mechanisms of the Xenopus laevis embryonic cell cycle by quantifying the underlying landscape and flux. We uncovered the Mexican hat landscape of the Xenopus laevis embryonic cell cycle with several local basins and barriers on the oscillation path. The local basins characterize the different phases of the Xenopus laevis embryonic cell cycle, and the local barriers represent the checkpoints. The checkpoint mechanism of the cell cycle is revealed by the landscape basins and barriers. While landscape shape determines the stabilities of the states on the oscillation path, the curl flux force determines the stability of the cell cycle flow. Replication is fundamental for biology of living cells. We quantify the input energy (through the entropy production) as the thermodynamic requirement for initiation and sustainability of single cell life (cell cycle). Furthermore, we also quantify curl flux originated from the input energy as the dynamical requirement for the emergence of a new stable phase (cell cycle). This can provide a new quantitative insight for the origin of single cell life. In fact, the curl flux originated from the energy input or nutrition supply determines the speed and guarantees the progression of the cell cycle. The speed of the cell cycle is a hallmark of cancer. We characterized the quality of the cell cycle by the coherence time and found it is supported by the flux and energy cost. We are also able to quantify the degree of time irreversibility by the cross correlation function forward and backward in time from the stochastic traces in the simulation or experiments, providing a way for the quantification of the time irreversibility and the flux. Through global sensitivity analysis upon landscape and flux, we can identify the key elements for controlling the cell cycle speed. This can help to design an effective strategy for drug discovery against cancer.

ESCRT-I function is required for Tyrp1 transport from early endosomes to the melanosome limiting membrane

PubMed Central

Truschel, Steven T.; Simoes, Sabrina; Setty, Subba Rao Gangi; Harper, Dawn C.; Tenza, Danièle; Thomas, Penelope C.; Herman, Kathryn E.; Sackett, Sara D.; Cowan, David C.; Theos, Alexander C.; Raposo, Graça; Marks, Michael S.

2009-01-01

Melanosomes are lysosome-related organelles that coexist with lysosomes within melanocytes. The pathways by which melanosomal proteins are diverted from endocytic organelles toward melanosomes are incompletely defined. In melanocytes from mouse models of Hermansky-Pudlak syndrome (HPS) that lack BLOC-1, melanosomal proteins such as Tyrp1 accumulate in early endosomes. Whether this accumulation represents an anomalous pathway or an arrested normal intermediate in melanosome protein trafficking is not clear. Here we show that early endosomes are requisite intermediates in the trafficking of Tyrp1 from the Golgi to late stage melanosomes in normal melanocytic cells. Kinetic analyses show that very little newly synthesized Tyrp1 traverses the cell surface and that internalized Tyrp1 is inefficiently sorted to melanosomes. Nevertheless, nearly all Tyrp1 traverses early endosomes since it becomes trapped within enlarged, modified endosomes upon overexpression of Hrs. Although Tyrp1 localization is not affected by Hrs depletion, depletion of the ESCRT-I component, Tsg101, or inhibition of ESCRT function by dominant negative approaches results in a dramatic redistribution of Tyrp1 to aberrant endosomal membranes that are largely distinct from those harboring traditional ESCRT-dependent, ubiquitylated cargoes such as MART-1. The lysosomal protein content of some of these membranes and the lack of Tyrp1 recycling to the plasma membrane in Tsg101-depleted cells suggests that ESCRT-I functions downstream of BLOC-1. Our data delineate a novel pathway for Tyrp1 trafficking and illustrate a requirement for ESCRT-I function in controlling protein sorting from vacuolar endosomes to the limiting membrane of a lysosome-related organelle. PMID:19624486

Effect of KOH concentration on LEO cycle life of IPV nickel-hydrogen flight cells-update 2

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Hall, Stephen W.

1991-01-01

An update of validation test results confirming the breakthrough in low earth orbit (LEO) cycle life of nickel-hydrogen cells containing 26 percent KOH electrolyte is presented. A breakthrough in the LEO cycle life of individual pressure vessel (IPV nickel-hydrogen cells has been previously reported. The cycle life of boiler plate cells containing 26 percent potassium hydroxide (KOH) electrolyte was about 40 000 LEO cycles compared to 3500 cycles for cells containing 31 percent KOH. This test was conducted at Hughes Aircraft Company under a NASA Lewis contract. The purpose was to investigate the effect of KOH concentration on cycle life. The cycle regime was a stressful accelerated LEO, which consisted of a 27.5 min charge followed by a 17.5 min discharge (2x normal rate). The depth of discharge (DOD) was 80 percent. The cell temperature was maintained at 23 C. The boiler plate test results are in the process of being validated using flight hardware and real time LEO test at the Naval Weapons Support Center (NWSC), Crane, Indiana under a NASA Lewis Contract. Six 48 Ah Hughes recirculation design IPV nickel-hydrogen flight battery cells are being evaluated. Three of the cells contain 26 percent KOH (test cells), and three contain 31 percent KOH (control cells). They are undergoing real time LEO cycle life testing. The cycle regime is a 90-min LEO orbit consisting of a 54-min charge followed by a 36-min discharge. The depth-of-discharge is 80 percent. The cell temperature is maintained at 10 C. The three 31 percent KOH cells failed (cycles 3729, 4165, and 11355). One of the 26 percent KOH cells failed at cycle 15314. The other two 26 percent KOH cells were cycled for over 16600 cycles during the continuing test.

Cell-cycle control in the face of damage--a matter of life or death.

PubMed

Clarke, Paul R; Allan, Lindsey A

2009-03-01

Cells respond to DNA damage or defects in the mitotic spindle by activating checkpoints that arrest the cell cycle. Alternatively, damaged cells can undergo cell death by the process of apoptosis. The correct balance between these pathways is important for the maintenance of genomic integrity while preventing unnecessary cell death. Although the molecular mechanisms of the cell cycle and apoptosis have been elucidated, the links between them have not been clear. Recent work, however, indicates that common components directly link the regulation of apoptosis with cell-cycle checkpoints operating during interphase, whereas in mitosis, the control of apoptosis is directly coupled to the cell-cycle machinery. These findings shed new light on how the balance between cell-cycle progression and cell death is controlled.

The cell cycle of early mammalian embryos: lessons from genetic mouse models.

PubMed

Artus, Jérôme; Babinet, Charles; Cohen-Tannoudji, Michel

2006-03-01

Genes coding for cell cycle components predicted to be essential for its regulation have been shown to be dispensable in mice, at the whole organism level. Such studies have highlighted the extraordinary plasticity of the embryonic cell cycle and suggest that many aspects of in vivo cell cycle regulation remain to be discovered. Here, we discuss the particularities of the mouse early embryonic cell cycle and review the mutations that result in cell cycle defects during mouse early embryogenesis, including deficiencies for genes of the cyclin family (cyclin A2 and B1), genes involved in cell cycle checkpoints (Mad2, Bub3, Chk1, Atr), genes involved in ubiquitin and ubiquitin-like pathways (Uba3, Ubc9, Cul1, Cul3, Apc2, Apc10, Csn2) as well as genes the function of which had not been previously ascribed to cell cycle regulation (Cdc2P1, E4F and Omcg1).

40 CFR Appendix A-1 to Part 60 - Test Methods 1 through 2F

Code of Federal Regulations, 2012 CFR

2012-07-01

... points are combined to form a single adjusted traverse point, treat the adjusted point as two separate... checks during the traverse (at least once per hour). Record all necessary data on a form similar to that...

40 CFR Appendix A-1 to Part 60 - Test Methods 1 through 2F

Code of Federal Regulations, 2010 CFR

2010-07-01

... points are combined to form a single adjusted traverse point, treat the adjusted point as two separate... checks during the traverse (at least once per hour). Record all necessary data on a form similar to that...

40 CFR Appendix A-1 to Part 60 - Test Methods 1 through 2F

Code of Federal Regulations, 2013 CFR

2013-07-01

... points are combined to form a single adjusted traverse point, treat the adjusted point as two separate... checks during the traverse (at least once per hour). Record all necessary data on a form similar to that...

40 CFR Appendix A-1 to Part 60 - Test Methods 1 through 2F

Code of Federal Regulations, 2011 CFR

2011-07-01

... points are combined to form a single adjusted traverse point, treat the adjusted point as two separate... checks during the traverse (at least once per hour). Record all necessary data on a form similar to that...

Model-Based Analysis of Cell Cycle Responses to Dynamically Changing Environments

PubMed Central

Seaton, Daniel D; Krishnan, J

2016-01-01

Cell cycle progression is carefully coordinated with a cell’s intra- and extracellular environment. While some pathways have been identified that communicate information from the environment to the cell cycle, a systematic understanding of how this information is dynamically processed is lacking. We address this by performing dynamic sensitivity analysis of three mathematical models of the cell cycle in Saccharomyces cerevisiae. We demonstrate that these models make broadly consistent qualitative predictions about cell cycle progression under dynamically changing conditions. For example, it is shown that the models predict anticorrelated changes in cell size and cell cycle duration under different environments independently of the growth rate. This prediction is validated by comparison to available literature data. Other consistent patterns emerge, such as widespread nonmonotonic changes in cell size down generations in response to parameter changes. We extend our analysis by investigating glucose signalling to the cell cycle, showing that known regulation of Cln3 translation and Cln1,2 transcription by glucose is sufficient to explain the experimentally observed changes in cell cycle dynamics at different glucose concentrations. Together, these results provide a framework for understanding the complex responses the cell cycle is capable of producing in response to dynamic environments. PMID:26741131

A dual-color marker system for in vivo visualization of cell cycle progression in Arabidopsis.

PubMed

Yin, Ke; Ueda, Minako; Takagi, Hitomi; Kajihara, Takehiro; Sugamata Aki, Shiori; Nobusawa, Takashi; Umeda-Hara, Chikage; Umeda, Masaaki

2014-11-01

Visualization of the spatiotemporal pattern of cell division is crucial to understand how multicellular organisms develop and how they modify their growth in response to varying environmental conditions. The mitotic cell cycle consists of four phases: S (DNA replication), M (mitosis and cytokinesis), and the intervening G1 and G2 phases; however, only G2/M-specific markers are currently available in plants, making it difficult to measure cell cycle duration and to analyze changes in cell cycle progression in living tissues. Here, we developed another cell cycle marker that labels S-phase cells by manipulating Arabidopsis CDT1a, which functions in DNA replication origin licensing. Truncations of the CDT1a coding sequence revealed that its carboxy-terminal region is responsible for proteasome-mediated degradation at late G2 or in early mitosis. We therefore expressed this region as a red fluorescent protein fusion protein under the S-specific promoter of a histone 3.1-type gene, HISTONE THREE RELATED2 (HTR2), to generate an S/G2 marker. Combining this marker with the G2/M-specific CYCB1-GFP marker enabled us to visualize both S to G2 and G2 to M cell cycle stages, and thus yielded an essential tool for time-lapse imaging of cell cycle progression. The resultant dual-color marker system, Cell Cycle Tracking in Plant Cells (Cytrap), also allowed us to identify root cells in the last mitotic cell cycle before they entered the endocycle. Our results demonstrate that Cytrap is a powerful tool for in vivo monitoring of the plant cell cycle, and thus for deepening our understanding of cell cycle regulation in particular cell types during organ development. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

A Short-Term Advantage for Syngamy in the Origin of Eukaryotic Sex: Effects of Cell Fusion on Cell Cycle Duration and Other Effects Related to the Duration of the Cell Cycle—Relationship between Cell Growth Curve and the Optimal Size of the Species, and Circadian Cell Cycle in Photosynthetic Unicellular Organisms

PubMed Central

Mancebo Quintana, J. M.; Mancebo Quintana, S.

2012-01-01

The origin of sex is becoming a vexatious issue for Evolutionary Biology. Numerous hypotheses have been proposed, based on the genetic effects of sex, on trophic effects or on the formation of cysts and syncytia. Our approach addresses the change in cell cycle duration which would cause cell fusion. Several results are obtained through graphical and mathematical analysis and computer simulations. (1) In poor environments, cell fusion would be an advantageous strategy, as fusion between cells of different size shortens the cycle of the smaller cell (relative to the asexual cycle), and the majority of mergers would occur between cells of different sizes. (2) The easiest-to-evolve regulation of cell proliferation (sexual/asexual) would be by modifying the checkpoints of the cell cycle. (3) A regulation of this kind would have required the existence of the G2 phase, and sex could thus be the cause of the appearance of this phase. Regarding cell cycle, (4) the exponential curve is the only cell growth curve that has no effect on the optimal cell size in unicellular species; (5) the existence of a plateau with no growth at the end of the cell cycle explains the circadian cell cycle observed in unicellular algae. PMID:22666626

Cell Cycle Regulation of Stem Cells by MicroRNAs.

PubMed

Mens, Michelle M J; Ghanbari, Mohsen

2018-06-01

MicroRNAs (miRNAs) are a class of small non-coding RNA molecules involved in the regulation of gene expression. They are involved in the fine-tuning of fundamental biological processes such as proliferation, differentiation, survival and apoptosis in many cell types. Emerging evidence suggests that miRNAs regulate critical pathways involved in stem cell function. Several miRNAs have been suggested to target transcripts that directly or indirectly coordinate the cell cycle progression of stem cells. Moreover, previous studies have shown that altered expression levels of miRNAs can contribute to pathological conditions, such as cancer, due to the loss of cell cycle regulation. However, the precise mechanism underlying miRNA-mediated regulation of cell cycle in stem cells is still incompletely understood. In this review, we discuss current knowledge of miRNAs regulatory role in cell cycle progression of stem cells. We describe how specific miRNAs may control cell cycle associated molecules and checkpoints in embryonic, somatic and cancer stem cells. We further outline how these miRNAs could be regulated to influence cell cycle progression in stem cells as a potential clinical application.

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.

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

Site selection and traverse planning to support a lunar polar rover mission: A case study at Haworth Crater

NASA Astrophysics Data System (ADS)

Heldmann, Jennifer L.; Colaprete, Anthony; Elphic, Richard C.; Bussey, Ben; McGovern, Andrew; Beyer, Ross; Lees, David; Deans, Matt

2016-10-01

Studies of lunar polar volatile deposits are of interest for scientific purposes to understand the nature and evolution of the volatiles, and also for exploration reasons as a possible in situ resource to enable long term human exploration and settlement of the Moon. Both theoretical and observational studies have suggested that significant quantities of volatiles exist in the polar regions, although the lateral and horizontal distribution remains unknown at the km scale and finer resolution. A lunar polar rover mission is required to further characterize the distribution, quantity, and character of lunar polar volatile deposits at these higher spatial resolutions. Here we present a case study for NASA's Resource Prospector (RP) mission concept for a lunar polar rover and utilize this mission architecture and associated constraints to evaluate whether a suitable landing site exists to support an RP flight mission. We evaluate the landing site criteria to characterize the Haworth Crater region in terms of expected hydrogen abundance, surface topography, and prevalence of shadowed regions, as well as solar illumination and direct to Earth communications as a function of time to develop a notional rover traverse plan that addresses both science and engineering requirements. We also present lessons-learned regarding lunar traverse path planning focusing on the critical nature of landing site selection, the influence of illumination patterns on traverse planning, the effects of performing shadowed rover operations, the influence of communications coverage on traverse plan development, and strategic planning to maximize rover lifetime and science at end of mission. Here we present a detailed traverse path scenario for a lunar polar volatiles rover mission and find that the particular site north of Haworth Crater studied here is suitable for further characterization of polar volatile deposits.

Mobile robots traversability awareness based on terrain visual sensory data fusion

NASA Astrophysics Data System (ADS)

Shirkhodaie, Amir

2007-04-01

In this paper, we have presented methods that significantly improve the robot awareness of its terrain traversability conditions. The terrain traversability awareness is achieved by association of terrain image appearances from different poses and fusion of extracted information from multimodality imaging and range sensor data for localization and clustering environment landmarks. Initially, we describe methods for extraction of salient features of the terrain for the purpose of landmarks registration from two or more images taken from different via points along the trajectory path of the robot. The method of image registration is applied as a means of overlaying (two or more) of the same terrain scene at different viewpoints. The registration geometrically aligns salient landmarks of two images (the reference and sensed images). A Similarity matching techniques is proposed for matching the terrain salient landmarks. Secondly, we present three terrain classifier models based on rule-based, supervised neural network, and fuzzy logic for classification of terrain condition under uncertainty and mapping the robot's terrain perception to apt traversability measures. This paper addresses the technical challenges and navigational skill requirements of mobile robots for traversability path planning in natural terrain environments similar to Mars surface terrains. We have described different methods for detection of salient terrain features based on imaging texture analysis techniques. We have also presented three competing techniques for terrain traversability assessment of mobile robots navigating in unstructured natural terrain environments. These three techniques include: a rule-based terrain classifier, a neural network-based terrain classifier, and a fuzzy-logic terrain classifier. Each proposed terrain classifier divides a region of natural terrain into finite sub-terrain regions and classifies terrain condition exclusively within each sub-terrain region based on terrain spatial and textural cues.

Scratch2 prevents cell cycle re-entry by repressing miR-25 in postmitotic primary neurons.

PubMed

Rodríguez-Aznar, Eva; Barrallo-Gimeno, Alejandro; Nieto, M Angela

2013-03-20

During the development of the nervous system the regulation of cell cycle, differentiation, and survival is tightly interlinked. Newly generated neurons must keep cell cycle components under strict control, as cell cycle re-entry leads to neuronal degeneration and death. However, despite their relevance, the mechanisms controlling this process remain largely unexplored. Here we show that Scratch2 is involved in the control of the cell cycle in neurons in the developing spinal cord of the zebrafish embryo. scratch2 knockdown induces postmitotic neurons to re-enter mitosis. Scratch2 prevents cell cycle re-entry by maintaining high levels of the cycle inhibitor p57 through the downregulation of miR-25. Thus, Scratch2 appears to safeguard the homeostasis of postmitotic primary neurons by preventing cell cycle re-entry.

An extensive program of periodic alternative splicing linked to cell cycle progression

PubMed Central

Dominguez, Daniel; Tsai, Yi-Hsuan; Weatheritt, Robert; Wang, Yang; Blencowe, Benjamin J; Wang, Zefeng

2016-01-01

Progression through the mitotic cell cycle requires periodic regulation of gene function at the levels of transcription, translation, protein-protein interactions, post-translational modification and degradation. However, the role of alternative splicing (AS) in the temporal control of cell cycle is not well understood. By sequencing the human transcriptome through two continuous cell cycles, we identify ~1300 genes with cell cycle-dependent AS changes. These genes are significantly enriched in functions linked to cell cycle control, yet they do not significantly overlap genes subject to periodic changes in steady-state transcript levels. Many of the periodically spliced genes are controlled by the SR protein kinase CLK1, whose level undergoes cell cycle-dependent fluctuations via an auto-inhibitory circuit. Disruption of CLK1 causes pleiotropic cell cycle defects and loss of proliferation, whereas CLK1 over-expression is associated with various cancers. These results thus reveal a large program of CLK1-regulated periodic AS intimately associated with cell cycle control. DOI: http://dx.doi.org/10.7554/eLife.10288.001 PMID:27015110

A new perspective of carcinogenesis from protracted high-let radiation arises from the two-stage clonal expansion model

NASA Astrophysics Data System (ADS)

Curtis, S. B.; Luebeck, E. G.; Hazelton, W. D.; Moolgavkar, S. H.

When applied to the Colorado Plateau miner population, the two-stage clonal expansion (TSCE) model of radiation carcinogenesis predicts that radiation-induced promotion dominates radiation-induced initiation. Thus, according to the model, at least for alpha-particle radiation from inhaled radon daughters, lung cancer induction over long periods of protracted irradiation appears to be dominated by radiation-induced modification of the proliferation kinetics of already-initiated cells rather than by direct radiation-induced initiation (i.e., mutation) of normal cells. We explore the possible consequences of this result for radiation exposures to space travelers on long missions. Still unknown is the LET dependence of this effect. Speculations of the cause of this phenomenon include the suggestion that modification of cell kinetics is caused by a "bystander" effect, i.e., the traversal of normal cells by alpha particles, followed by the signaling of these cells to nearby initiated cells which then modify their proliferation kinetics.

Cellular telephone use during free-living walking significantly reduces average walking speed.

PubMed

Barkley, Jacob E; Lepp, Andrew

2016-03-31

Cellular telephone (cell phone) use decreases walking speed in controlled laboratory experiments and there is an inverse relationship between free-living walking speed and heart failure risk. The purpose of this study was to examine the impact of cell phone use on walking speed in a free-living environment. Subjects (n = 1142) were randomly observed walking on a 50 m University campus walkway. The time it took each subject to walk 50 m was recorded and subjects were coded into categories: cell phone held to the ear (talking, n = 95), holding and looking at the cell phone (texting, n = 118), not visibly using the cell phone (no use, n = 929). Subjects took significantly (p < 0.001) longer traversing the walkway when talking (39.3 s) and texting (37.9 s) versus no use (35.3 s). As was the case with the previous laboratory experiments, cell phone use significantly reduces average speed during free-living walking.

Multiscale Model of Swarming Bacteria

NASA Astrophysics Data System (ADS)

Alber, Mark

2011-03-01

Many bacteria can rapidly traverse surfaces from which they are extracting nutrient for growth. They generate flat, spreading colonies, called swarms because they resemble swarms of insects. In the beginning of the talk, swarms of the M. xanthus will be described in detail. Individual M. xanthus cells are elongated; they always move in the direction of their long axis; and they are in constant motion, repeatedly touching each other. As a cell glides, the slime capsule of a cell interacts with the bare agar surface, non-oriented slime which arises from the surface contact with the slime capsule, or oriented slime trails. Remarkably, cells regularly reverse their gliding directions. In this talk a detailed cell- and behavior-based computational model of M. xanthus swarming will be used to demonstrate that reversals of gliding direction and cell bending are essential for swarming and that specific reversal frequencies result in optimal swarming rate of the whole population. This suggests that the circuit regulating reversals evolved to its current sensitivity under selection for growth achieved by swarming.

Mechanism of hard-nanomaterial clearance by the liver.

PubMed

Tsoi, Kim M; MacParland, Sonya A; Ma, Xue-Zhong; Spetzler, Vinzent N; Echeverri, Juan; Ouyang, Ben; Fadel, Saleh M; Sykes, Edward A; Goldaracena, Nicolas; Kaths, Johann M; Conneely, John B; Alman, Benjamin A; Selzner, Markus; Ostrowski, Mario A; Adeyi, Oyedele A; Zilman, Anton; McGilvray, Ian D; Chan, Warren C W

2016-11-01

The liver and spleen are major biological barriers to translating nanomedicines because they sequester the majority of administered nanomaterials and prevent delivery to diseased tissue. Here we examined the blood clearance mechanism of administered hard nanomaterials in relation to blood flow dynamics, organ microarchitecture and cellular phenotype. We found that nanomaterial velocity reduces 1,000-fold as they enter and traverse the liver, leading to 7.5 times more nanomaterial interaction with hepatic cells relative to peripheral cells. In the liver, Kupffer cells (84.8 ± 6.4%), hepatic B cells (81.5 ± 9.3%) and liver sinusoidal endothelial cells (64.6 ± 13.7%) interacted with administered PEGylated quantum dots, but splenic macrophages took up less material (25.4 ± 10.1%) due to differences in phenotype. The uptake patterns were similar for two other nanomaterial types and five different surface chemistries. Potential new strategies to overcome off-target nanomaterial accumulation may involve manipulating intra-organ flow dynamics and modulating the cellular phenotype to alter hepatic cell interactions.

Analysis of growth of tetraploid nuclei in roots of Vicia faba.

PubMed

Bansal, J; Davidson, D

1978-03-01

Growth of nuclei of a marked population of cells was determined from G1 to prophase in roots of Vicia faba. The cells were marked by inducing them to become tetraploid by treatment with 0.002% colchicine for 1 hr. Variation in nuclear volume is large; it is established in early G1 and maintained through interphase and into prophase. One consequence of this variation is that there is considerable overlap between volumes of nuclei of different ages in the cell cycle; nuclear volume, we suggest, cannot be used as an accurate indicator of the age of the cell in its growth cycle. Nuclei exhibit considerable variation in their growth rate through the cell cycle. Of the marked population of cells, about 65% had completed a cell cycle 14--15 hr after they were formed. These tetraploid nuclei have a cell cycle duration similar to that of fast cycling diploid cells of the same roots. Since they do complete a cell cycle, at least 65% of the nuclei studied must come from rapidly proliferating cells, showing that variability in nuclear volumes must be present in growing cells and cannot be attributed solely to the presence, in our samples, of non-cycling cells.

Flow cytometry analysis of cell cycle and specific cell synchronization with butyrate

USDA-ARS?s Scientific Manuscript database

Synchronized cells have been invaluable in many kinds of cell cycle and cell proliferation studies. Butyrate induces cell cycle arrest and apoptosis in MDBK cells. The possibility of using butyrate-blocked cells to obtain synchronized cells was explored and the properties of butyrate-induced cell ...

The sea as science: ocean research institutions and strategies in Portugal in the twentieth century (from the First Republic to democracy).

PubMed

Rollo, Maria Fernanda; Queiroz, Maria Inês; Brandão, Tiago

2014-01-01

Historical perspective has revealed the many aspects of Portugal's interest in the sea, evident in a series of initiatives and entities throughout the twentieth century. From the beginning of the century until the 1974 Revolution, the genesis of organizations devoted to the scientific study of the sea is analyzed, observing their specific missions in the context of the formulation of science policy, and more specifically "ocean policies." The Portuguese valued knowledge of the sea due to their maritime vocation, coastal life and geographic position. Traversing different historical and political contexts and development cycles, the assumptions and political implications that accentuate the strategic dimension of science policy, visible in the geopolitical affirmation of oceanography, are studied.

Bard Denali inferior vena cava filter fracture and embolization resulting in cardiac tamponade: a device failure analysis.

PubMed

Kuo, William T; Robertson, Scott W

2015-01-01

A 46-year-old woman underwent inferior vena cava filter placement before bariatric surgery and returned within 6 months for routine removal. She complained of a 1-week history of severe chest pain, and during retrieval, two fractured filter components were identified including one arm in the right ventricle. The filter body and one fragment were successfully retrieved, but the fragment in the right ventricle was refractory to percutaneous retrieval. During open-heart surgery, the fragment was found traversing through the ventricular wall resulting in cardiac tamponade. Electron microscopic fragment analysis revealed high-cycle metal fatigue indicating the filter design failed to withstand this patient's natural inferior vena cava biomechanical motions. Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.

Effect of KOH concentration on LEO cycle life of IPV nickel-hydrogen flight battery cells

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Hall, Stephen W.

1990-01-01

A breakthrough in low earth orbit (LEO) cycle life of individual pressure vessel (IPV) nickel hydrogen battery cells was reported. The cycle life of boiler plate cells containing 26 percent potassium hydroxide (KOH) electrolyte was about 40,000 LEO cycles compared to 3500 cycles for cells containing 31 percent KOH. The effect of KOH concentration on cycle life was studied. The cycle regime was a stressful accelerated LEO, which consisted of a 27.5 min charge followed by a 17.5 min charge (2 x normal rate). The depth of discharge (DOD) was 80 percent. The cell temperature was maintained at 23 C. The next step is to validate these results using flight hardware and a real time LEO test. NASA Lewis has a contract with the Naval Weapons Support Center (NWSC), Crane, Indiana, to validate the boiler plate test results. Six 48 A-hr Hughes recirculation design IPV nickel-hydrogen flight battery cells are being evaluated. Three of the cells contain 26 percent KOH (test cells) and three contain 31 percent KOH (control cells). They are undergoing real time LEO cycle life testing. The cycle regime is a 90-min LEO orbit consisting of a 54-min charge followed by a 36-min discharge. The depth-of-discharge is 80 percent. The cell temperature is maintained at 10 C. The cells were cycled for over 8000 cycles in the continuing test. There were no failures for the cells containing 26 percent KOH. There was two failures, however, for the cells containing 31 percent KOH.

Effect of KOH concentration on LEO cycle life of IPV nickel-hydrogen flight battery cells

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Hall, Stephen W.

1990-01-01

A breakthrough in the low-earth-orbit (LEO) cycle life of individual pressure vessel (IPV) nickel hydrogen battery cells is reported. The cycle life of boiler plate cells containing 26 percent potassium hydroxide (KOH) electrolyte was about 40,000 LEO cycles compared to 3500 cycles for cells containing 31 percent KOH. The effect of KOH concentration on cycle life was studied. The cycle regime was a stressful accelerated LEO, which consisted of a 27.5 min charge followed by a 17.5 min charge (2 x normal rate). The depth of discharge (DOD) was 80 percent. The cell temperature was maintained at 23 C. The next step is to validate these results using flight hardware and real time LEO test. NASA Lewis has a contract with the Naval Weapons Support Center (NWSC), Crane, Indiana to validate the boiler plate test results. Six 48 A-hr Hughes recirculation design IPV nickel-hydrogen flight battery cells are being evaluated. Three of the cells contain 26 percent KOH (test cells) and three contain 31 percent KOH (control cells). They are undergoing real time LEO cycle life testing. The cycle regime is a 90-min LEO orbit consisting of a 54-min charge followed by a 36-min discharge. The depth-of-discharge is 80 percent. The cell temperature is maintained at 10 C. The cells were cycled for over 8000 cycles in the continuing test. There were no failures for the cells containing 26 percent KOH. There were two failures, however, for the cells containing 31 percent KOH.

Genome mapping

USDA-ARS?s Scientific Manuscript database

Genome maps can be thought of much like road maps except that, instead of traversing across land, they traverse across the chromosomes of an organism. Genetic markers serve as landmarks along the chromosome and provide researchers information as to how close they may be to a gene or region of inter...

Conformally symmetric traversable wormholes

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

Boehmer, Christian G.; Harko, Tiberiu; Lobo, Francisco S. N.

2007-10-15

Exact solutions of traversable wormholes are found under the assumption of spherical symmetry and the existence of a nonstatic conformal symmetry, which presents a more systematic approach in searching for exact wormhole solutions. In this work, a wide variety of solutions are deduced by considering choices for the form function, a specific linear equation of state relating the energy density and the pressure anisotropy, and various phantom wormhole geometries are explored. A large class of solutions impose that the spatial distribution of the exotic matter is restricted to the throat neighborhood, with a cutoff of the stress-energy tensor at amore » finite junction interface, although asymptotically flat exact solutions are also found. Using the 'volume integral quantifier', it is found that the conformally symmetric phantom wormhole geometries may, in principle, be constructed by infinitesimally small amounts of averaged null energy condition violating matter. Considering the tidal acceleration traversability conditions for the phantom wormhole geometry, specific wormhole dimensions and the traversal velocity are also deduced.« less

Visual terrain mapping for traversable path planning of mobile robots

NASA Astrophysics Data System (ADS)

Shirkhodaie, Amir; Amrani, Rachida; Tunstel, Edward W.

2004-10-01

In this paper, we have primarily discussed technical challenges and navigational skill requirements of mobile robots for traversability path planning in natural terrain environments similar to Mars surface terrains. We have described different methods for detection of salient terrain features based on imaging texture analysis techniques. We have also presented three competing techniques for terrain traversability assessment of mobile robots navigating in unstructured natural terrain environments. These three techniques include: a rule-based terrain classifier, a neural network-based terrain classifier, and a fuzzy-logic terrain classifier. Each proposed terrain classifier divides a region of natural terrain into finite sub-terrain regions and classifies terrain condition exclusively within each sub-terrain region based on terrain visual clues. The Kalman Filtering technique is applied for aggregative fusion of sub-terrain assessment results. The last two terrain classifiers are shown to have remarkable capability for terrain traversability assessment of natural terrains. We have conducted a comparative performance evaluation of all three terrain classifiers and presented the results in this paper.

IGY to IPY, the U.S. Antarctic oversnow and airborne geophysical-glaciological research program from 1957 to 1964 from the view of a young graduate student

USGS Publications Warehouse

Behrendt, John C.

2007-01-01

When 12 countries established scientific stations in Antarctica for the 1957-58 (IGY), the Cold War was at its height, seven countries had made claims in Antarctica, and the Antarctic Treaty was in the future. The only major field project of the U.S. IGY Antarctic program was series of oversnow traverses, starting in 1957, making seismic reflection ice soundings (and other geophysical measurements) and glaciological studies. The U.S.S.R. and France made similar traverses coordinated through the IGY. Although geology and topographic mapping were not part of the IGY program because of the claims issue and the possibility of mineral resources, the oversnow traverse parties did geologic work, during which unknown mountains were discovered. The oversnow traverses continued through 1966 and resulted in an excellent first approximation of the snow surface elevation, ice thickness and bed topography of Antarctica, as well as the mean annual temperature of that era and snow accumulation.

Driving ATHLETE: Analysis of Operational Efficiency

NASA Technical Reports Server (NTRS)

Townsend, Julie; Mittman, David

2012-01-01

The All-Terrain Hex-Limbed Extra-Terrestrial Explorer (ATHLETE) is a modular mobility and manipulation platform being developed to support NASA operations in a variety of missions, including exploration of planetary surfaces. The agile system consists of a symmetrical arrangement of six limbs, each with seven articulated degrees of freedom and a powered wheel. This design enables transport of bulky payloads over a wide range of terrain and is envisioned as a tool to mobilize habitats, power-generation equipment, and other supplies for long-range exploration and outpost construction. In FY2010, ATHLETE traversed more than 80 km in field environments over eight weeks of testing, demonstrating that the concept is well suited to long-range travel. Although ATHLETE is designed to travel at speeds of up to 5 kilometers per hour, the observed average traverse rate during field-testing rarely exceeded 1.5 kilometers per hour. This paper investigates sources of inefficiency in ATHLETE traverse operations and identifies targets for improvement of overall traverse rate.

Driving ATHLETE: Analysis of Operational Efficiency

NASA Technical Reports Server (NTRS)

Townsend, Julie; Mittman, David

2012-01-01

The All-Terrain Hex-Limbed Extra-Terrestrial Explorer (ATHLETE) is a modular mobility and manipulation platform being developed to support NASA operations in a variety of missions, including exploration of planetary surfaces. The agile system consists of a symmetrical arrangement of six limbs, each with seven articulated degrees of freedom and a powered wheel. This design enables transport of bulky payloads over a wide range of terrain and is envisioned as a tool to mobilize habitats, power-generation equipment, and other supplies for long-range exploration and outpost construction. In 2010, ATHLETE traversed more than 80 km in field environments over eight weeks of testing, demonstrating that the concept is well suited to long-range travel. However, while ATHLETE is designed to travel at speeds of up to 5 kilometers per hour, the observed average traverse rate during field-testing rarely exceeded 1.5 kilometers per hour. This paper investigates sources of inefficiency in ATHLETE traverse operations and identifies targets for improvement of overall traverse rate.

Cell cycle in egg cell and its progression during zygotic development in rice.

PubMed

Sukawa, Yumiko; Okamoto, Takashi

2018-03-01

Rice egg is arrested at G1 phase probably by OsKRP2. After fusion with sperm, karyogamy, OsWEE1-mediated parental DNA integrity in zygote nucleus, zygote progresses cell cycle to produce two-celled embryo. In angiosperms, female and male gametes exist in gametophytes after the complementation of meiosis and the progression of nuclear/cell division of the haploid cell. Within the embryo sac, the egg cell is specially differentiated for fertilization and subsequent embryogenesis, and cellular programs for embryonic development, such as restarting the cell cycle and de novo gene expression, are halted. There is only limited knowledge about how the cell cycle in egg cells restarts toward zygotic division, although the conversion of the cell cycle from a quiescent and arrested state to an active state is the most evident transition of cell status from egg cell to zygote. This is partly due to the difficulty in direct access and analysis of egg cells, zygotes and early embryos, which are deeply embedded in ovaries. In this study, precise relative DNA amounts in the nuclei of egg cells, developing zygotes and cells of early embryos were measured, and the cell cycle of a rice egg cell was estimated as the G1 phase with a 1C DNA level. In addition, increases in DNA content in zygote nuclei via karyogamy and DNA replication were also detectable according to progression of the cell cycle. In addition, expression profiles for cell cycle-related genes in egg cells and zygotes were also addressed, and it was suggested that OsKRP2 and OsWEE1 function in the inhibition of cell cycle progression in egg cells and in checkpoint of parental DNA integrity in zygote nucleus, respectively.

Toll-like receptor 4 is involved in the cell cycle modulation and required for effective human cytomegalovirus infection in THP-1 macrophages

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

Arcangeletti, Maria-Cristina, E-mail: mariacristina.arcangeletti@unipr.it; Germini, Diego; Rodighiero, Isabella

2013-05-25

Suitable host cell metabolic conditions are fundamental for the effective development of the human cytomegalovirus (HCMV) lytic cycle. Indeed, several studies have demonstrated the ability of this virus to interfere with cell cycle regulation, mainly by blocking proliferating cells in G1 or G1/S. In the present study, we demonstrate that HCMV deregulates the cell cycle of THP-1 macrophages (a cell line irreversibly arrested in G0) by pushing them into S and G2 phases. Moreover, we show that HCMV infection of THP-1 macrophages leads to Toll-like receptor 4 (TLR4) activation. Since various studies have indicated TLR4 to be involved in promotingmore » cell proliferation, here we investigate the possible role of TLR4 in the observed HCMV-induced cell cycle perturbation. Our data strongly support TLR4 as a mediator of HCMV-triggered cell cycle activation in THP-1 macrophages favouring, in turn, the development of an efficient viral lytic cycle. - Highlights: ► We studied HCMV infection impact on THP-1 macrophage cell cycle. ► We analysed the role played by Toll-like receptor (TLR) 4 upon HCMV infection. ► HCMV pushes THP-1 macrophages (i.e. resting cells) to re-enter the cell cycle. ► TLR4 pathway inhibition strongly affects the effectiveness of HCMV replication. ► TLR4 pathway inhibition significantly decreases HCMV-induced cell cycle re-entry.« less

MER Field Geologic Traverse in Gusev Crater, Mars: Initial Results From the Perspective of Spirit

NASA Technical Reports Server (NTRS)

Crumpler, L.; Cabrol, N.; desMarais, D.; Farmer, J.; Golmbek, M.; Grant, J.; Greely, R.; Grotzinger, J.; Haskin, L.; Arvidson, R.

2004-01-01

This report casts the initial results of the traverse and science investigations by the Mars Exploration Rover (MER) Spirit at Gusev crater [1] in terms of data sets commonly used in field geologic investigations: Local mapping of geologic features, analyses of selected samples, and their location within the local map, and the regional context of the field traverse in terms of the larger geologic and physiographic region. These elements of the field method are represented in the MER characterization of the Gusev traverse by perspective-based geologic/morphologic maps, the placement of the results from Mossbauer, APXS, Microscopic Imager, Mini-TES and Pancam multispectral studies in context within this geologic/ morphologic map, and the placement of the overall traverse in the context of narrow-angle MOC (Mars Orbiter Camera) and descent images. A major campaign over a significance fraction of the mission will be the first robotic traverse of the ejecta from a Martian impact crater along an approximate radial from the crater center. The Mars Exploration Rovers have been conceptually described as 'robotic field geologists', that is, a suite of instruments with mobility that enables far-field traverses to multiple sites located within a regional map/image base at which in situ analyses may be done. Initial results from MER, where the field geologic method has been used throughout the initial course of the investigation, confirm that this field geologic model is applicable for remote planetary surface exploration. The field geologic method makes use of near-field geologic characteristics ('outcrops') to develop an understanding of the larger geologic context through continuous loop of rational steps focused on real-time hypothesis identification and testing. This poster equates 'outcrops' with the locations of in situ investigations and 'regional context' with the geology over distance of several kilometers. Using this fundamental field geologic method, we have identified the basic local geologic materials on the floor of Gusev at this site, their compositions and likely lithologies, origins, processes that have modified these materials, and their potential significance in the interpretation of the regional geology both spatially and temporally.

A gene delivery system for insect cells mediated by arginine-rich cell-penetrating peptides.

PubMed

Chen, Yung-Jen; Liu, Betty Revon; Dai, Yun-Hao; Lee, Cheng-Yi; Chan, Ming-Huan; Chen, Hwei-Hsien; Chiang, Huey-Jenn; Lee, Han-Jung

2012-02-10

Most bioactive macromolecules, such as protein, DNA and RNA, basically cannot permeate into cells freely from outside the plasma membrane. Cell-penetrating peptides (CPPs) are a group of short peptides that possess the ability to traverse the cell membrane and have been considered as candidates for mediating gene and drug delivery into living cells. In this study, we demonstrate that three arginine-rich CPPs (SR9, HR9 and PR9) are able to form stable complexes with plasmid DNA and deliver DNA into insect Sf9 cells in a noncovalent manner. The transferred plasmid DNA containing enhanced green fluorescent protein (EGFP) and red fluorescent protein (RFP) coding regions could be expressed in cells functionally assayed at both the protein and RNA levels. Furthermore, treatment of cells with CPPs and CPP/DNA complexes resulted in a viability of 84-93% indicating these CPPs are not cytotoxic. These results suggest that arginine-rich CPPs appear to be a promising tool for insect transgenesis. Copyright © 2011 Elsevier B.V. All rights reserved.

Restrictions in Cell Cycle Progression of Adult Vestibular Supporting Cells in Response to Ectopic Cyclin D1 Expression

PubMed Central

Loponen, Heidi; Ylikoski, Jukka; Albrecht, Jeffrey H.; Pirvola, Ulla

2011-01-01

Sensory hair cells and supporting cells of the mammalian inner ear are quiescent cells, which do not regenerate. In contrast, non-mammalian supporting cells have the ability to re-enter the cell cycle and produce replacement hair cells. Earlier studies have demonstrated cyclin D1 expression in the developing mouse supporting cells and its downregulation along maturation. In explant cultures of the mouse utricle, we have here focused on the cell cycle control mechanisms and proliferative potential of adult supporting cells. These cells were forced into the cell cycle through adenoviral-mediated cyclin D1 overexpression. Ectopic cyclin D1 triggered robust cell cycle re-entry of supporting cells, accompanied by changes in p27Kip1 and p21Cip1 expressions. Main part of cell cycle reactivated supporting cells were DNA damaged and arrested at the G2/M boundary. Only small numbers of mitotic supporting cells and rare cells with signs of two successive replications were found. Ectopic cyclin D1-triggered cell cycle reactivation did not lead to hyperplasia of the sensory epithelium. In addition, a part of ectopic cyclin D1 was sequestered in the cytoplasm, reflecting its ineffective nuclear import. Combined, our data reveal intrinsic barriers that limit proliferative capacity of utricular supporting cells. PMID:22073316

Restrictions in cell cycle progression of adult vestibular supporting cells in response to ectopic cyclin D1 expression.

PubMed

Loponen, Heidi; Ylikoski, Jukka; Albrecht, Jeffrey H; Pirvola, Ulla

2011-01-01

Sensory hair cells and supporting cells of the mammalian inner ear are quiescent cells, which do not regenerate. In contrast, non-mammalian supporting cells have the ability to re-enter the cell cycle and produce replacement hair cells. Earlier studies have demonstrated cyclin D1 expression in the developing mouse supporting cells and its downregulation along maturation. In explant cultures of the mouse utricle, we have here focused on the cell cycle control mechanisms and proliferative potential of adult supporting cells. These cells were forced into the cell cycle through adenoviral-mediated cyclin D1 overexpression. Ectopic cyclin D1 triggered robust cell cycle re-entry of supporting cells, accompanied by changes in p27(Kip1) and p21(Cip1) expressions. Main part of cell cycle reactivated supporting cells were DNA damaged and arrested at the G2/M boundary. Only small numbers of mitotic supporting cells and rare cells with signs of two successive replications were found. Ectopic cyclin D1-triggered cell cycle reactivation did not lead to hyperplasia of the sensory epithelium. In addition, a part of ectopic cyclin D1 was sequestered in the cytoplasm, reflecting its ineffective nuclear import. Combined, our data reveal intrinsic barriers that limit proliferative capacity of utricular supporting cells.

Slow-cycling stem cells in hydra contribute to head regeneration

PubMed Central

Govindasamy, Niraimathi; Murthy, Supriya; Ghanekar, Yashoda

2014-01-01

ABSTRACT Adult stem cells face the challenge of maintaining tissue homeostasis by self-renewal while maintaining their proliferation potential over the lifetime of an organism. Continuous proliferation can cause genotoxic/metabolic stress that can compromise the genomic integrity of stem cells. To prevent stem cell exhaustion, highly proliferative adult tissues maintain a pool of quiescent stem cells that divide only in response to injury and thus remain protected from genotoxic stress. Hydra is a remarkable organism with highly proliferative stem cells and ability to regenerate at whole animal level. Intriguingly, hydra does not display consequences of high proliferation, such as senescence or tumour formation. In this study, we investigate if hydra harbours a pool of slow-cycling stem cells that could help prevent undesirable consequences of continuous proliferation. Hydra were pulsed with the thymidine analogue 5-ethynyl-2′-deoxyuridine (EdU) and then chased in the absence of EdU to monitor the presence of EdU-retaining cells. A significant number of undifferentiated cells of all three lineages in hydra retained EdU for about 8–10 cell cycles, indicating that these cells did not enter cell cycle. These label-retaining cells were resistant to hydroxyurea treatment and were predominantly in the G2 phase of cell cycle. Most significantly, similar to mammalian quiescent stem cells, these cells rapidly entered cell division during head regeneration. This study shows for the first time that, contrary to current beliefs, cells in hydra display heterogeneity in their cell cycle potential and the slow-cycling cells in this population enter cell cycle during head regeneration. These results suggest an early evolution of slow-cycling stem cells in multicellular animals. PMID:25432513

Investigating Conservation of the Cell-Cycle-Regulated Transcriptional Program in the Fungal Pathogen, Cryptococcus neoformans

PubMed Central

Sierra, Crystal S.; Haase, Steven B.

2016-01-01

The pathogenic yeast Cryptococcus neoformans causes fungal meningitis in immune-compromised patients. Cell proliferation in the budding yeast form is required for C. neoformans to infect human hosts, and virulence factors such as capsule formation and melanin production are affected by cell-cycle perturbation. Thus, understanding cell-cycle regulation is critical for a full understanding of virulence factors for disease. Our group and others have demonstrated that a large fraction of genes in Saccharomyces cerevisiae is expressed periodically during the cell cycle, and that proper regulation of this transcriptional program is important for proper cell division. Despite the evolutionary divergence of the two budding yeasts, we found that a similar percentage of all genes (~20%) is periodically expressed during the cell cycle in both yeasts. However, the temporal ordering of periodic expression has diverged for some orthologous cell-cycle genes, especially those related to bud emergence and bud growth. Genes regulating DNA replication and mitosis exhibited a conserved ordering in both yeasts, suggesting that essential cell-cycle processes are conserved in periodicity and in timing of expression (i.e. duplication before division). In S. cerevisiae cells, we have proposed that an interconnected network of periodic transcription factors (TFs) controls the bulk of the cell-cycle transcriptional program. We found that temporal ordering of orthologous network TFs was not always maintained; however, the TF network topology at cell-cycle commitment appears to be conserved in C. neoformans. During the C. neoformans cell cycle, DNA replication genes, mitosis genes, and 40 genes involved in virulence are periodically expressed. Future work toward understanding the gene regulatory network that controls cell-cycle genes is critical for developing novel antifungals to inhibit pathogen proliferation. PMID:27918582

AS160 controls eukaryotic cell cycle and proliferation by regulating the CDK inhibitor p21.

PubMed

Gongpan, Pianchou; Lu, Yanting; Wang, Fang; Xu, Yuhui; Xiong, Wenyong

2016-07-02

AS160 (TBC1D4) has been implicated in multiple biological processes. However, the role and the mechanism of action of AS160 in the regulation of cell proliferation remain unclear. In this study, we demonstrated that AS160 knockdown led to blunted cell proliferation in multiple cell types, including fibroblasts and cancer cells. The results of cell cycle analysis showed that these cells were arrested in the G1 phase. Intriguingly, this inhibition of cell proliferation and the cell cycle arrest caused by AS160 depletion were glucose independent. Moreover, AS160 silencing led to a marked upregulation of the expression of the cyclin-dependent kinase inhibitor p21. Furthermore, whereas AS160 overexpression resulted in p21 downregulation and rescued the arrested cell cycle in AS160-depeleted cells, p21 silencing rescued the inhibited cell cycle and proliferation in the cells. Thus, our results demonstrated that AS160 regulates glucose-independent eukaryotic cell proliferation through p21-dependent control of the cell cycle, and thereby revealed a molecular mechanism of AS160 modulation of cell cycle and proliferation that is of general physiological significance.

Monte Carlo calculation of the maximum therapeutic gain of tumor antivascular alpha therapy

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

Huang, Chen-Yu; Oborn, Bradley M.; Guatelli, Susanna

Purpose: Metastatic melanoma lesions experienced marked regression after systemic targeted alpha therapy in a phase 1 clinical trial. This unexpected response was ascribed to tumor antivascular alpha therapy (TAVAT), in which effective tumor regression is achieved by killing endothelial cells (ECs) in tumor capillaries and, thus, depriving cancer cells of nutrition and oxygen. The purpose of this paper is to quantitatively analyze the therapeutic efficacy and safety of TAVAT by building up the testing Monte Carlo microdosimetric models. Methods: Geant4 was adapted to simulate the spatial nonuniform distribution of the alpha emitter {sup 213}Bi. The intraluminal model was designed tomore » simulate the background dose to normal tissue capillary ECs from the nontargeted activity in the blood. The perivascular model calculates the EC dose from the activity bound to the perivascular cancer cells. The key parameters are the probability of an alpha particle traversing an EC nucleus, the energy deposition, the lineal energy transfer, and the specific energy. These results were then applied to interpret the clinical trial. Cell survival rate and therapeutic gain were determined. Results: The specific energy for an alpha particle hitting an EC nucleus in the intraluminal and perivascular models is 0.35 and 0.37 Gy, respectively. As the average probability of traversal in these models is 2.7% and 1.1%, the mean specific energy per decay drops to 1.0 cGy and 0.4 cGy, which demonstrates that the source distribution has a significant impact on the dose. Using the melanoma clinical trial activity of 25 mCi, the dose to tumor EC nucleus is found to be 3.2 Gy and to a normal capillary EC nucleus to be 1.8 cGy. These data give a maximum therapeutic gain of about 180 and validate the TAVAT concept. Conclusions: TAVAT can deliver a cytotoxic dose to tumor capillaries without being toxic to normal tissue capillaries.« less

Superficial Deposits at Gusev Crater Along Spirit Rover Traverses

NASA Technical Reports Server (NTRS)

Grant, J. A.; Arvidson, R.; Bell, J. F., III; Cabrol, N. A.; Carr, M. H.; Christensen, P.; Crumpler, L.; DesMarsais, D.; Ehlmann, B. L.; Ming, Douglas W.

2004-01-01

The Mars Exploration Rover Spirit has traversed a fairly flat, rock-strewn terrain whose surface is shaped primarily by impact events, although some of the landscape has been altered by eolian processes.Impacts ejected basaltic rocks that probably were part of locally formed lava flows from at least 10 meters depth.Some rocks have been textured and/or partially buried by windblown sediments less than 2 millimeters in diameter that concentrate within shallow, partially filled, circular impact depressions referred to as hollows.The terrain traversed during the 90-sol (martian solar day) nominal mission shows no evidence for an ancient lake in Gusev crater.

Surficial deposits at Gusev crater along Spirit Rover traverses

USGS Publications Warehouse

Grant, J. A.; Arvidson, R.; Bell, J.F.; Cabrol, N.A.; Carr, M.H.; Christensen, P.; Crumpler, L.; Des Marais, D.J.; Ehlmann, B.L.; Farmer, J.; Golombek, M.; Grant, F.D.; Greeley, R.; Herkenhoff, K.; Li, R.; McSween, H.Y.; Ming, D. W.; Moersch, J.; Rice, J. W.; Ruff, S.; Richter, L.; Squyres, S.; Sullivan, R.; Weitz, C.

2004-01-01

The Mars Exploration Rover Spirit has traversed a fairly flat, rock-strewn terrain whose surface is shaped primarily by impact events, although some of the landscape has been altered by eolian processes. Impacts ejected basaltic rocks that probably were part of locally formed lava flows from at least 10 meters depth. Some rocks have been textured and/or partially buried by windblown sediments less than 2 millimeters in diameter that concentrate within shallow, partially filled, circular impact depressions referred to as hollows. The terrain traversed during the 90-sol (martian solar day) nominal mission shows no evidence for an ancient lake in Gusev crater.

A dual transcriptional reporter and CDK-activity sensor marks cell cycle entry and progression in C. elegans

PubMed Central

van Rijnberk, Lotte M.; van der Horst, Suzanne E. M.; van den Heuvel, Sander; Ruijtenberg, Suzan

2017-01-01

Development, tissue homeostasis and tumor suppression depend critically on the correct regulation of cell division. Central in the cell division process is the decision whether to enter the next cell cycle and commit to going through the S and M phases, or to remain temporarily or permanently arrested. Cell cycle studies in genetic model systems could greatly benefit from visualizing cell cycle commitment in individual cells without the need of fixation. Here, we report the development and characterization of a reporter to monitor cell cycle entry in the nematode C. elegans. This reporter combines the mcm-4 promoter, to reveal Rb/E2F-mediated transcriptional control, and a live-cell sensor for CDK-activity. The CDK sensor was recently developed for use in human cells and consists of a DNA Helicase fragment fused to eGFP. Upon phosphorylation by CDKs, this fusion protein changes in localization from the nucleus to the cytoplasm. The combined regulation of transcription and subcellular localization enabled us to visualize the moment of cell cycle entry in dividing seam cells during C. elegans larval development. This reporter is the first to reflect cell cycle commitment in C. elegans and will help further genetic studies of the mechanisms that underlie cell cycle entry and exit. PMID:28158315

The Adder Phenomenon Emerges from Independent Control of Pre- and Post-Start Phases of the Budding Yeast Cell Cycle.

PubMed

Chandler-Brown, Devon; Schmoller, Kurt M; Winetraub, Yonatan; Skotheim, Jan M

2017-09-25

Although it has long been clear that cells actively regulate their size, the molecular mechanisms underlying this regulation have remained poorly understood. In budding yeast, cell size primarily modulates the duration of the cell-division cycle by controlling the G1/S transition known as Start. We have recently shown that the rate of progression through Start increases with cell size, because cell growth dilutes the cell-cycle inhibitor Whi5 in G1. Recent phenomenological studies in yeast and bacteria have shown that these cells add an approximately constant volume during each complete cell cycle, independent of their size at birth. These results seem to be in conflict, as the phenomenological studies suggest that cells measure the amount they grow, rather than their size, and that size control acts over the whole cell cycle, rather than specifically in G1. Here, we propose an integrated model that unifies the adder phenomenology with the molecular mechanism of G1/S cell-size control. We use single-cell microscopy to parameterize a full cell-cycle model based on independent control of pre- and post-Start cell-cycle periods. We find that our model predicts the size-independent amount of cell growth during the full cell cycle. This suggests that the adder phenomenon is an emergent property of the independent regulation of pre- and post-Start cell-cycle periods rather than the consequence of an underlying molecular mechanism measuring a fixed amount of growth. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impedance measurements on a spiral-wound nickel/metal hydride cell cycled in a simulated Leo orbit

NASA Technical Reports Server (NTRS)

Reid, Margaret A.

1993-01-01

A spiral-wound size C cell was cycled at 25 C in a low earth orbit (LEO) regime at 50 percent depth of discharge (DOD) with approximately five percent over-charge. The nominal capacity was 3.5 AH. The cell was cycled for 2000 cycles. Capacity checks and impedance measurements over the complete range of state of charge were made upon receipt and after 500, 1000, and 2000 cycles. The capacity of the cell was essentially unchanged until after the impedance measurements at 2000 cycles. Only small changes in the impedance parameters were observed, but there was somewhat more scatter in the data after 2000 cycles. When the cell was returned to LEO cycling after 2000 cycles, only 38 percent of the capacity could be obtained. It is believed that the cell failed because of an equipment failure at the end of the final impedance measurements which allowed an over-discharge.

Lunar Surface Potential Changes Possible Associated with Traversals of the Bow Shock

NASA Technical Reports Server (NTRS)

Collier, M. R.; Stubbs, T. J.; Hills, H. K.

2008-01-01

We report an analysis of seven Apollo 14 Apollo Lunar Surface Experiments Package (ALSEP) Suprathermal Ion Detector Experiment (SIDE) "resonance" events from January 1972 through January 1973. The events appear to be associated with traversals of the Moon through the terrestrial bow shock.

TGEV nucleocapsid protein induces cell cycle arrest and apoptosis through activation of p53 signaling

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

Ding, Li; College of Life Sciences, Hainan Normal University, Haikou, Hainan 571158; Huang, Yong

2014-03-07

Highlights: • TGEV N protein reduces cell viability by inducing cell cycle arrest and apoptosis. • TGEV N protein induces cell cycle arrest and apoptosis by regulating p53 signaling. • TGEV N protein plays important roles in TGEV-induced cell cycle arrest and apoptosis. - Abstract: Our previous studies showed that TGEV infection could induce cell cycle arrest and apoptosis via activation of p53 signaling in cultured host cells. However, it is unclear which viral gene causes these effects. In this study, we investigated the effects of TGEV nucleocapsid (N) protein on PK-15 cells. We found that TGEV N protein suppressedmore » cell proliferation by causing cell cycle arrest at the S and G2/M phases and apoptosis. Characterization of various cellular proteins that are involved in regulating cell cycle progression demonstrated that the expression of N gene resulted in an accumulation of p53 and p21, which suppressed cyclin B1, cdc2 and cdk2 expression. Moreover, the expression of TGEV N gene promoted translocation of Bax to mitochondria, which in turn caused the release of cytochrome c, followed by activation of caspase-3, resulting in cell apoptosis in the transfected PK-15 cells following cell cycle arrest. Further studies showed that p53 inhibitor attenuated TGEV N protein induced cell cycle arrest at S and G2/M phases and apoptosis through reversing the expression changes of cdc2, cdk2 and cyclin B1 and the translocation changes of Bax and cytochrome c induced by TGEV N protein. Taken together, these results demonstrated that TGEV N protein might play an important role in TGEV infection-induced p53 activation and cell cycle arrest at the S and G2/M phases and apoptosis occurrence.« less

A single cyclin–CDK complex is sufficient for both mitotic and meiotic progression in fission yeast

PubMed Central

Gutiérrez-Escribano, Pilar; Nurse, Paul

2015-01-01

The dominant model for eukaryotic cell cycle control proposes that cell cycle progression is driven by a succession of CDK complexes with different substrate specificities. However, in fission yeast it has been shown that a single CDK complex generated by the fusion of the Cdc13 cyclin with the CDK protein Cdc2 can drive the mitotic cell cycle. Meiosis is a modified cell cycle programme in which a single S-phase is followed by two consecutive rounds of chromosome segregation. Here we systematically analyse the requirements of the different fission yeast cyclins for meiotic cell cycle progression. We also show that a single Cdc13–Cdc2 complex, in the absence of the other cyclins, can drive the meiotic cell cycle. We propose that qualitatively different CDK complexes are not absolutely required for cell cycle progression either during mitosis or meiosis, and that a single CDK complex can drive both cell cycle programmes. PMID:25891897

Effects of Traverse Scanning Speed of Spray Nozzle on the Microstructure and Mechanical Properties of Cold-Sprayed Ti6Al4V Coatings

NASA Astrophysics Data System (ADS)

Tan, Adrian Wei-Yee; Sun, Wen; Phang, Yun Peng; Dai, Minghui; Marinescu, Iulian; Dong, Zhili; Liu, Erjia

2017-10-01

Cold spray has the potential to restore damaged aerospace components made from titanium alloy, Ti6Al4V at low temperature (200-400 °C). Traverse scanning speed during deposition is one of the key factors that affect the quality of the Ti6Al4V coatings as it influences the thermal build-up and coating thickness per pass. As there are fewer reported studies on this, this work investigated the effects of different traverse scanning speeds (100, 300 and 500 mm/s) of cold spray nozzle on the microstructure and mechanical properties of cold-sprayed Ti6Al4V coatings. The cross-sectional analysis showed coating porosities reduces with slower traverse speed, from 3.2 to 0.5%. In addition, the microhardness of the coatings increased from about 361-385 HV due to strain hardening. However, the adhesion strength of the coatings to the substrates significantly decreased with reduced traverse speed from about 60 MPa (glue failure) at 500 mm/s to 2.5 MPa (interface failure) at 100 mm/s. Therefore, this study revealed that the control of heat build-up and thickness per pass during the cold spray deposition of the Ti6Al4V coatings is crucial to attain the desirable properties of the coatings.

Hypoxia induces p53 accumulation in the S-phase and accumulation of hypophosphorylated retinoblastoma protein in all cell cycle phases of human melanoma cells.

PubMed Central

Danielsen, T.; Hvidsten, M.; Stokke, T.; Solberg, K.; Rofstad, E. K.

1998-01-01

Hypoxia has been shown to induce accumulation of p53 and of hypophosphorylated retinoblastoma protein (pRb) in tumour cells. In this study, the cell cycle dependence of p53 accumulation and pRb hypophosphorylation in four human melanoma cell lines that are wild type for p53 was investigated using two-parameter flow cytometry measurements of p53 or pRb protein content and DNA content. The hypoxia-induced increase in p53 protein was higher in S-phase than in G1 and G2 phases in all cell lines. The accumulation of p53 in S-phase during hypoxia was not related to hypoxia-induced apoptosis or substantial cell cycle specific cell inactivation during the first 24 h of reoxygenation. pRb was hypophosphorylated in all cell cycle phases by hypoxia treatment. The results did not support a direct link between p53 and pRb during hypoxia because p53 was induced in a cell cycle-specific manner, whereas no cell cycle-dependent differences in pRb hypophosphorylation were detected. Only a fraction of the cell populations (0.60+/-0.10) showed hypophosphorylated pRb. Thus, pRb is probably not the only mediator of the hypoxia-induced cell cycle block seen in all cells and all cell cycle phases. Moreover, the cell cycle-dependent induction of p53 by hypoxia suggests that the primary function of p53 accumulation during hypoxia is other than to arrest the cells. Images Figure 4 Figure 7 PMID:9862563

Nuclear receptor TLX regulates cell cycle progression in neural stem cells of the developing brain.

PubMed

Li, Wenwu; Sun, Guoqiang; Yang, Su; Qu, Qiuhao; Nakashima, Kinichi; Shi, Yanhong

2008-01-01

TLX is an orphan nuclear receptor that is expressed exclusively in vertebrate forebrains. Although TLX is known to be expressed in embryonic brains, the mechanism by which it influences neural development remains largely unknown. We show here that TLX is expressed specifically in periventricular neural stem cells in embryonic brains. Significant thinning of neocortex was observed in embryonic d 14.5 TLX-null brains with reduced nestin labeling and decreased cell proliferation in the germinal zone. Cell cycle analysis revealed both prolonged cell cycles and increased cell cycle exit in TLX-null embryonic brains. Increased expression of a cyclin-dependent kinase inhibitor p21 and decreased expression of cyclin D1 provide a molecular basis for the deficiency of cell cycle progression in embryonic brains of TLX-null mice. Furthermore, transient knockdown of TLX by in utero electroporation led to precocious cell cycle exit and differentiation of neural stem cells followed by outward migration. Together these results indicate that TLX plays an important role in neural development by regulating cell cycle progression and exit of neural stem cells in the developing brain.

Nuclear Receptor TLX Regulates Cell Cycle Progression in Neural Stem Cells of the Developing Brain

PubMed Central

Li, Wenwu; Sun, Guoqiang; Yang, Su; Qu, Qiuhao; Nakashima, Kinichi; Shi, Yanhong

2008-01-01

TLX is an orphan nuclear receptor that is expressed exclusively in vertebrate forebrains. Although TLX is known to be expressed in embryonic brains, the mechanism by which it influences neural development remains largely unknown. We show here that TLX is expressed specifically in periventricular neural stem cells in embryonic brains. Significant thinning of neocortex was observed in embryonic d 14.5 TLX-null brains with reduced nestin labeling and decreased cell proliferation in the germinal zone. Cell cycle analysis revealed both prolonged cell cycles and increased cell cycle exit in TLX-null embryonic brains. Increased expression of a cyclin-dependent kinase inhibitor p21 and decreased expression of cyclin D1 provide a molecular basis for the deficiency of cell cycle progression in embryonic brains of TLX-null mice. Furthermore, transient knockdown of TLX by in utero electroporation led to precocious cell cycle exit and differentiation of neural stem cells followed by outward migration. Together these results indicate that TLX plays an important role in neural development by regulating cell cycle progression and exit of neural stem cells in the developing brain. PMID:17901127

Cell cycle gene expression under clinorotation

NASA Astrophysics Data System (ADS)

Artemenko, Olga

2016-07-01

Cyclins and cyclin-dependent kinase (CDK) are main regulators of the cell cycle of eukaryotes. It's assumes a significant change of their level in cells under microgravity conditions and by other physical factors actions. The clinorotation use enables to determine the influence of gravity on simulated events in the cell during the cell cycle - exit from the state of quiet stage and promotion presynthetic phase (G1) and DNA synthesis phase (S) of the cell cycle. For the clinorotation effect study on cell proliferation activity is the necessary studies of molecular mechanisms of cell cycle regulation and development of plants under altered gravity condition. The activity of cyclin D, which is responsible for the events of the cell cycle in presynthetic phase can be controlled by the action of endogenous as well as exogenous factors, but clinorotation is one of the factors that influence on genes expression that regulate the cell cycle.These data can be used as a model for further research of cyclin - CDK complex for study of molecular mechanisms regulation of growth and proliferation. In this investigation we tried to summarize and analyze known literature and own data we obtained relatively the main regulators of the cell cycle in altered gravity condition.

KOH concentration effect on cycle life of nickel-hydrogen cells

NASA Technical Reports Server (NTRS)

Lim, Hong S.; Verzwyvelt, S. A.

1987-01-01

A cycle life test of Ni/H2 cells containing electrolytes of various KOH concentrations and a sintered type nickel electrode was carried out at 23 C using a 45 min accelerated low Earth orbit (LEO) cycle regime at 80 percent depth of discharge. One of three cells containing 26 percent KOH has achieved over 28,000 cycles, and the other two 19,000 cycles, without a sign of failure. Two other cells containing 31 percent KOH electrolyte, which is the concentration presently used in aerospace cells, failed after 2,979 and 3,620 cycles. This result indicates that the cycle life of the present type of Ni/H2 cells may be extended by a factor of 5 to 10 simply by lowering the KOH concentration. Long cycle life of a Ni/H2 battery at high depth-of-discharge operation is desired, particularly for an LEO spacecraft application. Typically, battery life of about 30,000 cycles is required for a five year mission in an LEO. Such a cycle life with presently available cells can be assured only at a very low depth-of-discharge operation. Results of testing already show that the cycle life of an Ni/H2 cell is tremendously improved by simply using an electrolyte of low KOH concentration.

The alpha-fetoprotein (AFP) third domain: a search for AFP interaction sites of cell cycle proteins.

PubMed

Mizejewski, G J

2016-09-01

The carboxy-terminal third domain of alpha-fetoprotein (AFP-3D) is known to harbor binding and/or interaction sites for hydrophobic ligands, receptors, and binding proteins. Such reports have established that AFP-3D consists of amino acid (AA) sequence stretches on the AFP polypeptide that engages in protein-to-protein interactions with various ligands and receptors. Using a computer software program specifically designed for such interactions, the present report identified AA sequence fragments on AFP-3D that could potentially interact with a variety of cell cycle proteins. The cell cycle proteins identified were (1) cyclins, (2) cyclin-dependent kinases, (3) cell cycle-associated proteins (inhibitors, checkpoints, initiators), and (4) ubiquitin ligases. Following detection of the AFP-3D to cell cycle protein interaction sites, the computer-derived AFP localization AA sequences were compared and aligned with previously reported hydrophobic ligand and receptor interaction sites on AFP-3D. A literature survey of the association of cell cycle proteins with AFP showed both positive relationships and correlations. Previous reports of experimental AFP-derived peptides effects on various cell cycle proteins served to confirm and verify the present computer cell cycle protein identifications. Cell cycle protein interactions with AFP-CD peptides have been reported in cultured MCF-7 breast cancer cells subjected to mRNA microarray analysis. After 7 days in culture with MCF-7 cells, the AFP-derived peptides were shown to downregulate cyclin E, SKP2, checkpoint suppressors, cyclin-dependent kinases, and ubiquitin ligases that modulate cyclin E/CdK2 transition from the G1 to the S-phase of the cell cycle. Thus, the experimental data on AFP-CD interaction with cell cycle proteins were consistent with the "in silico" findings.

Analyzing the dynamics of cell cycle processes from fixed samples through ergodic principles

PubMed Central

Wheeler, Richard John

2015-01-01

Tools to analyze cyclical cellular processes, particularly the cell cycle, are of broad value for cell biology. Cell cycle synchronization and live-cell time-lapse observation are widely used to analyze these processes but are not available for many systems. Simple mathematical methods built on the ergodic principle are a well-established, widely applicable, and powerful alternative analysis approach, although they are less widely used. These methods extract data about the dynamics of a cyclical process from a single time-point “snapshot” of a population of cells progressing through the cycle asynchronously. Here, I demonstrate application of these simple mathematical methods to analysis of basic cyclical processes—cycles including a division event, cell populations undergoing unicellular aging, and cell cycles with multiple fission (schizogony)—as well as recent advances that allow detailed mapping of the cell cycle from continuously changing properties of the cell such as size and DNA content. This includes examples using existing data from mammalian, yeast, and unicellular eukaryotic parasite cell biology. Through the ongoing advances in high-throughput cell analysis by light microscopy, electron microscopy, and flow cytometry, these mathematical methods are becoming ever more important and are a powerful complementary method to traditional synchronization and time-lapse cell cycle analysis methods. PMID:26543196

Angular-dependent light scattering from cancer cells in different phases of the cell cycle.

PubMed

Lin, Xiaogang; Wan, Nan; Weng, Lingdong; Zhou, Yong

2017-10-10

Cancer cells in different phases of the cell cycle result in significant differences in light scattering properties. In order to harvest cancer cells in particular phases of the cell cycle, we cultured cancer cells through the process of synchronization. Flow cytometric analysis was applied to check the results of cell synchronization and prepare for light scattering measurements. Angular-dependent light scattering measurements of cancer cells arrested in the G1, S, and G2 phases have been performed. Based on integral calculations for scattering intensities from 5° to 10° and from 110° to 150°, conclusions have been reached. Clearly, the sizes of the cancer cells in different phases of the cell cycle dominated the forward scatter. Accompanying the increase of cell size with the progression of the cell cycle, the forward scattering intensity also increased. Meanwhile, the DNA content of cancer cells in every phase of the cell cycle is responsible for light scattering at large scatter angles. The higher the DNA content of cancer cells was, the greater the positive effect on the high-scattering intensity. As expected, understanding the relationships between the light scattering from cancer cells and cell cycles will aid in the development of cancer diagnoses. Also, it may assist in the guidance of antineoplastic drugs clinically.

Chloroplast Dysfunction Causes Multiple Defects in Cell Cycle Progression in the Arabidopsis crumpled leaf Mutant1[C][W

PubMed Central

Hudik, Elodie; Yoshioka, Yasushi; Domenichini, Séverine; Bourge, Mickaël; Soubigout-Taconnat, Ludivine; Mazubert, Christelle; Yi, Dalong; Bujaldon, Sandrine; Hayashi, Hiroyuki; De Veylder, Lieven; Bergounioux, Catherine; Benhamed, Moussa; Raynaud, Cécile

2014-01-01

The majority of research on cell cycle regulation is focused on the nuclear events that govern the replication and segregation of the genome between the two daughter cells. However, eukaryotic cells contain several compartmentalized organelles with specialized functions, and coordination among these organelles is required for proper cell cycle progression, as evidenced by the isolation of several mutants in which both organelle function and overall plant development were affected. To investigate how chloroplast dysfunction affects the cell cycle, we analyzed the crumpled leaf (crl) mutant of Arabidopsis (Arabidopsis thaliana), which is deficient for a chloroplastic protein and displays particularly severe developmental defects. In the crl mutant, we reveal that cell cycle regulation is altered drastically and that meristematic cells prematurely enter differentiation, leading to reduced plant stature and early endoreduplication in the leaves. This response is due to the repression of several key cell cycle regulators as well as constitutive activation of stress-response genes, among them the cell cycle inhibitor SIAMESE-RELATED5. One unique feature of the crl mutant is that it produces aplastidic cells in several organs, including the root tip. By investigating the consequence of the absence of plastids on cell cycle progression, we showed that nuclear DNA replication occurs in aplastidic cells in the root tip, which opens future research prospects regarding the dialogue between plastids and the nucleus during cell cycle regulation in higher plants. PMID:25037213

The young Ramón y Cajal as a cell-theory dissenter.

PubMed

Iturbe, Ulises; Pretó, Juli; Lazcano, Antonio

2008-06-01

The intellectual development of scientists normally traverses several different phases as they mature in their professions. In many cases, strong support of certain ideas and theories gives way to more critical, productive views that set the stage for major theories and discoveries. This appears to have been the case of Santiago Ramón y Cajal (1852-1934). In his youth, he supported the protoplasmic theory of life, and as he matured he maintained a critical, yet open view of the cell theory, which postulated that life phenomena could not take place below the cellular level. In later years, however, an older and wiser Ramón y Cajal abandoned all traces of dissent and joined in fully supporting a refined version of cell theory, to which his own discoveries significantly contributed.

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

Gabrielson, Marike; Reizer, Edwin; Stål, Olle

An increasing body of evidence is pointing towards mitochondrial regulation of the cell cycle. In a previous study of HER2-positive tumours we could demonstrate a common loss in the gene encoding for the mitochondrial transporter SLC25A43 and also a significant relation between SLC25A43 protein expression and S-phase fraction. Here, we investigated the consequence of suppressed SLC25A43 expression on cell cycle progression and proliferation in breast epithelial cells. In the present study, we suppressed SLC25A43 using siRNA in immortalised non-cancerous breast epithelial MCF10A cells and HER2-positive breast cancer cells BT-474. Viability, apoptosis, cell proliferation rate, cell cycle phase distribution, and nuclearmore » Ki-67 and p21, were assessed by flow cytometry. Cell cycle related gene expressions were analysed using real-time PCR. We found that SLC25A43 knockdown in MCF10A cells significantly inhibited cell cycle progression during G{sub 1}-to-S transition, thus significantly reducing the proliferation rate and fraction of Ki-67 positive MCF10A cells. In contrast, suppressed SLC25A43 expression in BT-474 cells resulted in a significantly increased proliferation rate together with an enhanced G{sub 1}-to-S transition. This was reflected by an increased fraction of Ki-67 positive cells and reduced level of nuclear p21. In line with our previous results, we show a role for SLC25A43 as a regulator of cell cycle progression and proliferation through a putative mitochondrial checkpoint. These novel data further strengthen the connection between mitochondrial function and the cell cycle, both in non-malignant and in cancer cells. - Highlights: • Proposed cell cycle regulation through the mitochondrial transporter SLC25A43. • SLC25A43 alters cell proliferation rate and cell cycle progression. • Suppressed SLC25A43 influences transcription of cell cycle regulatory genes.« less

Deregulated expression of Cdc6 as BCR/ABL-dependent survival factor in chronic myeloid leukemia cells.

PubMed

Zhang, Jia-Hua; He, Yan-Li; Zhu, Rui; Du, Wen; Xiao, Jun-Hua

2017-06-01

Chronic myeloid leukemia is characterized by the presence of the reciprocal translocation t(9;22) and the BCR/ABL oncogene. The BCR/ABL oncogene activates multiple signaling pathways and involves the dysregulation of oncogenes during the progression of chronic myeloid leukemia. The cell division cycle protein 6, an essential regulator of DNA replication, is elevated in some human cancer cells. However, the expression of cell division cycle protein 6 in chronic myeloid leukemia and the underlying regulatory mechanism remain to be elucidated. In this study, our data showed that cell division cycle protein 6 expression was significantly upregulated in primary chronic myeloid leukemia cells and the chronic myeloid leukemia cell line K562 cells, as compared to the normal bone marrow mononuclear cells. BCR/ABL kinase inhibitor STI571 or BCR/ABL small interfering RNA could significantly downregulate cell division cycle protein 6 messenger RNA expression in K562 cells. Moreover, phosphoinositide 3-kinase/AKT pathway inhibitor LY294002 and Janus kinase/signal transducer and activator of transcription pathway inhibitor AG490 could downregulate cell division cycle protein 6 expression in K562 cells, but not RAS/mitogen-activated protein kinase pathway inhibitor PD98059 had such effect. Cell division cycle protein 6 gene silencing by small interfering RNA effectively resulted in decrease of proliferation, increase of apoptosis, and arrest of cell cycle in K562 cells. These findings have demonstrated that cell division cycle protein 6 overexpression may contribute to the high proliferation and low apoptosis in chronic myeloid leukemia cells and can be regulated by BCR/ABL signal transduction through downstream phosphoinositide 3-kinase/Akt and Janus kinase/signal transducer and activator of transcription pathways, suggesting cell division cycle protein 6 as a potential therapeutic target in chronic myeloid leukemia.

Modeling Bi-modality Improves Characterization of Cell Cycle on Gene Expression in Single Cells

PubMed Central

Danaher, Patrick; Finak, Greg; Krouse, Michael; Wang, Alice; Webster, Philippa; Beechem, Joseph; Gottardo, Raphael

2014-01-01

Advances in high-throughput, single cell gene expression are allowing interrogation of cell heterogeneity. However, there is concern that the cell cycle phase of a cell might bias characterizations of gene expression at the single-cell level. We assess the effect of cell cycle phase on gene expression in single cells by measuring 333 genes in 930 cells across three phases and three cell lines. We determine each cell's phase non-invasively without chemical arrest and use it as a covariate in tests of differential expression. We observe bi-modal gene expression, a previously-described phenomenon, wherein the expression of otherwise abundant genes is either strongly positive, or undetectable within individual cells. This bi-modality is likely both biologically and technically driven. Irrespective of its source, we show that it should be modeled to draw accurate inferences from single cell expression experiments. To this end, we propose a semi-continuous modeling framework based on the generalized linear model, and use it to characterize genes with consistent cell cycle effects across three cell lines. Our new computational framework improves the detection of previously characterized cell-cycle genes compared to approaches that do not account for the bi-modality of single-cell data. We use our semi-continuous modelling framework to estimate single cell gene co-expression networks. These networks suggest that in addition to having phase-dependent shifts in expression (when averaged over many cells), some, but not all, canonical cell cycle genes tend to be co-expressed in groups in single cells. We estimate the amount of single cell expression variability attributable to the cell cycle. We find that the cell cycle explains only 5%–17% of expression variability, suggesting that the cell cycle will not tend to be a large nuisance factor in analysis of the single cell transcriptome. PMID:25032992

Equilibrium between cell division and apoptosis in immortal cells as an alternative to the G1 restriction mechanism in mammalian cells.

PubMed

Dedov, Vadim N; Dedova, Irina V; Nicholson, Garth A

2004-04-01

Starvation arrests cultured mammalian cells in the G(1) restriction point of the cell cycle, whereas cancer cells generally lose the regulatory control of the cell cycle. Human lymphocytes, infected with Epstein-Barr virus (EBV), also lose their cell cycle control and produce immortal lymphoblastoid cell lines. We show that during starvation, EBV-lymphoblasts override the cell cycle arrest in the G(1) restriction point and continue cell division. Simultaneously, starvation activates apoptosis in an approximately half of the daughter cells in each cell generation. Continuos cell division and partial removal of cells by apoptosis results in stabilization of viable cell numbers, where a majority of viable cells are in the G(1) phase of the cell cycle. In contrast to starvation, anticancer drug etoposide activates apoptosis indiscriminately in all EBV-lymphoblasts and convertes all the viable cells into apoptotic. We conclude that the removal of surplus cells by apoptosis may represent a survival mechanism of transformed (i.e., cancer) cell population in nutrient restricted conditions, whereas nontransformed mammalian cells are arrested in the G(1) restriction point of the cell cycle.

[Effects of methyl tertiary butyl ether on cell cycle and cell apoptosis].

PubMed

Zhou, W; Huang, G; Zhang, H; Ye, S

2000-07-01

To explore the effects of the new gasoline additive, methyl tertiary butyl ether (MTBE) on cell cycle and cell apoptosis. Flow cytometry was used to evaluate the effect of MTBE (1, 2, 4 microl/ml, 24 h) on NIH/3T3 cell cycles; and the effect of MTBE on Hela cell apoptosis was evaluated by detecting cell survival using crystal violet staining. Flow cytometry showed that MTBE could change NIH/3T3 cell cycles, decrease the number of cells in S stage, and arrest cells at G(2) + M stage. The results suggested that MTBE could affect NIH/3T3 cell cycles and induce cell proliferation. This situation existed 48 hours after the treatment, and cell cycles came back normal 96 hours after the treatment. By detecting cell survival using crystal violet staining, we found that MTBE could inhibit the apoptosis of Hela cells which was induced by tumor necrosis factor (TNF)alpha and cycloheximide. MTBE's carcinogenicity to animals may relate to induction of cell proliferation and inhibition of cell apoptosis.

KOH concentration effect on the cycle life of nickel-hydrogen cells. 4: Results of failure analyse

NASA Technical Reports Server (NTRS)

Lim, H. S.; Verzwyvelt, S. A.

1989-01-01

Effects of KOH concentrations on failure modes and mechanisms of nickel-hydrogen cells were studied using long cycled boiler plate cells containing electrolytes of various KOH concentrations ranging 21 to 36 percent. Life of these cells were up to 40,000 cycles in an accelerated low earth orbit (LEO) cycle regime at 80 percent depth of discharge. An interim life test results were reported earlier in J. Power Sources, 22, 213-220, 1988. The results of final life test, end-of-life cell performance, and teardown analyses are discussed. These teardown analyses included visual observations, measurements of nickel electrode capacity in an electrolyte-flooded cell, dimensional changes of cell components, SEM studies on cell cross section, BET surface area and pore volume distribution in cycled nickel electrodes, and chemical analyses. Cycle life of a nickel-hydrogen cell was improved tremendously as KOH concentration was decreased from 36 to 31 percent and from 31 to 26 percent while effect of further concentration decrease was complicated as described in our earlier report. Failure mode of high concentration (31 to 36 percent) cells was gradual capacity decrease, while that of low concentration (21 to 26 percent) cells was mainly formation of a soft short. Long cycled (25,000 to 40,000 cycles) nickel electrodes were expanded more than 50 percent of the initial value, but no correlation was found between this expansion and measured capacity. All electrodes cycled in low concentration (21 to 26 percent) cells had higher capacity than those cycled in high concentration (31 to 36 percent) cells.

The cell-cycle interactome: a source of growth regulators?

PubMed

Blomme, Jonas; Inzé, Dirk; Gonzalez, Nathalie

2014-06-01

When plants develop, cell proliferation and cell expansion are tightly controlled in order to generate organs with a determinate final size such as leaves. Several studies have demonstrated the importance of the cell proliferation phase for leaf growth, illustrating that cell-cycle regulation is crucial for correct leaf development. A large and complex set of interacting proteins that constitute the cell-cycle interactome controls the transition from one cell-cycle phase to another. Here, we review the current knowledge on cell-cycle regulators from this interactome affecting final leaf size when their expression is altered, mainly in Arabidopsis. In addition to the description of mutants of CYCLIN-DEPENDENT KINASES (CDKs), CYCLINS (CYCs), and their transcriptional and post-translational regulators, a phenotypic analysis of gain- and loss-of-function mutants for 27 genes encoding proteins that interact with cell-cycle proteins is presented. This compilation of information shows that when cell-cycle-related genes are mis-expressed, leaf growth is often altered and that, seemingly, three main trends appear to be crucial in the regulation of final organ size by cell-cycle-related genes: (i) cellular compensation; (ii) gene dosage; and (iii) correct transition through the G2/M phase by ANAPHASE PROMOTING COMPLEX/CYCLOSOME (APC/C) activation. In conclusion, this meta-analysis shows that the cell-cycle interactome is enriched in leaf growth regulators, and illustrates the potential to identify new leaf growth regulators among putative new cell-cycle regulators. © The Author 2013. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Performance of Li-Ion Cells Under Battery Voltage Charge Control

NASA Technical Reports Server (NTRS)

Rao, Gopalakrishna M.; Vaidyanathan, Hari; Day, John H. (Technical Monitor)

2001-01-01

A study consisting of electrochemical characterization and Low-Earth-Orbit (LEO) cycling of Li-Ion cells from three vendors was initiated in 1999 to determine the cycling performance and to infuse the new technology in the future NASA missions. The 8-cell batteries included in this evaluation are prismatic cells manufactured by Mine Safety Appliances Company (MSA), cylindrical cells manufactured by SAFT and prismatic cells manufactured by Yardney Technical Products, Inc. (YTP). The three batteries were cycle tested in the LEO regime at 40% depth of discharge, and under a charge control technique that consists of battery voltage clamp with a current taper. The initial testing was conducted at 20 C; however, the batteries were cycled also intermittently at low temperatures. YTP 20 Ah cells consisted of mixed-oxide (Co and Ni) positive, graphitic carbon negative, LIPF6 salt mixed with organic carbonate solvents. The battery voltage clamp was 32 V. The low temperature cycling tests started after 4575 cycles at 20 C. The cells were not capable of cycling. at low temperature since the charge acceptance at battery level was poor. There was a cell in the battery that showed too high an end-of-charge (EOC) voltage thereby limiting the ability to charge the rest of the cells in the battery. The battery has completed 6714 cycles. SAFT 12 Ah cells consisted of mixed-oxide (Co and NO positive, graphitic carbon negative, LiPF6 salt mixed with organic carbonate solvents. The battery voltage clamp was for 30.8 V. The low temperature cycling tests started after 4594 cycles at 20 C. A cell that showed low end of discharge (EOD) and EOC voltages and three other cells that showed higher EOC voltages limited the charge acceptance at the selected voltage limit during charge. The cells were capable of cycling at 10 C and 0 C but the charge voltage limit had to be increased to 34.3 V (4.3 V per cell). The low temperature cycling may have induced poor chargeability since the voltage had to be increased to achieve the required charge input. The battery has completed 6226 cycles. MSA 10 Ah cells consisted of Co oxide positive, graphitic carbon negative, LiPF6 salt mixed with organic carbonate solvents. The battery voltage clamp was 30.8 V. The low temperature cycling tests were started after 2182 cycles at 20 C. The cells were capable of cycling at 10 C and 0 C. Like SAFT, the voltage limit on charge had to be increased to 36 V (4.5 V per cell). There was a cell (cell S/N 13) in the battery that showed poor performance features such as low EOD voltage and high EOC voltage. The battery has completed 3441 cycles. A reconditioning procedure that consisted of C15 charge to a taper current of C/100 and C/20 discharge improved the voltage behavior of SAFT and MSA cells with no significant effect on YTP cells. We have demonstrated that the charge operation with VT clamp at battery rather than at cell level is feasible for onboard Li-Ion battery operation.

Newly synthesized and recycling pools of the apical protein gp135 do not occupy the same compartments.

PubMed

Stoops, Emily H; Hull, Michael; Caplan, Michael J

2016-12-01

Polarized epithelial cells sort newly synthesized and recycling plasma membrane proteins into distinct trafficking pathways directed to either the apical or basolateral membrane domains. While the trans-Golgi network is a well-established site of protein sorting, increasing evidence indicates a key role for endosomes in the initial trafficking of newly synthesized proteins. Both basolateral and apical proteins have been shown to traverse endosomes en route to the plasma membrane. In particular, apical proteins traffic through either subapical early or recycling endosomes. Here we use the SNAP tag system to analyze the trafficking of the apical protein gp135, also known as podocalyxin. We show that newly synthesized gp135 traverses the apical recycling endosome, but not the apical early endosomes (AEEs). In contrast, post-endocytic gp135 is delivered to the AEE before recycling back to the apical membrane. The pathways pursued by the newly synthesized and recycling gp135 populations do not detectably intersect, demonstrating that the biosynthetic and post-endocytic pools of this protein are subjected to distinct sorting processes. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pollen and spores of terrestrial plants

USGS Publications Warehouse

Bernhardt, Christopher E.; Willard, Debra A.; Shennan, Ian; Long, Antony J.; Horton, Benjamin P.

2015-01-01

Pollen and spores are valuable tools in reconstructing past sea level and climate because of their ubiquity, abundance, and durability as well as their reciprocity with source vegetation to environmental change (Cronin, 1999; Traverse, 2007; Willard and Bernhardt, 2011). Pollan is found in many sedimentary environments, from freshwater to saltwater, terrestrial to marine. It can be abundant in a minimal amount of sample material, for example half a gram, as concentrations can be as high as four million grains per gram (Traverse, 2007). The abundance of pollen in a sample lends it to robust statistical analysis for the quantitative reconstruction of environments. The outer cell wall is resistant to decay in sediments and allows palynomorphs (pollen and spores) to record changes in plant communities and sea level over millions of years. These characteristics make pollen and spores a powerful tool to use in sea-level research.This chapter describes the biology of pollen and spores and how they are transported and preserved in sediments. We present a methodology for isolating pollen from sediments and a general language and framework to identify pollen as well as light micrographs of a selection of common pollen grains, We then discuss their utility in sea-level research.

Leaf maximum photosynthetic rate and venation are linked by hydraulics.

PubMed

Brodribb, Tim J; Feild, Taylor S; Jordan, Gregory J

2007-08-01

Leaf veins are almost ubiquitous across the range of terrestrial plant diversity, yet their influence on leaf photosynthetic performance remains uncertain. We show here that specific physical attributes of the vascular plumbing network are key limiters of the hydraulic and photosynthetic proficiency of any leaf. Following the logic that leaf veins evolved to bypass inefficient water transport through living mesophyll tissue, we examined the hydraulic pathway beyond the distal ends of the vein system as a possible limiter of water transport in leaves. We tested a mechanistic hypothesis that the length of this final traverse, as water moves from veins across the mesophyll to where it evaporates from the leaf, governs the hydraulic efficiency and photosynthetic carbon assimilation of any leaf. Sampling 43 species across the breadth of plant diversity from mosses to flowering plants, we found that the post-vein traverse as determined by characters such as vein density, leaf thickness, and cell shape, was strongly correlated with the hydraulic conductivity and maximum photosynthetic rate of foliage. The shape of this correlation provided clear support for the a priori hypothesis that vein positioning limits photosynthesis via its influence on leaf hydraulic efficiency.

Inhibitor effects during the cell cycle in Chlamydomonas reinhardtii. Determination of transition points in asynchronous cultures

PubMed Central

1975-01-01

A wide variety of inhibitors (drugs, antibiotics, and antimetabolites) will block cell division within an ongoing cell cycle in autotrophic cultures of Chlamydomonas reinhardtii. To determine when during the cell cycle a given inhibitor is effective in preventing cell division, a technique is described which does not rely on the use of synchronous cultures. The technique permits the measurement of transition points, the cell cycle stage at which the subsequent cell division becomes insensitive to the effects of an inhibitor. A map of transition points in the cell cycle reveals that they are grouped into two broad periods, the second and fourth quarters. In general, inhibitors which block organellar DNA, RNA, and protein synthesis have second-quarter transition points, while those which inhibit nuclear cytoplasmic macromolecular synthesis have fourth-quarter transition points. The specific grouping of these transition points into two periods suggests that the synthesis of organellar components is completed midway through the cell cycle and that the synthesis of nonorganellar components required for cell division is not completed until late in the cell cycle. PMID:1176526

The Direct Injection of Electron Pulses into Air -- An SREMP Simulation Tool

DTIC Science & Technology

1981-06-01

Traversing AURORA Test Cell. Thermoluminescent Dosimetry - In order to determine the extent of the ionization produced by the electron beam, a...was sensitive only to electrons above ~ 1.7 MeV. The TLDs which were used for this experiment were Teledyne-Isotopes type SD-CaF2 :Mn-0.4L. These...collision stopping power of 1.55 ~ 0.1 MeV-cm2 /g for electrons between 0.5 and 9.5 MeV. The dose deposited in such a TLD by electrons can be shown to be

Identification of Primary Transcriptional Regulation of Cell Cycle-Regulated Genes upon DNA Damage

PubMed Central

Zhou, Tong; Chou, Jeff; Mullen, Thomas E.; Elkon, Rani; Zhou, Yingchun; Simpson, Dennis A.; Bushel, Pierre R.; Paules, Richard S.; Lobenhofer, Edward K.; Hurban, Patrick; Kaufmann, William K.

2007-01-01

The changes in global gene expression in response to DNA damage may derive from either direct induction or repression by transcriptional regulation or indirectly by synchronization of cells to specific cell cycle phases, such as G1 or G2. We developed a model that successfully estimated the expression levels of >400 cell cycle-regulated genes in normal human fibroblasts based on the proportions of cells in each phase of the cell cycle. By isolating effects on the gene expression associated with the cell cycle phase redistribution after genotoxin treatment, the direct transcriptional target genes were distinguished from genes for which expression changed secondary to cell synchronization. Application of this model to ionizing radiation (IR)-treated normal human fibroblasts identified 150 of 406 cycle-regulated genes as putative direct transcriptional targets of IR-induced DNA damage. Changes in expression of these genes after IR treatment derived from both direct transcriptional regulation and cell cycle synchronization. PMID:17404513

The Yeast Cyclin-Dependent Kinase Routes Carbon Fluxes to Fuel Cell Cycle Progression.

PubMed

Ewald, Jennifer C; Kuehne, Andreas; Zamboni, Nicola; Skotheim, Jan M

2016-05-19

Cell division entails a sequence of processes whose specific demands for biosynthetic precursors and energy place dynamic requirements on metabolism. However, little is known about how metabolic fluxes are coordinated with the cell division cycle. Here, we examine budding yeast to show that more than half of all measured metabolites change significantly through the cell division cycle. Cell cycle-dependent changes in central carbon metabolism are controlled by the cyclin-dependent kinase (Cdk1), a major cell cycle regulator, and the metabolic regulator protein kinase A. At the G1/S transition, Cdk1 phosphorylates and activates the enzyme Nth1, which funnels the storage carbohydrate trehalose into central carbon metabolism. Trehalose utilization fuels anabolic processes required to reliably complete cell division. Thus, the cell cycle entrains carbon metabolism to fuel biosynthesis. Because the oscillation of Cdk activity is a conserved feature of the eukaryotic cell cycle, we anticipate its frequent use in dynamically regulating metabolism for efficient proliferation. Copyright © 2016 Elsevier Inc. All rights reserved.

Dipole-resonance assisted isomerization in the electronic ground state using few-cycle infrared pulses.

PubMed

Skocek, Oliver; Uiberacker, Christoph; Jakubetz, Werner

2011-06-30

A computational investigation of HCN → HNC isomerization in the electronic ground state by one- and few-cycle infrared pulses is presented. Starting from a vibrationally pre-excited reagent state, isomerization yields of more than 50% are obtained using single one- to five-cycle pulses. The principal mechanism includes two steps of population transfer by dipole-resonance (DR), and hence, the success of the method is closely linked to the polarity of the system and, in particular, the stepwise change of the dipole moment from reactant to transition state and on to products. The yield drops massively if the diagonal dipole matrix elements are artificially set to zero. In detail, the mechanism includes DR-induced preparation of a delocalized vibrational wavepacket, which traverses the barrier region and is finally trapped in the product well by DR-dominated de-excitation. The excitation and de-excitation steps are triggered by pulse lobes of opposite field direction. As the number of optical cycles is increased, the leading field lobes prepare a vibrational superposition state by off-resonant ladder climbing, which is then subjected to the three steps of the principal isomerization mechanism. DR excitation is more efficient from a preformed vibrational wavepacket than from a molecular eigenstate. The entire process can be loosely described as Tannor-Kosloff-Rice type transfer mechanism on a single potential surface effected by a single pulse, individual field lobes assuming the roles of pump- and dump-pulses. Pre-excitation to a transient wavepacket can be enhanced by applying a separate, comparatively weak few-cycle prepulse, in which the prepulse prepares a vibrational wavepacket. The two-pulse setup corresponds to a double Tannor-Kosloff-Rice control scheme on a single potential surface.

Towards Predicting the Response of a Solid Tumour to Chemotherapy and Radiotherapy Treatments: Clinical Insights from a Computational Model

PubMed Central

Powathil, Gibin G.; Adamson, Douglas J. A.; Chaplain, Mark A. J.

2013-01-01

In this paper we use a hybrid multiscale mathematical model that incorporates both individual cell behaviour through the cell-cycle and the effects of the changing microenvironment through oxygen dynamics to study the multiple effects of radiation therapy. The oxygenation status of the cells is considered as one of the important prognostic markers for determining radiation therapy, as hypoxic cells are less radiosensitive. Another factor that critically affects radiation sensitivity is cell-cycle regulation. The effects of radiation therapy are included in the model using a modified linear quadratic model for the radiation damage, incorporating the effects of hypoxia and cell-cycle in determining the cell-cycle phase-specific radiosensitivity. Furthermore, after irradiation, an individual cell's cell-cycle dynamics are intrinsically modified through the activation of pathways responsible for repair mechanisms, often resulting in a delay/arrest in the cell-cycle. The model is then used to study various combinations of multiple doses of cell-cycle dependent chemotherapies and radiation therapy, as radiation may work better by the partial synchronisation of cells in the most radiosensitive phase of the cell-cycle. Moreover, using this multi-scale model, we investigate the optimum sequencing and scheduling of these multi-modality treatments, and the impact of internal and external heterogeneity on the spatio-temporal patterning of the distribution of tumour cells and their response to different treatment schedules. PMID:23874170

A Multiplexed High-Content Screening Approach Using the Chromobody Technology to Identify Cell Cycle Modulators in Living Cells.

PubMed

Schorpp, Kenji; Rothenaigner, Ina; Maier, Julia; Traenkle, Bjoern; Rothbauer, Ulrich; Hadian, Kamyar

2016-10-01

Many screening hits show relatively poor quality regarding later efficacy and safety. Therefore, small-molecule screening efforts shift toward high-content analysis providing more detailed information. Here, we describe a novel screening approach to identify cell cycle modulators with low toxicity by combining the Cell Cycle Chromobody (CCC) technology with the CytoTox-Glo (CTG) cytotoxicity assay. The CCC technology employs intracellularly functional single-domain antibodies coupled to a fluorescent protein (chromobodies) to visualize the cell cycle-dependent redistribution of the proliferating cell nuclear antigen (PCNA) in living cells. This image-based cell cycle analysis was combined with determination of dead-cell protease activity in cell culture supernatants by the CTG assay. We adopted this multiplex approach to high-throughput format and screened 960 Food and Drug Administration (FDA)-approved drugs. By this, we identified nontoxic compounds, which modulate different cell cycle stages, and validated selected hits in diverse cell lines stably expressing CCC. Additionally, we independently validated these hits by flow cytometry as the current state-of-the-art format for cell cycle analysis. This study demonstrates that CCC imaging is a versatile high-content screening approach to identify cell cycle modulators, which can be multiplexed with cytotoxicity assays for early elimination of toxic compounds during screening. © 2016 Society for Laboratory Automation and Screening.

Cell cycle activation in p21 dependent pathway: An alternative mechanism of organophosphate induced dopaminergic neurodegeneration.

PubMed

Wani, Willayat Yousuf; Kandimalla, Ramesh J L; Sharma, Deep Raj; Kaushal, Alka; Ruban, Anand; Sunkaria, Aditya; Vallamkondu, Jayalakshmi; Chiarugi, Alberto; Reddy, P Hemachandra; Gill, Kiran Dip

2017-07-01

In the previous study, we demonstrated that dichlorvos induces oxidative stress in dopaminergic neuronal cells and subsequent caspase activation mediates apoptosis. In the present study, we evaluated the effect and mechanism of dichlorvos induced oxidative stress on cell cycle activation in NGF-differentiated PC12 cells. Dichlorvos exposure resulted in oxidative DNA damage along with activation of cell cycle machinery in differentiated PC12 cells. Dichlorvos exposed cells exhibited an increased expression of p53, cyclin-D1, pRb and decreased expression of p21suggesting a re-entry of differentiated cells into the cell cycle. Cell cycle analysis of dichlorvos exposed cells revealed a reduction of cells in the G 0 /G 1 phase of the cell cycle (25%), and a concomitant increase of cells in S phase (30%) and G2/M phase (43.3%) compared to control PC12 cells. Further, immunoblotting of cytochrome c, Bax, Bcl-2 and cleaved caspase-3 revealed that dichlorvos induces a caspase-dependent cell death in PC12 cells. These results suggest that Dichlorvos exposure has the potential to generate oxidative stress which evokes activation of cell cycle machinery leading to apoptotic cell death via cytochrome c release from mitochondria and subsequent caspase-3 activation in differentiated PC12 cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Decoupling of Nuclear Division Cycles and Cell Size during the Coenocytic Growth of the Ichthyosporean Sphaeroforma arctica.

PubMed

Ondracka, Andrej; Dudin, Omaya; Ruiz-Trillo, Iñaki

2018-06-18

Coordination of the cell division cycle with the growth of the cell is critical to achieve cell size homeostasis [1]. Mechanisms coupling the cell division cycle with cell growth have been described across diverse eukaryotic taxa [2-4], but little is known about how these processes are coordinated in organisms that undergo more complex life cycles, such as coenocytic growth. Coenocytes (multinucleate cells formed by sequential nuclear divisions without cytokinesis) are commonly found across the eukaryotic kingdom, including in animal and plant tissues and several lineages of unicellular eukaryotes [5]. Among the organisms that form coenocytes are ichthyosporeans, a lineage of unicellular holozoans that are of significant interest due to their phylogenetic placement as one of the closest relatives of animals [6]. Here, we characterize the coenocytic cell division cycle in the ichthyosporean Sphaeroforma arctica. We observe that, in laboratory conditions, S. arctica cells undergo a uniform and easily synchronizable coenocytic cell cycle, reaching up to 128 nuclei per cell before cellularization and release of daughter cells. Cycles of nuclear division occur synchronously within the coenocyte and in regular time intervals (11-12 hr). We find that the growth of cell volume is dependent on concentration of nutrients in the media; in contrast, the rate of nuclear division cycles is constant over a range of nutrient concentrations. Together, the results suggest that nuclear division cycles in the coenocytic growth of S. arctica are driven by a timer, which ensures periodic and synchronous nuclear cycles independent of the cell size and growth. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Real-time tracking of cell cycle progression during CD8+ effector and memory T-cell differentiation

PubMed Central

Kinjyo, Ichiko; Qin, Jim; Tan, Sioh-Yang; Wellard, Cameron J.; Mrass, Paulus; Ritchie, William; Doi, Atsushi; Cavanagh, Lois L.; Tomura, Michio; Sakaue-Sawano, Asako; Kanagawa, Osami; Miyawaki, Atsushi; Hodgkin, Philip D.; Weninger, Wolfgang

2015-01-01

The precise pathways of memory T-cell differentiation are incompletely understood. Here we exploit transgenic mice expressing fluorescent cell cycle indicators to longitudinally track the division dynamics of individual CD8+ T cells. During influenza virus infection in vivo, naive T cells enter a CD62Lintermediate state of fast proliferation, which continues for at least nine generations. At the peak of the anti-viral immune response, a subpopulation of these cells markedly reduces their cycling speed and acquires a CD62Lhi central memory cell phenotype. Construction of T-cell family division trees in vitro reveals two patterns of proliferation dynamics. While cells initially divide rapidly with moderate stochastic variations of cycling times after each generation, a slow-cycling subpopulation displaying a CD62Lhi memory phenotype appears after eight divisions. Phenotype and cell cycle duration are inherited by the progeny of slow cyclers. We propose that memory precursors cell-intrinsically modulate their proliferative activity to diversify differentiation pathways. PMID:25709008

Real-time tracking of cell cycle progression during CD8+ effector and memory T-cell differentiation.

PubMed

Kinjyo, Ichiko; Qin, Jim; Tan, Sioh-Yang; Wellard, Cameron J; Mrass, Paulus; Ritchie, William; Doi, Atsushi; Cavanagh, Lois L; Tomura, Michio; Sakaue-Sawano, Asako; Kanagawa, Osami; Miyawaki, Atsushi; Hodgkin, Philip D; Weninger, Wolfgang

2015-02-24

The precise pathways of memory T-cell differentiation are incompletely understood. Here we exploit transgenic mice expressing fluorescent cell cycle indicators to longitudinally track the division dynamics of individual CD8(+) T cells. During influenza virus infection in vivo, naive T cells enter a CD62L(intermediate) state of fast proliferation, which continues for at least nine generations. At the peak of the anti-viral immune response, a subpopulation of these cells markedly reduces their cycling speed and acquires a CD62L(hi) central memory cell phenotype. Construction of T-cell family division trees in vitro reveals two patterns of proliferation dynamics. While cells initially divide rapidly with moderate stochastic variations of cycling times after each generation, a slow-cycling subpopulation displaying a CD62L(hi) memory phenotype appears after eight divisions. Phenotype and cell cycle duration are inherited by the progeny of slow cyclers. We propose that memory precursors cell-intrinsically modulate their proliferative activity to diversify differentiation pathways.

Identification of Cell Cycle-regulated Genes in Fission YeastD⃞

PubMed Central

Peng, Xu; Karuturi, R. Krishna Murthy; Miller, Lance D.; Lin, Kui; Jia, Yonghui; Kondu, Pinar; Wang, Long; Wong, Lim-Soon; Liu, Edison T.; Balasubramanian, Mohan K.; Liu, Jianhua

2005-01-01

Cell cycle progression is both regulated and accompanied by periodic changes in the expression levels of a large number of genes. To investigate cell cycle-regulated transcriptional programs in the fission yeast Schizosaccharomyces pombe, we developed a whole-genome oligonucleotide-based DNA microarray. Microarray analysis of both wild-type and cdc25 mutant cell cultures was performed to identify transcripts whose levels oscillated during the cell cycle. Using an unsupervised algorithm, we identified 747 genes that met the criteria for cell cycle-regulated expression. Peaks of gene expression were found to be distributed throughout the entire cell cycle. Furthermore, we found that four promoter motifs exhibited strong association with cell cycle phase-specific expression. Examination of the regulation of MCB motif-containing genes through the perturbation of DNA synthesis control/MCB-binding factor (DSC/MBF)-mediated transcription in arrested synchronous cdc10 mutant cell cultures revealed a subset of functional targets of the DSC/MBF transcription factor complex, as well as certain gene promoter requirements. Finally, we compared our data with those for the budding yeast Saccharomyces cerevisiae and found ∼140 genes that are cell cycle regulated in both yeasts, suggesting that these genes may play an evolutionarily conserved role in regulation of cell cycle-specific processes. Our complete data sets are available at http://giscompute.gis.a-star.edu.sg/~gisljh/CDC. PMID:15616197

Impact of high pressure freezing on DH5alpha Escherichia coli and red blood cells.

PubMed

Suppes, Galen J; Egan, Susan; Casillan, Alfred J; Wei Chan, Kok; Seckar, Bill

2003-10-01

The impact of high pressure and freezing on survivability of Escherichia coli and human red blood cells was evaluated to determine the utility of high-pressure transitions for preserving living cells. Based on microscopy and survivability, high pressures did not directly impact physical damage to living cells. E. coli studies showed that increased cell death is due to indirect phenomena with decreasing survivability at increasingly high pressures and exposure times. Pressurization rates up to 1.4kbar/min had negligible effects relative to exposures of >5min at high pressures.Both glycine and control of pH near 7.0 were successful in reducing the adverse impacts of high pressure. Survivability increased from <1% at 5min exposure to 2.1kbar of pressure to typical values >20%. The combination of glycine and the buffer salt led to even further improvements in survivability. Pressure changes were used to traverse temperature and pressures consistent with Ice I and Ice III phase boundaries of pure water.

Altered cell cycle-related gene expression in brain and lymphocytes from a transgenic mouse model of Alzheimer's disease [amyloid precursor protein/presenilin 1 (PS1)].

PubMed

Esteras, Noemí; Bartolomé, Fernando; Alquézar, Carolina; Antequera, Desireé; Muñoz, Úrsula; Carro, Eva; Martín-Requero, Ángeles

2012-09-01

Cumulative evidence indicates that aberrant re-expression of many cell cycle-related proteins and inappropriate neuronal cell cycle control are critical events in Alzheimer's disease (AD) pathogenesis. Evidence of cell cycle activation in post-mitotic neurons has also been observed in murine models of AD, despite the fact that most of these mice do not show massive loss of neuronal bodies. Dysfunction of the cell cycle appears to affect cells other than neurons, as peripheral cells, such as lymphocytes and fibroblasts from patients with AD, show an altered response to mitogenic stimulation. We sought to determine whether cell cycle disturbances are present simultaneously in both brain and peripheral cells from the amyloid precursor protein (APP)/presenilin 1 (PS1) mouse model of AD, in order to validate the use of peripheral cells from patients not only to study cell cycle abnormalities as a pathogenic feature of AD, but also as a means to test novel therapeutic approaches. By using cell cycle pathway-specific RT(2)Profiler™ PCR Arrays, we detected changes in a number of cell cycle-related genes in brain as well as in lymphocytes from APP/PS1 mice. Moreover, we found enhanced 5'-bromo-2'-deoxyuridine incorporation into DNA in lymphocytes from APP/PS1 mice, and increased expression of the cell proliferation marker proliferating cell nuclear antigen (PCNA), and the cyclin-dependent kinase (CDK) inhibitor Cdkn2a, as detected by immunohistochemistry in cortical neurons of the APP/PS1 mice. Taken together, the cell cycle-related changes in brain and blood cells reported here support the mitosis failure hypothesis in AD and validate the use of peripheral cells as surrogate tissue to study the molecular basis of AD pathogenesis. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Pseudolaric Acid B Induced Cell Cycle Arrest, Autophagy and Senescence in Murine Fibrosarcoma L929 Cell

PubMed Central

hua Yu, Jing; yu Liu, Chun; bin Zheng, Gui; Zhang, Li Ying; hui Yan, Ming; yan Zhang, Wen; ying Meng, Xian; fang Yu, Xiao

2013-01-01

Objective: PAB induced various cancer cell apoptosis, cell cycle arrest and senescence. But in cell line murine fibrosarcoma L929, PAB did not induce apoptosis, but autophagy, therefore it was thought by us as a good model to research the relationship of cell cycle arrest, autophagy and senescence bypass apoptosis. Methods: Inhibitory ratio was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis. Phase contrast microscopy visualized cell morphology. Hoechst 33258 staining for nuclear change, propidium iodode (PI) staining for cell cycle, monodansylcadaverine (MDC) staining for autophagy, and rodanmine 123 staining for mitochondrial membrane potential (MMP) were measured by fluorescence microscopy or flowcytometry. Apoptosis was determined by DNA ladder test. Protein kinase C (PKC) activity was detected by PKC assay kit. SA-β-galactosidase assay was used to detect senescence. Protein expression was examined by western blot. Results: PAB inhibited L929 cell growth in time-and dose-dependent manner. At 12 h, 80 μmol/L PAB induced obvious mitotic arrest; at 24 h, PAB began to induce autophagy; at 36 h, cell-treated with PAB slip into G1 cell cycle; and 3 d PAB induced senescence. In time sequence PAB induced firstly cell cycle arrest, then autophagy, then slippage into G1 phase, lastly senescence. Senescent cells had high level of autophagy, inhibiting autophagy led to apoptosis, and no senescence. PAB activated PKC activity to induce cell cycle arrest, autophagy and senescence, inhibiting PKC activity suppressed cell cycle arrest, autophagy and senescence. Conclusion: PAB induced cell cycle arrest, autophagy and senescence in murine fibrosarcoma L929 cell through PKC. PMID:23630435

SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP-1 cells

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

Bonifati, Serena; Daly, Michele B.; St Gelais, Corine

SAMHD1 limits HIV-1 infection in non-dividing myeloid cells by decreasing intracellular dNTP pools. HIV-1 restriction by SAMHD1 in these cells likely prevents activation of antiviral immune responses and modulates viral pathogenesis, thus highlighting a critical role of SAMHD1 in HIV-1 physiopathology. Here, we explored the function of SAMHD1 in regulating cell proliferation, cell cycle progression and apoptosis in monocytic THP-1 cells. Using the CRISPR/Cas9 technology, we generated THP-1 cells with stable SAMHD1 knockout. We found that silencing of SAMHD1 in cycling cells stimulates cell proliferation, redistributes cell cycle population in the G{sub 1}/G{sub 0} phase and reduces apoptosis. These alterationsmore » correlated with increased dNTP levels and more efficient HIV-1 infection in dividing SAMHD1 knockout cells relative to control. Our results suggest that SAMHD1, through its dNTPase activity, affects cell proliferation, cell cycle distribution and apoptosis, and emphasize a key role of SAMHD1 in the interplay between cell cycle regulation and HIV-1 infection.« less

Rethinking cell-cycle-dependent gene expression in Schizosaccharomyces pombe.

PubMed

Cooper, Stephen

2017-11-01

Three studies of gene expression during the division cycle of Schizosaccharomyces pombe led to the proposal that a large number of genes are expressed at particular times during the S. pombe cell cycle. Yet only a small fraction of genes proposed to be expressed in a cell-cycle-dependent manner are reproducible in all three published studies. In addition to reproducibility problems, questions about expression amplitudes, cell-cycle timing of expression, synchronization artifacts, and the problem with methods for synchronizing cells must be considered. These problems and complications prompt the idea that caution should be used before accepting the conclusion that there are a large number of genes expressed in a cell-cycle-dependent manner in S. pombe.

Luminous Enteric Bacteria of Marine Fishes: a Study of Their Distribution, Densities, and Dispersion †

PubMed Central

Ruby, E. G.; Morin, J. G.

1979-01-01

Three taxa of luminous bacteria (Photobacterium fischeri, P. phosphoreum, and Beneckea spp.) were found in the enteric microbial populations of 22 species of surface- and midwater-dwelling fishes. These bacteria often occurred in concentrations ranging between 105 and 107 colony-forming units per ml of enteric contents. By using a genetically marked strain, it was determined that luminous cells entering the fish during ingestion of seawater or contaminated particles traversed the alimentary tract and survived the digestive processes. After excretion, luminous bacteria proliferated extensively on the fecal material and became distributed into the surrounding seawater. Thus, this enteric habitat may serve as an enrichment of viable cells entering the planktonic luminous population. PMID:16345429

Increasing cellular coverage within integrated terrestrial/satellite mobile networks

NASA Technical Reports Server (NTRS)

Castro, Jonathan P.

1995-01-01

When applying the hierarchical cellular concept, the satellite acts as giant umbrella cell covering a region with some terrestrial cells. If a mobile terminal traversing the region arrives to the border-line or limits of a regular cellular ground service, network transition occurs and the satellite system continues the mobile coverage. To adequately assess the boundaries of service of a mobile satellite system an a cellular network within an integrated environment, this paper provides an optimized scheme to predict when a network transition may be necessary. Under the assumption of a classified propagation phenomenon and Lognormal shadowing, the study applies an analytical approach to estimate the location of a mobile terminal based on a reception of the signal strength emitted by a base station.

Prodrugs of phosphonates and phosphates: crossing the membrane barrier

PubMed Central

Wiemer, Andrew J.; Wiemer, David F.

2016-01-01

A substantial portion of metabolism involves transformation of phosphate esters, including pathways leading to nucleotides and oligonucleotides, carbohydrates, isoprenoids and steroids, and phosphorylated proteins. Because the natural substrates bear one or more negative charges, drugs that target these enzymes generally must be charged as well but small charged molecules can have difficulty traversing the cell membrane other than by endocytosis. The resulting dichotomy has stimulated abundant effort to develop effective prodrugs, compounds that carry little or no charge to enable them to transit biological membranes but then able to release the parent drug once inside the target cell. This chapter will present recent studies on advances in prodrug forms, along with representative examples of their application to marketed and developmental drugs. PMID:25391982

Molecular machinery of signal transduction and cell cycle regulation in Plasmodium.

PubMed

Koyama, Fernanda C; Chakrabarti, Debopam; Garcia, Célia R S

2009-05-01

The regulation of the Plasmodium cell cycle is not understood. Although the Plasmodium falciparum genome is completely sequenced, about 60% of the predicted proteins share little or no sequence similarity with other eukaryotes. This feature impairs the identification of important proteins participating in the regulation of the cell cycle. There are several open questions that concern cell cycle progression in malaria parasites, including the mechanism by which multiple nuclear divisions is controlled and how the cell cycle is managed in all phases of their complex life cycle. Cell cycle synchrony of the parasite population within the host, as well as the circadian rhythm of proliferation, are striking features of some Plasmodium species, the molecular basis of which remains to be elucidated. In this review we discuss the role of indole-related molecules as signals that modulate the cell cycle in Plasmodium and other eukaryotes, and we also consider the possible role of kinases in the signal transduction and in the responses it triggers.

The Abbreviated Pluripotent Cell Cycle

PubMed Central

Kapinas, Kristina; Grandy, Rodrigo; Ghule, Prachi; Medina, Ricardo; Becker, Klaus; Pardee, Arthur; Zaidi, Sayyed K.; Lian, Jane; Stein, Janet; van Wijnen, Andre; Stein, Gary

2013-01-01

Human embryonic stem cells and induced pluripotent stem cells proliferate rapidly and divide symmetrically producing equivalent progeny cells. In contrast, lineage committed cells acquire an extended symmetrical cell cycle. Self-renewal of tissue-specific stem cells is sustained by asymmetric cell division where one progeny cell remains a progenitor while the partner progeny cell exits the cell cycle and differentiates. There are three principal contexts for considering the operation and regulation of the pluripotent cell cycle: temporal, regulatory andstructural. The primary temporal context that the pluripotent self-renewal cell cycle of human embryonic stem cells (hESCs) is a short G1 period without reducing periods of time allocated to S phase, G2, and mitosis. The rules that govern proliferation in hESCs remain to be comprehensively established. However, several lines of evidence suggest a key role for the naïve transcriptome of hESCs, which is competent to stringently regulate the ESC cell cycle. This supports the requirements of pluripotent cells to self propagate while suppressing expression of genes that confer lineage commitment and/or tissue specificity. However, for the first time, we consider unique dimensions to the architectural organization and assembly of regulatory machinery for gene expression in nuclear microenviornments that define parameters of pluripotency. From both fundamental biological and clinical perspectives, understanding control of the abbreviated embryonic stem cell cycle can provide options to coordinate control of proliferation versus differentiation. Wound healing, tissue engineering, and cell-based therapy to mitigate developmental aberrations illustrate applications that benefit from knowledge of the biology of the pluripotent cell cycle. PMID:22552993

Proteomic analysis of the bacterial cell cycle

PubMed Central

Grünenfelder, Björn; Rummel, Gabriele; Vohradsky, Jiri; Röder, Daniel; Langen, Hanno; Jenal, Urs

2001-01-01

A global approach was used to analyze protein synthesis and stability during the cell cycle of the bacterium Caulobacter crescentus. Approximately one-fourth (979) of the estimated C. crescentus gene products were detected by two-dimensional gel electrophoresis, 144 of which showed differential cell cycle expression patterns. Eighty-one of these proteins were identified by mass spectrometry and were assigned to a wide variety of functional groups. Pattern analysis revealed that coexpression groups were functionally clustered. A total of 48 proteins were rapidly degraded in the course of one cell cycle. More than half of these unstable proteins were also found to be synthesized in a cell cycle-dependent manner, establishing a strong correlation between rapid protein turnover and the periodicity of the bacterial cell cycle. This is, to our knowledge, the first evidence for a global role of proteolysis in bacterial cell cycle control. PMID:11287652

Regulation of steroid hormone receptors and coregulators during the cell cycle highlights potential novel function in addition to roles as transcription factors

PubMed Central

Zheng, Yingfeng; Murphy, Leigh C.

2016-01-01

Cell cycle progression is tightly controlled by several kinase families including Cyclin-Dependent Kinases, Polo-Like Kinases, and Aurora Kinases. A large amount of data show that steroid hormone receptors and various components of the cell cycle, including cell cycle regulated kinases, interact, and this often results in altered transcriptional activity of the receptor. Furthermore, steroid hormones, through their receptors, can also regulate the transcriptional expression of genes that are required for cell cycle regulation. However, emerging data suggest that steroid hormone receptors may have roles in cell cycle progression independent of their transcriptional activity. The following is a review of how steroid receptors and their coregulators can regulate or be regulated by the cell cycle machinery, with a particular focus on roles independent of transcription in G2/M. PMID:26778927

Regulation of cell division cycle progression by bcl-2 expression: a potential mechanism for inhibition of programmed cell death

PubMed Central

1996-01-01

Expression of the bcl-2 gene has been shown to effectively confer resistance to programmed cell death under a variety of circumstances. However, despite a wealth of literature describing this phenomenon, very little is known about the mechanism of resistance. In the experiments described here, we show that bcl-2 gene expression can result in an inhibition of cell division cycle progression. These findings are based upon the analysis of cell cycle distribution, cell cycle kinetics, and relative phosphorylation of the retinoblastoma tumor suppressor protein, using primary tissues in vivo, ex vivo, and in vitro, as well as continuous cell lines. The effects of bcl-2 expression on cell cycle progression appear to be focused at the G1 to S phase transition, which is a critical control point in the decision between continued cell cycle progression or the induction programmed cell death. In all systems tested, bcl-2 expression resulted in a substantial 30-60% increase in the length of G1 phase; such an increase is very substantial in the context of other regulators of cell cycle progression. Based upon our findings, and the related findings of others, we propose a mechanism by which bcl-2 expression might exert its well known inhibition of programmed cell death by regulating the kinetics of cell cycle progression at a critical control point. PMID:8642331

The Effect of the Traverse Feed Rate on the Microstructure and Mechanical Properties of Laser Deposited Fe₃Al (Zr,B) Intermetallic Alloy.

PubMed

Łazińska, Magdalena; Durejko, Tomasz; Czujko, Tomasz; Bojar, Zbigniew

2018-05-14

The results of the fabrication of components made with Fe-30%Al-0.35%Zr-0.1%B alloy powder using the Laser Engineered Net Shaping (LENS TM ) system operated at different traverse feed rates are described in this paper. The temperature of the molten metal pool was recorded during this process. Depending on the assumed feed rate, the formation of Zr⁻based precipitates with various morphologies and distributions was observed in the structure of the investigated material. It was found that as the traverse speed increased, spheroidization, refinement, and a more homogeneous distribution of these precipitates occurred.

Targeted Approaches to Overcoming Endocrine Resistance in Breast Cancer

DTIC Science & Technology

2011-08-01

NM_001012271 BUB1 BUB1 budding uninhibited by benzimidazoles 1 homolog AF053305 CDC20 Cell division cycle 20 homolog BG256659 CDC25B Cell division cycle...by benzimidazoles 1 homolog), BIRC5/ Survivin, CDCA8 (cell division cycle-associated protein 8), AURKB (aurora kinase B), CDC25B (cell division cycle

Circadian clock regulation of the cell cycle in the zebrafish intestine.

PubMed

Peyric, Elodie; Moore, Helen A; Whitmore, David

2013-01-01

The circadian clock controls cell proliferation in a number of healthy tissues where cell renewal and regeneration are critical for normal physiological function. The intestine is an organ that typically undergoes regular cycles of cell division, differentiation and apoptosis as part of its role in digestion and nutrient absorption. The aim of this study was to explore circadian clock regulation of cell proliferation and cell cycle gene expression in the zebrafish intestine. Here we show that the zebrafish gut contains a directly light-entrainable circadian pacemaker, which regulates the daily timing of mitosis. Furthermore, this intestinal clock controls the expression of key cell cycle regulators, such as cdc2, wee1, p21, PCNA and cdk2, but only weakly influences cyclin B1, cyclin B2 and cyclin E1 expression. Interestingly, food deprivation has little impact on circadian clock function in the gut, but dramatically reduces cell proliferation, as well as cell cycle gene expression in this tissue. Timed feeding under constant dark conditions is able to drive rhythmic expression not only of circadian clock genes, but also of several cell cycle genes, suggesting that food can entrain the clock, as well as the cell cycle in the intestine. Rather surprisingly, we found that timed feeding is critical for high amplitude rhythms in cell cycle gene expression, even when zebrafish are maintained on a light-dark cycle. Together these results suggest that the intestinal clock integrates multiple rhythmic cues, including light and food, to function optimally.

Circadian Clock Regulation of the Cell Cycle in the Zebrafish Intestine

PubMed Central

Peyric, Elodie; Moore, Helen A.; Whitmore, David

2013-01-01

The circadian clock controls cell proliferation in a number of healthy tissues where cell renewal and regeneration are critical for normal physiological function. The intestine is an organ that typically undergoes regular cycles of cell division, differentiation and apoptosis as part of its role in digestion and nutrient absorption. The aim of this study was to explore circadian clock regulation of cell proliferation and cell cycle gene expression in the zebrafish intestine. Here we show that the zebrafish gut contains a directly light-entrainable circadian pacemaker, which regulates the daily timing of mitosis. Furthermore, this intestinal clock controls the expression of key cell cycle regulators, such as cdc2, wee1, p21, PCNA and cdk2, but only weakly influences cyclin B1, cyclin B2 and cyclin E1 expression. Interestingly, food deprivation has little impact on circadian clock function in the gut, but dramatically reduces cell proliferation, as well as cell cycle gene expression in this tissue. Timed feeding under constant dark conditions is able to drive rhythmic expression not only of circadian clock genes, but also of several cell cycle genes, suggesting that food can entrain the clock, as well as the cell cycle in the intestine. Rather surprisingly, we found that timed feeding is critical for high amplitude rhythms in cell cycle gene expression, even when zebrafish are maintained on a light-dark cycle. Together these results suggest that the intestinal clock integrates multiple rhythmic cues, including light and food, to function optimally. PMID:24013905

ARTD1 regulates cyclin E expression and consequently cell-cycle re-entry and G1/S progression in T24 bladder carcinoma cells.

PubMed

Léger, Karolin; Hopp, Ann-Katrin; Fey, Monika; Hottiger, Michael O

2016-08-02

ADP-ribosylation is involved in a variety of biological processes, many of which are chromatin-dependent and linked to important functions during the cell cycle. However, any study on ADP-ribosylation and the cell cycle faces the problem that synchronization with chemical agents or by serum starvation and subsequent growth factor addition already activates ADP-ribosylation by itself. Here, we investigated the functional contribution of ARTD1 in cell cycle re-entry and G1/S cell cycle progression using T24 urinary bladder carcinoma cells, which synchronously re-enter the cell cycle after splitting without any additional stimuli. In synchronized cells, ARTD1 knockdown, but not inhibition of its enzymatic activity, caused specific down-regulation of cyclin E during cell cycle re-entry and G1/S progression through alterations of the chromatin composition and histone acetylation, but not of other E2F-1 target genes. Although Cdk2 formed a functional complex with the residual cyclin E, p27(Kip 1) protein levels increased in G1 upon ARTD1 knockdown most likely due to inappropriate cyclin E-Cdk2-induced phosphorylation-dependent degradation, leading to decelerated G1/S progression. These results provide evidence that ARTD1 regulates cell cycle re-entry and G1/S progression via cyclin E expression and p27(Kip 1) stability independently of its enzymatic activity, uncovering a novel cell cycle regulatory mechanism.

Estrogen receptor alpha is cell cycle-regulated and regulates the cell cycle in a ligand-dependent fashion

PubMed Central

JavanMoghadam, Sonia; Weihua, Zhang; Hunt, Kelly K.; Keyomarsi, Khandan

2016-01-01

ABSTRACT Estrogen receptor alpha (ERα) has been implicated in several cell cycle regulatory events and is an important predictive marker of disease outcome in breast cancer patients. Here, we aimed to elucidate the mechanism through which ERα influences proliferation in breast cancer cells. Our results show that ERα protein is cell cycle-regulated in human breast cancer cells and that the presence of 17-β-estradiol (E2) in the culture medium shortened the cell cycle significantly (by 4.5 hours, P < 0.05) compared with unliganded conditions. The alterations in cell cycle duration were observed in the S and G2/M phases, whereas the G1 phase was indistinguishable under liganded and unliganded conditions. In addition, ERα knockdown in MCF-7 cells accelerated mitotic exit, whereas transfection of ERα-negative MDA-MB-231 cells with exogenous ERα significantly shortened the S and G2/M phases (by 9.1 hours, P < 0.05) compared with parental cells. Finally, treatment of MCF-7 cells with antiestrogens revealed that tamoxifen yields a slower cell cycle progression through the S and G2/M phases than fulvestrant does, presumably because of the destabilizing effect of fulvestrant on ERα protein. Together, these results show that ERα modulates breast cancer cell proliferation by regulating events during the S and G2/M phases of the cell cycle in a ligand-dependent fashion. These results provide the rationale for an effective treatment strategy that includes a cell cycle inhibitor in combination with a drug that lowers estrogen levels, such as an aromatase inhibitor, and an antiestrogen that does not result in the degradation of ERα, such as tamoxifen. PMID:27049344

Estrogen receptor alpha is cell cycle-regulated and regulates the cell cycle in a ligand-dependent fashion.

PubMed

JavanMoghadam, Sonia; Weihua, Zhang; Hunt, Kelly K; Keyomarsi, Khandan

2016-06-17

Estrogen receptor alpha (ERα) has been implicated in several cell cycle regulatory events and is an important predictive marker of disease outcome in breast cancer patients. Here, we aimed to elucidate the mechanism through which ERα influences proliferation in breast cancer cells. Our results show that ERα protein is cell cycle-regulated in human breast cancer cells and that the presence of 17-β-estradiol (E2) in the culture medium shortened the cell cycle significantly (by 4.5 hours, P < 0.05) compared with unliganded conditions. The alterations in cell cycle duration were observed in the S and G2/M phases, whereas the G1 phase was indistinguishable under liganded and unliganded conditions. In addition, ERα knockdown in MCF-7 cells accelerated mitotic exit, whereas transfection of ERα-negative MDA-MB-231 cells with exogenous ERα significantly shortened the S and G2/M phases (by 9.1 hours, P < 0.05) compared with parental cells. Finally, treatment of MCF-7 cells with antiestrogens revealed that tamoxifen yields a slower cell cycle progression through the S and G2/M phases than fulvestrant does, presumably because of the destabilizing effect of fulvestrant on ERα protein. Together, these results show that ERα modulates breast cancer cell proliferation by regulating events during the S and G2/M phases of the cell cycle in a ligand-dependent fashion. These results provide the rationale for an effective treatment strategy that includes a cell cycle inhibitor in combination with a drug that lowers estrogen levels, such as an aromatase inhibitor, and an antiestrogen that does not result in the degradation of ERα, such as tamoxifen.

High-throughput synchronization of mammalian cell cultures by spiral microfluidics.

PubMed

Lee, Wong Cheng; Bhagat, Ali Asgar S; Lim, Chwee Teck

2014-01-01

The development of mammalian cell cycle synchronization techniques has greatly advanced our understanding of many cellular regulatory events and mechanisms specific to different phases of the cell cycle. In this chapter, we describe a high-throughput microfluidic-based approach for cell cycle synchronization. By exploiting the relationship between cell size and its phase in the cell cycle, large numbers of synchronized cells can be obtained by size fractionation in a spiral microfluidic channel. Protocols for the synchronization of primary cells such as mesenchymal stem cells, and immortal cell lines such as Chinese hamster ovarian cells (CHO-CD36) and HeLa cells are provided as examples.

Cell cycle progression is an essential regulatory component of phospholipid metabolism and membrane homeostasis

PubMed Central

Sanchez-Alvarez, Miguel; Zhang, Qifeng; Finger, Fabian; Wakelam, Michael J. O.; Bakal, Chris

2015-01-01

We show that phospholipid anabolism does not occur uniformly during the metazoan cell cycle. Transition to S-phase is required for optimal mobilization of lipid precursors, synthesis of specific phospholipid species and endoplasmic reticulum (ER) homeostasis. Average changes observed in whole-cell phospholipid composition, and total ER lipid content, upon stimulation of cell growth can be explained by the cell cycle distribution of the population. TORC1 promotes phospholipid anabolism by slowing S/G2 progression. The cell cycle stage-specific nature of lipid biogenesis is dependent on p53. We propose that coupling lipid metabolism to cell cycle progression is a means by which cells have evolved to coordinate proliferation with cell and organelle growth. PMID:26333836

Cell cycle progression is an essential regulatory component of phospholipid metabolism and membrane homeostasis.

PubMed

Sanchez-Alvarez, Miguel; Zhang, Qifeng; Finger, Fabian; Wakelam, Michael J O; Bakal, Chris

2015-09-01

We show that phospholipid anabolism does not occur uniformly during the metazoan cell cycle. Transition to S-phase is required for optimal mobilization of lipid precursors, synthesis of specific phospholipid species and endoplasmic reticulum (ER) homeostasis. Average changes observed in whole-cell phospholipid composition, and total ER lipid content, upon stimulation of cell growth can be explained by the cell cycle distribution of the population. TORC1 promotes phospholipid anabolism by slowing S/G2 progression. The cell cycle stage-specific nature of lipid biogenesis is dependent on p53. We propose that coupling lipid metabolism to cell cycle progression is a means by which cells have evolved to coordinate proliferation with cell and organelle growth. © 2015 The Authors.

Coordinating cell proliferation and differentiation: Antagonism between cell cycle regulators and cell type-specific gene expression

PubMed Central

Ruijtenberg, Suzan; van den Heuvel, Sander

2016-01-01

ABSTRACT Cell proliferation and differentiation show a remarkable inverse relationship. Precursor cells continue division before acquiring a fully differentiated state, while terminal differentiation usually coincides with proliferation arrest and permanent exit from the division cycle. Mechanistic insight in the temporal coordination between cell cycle exit and differentiation has come from studies of cells in culture and genetic animal models. As initially described for skeletal muscle differentiation, temporal coordination involves mutual antagonism between cyclin-dependent kinases that promote cell cycle entry and transcription factors that induce tissue-specific gene expression. Recent insights highlight the contribution of chromatin-regulating complexes that act in conjunction with the transcription factors and determine their activity. In particular SWI/SNF chromatin remodelers contribute to dual regulation of cell cycle and tissue-specific gene expression during terminal differentiation. We review the concerted regulation of the cell cycle and cell type-specific transcription, and discuss common mutations in human cancer that emphasize the clinical importance of proliferation versus differentiation control. PMID:26825227

Redox Changes During the Cell Cycle in the Embryonic Root Meristem of Arabidopsis thaliana.

PubMed

de Simone, Ambra; Hubbard, Rachel; de la Torre, Natanael Viñegra; Velappan, Yazhini; Wilson, Michael; Considine, Michael J; Soppe, Wim J J; Foyer, Christine H

2017-12-20

The aim of this study was to characterize redox changes in the nuclei and cytosol occurring during the mitotic cell cycle in the embryonic roots of germinating Arabidopsis seedlings, and to determine how redox cycling was modified in mutants with a decreased capacity for ascorbate synthesis. Using an in vivo reduction-oxidation (redox) reporter (roGFP2), we show that transient oxidation of the cytosol and the nuclei occurred at G1 in the synchronized dividing cells of the Arabidopsis root apical meristem, with reduction at G2 and mitosis. This redox cycle was absent from low ascorbate mutants in which nuclei were significantly more oxidized than controls. The cell cycle-dependent increase in nuclear size was impaired in the ascorbate-deficient mutants, which had fewer cells per unit area in the root proliferation zone. The transcript profile of the dry seeds and size of the imbibed seeds was strongly influenced by low ascorbate but germination, dormancy release and seed aging characteristics were unaffected. These data demonstrate the presence of a redox cycle within the plant cell cycle and that the redox state of the nuclei is an important factor in cell cycle progression. Controlled oxidation is a key feature of the early stages of the plant cell cycle. However, sustained mild oxidation restricts nuclear functions and impairs progression through the cell cycle leading to fewer cells in the root apical meristem. Antioxid. Redox Signal. 27, 1505-1519.

Dihydroartemisinin inhibits indoxyl sulfate (IS)-promoted cell cycle progression in mesangial cells by targeting COX-2/mPGES-1/PGE2 cascade.

PubMed

Mungun, Harr-Keshauve; Li, Shuzhen; Zhang, Yue; Huang, Songming; Jia, Zhanjun; Ding, Guixia; Zhang, Aihua

2018-01-01

Dihydroartemisinin (DHA) is a semisynthetic derivative of artemisinin and has been used as an antimalarial drug. Recently, roles of artemisinin and its derivatives in treating diseases besides antimalarial effect were documented. Thus, this study was undertaken to investigate the role of DHA in indoxyl sulfate (IS)-promoted cell cycle progression in glomerular mesangial cells, as well as the potential mechanisms. Under the basal condition, DHA significantly retarded the cell cycle progression as shown by decreased cell percentage in S phase and increased cell percentage in G1/G0 phases in line with reduced cell cycle proteins cyclin A2 and cyclin D1. Interestingly, DHA also inactivated the COX-2/mPGES-1/PGE 2 cascade which has been shown to play a critical role in promoting the mesangial cell cycle progression by our previous studies. Next, we investigated the role of DHA in IS-triggered cell cycle progression in this mesangial cell line. As expected, DHA treatment significantly retarded IS-induced cell cycle progression and inhibited the activation of COX-2/mPGES-1/PGE 2 cascade induced by IS. In summary, these data indicated that DHA inhibited the cell cycle progression in glomerular mesangial cells under normal condition or IS challenge possibly through the inhibition of COX-2/mPGES-1/PGE 2 cascade, suggesting a potential of DHA in treating glomerular diseases with mesangial cell proliferation.

A genome-wide resource of cell cycle and cell shape genes of fission yeast

PubMed Central

Hayles, Jacqueline; Wood, Valerie; Jeffery, Linda; Hoe, Kwang-Lae; Kim, Dong-Uk; Park, Han-Oh; Salas-Pino, Silvia; Heichinger, Christian; Nurse, Paul

2013-01-01

To identify near complete sets of genes required for the cell cycle and cell shape, we have visually screened a genome-wide gene deletion library of 4843 fission yeast deletion mutants (95.7% of total protein encoding genes) for their effects on these processes. A total of 513 genes have been identified as being required for cell cycle progression, 276 of which have not been previously described as cell cycle genes. Deletions of a further 333 genes lead to specific alterations in cell shape and another 524 genes result in generally misshapen cells. Here, we provide the first eukaryotic resource of gene deletions, which describes a near genome-wide set of genes required for the cell cycle and cell shape. PMID:23697806

Systems-level feedback regulation of cell cycle transitions in Ostreococcus tauri.

PubMed

Kapuy, Orsolya; Vinod, P K; Bánhegyi, Gábor; Novák, Béla

2018-05-01

Ostreococcus tauri is the smallest free-living unicellular organism with one copy of each core cell cycle genes in its genome. There is a growing interest in this green algae due to its evolutionary origin. Since O. tauri is diverged early in the green lineage, relatively close to the ancestral eukaryotic cell, it might hold a key phylogenetic position in the eukaryotic tree of life. In this study, we focus on the regulatory network of its cell division cycle. We propose a mathematical modelling framework to integrate the existing knowledge of cell cycle network of O. tauri. We observe that feedback loop regulation of both G1/S and G2/M transitions in O. tauri is conserved, which can make the transition bistable. This is essential to make the transition irreversible as shown in other eukaryotic organisms. By performing sequence analysis, we also predict the presence of the Greatwall/PP2A pathway in the cell cycle of O. tauri. Since O. tauri cell cycle machinery is conserved, the exploration of the dynamical characteristic of the cell division cycle will help in further understanding the regulation of cell cycle in higher eukaryotes. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Revealing the cellular localization of STAT1 during the cell cycle by super-resolution imaging

PubMed Central

Gao, Jing; Wang, Feng; Liu, Yanhou; Cai, Mingjun; Xu, Haijiao; Jiang, Junguang; Wang, Hongda

2015-01-01

Signal transducers and activators of transcription (STATs) can transduce cytokine signals and regulate gene expression. The cellular localization and nuclear trafficking of STAT1, a representative of the STAT family with multiple transcriptional functions, is tightly related with transcription process, which usually happens in the interphase of the cell cycle. However, these priority questions regarding STAT1 distribution and localization at the different cell-cycle stages remain unclear. By using direct stochastic optical reconstruction microscopy (dSTORM), we found that the nuclear expression level of STAT1 increased gradually as the cell cycle carried out, especially after EGF stimulation. Furthermore, STAT1 formed clusters in the whole cell during the cell cycle, with the size and the number of clusters also increasing significantly from G1 to G2 phase, suggesting that transcription and other cell-cycle related activities can promote STAT1 to form more and larger clusters for fast response to signals. Our work reveals that the cellular localization and clustering distribution of STAT1 are associated with the cell cycle, and further provides an insight into the mechanism of cell-cycle regulated STAT1 signal transduction. PMID:25762114

Serial Charging Test on High Capacity Li-Ion Cells for the Orbiter Advanced Hydraulic Power System

NASA Technical Reports Server (NTRS)

Jeevarajan, Judith A.; Irlbeck, Brad

2006-01-01

Although it looks like module level voltage drives the cutoff for charge, the actual cutoff is due to unbalanced cell voltages that drive the module voltage up. Individual cell voltage drives the cutoff for discharge Low resistance cells are the first to reach the low-voltage cutoff Cell-to-Cell voltage differences are generally small and show similar trends for each cycle Increase for a distinct window during charge and at the end of discharge Increase in max to min cell voltage difference with time/cycles Decrease in max to min cell voltage difference during high current pulses with time/cycles Individual cell voltage trends (with respect to other cells) are very repeatable from cycle to cycle, although voltage slowly degrades with time/cycles (resistance growth) Much more difference observed near end of discharge Little change in order of cell voltage (cell with highest voltage to cell with lowest voltage) Temp sensor on the side of cell (between 2 cells) shows much greater rise during discharge than for single cell tests (18 C vs 5 C) Conclusion: Serial Charging of this string of cells is feasible as it has only a minor impact on useful capacity

Open data set of live cyanobacterial cells imaged using an X-ray laser

NASA Astrophysics Data System (ADS)

van der Schot, Gijs; Svenda, Martin; Maia, Filipe R. N. C.; Hantke, Max F.; Deponte, Daniel P.; Seibert, M. Marvin; Aquila, Andrew; Schulz, Joachim; Kirian, Richard A.; Liang, Mengning; Stellato, Francesco; Bari, Sadia; Iwan, Bianca; Andreasson, Jakob; Timneanu, Nicusor; Bielecki, Johan; Westphal, Daniel; Nunes de Almeida, Francisca; Odić, Duško; Hasse, Dirk; Carlsson, Gunilla H.; Larsson, Daniel S. D.; Barty, Anton; Martin, Andrew V.; Schorb, Sebastian; Bostedt, Christoph; Bozek, John D.; Carron, Sebastian; Ferguson, Ken; Rolles, Daniel; Rudenko, Artem; Epp, Sascha W.; Foucar, Lutz; Rudek, Benedikt; Erk, Benjamin; Hartmann, Robert; Kimmel, Nils; Holl, Peter; Englert, Lars; Loh, N. Duane; Chapman, Henry N.; Andersson, Inger; Hajdu, Janos; Ekeberg, Tomas

2016-08-01

Structural studies on living cells by conventional methods are limited to low resolution because radiation damage kills cells long before the necessary dose for high resolution can be delivered. X-ray free-electron lasers circumvent this problem by outrunning key damage processes with an ultra-short and extremely bright coherent X-ray pulse. Diffraction-before-destruction experiments provide high-resolution data from cells that are alive when the femtosecond X-ray pulse traverses the sample. This paper presents two data sets from micron-sized cyanobacteria obtained at the Linac Coherent Light Source, containing a total of 199,000 diffraction patterns. Utilizing this type of diffraction data will require the development of new analysis methods and algorithms for studying structure and structural variability in large populations of cells and to create abstract models. Such studies will allow us to understand living cells and populations of cells in new ways. New X-ray lasers, like the European XFEL, will produce billions of pulses per day, and could open new areas in structural sciences.

Open data set of live cyanobacterial cells imaged using an X-ray laser.

PubMed

van der Schot, Gijs; Svenda, Martin; Maia, Filipe R N C; Hantke, Max F; DePonte, Daniel P; Seibert, M Marvin; Aquila, Andrew; Schulz, Joachim; Kirian, Richard A; Liang, Mengning; Stellato, Francesco; Bari, Sadia; Iwan, Bianca; Andreasson, Jakob; Timneanu, Nicusor; Bielecki, Johan; Westphal, Daniel; Nunes de Almeida, Francisca; Odić, Duško; Hasse, Dirk; Carlsson, Gunilla H; Larsson, Daniel S D; Barty, Anton; Martin, Andrew V; Schorb, Sebastian; Bostedt, Christoph; Bozek, John D; Carron, Sebastian; Ferguson, Ken; Rolles, Daniel; Rudenko, Artem; Epp, Sascha W; Foucar, Lutz; Rudek, Benedikt; Erk, Benjamin; Hartmann, Robert; Kimmel, Nils; Holl, Peter; Englert, Lars; Loh, N Duane; Chapman, Henry N; Andersson, Inger; Hajdu, Janos; Ekeberg, Tomas

2016-08-01

Structural studies on living cells by conventional methods are limited to low resolution because radiation damage kills cells long before the necessary dose for high resolution can be delivered. X-ray free-electron lasers circumvent this problem by outrunning key damage processes with an ultra-short and extremely bright coherent X-ray pulse. Diffraction-before-destruction experiments provide high-resolution data from cells that are alive when the femtosecond X-ray pulse traverses the sample. This paper presents two data sets from micron-sized cyanobacteria obtained at the Linac Coherent Light Source, containing a total of 199,000 diffraction patterns. Utilizing this type of diffraction data will require the development of new analysis methods and algorithms for studying structure and structural variability in large populations of cells and to create abstract models. Such studies will allow us to understand living cells and populations of cells in new ways. New X-ray lasers, like the European XFEL, will produce billions of pulses per day, and could open new areas in structural sciences.

Open data set of live cyanobacterial cells imaged using an X-ray laser

PubMed Central

van der Schot, Gijs; Svenda, Martin; Maia, Filipe R.N.C.; Hantke, Max F.; DePonte, Daniel P.; Seibert, M. Marvin; Aquila, Andrew; Schulz, Joachim; Kirian, Richard A.; Liang, Mengning; Stellato, Francesco; Bari, Sadia; Iwan, Bianca; Andreasson, Jakob; Timneanu, Nicusor; Bielecki, Johan; Westphal, Daniel; Nunes de Almeida, Francisca; Odić, Duško; Hasse, Dirk; Carlsson, Gunilla H.; Larsson, Daniel S.D.; Barty, Anton; Martin, Andrew V.; Schorb, Sebastian; Bostedt, Christoph; Bozek, John D.; Carron, Sebastian; Ferguson, Ken; Rolles, Daniel; Rudenko, Artem; Epp, Sascha W.; Foucar, Lutz; Rudek, Benedikt; Erk, Benjamin; Hartmann, Robert; Kimmel, Nils; Holl, Peter; Englert, Lars; Loh, N. Duane; Chapman, Henry N.; Andersson, Inger; Hajdu, Janos; Ekeberg, Tomas

2016-01-01

Structural studies on living cells by conventional methods are limited to low resolution because radiation damage kills cells long before the necessary dose for high resolution can be delivered. X-ray free-electron lasers circumvent this problem by outrunning key damage processes with an ultra-short and extremely bright coherent X-ray pulse. Diffraction-before-destruction experiments provide high-resolution data from cells that are alive when the femtosecond X-ray pulse traverses the sample. This paper presents two data sets from micron-sized cyanobacteria obtained at the Linac Coherent Light Source, containing a total of 199,000 diffraction patterns. Utilizing this type of diffraction data will require the development of new analysis methods and algorithms for studying structure and structural variability in large populations of cells and to create abstract models. Such studies will allow us to understand living cells and populations of cells in new ways. New X-ray lasers, like the European XFEL, will produce billions of pulses per day, and could open new areas in structural sciences. PMID:27479514

Cell cycle gene expression networks discovered using systems biology: Significance in carcinogenesis

PubMed Central

Scott, RE; Ghule, PN; Stein, JL; Stein, GS

2015-01-01

The early stages of carcinogenesis are linked to defects in the cell cycle. A series of cell cycle checkpoints are involved in this process. The G1/S checkpoint that serves to integrate the control of cell proliferation and differentiation is linked to carcinogenesis and the mitotic spindle checkpoint with the development of chromosomal instability. This paper presents the outcome of systems biology studies designed to evaluate if networks of covariate cell cycle gene transcripts exist in proliferative mammalian tissues including mice, rats and humans. The GeneNetwork website that contains numerous gene expression datasets from different species, sexes and tissues represents the foundational resource for these studies (www.genenetwork.org). In addition, WebGestalt, a gene ontology tool, facilitated the identification of expression networks of genes that co-vary with key cell cycle targets, especially Cdc20 and Plk1 (www.bioinfo.vanderbilt.edu/webgestalt). Cell cycle expression networks of such covariate mRNAs exist in multiple proliferative tissues including liver, lung, pituitary, adipose and lymphoid tissues among others but not in brain or retina that have low proliferative potential. Sixty-three covariate cell cycle gene transcripts (mRNAs) compose the average cell cycle network with p = e−13 to e−36. Cell cycle expression networks show species, sex and tissue variability and they are enriched in mRNA transcripts associated with mitosis many of which are associated with chromosomal instability. PMID:25808367

Artist's concept of Hadley-Apennine landing site with LRV traverses outlined

NASA Technical Reports Server (NTRS)

1971-01-01

An artist's concept of the Hadley-Apennine landing site, depicting the traverses planned on the Apollo 15 lunar landing mission using the Lunar Roving Vehicle (LRV). The Roman numerals indicate the three periods of extravehicular activity (EVA). The Arabic numbers represent the station stops. Art work by Jerry Elmore.

Lunar Reconnaissance Orbiter Camera

Science.gov Websites

them out » Traverse featurette Traverse the Apollo Landing Sites & More. By combining LROC imagery , data, and historical data, we've created detailed, interactive maps of the Apollo Landing Sites and taken by the original Apollo crews. ASU maintains the Apollo Digital Image Archive and the March to the

An Analysis of Special Operations Command - South’s Distributive Command and Control Concept

DTIC Science & Technology

2007-12-01

Special Ops aviation unit traverses Bermuda Triangle en route to new home”, News Service Release Number 03082525 (August 2003), http://news.soc.mil...7, 2007). U.S. Army Special Operations Command. “Special Ops Aviation Unit Traverses Bermuda Triangle En Route to New Home.” News Service Release

75 FR 53334 - Notice of Filing of Plats of Survey; Montana

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-31

... River, downstream, through sections 7 and 18, a portion of the subdivision of sections 7 and 18, a... present left bank of the Missouri River and informative traverse, downstream, through sections 7 and 18, the limits of erosion and informative traverse, downstream through sections 7 and 18 and certain...

Measurement of vortex flow fields

NASA Technical Reports Server (NTRS)

Mcdevitt, T. Kevin; Ambur, Todd A.; Orngard, Gary M.; Owen, F. Kevin

1992-01-01

A 3-D laser fluorescence anemometer (LFA) was designed, built, and demonstrated for use in the Langley 16 x 24 inch Water Tunnel. Innovative optical design flexibility combined with compact and portable data acquisition and control systems were incorporated into the instrument. This will allow its use by NASA in other test facilities. A versatile fiber optic system facilities normal and off-axis laser beam alignment, removes mirror losses and improves laser safety. This added optical flexibility will also enable simple adaptation for use in the adjacent jet facility. New proprietary concepts in transmitting color separation, light collection, and novel prism separation of the scattered light was also designed and built into the system. Off-axis beam traverse and alignment complexity led to the requirement for a specialized, programmable transverse controller, and the inclusion of an additional traverse for the off-axis arm. To meet this challenge, an 'in-house' prototype unit was designed and built and traverse control software developed specifically for the water tunnel traverse applications. A specialized data acquisition interface was also required. This was designed and built for the LFA system.

Mechanical Properties and Wear Behavior of AA5182/WC Nanocomposite Fabricated by Friction Stir Welding at Different Tool Traverse Speeds

NASA Astrophysics Data System (ADS)

Paidar, Moslem; Asgari, Ali; Ojo, Olatunji Oladimeji; Saberi, Abbas

2018-03-01

Grain growth inhibition at the heat-affected zone, improved weld strength and superior tribological properties of welds are desirable attributes of modern manufacturing. With the focused on these attributes, tungsten carbide (WC) nanoparticles were employed as reinforcements for the friction stir welding of 5-mm-thick AA5182 aluminum alloy by varying tool traverse speeds. The microstructure, microhardness, ultimate tensile strength, fracture and wear behavior of the resultant WC-reinforced welds were investigated, while unreinforced AA5182 welds were employed as controls for the study. The result shows that the addition of WC nanoparticles causes substantial grain refinement within the weld nugget. A decrease in traverse speed caused additional particle fragmentation, improved hardness value and enhanced weld strength in the reinforced welds. Improved wear rate and friction coefficient of welds were attained at a reduced traverse speed of 100 mm/min in the WC-reinforced welds. This improvement is attributed to the effects of reduced grain size/grain fragmentation and homogeneous dispersion of WC nanoparticles within the WC-reinforced weld nugget.

Spirit rover localization and topographic mapping at the landing site of Gusev crater, Mars

USGS Publications Warehouse

Li, R.; Archinal, B.A.; Arvidson, R. E.; Bell, J.; Christensen, P.; Crumpler, L.; Des Marais, D.J.; Di, K.; Duxbury, T.; Golombek, M.P.; Grant, J. A.; Greeley, R.; Guinn, J.; Johnson, Aaron H.; Kirk, R.L.; Maimone, M.; Matthies, L.H.; Malin, M.; Parker, T.; Sims, M.; Thompson, S.; Squyres, S. W.; Soderblom, L.A.

2006-01-01

By sol 440, the Spirit rover has traversed a distance of 3.76 km (actual distance traveled instead of odometry). Localization of the lander and the rover along the traverse has been successfully performed at the Gusev crater landing site. We localized the lander in the Gusev crater using two-way Doppler radio positioning and cartographic triangulations through landmarks visible in both orbital and ground images. Additional high-resolution orbital images were used to verify the determined lander position. Visual odometry and bundle adjustment technologies were applied to compensate for wheel slippage, azimuthal angle drift, and other navigation errors (which were as large as 10.5% in the Husband Hill area). We generated topographic products, including 72 ortho maps and three-dimensional (3-D) digital terrain models, 11 horizontal and vertical traverse profiles, and one 3-D crater model (up to sol 440). Also discussed in this paper are uses of the data for science operations planning, geological traverse surveys, surveys of wind-related features, and other science applications. Copyright 2006 by the American Geophysical Union.

Rover Graphical Simulator

NASA Technical Reports Server (NTRS)

Bon, Bruce; Seraji, Homayoun

2007-01-01

Rover Graphical Simulator (RGS) is a package of software that generates images of the motion of a wheeled robotic exploratory vehicle (rover) across terrain that includes obstacles and regions of varying traversability. The simulated rover moves autonomously, utilizing reasoning and decision-making capabilities of a fuzzy-logic navigation strategy to choose its path from an initial to a final state. RGS provides a graphical user interface for control and monitoring of simulations. The numerically simulated motion is represented as discrete steps with a constant time interval between updates. At each simulation step, a dot is placed at the old rover position and a graphical symbol representing the rover is redrawn at the new, updated position. The effect is to leave a trail of dots depicting the path traversed by the rover, the distances between dots being proportional to the local speed. Obstacles and regions of low traversability are depicted as filled circles, with buffer zones around them indicated by enclosing circles. The simulated robot is equipped with onboard sensors that can detect regional terrain traversability and local obstacles out to specified ranges. RGS won the NASA Group Achievement Award in 2002.

Porcine epidemic diarrhea virus through p53-dependent pathway causes cell cycle arrest in the G0/G1 phase.

PubMed

Sun, Pei; Wu, Haoyang; Huang, Jiali; Xu, Ying; Yang, Feng; Zhang, Qi; Xu, Xingang

2018-05-22

Porcine epidemic diarrhea virus (PEDV), an enteropathogenic Alphacoronavirus, has caused enormous economic losses in the swine industry. p53 protein exists in a wide variety of animal cells, which is involved in cell cycle regulation, apoptosis, cell differentiation and other biological functions. In this study, we investigated the effects of PEDV infection on the cell cycle of Vero cells and p53 activation. The results demonstrated that PEDV infection induces cell cycle arrest at G0/G1 phase in Vero cells, while UV-inactivated PEDV does not cause cell cycle arrest. PEDV infection up-regulates the levels of p21, cdc2, cdk2, cdk4, Cyclin A protein and down-regulates Cyclin E protein. Further research results showed that inhibition of p53 signaling pathway can reverse the cell cycle arrest in G0/G1 phase induced by PEDV infection and cancel out the up-regulation of p21 and corresponding Cyclin/cdk mentioned above. In addition, PEDV infection of the cells synchronized in various stages of cell cycle showed that viral subgenomic RNA and virus titer were higher in the cells released from G0/G1 phase synchronized cells than that in the cells released from the G1/S phase and G2/M phase synchronized or asynchronous cells after 18 h p.i.. This is the first report to demonstrate that the p53-dependent pathway plays an important role in PEDV induced cell cycle arrest and beneficially contributes to viral infection. Copyright © 2018 Elsevier B.V. All rights reserved.

Pharmacodynamic Modeling of Cell Cycle Effects for Gemcitabine and Trabectedin Combinations in Pancreatic Cancer Cells

PubMed Central

Miao, Xin; Koch, Gilbert; Ait-Oudhia, Sihem; Straubinger, Robert M.; Jusko, William J.

2016-01-01

Combinations of gemcitabine and trabectedin exert modest synergistic cytotoxic effects on two pancreatic cancer cell lines. Here, systems pharmacodynamic (PD) models that integrate cellular response data and extend a prototype model framework were developed to characterize dynamic changes in cell cycle phases of cancer cell subpopulations in response to gemcitabine and trabectedin as single agents and in combination. Extensive experimental data were obtained for two pancreatic cancer cell lines (MiaPaCa-2 and BxPC-3), including cell proliferation rates over 0–120 h of drug exposure, and the fraction of cells in different cell cycle phases or apoptosis. Cell cycle analysis demonstrated that gemcitabine induced cell cycle arrest in S phase, and trabectedin induced transient cell cycle arrest in S phase that progressed to G2/M phase. Over time, cells in the control group accumulated in G0/G1 phase. Systems cell cycle models were developed based on observed mechanisms and were used to characterize both cell proliferation and cell numbers in the sub G1, G0/G1, S, and G2/M phases in the control and drug-treated groups. The proposed mathematical models captured well both single and joint effects of gemcitabine and trabectedin. Interaction parameters were applied to quantify unexplainable drug-drug interaction effects on cell cycle arrest in S phase and in inducing apoptosis. The developed models were able to identify and quantify the different underlying interactions between gemcitabine and trabectedin, and captured well our large datasets in the dimensions of time, drug concentrations, and cellular subpopulations. PMID:27895579

Cell cycle pathway dysregulation in human keratinocytes during chronic exposure to low arsenite.

PubMed

Al-Eryani, Laila; Waigel, Sabine; Jala, Venkatakrishna; Jenkins, Samantha F; States, J Christopher

2017-09-15

Arsenic is naturally prevalent in the earth's crust and widely distributed in air and water. Chronic low arsenic exposure is associated with several cancers in vivo, including skin cancer, and with transformation in vitro of cell lines including immortalized human keratinocytes (HaCaT). Arsenic also is associated with cell cycle dysregulation at different exposure levels in multiple cell lines. In this work, we analyzed gene expression in HaCaT cells to gain an understanding of gene expression changes contributing to transformation at an early time point. HaCaT cells were exposed to 0 or 100nM NaAsO 2 for 7weeks. Total RNA was purified and analyzed by microarray hybridization. Differential expression with fold change≥|1.5| and p-value≤0.05 was determined using Partek Genomic Suite™ and pathway and network analyses using MetaCore™ software (FDR≤0.05). Cell cycle analysis was performed using flow cytometry. 644 mRNAs were differentially expressed. Cell cycle/cell cycle regulation pathways predominated in the list of dysregulated pathways. Genes involved in replication origin licensing were enriched in the network. Cell cycle assay analysis showed an increase in G2/M compartment in arsenite-exposed cells. Arsenite exposure induced differential gene expression indicating dysregulation of cell cycle control, which was confirmed by cell cycle analysis. The results suggest that cell cycle dysregulation is an early event in transformation manifested in cells unable to transit G2/M efficiently. Further study at later time points will reveal additional changes in gene expression related to transformation processes. Copyright © 2017 Elsevier Inc. All rights reserved.

Architecture and inherent robustness of a bacterial cell-cycle control system.

PubMed

Shen, Xiling; Collier, Justine; Dill, David; Shapiro, Lucy; Horowitz, Mark; McAdams, Harley H

2008-08-12

A closed-loop control system drives progression of the coupled stalked and swarmer cell cycles of the bacterium Caulobacter crescentus in a near-mechanical step-like fashion. The cell-cycle control has a cyclical genetic circuit composed of four regulatory proteins with tight coupling to processive chromosome replication and cell division subsystems. We report a hybrid simulation of the coupled cell-cycle control system, including asymmetric cell division and responses to external starvation signals, that replicates mRNA and protein concentration patterns and is consistent with observed mutant phenotypes. An asynchronous sequential digital circuit model equivalent to the validated simulation model was created. Formal model-checking analysis of the digital circuit showed that the cell-cycle control is robust to intrinsic stochastic variations in reaction rates and nutrient supply, and that it reliably stops and restarts to accommodate nutrient starvation. Model checking also showed that mechanisms involving methylation-state changes in regulatory promoter regions during DNA replication increase the robustness of the cell-cycle control. The hybrid cell-cycle simulation implementation is inherently extensible and provides a promising approach for development of whole-cell behavioral models that can replicate the observed functionality of the cell and its responses to changing environmental conditions.

Proposing an International Collaboration on Lightweight Autonomous Vehicles to Conduct Scientific Traverses and Surveys over Antarctica and the Surrounding Sea Ice

NASA Technical Reports Server (NTRS)

Carsey, Frank; Behar, Alberto

2004-01-01

We have continued to develop a concept for use of autonomous rovers, originally developed for use in planetary exploration, in polar science on Earth; the concept was the subject of a workshop, and this report summarizes and extends that workshop. The workshop on Antarctic Autonomous Scientific Vehicles and Traverses met at the National Geographic Society on February 14 and 15, 2001 to discuss scientific objectives and benefits of the use of autonomous rovers. The participants enthusiastically viewed rovers as being uniquely valuable for such tasks as data taking on tedious or repetitive routes, traverses in polar night, difficult or hazardous routes, extremely remote regions, routes requiring only simple instrumentation, traverses that must be conducted at low speed, augments of manned traverses, and scientific procedures not compatible with human presence or combustion engines. The workshop has concluded that instrumented autonomous vehicles, of the type being developed for planetary exploration, have the potential to contribute significantly to the way science in conducted in Antarctica while also aiding planetary technology development, and engaging the public's interest. Specific objectives can be supported in understanding ice sheet mass balance, sea ice heat and momentum exchange, and surface air chemistry processes. In the interval since the workshop, we have concluded that organized program to employ such rovers to perform scientific tasks in the Fourth International Polar Year would serve the objectives of that program well.

A Novel Interaction of Ecdysoneless (ECD) Protein with R2TP Complex Component RUVBL1 Is Required for the Functional Role of ECD in Cell Cycle Progression.

PubMed

Mir, Riyaz A; Bele, Aditya; Mirza, Sameer; Srivastava, Shashank; Olou, Appolinaire A; Ammons, Shalis A; Kim, Jun Hyun; Gurumurthy, Channabasavaiah B; Qiu, Fang; Band, Hamid; Band, Vimla

2015-12-28

Ecdysoneless (ECD) is an evolutionarily conserved protein whose germ line deletion is embryonic lethal. Deletion of Ecd in cells causes cell cycle arrest, which is rescued by exogenous ECD, demonstrating a requirement of ECD for normal mammalian cell cycle progression. However, the exact mechanism by which ECD regulates cell cycle is unknown. Here, we demonstrate that ECD protein levels and subcellular localization are invariant during cell cycle progression, suggesting a potential role of posttranslational modifications or protein-protein interactions. Since phosphorylated ECD was recently shown to interact with the PIH1D1 adaptor component of the R2TP cochaperone complex, we examined the requirement of ECD phosphorylation in cell cycle progression. Notably, phosphorylation-deficient ECD mutants that failed to bind to PIH1D1 in vitro fully retained the ability to interact with the R2TP complex and yet exhibited a reduced ability to rescue Ecd-deficient cells from cell cycle arrest. Biochemical analyses demonstrated an additional phosphorylation-independent interaction of ECD with the RUVBL1 component of the R2TP complex, and this interaction is essential for ECD's cell cycle progression function. These studies demonstrate that interaction of ECD with RUVBL1, and its CK2-mediated phosphorylation, independent of its interaction with PIH1D1, are important for its cell cycle regulatory function. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

A Novel Interaction of Ecdysoneless (ECD) Protein with R2TP Complex Component RUVBL1 Is Required for the Functional Role of ECD in Cell Cycle Progression

PubMed Central

Mir, Riyaz A.; Bele, Aditya; Mirza, Sameer; Srivastava, Shashank; Olou, Appolinaire A.; Ammons, Shalis A.; Kim, Jun Hyun; Gurumurthy, Channabasavaiah B.; Qiu, Fang; Band, Hamid

2015-01-01

Ecdysoneless (ECD) is an evolutionarily conserved protein whose germ line deletion is embryonic lethal. Deletion of Ecd in cells causes cell cycle arrest, which is rescued by exogenous ECD, demonstrating a requirement of ECD for normal mammalian cell cycle progression. However, the exact mechanism by which ECD regulates cell cycle is unknown. Here, we demonstrate that ECD protein levels and subcellular localization are invariant during cell cycle progression, suggesting a potential role of posttranslational modifications or protein-protein interactions. Since phosphorylated ECD was recently shown to interact with the PIH1D1 adaptor component of the R2TP cochaperone complex, we examined the requirement of ECD phosphorylation in cell cycle progression. Notably, phosphorylation-deficient ECD mutants that failed to bind to PIH1D1 in vitro fully retained the ability to interact with the R2TP complex and yet exhibited a reduced ability to rescue Ecd-deficient cells from cell cycle arrest. Biochemical analyses demonstrated an additional phosphorylation-independent interaction of ECD with the RUVBL1 component of the R2TP complex, and this interaction is essential for ECD's cell cycle progression function. These studies demonstrate that interaction of ECD with RUVBL1, and its CK2-mediated phosphorylation, independent of its interaction with PIH1D1, are important for its cell cycle regulatory function. PMID:26711270

Arachidonic acid induces macrophage cell cycle arrest through the JNK signaling pathway.

PubMed

Shen, Ziying; Ma, Yunqing; Ji, Zhonghao; Hao, Yang; Yan, Xuan; Zhong, Yuan; Tang, Xiaochun; Ren, Wenzhi

2018-02-09

Arachidonic acid (AA) has potent pro-apoptotic effects on cancer cells at a low concentration and on macrophages at a very high concentration. However, the effects of AA on the macrophage cell cycle and related signaling pathways have not been fully investigated. Herein we aim to observe the effect of AA on macrophages cell cycle. AA exposure reduced the viability and number of macrophages in a dose- and time-dependent manner. The reduction in RAW264.7 cell viability was not caused by apoptosis, as indicated by caspase-3 and activated caspase-3 detection. Further research illustrated that AA exposure induced RAW264.7 cell cycle arrested at S phase, and some cell cycle-regulated proteins were altered accordingly. Moreover, JNK signaling was stimulated by AA, and the stimulation was partially reversed by a JNK signaling inhibitor in accordance with cell cycle-related factors. In addition, nuclear and total Foxo1/3a and phosphorylated Foxo1/3a were elevated by AA in a dose- and time-dependent manner, and this elevation was suppressed by the JNK signaling inhibitor. Our study demonstrated that AA inhibits macrophage viability by inducing S phase cell cycle arrest. The JNK signaling pathway and the downstream FoxO transcription factors are involved in AA-induced RAW264.7 cell cycle arrest.

Glioblastoma Stem Cells Respond to Differentiation Cues but Fail to Undergo Commitment and Terminal Cell-Cycle Arrest

PubMed Central

Carén, Helena; Stricker, Stefan H.; Bulstrode, Harry; Gagrica, Sladjana; Johnstone, Ewan; Bartlett, Thomas E.; Feber, Andrew; Wilson, Gareth; Teschendorff, Andrew E.; Bertone, Paul; Beck, Stephan; Pollard, Steven M.

2015-01-01

Summary Glioblastoma (GBM) is an aggressive brain tumor whose growth is driven by stem cell-like cells. BMP signaling triggers cell-cycle exit and differentiation of GBM stem cells (GSCs) and, therefore, might have therapeutic value. However, the epigenetic mechanisms that accompany differentiation remain poorly defined. It is also unclear whether cell-cycle arrest is terminal. Here we find only a subset of GSC cultures exhibit astrocyte differentiation in response to BMP. Although overtly differentiated non-cycling astrocytes are generated, they remain vulnerable to cell-cycle re-entry and fail to appropriately reconfigure DNA methylation patterns. Chromatin accessibility mapping identified loci that failed to alter in response to BMP and these were enriched in SOX transcription factor-binding motifs. SOX transcription factors, therefore, may limit differentiation commitment. A similar propensity for cell-cycle re-entry and de-differentiation was observed in GSC-derived oligodendrocyte-like cells. These findings highlight significant obstacles to BMP-induced differentiation as therapy for GBM. PMID:26607953

A stochastic spatiotemporal model of a response-regulator network in the Caulobacter crescentus cell cycle

NASA Astrophysics Data System (ADS)

Li, Fei; Subramanian, Kartik; Chen, Minghan; Tyson, John J.; Cao, Yang

2016-06-01

The asymmetric cell division cycle in Caulobacter crescentus is controlled by an elaborate molecular mechanism governing the production, activation and spatial localization of a host of interacting proteins. In previous work, we proposed a deterministic mathematical model for the spatiotemporal dynamics of six major regulatory proteins. In this paper, we study a stochastic version of the model, which takes into account molecular fluctuations of these regulatory proteins in space and time during early stages of the cell cycle of wild-type Caulobacter cells. We test the stochastic model with regard to experimental observations of increased variability of cycle time in cells depleted of the divJ gene product. The deterministic model predicts that overexpression of the divK gene blocks cell cycle progression in the stalked stage; however, stochastic simulations suggest that a small fraction of the mutants cells do complete the cell cycle normally.

Cell Cycle Deregulation in the Neurons of Alzheimer’s Disease

PubMed Central

Moh, Calvin; Kubiak, Jacek Z.; Bajic, Vladan P.; Zhu, Xiongwei; Smith, Mark A.

2018-01-01

The cell cycle consists of four main phases: G1, S, G2, and M. Most cells undergo these cycles up to 40–60 times in their life. However, neurons remain in a nondividing, nonreplicating phase, G0. Neurons initiate but do not complete cell division, eventually entering apoptosis. Research has suggested that like cancer, Alzheimer’s disease (AD) involves dysfunction in neuronal cell cycle reentry, leading to the development of the two-hit hypothesis of AD. The first hit is abnormal cell cycle reentry, which typically results in neuronal apoptosis and prevention of AD. However, with the second hit of chronic oxidative damage preventing apoptosis, neurons gain “immortality” analogous to tumor cells. Once both of these hits are activated, AD can develop and produce senile plaques and neurofibrillary tangles throughout brain tissue. In this review, we propose a mechanism for neuronal cell cycle reentry and the development of AD. PMID:21630160

Comprehensive Mass Cytometry Analysis of Cell Cycle, Activation, and Coinhibitory Receptors Expression in CD4 T Cells from Healthy and HIV-Infected Individuals.

PubMed

Corneau, Aurélien; Cosma, Antonio; Even, Sophie; Katlama, Christine; Le Grand, Roger; Frachet, Véronique; Blanc, Catherine; Autran, Brigitte

2017-01-01

Mass cytometry allows large multiplex analysis of cell cycle stages together with differentiation, activation, and exhaustion markers, allowing further assessment of the quiescence status of resting CD4 T cells. Peripheral blood CD4 T lymphocytes from 8 individuals, 4 healthy donors, and 4 HIV-infected on antiretroviral treatment (T) were stained with the same 26 monoclonal antibodies and dyes targeting surface and intracellular markers of differentiation, activation, exhaustion, and cell cycle stages. Samples were run on a CYTOF-2. Patterns of naïve [TN] CD4 T cells strongly differed from all other memory subsets central-memory (CM), transitional-memory (TM), effector-memory (EM), and terminally differentiated RA-expressing (TEMRA) subsets, while stem-cell memory (SCM) and T follicular-helper cells (TfH) were close to CM and TM cells with the highest percentages in cell cycle. EM and TEMRA were the most altered by HIV infection, with an increased frequency of activated and cycling cells. Activation markers and coinhibitory receptor expression differed among cell cycle stages, with HLA-DR fitting better than CD25 or CD38 with cycle, and opposite PD-1 gradients along differentiation and cell cycle. "Resting" DR-CD25- CD4+ T cells contained similar amounts of cells in G1 than the activated DR ± CD25± ones but three fold lower cells in S-G2-M. This broad multiplex mass cytometry analysis demonstrates some subsets of the so-called "resting" CD25-DR- CD4+ T cells contain noticeable amounts of cells into cycle or expressing coinhibitory receptors, opening new avenues for a redefinition of resting peripheral blood CD4 T cells harboring the HIV reservoirs. © 2016 International Clinical Cytometry Society. © 2016 International Clinical Cytometry Society.

Redistribution of cell cycle by arsenic trioxide is associated with demethylation and expression changes of cell cycle related genes in acute promyelocytic leukemia cell line (NB4).

PubMed

Hassani, Saeed; Khaleghian, Ali; Ahmadian, Shahin; Alizadeh, Shaban; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir; Ghaffari, Seyed H

2018-01-01

PML-RARα perturbs the normal epigenetic setting, which is essential to oncogenic transformation in acute promyelocytic leukemia (APL). Transcription induction and recruitment of DNA methyltransferases (DNMTs) by PML-RARα and subsequent hypermethylation are components of this perturbation. Arsenic trioxide (ATO), an important drug in APL therapy, concurrent with degradation of PML-RARα induces cell cycle change and apoptosis. How ATO causes cell cycle alteration has remained largely unexplained. Here, we investigated DNA methylation patterns of cell cycle regulatory genes promoters, the effects of ATO on the methylated genes and cell cycle distribution in an APL cell line, NB4. Analysis of promoter methylation status of 22 cell cycle related genes in NB4 revealed that CCND1, CCNE1, CCNF, CDKN1A, GADD45α, and RBL1 genes were methylated 60.7, 84.6, 58.6, 8.7, 33.4, and 73.7%, respectively, that after treatment with 2 μM ATO for 48 h, turn into 0.6, 13.8, 0.1, 6.6, 10.7, and 54.5% methylated. ATO significantly reduced the expression of DNMT1, 3A, and 3B. ATO induced the expression of CCND1, CCNE1, and GADD45α genes, suppressed the expression of CCNF and CDKN1A genes, which were consistent with decreased number of cells in G1 and S phases and increased number of cells in G2/M phase. In conclusion, demethylation and alteration in the expression level of the cell cycle related genes may be possible mechanisms in ATO-induced cell cycle arrest in APL cells. It may suggest that ATO by demethylation of CCND1 and CCNE1 and their transcriptional activation accelerates G1 and S transition into the G2/M cell cycle arrest.

Route, mechanism, and implications of proton import during Na+/K+ exchange by native Na+/K+-ATPase pumps

PubMed Central

Vedovato, Natascia

2014-01-01

A single Na+/K+-ATPase pumps three Na+ outwards and two K+ inwards by alternately exposing ion-binding sites to opposite sides of the membrane in a conformational sequence coupled to pump autophosphorylation from ATP and auto-dephosphorylation. The larger flow of Na+ than K+ generates outward current across the cell membrane. Less well understood is the ability of Na+/K+ pumps to generate an inward current of protons. Originally noted in pumps deprived of external K+ and Na+ ions, as inward current at negative membrane potentials that becomes amplified when external pH is lowered, this proton current is generally viewed as an artifact of those unnatural conditions. We demonstrate here that this inward current also flows at physiological K+ and Na+ concentrations. We show that protons exploit ready reversibility of conformational changes associated with extracellular Na+ release from phosphorylated Na+/K+ pumps. Reversal of a subset of these transitions allows an extracellular proton to bind an acidic side chain and to be subsequently released to the cytoplasm. This back-step of phosphorylated Na+/K+ pumps that enables proton import is not required for completion of the 3 Na+/2 K+ transport cycle. However, the back-step occurs readily during Na+/K+ transport when external K+ ion binding and occlusion are delayed, and it occurs more frequently when lowered extracellular pH raises the probability of protonation of the externally accessible carboxylate side chain. The proton route passes through the Na+-selective binding site III and is distinct from the principal pathway traversed by the majority of transported Na+ and K+ ions that passes through binding site II. The inferred occurrence of Na+/K+ exchange and H+ import during the same conformational cycle of a single molecule identifies the Na+/K+ pump as a hybrid transporter. Whether Na+/K+ pump–mediated proton inflow may have any physiological or pathophysiological significance remains to be clarified. PMID:24688018

Cell cycle-dependent protein fingerprint from a single cancer cell: image cytometry coupled with single-cell capillary sieving electrophoresis.

PubMed

Hu, Shen; Le, Zhang; Krylov, Sergey; Dovichi, Norman J

2003-07-15

Study of cell cycle-dependent protein expression is important in oncology, stem cell research, and developmental biology. In this paper, we report the first protein fingerprint from a single cell with known phase in the cell cycle. To determine that phase, we treated HT-29 colon cancer cells with Hoescht 33342, a vital nuclear stain. A microscope was used to measure the fluorescence intensity from one treated cell; in this form of image cytometry, the fluorescence intensity is proportional to the cell's DNA content, which varies in a predictable fashion during the cell cycle. To generate the protein fingerprint, the cell was aspirated into the separation capillary and lysed. Proteins were fluorescently labeled with 3-(2-furoylquinoline-2-carboxaldehyde, separated by capillary sieving electrophoresis, and detected by laser-induced fluorescence. This form of electrophoresis is the capillary version of SDS-PAGE. The single-cell electropherogram partially resolved approximately 25 components in a 30-min separation, and the dynamic range of the detector exceeded 5000. There was a large cell-to-cell variation in protein expression, averaging 40% relative standard deviation across the electropherogram. The dominant source of variation was the phase of the cell in the cell cycle; on average, approximately 60% of the cell-to-cell variance in protein expression was associated with the cell cycle. Cells in the G1 and G2/M phases of the cell cycle had 27 and 21% relative standard deviations in protein expression, respectively. Cells in the G2/M phase generated signals that were twice the amplitude of the signals generated by G1 phase cells, as expected for cells that are soon to divide into two daughter cells. When electropherograms were normalized to total protein content, the expression of only one component was dependent on cell cycle at the 99% confidence limit. That protein is tentatively identified as cytokeratin 18 in a companion paper.

Cell cycle-dependent induction of autophagy, mitophagy and reticulophagy.

PubMed

Tasdemir, Ezgi; Maiuri, M Chiara; Tajeddine, Nicolas; Vitale, Ilio; Criollo, Alfredo; Vicencio, José Miguel; Hickman, John A; Geneste, Olivier; Kroemer, Guido

2007-09-15

When added to cells, a variety of autophagy inducers that operate through distinct mechanisms and target different organelles for autophagic destruction (mitochondria in mitophagy, endoplasmic reticulum in reticulophagy) rarely induce autophagic vacuolization in more than 50% or the cells. Here we show that this heterogeneity may be explained by cell cycle-specific effects. The BH3 mimetic ABT737, lithium, rapamycin, tunicamycin or nutrient depletion stereotypically induce autophagy preferentially in the G(1) and S phases of the cell cycle, as determined by simultaneous monitoring of cell cycle markers and the cytoplasmic aggregation of GFP-LC3 in autophagic vacuoles. These results point to a hitherto neglected crosstalk between autophagic vacuolization and cell cycle regulation.

Repressive histone methylation regulates cardiac myocyte cell cycle exit.

PubMed

El-Nachef, Danny; Oyama, Kyohei; Wu, Yun-Yu; Freeman, Miles; Zhang, Yiqiang; Robb MacLellan, W

2018-05-22

Mammalian cardiac myocytes (CMs) stop proliferating soon after birth and subsequent heart growth comes from hypertrophy, limiting the adult heart's regenerative potential after injury. The molecular events that mediate CM cell cycle exit are poorly understood. To determine the epigenetic mechanisms limiting CM cycling in adult CMs (ACMs) and whether trimethylation of lysine 9 of histone H3 (H3K9me3), a histone modification associated with repressed chromatin, is required for the silencing of cell cycle genes, we developed a transgenic mouse model where H3K9me3 is specifically removed in CMs by overexpression of histone demethylase, KDM4D. Although H3K9me3 is found across the genome, its loss in CMs preferentially disrupts cell cycle gene silencing. KDM4D binds directly to cell cycle genes and reduces H3K9me3 levels at these promotors. Loss of H3K9me3 preferentially leads to increased cell cycle gene expression resulting in enhanced CM cycling. Heart mass was increased in KDM4D overexpressing mice by postnatal day 14 (P14) and continued to increase until 9-weeks of age. ACM number, but not size, was significantly increased in KDM4D expressing hearts, suggesting CM hyperplasia accounts for the increased heart mass. Inducing KDM4D after normal development specifically in ACMs resulted in increased cell cycle gene expression and cycling. We demonstrated that H3K9me3 is required for CM cell cycle exit and terminal differentiation in ACMs. Depletion of H3K9me3 in adult hearts prevents and reverses permanent cell cycle exit and allows hyperplastic growth in adult hearts in vivo. Copyright © 2017. Published by Elsevier Ltd.

Thermophysical properties along Curiosity's traverse in Gale crater, Mars, derived from the REMS Ground Temperature Sensor

NASA Astrophysics Data System (ADS)

Vasavada, A. R.; Piqueux, S.

2016-12-01

The REMS instrument onboard the Mars Science Laboratory rover, Curiosity, has measured ground temperature nearly continuously at hourly intervals for two Mars years. Coverage of the entire diurnal cycle at 1 Hz is achieved every few martian days. We compare these measurements with predictions of surface-atmosphere thermal models to derive the apparent thermal inertia and thermally derived albedo along the rover's traverse, after accounting for the radiative effects of dust as well as atmospheric water ice during fall and winter, as is necessary to match the measured seasonal trend. The REMS measurements can distinguish between active sand, other loose materials, mudstone, and sandstone based on their thermophysical properties. However, the thermal inertias of bedrock-dominated surfaces ( 350-550 J m-2 K-1 s-½) are lower than expected. We use the detailed shape of the diurnal ground temperature curve to infer the effects of lateral mixing of different materials within the sensor footprint, as well as vertical heterogeneity. While results of this forward modeling approach are non-unique, we find surface configurations capable of creating the observed thermal responses that also are consistent with rover imagery. Bedrock thermal inertias isolated by this modeling are 1000-1900 J m-2 K-1 s-½ for mudstone and 700 J m-2 K-1 s-½ for sandstone. This methodology provides a better basis for inferring properties such as rock porosity, cement composition, and degree of cementation from the thermal inertia. These results highlight the advantages of deriving thermophysical properties from ground temperature records well-sampled in local time.

Thermophysical Properties Along Curiosity's Traverse in Gale Crater, Mars, Derived from the REMS Ground Temperature Sensor

NASA Technical Reports Server (NTRS)

Vasavada, Ashwin R.; Piqueux, Sylvain; Lewis, Kevin W.; Lemmon, Mark T.; Smith, Michael Doyle

2016-01-01

The REMS instrument onboard the Mars Science Laboratory rover, Curiosity, has measured ground temperature nearly continuously at hourly intervals for two Mars years. Coverage of the entire diurnal cycle at 1 Hz is available every few martian days. We compare these measurements with predictions of surface atmosphere thermal models to derive the apparent thermal inertia and thermally derived albedo along the rovers traverse after accounting for the radiative effects of atmospheric water ice during fall and winter, as is necessary to match the measured seasonal trend. The REMS measurements can distinguish between active sand, other loose materials, mudstone, and sandstone based on their thermophysical properties. However, the apparent thermal inertias of bedrock dominated surfaces [approx. 350-550 J m(exp. -2) K(exp. -1 s(exp. -1/2 )] are lower than expected. We use rover imagery and the detailed shape of the diurnal ground temperature curve to explore whether lateral or vertical heterogeneity in the surface materials within the sensor footprint might explain the low inertias. We find that the bedrock component of the surface can have a thermal inertia as high as 650-1700 J m(exp. -2) K(exp. -1) s(exp. -1/2) for mudstone sites and approx. 700 J m(exp. -2) K(exp. -1) s(exp. - 1/2) for sandstone sites in models runs that include lateral and vertical mixing. Although the results of our forward modeling approach may be non-unique, they demonstrate the potential to extract information about lateral and vertical variations in thermophysical properties from temporally resolved measurements of ground temperature.

Development, differentiation and manipulation of chicken germ cells.

PubMed

Nakamura, Yoshiaki; Kagami, Hiroshi; Tagami, Takahiro

2013-01-01

Germ cells are the only cell type capable of transmitting genetic information to the next generation. During development, they are set aside from all somatic cells of the embryo. In many species, germ cells form at the fringe of the embryo proper and then traverse through several developing somatic tissues on their migration to the emerging gonads. Primordial germ cells (PGCs) are the only cells in developing embryos with the potential to transmit genetic information to the next generation. Unlike other species, in avian embryos, PGCs use blood circulation for transport to the future gonadal region. This unique accessibility of avian PGCs during early development provides an opportunity to collect and transplant PGCs. The recent development of methods for production of germline chimeras by transfer of PGCs, and long-term cultivation methods of chicken PGCs without losing their germline transmission ability have provided important breakthroughs for the preservation of germplasm , for the production of transgenic birds and study the germ cell system. This review will describe the development, migration, differentiation and manipulation of germ cells, and discuss the prospects that germ cell technologies offer for agriculture, biotechnology and academic research. © 2013 The Authors Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

Current concepts on Escherichia coli K1 translocation of the blood-brain barrier.

PubMed

Xie, Yi; Kim, Kee Jun; Kim, Kwang Sik

2004-11-01

The mortality and morbidity associated with neonatal gram-negative meningitis have remained significant despite advances in antimicrobial chemotherapy. Escherichia coli K1 is the most common gram-negative organism causing neonatal meningitis. Our incomplete knowledge of the pathogenesis of this disease is one of the main reasons for this high mortality and morbidity. We have previously established both in vitro and in vivo models of the blood-brain barrier (BBB) using human brain microvascular endothelial cells (HBMEC) and hematogenous meningitis in neonatal rats, respectively. With these in vitro and in vivo models, we have shown that successful crossing of the BBB by circulating E. coli requires a high-degree of bacteremia, E. coli binding to and invasion of HBMEC, and E. coli traversal of the BBB as live bacteria. Our previous studies using TnphoA, signature-tagged mutagenesis and differential fluorescence induction identified several E. coli K1 determinants such as OmpA, Ibe proteins, AslA, TraJ and CNF1 contributing to invasion of HBMEC in vitro and traversal of the blood-brain barrier in vivo. We have shown that some of these determinants interact with specific receptors on HBMEC, suggesting E. coli translocation of the BBB is the result of specific pathogen-host cell interactions. Recent studies using functional genomics techniques have identified additional E. coli K1 factors that contribute to the high degree of bacteremia and HBMEC binding/invasion/transcytosis. In this review, we summarize the current knowledge on the mechanisms underlying the successful E. coli translocation of the BBB.

Laser scanning cytometry (LCS) allows detailed analysis of the cell cycle in PI stained human fibroblasts (TIG-7).

PubMed

Kawasaki, M; Sasaki, K; Satoh, T; Kurose, A; Kamada, T; Furuya, T; Murakami, T; Todoroki, T

1997-01-01

We have demonstrated a method for the in situ determination of the cell cycle phases of TIG-7 fibroblasts using a laser scanning cytometer (LSC) which has not only a function equivalent to flow cytometry (FCM) but also has a capability unique in itself. LSC allows a more detailed analysis of the cell cycle in cells stained with propidium iodide (PI) than FCM. With LSC it is possible to discriminate between mitotic cells and G2 cells, between post-mitotic cells and G1 cells, and between quiescent cells and cycling cells in a PI fluorescence peak (chromatin condensation) vs. fluorescence value (DNA content) cytogram for cells stained with PI. These were amply confirmed by experiments using colcemid and adriamycin. We were able to identify at least six cell subpopulations for PI stained cells using LSC; namely G1, S, G2, M, postmitotic and quiescent cell populations. LSC analysis facilitates the monitoring of effects of drugs on the cell cycle.

Checkpoints couple transcription network oscillator dynamics to cell-cycle progression.

PubMed

Bristow, Sara L; Leman, Adam R; Simmons Kovacs, Laura A; Deckard, Anastasia; Harer, John; Haase, Steven B

2014-09-05

The coupling of cyclin dependent kinases (CDKs) to an intrinsically oscillating network of transcription factors has been proposed to control progression through the cell cycle in budding yeast, Saccharomyces cerevisiae. The transcription network regulates the temporal expression of many genes, including cyclins, and drives cell-cycle progression, in part, by generating successive waves of distinct CDK activities that trigger the ordered program of cell-cycle events. Network oscillations continue autonomously in mutant cells arrested by depletion of CDK activities, suggesting the oscillator can be uncoupled from cell-cycle progression. It is not clear what mechanisms, if any, ensure that the network oscillator is restrained when progression in normal cells is delayed or arrested. A recent proposal suggests CDK acts as a master regulator of cell-cycle processes that have the potential for autonomous oscillatory behavior. Here we find that mitotic CDK is not sufficient for fully inhibiting transcript oscillations in arrested cells. We do find that activation of the DNA replication and spindle assembly checkpoints can fully arrest the network oscillator via overlapping but distinct mechanisms. Further, we demonstrate that the DNA replication checkpoint effector protein, Rad53, acts to arrest a portion of transcript oscillations in addition to its role in halting cell-cycle progression. Our findings indicate that checkpoint mechanisms, likely via phosphorylation of network transcription factors, maintain coupling of the network oscillator to progression during cell-cycle arrest.

Regulation of the Embryonic Cell Cycle During Mammalian Preimplantation Development.

PubMed

Palmer, N; Kaldis, P

2016-01-01

The preimplantation development stage of mammalian embryogenesis consists of a series of highly conserved, regulated, and predictable cell divisions. This process is essential to allow the rapid expansion and differentiation of a single-cell zygote into a multicellular blastocyst containing cells of multiple developmental lineages. This period of development, also known as the germinal stage, encompasses several important developmental transitions, which are accompanied by dramatic changes in cell cycle profiles and dynamics. These changes are driven primarily by differences in the establishment and enforcement of cell cycle checkpoints, which must be bypassed to facilitate the completion of essential cell cycle events. Much of the current knowledge in this area has been amassed through the study of knockout models in mice. These mouse models are powerful experimental tools, which have allowed us to dissect the relative dependence of the early embryonic cell cycles on various aspects of the cell cycle machinery and highlight the extent of functional redundancy between members of the same gene family. This chapter will explore the ways in which the cell cycle machinery, their accessory proteins, and their stimuli operate during mammalian preimplantation using mouse models as a reference and how this allows for the usually well-defined stages of the cell cycle to be shaped and transformed during this unique and critical stage of development. © 2016 Elsevier Inc. All rights reserved.

Targeting of cytosolic phospholipase A2α impedes cell cycle re-entry of quiescent prostate cancer cells.

PubMed

Yao, Mu; Xie, Chanlu; Kiang, Mei-Yee; Teng, Ying; Harman, David; Tiffen, Jessamy; Wang, Qian; Sved, Paul; Bao, Shisan; Witting, Paul; Holst, Jeff; Dong, Qihan

2015-10-27

Cell cycle re-entry of quiescent cancer cells has been proposed to be involved in cancer progression and recurrence. Cytosolic phospholipase A2α (cPLA2α) is an enzyme that hydrolyzes membrane glycerophospholipids to release arachidonic acid and lysophospholipids that are implicated in cancer cell proliferation. The aim of this study was to determine the role of cPLA2α in cell cycle re-entry of quiescent prostate cancer cells. When PC-3 and LNCaP cells were rendered to a quiescent state, the active form of cPLA2α with a phosphorylation at Ser505 was lower compared to their proliferating state. Conversely, the phospho-cPLA2α levels were resurgent during the induction of cell cycle re-entry. Pharmacological inhibition of cPLA2α with Efipladib upon induction of cell cycle re-entry inhibited the re-entry process, as manifested by refrained DNA synthesis, persistent high proportion of cells in G0/G1 and low percentage of cells in S and G2/M phases, together with a stagnant recovery of Ki-67 expression. Simultaneously, Efipladib prohibited the emergence of Skp2 while maintained p27 at a high level in the nuclear compartment during cell cycle re-entry. Inhibition of cPLA2α also prevented an accumulation of cyclin D1/CDK4, cyclin E/CDK2, phospho-pRb, pre-replicative complex proteins CDC6, MCM7, ORC6 and DNA synthesis-related protein PCNA during induction of cell cycle re-entry. Moreover, a pre-treatment of the prostate cancer cells with Efipladib during induction of cell cycle re-entry subsequently compromised their tumorigenic capacity in vivo. Hence, cPLA2α plays an important role in cell cycle re-entry by quiescent prostate cancer cells.

LPS-induced inflammatory response triggers cell cycle reactivation in murine neuronal cells through retinoblastoma proteins induction.

PubMed

D'Angelo, Barbara; Astarita, Carlo; Boffo, Silvia; Massaro-Giordano, Mina; Antonella Ianuzzi, Carmelina; Caporaso, Antonella; Macaluso, Marcella; Giordano, Antonio

2017-01-01

Cell cycle reactivation in adult neurons is an early hallmark of neurodegeneration. The lipopolysaccharide (LPS) is a well-known pro-inflammatory factor that provokes neuronal cell death via glial cells activation. The retinoblastoma (RB) family includes RB1/p105, retinoblastoma-like 1 (RBL1/p107), and retinoblastoma-like 2 (Rb2/p130). Several studies have indicated that RB proteins exhibit tumor suppressor activities, and play a central role in cell cycle regulation. In this study, we assessed LPS-mediated inflammatory effect on cell cycle reactivation and apoptosis of neuronally differentiated cells. Also, we investigated whether the LPS-mediated inflammatory response can influence the function and expression of RB proteins. Our results showed that LPS challenges triggered cell cycle reactivation of differentiated neuronal cells, indicated by an accumulation of cells in S and G2/M phase. Furthermore, we found that LPS treatment also induced apoptotic death of neurons. Interestingly, we observed that LPS-mediated inflammatory effect on cell cycle re-entry and apoptosis was concomitant with the aberrant expression of RBL1/p107 and RB1/p105. To the best of our knowledge, our study is the first to indicate a role of LPS in inducing cell cycle re-entry and/or apoptosis of differentiated neuronal cells, perhaps through mechanisms altering the expression of specific members of RB family proteins. This study provides novel information on the biology of post-mitotic neurons and could help in identifying novel therapeutic targets to prevent de novo cell cycle reactivation and/or apoptosis of neurons undergoing neurodegenerative processes.

Detection of Changes in the Medicago sativa Retinoblastoma-Related Protein (MsRBR1) Phosphorylation During Cell Cycle Progression in Synchronized Cell Suspension Culture.

PubMed

Ayaydin, Ferhan; Kotogány, Edit; Ábrahám, Edit; Horváth, Gábor V

2017-01-01

Deepening our knowledge on the regulation of the plant cell division cycle depends on techniques that allow for the enrichment of cell populations in defined cell cycle phases. Synchronization of cell division can be achieved using different plant tissues; however, well-established cell suspension cultures provide large amount of biological sample for further analyses. Here, we describe the methodology of the establishment, propagation, and analysis of a Medicago sativa suspension culture that can be used for efficient synchronization of the cell division. A novel 5-ethynyl-2'-deoxyuridine (EdU)-based method is used for the estimation of cell fraction that enters DNA synthesis phase of the cell cycle and we also demonstrate the changes in the phosphorylation level of Medicago sativa retinoblastoma-related protein (MsRBR1) during cell cycle progression.

Nucleosome architecture throughout the cell cycle

PubMed Central

Deniz, Özgen; Flores, Oscar; Aldea, Martí; Soler-López, Montserrat; Orozco, Modesto

2016-01-01

Nucleosomes provide additional regulatory mechanisms to transcription and DNA replication by mediating the access of proteins to DNA. During the cell cycle chromatin undergoes several conformational changes, however the functional significance of these changes to cellular processes are largely unexplored. Here, we present the first comprehensive genome-wide study of nucleosome plasticity at single base-pair resolution along the cell cycle in Saccharomyces cerevisiae. We determined nucleosome organization with a specific focus on two regulatory regions: transcription start sites (TSSs) and replication origins (ORIs). During the cell cycle, nucleosomes around TSSs display rearrangements in a cyclic manner. In contrast to gap (G1 and G2) phases, nucleosomes have a fuzzier organization during S and M phases, Moreover, the choreography of nucleosome rearrangements correlate with changes in gene expression during the cell cycle, indicating a strong association between nucleosomes and cell cycle-dependent gene functionality. On the other hand, nucleosomes are more dynamic around ORIs along the cell cycle, albeit with tighter regulation in early firing origins, implying the functional role of nucleosomes on replication origins. Our study provides a dynamic picture of nucleosome organization throughout the cell cycle and highlights the subsequent impact on transcription and replication activity. PMID:26818620

Cell reprogramming modelled as transitions in a hierarchy of cell cycles

NASA Astrophysics Data System (ADS)

Hannam, Ryan; Annibale, Alessia; Kühn, Reimer

2017-10-01

We construct a model of cell reprogramming (the conversion of fully differentiated cells to a state of pluripotency, known as induced pluripotent stem cells, or iPSCs) which builds on key elements of cell biology viz. cell cycles and cell lineages. Although reprogramming has been demonstrated experimentally, much of the underlying processes governing cell fate decisions remain unknown. This work aims to bridge this gap by modelling cell types as a set of hierarchically related dynamical attractors representing cell cycles. Stages of the cell cycle are characterised by the configuration of gene expression levels, and reprogramming corresponds to triggering transitions between such configurations. Two mechanisms were found for reprogramming in a two level hierarchy: cycle specific perturbations and a noise induced switching. The former corresponds to a directed perturbation that induces a transition into a cycle-state of a different cell type in the potency hierarchy (mainly a stem cell) whilst the latter is a priori undirected and could be induced, e.g. by a (stochastic) change in the cellular environment. These reprogramming protocols were found to be effective in large regimes of the parameter space and make specific predictions concerning reprogramming dynamics which are broadly in line with experimental findings.

Early induction of c-Myc is associated with neuronal cell death.

PubMed

Lee, Hyun-Pil; Kudo, Wataru; Zhu, Xiongwei; Smith, Mark A; Lee, Hyoung-gon

2011-11-14

Neuronal cell cycle activation has been implicated in neurodegenerative diseases such as Alzheimer's disease, while the initiating mechanism of cell cycle activation remains to be determined. Interestingly, our previous studies have shown that cell cycle activation by c-Myc (Myc) leads to neuronal cell death which suggests Myc might be a key regulator of cell cycle re-entry mediated neuronal cell death. However, the pattern of Myc expression in the process of neuronal cell death has not been addressed. To this end, we examined Myc induction by the neurotoxic agents camptothecin and amyloid-β peptide in a differentiated SH-SY5Y neuronal cell culture model. Myc expression was found to be significantly increased following either treatment and importantly, the induction of Myc preceded neuronal cell death suggesting it is an early event of neuronal cell death. Since ectopic expression of Myc in neurons causes the cell cycle activation and neurodegeneration in vivo, the current data suggest that induction of Myc by neurotoxic agents or other disease factors might be a key mediator in cell cycle activation and consequent cell death that is a feature of neurodegenerative diseases. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Cancer cells mimic in vivo spatial-temporal cell-cycle phase distribution and chemosensitivity in 3-dimensional Gelfoam® histoculture but not 2-dimensional culture as visualized with real-time FUCCI imaging.

PubMed

Yano, Shuya; Miwa, Shinji; Mii, Sumiyuki; Hiroshima, Yukihiko; Uehara, Fuminaru; Kishimoto, Hiroyuki; Tazawa, Hiroshi; Zhao, Ming; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M

2015-01-01

The phase of the cell cycle can determine whether a cancer cell can respond to a given drug. We previously reported monitoring of real-time cell cycle dynamics of cancer cells throughout a live tumor, intravitally in live mice, using a fluorescence ubiquitination-based cell-cycle indicator (FUCCI). Approximately 90% of cancer cells in the center and 80% of total cells of an established tumor are in G0/G1 phase. Longitudinal real-time imaging demonstrated that cytotoxic agents killed only proliferating cancer cells at the surface and, in contrast, had little effect on quiescent cancer cells, which are the vast majority of an established tumor. Moreover, resistant quiescent cancer cells restarted cycling after cessation of chemotherapy. These results suggested why most drugs currently in clinical use, which target cancer cells in S/G2/M, are mostly ineffective on solid tumors. In the present report, we used FUCCI imaging and Gelfoam® collagen-sponge-gel histoculture, to demonstrate in real time, that the cell-cycle phase distribution of cancer cells in Gelfoam® and in vivo tumors is highly similar, whereby only the surface cells proliferate and interior cells are quiescent in G0/G1. This is in contrast to 2D culture where most cancer cells cycle. Similarly, the cancer cells responded similarly to toxic chemotherapy in Gelfoam® culture as in vivo, and very differently than cancer cells in 2D culture which were much more chemosensitive. Gelfoam® culture of FUCCI-expressing cancer cells offers the opportunity to image the cell cycle of cancer cells continuously and to screen for novel effective therapies to target quiescent cells, which are the majority in a tumor and which would have a strong probability to be effective in vivo.

Serum Proteases Potentiate BMP-Induced Cell Cycle Re-entry of Dedifferentiating Muscle Cells during Newt Limb Regeneration.

PubMed

Wagner, Ines; Wang, Heng; Weissert, Philipp M; Straube, Werner L; Shevchenko, Anna; Gentzel, Marc; Brito, Goncalo; Tazaki, Akira; Oliveira, Catarina; Sugiura, Takuji; Shevchenko, Andrej; Simon, András; Drechsel, David N; Tanaka, Elly M

2017-03-27

Limb amputation in the newt induces myofibers to dedifferentiate and re-enter the cell cycle to generate proliferative myogenic precursors in the regeneration blastema. Here we show that bone morphogenetic proteins (BMPs) and mature BMPs that have been further cleaved by serum proteases induce cell cycle entry by dedifferentiating newt muscle cells. Protease-activated BMP4/7 heterodimers that are present in serum strongly induced myotube cell cycle re-entry with protease cleavage yielding a 30-fold potency increase of BMP4/7 compared with canonical BMP4/7. Inhibition of BMP signaling via muscle-specific dominant-negative receptor expression reduced cell cycle entry in vitro and in vivo. In vivo inhibition of serine protease activity depressed cell cycle re-entry, which in turn was rescued by cleaved-mimic BMP. This work identifies a mechanism of BMP activation that generates blastema cells from differentiated muscle. Copyright © 2017 Elsevier Inc. All rights reserved.

Duplication of the genome in normal and cancer cell cycles.

PubMed

Bandura, Jennifer L; Calvi, Brian R

2002-01-01

It is critical to discover the mechanisms of normal cell cycle regulation if we are to fully understand what goes awry in cancer cells. The normal eukaryotic cell tightly regulates the activity of origins of DNA replication so that the genome is duplicated exactly once per cell cycle. Over the last ten years much has been learned concerning the cell cycle regulation of origin activity. It is now clear that the proteins and cell cycle mechanisms that control origin activity are largely conserved from yeast to humans. Despite this conservation, the composition of origins of DNA replication in higher eukaryotes remains ill defined. A DNA consensus for predicting origins has yet to emerge, and it is of some debate whether primary DNA sequence determines where replication initiates. In this review we outline what is known about origin structure and the mechanism of once per cell cycle DNA replication with an emphasis on recent advances in mammalian cells. We discuss the possible relevance of these regulatory pathways for cancer biology and therapy.

The Formation of Tight Tumor Clusters Affects the Efficacy of Cell Cycle Inhibitors: A Hybrid Model Study

PubMed Central

Kim, MunJu; Reed, Damon; Rejniak, Katarzyna A.

2014-01-01

Cyclin-dependent kinases (CDKs) are vital in regulating cell cycle progression, and, thus, in highly proliferating tumor cells CDK inhibitors are gaining interest as potential anticancer agents. Clonogenic assay experiments are frequently used to determine drug efficacy against the survival and proliferation of cancer cells. While the anticancer mechanisms of drugs are usually described at the intracellular single-cell level, the experimental measurements are sampled from the entire cancer cell population. This approach may lead to discrepancies between the experimental observations and theoretical explanations of anticipated drug mechanisms. To determine how individual cell responses to drugs that inhibit CDKs affect the growth of cancer cell populations, we developed a spatially explicit hybrid agent-based model. In this model, each cell is equipped with internal cell cycle regulation mechanisms, but it is also able to interact physically with its neighbors. We model cell cycle progression, focusing on the G1 and G2/M cell cycle checkpoints, as well as on related essential components, such as CDK1, CDK2, cell size, and DNA damage. We present detailed studies of how the emergent properties (e.g., cluster formation) of an entire cell population depend on altered physical and physiological parameters. We analyze the effects of CDK1 and CKD2 inhibitors on population growth, time-dependent changes in cell cycle distributions, and the dynamic evolution of spatial cell patterns. We show that cell cycle inhibitors that cause cell arrest at different cell cycle phases are not necessarily synergistically super-additive. Finally, we demonstrate that the physical aspects of cell population growth, such as the formation of tight cell clusters versus dispersed colonies, alter the efficacy of cell cycle inhibitors, both in 2D and 3D simulations. This finding may have implications for interpreting the treatment efficacy results of in vitro experiments, in which treatment is applied before the cells can grow to produce clusters, especially because in vivo tumors, in contrast, form large masses before they are detected and treated. PMID:24607745

Effects of karanjin on cell cycle arrest and apoptosis in human A549, HepG2 and HL-60 cancer cells.

PubMed

Guo, Jian-Ru; Chen, Qian-Qian; Lam, Christopher Wai-Kei; Zhang, Wei

2015-07-26

We have investigated the potential anticancer effects of karanjin, a principal furanoflavonol constituent of the Chinese medicine Fordia cauliflora, using cytotoxic assay, cell cycle arrest, and induction of apoptosis in three human cancer cell lines (A549, HepG2 and HL-60 cells). MTT cytotoxic assay showed that karanjin could inhibit the proliferation and viability of all three cancer cells. The induction of cell cycle arrest was observed via a PI (propidium iodide)/RNase Staining Buffer detection kit and analyzed by flow cytometry: karanjin could dose-dependently induce cell cycle arrest at G2/M phase in the three cell lines. Cell apoptosis was assessed by Annexin V-FITC/PI staining: all three cancer cells treated with karanjin exhibited significantly increased apoptotic rates, especially in the percentage of late apoptosis cells. Karanjin can induce cancer cell death through cell cycle arrest and enhance apoptosis. This compound may be effective clinically for cancer pharmacotherapy.

Using Grid Cells for Navigation

PubMed Central

Bush, Daniel; Barry, Caswell; Manson, Daniel; Burgess, Neil

2015-01-01

Summary Mammals are able to navigate to hidden goal locations by direct routes that may traverse previously unvisited terrain. Empirical evidence suggests that this “vector navigation” relies on an internal representation of space provided by the hippocampal formation. The periodic spatial firing patterns of grid cells in the hippocampal formation offer a compact combinatorial code for location within large-scale space. Here, we consider the computational problem of how to determine the vector between start and goal locations encoded by the firing of grid cells when this vector may be much longer than the largest grid scale. First, we present an algorithmic solution to the problem, inspired by the Fourier shift theorem. Second, we describe several potential neural network implementations of this solution that combine efficiency of search and biological plausibility. Finally, we discuss the empirical predictions of these implementations and their relationship to the anatomy and electrophysiology of the hippocampal formation. PMID:26247860

Mechanisms and pathways of Toxoplasma gondii transepithelial migration

PubMed Central

Jones, Emily J.; Carding, Simon R.

2017-01-01

ABSTRACT Toxoplasma gondii is a ubiquitous parasite and a prevalent food-borne parasitic pathogen. Infection of the host occurs principally through oral consumption of contaminated food and water with the gastrointestinal tract being the primary route for entry into the host. To promote infection, T. gondii has evolved highly specialized strategies for rapid traversal of the single cell thick intestinal epithelial barrier. Parasite transmigration via the paracellular pathway between adjacent cells enables parasite dissemination to secondary sites of infection where chronic infection of muscle and brain tissue is established. It has recently been proposed that parasite interactions with the integral tight junction (TJ) protein occludin influences parasite transmigration of the intestinal epithelium. We review here the emerging mechanisms of T. gondii transmigration of the small intestinal epithelium alongside the developing role played in modulating the wider TJ-associated proteome to rewire host cell regulatory systems for the benefit of the parasite. PMID:28452683

Mechanisms and pathways of Toxoplasma gondii transepithelial migration.

PubMed

Jones, Emily J; Korcsmaros, Tamas; Carding, Simon R

2017-01-02

Toxoplasma gondii is a ubiquitous parasite and a prevalent food-borne parasitic pathogen. Infection of the host occurs principally through oral consumption of contaminated food and water with the gastrointestinal tract being the primary route for entry into the host. To promote infection, T. gondii has evolved highly specialized strategies for rapid traversal of the single cell thick intestinal epithelial barrier. Parasite transmigration via the paracellular pathway between adjacent cells enables parasite dissemination to secondary sites of infection where chronic infection of muscle and brain tissue is established. It has recently been proposed that parasite interactions with the integral tight junction (TJ) protein occludin influences parasite transmigration of the intestinal epithelium. We review here the emerging mechanisms of T. gondii transmigration of the small intestinal epithelium alongside the developing role played in modulating the wider TJ-associated proteome to rewire host cell regulatory systems for the benefit of the parasite.

The AMERE project: Enabling real-time detection of radiation effects in individual cells in deep space

NASA Astrophysics Data System (ADS)

De Vos, Winnok H.; Meesen, Geert; Szpirer, Cedric; Scohy, Sophie; Cherukuri, Chaitanya; Evrard, Olivier; Hutsebaut, Xavier; Beghuin, Didier

2012-12-01

A major concern for long-term deep space missions is the detrimental impact of cosmic radiation on human health. Especially the presence of high-energy particles of high atomic mass (HZE) represents a serious threat. To contribute to a fundamental understanding of space radiation effects and to help improving risk assessment for humans on the Moon, the ESA Lunar Lander mission model payload includes a package dedicated to cell-based radiobiology experiments in the form of an Autonomous Microscope for Examination of Radiation Effects (AMERE). The purpose of this setup is to enable real-time visualization of DNA damage repair in living cells after traversal of HZE particles on the Moon. To assess the feasibility of this challenging experiment, we have analysed the biological and technological demands. In this article, we discuss the experimental concept, the biological considerations and describe the implications for system design.

75 FR 54223 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-03

... Measures (SSM) as follows: 1 crossing with gates and non-traversable curb medians and 1 crossing with four...-Rule Quiet Zone or in a separate Pre-Rule Quiet Zone. A SSM consisting of gates with a non-traversable... that the addition of Hubbards Lane with its SSM, results in a Quiet Zone Risk Index (QZRI) for the 6...

Apparatus for obstacle traversion

DOEpatents

Borenstein, Johann

2004-08-10

An apparatus for traversing obstacles having an elongated, round, flexible body that includes a plurality of drive track assemblies. The plurality of drive track assemblies cooperate to provide forward propulsion wherever a propulsion member is in contact with any feature of the environment, regardless of how many or which ones of the plurality of drive track assemblies make contact with such environmental feature.

78 FR 43782 - Standard Instrument Approach Procedures, and Takeoff Minimums and Obstacle Departure Procedures...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-22

..., CANCELED Kalamazoo, MI, Kalamazoo/Battle Creek Intl, RNAV (GPS) RWY 17, Amdt 1 Traverse City, MI, Cherry Capitol, GPS RWY 36, Orig-B, CANCELED Traverse City, MI, Cherry Capitol, RNAV (GPS) RWY 36, Orig Dodge..., Cassville Muni, Takeoff Minimums and Obstacle DP, Amdt 1 Fredericktown, MO, A. Paul Vance Fredericktown Rgnl...

Perceiving and Traversing In-Class and Out-of-Class Learning: Accounts from Foreign Language Learners in Hong Kong

ERIC Educational Resources Information Center

Lai, Chun

2015-01-01

Learning takes place across different social contexts, and understanding how learners perceive and traverse different learning contexts enables educators to gain a more comprehensive view of their learning processes and to support their learning better. This study examined how undergraduate foreign language learners perceived their learning…

78 FR 37966 - Safety Zone; National Cherry Festival Air Show and Fireworks Display, West Grand Traverse Bay...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-25

...-AA00 Safety Zone; National Cherry Festival Air Show and Fireworks Display, West Grand Traverse Bay... the hazards associated with fireworks displays and aircraft involved in the National Cherry Festival... Festival fireworks display and air show. At the close of the comment period, no comments were received in...

M113A1 Day/Night Movement Rate Analysis

DTIC Science & Technology

1975-06-01

d. Each vehicle traversed the course usiig the path of the preced- ing vehicle, i.e., no " free play " in selecting a route was permitted. The test...traversed the course usling the path of the preced- ing vehicle, i.e., no " free play " in selecting a route was permitted. The test course varied from

"Until I Became a Professional, I Was Not, Consciously, Indigenous": One Intercultural Bilingual Educator's Trajectory in Indigenous Language Revitalization

ERIC Educational Resources Information Center

Hornberger, Nancy H.

2014-01-01

Drawing from long-term ethnographic research in the Andes, this paper examines one Quechua-speaking Indigenous bilingual educator's trajectory as she traversed (and traverses) from rural highland communities of southern Peru through development as teacher, teacher educator, researcher, and advocate for Indigenous identity and language…

Graph traversals, genes, and matroids: An efficient case of the travelling salesman problem

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

Gusfield, D.; Stelling, P.; Wang, Lusheng

1996-12-31

In this paper the authors consider graph traversal problems that arise from a particular technology for DNA sequencing - sequencing by hybridization (SBH). They first explain the connection of the graph problems to SBH and then focus on the traversal problems. They describe a practical polynomial time solution to the Travelling Salesman Problem in a rich class of directed graphs (including edge weighted binary de Bruijn graphs), and provide a bounded-error approximation algorithm for the maximum weight TSP in a superset of those directed graphs. The authors also establish the existence of a matroid structure defined on the set ofmore » Euler and Hamilton paths in the restricted class of graphs. 8 refs., 5 figs.« less

The Forkhead transcription factor Hcm1 regulates chromosome segregation genes and fills the S-phase gap in the transcriptional circuitry of the cell cycle.

PubMed

Pramila, Tata; Wu, Wei; Miles, Shawna; Noble, William Stafford; Breeden, Linda L

2006-08-15

Transcription patterns shift dramatically as cells transit from one phase of the cell cycle to another. To better define this transcriptional circuitry, we collected new microarray data across the cell cycle of budding yeast. The combined analysis of these data with three other cell cycle data sets identifies hundreds of new highly periodic transcripts and provides a weighted average peak time for each transcript. Using these data and phylogenetic comparisons of promoter sequences, we have identified a late S-phase-specific promoter element. This element is the binding site for the forkhead protein Hcm1, which is required for its cell cycle-specific activity. Among the cell cycle-regulated genes that contain conserved Hcm1-binding sites, there is a significant enrichment of genes involved in chromosome segregation, spindle dynamics, and budding. This may explain why Hcm1 mutants show 10-fold elevated rates of chromosome loss and require the spindle checkpoint for viability. Hcm1 also induces the M-phase-specific transcription factors FKH1, FKH2, and NDD1, and two cell cycle-specific transcriptional repressors, WHI5 and YHP1. As such, Hcm1 fills a significant gap in our understanding of the transcriptional circuitry that underlies the cell cycle.

Analyzing the dynamics of cell cycle processes from fixed samples through ergodic principles.

PubMed

Wheeler, Richard John

2015-11-05

Tools to analyze cyclical cellular processes, particularly the cell cycle, are of broad value for cell biology. Cell cycle synchronization and live-cell time-lapse observation are widely used to analyze these processes but are not available for many systems. Simple mathematical methods built on the ergodic principle are a well-established, widely applicable, and powerful alternative analysis approach, although they are less widely used. These methods extract data about the dynamics of a cyclical process from a single time-point "snapshot" of a population of cells progressing through the cycle asynchronously. Here, I demonstrate application of these simple mathematical methods to analysis of basic cyclical processes--cycles including a division event, cell populations undergoing unicellular aging, and cell cycles with multiple fission (schizogony)--as well as recent advances that allow detailed mapping of the cell cycle from continuously changing properties of the cell such as size and DNA content. This includes examples using existing data from mammalian, yeast, and unicellular eukaryotic parasite cell biology. Through the ongoing advances in high-throughput cell analysis by light microscopy, electron microscopy, and flow cytometry, these mathematical methods are becoming ever more important and are a powerful complementary method to traditional synchronization and time-lapse cell cycle analysis methods. © 2015 Wheeler. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Environmental tests of metallization systems for terrestrial photovoltaic cells

NASA Technical Reports Server (NTRS)

Alexander, P., Jr.

1985-01-01

Seven different solar cell metallization systems were subjected to temperature cycling tests and humidity tests. Temperature cycling excursions were -50 deg C to 150 deg C per cycle. Humidity conditions were 70 deg C at 98% relative humidity. The seven metallization systems were: Ti/Ag, Ti/Pd/Ag, Ti/Pd/Cu, Ni/Cu, Pd/Ni/Solder, Cr/Pd/Ag, and thick film Ag. All metallization systems showed a slight to moderate decrease in cell efficiencies after subjection to 1000 temperature cycles. Six of the seven metallization systems also evidenced slight increases in cell efficiencies after moderate numbers of cycles, generally less than 100 cycles. The copper based systems showed the largest decrease in cell efficiencies after temperature cycling. All metallization systems showed moderate to large decreases in cell efficiencies after 123 days of humidity exposure. The copper based systems again showed the largest decrease in cell efficiencies after humidity exposure. Graphs of the environmental exposures versus cell efficiencies are presented for each metallization system, as well as environmental exposures versus fill factors or series resistance.

Cell cycle-tailored targeting of metastatic melanoma: Challenges and opportunities.

PubMed

Haass, Nikolas K; Gabrielli, Brian

2017-07-01

The advent of targeted therapies of metastatic melanoma, such as MAPK pathway inhibitors and immune checkpoint antagonists, has turned dermato-oncology from the "bad guy" to the "poster child" in oncology. Current targeted therapies are effective, although here is a clear need to develop combination therapies to delay the onset of resistance. Many antimelanoma drugs impact on the cell cycle but are also dependent on certain cell cycle phases resulting in cell cycle phase-specific drug insensitivity. Here, we raise the question: Have combination trials been abandoned prematurely as ineffective possibly only because drug scheduling was not optimized? Firstly, if both drugs of a combination hit targets in the same melanoma cell, cell cycle-mediated drug insensitivity should be taken into account when planning combination therapies, timing of dosing schedules and choice of drug therapies in solid tumors. Secondly, if the combination is designed to target different tumor cell subpopulations of a heterogeneous tumor, one drug effective in a particular subpopulation should not negatively impact on the other drug targeting another subpopulation. In addition to the role of cell cycle stage and progression on standard chemotherapeutics and targeted drugs, we discuss the utilization of cell cycle checkpoint control defects to enhance chemotherapeutic responses or as targets themselves. We propose that cell cycle-tailored targeting of metastatic melanoma could further improve therapy outcomes and that our real-time cell cycle imaging 3D melanoma spheroid model could be utilized as a tool to measure and design drug scheduling approaches. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Transcriptome changes and cAMP oscillations in an archaeal cell cycle.

PubMed

Baumann, Anke; Lange, Christian; Soppa, Jörg

2007-06-11

The cell cycle of all organisms includes mass increase by a factor of two, replication of the genetic material, segregation of the genome to different parts of the cell, and cell division into two daughter cells. It is tightly regulated and typically includes cell cycle-specific oscillations of the levels of transcripts, proteins, protein modifications, and signaling molecules. Until now cell cycle-specific transcriptome changes have been described for four eukaryotic species ranging from yeast to human, but only for two prokaryotic species. Similarly, oscillations of small signaling molecules have been identified in very few eukaryotic species, but not in any prokaryote. A synchronization procedure for the archaeon Halobacterium salinarum was optimized, so that nearly 100% of all cells divide in a time interval that is 1/4th of the generation time of exponentially growing cells. The method was used to characterize cell cycle-dependent transcriptome changes using a genome-wide DNA microarray. The transcript levels of 87 genes were found to be cell cycle-regulated, corresponding to 3% of all genes. They could be clustered into seven groups with different transcript level profiles. Cluster-specific sequence motifs were detected around the start of the genes that are predicted to be involved in cell cycle-specific transcriptional regulation. Notably, many cell cycle genes that have oscillating transcript levels in eukaryotes are not regulated on the transcriptional level in H. salinarum. Synchronized cultures were also used to identify putative small signaling molecules. H. salinarum was found to contain a basal cAMP concentration of 200 microM, considerably higher than that of yeast. The cAMP concentration is shortly induced directly prior to and after cell division, and thus cAMP probably is an important signal for cell cycle progression. The analysis of cell cycle-specific transcriptome changes of H. salinarum allowed to identify a strategy of transcript level regulation that is different from all previously characterized species. The transcript levels of only 3% of all genes are regulated, a fraction that is considerably lower than has been reported for four eukaryotic species (6%-28%) and for the bacterium C. crescentus (19%). It was shown that cAMP is present in significant concentrations in an archaeon, and the phylogenetic profile of the adenylate cyclase indicates that this signaling molecule is widely distributed in archaea. The occurrence of cell cycle-dependent oscillations of the cAMP concentration in an archaeon and in several eukaryotic species indicates that cAMP level changes might be a phylogenetically old signal for cell cycle progression.

Human innate lymphoid cells (ILCs) in filarial infections.

PubMed

Bonne-Année, S; Nutman, T B

2018-02-01

Filarial infections are characteristically chronic and can cause debilitating diseases governed by parasite-induced innate and adaptive immune responses. Filarial parasites traverse or establish niches in the skin (migrating infective larvae), in nonmucosal tissues (adult parasite niche) and in the blood or skin (circulating microfilariae) where they intersect with the host immune response. While several studies have demonstrated that filarial parasites and their antigens can modulate myeloid cells (monocyte, macrophage and dendritic cell subsets), T- and B-lymphocytes and skin resident cell populations, the role of innate lymphoid cells during filarial infections has only recently emerged. Despite the identification and characterization of innate lymphoid cells (ILCs) in murine helminth infections, little is actually known about the role of human ILCs during parasitic infections. The focus of this review will be to highlight the composition of ILCs in the skin, lymphatics and blood; where the host-parasite interaction is well-defined and to examine the role of ILCs during filarial infections. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Environment of Space Interactions with Space Systems

NASA Technical Reports Server (NTRS)

2004-01-01

The primary product of this research project was a computer program named SAVANT. This program uses the Displacement Damage Dose (DDD) method of calculating radiation damage to solar cells. This calculation method was developed at the Naval Research Laboratory, and uses fundamental physical properties of the solar cell materials to predict radiation damage to the solar cells. This means that fewer experimental measurements are required to characterize the radiation damage to the cells, which results in a substantial cost savings to qualify solar cells for orbital missions. In addition, the DDD method makes it easier to characterize cells that are already being used, but have not been fully tested using the older technique of characterizing radiation damage. The computer program combines an orbit generator with NASA's AP-8 and AE-8 models of trapped protons and electrons. This allows the user to specify an orbit, and the program will calculate how the spacecraft moves during the mission, and the radiation environment that it encounters. With the spectrum of the particles, the program calculates how they would slow down while traversing the coverglass, and provides a slowed-down spectrum.

Ecdysone signaling induces two phases of cell cycle exit in Drosophila cells

PubMed Central

Guo, Yongfeng; Flegel, Kerry; Kumar, Jayashree; McKay, Daniel J.

2016-01-01

ABSTRACT During development, cell proliferation and differentiation must be tightly coordinated to ensure proper tissue morphogenesis. Because steroid hormones are central regulators of developmental timing, understanding the links between steroid hormone signaling and cell proliferation is crucial to understanding the molecular basis of morphogenesis. Here we examined the mechanism by which the steroid hormone ecdysone regulates the cell cycle in Drosophila. We find that a cell cycle arrest induced by ecdysone in Drosophila cell culture is analogous to a G2 cell cycle arrest observed in the early pupa wing. We show that in the wing, ecdysone signaling at the larva-to-puparium transition induces Broad which in turn represses the cdc25c phosphatase String. The repression of String generates a temporary G2 arrest that synchronizes the cell cycle in the wing epithelium during early pupa wing elongation and flattening. As ecdysone levels decline after the larva-to-puparium pulse during early metamorphosis, Broad expression plummets, allowing String to become re-activated, which promotes rapid G2/M progression and a subsequent synchronized final cell cycle in the wing. In this manner, pulses of ecdysone can both synchronize the final cell cycle and promote the coordinated acquisition of terminal differentiation characteristics in the wing. PMID:27737823

DNA replication checkpoint promotes G1-S transcription by inactivating the MBF repressor Nrm1

PubMed Central

de Bruin, R. A. M.; Kalashnikova, T. I.; Aslanian, A.; Wohlschlegel, J.; Chahwan, C.; Yates, J. R.; Russell, P.; Wittenberg, C.

2008-01-01

The cell cycle transcriptional program imposes order on events of the cell-cycle and is a target for signals that regulate cell-cycle progression, including checkpoints required to maintain genome integrity. Neither the mechanism nor functional significance of checkpoint regulation of the cell-cycle transcription program are established. We show that Nrm1, an MBF-specific transcriptional repressor acting at the transition from G1 to S phase of the cell cycle, is at the nexus between the cell cycle transcriptional program and the DNA replication checkpoint in fission yeast. Phosphorylation of Nrm1 by the Cds1 (Chk2) checkpoint protein kinase, which is activated in response to DNA replication stress, promotes its dissociation from the MBF transcription factor. This leads to the expression of genes encoding components that function in DNA replication and repair pathways important for cell survival in response to arrested DNA replication. PMID:18682565

The B-MYB Transcriptional Network Guides Cell Cycle Progression and Fate Decisions to Sustain Self-Renewal and the Identity of Pluripotent Stem Cells

PubMed Central

Zhan, Ming; Riordon, Daniel R.; Yan, Bin; Tarasova, Yelena S.; Bruweleit, Sarah; Tarasov, Kirill V.; Li, Ronald A.; Wersto, Robert P.; Boheler, Kenneth R.

2012-01-01

Embryonic stem cells (ESCs) are pluripotent and have unlimited self-renewal capacity. Although pluripotency and differentiation have been examined extensively, the mechanisms responsible for self-renewal are poorly understood and are believed to involve an unusual cell cycle, epigenetic regulators and pluripotency-promoting transcription factors. Here we show that B-MYB, a cell cycle regulated phosphoprotein and transcription factor critical to the formation of inner cell mass, is central to the transcriptional and co-regulatory networks that sustain normal cell cycle progression and self-renewal properties of ESCs. Phenotypically, B-MYB is robustly expressed in ESCs and induced pluripotent stem cells (iPSCs), and it is present predominantly in a hypo-phosphorylated state. Knockdown of B-MYB results in functional cell cycle abnormalities that involve S, G2 and M phases, and reduced expression of critical cell cycle regulators like ccnb1 and plk1. By conducting gene expression profiling on control and B-MYB deficient cells, ChIP-chip experiments, and integrative computational analyses, we unraveled a highly complex B-MYB-mediated transcriptional network that guides ESC self-renewal. The network encompasses critical regulators of all cell cycle phases and epigenetic regulators, pluripotency transcription factors, and differentiation determinants. B-MYB along with E2F1 and c-MYC preferentially co-regulate cell cycle target genes. B-MYB also co-targets genes regulated by OCT4, SOX2 and NANOG that are significantly associated with stem cell differentiation, embryonic development, and epigenetic control. Moreover, loss of B-MYB leads to a breakdown of the transcriptional hierarchy present in ESCs. These results coupled with functional studies demonstrate that B-MYB not only controls and accelerates cell cycle progression in ESCs it contributes to fate decisions and maintenance of pluripotent stem cell identity. PMID:22936984

The B-MYB transcriptional network guides cell cycle progression and fate decisions to sustain self-renewal and the identity of pluripotent stem cells.

PubMed

Zhan, Ming; Riordon, Daniel R; Yan, Bin; Tarasova, Yelena S; Bruweleit, Sarah; Tarasov, Kirill V; Li, Ronald A; Wersto, Robert P; Boheler, Kenneth R

2012-01-01

Embryonic stem cells (ESCs) are pluripotent and have unlimited self-renewal capacity. Although pluripotency and differentiation have been examined extensively, the mechanisms responsible for self-renewal are poorly understood and are believed to involve an unusual cell cycle, epigenetic regulators and pluripotency-promoting transcription factors. Here we show that B-MYB, a cell cycle regulated phosphoprotein and transcription factor critical to the formation of inner cell mass, is central to the transcriptional and co-regulatory networks that sustain normal cell cycle progression and self-renewal properties of ESCs. Phenotypically, B-MYB is robustly expressed in ESCs and induced pluripotent stem cells (iPSCs), and it is present predominantly in a hypo-phosphorylated state. Knockdown of B-MYB results in functional cell cycle abnormalities that involve S, G2 and M phases, and reduced expression of critical cell cycle regulators like ccnb1 and plk1. By conducting gene expression profiling on control and B-MYB deficient cells, ChIP-chip experiments, and integrative computational analyses, we unraveled a highly complex B-MYB-mediated transcriptional network that guides ESC self-renewal. The network encompasses critical regulators of all cell cycle phases and epigenetic regulators, pluripotency transcription factors, and differentiation determinants. B-MYB along with E2F1 and c-MYC preferentially co-regulate cell cycle target genes. B-MYB also co-targets genes regulated by OCT4, SOX2 and NANOG that are significantly associated with stem cell differentiation, embryonic development, and epigenetic control. Moreover, loss of B-MYB leads to a breakdown of the transcriptional hierarchy present in ESCs. These results coupled with functional studies demonstrate that B-MYB not only controls and accelerates cell cycle progression in ESCs it contributes to fate decisions and maintenance of pluripotent stem cell identity.

HCdc14A is involved in cell cycle regulation of human brain vascular endothelial cells following injury induced by high glucose, free fatty acids and hypoxia.

PubMed

Su, Jingjing; Zhou, Houguang; Tao, Yinghong; Guo, Zhuangli; Zhang, Shuo; Zhang, Yu; Huang, Yanyan; Tang, Yuping; Hu, Renming; Dong, Qiang

2015-01-01

Cell cycle processes play a vital role in vascular endothelial proliferation and dysfunction. Cell division cycle protein 14 (Cdc14) is an important cell cycle regulatory phosphatase. Previous studies in budding yeast demonstrated that Cdc14 could trigger the inactivation of mitotic cyclin-dependent kinases (Cdks), which are required for mitotic exit and cytokinesis. However, the exact function of human Cdc14 (hCdc14) in cell cycle regulation during vascular diseases is yet to be elucidated. There are two HCdc14 homologs: hCdc14A and hCdc14B. In the current study, we investigated the potential role of hCdc14A in high glucose-, free fatty acids (FFAs)-, and hypoxia-induced injury in cultured human brain vascular endothelial cells (HBVECs). Data revealed that high glucose, FFA, and hypoxia down-regulated hCdc14A expression remarkably, and also affected the expression of other cell cycle-related proteins such as cyclin B, cyclin D, cyclin E, and p53. Furthermore, the combined addition of the three stimuli largely blocked cell cycle progression, decreased cell proliferation, and increased apoptosis. We also determined that hCdc14A was localized mainly to centrosomes during interphase and spindles during mitosis using confocal microscopy, and that it could affect the expression of other cycle-related proteins. More importantly, the overexpression of hCdc14A accelerated cell cycle progression, enhanced cell proliferation, and promoted neoplastic transformation, whereas the knockdown of hCdc14A using small interfering RNA produced the opposite effects. Therefore, these findings provide novel evidence that hCdc14A might be involved in cell cycle regulation in cultured HBVECs during high glucose-, FFA-, and hypoxia-induced injury. Copyright © 2014 Elsevier Inc. All rights reserved.

Two inhibitory systems and CKIs regulate cell cycle exit of mammalian cardiomyocytes after birth

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

Tane, Shoji; Okayama, Hitomi; Ikenishi, Aiko

Mammalian cardiomyocytes actively proliferate during embryonic stages, following which they exit their cell cycle after birth, and the exit is maintained. Previously, we showed that two inhibitory systems (the G1-phase inhibitory system: repression of cyclin D1 expression; the M-phase inhibitory system: inhibition of CDK1 activation) maintain the cell cycle exit of mouse adult cardiomyocytes. We also showed that two CDK inhibitors (CKIs), p21{sup Cip1} and p27{sup Kip1}, regulate the cell cycle exit in a portion of postnatal cardiomyocytes. It remains unknown whether the two inhibitory systems are involved in the cell cycle exit of postnatal cardiomyocytes and whether p21{sup Cip1}more » and p27{sup Kip1} also inhibit entry to M-phase. Here, we showed that more than 40% of cardiomyocytes entered an additional cell cycle by induction of cyclin D1 expression at postnatal stages, but M-phase entry was inhibited in the majority of cardiomyocytes. Marked cell cycle progression and endoreplication were observed in cardiomyocytes of p21{sup Cip1} knockout mice at 4 weeks of age. In addition, tri- and tetranucleated cardiomyocytes increased significantly in p21{sup Cip1} knockout mice. These data showed that the G1-phase inhibitory system and two CKIs (p21{sup Cip1} and p27{sup Kip1}) inhibit entry to an additional cell cycle in postnatal cardiomyocytes, and that the M-phase inhibitory system and p21{sup Cip1} inhibit M-phase entry of cardiomyocytes which have entered the additional cell cycle. - Highlights: • Many postnatal cardiomyocytes entered an additional cell cycle by cyclin D1 induction. • The majority of cardiomyocytes could not enter M-phase after cyclin D1 induction. • Cell cycle progressed markedly in p21{sup Cip1} knockout mice after postnatal day 14. • Tri- and tetranucleated cardiomyocytes increased in p21{sup Cip1} knockout mice.« less

Dynamics of Human Telomerase Holoenzyme Assembly and Subunit Exchange across the Cell Cycle*

PubMed Central

Vogan, Jacob M.; Collins, Kathleen

2015-01-01

Human telomerase acts on telomeres during the genome synthesis phase of the cell cycle, accompanied by its concentration in Cajal bodies and transient colocalization with telomeres. Whether the regulation of human telomerase holoenzyme assembly contributes to the cell cycle restriction of telomerase function is unknown. We investigated the steady-state levels, assembly, and exchange dynamics of human telomerase subunits with quantitative in vivo cross-linking and other methods. We determined the physical association of telomerase subunits in cells blocked or progressing through the cell cycle as synchronized by multiple protocols. The total level of human telomerase RNA (hTR) was invariant across the cell cycle. In vivo snapshots of telomerase holoenzyme composition established that hTR remains bound to human telomerase reverse transcriptase (hTERT) throughout all phases of the cell cycle, and subunit competition assays suggested that hTERT-hTR interaction is not readily exchangeable. In contrast, the telomerase holoenzyme Cajal body-associated protein, TCAB1, was released from hTR in mitotic cells coincident with TCAB1 delocalization from Cajal bodies. This telomerase holoenzyme disassembly was reversible with cell cycle progression without any change in total TCAB1 protein level. Consistent with differential cell cycle regulation of hTERT-hTR and TCAB1-hTR protein-RNA interactions, overexpression of hTERT or TCAB1 had limited if any influence on hTR assembly of the other subunit. Overall, these findings revealed a cell cycle regulation that disables human telomerase association with telomeres while preserving the co-folded hTERT-hTR ribonucleoprotein catalytic core. Studies here, integrated with previous work, led to a unifying model for telomerase subunit assembly and trafficking in human cells. PMID:26170453

Distinguishing between stochasticity and determinism: Examples from cell cycle duration variability.

PubMed

Pearl Mizrahi, Sivan; Sandler, Oded; Lande-Diner, Laura; Balaban, Nathalie Q; Simon, Itamar

2016-01-01

We describe a recent approach for distinguishing between stochastic and deterministic sources of variability, focusing on the mammalian cell cycle. Variability between cells is often attributed to stochastic noise, although it may be generated by deterministic components. Interestingly, lineage information can be used to distinguish between variability and determinism. Analysis of correlations within a lineage of the mammalian cell cycle duration revealed its deterministic nature. Here, we discuss the sources of such variability and the possibility that the underlying deterministic process is due to the circadian clock. Finally, we discuss the "kicked cell cycle" model and its implication on the study of the cell cycle in healthy and cancerous tissues. © 2015 WILEY Periodicals, Inc.

Ubiquitin specific protease 2 acts as a key modulator for the regulation of cell cycle by adiponectin and leptin in cancer cells.

PubMed

Nepal, Saroj; Shrestha, Anup; Park, Pil-Hoon

2015-09-05

Adiponectin and leptin, both produced from adipose tissue, cause cell cycle arrest and progression, respectively in cancer cells. Ubiquitin specific protease-2 (USP-2), a deubiquitinating enzyme, is known to impair proteasome-induced degradation of cyclin D1, a critical cell cycle regulator. Herein, we investigated the effects of these adipokines on USP-2 expression and its potential role in the modulation of cell cycle. Treatment with globular adiponectin (gAcrp) decreased, whereas leptin increased USP-2 expression both in human hepatoma and breast cancer cells. In addition, overexpression or gene silencing of USP-2 affected cyclin D1 expression and cell cycle progression/arrest by adipokines. Adiponectin and leptin also modulated in vitro proteasomal activity, which was partially dependent on USP-2 expression. Taken together, our results reveal that modulation of USP-2 expression plays a crucial role in cell cycle regulation by adipokines. Thus, USP-2 would be a promising therapeutic target for the modulation of cancer cell growth by adipokines. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

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.

Cell cycle re-entry sensitizes podocytes to injury induced death.

PubMed

Hagen, Manuel; Pfister, Eva; Kosel, Andrea; Shankland, Stuart; Pippin, Jeffrey; Amann, Kerstin; Daniel, Christoph

2016-07-17

Podocytes are terminally differentiated renal cells, lacking the ability to regenerate by proliferation. However, during renal injury, podocytes re-enter into the cell cycle but fail to divide. Earlier studies suggested that re-entry into cell cycle results in loss of podocytes, but a direct evidence for this is lacking. Therefore, we established an in vitro model to test the consequences of re-entry into the cell cycle on podocyte survival. A mouse immortalized podocyte cell line was differentiated to non-permissive podocytes and stimulated with e.g. growth factors. Stimulated cells were analyzed for mRNA-expression or stained for cell cycle analysis using flow cytometry and immunocytofluorescence microscopy. After stimulation to re-entry into cell cycle, podocytes were stressed with puromycin aminonucleoside (PAN) and analyzed for survival. During permissive stage more than 40% of immortalized podocytes were in the S-phase. In contrast, S-phase in non-permissive differentiated podocytes was reduced to 5%. Treatment with b-FGF dose dependently induced re-entry into cell cycle increasing the number of podocytes in the S-phase to 10.7% at an optimal bFGF dosage of 10 ng/ml. Forty eight hours after stimulation with bFGF the number of bi-nucleated podocytes significantly increased. A secondary injury stimulus significantly reduced podocyte survival preferentially in bi-nucleated podocytes In conclusion, stimulation of podocytes using bFGF was able to induce re-entry of podocytes into the cell cycle and to sensitize the cells for cell death by secondary injuries. Therefore, this model is appropriate for testing new podocyte protective substances that can be used for therapy.

Susceptibility of Hep3B cells in different phases of cell cycle to tBid.

PubMed

Ma, Shi-Hong; Chen, George G; Ye, Caiguo; Leung, Billy C S; Ho, Rocky L K; Lai, Paul B S

2011-01-01

tBid is a pro-apoptotic molecule. Apoptosis inducers usually act in a cell cycle-specific fashion. The aim of this study was to elucidate whether effect of tBid on hepatocellular carcinoma (HCC) Hep3B cells was cell cycle phase specific. We synchronized Hep3B cells at G0/G1, S or G2/M phases by chemicals or flow sorting and tested the susceptibility of the cells to recombinant tBid. Cell viability was measured by MTT assay and apoptosis by TUNEL. The results revealed that tBid primarily targeted the cells at G0/G1 phase of cell cycle, and it also increased the cells at the G2/M phase. 5-Fluorouracil (5-FU), on the other hand, arrested Hep3B cells at the G0/G1 phase, but significantly reduced cells at G2/M phase. The levels of cell cycle-related proteins and caspases were altered in line with the change in the cell cycle. The combination of tBid with 5-FU caused more cells to be apoptotic than either agent alone. Therefore, the complementary effect of tBid and 5-FU on different phases of the cell cycle may explain their synergistric effect on Hep3B cells. The elucidation of the phase-specific effect of tBid points to a possible therapeutic option that combines different phase specific agents to overcome resistance of HCC. Copyright © 2010 Elsevier B.V. All rights reserved.

Thermal stress cycling of GaAs solar cells

NASA Technical Reports Server (NTRS)

Francis, Robert W.

1987-01-01

Thermal stress cycling was performed on gallium arsenide solar cells to investigate their electrical, mechanical, and structural integrity. Cells were cycled under low Earth orbit (LEO) simulated temperature conditions in vacuum. Cell evaluations consisted of power output values, spectral response, optical microscopy and ion microprobe mass analysis, and depth profiles on both front surface inter-grid areas and metallization contact grid lines. Cells were examined for degradation after 500, 5,000, 10,000 and 15,245 thermal cycles. No indication of performance degradation was found for any vendor's cell lot.

Effect of LEO cycling on 125 Ah advanced design IPV nickel-hydrogen flight cells. An update

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Hall, Stephen W.

1991-01-01

Validation testing of the NASA Lewis 125 Ah advanced design individual pressure vessel (IPV) nickel-hydrogen flight cells was conducted. Work consisted of characterization, storage, and cycle life testing. There was no capacity degradation after 52 days of storage with the cells in the discharged state, an open circuit, 0 C, and a hydrogen pressure of 14.5 psia. The catalyzed wall wick cells were cycled for over 11,000 cycles with no cell failures in the continuing test. One of the noncatalyzed wall wick cells failed.

Exploring a Link Between NF-KB and G2/M Cell Cycle Arrest in Breast Cancer Cells

DTIC Science & Technology

2005-04-01

studies with esophageal squamous cell carcinom a lines have shown that IR induced p21waf1/ ciP ’ and a G2 cell cycle arrest that could als o be...i AD Award Number : DAMD17-02-1-062 3 TITLE : Exploring a Link Between NF-KB and G 2 /M Cell Cycle Arres t in Breast Cancer Cell s PRINCIPAL...Mar 2005 ) 4 . TITLE AND SUBTITL E Exploring a Link Between NF-kB and G 2 /M Cell Cycle Arres t in Breast Cancer Cells 5. FUND/NG NUMBERS DAMD17-02-1

Temporal remodeling of the cell cycle accompanies differentiation in the Drosophila germline.

PubMed

Hinnant, Taylor D; Alvarez, Arturo A; Ables, Elizabeth T

2017-09-01

Development of multicellular organisms relies upon the coordinated regulation of cellular differentiation and proliferation. Growing evidence suggests that some molecular regulatory pathways associated with the cell cycle machinery also dictate cell fate; however, it remains largely unclear how the cell cycle is remodeled in concert with cell differentiation. During Drosophila oogenesis, mature oocytes are created through a series of precisely controlled division and differentiation steps, originating from a single tissue-specific stem cell. Further, germline stem cells (GSCs) and their differentiating progeny remain in a predominantly linear arrangement as oogenesis proceeds. The ability to visualize the stepwise events of differentiation within the context of a single tissue make the Drosophila ovary an exceptional model for study of cell cycle remodeling. To describe how the cell cycle is remodeled in germ cells as they differentiate in situ, we used the Drosophila Fluorescence Ubiquitin-based Cell Cycle Indicator (Fly-FUCCI) system, in which degradable versions of GFP::E2f1 and RFP::CycB fluorescently label cells in each phase of the cell cycle. We found that the lengths of the G1, S, and G2 phases of the cell cycle change dramatically over the course of differentiation, and identified the 4/8-cell cyst as a key developmental transition state in which cells prepare for specialized cell cycles. Our data suggest that the transcriptional activator E2f1, which controls the transition from G1 to S phase, is a key regulator of mitotic divisions in the early germline. Our data support the model that E2f1 is necessary for proper GSC proliferation, self-renewal, and daughter cell development. In contrast, while E2f1 degradation by the Cullin 4 (Cul4)-containing ubiquitin E3 ligase (CRL4) is essential for developmental transitions in the early germline, our data do not support a role for E2f1 degradation as a mechanism to limit GSC proliferation or self-renewal. Taken together, these findings provide further insight into the regulation of cell proliferation and the acquisition of differentiated cell fate, with broad implications across developing tissues. Copyright © 2017 Elsevier Inc. All rights reserved.

Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells

PubMed Central

Kraehling, Jan R.; Chidlow, John H.; Rajagopal, Chitra; Sugiyama, Michael G.; Fowler, Joseph W.; Lee, Monica Y.; Zhang, Xinbo; Ramírez, Cristina M.; Park, Eon Joo; Tao, Bo; Chen, Keyang; Kuruvilla, Leena; Larriveé, Bruno; Folta-Stogniew, Ewa; Ola, Roxana; Rotllan, Noemi; Zhou, Wenping; Nagle, Michael W.; Herz, Joachim; Williams, Kevin Jon; Eichmann, Anne; Lee, Warren L.; Fernández-Hernando, Carlos; Sessa, William C.

2016-01-01

In humans and animals lacking functional LDL receptor (LDLR), LDL from plasma still readily traverses the endothelium. To identify the pathways of LDL uptake, a genome-wide RNAi screen was performed in endothelial cells and cross-referenced with GWAS-data sets. Here we show that the activin-like kinase 1 (ALK1) mediates LDL uptake into endothelial cells. ALK1 binds LDL with lower affinity than LDLR and saturates only at hypercholesterolemic concentrations. ALK1 mediates uptake of LDL into endothelial cells via an unusual endocytic pathway that diverts the ligand from lysosomal degradation and promotes LDL transcytosis. The endothelium-specific genetic ablation of Alk1 in Ldlr-KO animals leads to less LDL uptake into the aortic endothelium, showing its physiological role in endothelial lipoprotein metabolism. In summary, identification of pathways mediating LDLR-independent uptake of LDL may provide unique opportunities to block the initiation of LDL accumulation in the vessel wall or augment hepatic LDLR-dependent clearance of LDL. PMID:27869117

Recent thymic emigrants are tolerized in the absence of inflammation

PubMed Central

Friesen, Travis J.; Ji, Qingyong

2016-01-01

T cell development requires a period of postthymic maturation. Why this is the case has remained a mystery, particularly given the rigors of intrathymic developmental checkpoints, successfully traversed by only ∼5% of thymocytes. We now show that the first few weeks of T cell residence in the lymphoid periphery define a period of heightened susceptibility to tolerance induction to tissue-restricted antigens (TRAs), the outcome of which depends on the context in which recent thymic emigrants (RTEs) encounter antigen. After encounter with TRAs in the absence of inflammation, RTEs exhibited defects in proliferation, diminished cytokine production, elevated expression of anergy-associated genes, and diminished diabetogenicity. These properties were mirrored in vitro by enhanced RTE susceptibility to regulatory T cell–mediated suppression. In the presence of inflammation, RTEs and mature T cells were, in contrast, equally capable of inducing diabetes, proliferating, and producing cytokines. Thus, recirculating RTEs encounter TRAs during a transitional developmental stage that facilitates tolerance induction, but inflammation converts antigen-exposed, tolerance-prone RTEs into competent effector cells. PMID:27139493

Bipolar battery with array of sealed cells

DOEpatents

Kaun, Thomas D.; Smaga, John A.

1987-01-01

A lithium alloy/metal sulfide battery as a dipolar battery is disclosed with an array of stacked cells with the anode and cathode electrode materials in each cell sealed in a confining structure and separated from one another except across separator material interposed therebetween. The separator material is contained in a module having separate perforated metallic sheets that sandwich opposite sides of the separator material for the cell and an annular insulating spacer that surrounds the separator material beyond the perforations and is also sandwiched between and sealed to the sheets. The peripheral edges of the sheets project outwardly beyond the spacer, traverse the side edges of the adjacent electrode material to form cup-like electrode holders, and are fused to the adjacent current collector or end face members of the array. Electrolyte is infused into the electrolyte cavity through the perforations of one of the metallic sheets with the perforations also functioning to allow ionic conductance across the separator material between the adjacent electrodes. A gas-tight housing provides an enclosure of the array.

Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells.

PubMed

Kraehling, Jan R; Chidlow, John H; Rajagopal, Chitra; Sugiyama, Michael G; Fowler, Joseph W; Lee, Monica Y; Zhang, Xinbo; Ramírez, Cristina M; Park, Eon Joo; Tao, Bo; Chen, Keyang; Kuruvilla, Leena; Larriveé, Bruno; Folta-Stogniew, Ewa; Ola, Roxana; Rotllan, Noemi; Zhou, Wenping; Nagle, Michael W; Herz, Joachim; Williams, Kevin Jon; Eichmann, Anne; Lee, Warren L; Fernández-Hernando, Carlos; Sessa, William C

2016-11-21

In humans and animals lacking functional LDL receptor (LDLR), LDL from plasma still readily traverses the endothelium. To identify the pathways of LDL uptake, a genome-wide RNAi screen was performed in endothelial cells and cross-referenced with GWAS-data sets. Here we show that the activin-like kinase 1 (ALK1) mediates LDL uptake into endothelial cells. ALK1 binds LDL with lower affinity than LDLR and saturates only at hypercholesterolemic concentrations. ALK1 mediates uptake of LDL into endothelial cells via an unusual endocytic pathway that diverts the ligand from lysosomal degradation and promotes LDL transcytosis. The endothelium-specific genetic ablation of Alk1 in Ldlr-KO animals leads to less LDL uptake into the aortic endothelium, showing its physiological role in endothelial lipoprotein metabolism. In summary, identification of pathways mediating LDLR-independent uptake of LDL may provide unique opportunities to block the initiation of LDL accumulation in the vessel wall or augment hepatic LDLR-dependent clearance of LDL.

Cdk1 activity acts as a quantitative platform for coordinating cell cycle progression with periodic transcription

PubMed Central

Banyai, Gabor; Baïdi, Feriel; Coudreuse, Damien; Szilagyi, Zsolt

2016-01-01

Cell proliferation is regulated by cyclin-dependent kinases (Cdks) and requires the periodic expression of particular gene clusters in different cell cycle phases. However, the interplay between the networks that generate these transcriptional oscillations and the core cell cycle machinery remains largely unexplored. In this work, we use a synthetic regulable Cdk1 module to demonstrate that periodic expression is governed by quantitative changes in Cdk1 activity, with different clusters directly responding to specific activity levels. We further establish that cell cycle events neither participate in nor interfere with the Cdk1-driven transcriptional program, provided that cells are exposed to the appropriate Cdk1 activities. These findings contrast with current models that propose self-sustained and Cdk1-independent transcriptional oscillations. Our work therefore supports a model in which Cdk1 activity serves as a quantitative platform for coordinating cell cycle transitions with the expression of critical genes to bring about proper cell cycle progression. PMID:27045731

Mechanistic mathematical modelling of mercaptopurine effects on cell cycle of human acute lymphoblastic leukaemia cells

PubMed Central

Panetta, J C; Evans, W E; Cheok, M H

2006-01-01

The antimetabolite mercaptopurine (MP) is widely used to treat childhood acute lymphoblastic leukaemia (ALL). To study the dynamics of MP on the cell cycle, we incubated human T-cell leukaemia cell lines (Molt-4 sensitive and resistant subline and P12 resistant) with 10 μM MP and measured total cell count, cell cycle distribution, percent viable, percent apoptotic, and percent dead cells serially over 72 h. We developed a mathematical model of the cell cycle dynamics after treatment with MP and used it to show that the Molt-4 sensitive controls had a significantly higher rate of cells entering apoptosis (2.7-fold, P<0.00001) relative to the resistant cell lines. Additionally, when treated with MP, the sensitive cell line showed a significant increase in the rate at which cells enter apoptosis compared to its controls (2.4-fold, P<0.00001). Of note, the resistant cell lines had a higher rate of antimetabolite incorporation into the DNA of viable cells (>1.4-fold, P<0.01). Lastly, in contrast to the other cell lines, the Molt-4 resistant subline continued to cycle, though at a rate slower relative to its control, rather than proceed to apoptosis. This led to a larger S-phase block in the Molt-4 resistant cell line, but not a higher rate of cell death. Gene expression of apoptosis, cell cycle, and repair genes were consistent with mechanistic dynamics described by the model. In summary, the mathematical model provides a quantitative assessment to compare the cell cycle effects of MP in cells with varying degrees of MP resistance. PMID:16333308

Contact guidance is cell cycle-dependent.

PubMed

Pourfarhangi, Kamyar Esmaeili; De La Hoz, Edgar Cardenas; Cohen, Andrew R; Gligorijevic, Bojana

2018-09-01

Cancer cell migration is essential for metastasis, during which cancer cells move through the tumor and reach the blood vessels. In vivo , cancer cells are exposed to contact guidance and chemotactic cues. Depending on the strength of such cues, cells will migrate in a random or directed manner. While similar cues may also stimulate cell proliferation, it is not clear whether cell cycle progression affects migration of cancer cells and whether this effect is different in random versus directed migration. In this study, we tested the effect of cell cycle progression on contact guided migration in 2D and 3D environments, in the breast carcinoma cell line, FUCCI-MDA-MB-231. The results were quantified from live cell microscopy images using the open source lineage editing and validation image analysis tools (LEVER). In 2D, cells were placed inside 10 μ m-wide microchannels to stimulate contact guidance, with or without an additional chemotactic gradient of the soluble epidermal growth factor. In 3D, contact guidance was modeled by aligned collagen fibers. In both 2D and 3D, contact guidance was cell cycle-dependent, while the addition of the chemo-attractant gradient in 2D increased cell velocity and persistence in directionally migrating cells, regardless of their cell cycle phases. In both 2D and 3D contact guidance, cells in the G1 phase of the cell cycle outperformed cells in the S/G2 phase in terms of migration persistence and instantaneous velocity. These data suggest that in the presence of contact guidance cues in vivo , breast carcinoma cells in the G1 phase of the cell cycle may be more efficient in reaching the neighboring vasculature.

Traversable geometric dark energy wormholes constrained by astrophysical observations

NASA Astrophysics Data System (ADS)

Wang, Deng; Meng, Xin-he

2016-09-01

In this paper, we introduce the astrophysical observations into the wormhole research. We investigate the evolution behavior of the dark energy equation of state parameter ω by constraining the dark energy model, so that we can determine in which stage of the universe wormholes can exist by using the condition ω <-1. As a concrete instance, we study the Ricci dark energy (RDE) traversable wormholes constrained by astrophysical observations. Particularly, we find from Fig. 5 of this work, when the effective equation of state parameter ω _X<-1 (or z<0.109), i.e., the null energy condition (NEC) is violated clearly, the wormholes will exist (open). Subsequently, six specific solutions of statically and spherically symmetric traversable wormhole supported by the RDE fluids are obtained. Except for the case of a constant redshift function, where the solution is not only asymptotically flat but also traversable, the five remaining solutions are all non-asymptotically flat, therefore, the exotic matter from the RDE fluids is spatially distributed in the vicinity of the throat. Furthermore, we analyze the physical characteristics and properties of the RDE traversable wormholes. It is worth noting that, using the astrophysical observations, we obtain the constraints on the parameters of the RDE model, explore the types of exotic RDE fluids in different stages of the universe, limit the number of available models for wormhole research, reduce theoretically the number of the wormholes corresponding to different parameters for the RDE model, and provide a clearer picture for wormhole investigations from the new perspective of observational cosmology.

Morphology and texture of particles along the Spirit rover traverse from sol 450 to sol 745

NASA Astrophysics Data System (ADS)

Yingst, R. A.; Crumpler, L.; Farrand, W. H.; Li, R.; Cabrol, N. A.; Neakrase, L. D.

2008-12-01

We quantified and classified the shape, roundness, size, and texture of 935 loose surface particles along the Spirit rover traverse from sols 450-745 to assess origin, transport, and other alteration mechanisms that altered particles during and after formation. Variation in particle morphologic parameters along traverse is consistent with crossing mapped geologic unit boundaries. Texture is divided into four types: vesicular, smooth and flat-faceted, rough and flat-faceted, and very rough. Sphericity and roundness are intermediate and low, respectively, comparable to particles moved by high-energy transport or to crushed particles. This indicates intermittent, high-energy emplacement or modification of a single lithology, rather than systematic, continuous low-energy abrasion or wear over time. Comparison with particle morphology at other Mars landing sites is consistent with the hypothesis that no secondary systematic transport or wide-scale chemical alteration was active at a significant enough level to alter macromorphology. In particular, particle morphology at the Mars Pathfinder site shows stronger evidence of abrasion than along the Spirit traverse, suggesting Mars Pathfinder particles have undergone abrasion processes that particles in this study area have not. Additionally, morphology indices have correlation coefficients near zero, indicating that a fluvial transport mechanism is likely not responsible for morphology. Morphology and texture are instead related to origin and composition rather than subsequent modification. Morphology and texture support a volcanic origin, possibly without modification, but most likely altered primarily by ballistic impact, implying that the Spirit landing site and traverse may be utilized in the future as a standard site for characterization of impact-derived morphology.

Cdk2 Phosphorylation on Threonine39 by AKT and Its Implication on Cyclin Binding, Cellular Localization, and Cell Cycle Progression

DTIC Science & Technology

2008-10-01

cell cycle progression in most cell types. Mouse embryos develop normally until mid gestation without all interphase Cdks 28. Pertinent to the...Ciemerych and P. Sicinski, "Cell cycle in mouse development ," 24(17), 2877 (2005). Ref Type: Journal 5 K. Coulonval, et al., "Phosphorylations of...34 Development 135(20), 3389 (2008). Ref Type: Journal 30 J. P. Tassan, et al., "Cell cycle analysis of the activity, subcellular localization, and subunit

Effect of cold atmospheric pressure He-plasma jet on DNA change and mutation

NASA Astrophysics Data System (ADS)

Yaopromsiri, C.; Yu, L. D.; Sarapirom, S.; Thopan, P.; Boonyawan, D.

2015-12-01

Cold atmospheric pressure plasma jet (CAPPJ) effect on DNA change was studied for assessment of its safety. The experiment utilized a home-developed CAPPJ using 100% helium to directly treat naked DNA plasmid pGFP (plasmid green fluorescent protein). A traversal electric field was applied to separate the plasma components and both dry and wet sample conditions were adopted to investigate various factor roles in changing DNA. Plasma species were measured by using optical emission spectroscopy. DNA topological form change was analyzed by gel electrophoresis. The plasma jet treated DNA was transferred into bacterial Escherichia coli cells for observing mutation. The results show that the He-CAPPJ could break DNA strands due to actions from charge, radicals and neutrals and potentially cause genetic modification of living cells.

The Cell Cycle: An Activity Using Paper Plates to Represent Time Spent in Phases of the Cell Cycle

ERIC Educational Resources Information Center

Scherer, Yvette D.

2014-01-01

In this activity, students are given the opportunity to combine skills in math and geometry for a biology lesson in the cell cycle. Students utilize the data they collect and analyze from an online onion-root-tip activity to create a paper-plate time clock representing a 24-hour cell cycle. By dividing the paper plate into appropriate phases of…

Cell cycle behavior of laboratory and field populations of the Florida red tide dinoflagellate, Karenia brevis

NASA Astrophysics Data System (ADS)

Van Dolah, Frances M.; Leighfield, Tod A.; Kamykowski, Daniel; Kirkpatrick, Gary J.

2008-01-01

As a component of the ECOHAB Florida Regional Field Program, this study addresses cell cycle behavior and its importance to bloom formation of the Florida red tide dinoflagellate, Karenia brevis. The cell cycle of K. brevis was first studied by flow cytometry in laboratory batch cultures, and a laboratory mesocosm column, followed by field populations over the 5-year course of the ECOHAB program. Under all conditions studied, K. brevis displayed diel phased cell division with S-phase beginning a minimum of 6 h after the onset of light and continuing for 12-14 h. Mitosis occurred during the dark, and was generally completed by the start of the next day. The timing of cell cycle phases relative to the diel cycle did not differ substantially in bloom populations displaying radically different growth rates ( μmin 0.17-0.55) under different day lengths and temperature conditions. The rhythm of cell cycle progression is independent from the rhythm controlling vertical migration, as similar cell cycle distributions are found at all depths of the water column in field samples. The implications of these findings are discussed in light of our current understanding of the dinoflagellate cell cycle and the development of improved models for K. brevis bloom growth.

Repeated cycles of 5-fluorouracil chemotherapy impaired anti-tumor functions of cytotoxic T cells in a CT26 tumor-bearing mouse model.

PubMed

Wu, Yanhong; Deng, Zhenling; Wang, Huiru; Ma, Wenbo; Zhou, Chunxia; Zhang, Shuren

2016-09-20

Recently, the immunostimulatory roles of chemotherapeutics have been increasingly revealed, although bone marrow suppression is still a common toxicity of chemotherapy. While the numbers and ratios of different immune subpopulations are analyzed after chemotherapy, changes to immune status after each cycle of treatment are less studied and remain unclear. To determine the tumor-specific immune status and functions after different cycles of chemotherapy, we treated CT26 tumor-bearing mice with one to four cycles of 5-fluorouracil (5-FU). Overall survival was not improved when more than one cycle of 5-FU was administered. Here we present data concerning the immune statuses after one and three cycles of chemotherapy. We analyzed the amount of spleen cells from mice treated with one and three cycles of 5-FU as well as assayed their proliferation and cytotoxicity against the CT26 tumor cell line. We found that the absolute numbers of CD8 T-cells and NK cells were not influenced significantly after either one or three cycles of chemotherapy. However, after three cycles of 5-FU, proliferated CD8 T-cells were decreased, and CT26-specific cytotoxicity and IFN-γ secretion of spleen cells were impaired in vitro. After one cycle of 5-FU, there was a greater percentage of tumor infiltrating CD8 T-cells. In addition, more proliferated CD8 T-cells, enhanced tumor-specific cytotoxicity as well as IFN-γ secretion of spleen cells against CT26 in vitro were observed. Given the increased expression of immunosuppressive factors, such as PD-L1 and TGF-β, we assessed the effect of early introduction of immunotherapy in combination with chemotherapy. We found that mice treated with cytokine induced killer cells and PD-L1 monoclonal antibodies after one cycle of 5-FU had a better anti-tumor performance than those treated with chemotherapy or immunotherapy alone. These data suggest that a single cycle of 5-FU treatment promoted an anti-tumor immune response, whereas repeated chemotherapy cycles impaired anti-tumor immune functions. Though the amount of immune cells could recover after chemotherapy suspension, their anti-tumor functions were damaged by multiple rounds of chemotherapy. These findings also point towards early implementation of immunotherapy to improve the anti-tumor effect.

On the relationship between cell cycle analysis with ergodic principles and age-structured cell population models.

PubMed

Kuritz, K; Stöhr, D; Pollak, N; Allgöwer, F

2017-02-07

Cyclic processes, in particular the cell cycle, are of great importance in cell biology. Continued improvement in cell population analysis methods like fluorescence microscopy, flow cytometry, CyTOF or single-cell omics made mathematical methods based on ergodic principles a powerful tool in studying these processes. In this paper, we establish the relationship between cell cycle analysis with ergodic principles and age structured population models. To this end, we describe the progression of a single cell through the cell cycle by a stochastic differential equation on a one dimensional manifold in the high dimensional dataspace of cell cycle markers. Given the assumption that the cell population is in a steady state, we derive transformation rules which transform the number density on the manifold to the steady state number density of age structured population models. Our theory facilitates the study of cell cycle dependent processes including local molecular events, cell death and cell division from high dimensional "snapshot" data. Ergodic analysis can in general be applied to every process that exhibits a steady state distribution. By combining ergodic analysis with age structured population models we furthermore provide the theoretic basis for extensions of ergodic principles to distribution that deviate from their steady state. Copyright © 2016 Elsevier Ltd. All rights reserved.

Autophagy mediates cell cycle response by regulating nucleocytoplasmic transport of PAX6 in limbal stem cells under ultraviolet-A stress

PubMed Central

Laggner, Maria; Pollreisz, Andreas; Schmidinger, Gerald; Schmidt-Erfurth, Ursula; Chen, Ying-Ting

2017-01-01

Limbal stem cells (LSC) account for homeostasis and regeneration of corneal epithelium. Solar ultraviolet A (UVA) is the major source causing oxidative damage in the ocular surface. Autophagy, a lysosomal degradation mechanism, is essential for physiologic function and stress defense of stem cells. PAX6, a master transcription factor governing corneal homeostasis by regulating cell cycle and cell fate of LSC, responds to oxidative stress by nucleocytoplasmic shuttling. Impaired autophagy and deregulated PAX6 have been reported in oxidative stress-related ocular surface disorders. We hypothesize a functional role for autophagy and PAX6 in LSC’s stress response to UVA. Therefore, human LSC colonies were irradiated with a sub-lethal dose of UVA and autophagic activity and intracellular reactive oxygen species (ROS) were measured by CYTO-ID assay and CM-H2DCFDA live staining, respectively. Following UVA irradiation, the percentage of autophagic cells significantly increased in LSC colonies while intracellular ROS levels remained unaffected. siRNA-mediated knockdown (KD) of ATG7 abolished UVA-induced autophagy and led to an excessive accumulation of ROS. Upon UVA exposure, LSCs displayed nuclear-to-cytoplasmic translocation of PAX6, while ATG7KD or antioxidant pretreatment largely attenuated the intracellular trafficking event. Immunofluorescence showing downregulation of proliferative marker PCNA and induction of cell cycle regulator p21 indicates cell cycle arrest in UVA-irradiated LSC. Abolishing autophagy, adenoviral-assisted restoration of nuclear PAX6 or antioxidant pretreatment abrogated the UVA-induced cell cycle arrest. Adenoviral expression of an ectopic PAX gene, PAX7, did not affect UVA cell cycle response. Furthermore, knocking down PAX6 attenuated the cell cycle progression of irradiated ATG7KD LSC by de-repressing p21 expression. Collectively, our data suggest a crosstalk between autophagy and PAX6 in regulating cell cycle response of ocular progenitors under UVA stress. Autophagy deficiency leads to impaired intracellular trafficking of PAX6, perturbed redox balance and uncurbed cell cycle progression in UVA-stressed LSCs. The coupling of autophagic machinery and PAX6 in cell cycle regulation represents an attractive therapeutic target for hyperproliferative ocular surface disorders associated with solar radiation. PMID:28700649

Lithium Ion Testing at NSWC Crane in Support of NASA Goddard Space Flight Center

NASA Technical Reports Server (NTRS)

Brown, Harry; Jung, David; Lee, Leonine

2010-01-01

This viewgraph presentation reviews Lithium Ion Cell testing at the Naval Surface Warfare Center in Crane, India. The contents include: 1) Quallion 15 Ahr Lithium-Ion Cells, LEO Life Cycle Test; 2) Lithion 50 Ahr Lithium-Ion Cells, LEO Life Cycle Test; 3) ABSL 5 Ahr Lithium-Ion Battery, LRO-LLO Life Cycle Test, SDO-GEO Life Cycle Test; and 4) A123 40 Ahr Lithium-Ion Battery, GPM Life Cycle Test, MMS Life Cycle Test.

On the Moon with Apollo 15, A Guidebook to Hadley Rille and the Apennine Mountains.

ERIC Educational Resources Information Center

Simmons, Gene

The booklet, published before the Apollo 15 mission, gives a timeline for the mission; describes and illustrates the physiography of the landing site; and describes and illustrates each lunar surface scientific experiment. Separate timelines are included for all traverses (the traverses are the Moon walks and, for Apollo 15, the Moon rides in the…

Astronauts Young and Duke collect rock samples along simulated lunar traverse

NASA Technical Reports Server (NTRS)

1971-01-01

Astronauts John W. Young, left, prime crew commander for Apollo 16, and Charles M. Duke Jr., lunar module pilot, collect rock samples along a simulated lunar traverse route in the Coso Hills, near Ridgecrest, California. Astronaut Eugene A. Cernan, right background, prime crew commander for Apollo 17, looks on. The astronauts trained at the U.S. Naval Ordnance Test Station.

Low-Speed Wind Tunnel Flow Quality Determination

DTIC Science & Technology

2011-09-01

Traverse Motor The traverse motor for the BiSlide is a NEMA Type 34D, Slo-Syn® stepper motor, allowing the operator to position items in the test... norm (w1)^2/sum(w1)^2,’k’); %% plot on log-log scale ylabel(‘RMS Power/Frequency (V^2)’) xlabel(‘Frequency (Hz)’) title(‘Power Spectrum’) end

"Constructing" the Cell Cycle in 3D

ERIC Educational Resources Information Center

Koc, Isil; Turan, Merve

2012-01-01

The cycle of duplication and division, known as the "cell cycle," is the essential mechanism by which all living organisms reproduce. This activity allows students to develop an understanding of the main events that occur during the typical eukaryotic cell cycle mostly in the process of mitotic phase that divides the duplicated genetic material…

An Experimental Investigation of an Airfoil Traversing Across a Shear Flow

NASA Astrophysics Data System (ADS)

Hamedani, Borhan A.; Naguib, Ahmed; Koochesfahani, Manoochehr

2017-11-01

While the aerodynamics of an airfoil in a uniform approach flow is well understood, less attention has been paid to airfoils in non-uniform flows. An aircraft encounters such flow, for example, during landing through the air wake of an aircraft carrier. The present work is focused on investigating the fundamental aerodynamics of airfoils in such an environment using canonical flow experiments. To generate a shear approach flow, a shaped honeycomb block is employed in a wind tunnel setup. Direct force measurements are performed on a NACA 0012 airfoil, with an aspect ratio of 1.8, as the airfoil traverses steadily across the shear region. Measurements are conducted at a chord Reynolds number Rec 75k, based on the mean approach stream velocity at the center of the shear zone, for a range of airfoil traverse velocities and angles of attack (0 - 12 degree). The results are compared to those obtained for the same airfoil when placed statically at different points along the traverse path inside the shear zone. The comparison enables examination of the applicability of quasi-steady analysis in computing the forces on the moving airfoil. This work is supported by ONR Grant Number N00014-16-1-2760.

Microstructure and Residual Stress Distributions Under the Influence of Welding Speed in Friction Stir Welded 2024 Aluminum Alloy

NASA Astrophysics Data System (ADS)

Moghadam, Danial Ghahremani; Farhangdoost, Khalil; Nejad, Reza Masoudi

2016-06-01

Friction stir welding was conducted on 8-mm-thick plates made of AA2024-T351 aluminum alloy at tool traverse speeds between 8 and 31.5 mm/minutes and tool rotational speed between 400 and 800 rpm. Metallographic analyses and mechanical tests including hardness, tensile, residual stress, and fracture toughness tests were carried out to evaluate the microstructural and mechanical properties of the joints as a function of the process parameters. The finite element simulation of the FSW process was also performed using a thermal model. The hardness test results show that the increase in rotational speed or decrease in traverse speed of the tool would cause a decrease in weld zone hardness. The best tensile properties are obtained at rotational/traverse speed ratio between 20 and 32. Also, the longitudinal residual stress profiles were evaluated by employing X-ray diffraction method. The numerical and experimental results showed that the increase in a traverse or rotational speed would increase the residual stress of the weld zone. From the fracture toughness results, it was found that the welding process decreases the joints fracture toughness 18 to 49 pct with respect to the base metal.

Localization and physical properties experiments conducted by Spirit at Gusev crater

USGS Publications Warehouse

Arvidson, R. E.; Anderson, R.C.; Bartlett, P.; Bell, J.F.; Blaney, D.; Christensen, P.R.; Chu, P.; Crumpler, L.; Davis, K.; Ehlmann, B.L.; Fergason, R.; Golombek, M.P.; Gorevan, S.; Grant, J. A.; Greeley, R.; Guinness, E.A.; Haldemann, A.F.C.; Herkenhoff, K.; Johnson, J.; Landis, G.; Li, R.; Lindemann, R.; McSween, H.; Ming, D. W.; Myrick, T.; Richter, L.; Seelos, F.P.; Squyres, S. W.; Sullivan, R.J.; Wang, A.; Wilson, Jim

2004-01-01

The precise location and relative elevation of Spirit during its traverses from the Columbia Memorial station to Bonneville crater were determined with bundle-adjusted retrievals from rover wheel turns, suspension and tilt angles, and overlapping images. Physical properties experiments show a decrease of 0.2% per Mars solar day in solar cell output resulting from deposition of airborne dust, cohesive soil-like deposits in plains and hollows, bright and dark rock coatings, and relatively weak volcanic rocks of basaltic composition. Volcanic, impact, aeolian, and water-related processes produced the encountered landforms and materials.

Localization and physical properties experiments conducted by Spirit at Gusev Crater.

PubMed

Arvidson, R E; Anderson, R C; Bartlett, P; Bell, J F; Blaney, D; Christensen, P R; Chu, P; Crumpler, L; Davis, K; Ehlmann, B L; Fergason, R; Golombek, M P; Gorevan, S; Grant, J A; Greeley, R; Guinness, E A; Haldemann, A F C; Herkenhoff, K; Johnson, J; Landis, G; Li, R; Lindemann, R; McSween, H; Ming, D W; Myrick, T; Richter, L; Seelos, F P; Squyres, S W; Sullivan, R J; Wang, A; Wilson, J

2004-08-06

The precise location and relative elevation of Spirit during its traverses from the Columbia Memorial station to Bonneville crater were determined with bundle-adjusted retrievals from rover wheel turns, suspension and tilt angles, and overlapping images. Physical properties experiments show a decrease of 0.2% per Mars solar day in solar cell output resulting from deposition of airborne dust, cohesive soil-like deposits in plains and hollows, bright and dark rock coatings, and relatively weak volcanic rocks of basaltic composition. Volcanic, impact, aeolian, and water-related processes produced the encountered landforms and materials.

Defining the conserved internal architecture of a protein kinase.

PubMed

Kornev, Alexandr P; Taylor, Susan S

2010-03-01

Protein kinases constitute a large protein family of important regulators in all eukaryotic cells. All of the protein kinases have a similar bilobal fold, and their key structural features have been well studied. However, the recent discovery of non-contiguous hydrophobic ensembles inside the protein kinase core shed new light on the internal organization of these molecules. Two hydrophobic "spines" traverse both lobes of the protein kinase molecule, providing a firm but flexible connection between its key elements. The spine model introduces a useful framework for analysis of intramolecular communications, molecular dynamics, and drug design. Published by Elsevier B.V.