The effect of Bcr-Abl protein tyrosine kinase on maturation and proliferation of primitive haematopoietic cells.

PubMed Central

Buckle, A. M.; Mottram, R.; Pierce, A.; Lucas, G. S.; Russell, N.; Miyan, J. A.; Whetton, A. D.

2000-01-01

BACKGROUND: Chronic Myeloid Leukaemia (CML) is characterised by the chromosomal translocation resulting in expression of the Bcr-Abl protein tyrosine kinase (PTK) in early stem cells and their progeny. However the precise nature of Bcr-Abl effects in primitive CML stem cells remains a matter of active debate. MATERIALS AND METHODS: Extremely primitive Bcr-Abl fusion positive cells were purified from patients with CML using multiparameter flow cytometric analysis of CD34, Thy, and lineage marker (Lin) expression, plus rhodamine-123 (Rh-123) brightness. Progenitor cells of increasing maturity were examined for cycling status by flow cytometry and their proliferative status directly correlated with cell phenotype. The activation status of a key transcription factor, signal transducers and activators of transcription (STAT-5), was also analyzed by immunocytochemistry. RESULTS: The most primitive stem cells currently defined (CD34+Lin-Thy+ Rh-1231o) were present as a lower proportion of the stem cell compartment (CD34+Lin-) of CML patients at presentation than of normal individuals (2.3% +/- 0.4 compared with 5.1% +/- 0.6 respectively). Conversely there was a significantly higher proportion of the more mature cells (CD34+Lin-Thy-Rh-123 hi) in CML patients than in normal individuals (79.3 +/- 1.8 compared with 70.9 +/- 3.3). No primitive subpopulation of CML CD34+Lin- cells was cycling to a significantly greater degree than cells from normal donors, in fact, late progenitor cells (CD34+Lin+) were cycling significantly less in CML samples than normal samples. STAT5, however, was observed to be activated in CML cells. CONCLUSIONS: We conclude that no subpopulation of CML stem cells displays significantly increased cell cycling. Thus, increased cycling cannot be a direct consequence of Bcr-Abl PTK acquisition in highly enriched stem cells from patients with CML. In vivo CML need not be considered a disease of unbridled stem cell proliferation, but a subtle defect in the balance between self renewal and maturation. PMID:11126203

Software Assurance Curriculum Project Volume 1: Master of Software Assurance Reference Curriculum

DTIC Science & Technology

2010-08-01

activity by providing a check on the relevance and currency of the process used to develop the MSwA2010 curriculum content. Figure 2 is an expansion of...random oracle model, symmetric crypto primitives, modes of operations, asymmetric crypto primitives (Chapter 5) [16] Detailed design...encryption, public key encryption, digital signatures, message authentication codes, crypto protocols, cryptanalysis, and further detailed crypto

Calculations of and evidence for chain packing stress in inverse lyotropic bicontinuous cubic phases.

PubMed

Shearman, Gemma C; Khoo, Bee J; Motherwell, Mary-Lynn; Brakke, Kenneth A; Ces, Oscar; Conn, Charlotte E; Seddon, John M; Templer, Richard H

2007-06-19

Inverse bicontinuous cubic lyotropic phases are a complex solution to the dilemma faced by all self-assembled water-amphiphile systems: how to satisfy the incompatible requirements for uniform interfacial curvature and uniform molecular packing. The solution reached in this case is for the water-amphiphile interfaces to deform hyperbolically onto triply periodic minimal surfaces. We have previously suggested that although the molecular packing in these structures is rather uniform the relative phase behavior of the gyroid, double diamond, and primitive inverse bicontinuous cubic phases can be understood in terms of subtle differences in packing frustration. In this work, we have calculated the packing frustration for these cubics under the constraint that their interfaces have constant mean curvature. We find that the relative packing stress does indeed differ between phases. The gyroid cubic has the least packing stress, and at low water volume fraction, the primitive cubic has the greatest packing stress. However, at very high water volume fraction, the double diamond cubic becomes the structure with the greatest packing stress. We have tested the model in two ways. For a system with a double diamond cubic phase in excess water, the addition of a hydrophobe may release packing frustration and preferentially stabilize the primitive cubic, since this has previously been shown to have lower curvature elastic energy. We have confirmed this prediction by adding the long chain alkane tricosane to 1-monoolein in excess water. The model also predicts that if one were able to hydrate the double diamond cubic to high water volume fractions, one should destabilize the phase with respect to the primitive cubic. We have found that such highly swollen metastable bicontinuous cubic phases can be formed within onion vesicles. Data from monoelaidin in excess water display a well-defined transition, with the primitive cubic appearing above a water volume fraction of 0.75. Both of these results lend support to the proposition that differences in the packing frustration between inverse bicontinuous cubic phases play a pivotal role in their relative phase stability.

Primitive Sca-1 Positive Bone Marrow HSC in Mouse Model of Aplastic Anemia: A Comparative Study through Flowcytometric Analysis and Scanning Electron Microscopy

PubMed Central

Chatterjee, Sumanta; Basak, Pratima; Das, Prosun; Das, Madhurima; Pereira, Jacintha Archana; Dutta, Ranjan Kumar; Chaklader, Malay; Chaudhuri, Samaresh; Law, Sujata

2010-01-01

Self-renewing Hematopoietic Stem Cells (HSCs) are responsible for reconstitution of all blood cell lineages. Sca-1 is the “stem cell antigen” marker used to identify the primitive murine HSC population, the expression of which decreases upon differentiation to other mature cell types. Sca-1+ HSCs maintain the bone marrow stem cell pool throughout the life. Aplastic anemia is a disease considered to involve primary stem cell deficiency and is characterized by severe pancytopenia and a decline in healthy blood cell generation system. Studies conducted in our laboratory revealed that the primitive Sca-1+ BM-HSCs (bone marrow hematopoietic stem cell) are significantly affected in experimental Aplastic animals pretreated with chemotherapeutic drugs (Busulfan and Cyclophosphamide) and there is increased Caspase-3 activity with consecutive high Annexin-V positivity leading to premature apoptosis in the bone marrow hematopoietic stem cell population in Aplastic condition. The Sca-1bright, that is, “more primitive” BM-HSC population was more affected than the “less primitive” BM-HSC Sca-1dim  population. The decreased cell population and the receptor expression were directly associated with an empty and deranged marrow microenvironment, which is evident from scanning electron microscopy (SEM). The above experimental evidences hint toward the manipulation of receptor expression for the benefit of cytotherapy by primitive stem cell population in Aplastic anemia cases. PMID:21048851

Advanced Numerical Techniques of Performance Evaluation. Volume 2

DTIC Science & Technology

1990-06-01

multiprocessor environment. This factor is determined by the overhead of the primitives available in the system ( semaphore , monitor , or message... semaphore , monitor , or message passing primitives ) and U the programming ability of the user who implements the simulation. " t,: the sequential...Warp Operating System . i Pro" lftevcnth ACM Symposum on Operating Systems Princlplcs, pages 77 9:3, Auslin, TX, Nov wicr 1987. ACM. [121 D.R. Jefferson

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

Meijne, E.I.; van der Winden-van Groenewegen, R.J.; Ploemacher, R.E.

The sensitivity for x-irradiation of a series of hematopoietic stem cell populations has been determined. The most primitive cells identified, cells with marrow-repopulating ability (MRA), showed the highest degree of radioresistance. These MRA cells which generate many secondary day-twelve spleen colony-forming units (MRA(CFU-S-12)) or colony-forming units in culture (MRA(CFU-C)) in the marrow of primary recipients had Do values equal to 1.18 and 1.13 Gy, respectively. The more mature CFU-S-12 had intermediate radiosensitivity (Do = 0.94 Gy), whereas the less primitive CFU-S-7 were the most radiosensitive (Do = 0.71 Gy). The in vitro colony-forming precursor cells (CFU-C) showed low radiosensitivity. Thesemore » data clearly show that the most primitive hematopoietic stem cell measured is less sensitive to ionizing radiation than generally has been assumed on the basis of measurements on CFU-S-7 or CFU-S-12.« less

The cryopreservation protocol optimal for progenitor recovery is not optimal for preservation of marrow repopulating ability.

PubMed

Balint, B; Ivanović, Z; Petakov, M; Taseski, J; Jovcić, G; Stojanović, N; Milenković, P

1999-03-01

The efficiency of five different cryopreservation protocols (our original controlled-rate and noncontrolled-rate protocols) was evaluated on the basis of the recovery after thawing of very primitive pluripotent hemopoietic stem cells (MRA(CFU-GM), pluripotent progenitors (CFU-Sd12) and committed granulocyte-monocyte progenitors (CFU-GM) in mouse bone marrow. Although the nucleated cell recovery and viability determined immediately after the thawing and washing of the cells were found to be similar, whether controlled-rate or noncontrolled-rate cryopreservation protocols were used, the recovery of MRA(CFU-GM), CFU-Sd12 and CFU-GM varied depending on the type of protocol and the cryoprotector (DMSO) concentrations used. It was shown that the controlled-rate protocol was more efficient, enabling better MRA(CFU-GM), CFU-Sd12 and CFU-GM recovery from frozen samples. The most efficient was the controlled-rate protocol of cryopreservation designed to compensate for the release of fusion heat, which enabled a better survival of CFU-Sd12 and CFU-GM when combined with a lower (5%) DMSO concentration. On the contrary, a satisfactory survival rate of very primitive stem cells (MRA(CFU-GM)) was achieved only when 10% DMSO was included with a five-step protocol of cryopreservation. These results point to adequately used controlled-rate freezing as essential for a highly efficient cryopreservation of some of the categories of hematopoietic stem and progenitor cells. At the same time, it was obvious that a higher DMSO concentration was necessary for the cryopreservation of very primitive stem cells, but not, however, for more mature progenitor cells (CFU-S, CFU-GM). These results imply the existence of a mechanism that decreases the intracellular concentration of DMSO in primitive MRA cells, which is not the case for less primitive progenitors.

CD34 Antigen and the MPL Receptor Expression Defines a Novel Class of Human Cord Blood-Derived Primitive Hematopoietic Stem Cells.

PubMed

Matsuoka, Yoshikazu; Takahashi, Masaya; Sumide, Keisuke; Kawamura, Hiroshi; Nakatsuka, Ryusuke; Fujioka, Tatsuya; Sonoda, Yoshiaki

2017-06-09

In the murine hematopoietic stem cell (HSC) compartment, thrombopoietin (THPO)/MPL (THPO receptor) signaling plays an important role in the maintenance of adult quiescent HSCs. However, the role of THPO/MPL signaling in the human primitive HSC compartment has not yet been elucidated. We have identified very primitive human cord blood (CB)-derived CD34- severe combined immunodeficiency (SCID)-repopulating cells (SRCs) using the intra-bone marrow injection method. In this study, we investigated the roles of the MPL expression in the human primitive HSC compartment. The SRC activities of the highly purified CB-derived 18Lin-CD34+/-MPL+/- cells were analyzed using NOG mice. In the primary recipient mice, nearly all mice that received CD34+/-MPL+/- cells were repopulated with human CD45+ cells. Nearly all of these mice that received CD34+MPL+/- and CD34-MPL- cells showed a secondary repopulation. Interestingly, the secondary recipient mice that received CD34+/-MPL- cells showed a distinct tertiary repopulation. These results clearly indicate that the CD34+/- SRCs not expressing MPL sustain a long-term (LT) (>1 year) human cell repopulation in NOG mice. Moreover, CD34- SRCs generate CD34+CD38-CD90+ SRCs in vitro and in vivo. These findings provide a new concept that CD34-MPL- SRCs reside at the apex of the human HSC hierarchy.

Cinemicrographic study of the cell movement in the primitive-streak-stage mouse embryo.

PubMed

Nakatsuji, N; Snow, M H; Wylie, C C

1986-07-01

Migration of the mesoderm cells in the primitive-streak-stage mouse embryo was directly studied by cinemicrography using whole embryo culture and Nomarski differential interference contrast optics. Relative transparency and small size of the early mouse embryos enabled direct observation of the individual cells and their cell processes. Seven-day-old mouse embryos were isolated and cultured in a small chamber in a medium consisting of 50% rat serum and 50% Dulbecco's modified minimum essential medium. The mesoderm cells move away from the primitive streak in both anterior and antimesometrial (distal) directions at a mean velocity of 46 micron h-1. They extend cell processes and constantly change cell shape. They do not translocate extensively as isolated single cells, but usually maintain attachment to other mesoderm cells. They show frequent cell division preceded by rounding up of the cell bodies, and accompanied by vigorous blebbing before and after cytokinesis. This study shows that it is possible to examine the motility of embryonic cells inside the mammalian embryo by direct observation if the embryo is small and transparent enough for the use of the Nomarski optics.

Experimental analysis of control mechanisms in somite segmentation in avian embryos. II. Reduction of material in the gastrula stages of the chick.

PubMed

Bellairs, R; Veini, M

1984-02-01

A new theory of control of somite segmentation in chick embryos is proposed. This supposses that tiny clusters of already programmed cells are present throughout the presumptive somite area at stage 4, but that in order to fulfill their destiny they probably depend on the addition of further cells from the primitive streak. Evidence is based on the two groups of experiments: a) Experiments involving transection across the primitive streak at various stages, (which results in a 'tail' which possesses mesodermal derivatives) and across the segmental plate (which results in a 'tail' lacking mesodermal derivatives). b) Experiments in which parts of embryos have been explanted with or without their primitive streak. It is suggested that the initial clusters of pre-programmed cells move further and further posteriorly, developing into somitomeres (the precursors of true somites) only as they receive re-inforcements from the primitive streak or, ultimately, from the tail bud.

USAF Summer Research Program - 1993 Graduate Student Research Program Final Reports, Volume 6, AEDC, FJSRL and WHMC

DTIC Science & Technology

1993-12-01

Mechanical Engineering Associate, PhD Laboratory: PL/VT Division Engineering University of Texas, San Anton Vol-Page No: 3-26 San Antonio, TX 7824-9065...parameters. The modules can be primitive or compound. Primitive modules represent the elementary computation units and define their interfaces. The... linear under varying conditions for the range of processor numbers. Discussion Performance: Our evaluation of the performance measurement results is the

Development of a fractional-step method for the unsteady incompressible Navier-Stokes equations in generalized coordinate systems

NASA Technical Reports Server (NTRS)

Rosenfeld, Moshe; Kwak, Dochan; Vinokur, Marcel

1992-01-01

A fractional step method is developed for solving the time-dependent three-dimensional incompressible Navier-Stokes equations in generalized coordinate systems. The primitive variable formulation uses the pressure, defined at the center of the computational cell, and the volume fluxes across the faces of the cells as the dependent variables, instead of the Cartesian components of the velocity. This choice is equivalent to using the contravariant velocity components in a staggered grid multiplied by the volume of the computational cell. The governing equations are discretized by finite volumes using a staggered mesh system. The solution of the continuity equation is decoupled from the momentum equations by a fractional step method which enforces mass conservation by solving a Poisson equation. This procedure, combined with the consistent approximations of the geometric quantities, is done to satisfy the discretized mass conservation equation to machine accuracy, as well as to gain the favorable convergence properties of the Poisson solver. The momentum equations are solved by an approximate factorization method, and a novel ZEBRA scheme with four-color ordering is devised for the efficient solution of the Poisson equation. Several two- and three-dimensional laminar test cases are computed and compared with other numerical and experimental results to validate the solution method. Good agreement is obtained in all cases.

Polycyclic aromatic hydrocarbons - Primitive pigment systems in the prebiotic environment

NASA Technical Reports Server (NTRS)

Deamer, D. W.

1992-01-01

The chemical evolution of meteoritic organics in the primitive earth is examined experimentally with attention given to the photochemical effects of hydrocarbon/water mixtures. Also addressed are the generation of amphiphilic products by photochemical reactions and the transduction of light energy into potentially useful forms. Polycyclic aromatic hydrocarbons (PAHs) absorb light and exist in carbonaceous chondrites; PAHs are therefore examined as primitive pigments by means of salt solutions with pyrene, fluoranthene, and pyrene derivatives with hexadecane. The hexadecane undergoes photochemical oxidation and yields long-chain amphiphiles with oxygen supplied by water, and acid pH shifts also occur. PAHs are also tested in lipid bilayer membranes to examine light-energy transduction. Protons are found to accumulate within the membrane-bounded volume to form proton gradients, and this reaction is theorized to be a good model of primitive photochemical reactions that related to the transduction of light energy into useable forms.

CD34 Antigen and the MPL Receptor Expression Defines a Novel Class of Human Cord Blood-Derived Primitive Hematopoietic Stem Cells

PubMed Central

Matsuoka, Yoshikazu; Takahashi, Masaya; Sumide, Keisuke; Kawamura, Hiroshi; Nakatsuka, Ryusuke; Fujioka, Tatsuya; Sonoda, Yoshiaki

2017-01-01

In the murine hematopoietic stem cell (HSC) compartment, thrombopoietin (THPO)/MPL (THPO receptor) signaling plays an important role in the maintenance of adult quiescent HSCs. However, the role of THPO/MPL signaling in the human primitive HSC compartment has not yet been elucidated. We have identified very primitive human cord blood (CB)-derived CD34– severe combined immunodeficiency (SCID)-repopulating cells (SRCs) using the intra-bone marrow injection method. In this study, we investigated the roles of the MPL expression in the human primitive HSC compartment. The SRC activities of the highly purified CB-derived 18Lin–CD34+/–MPL+/– cells were analyzed using NOG mice. In the primary recipient mice, nearly all mice that received CD34+/–MPL+/– cells were repopulated with human CD45+ cells. Nearly all of these mice that received CD34+MPL+/– and CD34–MPL– cells showed a secondary repopulation. Interestingly, the secondary recipient mice that received CD34+/–MPL– cells showed a distinct tertiary repopulation. These results clearly indicate that the CD34+/– SRCs not expressing MPL sustain a long-term (LT) (>1 year) human cell repopulation in NOG mice. Moreover, CD34– SRCs generate CD34+CD38–CD90+ SRCs in vitro and in vivo. These findings provide a new concept that CD34–MPL– SRCs reside at the apex of the human HSC hierarchy. PMID:27938494

Two different pathways for the transport of primitive and definitive blood cells from the yolk sac to the embryo in humans.

PubMed

Pereda, Jaime; Monge, Juan I; Niimi, Gen

2010-08-01

During the early human embryonic period nutrients and blood cells are temporarily provided by the extraembryonic yolk sac (YS). The YS before week six is involved not only in primitive but also in definitive erythropoiesis. While the destiny of primitive erythroid cells that fill the blood vessels of the YS is well known, the final destination of erythrocytes present in the endodermal vesicular system is unknown. In the present study we have investigated, step by step, the destiny of the erythrocytes present in the endodermal vesicles during the embryonic period. Twelve human YSs and their corresponding yolk stalks were analyzed between weeks 4 and 7 of embryonic age by light and scanning electron microscopy. It is shown that erythrocytes (according to their size and morphological features) located within the endodermal vesicles of the YS wall are pulled out through endodermal pits into the YS cavity, from where they reach the lumen of the primitive gut of the embryo through the vitelline duct, a temporary pathway communicating both compartments. During the study period no erythrocytes were seen within the embryo's vascular network where only primitive erythroblasts were identified. Our results indicate that the vitelline duct plays an important transient role as a pathway for the transport of nutrients and blood cells between the YS and the embryo before week five of embryonic development that ends just at the time when YS-embryo circulation becomes established. (c) 2010 Wiley-Liss, Inc.

Evidence of Mobilization of Pluripotent Stem Cells into Peripheral Blood of Patients with Myocardial Ischemia

PubMed Central

Abdel-Latif, Ahmed; Zuba-Surma, Ewa K.; Ziada, Khaled M.; Kucia, Magdalena; Cohen, Donald A.; Kaplan, Alan M.; Zant, Gary Van; Selim, Samy; Smyth, Susan S.; Ratajczak, Mariusz Z.

2010-01-01

Objective The ischemic myocardium releases multiple chemotactic factors responsible for the mobilization and recruitment of bone marrow-derived cells to injured myocardium. However, the mobilization of primitive pluripotent stem cells (PSCs) enriched in Very Small Embryonic-Like stem cells (VSELs) in various cardiac ischemic scenarios is not well understood. Methods Fifty four ischemic heart disease patients, including subjects with stable angina, non-ST elevation (NSTME) myocardial infarction (MI) and ST elevation myocardial infarction (STEMI), and twelve matched controls were enrolled. The absolute numbers of circulating stem/primitive cells in samples of peripheral blood (PB) were quantitated by Image Stream Analysis and conventional flow cytometry. Gene expression of PSC (Oct-4 and Nanog), early cardiomyocyte (Nkx-2.5 and GATA-4), and endothelial (vWF) markers was analyzed by real-time PCR. Results The absolute numbers of PSCs, stem cell populations enriched in VSELs and hematopoietic stem cells (HSCs) present in PB were significantly higher in STEMI patients at presentation and declined over time. There was a corresponding increase in pluripotent, cardiac and endothelial gene expression in unfractionated PB cells and sorted PB-derived primitive CD34+ cells. The absolute numbers of circulating VSELs and HSCs in STEMI correlated negatively with patients' age. Conclusions Myocardial ischemia mobilizes primitive PSCs including pluripotent VSELs into the circulation. The peak of mobilization occurs within 12 hours in patients presenting with STEMI, which may represent a therapeutic window for future clinical applications. Reduced stem cell mobilization with advancing age could explain, in part, the observation that age is associated with poor prognosis in patients with MI. PMID:20800644

Direct volumetric rendering based on point primitives in OpenGL.

PubMed

da Rosa, André Luiz Miranda; de Almeida Souza, Ilana; Yuuji Hira, Adilson; Zuffo, Marcelo Knörich

2006-01-01

The aim of this project is to present a renderization by software algorithm of acquired volumetric data. The algorithm was implemented in Java language and the LWJGL graphical library was used, allowing the volume renderization by software and thus preventing the necessity to acquire specific graphical boards for the 3D reconstruction. The considered algorithm creates a model in OpenGL, through point primitives, where each voxel becomes a point with the color values related to this pixel position in the corresponding images.

Hierarchical and Parallelizable Direct Volume Rendering for Irregular and Multiple Grids

NASA Technical Reports Server (NTRS)

Wilhelms, Jane; VanGelder, Allen; Tarantino, Paul; Gibbs, Jonathan

1996-01-01

A general volume rendering technique is described that efficiently produces images of excellent quality from data defined over irregular grids having a wide variety of formats. Rendering is done in software, eliminating the need for special graphics hardware, as well as any artifacts associated with graphics hardware. Images of volumes with about one million cells can be produced in one to several minutes on a workstation with a 150 MHz processor. A significant advantage of this method for applications such as computational fluid dynamics is that it can process multiple intersecting grids. Such grids present problems for most current volume rendering techniques. Also, the wide range of cell sizes (by a factor of 10,000 or more), which is typical of such applications, does not present difficulties, as it does for many techniques. A spatial hierarchical organization makes it possible to access data from a restricted region efficiently. The tree has greater depth in regions of greater detail, determined by the number of cells in the region. It also makes it possible to render useful 'preview' images very quickly (about one second for one-million-cell grids) by displaying each region associated with a tree node as one cell. Previews show enough detail to navigate effectively in very large data sets. The algorithmic techniques include use of a kappa-d tree, with prefix-order partitioning of triangles, to reduce the number of primitives that must be processed for one rendering, coarse-grain parallelism for a shared-memory MIMD architecture, a new perspective transformation that achieves greater numerical accuracy, and a scanline algorithm with depth sorting and a new clipping technique.

Mechanical, electronic and thermodynamic properties of full Heusler compounds Fe2VX(X = Al, Ga)

NASA Astrophysics Data System (ADS)

Khalfa, M.; Khachai, H.; Chiker, F.; Baki, N.; Bougherara, K.; Yakoubi, A.; Murtaza, G.; Harmel, M.; Abu-Jafar, M. S.; Omran, S. Bin; Khenata, R.

2015-11-01

The electronic structure, mechanical and thermodynamic properties of Fe2VX, (with X = Al and Ga), have been studied self consistently by employing state-of-the-art full-potential linearized approach of augmented plane wave plus local orbitals (FP-LAPW + lo) method. The exchange-correlation potential is treated with the local density and generalized gradient approximations (LDA and GGA). Our predicted ground state properties such as lattice constants, bulk modulus and elastic constants appear more accurate when we employed the GGA rather than the LDA, and these results are in very good agreement with the available experimental and theoretical data. Further, thermodynamic properties of Fe2VAl and Fe2VGa are predicted with pressure and temperature in the ranges of 0-40 GPa and 0-1500 K using the quasi-harmonic Debye model. We have obtained successfully the variations of the heat capacities, primitive cell volume and volume expansion coefficient.

Why are hematopoietic stem cells so 'sexy'? on a search for developmental explanation.

PubMed

Ratajczak, M Z

2017-08-01

Evidence has accumulated that normal human and murine hematopoietic stem cells express several functional pituitary and gonadal sex hormones, and that, in fact, some sex hormones, such as androgens, have been employed for many years to stimulate hematopoiesis in patients with bone marrow aplasia. Interestingly, sex hormone receptors are also expressed by leukemic cell lines and blasts. In this review, I will discuss the emerging question of why hematopoietic cells express these receptors. A tempting hypothetical explanation for this phenomenon is that hematopoietic stem cells are related to subpopulation of migrating primordial germ cells. To support of this notion, the anatomical sites of origin of primitive and definitive hematopoiesis during embryonic development are tightly connected with the migratory route of primordial germ cells: from the proximal epiblast to the extraembryonic endoderm at the bottom of the yolk sac and then back to the embryo proper via the primitive streak to the aorta-gonado-mesonephros (AGM) region on the way to the genital ridges. The migration of these cells overlaps with the emergence of primitive hematopoiesis in the blood islands at the bottom of the yolk sac, and definitive hematopoiesis that occurs in hemogenic endothelium in the embryonic dorsal aorta in AGM region.

Evaluating Interaction of Cord Blood Hematopoietic Stem/Progenitor Cells with Functionally Integrated Three-Dimensional Microenvironments.

PubMed

Mokhtari, Saloomeh; Baptista, Pedro M; Vyas, Dipen A; Freeman, Charles Jordan; Moran, Emma; Brovold, Matthew; Llamazares, Guillermo A; Lamar, Zanneta; Porada, Christopher D; Soker, Shay; Almeida-Porada, Graça

2018-03-01

Despite advances in ex vivo expansion of cord blood-derived hematopoietic stem/progenitor cells (CB-HSPC), challenges still remain regarding the ability to obtain, from a single unit, sufficient numbers of cells to treat an adolescent or adult patient. We and others have shown that CB-HSPC can be expanded ex vivo in two-dimensional (2D) cultures, but the absolute percentage of the more primitive stem cells decreases with time. During development, the fetal liver is the main site of HSPC expansion. Therefore, here we investigated, in vitro, the outcome of interactions of primitive HSPC with surrogate fetal liver environments. We compared bioengineered liver constructs made from a natural three-dimensional-liver-extracellular-matrix (3D-ECM) seeded with hepatoblasts, fetal liver-derived (LvSt), or bone marrow-derived stromal cells, to their respective 2D culture counterparts. We showed that the inclusion of cellular components within the 3D-ECM scaffolds was necessary for maintenance of HSPC viability in culture, and that irrespective of the microenvironment used, the 3D-ECM structures led to the maintenance of a more primitive subpopulation of HSPC, as determined by flow cytometry and colony forming assays. In addition, we showed that the timing and extent of expansion depends upon the biological component used, with LvSt providing the optimal balance between preservation of primitive CB HSPC and cellular differentiation. Stem Cells Translational Medicine 2018;7:271-282. © 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Hard Spheres on the Primitive Surface

NASA Astrophysics Data System (ADS)

Dotera, Tomonari; Takahashi, Yusuke

2015-03-01

Recently hierarchical structures associated with the gyroid in several soft-matter systems have been reported. One of fundamental questions is regular arrangement or tiling on minimal surfaces. We have found certain numbers of hard spheres per unit cell on the gyroid surface are entropically self-organized. Here, new results for the primitive surface are presented. 56/64/72 per unit cell on the primitive minimal surface are entropically self-organized. Numerical evidences for the fluid-solid transition as a function of hard sphere radius are obtained in terms of the acceptance ratio of Monte Carlo moves and order parameters. These arrangements, which are the extensions of the hexagonal arrangement on a flat surface, can be viewed as hyperbolic tiling on the Poincaré disk with a negative Gaussian curvature.

Influence of sediment recycling on the trace element composition of primitive arc lavas

NASA Astrophysics Data System (ADS)

Collinet, M.; Jagoutz, O. E.

2017-12-01

Primitive calc-alkaline lavas from continental arcs are, on average, enriched in incompatible elements compared to those from intra-oceanic arcs. This relative enrichment is observed in different groups of trace elements: LILE (e.g. K, Rb), LREE to MREE (La-Dy) and HFSE (e.g.Zr, Nb) and is thought to result from (1) a transfer of material from the subducting slab to the mantle wedge at higher temperature than in intra-oceanic margins and/or (2) lower average degrees of melting in the mantle wedge, as a consequence of thicker overlying crusts and higher average pressures of melting. In addition to thicker overlying crusts and generally higher slab temperatures, continental margins are characterized by larger volumes of rock exposed above sea level and enhanced erosion rates compared to intra-oceanic arcs. As several geochemical signatures of arc lavas attest to the importance of sediment recycling in subduction zones, we explore the possibility that the high concentrations of incompatible elements in primitive lavas from continental arcs directly reflect a larger input of sediment to the subduction system. Previous efforts to quantify the sediment flux to oceanic trenches focused on the thickness of pelagic and hemipelagic sediments on top of the plate entering the subduction zone (Plank and Langmuir, 1993, Nature). These estimates primarily relied on the sediment layer drilled outboard from the subduction system and likely underestimate the volume of sediment derived from the arc itself. Accordingly, we find that such estimates of sediment flux do not correlate with the concentration of incompatible elements in primitive arc lavas. To account for regional contributions of coarser detrital sediments, usually delivered to oceanic trenches by turbidity currents, we apply to arc segments a model that quantifies the sediment load of rivers based on the average relief, area, temperature and runoff of their respective drainage areas (Syvitski et al., 2003, Sediment. Geol.). Our new estimates of sediment fluxes correlate positively with incompatible element concentrations in primitive arc lavas. We conclude that a large fraction of the local terrigenous sediments is subducted and contributes to the observed dichotomy in the trace element budget between primitive lavas from continental and oceanic margins.

β-Globin-Expressing Definitive Erythroid Progenitor Cells Generated from Embryonic and Induced Pluripotent Stem Cell-Derived Sacs.

PubMed

Fujita, Atsushi; Uchida, Naoya; Haro-Mora, Juan J; Winkler, Thomas; Tisdale, John

2016-06-01

Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells represent a potential alternative source for red blood cell transfusion. However, when using traditional methods with embryoid bodies, ES cell-derived erythroid cells predominantly express embryonic type ɛ-globin, with lesser fetal type γ-globin and very little adult type β-globin. Furthermore, no β-globin expression is detected in iPS cell-derived erythroid cells. ES cell-derived sacs (ES sacs) have been recently used to generate functional platelets. Due to its unique structure, we hypothesized that ES sacs serve as hemangioblast-like progenitors capable to generate definitive erythroid cells that express β-globin. With our ES sac-derived erythroid differentiation protocol, we obtained ∼120 erythroid cells per single ES cell. Both primitive (ɛ-globin expressing) and definitive (γ- and β-globin expressing) erythroid cells were generated from not only ES cells but also iPS cells. Primitive erythropoiesis is gradually switched to definitive erythropoiesis during prolonged ES sac maturation, concurrent with the emergence of hematopoietic progenitor cells. Primitive and definitive erythroid progenitor cells were selected on the basis of glycophorin A or CD34 expression from cells within the ES sacs before erythroid differentiation. This selection and differentiation strategy represents an important step toward the development of in vitro erythroid cell production systems from pluripotent stem cells. Further optimization to improve expansion should be required for clinical application. Stem Cells 2016;34:1541-1552. © 2016 AlphaMed Press.

Isolation and characterisation of cancer stem cells from canine osteosarcoma.

PubMed

Wilson, H; Huelsmeyer, M; Chun, R; Young, K M; Friedrichs, K; Argyle, D J

2008-01-01

There is increasing evidence that cancer is a stem cell disease. This study sought to isolate and characterise cancer stem cells from canine osteosarcoma. One human and three canine cell lines were cultured in non-adherent culture conditions using serum-starved, semi-solid media. Primitive sarcosphere colonies from all cell lines were identified under these conditions and were characterised using molecular and cytochemical techniques for embryonic stem cell markers. Expression of the embryonic stem cell-associated genes Nanog, Oct4 and STAT3 indicated a primitive phenotype. Sarcospheres could be reproduced consistently when passaged multiple times and produced adherent cell cultures when returned to normal growth conditions. Similarities between human and canine osteosarcoma cell lines add credence to the potential of the dog as a model for human disease.

A direct Primitive Variable Recovery Scheme for hyperbolic conservative equations: The case of relativistic hydrodynamics.

PubMed

Aguayo-Ortiz, A; Mendoza, S; Olvera, D

2018-01-01

In this article we develop a Primitive Variable Recovery Scheme (PVRS) to solve any system of coupled differential conservative equations. This method obtains directly the primitive variables applying the chain rule to the time term of the conservative equations. With this, a traditional finite volume method for the flux is applied in order avoid violation of both, the entropy and "Rankine-Hugoniot" jump conditions. The time evolution is then computed using a forward finite difference scheme. This numerical technique evades the recovery of the primitive vector by solving an algebraic system of equations as it is often used and so, it generalises standard techniques to solve these kind of coupled systems. The article is presented bearing in mind special relativistic hydrodynamic numerical schemes with an added pedagogical view in the appendix section in order to easily comprehend the PVRS. We present the convergence of the method for standard shock-tube problems of special relativistic hydrodynamics and a graphical visualisation of the errors using the fluctuations of the numerical values with respect to exact analytic solutions. The PVRS circumvents the sometimes arduous computation that arises from standard numerical methods techniques, which obtain the desired primitive vector solution through an algebraic polynomial of the charges.

A direct Primitive Variable Recovery Scheme for hyperbolic conservative equations: The case of relativistic hydrodynamics

PubMed Central

Mendoza, S.; Olvera, D.

2018-01-01

In this article we develop a Primitive Variable Recovery Scheme (PVRS) to solve any system of coupled differential conservative equations. This method obtains directly the primitive variables applying the chain rule to the time term of the conservative equations. With this, a traditional finite volume method for the flux is applied in order avoid violation of both, the entropy and “Rankine-Hugoniot” jump conditions. The time evolution is then computed using a forward finite difference scheme. This numerical technique evades the recovery of the primitive vector by solving an algebraic system of equations as it is often used and so, it generalises standard techniques to solve these kind of coupled systems. The article is presented bearing in mind special relativistic hydrodynamic numerical schemes with an added pedagogical view in the appendix section in order to easily comprehend the PVRS. We present the convergence of the method for standard shock-tube problems of special relativistic hydrodynamics and a graphical visualisation of the errors using the fluctuations of the numerical values with respect to exact analytic solutions. The PVRS circumvents the sometimes arduous computation that arises from standard numerical methods techniques, which obtain the desired primitive vector solution through an algebraic polynomial of the charges. PMID:29659602

A Cartesian, cell-based approach for adaptively-refined solutions of the Euler and Navier-Stokes equations

NASA Technical Reports Server (NTRS)

Coirier, William J.; Powell, Kenneth G.

1994-01-01

A Cartesian, cell-based approach for adaptively-refined solutions of the Euler and Navier-Stokes equations in two dimensions is developed and tested. Grids about geometrically complicated bodies are generated automatically, by recursive subdivision of a single Cartesian cell encompassing the entire flow domain. Where the resulting cells intersect bodies, N-sided 'cut' cells are created using polygon-clipping algorithms. The grid is stored in a binary-tree structure which provides a natural means of obtaining cell-to-cell connectivity and of carrying out solution-adaptive mesh refinement. The Euler and Navier-Stokes equations are solved on the resulting grids using a finite-volume formulation. The convective terms are upwinded: a gradient-limited, linear reconstruction of the primitive variables is performed, providing input states to an approximate Riemann solver for computing the fluxes between neighboring cells. The more robust of a series of viscous flux functions is used to provide the viscous fluxes at the cell interfaces. Adaptively-refined solutions of the Navier-Stokes equations using the Cartesian, cell-based approach are obtained and compared to theory, experiment, and other accepted computational results for a series of low and moderate Reynolds number flows.

A Cartesian, cell-based approach for adaptively-refined solutions of the Euler and Navier-Stokes equations

NASA Technical Reports Server (NTRS)

Coirier, William J.; Powell, Kenneth G.

1995-01-01

A Cartesian, cell-based approach for adaptively-refined solutions of the Euler and Navier-Stokes equations in two dimensions is developed and tested. Grids about geometrically complicated bodies are generated automatically, by recursive subdivision of a single Cartesian cell encompassing the entire flow domain. Where the resulting cells intersect bodies, N-sided 'cut' cells are created using polygon-clipping algorithms. The grid is stored in a binary-tree data structure which provides a natural means of obtaining cell-to-cell connectivity and of carrying out solution-adaptive mesh refinement. The Euler and Navier-Stokes equations are solved on the resulting grids using a finite-volume formulation. The convective terms are upwinded: A gradient-limited, linear reconstruction of the primitive variables is performed, providing input states to an approximate Riemann solver for computing the fluxes between neighboring cells. The more robust of a series of viscous flux functions is used to provide the viscous fluxes at the cell interfaces. Adaptively-refined solutions of the Navier-Stokes equations using the Cartesian, cell-based approach are obtained and compared to theory, experiment and other accepted computational results for a series of low and moderate Reynolds number flows.

Targeting Aberrant Glutathione Metabolism to Eradicate Human Acute Myelogenous Leukemia Cells*

PubMed Central

Pei, Shanshan; Minhajuddin, Mohammad; Callahan, Kevin P.; Balys, Marlene; Ashton, John M.; Neering, Sarah J.; Lagadinou, Eleni D.; Corbett, Cheryl; Ye, Haobin; Liesveld, Jane L.; O'Dwyer, Kristen M.; Li, Zheng; Shi, Lei; Greninger, Patricia; Settleman, Jeffrey; Benes, Cyril; Hagen, Fred K.; Munger, Joshua; Crooks, Peter A.; Becker, Michael W.; Jordan, Craig T.

2013-01-01

The development of strategies to eradicate primary human acute myelogenous leukemia (AML) cells is a major challenge to the leukemia research field. In particular, primitive leukemia cells, often termed leukemia stem cells, are typically refractory to many forms of therapy. To investigate improved strategies for targeting of human AML cells we compared the molecular mechanisms regulating oxidative state in primitive (CD34+) leukemic versus normal specimens. Our data indicate that CD34+ AML cells have elevated expression of multiple glutathione pathway regulatory proteins, presumably as a mechanism to compensate for increased oxidative stress in leukemic cells. Consistent with this observation, CD34+ AML cells have lower levels of reduced glutathione and increased levels of oxidized glutathione compared with normal CD34+ cells. These findings led us to hypothesize that AML cells will be hypersensitive to inhibition of glutathione metabolism. To test this premise, we identified compounds such as parthenolide (PTL) or piperlongumine that induce almost complete glutathione depletion and severe cell death in CD34+ AML cells. Importantly, these compounds only induce limited and transient glutathione depletion as well as significantly less toxicity in normal CD34+ cells. We further determined that PTL perturbs glutathione homeostasis by a multifactorial mechanism, which includes inhibiting key glutathione metabolic enzymes (GCLC and GPX1), as well as direct depletion of glutathione. These findings demonstrate that primitive leukemia cells are uniquely sensitive to agents that target aberrant glutathione metabolism, an intrinsic property of primary human AML cells. PMID:24089526

A gene trap transposon eliminates haematopoietic expression of zebrafish Gfi1aa, but does not interfere with haematopoiesis.

PubMed

Thambyrajah, Roshana; Ucanok, Deniz; Jalali, Maryam; Hough, Yasmin; Wilkinson, Robert Neil; McMahon, Kathryn; Moore, Chris; Gering, Martin

2016-09-01

A transposon-mediated gene trap screen identified the zebrafish line qmc551 that expresses a GFP reporter in primitive erythrocytes and also in haemogenic endothelial cells, which give rise to haematopoietic stem and progenitor cells (HSPCs) that seed sites of larval and adult haematopoiesis. The transposon that mediates this GFP expression is located in intron 1 of the gfi1aa gene, one of three zebrafish paralogs that encode transcriptional repressors homologous to mammalian Gfi1 and Gfi1b proteins. In qmc551 transgenics, GFP expression is under the control of the endogenous gfi1aa promoter, recapitulates early gfi1aa expression and allows live observation of gfi1aa promoter activity. While the transposon integration interferes with the expression of gfi1aa mRNA in haematopoietic cells, homozygous qmc551 fish are viable and fertile, and display normal primitive and definitive haematopoiesis. Retained expression of Gfi1b in primitive erythrocytes and up-regulation of Gfi1ab at the onset of definitive haematopoiesis in homozygous qmc551 carriers, are sufficient to allow normal haematopoiesis. This finding contradicts previously published morpholino data that suggested an essential role for zebrafish Gfi1aa in primitive erythropoiesis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Solution-Adaptive Cartesian Cell Approach for Viscous and Inviscid Flows

NASA Technical Reports Server (NTRS)

Coirier, William J.; Powell, Kenneth G.

1996-01-01

A Cartesian cell-based approach for adaptively refined solutions of the Euler and Navier-Stokes equations in two dimensions is presented. Grids about geometrically complicated bodies are generated automatically, by the recursive subdivision of a single Cartesian cell encompassing the entire flow domain. Where the resulting cells intersect bodies, polygonal cut cells are created using modified polygon-clipping algorithms. The grid is stored in a binary tree data structure that provides a natural means of obtaining cell-to-cell connectivity and of carrying out solution-adaptive mesh refinement. The Euler and Navier-Stokes equations are solved on the resulting grids using a finite volume formulation. The convective terms are upwinded: A linear reconstruction of the primitive variables is performed, providing input states to an approximate Riemann solver for computing the fluxes between neighboring cells. The results of a study comparing the accuracy and positivity of two classes of cell-centered, viscous gradient reconstruction procedures is briefly summarized. Adaptively refined solutions of the Navier-Stokes equations are shown using the more robust of these gradient reconstruction procedures, where the results computed by the Cartesian approach are compared to theory, experiment, and other accepted computational results for a series of low and moderate Reynolds number flows.

Large-scale production of embryonic red blood cells from human embryonic stem cells.

PubMed

Olivier, Emmanuel N; Qiu, Caihong; Velho, Michelle; Hirsch, Rhoda Elison; Bouhassira, Eric E

2006-12-01

To develop a method to produce in culture large number of erythroid cells from human embryonic stem cells. Human H1 embryonic stem cells were differentiated into hematopoietic cells by coculture with a human fetal liver cell line, and the resulting CD34-positive cells were expanded in vitro in liquid culture using a three-step method. The erythroid cells produced were then analyzed by light microscopy and flow cytometry. Globin expression was characterized by quantitative reverse-transcriptase polymerase chain reaction and by high-performance liquid chromatography. CD34-positive cells produced from human embryonic stem cells could be efficiently differentiated into erythroid cells in liquid culture leading to a more than 5000-fold increase in cell number. The erythroid cells produced are similar to primitive erythroid cells present in the yolk sac of early human embryos and did not enucleate. They are fully hemoglobinized and express a mixture of embryonic and fetal globins but no beta-globin. We have developed an experimental protocol to produce large numbers of primitive erythroid cells starting from undifferentiated human embryonic stem cells. As the earliest human erythroid cells, the nucleated primitive erythroblasts, are not very well characterized because experimental material at this stage of development is very difficult to obtain, this system should prove useful to answer a number of experimental questions regarding the biology of these cells. In addition, production of mature red blood cells from human embryonic stem cells is of great potential practical importance because it could eventually become an alternate source of cell for transfusion.

CD71(high) population represents primitive erythroblasts derived from mouse embryonic stem cells.

PubMed

Chao, Ruihua; Gong, Xueping; Wang, Libo; Wang, Pengxiang; Wang, Yuan

2015-01-01

The CD71/Ter119 combination has been widely used to reflect dynamic maturation of erythrocytes in vivo. However, because CD71 is expressed on all proliferating cells, it is unclear whether it can be utilized as an erythrocyte-specific marker during differentiation of embryonic stem cells (ESCs). In this study, we revealed that a population expressing high level of CD71 (CD71(high)) during mouse ESC differentiation represented an in vitro counterpart of yolk sac-derived primitive erythroblasts (EryPs) isolated at 8.5days post coitum. In addition, these CD71(high) cells went through "maturational globin switching" and enucleated during terminal differentiation in vitro that were similar to the yolk sac-derived EryPs in vivo. We further demonstrated that the formation of CD71(high) population was regulated differentially by key factors including Scl, HoxB4, Eaf1, and Klf1. Taken together, our study provides a technical advance that allows efficient segregation of EryPs from differentiated ESCs in vitro for further understanding molecular regulation during primitive erythropoiesis. Copyright © 2014. Published by Elsevier B.V.

Attributed relational graphs for cell nucleus segmentation in fluorescence microscopy images.

PubMed

Arslan, Salim; Ersahin, Tulin; Cetin-Atalay, Rengul; Gunduz-Demir, Cigdem

2013-06-01

More rapid and accurate high-throughput screening in molecular cellular biology research has become possible with the development of automated microscopy imaging, for which cell nucleus segmentation commonly constitutes the core step. Although several promising methods exist for segmenting the nuclei of monolayer isolated and less-confluent cells, it still remains an open problem to segment the nuclei of more-confluent cells, which tend to grow in overlayers. To address this problem, we propose a new model-based nucleus segmentation algorithm. This algorithm models how a human locates a nucleus by identifying the nucleus boundaries and piecing them together. In this algorithm, we define four types of primitives to represent nucleus boundaries at different orientations and construct an attributed relational graph on the primitives to represent their spatial relations. Then, we reduce the nucleus identification problem to finding predefined structural patterns in the constructed graph and also use the primitives in region growing to delineate the nucleus borders. Working with fluorescence microscopy images, our experiments demonstrate that the proposed algorithm identifies nuclei better than previous nucleus segmentation algorithms.

Tubulin post-translational modifications in the primitive protist Trichomonas vaginalis.

PubMed

Delgado-Viscogliosi, P; Brugerolle, G; Viscogliosi, E

1996-01-01

Using several specific monoclonal antibodies, we investigated the occurrence and distribution of different post-translationally modified tubulin during interphase and division of the primitive flagellated protist Trichomonas vaginalis. Immunoblotting and immunofluorescence experiments revealed that interphasic microtubular structures of T. vaginalis contained acetylated and glutamylated but non-tyrosinated and non-glycylated [Brugerolle and Adoutte, 1988: Bio Systems 21: 255-268] tubulin. Immunofluorescence studies performed on dividing cells showed that the extranuclear mitotic spindle (or paradesmosis) was acetylated and glutamylated, which contrast with the ephemeral nature of this structure. Newly formed short axostyles also contained acetylated and glutamylated tubulin suggesting that both post-translational modifications might take place very early after assembly of microtubular structures. Our results indicate that acetylation and glutamylation of tubulin appeared early in the history of eukaryotes and could reflect the occurrence of post-translational modifications of tubulin in the primitive eukaryotic cells. These cells probably had a highly ordered cross-linked microtubular cytoskeleton in which microtubules showed a low level of subunit exchange dynamics.

Targeting the aryl hydrocarbon receptor nuclear translocator complex with DMOG and Stemregenin 1 improves primitive hematopoietic stem cell expansion.

PubMed

Jackson, Carlo Stephan; Durandt, Chrisna; Janse van Rensburg, Ilse; Praloran, Vincent; Brunet de la Grange, Philippe; Pepper, Michael Sean

2017-05-01

Culture conditions used for the expansion of hematopoietic stem and progenitor cells (HSCs and HPCs, collectively HSPCs) should ideally favor the self renewal of long-term HSCs. At 20% O 2 , the synthesis of HIF-1α is balanced by its hydroxylation and proteasomal degradation. This favors HSPC differentiation, but can be prevented by culturing CD34+ cord blood cells in the presence of dimethyloxaloylglycine (DMOG). This differentiation may also be reduced by culturing the cells in the presence of Stemregenin 1, an antagonist of the aryl hydrocarbon receptor (AhR). The objective of this study was to investigate how hypoxia, DMOG and Stemregenin 1 might affect the expansion of HSPCs with the aim of identifying optimal conditions for expansion in culture. It was found that DMOG decreased proliferation but was effective in preserving the number of cells in the primitive hematopoietic sub-populations in vitro. The effect of DMOG was similar to hypoxia, although differences were observed with regard to the side population and CD34+ sub-populations. Stemregenin 1 on the other hand increased the size of the primitive as well as the other HSC sub-populations. The use of Stemregenin 1 with DMOG increased the proportion of primitive HSCs to 3.54% compared to 2.61% for Stemregenin 1 alone. In vivo engraftment studies confirmed these findings and showed that fewer cells (3710) are required for long-term engraftment when HSCs are grown in Stemregenin 1 together with hypoxia than in Stemregenin 1 under conditions of normoxia (13430). Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-13

Advanced Malignant Solid Neoplasm; RB1 Positive; Recurrent Childhood Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Kidney Wilms Tumor; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Glioma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma

Fanconi anemia genes are highly expressed in primitive CD34+ hematopoietic cells

PubMed Central

Aubé, Michel; Lafrance, Matthieu; Brodeur, Isabelle; Delisle, Marie-Chantal; Carreau, Madeleine

2003-01-01

Background Fanconi anemia (FA) is a complex recessive genetic disease characterized by progressive bone marrow failure (BM) and a predisposition to cancer. We have previously shown using the Fancc mouse model that the progressive BM failure results from a hematopoietic stem cell defect suggesting that function of the FA genes may reside in primitive hematopoietic stem cells. Methods Since genes involved in stem cell differentiation and/or maintenance are usually regulated at the transcription level, we used a semiquantitative RT-PCR method to evaluate FA gene transcript levels in purified hematopoietic stem cells. Results We show that most FA genes are highly expressed in primitive CD34-positive and negative cells compared to lower levels in more differentiated cells. However, in CD34- stem cells the Fancc gene was found to be expressed at low levels while Fancg was undetectable in this population. Furthermore, Fancg expression is significantly decreased in Fancc -/- stem cells as compared to wild-type cells while the cancer susceptibility genes Brca1 and Fancd1/Brac2 are upregulated in Fancc-/- hematopoietic cells. Conclusions These results suggest that FA genes are regulated at the mRNA level, that increased Fancc expression in LTS-CD34+ cells correlates with a role at the CD34+ differentiation stage and that lack of Fancc affects the expression of other FA gene, more specifically Fancg and Fancd1/Brca2, through an unknown mechanism. PMID:12809565

Individual blastomeres of 16- and 32-cell mouse embryos are able to develop into foetuses and mice.

PubMed

Tarkowski, Andrzej K; Suwińska, Aneta; Czołowska, Renata; Ożdżeński, Wacław

2010-12-15

Cell and developmental studies have clarified how, by the time of implantation, the mouse embryo forms three primary cell lineages: epiblast (EPI), primitive endoderm (PE), and trophectoderm (TE). However, it still remains unknown when cells allocated to these three lineages become determined in their developmental fate. To address this question, we studied the developmental potential of single blastomeres derived from 16- and 32-cell stage embryos and supported by carrier, tetraploid blastomeres. We were able to generate singletons, identical twins, triplets, and quadruplets from individual inner and outer cells of 16-cell embryos and, sporadically, foetuses from single cells of 32-cell embryos. The use of embryos constitutively expressing GFP as the donors of single diploid blastomeres enabled us to identify their cell progeny in the constructed 2n↔4n blastocysts. We showed that the descendants of donor blastomeres were able to locate themselves in all three first cell lineages, i.e., epiblast, primitive endoderm, and trophectoderm. In addition, the application of Cdx2 and Gata4 markers for trophectoderm and primitive endoderm, respectively, showed that the expression of these two genes in the descendants of donor blastomeres was either down- or up-regulated, depending on the cell lineage they happened to occupy. Thus, our results demonstrate that up to the early blastocysts stage, the destiny of at least some blastomeres, although they have begun to express markers of different lineage, is still labile. Copyright © 2010 Elsevier Inc. All rights reserved.

Characterization of selected elementary motion detector cells to image primitives.

PubMed

Benson, Leslie A; Barrett, Steven F; Wright, Cameron H G

2008-01-01

Developing a visual sensing system, complete with motion processing hardware and software would have many applications to current technology. It could be mounted on many autonomous vehicles to provide information about the navigational environment, as well as obstacle avoidance features. Incorporating the motion processing capabilities into the sensor requires a new approach to the algorithm implementation. This research, and that of many others, have turned to nature for inspiration. Elementary motion detector (EMD) cells are involved in a biological preprocessing network to provide information to the motion processing lobes of the house degrees y Musca domestica. This paper describes the response of the photoreceptor inputs to the EMDs. The inputs to the EMD components are tested as they are stimulated with varying image primitives. This is the first of many steps in characterizing the EMD response to image primitives.

Mesenchymal Stem Cells and the Origin of Ewing's Sarcoma

PubMed Central

Lin, Patrick P.; Wang, Yongxing; Lozano, Guillermina

2011-01-01

The origin of Ewing's sarcoma is a subject of much debate. Once thought to be derived from primitive neuroectodermal cells, many now believe it to arise from a mesenchymal stem cell (MSC). Expression of the EWS-FLI1 fusion gene in MSCs changes cell morphology to resemble Ewing's sarcoma and induces expression of neuroectodermal markers. In murine cells, transformation to sarcomas can occur. In knockdown experiments, Ewing's sarcoma cells develop characteristics of MSCs and the ability to differentiate into mesodermal lineages. However, it cannot be concluded that MSCs are the cell of origin. The concept of an MSC still needs to be rigorously defined, and there may be different subpopulations of mesenchymal pluripotential cells. Furthermore, EWS-FLI1 by itself does not transform human cells, and cooperating mutations appear to be necessary. Therefore, while it is possible that Ewing's sarcoma may originate from a primitive mesenchymal cell, the idea needs to be refined further. PMID:20953407

Finite-volume application of high order ENO schemes to multi-dimensional boundary-value problems

NASA Technical Reports Server (NTRS)

Casper, Jay; Dorrepaal, J. Mark

1990-01-01

The finite volume approach in developing multi-dimensional, high-order accurate essentially non-oscillatory (ENO) schemes is considered. In particular, a two dimensional extension is proposed for the Euler equation of gas dynamics. This requires a spatial reconstruction operator that attains formal high order of accuracy in two dimensions by taking account of cross gradients. Given a set of cell averages in two spatial variables, polynomial interpolation of a two dimensional primitive function is employed in order to extract high-order pointwise values on cell interfaces. These points are appropriately chosen so that correspondingly high-order flux integrals are obtained through each interface by quadrature, at each point having calculated a flux contribution in an upwind fashion. The solution-in-the-small of Riemann's initial value problem (IVP) that is required for this pointwise flux computation is achieved using Roe's approximate Riemann solver. Issues to be considered in this two dimensional extension include the implementation of boundary conditions and application to general curvilinear coordinates. Results of numerical experiments are presented for qualitative and quantitative examination. These results contain the first successful application of ENO schemes to boundary value problems with solid walls.

Spontaneous circulation of myeloid-lymphoid-initiating cells and SCID-repopulating cells in sickle cell crisis.

PubMed

Lamming, Christopher E D; Augustin, Lance; Blackstad, Mark; Lund, Troy C; Hebbel, Robert P; Verfaillie, Catherine M

2003-03-01

The only curative therapy for sickle cell disease (SCD) is allogeneic hematopoietic stem cell (HSC) transplantation. Gene therapy approaches for autologous HSC transplantation are being developed. Although earlier engraftment is seen when cells from GCSF-mobilized blood are transplanted than when bone marrow is transplanted, administration of GCSF to patients with SCD can cause significant morbidity. We tested whether primitive hematopoietic progenitors are spontaneously mobilized in the blood of patients with SCD during acute crisis (AC-SCD patients). The frequency of myeloid-lymphoid-initiating cells (ML-ICs) and SCID-repopulating cells (SRCs) was significantly higher in blood from AC-SCD patients than in blood from patients with steady-state SCD or from normal donors. The presence of SRCs in peripheral blood was not associated with detection of long-term culture-initiating cells, consistent with the notion that SRCs are more primitive than long-term culture-initiating cells. As ML-ICs and SRCs were both detected in blood of AC-SCD patients only, these assays may both measure primitive progenitors. The frequency of ML-ICs also correlated with increases in stem cell factor, GCSF, and IL-8 levels in AC-SCD compared with steady-state SCD and normal-donor sera. Because significant numbers of ML-ICs and SRCs are mobilized in the blood without exogenous cytokine treatment during acute crisis of SCD, collection of peripheral blood progenitors during crisis may yield a source of autologous HSCs suitable for ex-vivo correction by gene therapy approaches and subsequent transplantation.

The Coherent Interlayer Resistance of a Single, Misoriented Interface between Two Graphite Stacks

NASA Astrophysics Data System (ADS)

Lake, Roger K.; Habib, K. M. Masum; Sylvia, Somaia; Ge, Supeng; Neupane, Mahesh

2014-03-01

The coherent, interlayer resistance of a misoriented, rotated interface between two stacks of AB graphite is determined for a variety of misorientation angles ranging from 0° to 27 .29° . The quantum-resistance of the ideal AB stack is on the order of 1 to 10 m Ωμm2 depending on the Fermi energy. For small rotation angles <= 7 .34° , the coherent interlayer resistance exponentially approaches the ideal quantum resistance at energies away from the charge neutrality point. Over a range of intermediate angles, the resistance increases exponentially with primitive cell size for minimum size cells. A change of misorientation angle by one degree can increase the primitive cell size by three orders of magnitude. These large cell sizes may not follow the exponential trend of the minimal cells especially at energies a few hundred meV away from the charge neutrality point. At such energies, their coherent interlayer resistance is likely to coincide with that of a nearby rotation angle with a much smaller primitive cell. The energy dependence of the interlayer transmission is described and analyzed. This work was supported in part by FAME, one of six centers of STARnet, a Semiconductor Research Corporation program sponsored by MARCO and DARPA.

Local bone marrow renin-angiotensin system in primitive, definitive and neoplastic haematopoiesis.

PubMed

Haznedaroglu, Ibrahim C; Beyazit, Yavuz

2013-03-01

The locally active ligand peptides, mediators, receptors and signalling pathways of the haematopoietic BM (bone marrow) autocrine/paracrine RAS (renin-angiotensin system) affect the essential steps of definitive blood cell production. Haematopoiesis, erythropoiesis, myelopoiesis, formation of monocytic and lymphocytic lineages, thrombopoiesis and other stromal cellular elements are regulated by the local BM RAS. The local BM RAS is present and active even in primitive embryonic haematopoiesis. ACE (angiotensin-converting enzyme) is expressed on the surface of the first endothelial and haematopoietic cells, forming the marrow cavity in the embryo. ACE marks early haematopoietic precursor cells and long-term blood-forming CD34(+) BM cells. The local autocrine tissue BM RAS may also be active in neoplastic haematopoiesis. Critical RAS mediators such as renin, ACE, AngII (angiotensin II) and angiotensinogen have been identified in leukaemic blast cells. The local tissue RAS influences tumour growth and metastases in an autocrine and paracrine fashion via the modulation of numerous carcinogenic events, such as angiogenesis, apoptosis, cellular proliferation, immune responses, cell signalling and extracellular matrix formation. The aim of the present review is to outline the known functions of the local BM RAS within the context of primitive, definitive and neoplastic haematopoiesis. Targeting the actions of local RAS molecules could represent a valuable therapeutic option for the management of neoplastic disorders.

Comparison of Gene Expression in Human Embryonic Stem Cells, hESC-Derived Mesenchymal Stem Cells and Human Mesenchymal Stem Cells.

PubMed

Barbet, Romain; Peiffer, Isabelle; Hatzfeld, Antoinette; Charbord, Pierre; Hatzfeld, Jacques A

2011-01-01

We present a strategy to identify developmental/differentiation and plasma membrane marker genes of the most primitive human Mesenchymal Stem Cells (hMSCs). Using sensitive and quantitative TaqMan Low Density Arrays (TLDA) methodology, we compared the expression of 381 genes in human Embryonic Stem Cells (hESCs), hESC-derived MSCs (hES-MSCs), and hMSCs. Analysis of differentiation genes indicated that hES-MSCs express the sarcomeric muscle lineage in addition to the classical mesenchymal lineages, suggesting they are more primitive than hMSCs. Transcript analysis of membrane antigens suggests that IL1R1(low), BMPR1B(low), FLT4(low), LRRC32(low), and CD34 may be good candidates for the detection and isolation of the most primitive hMSCs. The expression in hMSCs of cytokine genes, such as IL6, IL8, or FLT3LG, without expression of the corresponding receptor, suggests a role for these cytokines in the paracrine control of stem cell niches. Our database may be shared with other laboratories in order to explore the considerable clinical potential of hES-MSCs, which appear to represent an intermediate developmental stage between hESCs and hMSCs.

Flavopiridol in Treating Children With Relapsed or Refractory Solid Tumors or Lymphomas

ClinicalTrials.gov

2013-07-01

Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Retinoblastoma; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

Krüppel-Like Factor 1 (KLF1), KLF2, and Myc Control a Regulatory Network Essential for Embryonic Erythropoiesis

PubMed Central

Pang, Christopher J.; Lemsaddek, Wafaa; Alhashem, Yousef N.; Bondzi, Cornelius; Redmond, Latasha C.; Ah-Son, Nicolas; Dumur, Catherine I.; Archer, Kellie J.; Haar, Jack L.

2012-01-01

The Krüppel-like factor 1 (KLF1) and KLF2 positively regulate embryonic β-globin expression and have additional overlapping roles in embryonic (primitive) erythropoiesis. KLF1−/− KLF2−/− double knockout mice are anemic at embryonic day 10.5 (E10.5) and die by E11.5, in contrast to single knockouts. To investigate the combined roles of KLF1 and KLF2 in primitive erythropoiesis, expression profiling of E9.5 erythroid cells was performed. A limited number of genes had a significantly decreasing trend of expression in wild-type, KLF1−/−, and KLF1−/− KLF2−/− mice. Among these, the gene for Myc (c-Myc) emerged as a central node in the most significant gene network. The expression of the Myc gene is synergistically regulated by KLF1 and KLF2, and both factors bind the Myc promoters. To characterize the role of Myc in primitive erythropoiesis, ablation was performed specifically in mouse embryonic proerythroblast cells. After E9.5, these embryos exhibit an arrest in the normal expansion of circulating red cells and develop anemia, analogous to KLF1−/− KLF2−/− embryos. In the absence of Myc, circulating erythroid cells do not show the normal increase in α- and β-like globin gene expression but, interestingly, have accelerated erythroid cell maturation between E9.5 and E11.5. This study reveals a novel regulatory network by which KLF1 and KLF2 regulate Myc to control the primitive erythropoietic program. PMID:22566683

Oxaliplatin and Irinotecan in Treating Young Patients With Refractory Solid Tumors or Lymphomas

ClinicalTrials.gov

2013-06-04

Childhood Burkitt Lymphoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway Glioma; Recurrent Colon Cancer; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Melanoma; Recurrent Nasopharyngeal Cancer; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

Is alkaline phosphatase the smoking gun for highly refractory primitive leukemic cells?

PubMed Central

Rico, Laura G.; Juncà, Jordi; Ward, Mike D.; Bradford, Jolene; Petriz, Jordi

2016-01-01

With the aim to detect candidate malignant primitive progenitor populations, we modified an original alkaline phosphatase (ALP) stem cell detection method based on the identification of alkaline phosphatase fluorescent cells in combination with flow cytometry immunophenotyping. Over a period of one year, we have been using this technique to study its activity in patients with leukemia and lymphoma, showing that changes in the alkaline phosphatase levels can be used to detect rare populations of highly refractory malignant cells. By screening different blood cancers, we have observed that this activity is not always restricted to CD34+ leukemic cells, and can be overexpressed in CD34 negative leukemia. We have verified that this method gives accurate and reproducible measurements and our preliminary results suggest that CD34+/ALPhigh cells appear to sustain leukemogenesis over time. PMID:27732563

Primitive macrophages control HSPC mobilization and definitive haematopoiesis.

PubMed

Travnickova, Jana; Tran Chau, Vanessa; Julien, Emmanuelle; Mateos-Langerak, Julio; Gonzalez, Catherine; Lelièvre, Etienne; Lutfalla, Georges; Tavian, Manuela; Kissa, Karima

2015-02-17

In vertebrates, haematopoietic stem/progenitor cells (HSPCs) first emerge in the aorta-gonad-mesonephros (AGM) before colonizing transitory and subsequently definitive haematopoietic organs allowing haematopoiesis throughout adult life. Here we identify an unexpected primitive macrophage population accumulated in the dorsal mesenteric mesoderm surrounding the dorsal aorta of the human embryo and study its function in the transparent zebrafish embryo. Our study reveals dynamic interactions occurring between the HSPCs and primitive macrophages in the AGM. Specific chemical and inducible genetic depletion of macrophages or inhibition of matrix metalloproteinases (Mmps) leads to an accumulation of HSPCs in the AGM and a decrease in the colonization of haematopoietic organs. Finally, in vivo zymography demonstrates the function of primitive macrophages in extracellular matrix degradation, which allows HSPC migration through the AGM stroma, their intravasation, leading to the colonization of haematopoietic organs and the establishment of definitive haematopoiesis.

Neocortical layers I and II of the hedgehog (Erinaceus europaeus). I. Intrinsic organization.

PubMed

Valverde, F; Facal-Valverde, M V

1986-01-01

The intrinsic organization and interlaminar connections in neocortical layers I and II have been studied in adult hedgehogs (Erinaceus europaeus) using the Golgi method. Layer I contains a dense plexus of horizontal fibers, the terminal dendritic bouquets of pyramidal cells of layer II and of underlying layers, and varieties of intrinsic neurons. Four main types of cells were found in layer I. Small horizontal cells represent most probably persisting foetal horizontal cells described for other mammals. Large horizontal cells, tufted cells, and spinous horizontal cells were also found in this layer. Layer II contains primitive pyramidal cells representing the most outstanding feature of the neocortex of the hedgehog. Most pyramidal cells in layer II have two, three or more apical dendrites, richly covered by spines predominating over the basal dendrites. These cells resemble pyramidal cells found in the piriform cortex, hippocampus and other olfactory areas. It is suggested that the presence of these neurons reflects the retention of a primitive character in neocortical evolution. Cells with intrinsic axons were found among pyramidal cells in layer II. These have smooth dendrites penetrating layer I and local axons forming extremely complex terminal arborizations around the bodies and proximal dendritic portions of pyramidal cells. They most probably effect numerous axo-somatic contacts resembling basket cells. The similarity of some axonal terminals with the chandelier type of axonal arborization is discussed. Other varieties of cells located in deep cortical layers and having ascending axons for layers I and II were also studied. It is concluded that the two first neocortical layers represent a level of important integration in this primitive mammal.

Spontaneous circulation of myeloid-lymphoid–initiating cells and SCID-repopulating cells in sickle cell crisis

PubMed Central

Lamming, Christopher E.D.; Augustin, Lance; Blackstad, Mark; Lund, Troy C.; Hebbel, Robert P.; Verfaillie, Catherine M.

2003-01-01

The only curative therapy for sickle cell disease (SCD) is allogeneic hematopoietic stem cell (HSC) transplantation. Gene therapy approaches for autologous HSC transplantation are being developed. Although earlier engraftment is seen when cells from GCSF-mobilized blood are transplanted than when bone marrow is transplanted, administration of GCSF to patients with SCD can cause significant morbidity. We tested whether primitive hematopoietic progenitors are spontaneously mobilized in the blood of patients with SCD during acute crisis (AC-SCD patients). The frequency of myeloid-lymphoid–initiating cells (ML-ICs) and SCID-repopulating cells (SRCs) was significantly higher in blood from AC-SCD patients than in blood from patients with steady-state SCD or from normal donors. The presence of SRCs in peripheral blood was not associated with detection of long-term culture–initiating cells, consistent with the notion that SRCs are more primitive than long-term culture–initiating cells. As ML-ICs and SRCs were both detected in blood of AC-SCD patients only, these assays may both measure primitive progenitors. The frequency of ML-ICs also correlated with increases in stem cell factor, GCSF, and IL-8 levels in AC-SCD compared with steady-state SCD and normal-donor sera. Because significant numbers of ML-ICs and SRCs are mobilized in the blood without exogenous cytokine treatment during acute crisis of SCD, collection of peripheral blood progenitors during crisis may yield a source of autologous HSCs suitable for ex-vivo correction by gene therapy approaches and subsequent transplantation. PMID:12639987

Importance of Sox2 in maintenance of cell proliferation and multipotency of mesenchymal stem cells in low-density culture.

PubMed

Yoon, D S; Kim, Y H; Jung, H S; Paik, S; Lee, J W

2011-10-01

This study has aimed to repopulate 'primitive' cells from late-passage mesenchymal stem cells (MSCs) of poor multipotentiality and low cell proliferation rate, by simply altering plating density. Effects of low density culture compared t high density culture on late-passage bone marrow (BM)-derived MSCs and pluripotency markers of multipotentiality were investigated. Cell proliferation, gene expression, RNA interference and differentiation potential were assayed. We repopulated 'primitive' cells by replating late-passage MSCs at low density (17 cells/cm(2) ) regardless of donor age. Repopulated MSCs from low-density culture were smaller cells with spindle shaped morphology compared to MSCs from high-density culture. The latter had enhanced colony-forming ability, proliferation rate, and adipogenic and chondrogenic potential. Strong expression of osteogenic-related genes (Cbfa1, Dlx5, alkaline phosphatase and type Ι collagen) in late-passage MSCs was reduced by replating at low density, whereas expression of three pluripotency markers (Sox2, Nanog and Oct-4), Osterix and Msx2 reverted to levels of early-passage MSCs. Knockdown of Sox2 and Msx2 but not Nanog, using RNA interference, showed significant decrease in colony-forming ability. Specifically, knockdown of Sox2 significantly inhibited multipotentiality and cell proliferation. Our data suggest that plating density should be considered to be a critical factor for enrichment of 'primitive' cells from heterogeneous BM and that replicative senescence and multipotentiality of MSCs during in vitro expansion may be predominantly regulated through Sox2. © 2011 Blackwell Publishing Ltd.

Impact of modeled microgravity on migration, differentiation, and cell cycle control of primitive human hematopoietic progenitor cells.

PubMed

Plett, P Artur; Abonour, Rafat; Frankovitz, Stacy M; Orschell, Christie M

2004-08-01

Migration, proliferation, and differentiation of bone marrow (BM) hematopoietic stem cells (HSC) are important factors in maintaining hematopoietic homeostasis. Homeostatic control of erythrocytes and lymphocytes is perturbed in humans exposed to microgravity (micro-g), resulting in space flight-induced anemia and immunosuppression. We sought to determine whether any of these anomalies can be explained by micro-g-induced changes in migration, proliferation, and differentiation of human BM CD34+ cells, and whether such changes can begin to explain any of the shifts in hematopoietic homeostasis observed in astronauts. BM CD34+ cells were cultured in modeled micro-g (mmicro-g) using NASA's rotating wall vessels (RWV), or in control cultures at earth gravity for 2 to 18 days. Cells were harvested at different times and CD34+ cells assessed for migration potential, cell-cycle kinetics and regulatory proteins, and maturation status. Culture of BM CD34+ cells in RWV for 2 to 3 days resulted in a significant reduction of stromal cell-derived factor 1 (SDF-1alpha)-directed migration, which correlated with decreased expression of F-actin. Modeled micro-g induced alterations in cell-cycle kinetics that were characterized by prolonged S phase and reduced cyclin A expression. Differentiation of primitive CD34+ cells cultured for 14 to 18 days in RWV favored myeloid cell development at the expense of erythroid development, which was significantly reduced compared to controls. These results illustrate that mmicro-g significantly inhibits the migration potential, cell-cycle progression, and differentiation patterns of primitive BM CD34+ cells, which may contribute to some of the hematologic abnormalities observed in humans during space flight.

Msx1-modulated muscle satellite cells retain a primitive state and exhibit an enhanced capacity for osteogenic differentiation

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

Ding, Ke, E-mail: dingke@med.uestc.edu.cn; Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu 610072; Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing 400038

Multipotent muscle satellite cells (MuSCs) have been identified as potential seed cells for bone tissue engineering. However, MuSCs exhibit a rapid loss of stemness after in vitro culturing, thereby compromising their therapeutic efficiency. Muscle segment homeobox gene 1 (msx1) has been found to induce the dedifferentiation of committed progenitor cells, as well as terminally differentiated myotubes. In this study, a Tet-off retroviral gene delivery system was used to modulate msx1 expression. After ten passages, MuSCs that did not express msx-1 (e.g., the non-msx1 group) were compared with MuSCs with induced msx-1 expression (e.g., the msx1 group). The latter group exhibitedmore » a more juvenile morphology, it contained a significantly lower percentage of senescent cells characterized by positive β-galactosidase staining, and it exhibited increased proliferation and a higher proliferation index. Immunocytochemical stainings further detected a more primitive gene expression profile for the msx1 group, while osteogenic differentiation assays and ectopic bone formation assays demonstrated an improved capacity for the msx1 group to undergo osteogenic differentiation. These results suggest that transient expression of msx1 in MuSCs can retain a primitive state, thereby enhancing their capacity for osteogenic differentiation and restoring the potential for MuSCs to serve as seed cells for bone tissue engineering.« less

Msx1-modulated muscle satellite cells retain a primitive state and exhibit an enhanced capacity for osteogenic differentiation.

PubMed

Ding, Ke; Liu, Wen-Ying; Zeng, Qiang; Hou, Fang; Xu, Jian-Zhong; Yang, Zhong

2017-03-01

Multipotent muscle satellite cells (MuSCs) have been identified as potential seed cells for bone tissue engineering. However, MuSCs exhibit a rapid loss of stemness after in vitro culturing, thereby compromising their therapeutic efficiency. Muscle segment homeobox gene 1 (msx1) has been found to induce the dedifferentiation of committed progenitor cells, as well as terminally differentiated myotubes. In this study, a Tet-off retroviral gene delivery system was used to modulate msx1 expression. After ten passages, MuSCs that did not express msx-1 (e.g., the non-msx1 group) were compared with MuSCs with induced msx-1 expression (e.g., the msx1 group). The latter group exhibited a more juvenile morphology, it contained a significantly lower percentage of senescent cells characterized by positive β-galactosidase staining, and it exhibited increased proliferation and a higher proliferation index. Immunocytochemical stainings further detected a more primitive gene expression profile for the msx1 group, while osteogenic differentiation assays and ectopic bone formation assays demonstrated an improved capacity for the msx1 group to undergo osteogenic differentiation. These results suggest that transient expression of msx1 in MuSCs can retain a primitive state, thereby enhancing their capacity for osteogenic differentiation and restoring the potential for MuSCs to serve as seed cells for bone tissue engineering. Copyright © 2017 Elsevier Inc. All rights reserved.

Disruption of IKAROS activity in primitive chronic-phase CML cells mimics myeloid disease progression

PubMed Central

Beer, Philip A.; Knapp, David J. H. F.; Miller, Paul H.; Kannan, Nagarajan; Sloma, Ivan; Heel, Kathy; Babovic, Sonja; Bulaeva, Elizabeth; Rabu, Gabrielle; Terry, Jefferson; Druker, Brian J.; Loriaux, Marc M.; Loeb, Keith R.; Radich, Jerald P.; Erber, Wendy N.

2015-01-01

Without effective therapy, chronic-phase chronic myeloid leukemia (CP-CML) evolves into an acute leukemia (blast crisis [BC]) that displays either myeloid or B-lymphoid characteristics. This transition is often preceded by a clinically recognized, but biologically poorly characterized, accelerated phase (AP). Here, we report that IKAROS protein is absent or reduced in bone marrow blasts from most CML patients with advanced myeloid disease (AP or BC). This contrasts with primitive CP-CML cells and BCR-ABL1–negative acute myeloid leukemia blasts, which express readily detectable IKAROS. To investigate whether loss of IKAROS contributes to myeloid disease progression in CP-CML, we examined the effects of forced expression of a dominant-negative isoform of IKAROS (IK6) in CP-CML patients’ CD34+ cells. We confirmed that IK6 disrupts IKAROS activity in transduced CP-CML cells and showed that it confers on them features of AP-CML, including a prolonged increased output in vitro and in xenografted mice of primitive cells with an enhanced ability to differentiate into basophils. Expression of IK6 in CD34+ CP-CML cells also led to activation of signal transducer and activator of transcription 5 and transcriptional repression of its negative regulators. These findings implicate loss of IKAROS as a frequent step and potential diagnostic harbinger of progressive myeloid disease in CML patients. PMID:25370416

Tanespimycin in Treating Young Patients With Recurrent or Refractory Leukemia or Solid Tumors

ClinicalTrials.gov

2013-06-03

Childhood Chronic Myelogenous Leukemia; Childhood Desmoplastic Small Round Cell Tumor; Disseminated Neuroblastoma; Metastatic Childhood Soft Tissue Sarcoma; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma

Molecular-Guided Therapy for Childhood Cancer

ClinicalTrials.gov

2017-07-07

Neuroblastoma; Medulloblastoma; Glioma; Ependymoma; Choroid Plexus Neoplasms; Craniopharyngioma; Dysembryoplastic Neuroepithelial Tumor; Meningioma; Primitive Neuroectodermal Tumors (PNETs); Germ Cell Tumors; Rhabdomyosarcoma; Non-rhabdomyosarcoma; Ewings Sarcoma; Osteosarcoma; Wilms Tumor; Renal Cell Carcinoma; Malignant Rhabdoid Tumor; Clear Cell Sarcoma; Liver Tumors

Essential roles for Cdx in murine primitive hematopoiesis.

PubMed

Brooke-Bisschop, Travis; Savory, Joanne G A; Foley, Tanya; Ringuette, Randy; Lohnes, David

2017-02-15

The Cdx transcription factors play essential roles in primitive hematopoiesis in the zebrafish where they exert their effects, in part, through regulation of hox genes. Defects in hematopoiesis have also been reported in Cdx mutant murine embryonic stem cell models, however, to date no mouse model reflecting the zebrafish Cdx mutant hematopoietic phenotype has been described. This is likely due, in part, to functional redundancy among Cdx members and the early lethality of Cdx2 null mutants. To circumvent these limitations, we used Cre-mediated conditional deletion to assess the impact of concomitant loss of Cdx1 and Cdx2 on murine primitive hematopoiesis. We found that Cdx1/Cdx2 double mutants exhibited defects in primitive hematopoiesis and yolk sac vasculature concomitant with reduced expression of several genes encoding hematopoietic transcription factors including Scl/Tal1. Chromatin immunoprecipitation analysis revealed that Scl was occupied by Cdx2 in vivo, and Cdx mutant hematopoietic yolk sac differentiation defects could be rescued by expression of exogenous Scl. These findings demonstrate critical roles for Cdx members in murine primitive hematopoiesis upstream of Scl. Copyright © 2017 Elsevier Inc. All rights reserved.

The Evolution of the Earliest Cells.

ERIC Educational Resources Information Center

Schopf, J. William

1978-01-01

Describes the unicellular microorganisms of three billion years ago. Explains how these primitive cells gave rise to biochemical systems and the present oxygen-rich atmosphere. Numerous diagrams, charts, and illustrations. (MA)

Ultrastrukturelle Untersuchungen zur Morphologie und Genese der Spermien von Archaeogastropoda

NASA Astrophysics Data System (ADS)

Kohnert, R.; Storch, V.

1983-03-01

The sperm cells of Patella coerulea (Patellacea), Monodonta turbinata, and Gibbula tumida (Trochacea) were investigated by means of transmission electron microscopy. They belong to the primitive type (sensu Franzén) and have more features in common with primitive Bivalvia sperms than with Neritacea. Their head contains an apical acrosome and a roundish nucleus followed by 4 or 5 mitochondria and a centriolar apparatus which consists of two centrioles, one of which bears a flagellum. The sperm cells of Monodonta and Gibbula are very similar to each other and differ mainly in size; Patella exhibits more differences (very small acrosome, subacrosomal space, variable number of spherical mitochondria (origin of spermic dimorphism ?). The development of the sperm cells shows no peculiarities.

Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-20

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Hodgkin Lymphoma; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; EZH2 Gain of Function; EZH2 Gene Mutation; Histiocytosis; Loss of BRG1 Protein Expression; Loss of INI 1 Protein Expression; Low Grade Glioma; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Hodgkin Lymphoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Central Nervous System Neoplasm; Refractory Hodgkin Lymphoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Soft Tissue Sarcoma; Rhabdoid Tumor; SMARCA4 Gene Inactivation; SMARCB1 Gene Inactivation; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Wilms Tumor

Induced-Pluripotent-Stem-Cell-Derived Primitive Macrophages Provide a Platform for Modeling Tissue-Resident Macrophage Differentiation and Function.

PubMed

Takata, Kazuyuki; Kozaki, Tatsuya; Lee, Christopher Zhe Wei; Thion, Morgane Sonia; Otsuka, Masayuki; Lim, Shawn; Utami, Kagistia Hana; Fidan, Kerem; Park, Dong Shin; Malleret, Benoit; Chakarov, Svetoslav; See, Peter; Low, Donovan; Low, Gillian; Garcia-Miralles, Marta; Zeng, Ruizhu; Zhang, Jinqiu; Goh, Chi Ching; Gul, Ahmet; Hubert, Sandra; Lee, Bernett; Chen, Jinmiao; Low, Ivy; Shadan, Nurhidaya Binte; Lum, Josephine; Wei, Tay Seok; Mok, Esther; Kawanishi, Shohei; Kitamura, Yoshihisa; Larbi, Anis; Poidinger, Michael; Renia, Laurent; Ng, Lai Guan; Wolf, Yochai; Jung, Steffen; Önder, Tamer; Newell, Evan; Huber, Tara; Ashihara, Eishi; Garel, Sonia; Pouladi, Mahmoud A; Ginhoux, Florent

2017-07-18

Tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that give rise to primitive YS macrophages. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMacs) can terminally differentiate into specialized macrophages with the help of growth factors and organ-specific cues. Co-culturing human or murine iMacs with iPSC-derived neurons promoted differentiation into microglia-like cells in vitro. Furthermore, murine iMacs differentiated in vivo into microglia after injection into the brain and into functional alveolar macrophages after engraftment in the lung. Finally, iPSCs from a patient with familial Mediterranean fever differentiated into iMacs with pro-inflammatory characteristics, mimicking the disease phenotype. Altogether, iMacs constitute a source of tissue-resident macrophage precursors that can be used for biological, pathophysiological, and therapeutic studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Studying the hopping parameters of half-Heusler NaAuS using maximally localized Wannier function

NASA Astrophysics Data System (ADS)

Sihi, Antik; Lal, Sohan; Pandey, Sudhir K.

2018-04-01

Here, the electronic behavior of half-Heusler NaAuS is studied using PBEsol exchange correlation functional by plotting the band structure curve. These bands are reproduced using maximally localized Wannier function using WANNIER90. Tight-binding bands are nicely matched with density functional theory bands. By fitting the tight-binding model, hopping parameter for NaAuS is obtained by including Na 2s, 2p, Au 6s, 5p, 5d and S 3s, 3p orbitals within the energy interval of -5 to 16 eV around the Fermi level. In present study, hopping integrals for NaAuS are computed for the first primitive unit cell atoms as well as the first nearest neighbor primitive unit cell. The most dominating hopping integrals are found for Na (3s) - S (3s), Na (2px) - S (2px), Au (6s) - S (3px), Au (6s) - S (3py) and Au (6s) - S (3pz) orbitals. The hopping integrals for the first nearest neighbor primitive unit cell are also discussed in this manuscript. In future, these hopping integrals are very important to find the topological invariant for NaAuS compound.

Enforced expression of KDR receptor promotes proliferation, survival and megakaryocytic differentiation of TF1 progenitor cell line.

PubMed

Coppola, S; Narciso, L; Feccia, T; Bonci, D; Calabrò, L; Morsilli, O; Gabbianelli, M; De Maria, R; Testa, U; Peschle, C

2006-01-01

Vascular endothelial growth factor (VEGF) receptor-2/kinase insert domain-containing receptor (KDR) is expressed in primitive hematopoietic cells, in megakaryocytes and platelets. In primitive hematopoiesis KDR mediates cell survival via autocrine VEGF, while its effect on cell growth and differentiation has not been elucidated. We induced enforced KDR expression in the granulocyte macrophage-colony-stimulating factor (GM-CSF)-dependent TF1 progenitor cell line (TF1-KDR), treated the cells with VEGF and analyzed their response. In GM-CSF-deprived cells, VEGF induces cell proliferation and protection against apoptosis, followed by enhanced expression of megakaryocytic (MK) markers. Combined with GM-CSF, VEGF induces a mild proliferative stimulus, followed by cell adherence, accumulation in G0/G1, massive MK differentiation and Fas-mediated apoptosis. Accordingly, we observed that MK-differentiating cells, derived from hematopoietic progenitors, produce VEGF, express KDR, inhibition of which reduces MK differentiation, indicating a key role of KDR in megakaryopoiesis. In conclusion, TF1-KDR cells provide a reliable model to investigate the biochemical and molecular mechanisms underlying hematopoietic progenitor proliferation, survival and MK differentiation.

Dual mTORC2/mTORC1 targeting results in potent suppressive effects on acute myeloid leukemia (AML) progenitors*

PubMed Central

Altman, Jessica K.; Sassano, Antonella; Kaur, Surinder; Glaser, Heather; Kroczynska, Barbara; Redig, Amanda J.; Russo, Suzanne; Barr, Sharon; Platanias, Leonidas C.

2011-01-01

Purpose To determine whether mTORC2 and RI-mTORC1 complexes are present in AML cells and to examine the effects of dual mTORC2/mTORC1 inhibition on primitive AML leukemic progenitors. Experimental Design Combinations of different experimental approaches were used, including immunoblotting to detect phosphorylated/activated forms of elements of the mTOR pathway in leukemic cell lines and primary AML blasts; cell proliferation assays; direct assessment of mRNA translation in polysomal fractions of leukemic cells; and clonogenic assays in methylcellulose to evaluate leukemic progenitor colony formation. Results mTORC2 complexes are active in AML cells and play critical roles in leukemogenesis. Rapamycin insensitive (RI) mTORC1 complexes are also formed and regulate the activity of the translational repressor 4E-BP1 in AML cells. OSI-027, blocks mTORC1 and mTORC2 activities and suppresses mRNA translation of cyclin D1 and other genes that mediate proliferative responses in AML cells. Moreover, OSI-027 acts as a potent suppressor of primitive leukemic precursors from AML patients and is much more effective than rapamycin in eliciting antileukemic effects in vitro. Conclusions Dual targeting of mTORC2 and mTORC1 results in potent suppressive effects on primitive leukemic progenitors from AML patients. Inhibition of the mTOR catalytic site with OSI-027 results in suppression of both mTORC2 and RI-mTORC1 complexes and elicits much more potent antileukemic responses than selective mTORC1 targeting with rapamycin. PMID:21415215

GOOSE: semantic search on internet connected sensors

NASA Astrophysics Data System (ADS)

Schutte, Klamer; Bomhof, Freek; Burghouts, Gertjan; van Diggelen, Jurriaan; Hiemstra, Peter; van't Hof, Jaap; Kraaij, Wessel; Pasman, Huib; Smith, Arthur; Versloot, Corne; de Wit, Joost

2013-05-01

More and more sensors are getting Internet connected. Examples are cameras on cell phones, CCTV cameras for traffic control as well as dedicated security and defense sensor systems. Due to the steadily increasing data volume, human exploitation of all this sensor data is impossible for effective mission execution. Smart access to all sensor data acts as enabler for questions such as "Is there a person behind this building" or "Alert me when a vehicle approaches". The GOOSE concept has the ambition to provide the capability to search semantically for any relevant information within "all" (including imaging) sensor streams in the entire Internet of sensors. This is similar to the capability provided by presently available Internet search engines which enable the retrieval of information on "all" web pages on the Internet. In line with current Internet search engines any indexing services shall be utilized cross-domain. The two main challenge for GOOSE is the Semantic Gap and Scalability. The GOOSE architecture consists of five elements: (1) an online extraction of primitives on each sensor stream; (2) an indexing and search mechanism for these primitives; (3) a ontology based semantic matching module; (4) a top-down hypothesis verification mechanism and (5) a controlling man-machine interface. This paper reports on the initial GOOSE demonstrator, which consists of the MES multimedia analysis platform and the CORTEX action recognition module. It also provides an outlook into future GOOSE development.

Mechanical properties of ceramic structures based on Triply Periodic Minimal Surface (TPMS) processed by 3D printing

NASA Astrophysics Data System (ADS)

Restrepo, S.; Ocampo, S.; Ramírez, J. A.; Paucar, C.; García, C.

2017-12-01

Repairing tissues and organs has been the main goal of surgical procedures. Since the 1990s, the main goal of tissue engineering has been reparation, using porous scaffolds that serve as a three-dimensional template for the initial fixation of cells and subsequent tissue formation both in vitro and in vivo. A scaffold must have specific characteristics of porosity, interconnectivity, surface area, pore volume, surface tortuosity, permeability and mechanical properties, which makes its design, manufacturing and characterization a complex process. Inspired by nature, triply periodic minimal surfaces (TPMS) have emerged as an alternative for the manufacture of porous pieces with design requirements, such as scaffolds for tissue repair. In the present work, we used the technique of 3D printing to obtain ceramic structures with Gyroid, Schwarz Primitive and Schwarz Diamond Surfaces shapes, three TPMS that fulfil the geometric requirements of a bone tissue scaffold. The main objective of this work is to compare the mechanical properties of ceramic pieces of three different forms of TPMS printed in 3D using a commercial ceramic paste. In this way it will be possible to clarify which is the TPMS with appropriate characteristics to construct scaffolds of ceramic materials for bone repair. A dependence of the mechanical properties with the geometry was found being the Primitive Surface which shows the highest mechanical properties.

Development of an interpretive simulation tool for the proton radiography technique

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

Levy, M. C., E-mail: levymc@stanford.edu; Lawrence Livermore National Laboratory, Livermore, California 94551; Ryutov, D. D.

2015-03-15

Proton radiography is a useful diagnostic of high energy density (HED) plasmas under active theoretical and experimental development. In this paper, we describe a new simulation tool that interacts realistic laser-driven point-like proton sources with three dimensional electromagnetic fields of arbitrary strength and structure and synthesizes the associated high resolution proton radiograph. The present tool’s numerical approach captures all relevant physics effects, including effects related to the formation of caustics. Electromagnetic fields can be imported from particle-in-cell or hydrodynamic codes in a streamlined fashion, and a library of electromagnetic field “primitives” is also provided. This latter capability allows users tomore » add a primitive, modify the field strength, rotate a primitive, and so on, while quickly generating a high resolution radiograph at each step. In this way, our tool enables the user to deconstruct features in a radiograph and interpret them in connection to specific underlying electromagnetic field elements. We show an example application of the tool in connection to experimental observations of the Weibel instability in counterstreaming plasmas, using ∼10{sup 8} particles generated from a realistic laser-driven point-like proton source, imaging fields which cover volumes of ∼10 mm{sup 3}. Insights derived from this application show that the tool can support understanding of HED plasmas.« less

Mask pattern generator employing EPL technology

NASA Astrophysics Data System (ADS)

Yoshioka, Nobuyuki; Yamabe, Masaki; Wakamiya, Wataru; Endo, Nobuhiro

2003-08-01

Mask cost is one of crucial issues in device fabrication, especially in SoC (System on a Chip) with small-volume production. The cost mainly depends on productivity of mask manufacturing tools such as mask writers and defect inspection tools. EPL (Electron Projection Lithography) has been developing as a high-throughput electron beam exposure technology that will succeed optical lithography. The application of EPL technology to mask writing will result in high productivity and contribute to decrease the mask cost. The concept of a mask pattern generator employing EPL technology is proposed in this paper. It is very similar to EPL technology used for pattern printing on a wafer. The mask patterns on the glass substrate are exposed by projecting the basic circuit patterns formed on the mother EPL mask. One example of the mother EPL mask is a stencil type made with 200-mm Si wafer. The basic circuit patterns are IP patterns and logical primitive patterns such as cell libraries (AND, OR, Inverter, Flip-Flop and etc.) to express the SoC device patterns. Since the SoC patterns are exposed with its collective units such as IP and logical primitive patterns by using this method, the high throughput will be expected comparing with conventional mask E-beam writers. In this paper, the mask pattern generator with the EPL technology is proposed. The concept, its advantages and issues to be solved are discussed.

On the vertical structure and stability of the Lofoten vortex in the Norwegian Sea

NASA Astrophysics Data System (ADS)

Bashmachnikov, I. L.; Sokolovskiy, M. A.; Belonenko, T. V.; Volkov, D. L.; Isachsen, P. E.; Carton, X.

2017-10-01

The Lofoten Vortex (LV), a quasi-permanent anticyclonic eddy in the Lofoten Basin of the Norwegian Sea, is investigated with an eddy-permitting primitive equation model nested into the ECCO2 ocean state estimate. The LV, as simulated by the model, extends from the sea surface to the ocean bottom at about 3000 m and has the subsurface core between 50 m and 1100 m depths. Above and below the vortex core the relative vorticity signal decreases in amplitude while the radius increases by as much as 25-30% relative to the values in the core. Analyzing the model run, we show that the vertical structure of the LV can be casted into four standard configurations, each of which forms a distinct cluster in the parameter space of potential vorticity anomalies in and above the LV core. The stability of the LV for each of the configurations is then studied with three-layer and a two-layer (in winter) quasi-geostrophic (QG) models over a flat bottom as well as over a realistic topography. The QG results show a number of common features with those of the primitive equation model. Thus, among the azimuthal modes dominating the LV instability, both the QG model and the primitive equation model show a major role the 2nd and 3rd modes. In the QG model simulations the LV is the subject of a rather strong dynamic instability, penetrating deep into the core. The results predict 50-95% volume loss from the vortex within 4-5 months. Such a drastic effect is not observed in the primitive equation model, where, for the same intensity of perturbations, only 10-30% volume loss during the same period is detected. Taking into account the gently sloping topography of the central part of the Lofoten basin and the mean flow in the QG model, brings the rate of development of instability close to that in the primitive equation model. Some remaining differences in the two models are discussed. Overall, the LV decay rate obtained in the models is slow enough for eddy mergers and convection to restore the thermodynamic properties of the LV, primarily re-building its potential energy anomaly. This justifies the quasi-permanent presence of the LV in the Lofoten Basin.

Lysophosphatidic acid acts as a nutrient-derived developmental cue to regulate early hematopoiesis

PubMed Central

Li, Haisen; Yue, Rui; Wei, Bin; Gao, Ge; Du, Jiulin; Pei, Gang

2014-01-01

Primitive hematopoiesis occurs in the yolk sac blood islands during vertebrate embryogenesis, where abundant phosphatidylcholines (PC) are available as important nutrients for the developing embryo. However, whether these phospholipids also generate developmental cues to promote hematopoiesis is largely unknown. Here, we show that lysophosphatidic acid (LPA), a signaling molecule derived from PC, regulated hemangioblast formation and primitive hematopoiesis. Pharmacological and genetic blockage of LPA receptor 1 (LPAR1) or autotoxin (ATX), a secretory lysophospholipase that catalyzes LPA production, inhibited hematopoietic differentiation of mouse embryonic stem cells and impaired the formation of hemangioblasts. Mechanistic experiments revealed that the regulatory effect of ATX-LPA signaling was mediated by PI3K/Akt-Smad pathway. Furthermore, during in vivo embryogenesis in zebrafish, LPA functioned as a developmental cue for hemangioblast formation and primitive hematopoiesis. Taken together, we identified LPA as an important nutrient-derived developmental cue for primitive hematopoiesis as well as a novel mechanism of hemangioblast regulation. PMID:24829209

Lysophosphatidic acid acts as a nutrient-derived developmental cue to regulate early hematopoiesis.

PubMed

Li, Haisen; Yue, Rui; Wei, Bin; Gao, Ge; Du, Jiulin; Pei, Gang

2014-06-17

Primitive hematopoiesis occurs in the yolk sac blood islands during vertebrate embryogenesis, where abundant phosphatidylcholines (PC) are available as important nutrients for the developing embryo. However, whether these phospholipids also generate developmental cues to promote hematopoiesis is largely unknown. Here, we show that lysophosphatidic acid (LPA), a signaling molecule derived from PC, regulated hemangioblast formation and primitive hematopoiesis. Pharmacological and genetic blockage of LPA receptor 1 (LPAR1) or autotoxin (ATX), a secretory lysophospholipase that catalyzes LPA production, inhibited hematopoietic differentiation of mouse embryonic stem cells and impaired the formation of hemangioblasts. Mechanistic experiments revealed that the regulatory effect of ATX-LPA signaling was mediated by PI3K/Akt-Smad pathway. Furthermore, during in vivo embryogenesis in zebrafish, LPA functioned as a developmental cue for hemangioblast formation and primitive hematopoiesis. Taken together, we identified LPA as an important nutrient-derived developmental cue for primitive hematopoiesis as well as a novel mechanism of hemangioblast regulation. © 2014 The Authors.

Transcriptional Networks in Single Perivascular Cells Sorted from Human Adipose Tissue Reveal a Hierarchy of Mesenchymal Stem Cells.

PubMed

Hardy, W Reef; Moldovan, Nicanor I; Moldovan, Leni; Livak, Kenneth J; Datta, Krishna; Goswami, Chirayu; Corselli, Mirko; Traktuev, Dmitry O; Murray, Iain R; Péault, Bruno; March, Keith

2017-05-01

Adipose tissue is a rich source of multipotent mesenchymal stem-like cells, located in the perivascular niche. Based on their surface markers, these have been assigned to two main categories: CD31 - /CD45 - /CD34 + /CD146 - cells (adventitial stromal/stem cells [ASCs]) and CD31 - /CD45 - /CD34 - /CD146 + cells (pericytes [PCs]). These populations display heterogeneity of unknown significance. We hypothesized that aldehyde dehydrogenase (ALDH) activity, a functional marker of primitivity, could help to better define ASC and PC subclasses. To this end, the stromal vascular fraction from a human lipoaspirate was simultaneously stained with fluorescent antibodies to CD31, CD45, CD34, and CD146 antigens and the ALDH substrate Aldefluor, then sorted by fluorescence-activated cell sorting. Individual ASCs (n = 67) and PCs (n = 73) selected from the extremities of the ALDH-staining spectrum were transcriptionally profiled by Fluidigm single-cell quantitative polymerase chain reaction for a predefined set (n = 429) of marker genes. To these single-cell data, we applied differential expression and principal component and clustering analysis, as well as an original gene coexpression network reconstruction algorithm. Despite the stochasticity at the single-cell level, covariation of gene expression analysis yielded multiple network connectivity parameters suggesting that these perivascular progenitor cell subclasses possess the following order of maturity: (a) ALDH br ASC (most primitive); (b) ALDH dim ASC; (c) ALDH br PC; (d) ALDH dim PC (least primitive). This order was independently supported by specific combinations of class-specific expressed genes and further confirmed by the analysis of associated signaling pathways. In conclusion, single-cell transcriptional analysis of four populations isolated from fat by surface markers and enzyme activity suggests a developmental hierarchy among perivascular mesenchymal stem cells supported by markers and coexpression networks. Stem Cells 2017;35:1273-1289. © 2017 AlphaMed Press.

Advanced texture filtering: a versatile framework for reconstructing multi-dimensional image data on heterogeneous architectures

NASA Astrophysics Data System (ADS)

Zellmann, Stefan; Percan, Yvonne; Lang, Ulrich

2015-01-01

Reconstruction of 2-d image primitives or of 3-d volumetric primitives is one of the most common operations performed by the rendering components of modern visualization systems. Because this operation is often aided by GPUs, reconstruction is typically restricted to first-order interpolation. With the advent of in situ visualization, the assumption that rendering algorithms are in general executed on GPUs is however no longer adequate. We thus propose a framework that provides versatile texture filtering capabilities: up to third-order reconstruction using various types of cubic filtering and interpolation primitives; cache-optimized algorithms that integrate seamlessly with GPGPU rendering or with software rendering that was optimized for cache-friendly "Structure of Array" (SoA) access patterns; a memory management layer (MML) that gracefully hides the complexities of extra data copies necessary for memory access optimizations such as swizzling, for rendering on GPGPUs, or for reconstruction schemes that rely on pre-filtered data arrays. We prove the effectiveness of our software architecture by integrating it into and validating it using the open source direct volume rendering (DVR) software DeskVOX.

Y-doped Li 8ZrO 6: A Li-Ion Battery Cathode Material with High Capacity

DOE PAGES

Huang, Shuping; Wilson, Benjamin E.; Wang, Bo; ...

2015-08-11

We study—experimentally and theoretically—the energetics, structural changes, and charge flows during the charging and discharging processes for a new high-capacity cathode material, Li 8ZrO 6 (LZO), which we study both pure and yttrium-doped. We quantum mechanically calculated the stable delithiated configurations, the delithiation energy, the charge flow during delithiation, and the stability of the delithiated materials. We find that Li atoms are easier to extract from tetrahedral sites than octahedral ones. We calculate a large average voltage of 4.04 eV vs Li/Li + for delithiation of the first Li atom in a primitive cell, which is confirmed by galvanostatic charge/dischargemore » cycling data. Energy calculations indicate that topotactic delithiation is kinetically favored over decomposition into Li, ZrO 2, and O 2 during the charging process, although the thermodynamic energy of the topotactic reaction is less favorable. When one or two lithium atoms are extracted from a primitive cell of LZO, its volume and structure change little, whereas extraction of the third lithium greatly distorts the layered structure. The Li 6ZrO 6 and Li 5ZrO 6 delithiation products can be thermodynamically metastable to release of O 2. Experimentally, materials with sufficiently small particle size for efficient delithiation and relithiation were achieved within an yttrium-doped LZO/carbon composite cathode that exhibited an initial discharge capacity of at least 200 mAh/g over the first 10 cycles, with 142 mAh/g maintained after 60 cycles. Computations predict that during the charging process, the oxygen ion near the Li vacancy is oxidized for both pure LZO and yttrium-doped LZO, which leads to a small-polaron hole.« less

Y-doped Li 8ZrO 6: A Li-Ion Battery Cathode Material with High Capacity

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

Huang, Shuping; Wilson, Benjamin E.; Wang, Bo

We study—experimentally and theoretically—the energetics, structural changes, and charge flows during the charging and discharging processes for a new high-capacity cathode material, Li 8ZrO 6 (LZO), which we study both pure and yttrium-doped. We quantum mechanically calculated the stable delithiated configurations, the delithiation energy, the charge flow during delithiation, and the stability of the delithiated materials. We find that Li atoms are easier to extract from tetrahedral sites than octahedral ones. We calculate a large average voltage of 4.04 eV vs Li/Li + for delithiation of the first Li atom in a primitive cell, which is confirmed by galvanostatic charge/dischargemore » cycling data. Energy calculations indicate that topotactic delithiation is kinetically favored over decomposition into Li, ZrO 2, and O 2 during the charging process, although the thermodynamic energy of the topotactic reaction is less favorable. When one or two lithium atoms are extracted from a primitive cell of LZO, its volume and structure change little, whereas extraction of the third lithium greatly distorts the layered structure. The Li 6ZrO 6 and Li 5ZrO 6 delithiation products can be thermodynamically metastable to release of O 2. Experimentally, materials with sufficiently small particle size for efficient delithiation and relithiation were achieved within an yttrium-doped LZO/carbon composite cathode that exhibited an initial discharge capacity of at least 200 mAh/g over the first 10 cycles, with 142 mAh/g maintained after 60 cycles. Computations predict that during the charging process, the oxygen ion near the Li vacancy is oxidized for both pure LZO and yttrium-doped LZO, which leads to a small-polaron hole.« less

Morphology of isolated mouse inner cell masses developing in vitro

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

Wiley, L.M.; Spindle, A.I.; Pedersen, R.A.

1978-01-01

The purpose of this study was to examine the developmental capacity of the mouse inner cell mass (ICM) in the absence of the trophoblast. ICMs were isolated from blastocysts by immunosurgery and cultured under conditions that support egg cylinder formation by intact blastocysts. After 2 or 3 days of culture, the ICMs consisted of an outer layer of endoderm and an inner layer of ectoderm that had cavitated centrally. By 4 or 5 days of culture, 25 to 60% of these ICMs had developed into paired cysts, apparently by secondary cavity formation. The inner cell layer surrounding this secondary cavitymore » resembled the extraembryonic ectoderm of cultured egg cylinders. By 6 days of culture, 60% of the ICMs had expanded into yolk sac-like structures that subsequently produced capillaries containing blood cells. The ICMs appeared to develop mesoderm in two distinct ways. A few of them developed mesoderm as a third layer of cells in the cleft separating endoderm and ectoderm, presumably by migrating from the inner, ectodermal layer, through the primitive streak, as in the intact egg cylinder. In the rest of the ICMs the embryonic ectoderm gradually differentiated into mesoderm while still in the inner layer, without primitive streak formation. We suggest, therefore, that the continuous presence of the trophoblast or of its derivatives is not required for the cytodifferentiation of mesoderm although it may be important in establishing embryonic polarity or in providinginductive signals necessary for the morphogenetic aspects of mesoderm differentiation, specifically primitive streak formation.« less

The ECM moves during primitive streak formation--computation of ECM versus cellular motion.

PubMed

Zamir, Evan A; Rongish, Brenda J; Little, Charles D

2008-10-14

Galileo described the concept of motion relativity--motion with respect to a reference frame--in 1632. He noted that a person below deck would be unable to discern whether the boat was moving. Embryologists, while recognizing that embryonic tissues undergo large-scale deformations, have failed to account for relative motion when analyzing cell motility data. A century of scientific articles has advanced the concept that embryonic cells move ("migrate") in an autonomous fashion such that, as time progresses, the cells and their progeny assemble an embryo. In sharp contrast, the motion of the surrounding extracellular matrix scaffold has been largely ignored/overlooked. We developed computational/optical methods that measure the extent embryonic cells move relative to the extracellular matrix. Our time-lapse data show that epiblastic cells largely move in concert with a sub-epiblastic extracellular matrix during stages 2 and 3 in primitive streak quail embryos. In other words, there is little cellular motion relative to the extracellular matrix scaffold--both components move together as a tissue. The extracellular matrix displacements exhibit bilateral vortical motion, convergence to the midline, and extension along the presumptive vertebral axis--all patterns previously attributed solely to cellular "migration." Our time-resolved data pose new challenges for understanding how extracellular chemical (morphogen) gradients, widely hypothesized to guide cellular trajectories at early gastrulation stages, are maintained in this dynamic extracellular environment. We conclude that models describing primitive streak cellular guidance mechanisms must be able to account for sub-epiblastic extracellular matrix displacements.

The neonatal marmoset monkey ovary is very primitive exhibiting many oogonia

PubMed Central

Fereydouni, B; Drummer, C; Aeckerle, N; Schlatt, S; Behr, R

2014-01-01

Oogonia are characterized by diploidy and mitotic proliferation. Human and mouse oogonia express several factors such as OCT4, which are characteristic of pluripotent cells. In human, almost all oogonia enter meiosis between weeks 9 and 22 of prenatal development or undergo mitotic arrest and subsequent elimination from the ovary. As a consequence, neonatal human ovaries generally lack oogonia. The same was found in neonatal ovaries of the rhesus monkey, a representative of the old world monkeys (Catarrhini). By contrast, proliferating oogonia were found in adult prosimians (now called Strepsirrhini), which is a group of ‘lower’ primates. The common marmoset monkey (Callithrix jacchus) belongs to the new world monkeys (Platyrrhini) and is increasingly used in reproductive biology and stem cell research. However, ovarian development in the marmoset monkey has not been widely investigated. Herein, we show that the neonatal marmoset ovary has an extremely immature histological appearance compared with the human ovary. It contains numerous oogonia expressing the pluripotency factors OCT4A, SALL4, and LIN28A (LIN28). The pluripotency factor-positive germ cells also express the proliferation marker MKI67 (Ki-67), which has previously been shown in the human ovary to be restricted to premeiotic germ cells. Together, the data demonstrate the primitiveness of the neonatal marmoset ovary compared with human. This study may introduce the marmoset monkey as a non-human primate model to experimentally study the aspects of primate primitive gonad development, follicle assembly, and germ cell biology in vivo. PMID:24840529

All of the human beta-type globin genes compete for LCR enhancer activity in embryonic erythroid cells of yeast artificial chromosome transgenic mice.

PubMed

Okamura, Eiichi; Matsuzaki, Hitomi; Campbell, Andrew D; Engel, James Douglas; Fukamizu, Akiyoshi; Tanimoto, Keiji

2009-12-01

In primitive erythroid cells of human beta-globin locus transgenic mice (TgM), the locus control region (LCR)-proximal epsilon- and gamma-globin genes are transcribed, whereas the distal delta- and beta-globin genes are silent. It is generally accepted that the beta-globin gene is competitively suppressed by gamma-globin gene expression at this developmental stage. Previously, however, we observed that epsilon-globin gene expression was severely attenuated when its distance from the LCR was extended, implying that beta-globin gene might also be silenced because of its great distance from the LCR. Here, to clarify the beta-globin gene silencing mechanism, we established TgM lines carrying either gamma- or epsilon- plus gamma-globin promoter deletions, without significantly altering the distance between the beta-globin gene and the LCR. Precocious expression of delta- and beta-globin genes was observed in primitive erythroid cells of mutant, but not wild-type TgM, which was most evident when both the epsilon and gamma promoters were deleted. Thus, we clearly demonstrated that the repression of the delta- and beta-globin genes in primitive erythroid cells is dominated by competitive silencing by the epsilon- and gamma-globin gene promoters, and that epsilon- and the other beta-like globin genes might be activated by two distinct mechanisms by the LCR.

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

PubMed Central

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

2011-01-01

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

Human primitive brain displays negative mitochondrial-nuclear expression correlation of respiratory genes.

PubMed

Barshad, Gilad; Blumberg, Amit; Cohen, Tal; Mishmar, Dan

2018-06-14

Oxidative phosphorylation (OXPHOS), a fundamental energy source in all human tissues, requires interactions between mitochondrial (mtDNA)- and nuclear (nDNA)-encoded protein subunits. Although such interactions are fundamental to OXPHOS, bi-genomic coregulation is poorly understood. To address this question, we analyzed ∼8500 RNA-seq experiments from 48 human body sites. Despite well-known variation in mitochondrial activity, quantity, and morphology, we found overall positive mtDNA-nDNA OXPHOS genes' co-expression across human tissues. Nevertheless, negative mtDNA-nDNA gene expression correlation was identified in the hypothalamus, basal ganglia, and amygdala (subcortical brain regions, collectively termed the "primitive" brain). Single-cell RNA-seq analysis of mouse and human brains revealed that this phenomenon is evolutionarily conserved, and both are influenced by brain cell types (involving excitatory/inhibitory neurons and nonneuronal cells) and by their spatial brain location. As the "primitive" brain is highly oxidative, we hypothesized that such negative mtDNA-nDNA co-expression likely controls for the high mtDNA transcript levels, which enforce tight OXPHOS regulation, rather than rewiring toward glycolysis. Accordingly, we found "primitive" brain-specific up-regulation of lactate dehydrogenase B ( LDHB ), which associates with high OXPHOS activity, at the expense of LDHA , which promotes glycolysis. Analyses of co-expression, DNase-seq, and ChIP-seq experiments revealed candidate RNA-binding proteins and CEBPB as the best regulatory candidates to explain these phenomena. Finally, cross-tissue expression analysis unearthed tissue-dependent splice variants and OXPHOS subunit paralogs and allowed revising the list of canonical OXPHOS transcripts. Taken together, our analysis provides a comprehensive view of mito-nuclear gene co-expression across human tissues and provides overall insights into the bi-genomic regulation of mitochondrial activities. © 2018 Barshad et al.; Published by Cold Spring Harbor Laboratory Press.

Ambient occlusion effects for combined volumes and tubular geometry.

PubMed

Schott, Mathias; Martin, Tobias; Grosset, A V Pascal; Smith, Sean T; Hansen, Charles D

2013-06-01

This paper details a method for interactive direct volume rendering that computes ambient occlusion effects for visualizations that combine both volumetric and geometric primitives, specifically tube-shaped geometric objects representing streamlines, magnetic field lines or DTI fiber tracts. The algorithm extends the recently presented the directional occlusion shading model to allow the rendering of those geometric shapes in combination with a context providing 3D volume, considering mutual occlusion between structures represented by a volume or geometry. Stream tube geometries are computed using an effective spline-based interpolation and approximation scheme that avoids self-intersection and maintains coherent orientation of the stream tube segments to avoid surface deforming twists. Furthermore, strategies to reduce the geometric and specular aliasing of the stream tubes are discussed.

Ambient Occlusion Effects for Combined Volumes and Tubular Geometry

PubMed Central

Schott, Mathias; Martin, Tobias; Grosset, A.V. Pascal; Smith, Sean T.; Hansen, Charles D.

2013-01-01

This paper details a method for interactive direct volume rendering that computes ambient occlusion effects for visualizations that combine both volumetric and geometric primitives, specifically tube-shaped geometric objects representing streamlines, magnetic field lines or DTI fiber tracts. The algorithm extends the recently presented the directional occlusion shading model to allow the rendering of those geometric shapes in combination with a context providing 3D volume, considering mutual occlusion between structures represented by a volume or geometry. Stream tube geometries are computed using an effective spline-based interpolation and approximation scheme that avoids self-intersection and maintains coherent orientation of the stream tube segments to avoid surface deforming twists. Furthermore, strategies to reduce the geometric and specular aliasing of the stream tubes are discussed. PMID:23559506

The birth of embryonic pluripotency

PubMed Central

Boroviak, Thorsten; Nichols, Jennifer

2014-01-01

Formation of a eutherian mammal requires concurrent establishment of embryonic and extraembryonic lineages. The functions of the trophectoderm and primitive endoderm are to enable implantation in the maternal uterus, axis specification and delivery of nutrients. The pluripotent epiblast represents the founding cell population of the embryo proper, which is protected from ectopic and premature differentiation until it is required to respond to inductive cues to form the fetus. While positional information plays a major role in specifying the trophoblast lineage, segregation of primitive endoderm from epiblast depends upon gradual acquisition of transcriptional identity, directed but not initiated by fibroblast growth factor (FGF) signalling. Following early cleavage divisions and formation of the blastocyst, cells of the inner cell mass lose totipotency. Developing epiblast cells transiently attain the state of naive pluripotency and competence to self-renew in vitro as embryonic stem cells and in vivo by means of diapause. This property is lost after implantation as the epiblast epithelializes and becomes primed in preparation for gastrulation and subsequent organogenesis. PMID:25349450

The Modern Primitives: Applying New Technological Approaches to Explore the Biology of the Earliest Red Blood Cells

PubMed Central

Fraser, Stuart T.

2013-01-01

One of the most critical stages in mammalian embryogenesis is the independent production of the embryo's own circulating, functional red blood cells. Correspondingly, erythrocytes are the first cell type to become functionally mature during embryogenesis. Failure to achieve this invariably leads to in utero lethality. The recent application of technologies such as transcriptome analysis, flow cytometry, mutant embryo analysis, and transgenic fluorescent gene expression reporter systems has shed new light on the distinct erythroid lineages that arise early in development. Here, I will describe the similarities and differences between the distinct erythroid populations that must form for the embryo to survive. While much of the focus of this review will be the poorly understood primitive erythroid lineage, a discussion of other erythroid and hematopoietic lineages, as well as the cell types making up the different niches that give rise to these lineages, is essential for presenting an appropriate developmental context of these cells. PMID:24222861

Primitive control of cellular metabolism

NASA Technical Reports Server (NTRS)

Mitz, M. A.

1974-01-01

It is pointed out that control substances must have existed from the earliest times in the evolution of life and that the same control mechanisms must exist today. The investigation reported is concerned with the concept that carbon dioxide is a primitive regulator of cell function. The effects of carbon dioxide on cellular materials are examined, taking into account questions of solubilization, dissociation, changes of charge, stabilization, structural changes, wettability, the exclusion of other gases, the activation of compounds, changes in plasticity, and changes in membrane permeability.

Friend of GATA (FOG) Interacts with the Nucleosome Remodeling and Deacetylase Complex (NuRD) to Support Primitive Erythropoiesis in Xenopus laevis

PubMed Central

Mimoto, Mizuho S.; Christian, Jan L.

2012-01-01

Friend of GATA (FOG) plays many diverse roles in adult and embryonic hematopoiesis, however the mechanisms by which it functions and the roles of potential interaction partners are not completely understood. Previous work has shown that overexpression of FOG in Xenopus laevis causes loss of blood suggesting that in contrast to its role in mammals, FOG might normally function to repress erythropoiesis in this species. Using loss-of-function analysis, we demonstrate that FOG is essential to support primitive red blood cell (RBC) development in Xenopus. Moreover, we show that it is specifically required to prevent excess apoptosis of circulating primitive RBCs and that in the absence of FOG, the pro-apoptotic gene Bim-1 is strongly upregulated. To identify domains of FOG that are essential for blood development and, conversely, to begin to understand the mechanism by which overexpressed FOG represses primitive erythropoiesis, we asked whether FOG mutants that are unable to interact with known co-factors retain their ability to rescue blood formation in FOG morphants and whether they repress erythropoiesis when overexpressed in wild type embryos. We find that interaction of FOG with the Nucleosome Remodeling and Deacetylase complex (NuRD), but not with C-terminal Binding Protein, is essential for normal primitive RBC development. In contrast, overexpression of all mutant and wild type constructs causes a comparable repression of primitive erythropoiesis. Together, our data suggest that a requirement for FOG and its interaction with NuRD during primitive erythropoiesis are conserved in Xenopus and that loss of blood upon FOG overexpression is due to a dominant-interfering effect. PMID:22235346

Oparin's coacervates as an important milestone in chemical evolution

NASA Astrophysics Data System (ADS)

Kolb, Vera M.

2015-09-01

Although Oparin's coacervate model for the origin of life by chemical evolution is almost 100 years old, it is still valid. However, the structure of his originally proposed coacervate is not considered prebiotic, based on some recent developments in prebiotic chemistry. We have remedied this deficiency of the Oparin's model, by substituting his coacervate with a prebiotically feasible one. Oparin's coacervates are aqueous structures, but have a boundary with the rest of the aqueous medium. They exhibit properties of self-replication, and provide a path to a primitive metabolism, via chemical competition and thus a primitive selection. Thus, coacervates are good models for proto-cells. We review here some salient points of Oparin's model and address also some philosophical views on the beginning of natural selection in primitive chemical systems.

Characterization of Epithelial Progenitors in Normal Human Palatine Tonsils and Their HPV16 E6/E7-Induced Perturbation

PubMed Central

Kang, Sung Yoon Catherine; Kannan, Nagarajan; Zhang, Lewei; Martinez, Victor; Rosin, Miriam P.; Eaves, Connie J.

2015-01-01

Summary Human palatine tonsils are oropharyngeal lymphoid tissues containing multiple invaginations (crypts) in which the continuity of the outer surface epithelium is disrupted and the isolated epithelial cells intermingle with other cell types. We now show that primitive epithelial cells detectable in vitro in 2D colony assays and in a 3D culture system are CD44+NGFR+ and present in both surface and crypt regions. Transcriptome analysis indicated a high similarity between CD44+NGFR+ cells in both regions, although those isolated from the crypt contained a higher proportion of the most primitive (holo)clonogenic cells. Lentiviral transduction of CD44+NGFR+ cells from both regions with human papillomavirus 16-encoded E6/E7 prolonged their growth in 2D cultures and caused aberrant differentiation in 3D cultures. Our findings therefore reveal a shared, site-independent, hierarchical organization, differentiation potential, and transcriptional profile of normal human tonsillar epithelial progenitor cells. They also introduce a new model for investigating the mechanisms of their transformation. PMID:26527383

Reversible grasp reflexes in normal pressure hydrocephalus.

PubMed

Thomas, Rhys H; Bennetto, Luke; Silva, Mark T

2009-05-01

We present two cases of normal pressure hydrocephalus in combination with grasp reflexes. In both cases the grasp reflexes disappeared following high volume cerebrospinal fluid removal. In one of the cases the grasp reflexes returned over a period of weeks but again resolved following definitive cerebrospinal fluid shunting surgery, and remained absent until final follow up at 9 months. We hypothesise that resolving grasp reflexes following high volume CSF removal has both diagnostic and prognostic value in normal pressure hydrocephalus, encouraging larger studies on the relevance of primitive reflexes in NPH.

Innovative Science and Technology (IST) in Support of SDI (Strategic Defense Initiative) BM/C3 (Battle Management/Command, Control and Communications)

DTIC Science & Technology

1988-08-01

primitive model would be unthinkable. Similarly, while human operators once made plugboard connections to complete telephone circuits for long-distance...calls, the current volume of U.S. long-distance telephone traffic could not be serviced if the entire U.S. population sat before telephone plugboards

Teleost growth factor independence (gfi) genes differentially regulate successive waves of hematopoiesis.

PubMed

Cooney, Jeffrey D; Hildick-Smith, Gordon J; Shafizadeh, Ebrahim; McBride, Paul F; Carroll, Kelli J; Anderson, Heidi; Shaw, George C; Tamplin, Owen J; Branco, Diana S; Dalton, Arthur J; Shah, Dhvanit I; Wong, Clara; Gallagher, Patrick G; Zon, Leonard I; North, Trista E; Paw, Barry H

2013-01-15

Growth Factor Independence (Gfi) transcription factors play essential roles in hematopoiesis, differentially activating and repressing transcriptional programs required for hematopoietic stem/progenitor cell (HSPC) development and lineage specification. In mammals, Gfi1a regulates hematopoietic stem cells (HSC), myeloid and lymphoid populations, while its paralog, Gfi1b, regulates HSC, megakaryocyte and erythroid development. In zebrafish, gfi1aa is essential for primitive hematopoiesis; however, little is known about the role of gfi1aa in definitive hematopoiesis or about additional gfi factors in zebrafish. Here, we report the isolation and characterization of an additional hematopoietic gfi factor, gfi1b. We show that gfi1aa and gfi1b are expressed in the primitive and definitive sites of hematopoiesis in zebrafish. Our functional analyses demonstrate that gfi1aa and gfi1b have distinct roles in regulating primitive and definitive hematopoietic progenitors, respectively. Loss of gfi1aa silences markers of early primitive progenitors, scl and gata1. Conversely, loss of gfi1b silences runx-1, c-myb, ikaros and cd41, indicating that gfi1b is required for definitive hematopoiesis. We determine the epistatic relationships between the gfi factors and key hematopoietic transcription factors, demonstrating that gfi1aa and gfi1b join lmo2, scl, runx-1 and c-myb as critical regulators of teleost HSPC. Our studies establish a comparative paradigm for the regulation of hematopoietic lineages by gfi transcription factors. Copyright © 2012 Elsevier Inc. All rights reserved.

Identification of centromere regions in chromosomes of a unicellular red alga, Cyanidioschyzon merolae.

PubMed

Kanesaki, Yu; Imamura, Sousuke; Matsuzaki, Motomichi; Tanaka, Kan

2015-05-08

To investigate the evolution of centromere architecture in plant cells, it is important to identify centromere regions of primitive algae, such as Cyanidioschyzon merolae. In a previous genome project, in silico analysis predicted an AT-rich region in each chromosome as putative centromere regions. Here, we identified a centromere position in each chromosome by ChIP-on-chip analysis using an anti-CENP-A antibody. The identified centromeres were of the regional type, about 2-3 kb in length and contained no consensus or repeat elements. Centromeres in primitive eukaryotic plant cells may have originated from these regional type centromeres. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

On cat's eyes and multiple disjoint cells natural convection flow in tall tilted cavities

NASA Astrophysics Data System (ADS)

Báez, Elsa; Nicolás, Alfredo

2014-10-01

Natural convection fluid flow in air-filled tall tilted cavities is studied numerically with a direct projection method applied on the unsteady Boussinesq approximation in primitive variables. The study is focused on the so called cat's eyes and multiple disjoint cells as the aspect ratio A and the angle of inclination ϕ of the cavity vary. Results have already been reported with primitive and stream function-vorticity variables. The former are validated with the latter ones, which in turn were validated through mesh size and time-step independence studies. The new results complemented with the previous ones lead to find out the fluid motion and heat transfer invariant properties of this thermal phenomenon, which is the novelty here.

Cellular reprogramming in skin cancer.

PubMed

Song, Ihn Young; Balmain, Allan

2015-06-01

Early primitive stem cells have long been viewed as the cancer cells of origin (tumor initiating target cells) due to their intrinsic features of self-renewal and longevity. However, emerging evidence suggests a surprising capacity for normal committed cells to function as reserve stem cells upon reprogramming as a consequence of tissue damage resulting in inflammation and wound healing. This results in an alternative concept positing that tumors may originate from differentiated cells that can re-acquire stem cell properties due to genetic or epigenetic reprogramming. It is likely that both models are correct, and that a continuum of potential cells of origin exists, ranging from early primitive stem cells to committed progenitor or even terminally differentiated cells. A combination of the nature of the target cell and the specific types of gene mutations introduced determine tumor cell lineage, as well as potential for malignant conversion. Evidence from mouse skin models of carcinogenesis suggests that initiated cells at different stages within a stem cell hierarchy have varying degrees of requirement for reprogramming (e.g. inflammation stimuli), depending on their degree of differentiation. This article will present evidence in favor of these concepts that has been developed from studies of several mouse models of skin carcinogenesis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Probabilistic Modeling of Ceramic Matrix Composite Strength

NASA Technical Reports Server (NTRS)

Shan, Ashwin R.; Murthy, Pappu L. N.; Mital, Subodh K.; Bhatt, Ramakrishna T.

1998-01-01

Uncertainties associated with the primitive random variables such as manufacturing process (processing temperature, fiber volume ratio, void volume ratio), constituent properties (fiber, matrix and interface), and geometric parameters (ply thickness, interphase thickness) have been simulated to quantify the scatter in the first matrix cracking strength (FMCS) and the ultimate tensile strength of SCS-6/RBSN (SiC fiber (SCS-6) reinforced reaction-bonded silicon nitride composite) ceramic matrix composite laminate at room temperature. Cumulative probability distribution function for the FMCS and ultimate tensile strength at room temperature (RT) of (0)(sub 8), (0(sub 2)/90(sub 2), and (+/-45(sub 2))(sub S) laminates have been simulated and the sensitivity of primitive variables to the respective strengths have been quantified. Computationally predicted scatter of the strengths for a uniaxial laminate have been compared with those from limited experimental data. Also the experimental procedure used in the tests has been described briefly. Results show a very good agreement between the computational simulation and the experimental data. Dominating failure modes in (0)(sub 8), (0/90)(sub s) and (+/-45)(sub S) laminates have been identified. Results indicate that the first matrix cracking strength for the (0)(sub S), and (0/90)(sub S) laminates is sensitive to the thermal properties, modulus and strengths of both the fiber and matrix whereas the ultimate tensile strength is sensitive to the fiber strength and the fiber volume ratio. In the case of a (+/-45)(sub S), laminate, both the FMCS and the ultimate tensile strengths have a small scatter range and are sensitive to the fiber tensile strength as well as the fiber volume ratio.

Computational investigations of the band structure, and thermodynamic and optical features of thorium-based oxide ThGeO4 using the full-potential linearized augmented plane-wave plus local orbital approach

NASA Astrophysics Data System (ADS)

Chiker, F.; Khachai, H.; Mathieu, C.; Bin-Omran, S.; Kada, Belkacem; Sun, Xiao-Wei; Sandeep; Rai, D. P.; Khenata, R.

2018-05-01

In this study, first-principles investigations were performed using the full-potential linearized augmented plane-wave method of the structural and optoelectronic properties of thorium germinate (ThGeO4), a high-K dielectric material. Under ambient conditions, the structural properties calculated for ThGeO4 in the zircon phase were in excellent agreement with the available experimental data. Furthermore, using the modified Becke -Johnson correction method, the calculated band gaps and optical constants accurately described this compound. Finally, the thermal properties were predicted over a temperature range of 0-700 K and pressures up to 11 GPa using the quasi-harmonic Debye model, where the variations in the heat capacity, primitive cell volume, and thermal expansion coefficients were determined successfully.

The terminal area simulation system. Volume 1: Theoretical formulation

NASA Technical Reports Server (NTRS)

Proctor, F. H.

1987-01-01

A three-dimensional numerical cloud model was developed for the general purpose of studying convective phenomena. The model utilizes a time splitting integration procedure in the numerical solution of the compressible nonhydrostatic primitive equations. Turbulence closure is achieved by a conventional first-order diagnostic approximation. Open lateral boundaries are incorporated which minimize wave reflection and which do not induce domain-wide mass trends. Microphysical processes are governed by prognostic equations for potential temperature water vapor, cloud droplets, ice crystals, rain, snow, and hail. Microphysical interactions are computed by numerous Orville-type parameterizations. A diagnostic surface boundary layer is parameterized assuming Monin-Obukhov similarity theory. The governing equation set is approximated on a staggered three-dimensional grid with quadratic-conservative central space differencing. Time differencing is approximated by the second-order Adams-Bashforth method. The vertical grid spacing may be either linear or stretched. The model domain may translate along with a convective cell, even at variable speeds.

Shortest multiple disconnected path for the analysis of entanglements in two- and three-dimensional polymeric systems

NASA Astrophysics Data System (ADS)

Kröger, Martin

2005-06-01

We present an algorithm which returns a shortest path and related number of entanglements for a given configuration of a polymeric system in 2 or 3 dimensions. Rubinstein and Helfand, and later Everaers et al. introduced a concept to extract primitive paths for dense polymeric melts made of linear chains (a multiple disconnected multibead 'path'), where each primitive path is defined as a path connecting the (space-fixed) ends of a polymer under the constraint of non-interpenetration (excluded volume) between primitive paths of different chains, such that the multiple disconnected path fulfills a minimization criterion. The present algorithm uses geometrical operations and provides a—model independent—efficient approximate solution to this challenging problem. Primitive paths are treated as 'infinitely' thin (we further allow for finite thickness to model excluded volume), and tensionless lines rather than multibead chains, excluded volume is taken into account without a force law. The present implementation allows to construct a shortest multiple disconnected path (SP) for 2D systems (polymeric chain within spherical obstacles) and an optimal SP for 3D systems (collection of polymeric chains). The number of entanglements is then simply obtained from the SP as either the number of interior kinks, or from the average length of a line segment. Further, information about structure and potentially also the dynamics of entanglements is immediately available from the SP. We apply the method to study the 'concentration' dependence of the degree of entanglement in phantom chain systems. Program summaryTitle of program:Z Catalogue number:ADVG Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADVG Program obtainable from: CPC Program Library, Queen's University of Belfast, N. Ireland Computer for which the program is designed and others on which it has been tested: Silicon Graphics (Irix), Sun (Solaris), PC (Linux) Operating systems or monitors under which the program has been tested: UNIX, Linux Program language used: USANSI Fortran 77 and Fortran 90 Memory required to execute with typical data: 1 MByte No. of lines in distributed program, including test data, etc.: 10 660 No. of bytes in distributed program, including test data, etc.: 119 551 Distribution formet:tar.gz Nature of physical problem: The problem is to obtain primitive paths substantiating a shortest multiple disconnected path (SP) for a given polymer configuration (chains of particles, with or without additional single particles as obstacles for the 2D case). Primitive paths are here defined as in [M. Rubinstein, E. Helfand, J. Chem. Phys. 82 (1985) 2477; R. Everaers, S.K. Sukumaran, G.S. Grest, C. Svaneborg, A. Sivasubramanian, K. Kremer, Science 303 (2004) 823] as the shortest line (path) respecting 'topological' constraints (from neighboring polymers or point obstacles) between ends of polymers. There is a unique solution for the 2D case. For the 3D case it is unique if we construct a primitive path of a single chain embedded within fixed line obstacles [J.S.B. Mitchell, Geometric shortest paths and network optimization, in: J.-R. Sack, J. Urrutia (Eds.), Handbook of Computational Geometry, Elsevier, Amsterdam, 2000, pp. 633-701]. For a large 3D configuration made of several chains, short is meant to be the Euclidean shortest multiple disconnected path (SP) where primitive paths are constructed for all chains simultaneously. While the latter problem, in general, does not possess a unique solution, the algorithm must return a locally optimal solution, robust against minor displacements of the disconnected path and chain re-labeling. The problem is solved if the number of kinks (or entanglements Z), explicitly deduced from the SP, is quite insensitive to the exact conformation of the SP which allows to estimate Z with a small error. Efficient method of solution: Primitive paths are constructed from the given polymer configuration (a non-shortest multiple disconnected path, including obstacles, if present) by first replacing each polymer contour by a line with a number of 'kinks' (beads, nodes) and 'segments' (edges). To obtain primitive paths, defined to be uncrossable by any other objects (neighboring primitive paths, line or point obstacles), the algorithm minimizes the length of all primitive paths consecutively, until a final minimum Euclidean length of the SP is reached. Fast geometric operations rather than dynamical methods are used to minimize the contour lengths of the primitive paths. Neighbor lists are used to keep track of potentially intersecting segments of other chains. Periodic boundary conditions are employed. A finite small line thickness is used in order to make sure that entanglements are not 'lost' due to finite precision of representation of numbers. Restrictions on the complexity of the problem: For a single chain embedded within fixed line or point obstacles, the algorithm returns the exact SP. For more complex problems, the algorithm returns a locally optimal SP. Except for exotic, probably rare, configurations it turns out that different locally optimal SPs possess quite an identical number of nodes. In general, the problem constructing the SP is known to be NP-hard [J.S.B. Mitchell, Geometric shortest paths and network optimization, in: J.-R. Sack, J. Urrutia (Eds.), Handbook of Computational Geometry, Elsevier, Amsterdam, 2000, pp. 633-701], and we offer a solution which should suffice to analyze physical problems, and gives an estimate about the precision and uniqueness of the result (from a standard deviation by varying the parameter: cyclicswitch). The program is NOT restricted to handle systems for which segment lengths of the SP exceed half the box size. Typical running time: Typical running times are approximately two orders of magnitude shorter compared with the ones needed for a corresponding molecular dynamics approach, and scale mostly linearly with system size. We provide a benchmark table.

A recursive vesicle-based model protocell with a primitive model cell cycle

NASA Astrophysics Data System (ADS)

Kurihara, Kensuke; Okura, Yusaku; Matsuo, Muneyuki; Toyota, Taro; Suzuki, Kentaro; Sugawara, Tadashi

2015-09-01

Self-organized lipid structures (protocells) have been proposed as an intermediate between nonliving material and cellular life. Synthetic production of model protocells can demonstrate the potential processes by which living cells first arose. While we have previously described a giant vesicle (GV)-based model protocell in which amplification of DNA was linked to self-reproduction, the ability of a protocell to recursively self-proliferate for multiple generations has not been demonstrated. Here we show that newborn daughter GVs can be restored to the status of their parental GVs by pH-induced vesicular fusion of daughter GVs with conveyer GVs filled with depleted substrates. We describe a primitive model cell cycle comprising four discrete phases (ingestion, replication, maturity and division), each of which is selectively activated by a specific external stimulus. The production of recursive self-proliferating model protocells represents a step towards eventual production of model protocells that are able to mimic evolution.

Correct Patterning of the Primitive Streak Requires the Anterior Visceral Endoderm

PubMed Central

Stuckey, Daniel W.; Di Gregorio, Aida; Clements, Melanie; Rodriguez, Tristan A.

2011-01-01

Anterior-posterior axis specification in the mouse requires signalling from a specialised extra-embryonic tissue called the anterior visceral endoderm (AVE). AVE precursors are induced at the distal tip of the embryo and move to the prospective anterior. Embryological and genetic analysis has demonstrated that the AVE is required for anterior patterning and for correctly positioning the site of primitive streak formation by inhibiting Nodal activity. We have carried out a genetic ablation of the Hex-expressing cells of the AVE (Hex-AVE) by knocking the Diphtheria toxin subunit A into the Hex locus in an inducible manner. Using this model we have identified that, in addition to its requirement in the anterior of the embryo, the Hex-AVE sub-population has a novel role between 5.5 and 6.5dpc in patterning the primitive streak. Embryos lacking the Hex-AVE display delayed initiation of primitive streak formation and miss-patterning of the anterior primitive streak. We demonstrate that in the absence of the Hex-AVE the restriction of Bmp2 expression to the proximal visceral endoderm is also defective and expression of Wnt3 and Nodal is not correctly restricted to the posterior epiblast. These results, coupled with the observation that reducing Nodal signalling in Hex-AVE ablated embryos increases the frequency of phenotypes observed, suggests that these primitive streak patterning defects are due to defective Nodal signalling. Together, our experiments demonstrate that the AVE is not only required for anterior patterning, but also that specific sub-populations of this tissue are required to pattern the posterior of the embryo. PMID:21445260

THE CELLULAR ORIGIN OF HUMAN IMMUNOGLOBULINS (γ2, γ1M, γ1A)

PubMed Central

Mellors, Robert C.; Korngold, Leonhard

1963-01-01

A study was made of the cellular origin of human immunoglobulins (γ2, γ1M, γ1A). The results indicated that two closely related families of cells form immunoglobulins in human lymphoid tissue: germinal (reticular) centers and plasma cells. Thus their cellular origin in addition to their known antigenic relations further justifies placing the immunoglobulins in one family of proteins. Immunoglobulins were also formed to a small extent in primitive reticular cells which resembled those of germinal centers but were separated from them. Possibly such cells were undergoing transition to the much more numerous plasma cells with which they were commonly associated. The mantles of small lymphocytes which surrounded germinal centers did not contain detectable quantities of immunoglobulins. While in general only one type of immunoglobulin was present in an individual cell or germinal center, γ2- and γ1M-globulin were identified on occasion in the same plasma cell and germinal center. A peculiarity of the fetal thymus gland was the presence of immunoglobulin, mainly γ1M, in a small number of cells of small and intermediate size and primitive reticular appearance and in Hassall's corpuscles. PMID:14077999

Self-organization of neural tissue architectures from pluripotent stem cells.

PubMed

Karus, Michael; Blaess, Sandra; Brüstle, Oliver

2014-08-15

Despite being a subject of intensive research, the mechanisms underlying the formation of neural tissue architectures during development of the central nervous system remain largely enigmatic. So far, studies into neural pattern formation have been restricted mainly to animal experiments. With the advent of pluripotent stem cells it has become possible to explore early steps of nervous system development in vitro. These studies have unraveled a remarkable propensity of primitive neural cells to self-organize into primitive patterns such as neural tube-like rosettes in vitro. Data from more advanced 3D culture systems indicate that this intrinsic propensity for self-organization can even extend to the formation of complex architectures such as a multilayered cortical neuroepithelium or an entire optic cup. These novel experimental paradigms not only demonstrate the enormous self-organization capacity of neural stem cells, they also provide exciting prospects for studying the earliest steps of human neural tissue development and the pathogenesis of brain malformations in reductionist in vitro paradigms. © 2014 Wiley Periodicals, Inc.

A Quantitative Proteomic Analysis of Hemogenic Endothelium Reveals Differential Regulation of Hematopoiesis by SOX17

PubMed Central

Clarke, Raedun L.; Robitaille, Aaron M.; Moon, Randall T.; Keller, Gordon

2015-01-01

Summary The in vitro derivation of hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) is complicated by the existence of multiple overlapping embryonic blood cell programs called primitive, erythromyeloid progenitor (EMP), and definitive. As HSCs are only generated during the definitive stage of hematopoiesis, deciphering the regulatory pathways that control the emergence of this program and identifying markers that distinguish it from the other programs are essential. To identify definitive specific pathways and marker sets, we used label-free proteomics to determine the proteome of embryo-derived and mouse embryonic stem cell-derived VE-CADHERIN+CD45− definitive hematopoietic progenitors. With this approach, we identified Stat1 as a marker that distinguishes the definitive erythroid lineage from the primitive- and EMP-derived lineages. Additionally, we provide evidence that the generation of the Stat1+ definitive lineage is dependent on Sox17. These findings establish an approach for monitoring the emergence of definitive hematopoiesis in the PSC differentiation cultures. PMID:26267830

Congenital Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumor: A Case Report and Review of the Literature.

PubMed

Jin, Shu-Guang; Jiang, Xiao-Ping; Zhong, Lin

2016-10-01

Ewing's sarcoma (EWS) and peripheral primitive neuroectodermal tumor (pPNET) are small round cell malignancies that develop in soft tissue and bone. They very rarely affect newborns. A diagnosis of EWS/pPNET depends mainly on immunohistochemistry and molecular/genetic assays. Since these tumors are highly aggressive, patient prognosis is typically very poor, and treatment remains a challenge. Here, we report a 13-day-old newborn diagnosed with congenital EWS/pPNET and describe its treatment. Copyright © 2014. Published by Elsevier B.V.

p28 in Treating Younger Patients With Recurrent or Progressive Central Nervous System Tumors

ClinicalTrials.gov

2017-08-03

Teratoid Tumor, Atypical; Choroid Plexus Neoplasms; Anaplastic Astrocytoma; Anaplastic Oligodendroglioma; Brainstem Tumors; Giant Cell Glioblastoma; Glioblastoma; Gliosarcoma; Medulloblastoma; Neuroectodermal Tumor, Primitive

Expression of hydroxyindole-O-methyltransferase enzyme in the human central nervous system and in pineal parenchymal cell tumors.

PubMed

Fukuda, Takahiro; Akiyama, Nobutake; Ikegami, Masahiro; Takahashi, Hitoshi; Sasaki, Atsushi; Oka, Hidehiro; Komori, Takashi; Tanaka, Yuko; Nakazato, Youichi; Akimoto, Jiro; Tanaka, Masahiko; Okada, Yoshikazu; Saito, Saburo

2010-05-01

Pineal parenchymal tumor (PPT) cells usually show immunoreactivity for synaptophysin, neuron-specific enolase, neurofilament protein, class III beta-tubulin, tau protein, PGP9.5, chromogranin, serotonin, retinal S-antigen, and rhodopsin, but these markers are not specific for PPTs. Melatonin is produced and secreted mainly bypineal parenchymal cells; hydroxyindole-O-methyltransferase (HIOMT) catalyzes the final reaction in melatonin biosynthesis. We hypothesized that HIOMT could serve as a tumor marker of PPTs, and we investigated HIOMT localization and HIOMT expression in samples of normal human tissue and in PPTs, primitive neuroectodermal tumors, and medulloblastomas. In normal tissue, HIOMT was expressed in retinal cells, pineal parenchymal cells, neurons of the Edinger-Westphal nucleus, microglia, macrophages, thyroid follicular epithelium, principal and oxyphil cells of parathyroid gland, adrenal cortical cells, hepatic parenchymal cells, renal tubule epithelium, and enteroendocrine cells of stomach and duodenum. The HIOMT was also expressed in all 46 PPTs studied. The proportions of HIOMT-immunoreactive cells successively decreased in the following tumors: pineocytoma, pineal parenchymal tumor of intermediate differentiation, and pineoblastoma. A few HIOMT-immunoreactive cells were observed in one of 6 primitive neuroectodermal tumors and 23 of 42 medulloblastomas. These results indicate that HIOMT immunohistochemistry may be useful for the diagnosis of PPTs and be a prognostic factor in PPTs.

Electric Double-Layer Structure in Primitive Model Electrolytes. Comparing Molecular Dynamics with Local-Density Approximations

DOE PAGES

Giera, Brian; Lawrence Livermore National Lab.; Henson, Neil; ...

2015-02-27

We evaluate the accuracy of local-density approximations (LDAs) using explicit molecular dynamics simulations of binary electrolytes comprised of equisized ions in an implicit solvent. The Bikerman LDA, which considers ions to occupy a lattice, poorly captures excluded volume interactions between primitive model ions. Instead, LDAs based on the Carnahan–Starling (CS) hard-sphere equation of state capture simulated values of ideal and excess chemical potential profiles extremely well, as is the relationship between surface charge density and electrostatic potential. Excellent agreement between the EDL capacitances predicted by CS-LDAs and computed in molecular simulations is found even in systems where ion correlations drivemore » strong density and free charge oscillations within the EDL, despite the inability of LDAs to capture the oscillations in the detailed EDL profiles.« less

Understanding Microbial Sensing in Inflammatory Bowel Disease Using Click Chemistry

DTIC Science & Technology

2017-10-01

pathogens and commensals. However, the technology available to track these molecules in host cells and tissues remains primitive. To address this...live, luminal bacteria into specific host intestinal immune cells and their subsequent degradation in host phagocytes. Notably, this approach also...click-chemistry, bacterial cell wall, bacterial outer membrane, peptidoglycan, lipopolysaccharide, endotoxin, capsular polysaccharide, inflammatory

Understanding Microbial Sensing in Inflammatory Bowel Disease Using Click Chemistry

DTIC Science & Technology

2017-10-01

both pathogens and commensals. However, the technology available to track these molecules in host cells and tissues remains primitive. To address this...from live, luminal bacteria into specific host intestinal immune cells and their subsequent degradation in host phagocytes. Notably, this approach...Bioorthogonal click-chemistry, bacterial cell wall, bacterial outer membrane, peptidoglycan, lipopolysaccharide, endotoxin, capsular polysaccharide

Septic disruption of lactiferous ducts with heterogeneous carcinoma of the breast in a lactating woman.

PubMed

Naim, Mohammed; John, Vanesa T; Gaur, Kavita; Anees, Afzal

2010-08-06

This report documents the diagnostic histopathological features of heterogeneous breast carcinoma following sepsis and disruption of the lactiferous ducts in a lactating woman and discusses the pathogenesis. Sections from the nipple revealed disrupted collecting lactiferous ducts presenting with intraduct precarcinoma and carcinoma of the epidermoid type, and attached reparative sprouts lined by lactiferous cells. Breast lobules showed generalised benign adenotic change with various foci of carcinoma microscopically identifiable as intraduct primitive lactiferal ectodermal carcinoma, lactating carcinoma, primitive neuroendocrine carcinoma and myoepithelioid granulomatous carcinoma. The findings led to the conclusion that the lactiferous ducts are susceptible to sepsis and disruption, which may predispose a patient to breast carcinoma. The pattern of carcinoma suggested that lactiferous epithelial cells behaved colonially, with different metaplastic changes, precarcinoma and carcinoma.

Adipogenic placenta-derived mesenchymal stem cells are not lineage restricted by withdrawing extrinsic factors: developing a novel visual angle in stem cell biology.

PubMed

Hu, C; Cao, H; Pan, X; Li, J; He, J; Pan, Q; Xin, J; Yu, X; Li, J; Wang, Y; Zhu, D; Li, L

2016-03-17

Current evidence implies that differentiated bone marrow mesenchymal stem cells (BMMSCs) can act as progenitor cells and transdifferentiate across lineage boundaries. However, whether this unrestricted lineage has specificities depending on the stem cell type is unknown. Placental-derived mesenchymal stem cells (PDMSCs), an easily accessible and less invasive source, are extremely useful materials in current stem cell therapies. No studies have comprehensively analyzed the transition in morphology, surface antigens, metabolism and multilineage potency of differentiated PDMSCs after their dedifferentiation. In this study, we showed that after withdrawing extrinsic factors, adipogenic PDMSCs reverted to a primitive cell population and retained stem cell characteristics. The mitochondrial network during differentiation and dedifferentiation may serve as a marker of absent or acquired pluripotency in various stem cell models. The new population proliferated faster than unmanipulated PDMSCs and could be differentiated into adipocytes, osteocytes and hepatocytes. The cell adhesion molecules (CAMs) signaling pathway and extracellular matrix (ECM) components modulate cell behavior and enable the cells to proliferate or differentiate during the differentiation, dedifferentiation and redifferentiation processes in our study. These observations indicate that the dedifferentiated PDMSCs are distinguishable from the original PDMSCs and may serve as a novel source in stem cell biology and cell-based therapeutic strategies. Furthermore, whether PDMSCs differentiated into other lineages can be dedifferentiated to a primitive cell population needs to be investigated.

Very small embryonic-like stem cells: implications in reproductive biology.

PubMed

Bhartiya, Deepa; Unni, Sreepoorna; Parte, Seema; Anand, Sandhya

2013-01-01

The most primitive germ cells in adult mammalian testis are the spermatogonial stem cells (SSCs) whereas primordial follicles (PFs) are considered the fundamental functional unit in ovary. However, this central dogma has recently been modified with the identification of a novel population of very small embryonic-like stem cells (VSELs) in the adult mammalian gonads. These stem cells are more primitive to SSCs and are also implicated during postnatal ovarian neo-oogenesis and primordial follicle assembly. VSELs are pluripotent in nature and characterized by nuclear Oct-4A, cell surface SSEA-4, and other pluripotent markers like Nanog, Sox2, and TERT. VSELs are considered to be the descendants of epiblast stem cells and possibly the primordial germ cells that persist into adulthood and undergo asymmetric cell division to replenish the gonadal germ cells throughout life. Elucidation of their role during infertility, endometrial repair, superovulation, and pathogenesis of various reproductive diseases like PCOS, endometriosis, cancer, and so on needs to be addressed. Hence, a detailed review of current understanding of VSEL biology is pertinent, which will hopefully open up new avenues for research to better understand various reproductive processes and cancers. It will also be relevant for future regenerative medicine, translational research, and clinical applications in human reproduction.

Stretching morphogenesis of the roof plate and formation of the central canal.

PubMed

Kondrychyn, Igor; Teh, Cathleen; Sin, Melvin; Korzh, Vladimir

2013-01-01

Neurulation is driven by apical constriction of actomyosin cytoskeleton resulting in conversion of the primitive lumen into the central canal in a mechanism driven by F-actin constriction, cell overcrowding and buildup of axonal tracts. The roof plate of the neural tube acts as the dorsal morphogenetic center and boundary preventing midline crossing by neural cells and axons. The roof plate zebrafish transgenics expressing cytosolic GFP were used to study and describe development of this structure in vivo for a first time ever. The conversion of the primitive lumen into the central canal causes significant morphogenetic changes of neuroepithelial cells in the dorsal neural tube. We demonstrated that the roof plate cells stretch along the D-V axis in parallel with conversion of the primitive lumen into central canal and its ventral displacement. Importantly, the stretching of the roof plate is well-coordinated along the whole spinal cord and the roof plate cells extend 3× in length to cover 2/3 of the neural tube diameter. This process involves the visco-elastic extension of the roof place cytoskeleton and depends on activity of Zic6 and the Rho-associated kinase (Rock). In contrast, stretching of the floor plate is much less extensive. The extension of the roof plate requires its attachment to the apical complex of proteins at the surface of the central canal, which depends on activity of Zic6 and Rock. The D-V extension of the roof plate may change a range and distribution of morphogens it produces. The resistance of the roof plate cytoskeleton attenuates ventral displacement of the central canal in illustration of the novel mechanical role of the roof plate during development of the body axis.

Stretching Morphogenesis of the Roof Plate and Formation of the Central Canal

PubMed Central

Kondrychyn, Igor; Teh, Cathleen; Sin, Melvin; Korzh, Vladimir

2013-01-01

Background Neurulation is driven by apical constriction of actomyosin cytoskeleton resulting in conversion of the primitive lumen into the central canal in a mechanism driven by F-actin constriction, cell overcrowding and buildup of axonal tracts. The roof plate of the neural tube acts as the dorsal morphogenetic center and boundary preventing midline crossing by neural cells and axons. Methodology/Principal Findings The roof plate zebrafish transgenics expressing cytosolic GFP were used to study and describe development of this structure in vivo for a first time ever. The conversion of the primitive lumen into the central canal causes significant morphogenetic changes of neuroepithelial cells in the dorsal neural tube. We demonstrated that the roof plate cells stretch along the D–V axis in parallel with conversion of the primitive lumen into central canal and its ventral displacement. Importantly, the stretching of the roof plate is well-coordinated along the whole spinal cord and the roof plate cells extend 3× in length to cover 2/3 of the neural tube diameter. This process involves the visco-elastic extension of the roof place cytoskeleton and depends on activity of Zic6 and the Rho-associated kinase (Rock). In contrast, stretching of the floor plate is much less extensive. Conclusions/Significance The extension of the roof plate requires its attachment to the apical complex of proteins at the surface of the central canal, which depends on activity of Zic6 and Rock. The D–V extension of the roof plate may change a range and distribution of morphogens it produces. The resistance of the roof plate cytoskeleton attenuates ventral displacement of the central canal in illustration of the novel mechanical role of the roof plate during development of the body axis. PMID:23409159

A preliminary neutron diffraction study of rasburicase, a recombinant urate oxidase enzyme, complexed with 8-azaxanthin

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

Budayova-Spano, Monika, E-mail: spano@embl-grenoble.fr; Institut Laue-Langevin, 6 Rue Jules Horowitz, BP 156, 38042 Grenoble; Bonneté, Françoise

2006-03-01

Neutron diffraction data of hydrogenated recombinant urate oxidase enzyme (Rasburicase), complexed with a purine-type inhibitor 8-azaxanthin, was collected to 2.1 Å resolution from a crystal grown in D{sub 2}O by careful control and optimization of crystallization conditions via knowledge of the phase diagram. Deuterium atoms were clearly seen in the neutron-scattering density map. Crystallization and preliminary neutron diffraction measurements of rasburicase, a recombinant urate oxidase enzyme expressed by a genetically modified Saccharomyces cerevisiae strain, complexed with a purine-type inhibitor (8-azaxanthin) are reported. Neutron Laue diffraction data were collected to 2.1 Å resolution using the LADI instrument from a crystal (grownmore » in D{sub 2}O) with volume 1.8 mm{sup 3}. The aim of this neutron diffraction study is to determine the protonation states of the inhibitor and residues within the active site. This will lead to improved comprehension of the enzymatic mechanism of this important enzyme, which is used as a protein drug to reduce toxic uric acid accumulation during chemotherapy. This paper illustrates the high quality of the neutron diffraction data collected, which are suitable for high-resolution structural analysis. In comparison with other neutron protein crystallography studies to date in which a hydrogenated protein has been used, the volume of the crystal was relatively small and yet the data still extend to high resolution. Furthermore, urate oxidase has one of the largest primitive unit-cell volumes (space group I222, unit-cell parameters a = 80, b = 96, c = 106 Å) and molecular weights (135 kDa for the homotetramer) so far successfully studied with neutrons.« less

Chemotaxis of primitive hematopoietic cells in response to stromal cell–derived factor-1

PubMed Central

Jo, Deog-Yeon; Rafii, Shahin; Hamada, Tsuneyoshi; Moore, Malcolm A.S.

2000-01-01

Stromal cell–derived factor-1 (SDF-1) provides a potent chemotactic stimulus for CD34+ hematopoietic cells. We cultured mobilized peripheral blood (PB) and umbilical cord blood (CB) for up to 5 weeks and examined the migratory activity of cobblestone area–forming cells (CAFCs) and long-term culture–initiating cells (LTC-ICs) in a transwell assay. In this system, SDF-1 or MS-5 marrow stromal cells placed in the lower chamber induced transmembrane and transendothelial migration by 2- and 5-week-old CAFCs and LTC-ICs in 3 hours. Transmigration was blocked by preincubation of input CD34+ cells with antibody to CXCR4. Transendothelial migration of CB CAFCs and LTC-ICs was higher than that of PB. We expanded CD34+ cells from CB in serum-free medium with thrombopoietin, flk-2 ligand, and c-kit ligand, with or without IL-3 and found that CAFCs cultured in the absence of IL-3 had a chemotactic response equivalent to noncultured cells, even after 5 weeks. However, addition of IL-3 to the culture reduced this response by 20–50%. These data indicate that SDF-1 induces chemotaxis of primitive hematopoietic cells signaling through CXCR4 and that the chemoattraction could be downmodulated by culture ex vivo. PMID:10619866

Structure and function of primitive immunoglobulin superfamily neural cell adhesion molecules: a lesson from studies on planarian.

PubMed

Fusaoka, Eri; Inoue, Takeshi; Mineta, Katsuhiko; Agata, Kiyokazu; Takeuchi, Kosei

2006-05-01

Precise wiring and proper remodeling of the neural network are essential for its normal function. The freshwater planarian is an attractive animal in which to study the formation and maintenance of the neural network due to its high regenerative capability and developmental plasticity. Although a recent study revealed that homologs of netrin and its receptors are required for regeneration and maintenance of the planarian central nervous system (CNS), the roles of cell adhesion in the formation and maintenance of the planarian neural network remain poorly understood. In the present study, we found primitive immunoglobulin superfamily cell adhesion molecules (IgCAMs) in a planarian that are homologous to vertebrate neural IgCAMs. We identified planarian orthologs of NCAM, L1CAM, contactin and DSCAM, and designated them DjCAM, DjLCAM, DjCTCAM and DjDSCAM, respectively. We further confirmed that they function as cell adhesion molecules using cell aggregation assays. DjCAM and DjDSCAM were found to be differentially expressed in the CNS. Functional analyses using RNA interference revealed that DjCAM is partly involved in axon formation, and that DjDSCAM plays crucial roles in neuronal cell migration, axon outgrowth, fasciculation and projection.

Acute erythremic myelosis (true erythroleukaemia): a variant of AML FAB-M6.

PubMed

Hasserjian, R P; Howard, J; Wood, A; Henry, K; Bain, B

2001-03-01

Classic erythroleukaemia (acute myeloid leukaemia M6, or M6 AML) is defined as an excess of myeloblasts in an erythroid predominant background. Leukaemia variants in which the primitive blast cells are demonstrably erythroid are extremely rare and poorly characterised. Variably referred to as "true erythroleukaemia" or "acute erythremic myelosis", they are often included within the M6 AML category even though they do not meet strict criteria for this type of AML. Two cases of acute erythroid neoplasia are presented with clinical, morphological, immunophenotypic, and cytogenetic analysis. Both patients presented with profound anaemia, one in a setting of long standing myelodysplasia. Bone marrow examination revealed a predominant population of highly dysplastic erythroid cells in both cases. In one case, the liver was infiltrated by neoplastic erythroid cells. Both patients died within four months of diagnosis. This report illustrates that cases of acute leukaemia occur in which the dominant neoplastic cell is a primitive erythroid cell without an accompanying increase in myeloblasts. This does not preclude the neoplastic clone originating in a multipotent haemopoietic stem cell, as suggested by cases arising in patients with myelodysplasia. Acute erythremic myelosis should be recognised as a distinct variant of M6 AML.

Downstream targets of HOXB4 in a cell line model of primitive hematopoietic progenitor cells.

PubMed

Lee, Han M; Zhang, Hui; Schulz, Vincent; Tuck, David P; Forget, Bernard G

2010-08-05

Enforced expression of the homeobox transcription factor HOXB4 has been shown to enhance hematopoietic stem cell self-renewal and expansion ex vivo and in vivo. To investigate the downstream targets of HOXB4 in hematopoietic progenitor cells, HOXB4 was constitutively overexpressed in the primitive hematopoietic progenitor cell line EML. Two genome-wide analytical techniques were used: RNA expression profiling using microarrays and chromatin immunoprecipitation (ChIP)-chip. RNA expression profiling revealed that 465 gene transcripts were differentially expressed in KLS (c-Kit(+), Lin(-), Sca-1(+))-EML cells that overexpressed HOXB4 (KLS-EML-HOXB4) compared with control KLS-EML cells that were transduced with vector alone. In particular, erythroid-specific gene transcripts were observed to be highly down-regulated in KLS-EML-HOXB4 cells. ChIP-chip analysis revealed that the promoter region for 1910 genes, such as CD34, Sox4, and B220, were occupied by HOXB4 in KLS-EML-HOXB4 cells. Side-by-side comparison of the ChIP-chip and RNA expression profiling datasets provided correlative information and identified Gp49a and Laptm4b as candidate "stemness-related" genes. Both genes were highly ranked in both dataset lists and have been previously shown to be preferentially expressed in hematopoietic stem cells and down-regulated in mature hematopoietic cells, thus making them attractive candidates for future functional studies in hematopoietic cells.

From catʼs eyes to multiple disjoint natural convection flow in tall tilted cavities: A direct primitive variables approach

NASA Astrophysics Data System (ADS)

Báez, Elsa; Nicolás, Alfredo

2013-11-01

Natural convection fluid flow in air-filled tall tilted cavities is studied numerically with a new direct projection method on the Boussinesq approximation in primitive variables. The study deals with “cat's eyes” instabilities and multiple disjoint cells as the aspect ratio A and the angle of inclination ϕ of the cavity vary. The flows are validated with those reported before using the stream function-vorticity variables. New cases, A=12 and 20 varying ϕ, lead to get more insight on the physical phenomenon.

Cell fate regulation in early mammalian development

NASA Astrophysics Data System (ADS)

Oron, Efrat; Ivanova, Natalia

2012-08-01

Preimplantation development in mammals encompasses a period from fertilization to implantation and results in formation of a blastocyst composed of three distinct cell lineages: epiblast, trophectoderm and primitive endoderm. The epiblast gives rise to the organism, while the trophectoderm and the primitive endoderm contribute to extraembryonic tissues that support embryo development after implantation. In many vertebrates, such as frog or fish, maternally supplied lineage determinants are partitioned within the egg. Cell cleavage that follows fertilization results in polarization of these factors between the individual blastomeres, which become restricted in their developmental fate. In contrast, the mouse oocyte and zygote lack clear polarity and, until the eight-cell stage, individual blastomeres retain the potential to form all lineages. How are cell lineages specified in the absence of a maternally supplied blueprint? This is a fundamental question in the field of developmental biology. The answer to this question lies in understanding the cell-cell interactions and gene networks involved in embryonic development prior to implantation and using this knowledge to create testable models of the developmental processes that govern cell fates. We provide an overview of classic and contemporary models of early lineage development in the mouse and discuss the emerging body of work that highlights similarities and differences between blastocyst development in the mouse and other mammalian species.

Homo naledi, a new species of the genus Homo from the Dinaledi Chamber, South Africa.

PubMed

Berger, Lee R; Hawks, John; de Ruiter, Darryl J; Churchill, Steven E; Schmid, Peter; Delezene, Lucas K; Kivell, Tracy L; Garvin, Heather M; Williams, Scott A; DeSilva, Jeremy M; Skinner, Matthew M; Musiba, Charles M; Cameron, Noel; Holliday, Trenton W; Harcourt-Smith, William; Ackermann, Rebecca R; Bastir, Markus; Bogin, Barry; Bolter, Debra; Brophy, Juliet; Cofran, Zachary D; Congdon, Kimberly A; Deane, Andrew S; Dembo, Mana; Drapeau, Michelle; Elliott, Marina C; Feuerriegel, Elen M; Garcia-Martinez, Daniel; Green, David J; Gurtov, Alia; Irish, Joel D; Kruger, Ashley; Laird, Myra F; Marchi, Damiano; Meyer, Marc R; Nalla, Shahed; Negash, Enquye W; Orr, Caley M; Radovcic, Davorka; Schroeder, Lauren; Scott, Jill E; Throckmorton, Zachary; Tocheri, Matthew W; VanSickle, Caroline; Walker, Christopher S; Wei, Pianpian; Zipfel, Bernhard

2015-09-10

Homo naledi is a previously-unknown species of extinct hominin discovered within the Dinaledi Chamber of the Rising Star cave system, Cradle of Humankind, South Africa. This species is characterized by body mass and stature similar to small-bodied human populations but a small endocranial volume similar to australopiths. Cranial morphology of H. naledi is unique, but most similar to early Homo species including Homo erectus, Homo habilis or Homo rudolfensis. While primitive, the dentition is generally small and simple in occlusal morphology. H. naledi has humanlike manipulatory adaptations of the hand and wrist. It also exhibits a humanlike foot and lower limb. These humanlike aspects are contrasted in the postcrania with a more primitive or australopith-like trunk, shoulder, pelvis and proximal femur. Representing at least 15 individuals with most skeletal elements repeated multiple times, this is the largest assemblage of a single species of hominins yet discovered in Africa.

Vismodegib and Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced or Metastatic Sarcoma

ClinicalTrials.gov

2016-06-09

Adult Alveolar Soft Part Sarcoma; Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Hemangioendothelioma; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Unclassified Pleomorphic Sarcoma; Chondrosarcoma; Clear Cell Sarcoma of the Kidney; Conjunctival Kaposi Sarcoma; Dermatofibrosarcoma Protuberans; Gastrointestinal Stromal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Ovarian Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Adult Unclassified Pleomorphic Sarcoma of Bone; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Kaposi Sarcoma; Recurrent Osteosarcoma; Recurrent Uterine Corpus Sarcoma; Small Intestine Leiomyosarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma; Unclassified Pleomorphic Sarcoma of Bone

Prolonged Growth Hormone/Insulin/Insulin-like Growth Factor Nutrient Response Signaling Pathway as a Silent Killer of Stem Cells and a Culprit in Aging.

PubMed

Ratajczak, Mariusz Z; Bartke, Andrzej; Darzynkiewicz, Zbigniew

2017-08-01

The dream of slowing down the aging process has always inspired mankind. Since stem cells are responsible for tissue and organ rejuvenation, it is logical that we should search for encoded mechanisms affecting life span in these cells. However, in adult life the hierarchy within the stem cell compartment is still not very well defined, and evidence has accumulated that adult tissues contain rare stem cells that possess a broad trans-germ layer differentiation potential. These most-primitive stem cells-those endowed with pluripotent or multipotent differentiation ability and that give rise to other cells more restricted in differentiation, known as tissue-committed stem cells (TCSCs) - are of particular interest. In this review we present the concept supported by accumulating evidence that a population of so-called very small embryonic-like stem cells (VSELs) residing in adult tissues positively impacts the overall survival of mammals, including humans. These unique cells are prevented in vertebrates from premature depletion by decreased sensitivity to growth hormone (GH), insulin (INS), and insulin-like growth factor (IGF) signaling, due to epigenetic changes in paternally imprinted genes that regulate their resistance to these factors. In this context, we can envision nutrient response GH/INS/IGF signaling pathway as a lethal factor for these most primitive stem cells and an important culprit in aging.

Resolving early mesoderm diversification through single-cell expression profiling.

PubMed

Scialdone, Antonio; Tanaka, Yosuke; Jawaid, Wajid; Moignard, Victoria; Wilson, Nicola K; Macaulay, Iain C; Marioni, John C; Göttgens, Berthold

2016-07-14

In mammals, specification of the three major germ layers occurs during gastrulation, when cells ingressing through the primitive streak differentiate into the precursor cells of major organ systems. However, the molecular mechanisms underlying this process remain unclear, as numbers of gastrulating cells are very limited. In the mouse embryo at embryonic day 6.5, cells located at the junction between the extra-embryonic region and the epiblast on the posterior side of the embryo undergo an epithelial-to-mesenchymal transition and ingress through the primitive streak. Subsequently, cells migrate, either surrounding the prospective ectoderm contributing to the embryo proper, or into the extra-embryonic region to form the yolk sac, umbilical cord and placenta. Fate mapping has shown that mature tissues such as blood and heart originate from specific regions of the pre-gastrula epiblast, but the plasticity of cells within the embryo and the function of key cell-type-specific transcription factors remain unclear. Here we analyse 1,205 cells from the epiblast and nascent Flk1(+) mesoderm of gastrulating mouse embryos using single-cell RNA sequencing, representing the first transcriptome-wide in vivo view of early mesoderm formation during mammalian gastrulation. Additionally, using knockout mice, we study the function of Tal1, a key haematopoietic transcription factor, and demonstrate, contrary to previous studies performed using retrospective assays, that Tal1 knockout does not immediately bias precursor cells towards a cardiac fate.

Peripheral primitive neuroectodermal tumor of the vulva: report of a case with imprint cytology.

PubMed

Takeshima, N; Tabata, T; Nishida, H; Furuta, N; Tsuzuku, M; Hirai, Y; Hasumi, K

2001-01-01

Peripheral primitive neuroectodermal tumor (PNET) of the vulva is an extremely rare disease, and, to our knowledge, only two cases have been previously reported. A 45-year-old woman presented with a mass in the right labium major. Three years after removal of the tumor, she noticed a new lesion in the same place and underwent a partial vulvectomy. The imprint cytology of the recurrent tumor showed a monomorphic appearance, composed of small round cells with scant cytoplasm against a hemorrhagic background. These tumor cells were loosely connective, but rosettelike structures were observed focally. On pathologic examination, the neoplasm was composed of small round tumor cells showing sinusoidal, diffuse or micropapillary growth. Immunohistochemically, the neoplastic cells stained positively for neuron-specific enolase, vimentin and HBA 71 and negatively for cytokeratin, HBA 45 and muscle-specific actin. The morphologic characteristics of the disease were well expressed in the imprint cytology, and this influenced the selection of immunohistochemical studies. Cytologic examination for vulvar tumors, even imprint cytology, can be a useful tool in obtaining an accurate pathologic diagnosis of a rare disease, such as peripheral PNET.

A recursive vesicle-based model protocell with a primitive model cell cycle

PubMed Central

Kurihara, Kensuke; Okura, Yusaku; Matsuo, Muneyuki; Toyota, Taro; Suzuki, Kentaro; Sugawara, Tadashi

2015-01-01

Self-organized lipid structures (protocells) have been proposed as an intermediate between nonliving material and cellular life. Synthetic production of model protocells can demonstrate the potential processes by which living cells first arose. While we have previously described a giant vesicle (GV)-based model protocell in which amplification of DNA was linked to self-reproduction, the ability of a protocell to recursively self-proliferate for multiple generations has not been demonstrated. Here we show that newborn daughter GVs can be restored to the status of their parental GVs by pH-induced vesicular fusion of daughter GVs with conveyer GVs filled with depleted substrates. We describe a primitive model cell cycle comprising four discrete phases (ingestion, replication, maturity and division), each of which is selectively activated by a specific external stimulus. The production of recursive self-proliferating model protocells represents a step towards eventual production of model protocells that are able to mimic evolution. PMID:26418735

Why did eukaryotes evolve only once? Genetic and energetic aspects of conflict and conflict mediation

PubMed Central

Blackstone, Neil W.

2013-01-01

According to multi-level theory, evolutionary transitions require mediating conflicts between lower-level units in favour of the higher-level unit. By this view, the origin of eukaryotes and the origin of multicellularity would seem largely equivalent. Yet, eukaryotes evolved only once in the history of life, whereas multicellular eukaryotes have evolved many times. Examining conflicts between evolutionary units and mechanisms that mediate these conflicts can illuminate these differences. Energy-converting endosymbionts that allow eukaryotes to transcend surface-to-volume constraints also can allocate energy into their own selfish replication. This principal conflict in the origin of eukaryotes can be mediated by genetic or energetic mechanisms. Genome transfer diminishes the heritable variation of the symbiont, but requires the de novo evolution of the protein-import apparatus and was opposed by selection for selfish symbionts. By contrast, metabolic signalling is a shared primitive feature of all cells. Redox state of the cytosol is an emergent feature that cannot be subverted by an individual symbiont. Hypothetical scenarios illustrate how metabolic regulation may have mediated the conflicts inherent at different stages in the origin of eukaryotes. Aspects of metabolic regulation may have subsequently been coopted from within-cell to between-cell pathways, allowing multicellularity to emerge repeatedly. PMID:23754817

Why did eukaryotes evolve only once? Genetic and energetic aspects of conflict and conflict mediation.

PubMed

Blackstone, Neil W

2013-07-19

According to multi-level theory, evolutionary transitions require mediating conflicts between lower-level units in favour of the higher-level unit. By this view, the origin of eukaryotes and the origin of multicellularity would seem largely equivalent. Yet, eukaryotes evolved only once in the history of life, whereas multicellular eukaryotes have evolved many times. Examining conflicts between evolutionary units and mechanisms that mediate these conflicts can illuminate these differences. Energy-converting endosymbionts that allow eukaryotes to transcend surface-to-volume constraints also can allocate energy into their own selfish replication. This principal conflict in the origin of eukaryotes can be mediated by genetic or energetic mechanisms. Genome transfer diminishes the heritable variation of the symbiont, but requires the de novo evolution of the protein-import apparatus and was opposed by selection for selfish symbionts. By contrast, metabolic signalling is a shared primitive feature of all cells. Redox state of the cytosol is an emergent feature that cannot be subverted by an individual symbiont. Hypothetical scenarios illustrate how metabolic regulation may have mediated the conflicts inherent at different stages in the origin of eukaryotes. Aspects of metabolic regulation may have subsequently been coopted from within-cell to between-cell pathways, allowing multicellularity to emerge repeatedly.

Software Design Document MCC CSCI (1). Volume 1 Sections 1.0-2.18

DTIC Science & Technology

1991-06-01

AssociationUserProtocol /simnet/common!include/prot ____________________ ____________________ ocol/p assoc.h Primitive long Standard C type...Information. 2.2.1.4.2 ProcessMessage ProcessMessage processes a message from another process. type describes the message as either one-way, a synchronous or...Macintosh Consoles. This is sometimes necessary due to normal clock skew so that operations among the MCC components will remain synchronized . This

Advances In Engineering Science, Volume 2.

DTIC Science & Technology

1976-11-01

UNDRAINED CLAY BEHAVIOR .... ............ .. 95 Jean-Herve Prevost and Kaare H~eg THEORY OF ORTHODONTIC MOTIONS...compo- nents at a lower level are terminal nodes of a tree. The bracketed numbers on the right hand side of the terminating nodes are the number of...primitive data objects in each instance of the defined object. The bracketed numbers on the right hand side of the non-terminal nodes in the tree are the

In Pursuit of Prostate Cancer Stem Cells

DTIC Science & Technology

2007-01-01

cells with different tumorigenicities and primitiveness in human PCa xenografts and cell lines. In this study, we seek to reevaluate the relevancy...us prostatospheres and establish primary xenografts in order to carry out our proposed experiments. Preliminary in vitro experiments indicate that...LIMITATION OF ABSTRACT 18 . NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT U b. ABSTRACT U c. THIS PAGE U UU 31

In vitro long-term culture of human primitive hematopoietic cells supported by murine stromal cell line MS-5.

PubMed

Nishi, N; Ishikawa, R; Inoue, H; Nishikawa, M; Yoneya, T; Kakeda, M; Tsumura, H; Ohashi, H; Mori, K J

1997-04-01

When Lin-CD34+CD38- cells from normal human cord blood were cocultured with MS-5, colony forming cells were maintained for over 8 weeks. Prevention of contact between MS-5 and Lin-CD34+CD38- cells by using a membrane filter was negligible for this activity, indicating that the activity of MS-5 on human primitive hematopoietic cells may be due to soluble factor(s) secreted from MS-5. We tried to purify this activity by a [3H]TdR incorporation assay. The activity was found in 150 kD fraction and was neutralized with anti-mSCF (stem cell factor) antibody. Another 20-30 kD fraction synergized with mSCF to stimulate the growth of Lin-CD34+CD38- cells but failed alone. This fraction supported the growth of the G-CSF (granulocyte-colony stimulating factor)-dependent cell line FD/GR3, FDC-P2 transfected with mG-CSF receptor cDNA. This synergy was canceled in the presence of soluble mG-CSF receptor. Addition of anti-mSCF antibody and soluble mG-CSF receptor to the culture completely abrogated the activity of MS-5-culture supernatant. These results indicate the activity of MS-5 on Lin-CD34+CD38- cells is due to synergistic effect of mSCF and mG-CSF.

Optimizing homeostatic cell renewal in hierarchical tissues

PubMed Central

Fider, Nicole A.

2018-01-01

In order to maintain homeostasis, mature cells removed from the top compartment of hierarchical tissues have to be replenished by means of differentiation and self-renewal events happening in the more primitive compartments. As each cell division is associated with a risk of mutation, cell division patterns have to be optimized, in order to minimize or delay the risk of malignancy generation. Here we study this optimization problem, focusing on the role of division tree length, that is, the number of layers of cells activated in response to the loss of terminally differentiated cells, which is related to the balance between differentiation and self-renewal events in the compartments. Using both analytical methods and stochastic simulations in a metapopulation-style model, we find that shorter division trees are advantageous if the objective is to minimize the total number of one-hit mutants in the cell population. Longer division trees on the other hand minimize the accumulation of two-hit mutants, which is a more likely evolutionary goal given the key role played by tumor suppressor genes in cancer initiation. While division tree length is the most important property determining mutant accumulation, we also find that increasing the size of primitive compartments helps to delay two-hit mutant generation. PMID:29447149

Identification of progenitor cancer stem cell in lentigo maligna melanoma.

PubMed

Bongiorno, M R; Doukaki, S; Malleo, F; Aricò, M

2008-07-01

The potential role of stem cells in neoplasia has aroused considerable interest over the past few years. A number of known biologic characteristics of melanomas support the theory that they may originate in a mutated stem cell. Melanocytic stem cell markers have been described recently. Moreover, the CD133 cells that show surface markers for CD34 are stem cells primitive. These stem cells are capable of differentiating into neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. The identification of cancer stem/initiating cells with a crucial role in tumor formation may open up new pharmacologic perspectives. The purpose of this study is to detect the expression of CD133 and CD34, two putative markers of cancer stem cells in the lentigo maligna melanoma. Thirty cases of lentigo maligna melanoma were analyzed using indirect immunohistochemical staining. The vast majority of the samples analyzed showed the presence of rare cells, which were clearly positive for CD133 and CD34. Strong CD133 and CD34 staining was found in the outer root sheath of the mid-lower hair follicles, intermixed with atypical melanocytes extending along layers of the hair follicles. A number of these staminal cells were adjacent and intermixed with melanoma cells. This study supports the stem cell origin of this tumor and suggests that the precursor of the melanoma in question is a stem-like cell rather than the primitive melanoblast committed to be exclusively involved in melanocytic differentiation.

Imatinib Mesylate in Treating Patients With Relapsed or Refractory Solid Tumors of Childhood

ClinicalTrials.gov

2015-04-14

Childhood Desmoplastic Small Round Cell Tumor; Childhood Synovial Sarcoma; Gastrointestinal Stromal Tumor; Lung Metastases; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma

Study of Genistein in Pediatric Oncology Patients (UVA-Gen001)

ClinicalTrials.gov

2017-06-20

Lymphoma; Childhood Lymphoma; Solid Tumor; Childhood Solid Tumor; Neuroblastoma; Ewing Sarcoma; Hodgkin Lymphoma; Non-Hodgkin Lymphoma; Rhabdomyosarcoma; Soft Tissue Sarcoma; Medulloblastoma; Germ Cell Tumor; Wilms Tumor; Brain Neoplasms; Medulloblastoma, Childhood; Neuroectodermal Tumors, Primitive

In vivo transduction of primitive mobilized hematopoietic stem cells after intravenous injection of integrating adenovirus vectors

PubMed Central

Richter, Maximilian; Saydaminova, Kamola; Yumul, Roma; Krishnan, Rohini; Liu, Jing; Nagy, Eniko-Eva; Singh, Manvendra; Izsvák, Zsuzsanna; Cattaneo, Roberto; Uckert, Wolfgang; Palmer, Donna; Ng, Philip; Haworth, Kevin G.; Kiem, Hans-Peter; Ehrhardt, Anja; Papayannopoulou, Thalia

2016-01-01

Current protocols for hematopoietic stem/progenitor cell (HSPC) gene therapy, involving the transplantation of ex vivo genetically modified HSPCs are complex and not without risk for the patient. We developed a new approach for in vivo HSPC transduction that does not require myeloablation and transplantation. It involves subcutaneous injections of granulocyte-colony-stimulating factor/AMD3100 to mobilize HSPCs from the bone marrow (BM) into the peripheral blood stream and the IV injection of an integrating, helper-dependent adenovirus (HD-Ad5/35++) vector system. These vectors target CD46, a receptor that is uniformly expressed on HSPCs. We demonstrated in human CD46 transgenic mice and immunodeficient mice with engrafted human CD34+ cells that HSPCs transduced in the periphery home back to the BM where they stably express the transgene. In hCD46 transgenic mice, we showed that our in vivo HSPC transduction approach allows for the stable transduction of primitive HSPCs. Twenty weeks after in vivo transduction, green fluorescent protein (GFP) marking in BM HSPCs (Lin−Sca1+Kit− cells) in most of the mice was in the range of 5% to 10%. The percentage of GFP-expressing primitive HSPCs capable of forming multilineage progenitor colonies (colony-forming units [CFUs]) increased from 4% of all CFUs at week 4 to 16% at week 12, indicating transduction and expansion of long-term surviving HSPCs. Our approach was well tolerated, did not result in significant transduction of nonhematopoietic tissues, and was not associated with genotoxicty. The ability to stably genetically modify HSPCs without the need of myeloablative conditioning is relevant for a broader clinical application of gene therapy. PMID:27554082

The role of immunohistochemistry in medullomyoblastoma--a case series highlighting divergent differentiation.

PubMed

Sachdeva, Man Updesh S; Vankalakunti, Mahesha; Rangan, Aruna; Radotra, Bishan D; Chhabra, Rajesh; Vasishta, Rakesh K

2008-04-25

To analyse the histo-morphology of cases of medullomyoblastoma and identifying its divergent differentiation. A retrospective review of all cases reported as medulloblastoma between the period of Jan 2000 to Dec 2006 was carried out on Hematoxylin and eosin (H & E) stained slides. The cases were screened on light microscopy for primitive neuroectodermal component of a medulloblastoma accompanied by areas of "myoid" differentiation, identified on the basis of presence of strap cells (indicating a clear skeletal muscle differentiation) and/or large anaplastic cells with vescicular nuclei and moderate to abundant amount of eosinophilic cytoplasm. All these cases were subjected to a panel of immunohistochemical stains, including Desmin, GFAP, NFP, HMB45, SMA, S100, CK and EMA. Ultrastructural analysis was done on tissue obtained from paraffin blocks in 2 cases. Male predominance (M:F = 5:1) was noted with an incidence of five percent of all cases of medulloblastoma (6 out of 120 cases) over a period of 6 years. Primitive neuroectodermal areas were accompanied with areas of "myoid" differentiation, 5 cases showing strap cells. Two cases with epithelial and cartilaginous differentiation were seen. Three cases showed focal melanocytic differentiation, identified only on HMB45 immunostaining. Four cases showed glial differentiation. Neuronal differentiation again was very focally seen in two cases, of which one was identified only by NFP immunostain. Seventh case is included in the study, however it is not considered to calculate incidence as it occurred beyond the period of 6 years of records search. Medullomyoblastoma is a rare childhood tumor of cerebellum. Majority of cases reveal divergent differentiation, which are identified with the help of panel of immunostains indicating multi-potential nature of primitive neuroectodermal cells.

Globin switches in yolk sac-like primitive and fetal-like definitive red blood cells produced from human embryonic stem cells.

PubMed

Qiu, Caihong; Olivier, Emmanuel N; Velho, Michelle; Bouhassira, Eric E

2008-02-15

We have previously shown that coculture of human embryonic stem cells (hESCs) for 14 days with immortalized fetal hepatocytes yields CD34(+) cells that can be expanded in serum-free liquid culture into large numbers of megaloblastic nucleated erythroblasts resembling yolk sac-derived cells. We show here that these primitive erythroblasts undergo a switch in hemoglobin (Hb) composition during late terminal erythroid maturation with the basophilic erythroblasts expressing predominantly Hb Gower I (zeta(2)epsilon(2)) and the orthochromatic erythroblasts hemoglobin Gower II (alpha(2)epsilon(2)). This suggests that the switch from Hb Gower I to Hb Gower II, the first hemoglobin switch in humans is a maturation switch not a lineage switch. We also show that extending the coculture of the hESCs with immortalized fetal hepatocytes to 35 days yields CD34(+) cells that differentiate into more developmentally mature, fetal liver-like erythroblasts, that are smaller, express mostly fetal hemoglobin, and can enucleate. We conclude that hESC-derived erythropoiesis closely mimics early human development because the first 2 human hemoglobin switches are recapitulated, and because yolk sac-like and fetal liver-like cells are sequentially produced. Development of a method that yields erythroid cells with an adult phenotype remains necessary, because the most mature cells that can be produced with current systems express less than 2% adult beta-globin mRNA.

Cellular Particle Dynamics simulation of biomechanical relaxation processes of multi-cellular systems

NASA Astrophysics Data System (ADS)

McCune, Matthew; Kosztin, Ioan

2013-03-01

Cellular Particle Dynamics (CPD) is a theoretical-computational-experimental framework for describing and predicting the time evolution of biomechanical relaxation processes of multi-cellular systems, such as fusion, sorting and compression. In CPD, cells are modeled as an ensemble of cellular particles (CPs) that interact via short range contact interactions, characterized by an attractive (adhesive interaction) and a repulsive (excluded volume interaction) component. The time evolution of the spatial conformation of the multicellular system is determined by following the trajectories of all CPs through numerical integration of their equations of motion. Here we present CPD simulation results for the fusion of both spherical and cylindrical multi-cellular aggregates. First, we calibrate the relevant CPD model parameters for a given cell type by comparing the CPD simulation results for the fusion of two spherical aggregates to the corresponding experimental results. Next, CPD simulations are used to predict the time evolution of the fusion of cylindrical aggregates. The latter is relevant for the formation of tubular multi-cellular structures (i.e., primitive blood vessels) created by the novel bioprinting technology. Work supported by NSF [PHY-0957914]. Computer time provided by the University of Missouri Bioinformatics Consortium.

Antitumor activity of a rhenium (I)-diselenoether complex in experimental models of human breast cancer.

PubMed

Collery, Philippe; Mohsen, Ahmed; Kermagoret, Anthony; Corre, Samantha; Bastian, Gérard; Tomas, Alain; Wei, Ming; Santoni, François; Guerra, Nadia; Desmaële, Didier; d'Angelo, Jean

2015-08-01

Rhenium (I)-diselenother (Re-diselenoether) is a water soluble metal-based compound, combining one atom of rhenium and two atoms of selenium. This compound has been reported to exhibit marked activities against several solid tumor cell lines. We now disclose an improved synthesis of this complex. The Re-diselenoether showed a potent inhibitory effect on MDA-MB231 cell division in vitro, which lasted when the complex was no longer present in the culture. Re-diselenoether induced a remarkable reduction of the volume of the primitive breast tumors and of the pulmonary metastases without clinical signs of toxicity, in mice-bearing a MDA-MB231 Luc+ tumor, orthotopically transplanted, after a daily oral administration at the dose of 10 mg/kg/d. Interestingly, an antagonism was observed when cisplatin was administered as a single i.p. injection 1 week after the end of the Re-diselenoether administration. In an effort to gain insight of the mechanisms of action of Re-diselenoether complex, interaction with 9-methylguanine as a nucleic acid base model was studied. We have shown that Re-diselenoether gave both mono- and bis-guanine Re adducts, the species assumed to be responsible for the DNA intrastrand lesions.

Gut endoderm takes flight from the wings of mesoderm.

PubMed

McDonald, Angela C H; Rossant, Janet

2014-12-01

The endoderm layer destined to be primitive gut is a mosaic of earlier visceral endoderm and definitive endoderm that arises later, during gastrulation. Live imaging now reveals that in mouse embryos, definitive endoderm cells egress from underlying mesoderm and intercalate into the overlying cell layer. This process requires SOX17-mediated control of basement membrane organization.

Granulocyte-colony stimulating factor and stem cell factor are the crucial factors in long-term culture of human primitive hematopoietic cells supported by a murine stromal cell line.

PubMed

Nishi, N; Ishikawa, R; Inoue, H; Nishikawa, M; Kakeda, M; Yoneya, T; Tsumura, H; Ohashi, H; Yamaguchi, Y; Motoki, K; Sudo, T; Mori, K J

1996-09-01

The findings that murine marrow stromal cell line MS-5 supported the proliferation of human lineage-negative (Lin-) CD34+CD38- bone marrow cells in long-term culture have been reported. In this study, we analyzed this proliferating activity of MS-5-conditioned medium (CM) on human primitive hematopoietic cells. When Lin-CD34+CD38- cells of normal human cord blood cells were co-cultured with MS-5, colony forming cells (CFCs) were maintained over 7 weeks in vitro. Prevention of contact between MS-5 and Lin-CD34+CD38- cells by using membrane filter (0.45 micron) was negligible for this activity. This indicated that the activity of MS-5 on human primitive hematopoietic cells is a soluble factor(s) secreted from MS-5, which is not induced by the contact between MS-5 and Lin-CD34+CD38- cells. We tried to purify this soluble activity. An active material with a molecular weight of about 150 kDa, determined by gel filtration chromatography, solely supported the growth of Lin-CD34+CD38- cells and Mo7e, a human megakaryocytic cell line. This activity not only reacted with anti-mouse stem cell factor (mSCF) antibody on Western blots, but it was also neutralized in the presence of anti-mSCF antibody. Another active material with a molecular weight of about 20-30 kDa synergized with mSCF to stimulate the growth of Lin-CD34+CD38- cells but failed to do so alone, although this synergy was inhibited in the presence of soluble mouse granulocyte-colony stimulating factor (mG-CSF) receptor, which is a chimeric protein consisting of the extracellular domain of mG-CSF receptor and the Fe region of human IgG1. In addition, the latter molecule supported the growth of the G-CSF dependent cell line FD/GR3, which is a murine myeloid leukemia cell line, FDC-P2, transfected with mG-CSF receptor cDNA. Adding of anti-mSCF antibody and soluble mG-CSF receptor to the culture completely abrogated the activity of MS-5-CM. Recombinant (r) mSCF and rmG-CSF had synergistic activity on the growth of Lin-CD34+CD38- cells. These results indicated that the activity on Lin-CD34+CD38- cells included in MS-5-CM is based upon the synergistic effects of mSCF and mG-CSF.

Unified structure theory of icosahedral quasicrystals: Evidence from neutron powder diffraction patterns that AlCrFeMnSi, AlCuLiMg, and TiNiFeSi icosahedral quasicrystals are twins of cubic crystals containing about 820 or 1012 atoms in a primitive unit cube

PubMed Central

Pauling, Linus

1988-01-01

A unified structure theory of icosahedral quasicrystals, combining the twinned-cubic-crystal theory and the Penrose-tiling-six-dimensional-projection theory, is described. Values of the primitive-cubic lattice constant for several quasicrystals are evaluated from x-ray and neutron diffraction data. The fact that the low-angle diffraction maxima can be indexed with cubic unit cells provides additional support for the twinned-cubic-crystal theory of icosahedral quasicrystals. PMID:16593990

Primary primitive neuroectodermal tumor of the cervix

PubMed Central

Li, Bo; Ouyang, Ling; Han, Xue; Zhou, Yang; Tong, Xin; Zhang, Shulang; Zhang, Qingfu

2013-01-01

Primary primitive neuroectodermal tumors (PNETs) are rare and high-grade malignant tumors that mostly occur in children and young adults. The most common sites are the trunk, limbs, and retroperitoneum. Herein, we present a case of a PNET involving the cervix uteri in a 27-year-old woman. The lesion showed characteristic histologic features of a PNET and was positive for the immunohistochemical markers cluster of differentiation (CD) 99, vimentin, neuron-specific enolase, neural cell adhesion molecule 1 (CD56), and CD117 (c-kit), further defining the tumor while helping to confirm PNET. The clinical Stage IIIB tumor was treated with chemotherapy and radiotherapy. PMID:23836982

Spectrum of hemoglobinopathies among the primitive tribes: a multicentric study in India.

PubMed

Mohanty, Dipika; Mukherjee, Malay B; Colah, Roshan B; Wadia, Mahrukh; Ghosh, Kanjaksha; Chottray, Guru Prasad; Jain, Dipty; Italia, Yazdi; Ashokan, Kumar S; Kaul, Rajni; Shukla, Deepak K; Muthuswamy, Vasantha

2015-03-01

We evaluated the spectrum of hemoglobinopathies among the primitive tribal groups from 4 states in India. A total of 15,200 individuals from 14 primitive tribal groups were studied by automated high-performance liquid chromatography. The hemoglobin S (HbS) allele frequency varied from 0.011 to 0.120 and the β-thalassemia allele frequency from 0.005 to 0.024. It is interesting to note that a very high HbS allele frequency was observed among the Dravidian (0.060-0.120) and Indo-European (0.060-0.076) as compared with Austro-Asiatic (0.011-0.022) speaking tribal groups. Although statistical analysis of the data did not show any ethnic differences within the states, regional differences were observed between the states for both HbS and β-thalassemia traits. HbS was found to be the most common hemoglobinopathy followed by β-thalassemia. A health plan for identifying sickle-cell homozygotes in the neonatal period with proper medical intervention is desirable. © 2013 APJPH.

Oxygen and the evolution of metabolic pathways

NASA Technical Reports Server (NTRS)

Jahnke, L. L.

1986-01-01

While a considerable amount of evidence has been accumulated about the history of oxygen on this planet, little is known about the relative amounts to which primitive cells might have been exposed. One clue may be found in the metabolic pathways of extant microorganisms. While eucaryotes are principally aerobic organisms, a number are capable of anaerobic growth by fermentation. One such eucaryotic microorganism, Saccharomyces cerevisiae, will grow in the complete absence of oxygen when supplemented with unsaturated fatty acid and sterol. Oxygen-requiring enzymes are involved in the synthesis of both of these compounds. Studies have demonstrated that the oxidative desaturation of palmitic acid and the conversion of squalene to sterols occur in the range of 10-(3) to 10(-2) PAL. Thus, if the oxygen requirements of these enzymatic processes are an indication, eucaryotes might be more primitive than anticipated from the microfossil record. Results of studies on the oxygen requirements for sterol and unsaturated fatty acid synthesis in a more primitive procaryotic system are also discussed.

Structural, optical, and thermal properties of MAX-phase Cr2AlB2

NASA Astrophysics Data System (ADS)

Li, Xiao-Hong; Cui, Hong-Ling; Zhang, Rui-Zhou

2018-04-01

First-principles calculations of the structural, optical, and thermal properties of Cr2AlB2 are performed using the pseudopotential plane-wave method within the generalized gradient approximation (GGA). Calculation of the elastic constant and phonon dispersion indicates that Cr2AlB2 is mechanically and thermodynamically stable. Analysis of the band structure and density of states indicates that Cr2AlB2 is metallic. The thermal properties under increasing temperature and pressure are investigated using the quasi-harmonic Debye model. The results show that anharmonic effects on Cr2AlB2 are important at low temperature and high pressure. The calculated equilibrium primitive cell volume is 95.91 Å3 at T = 300 K, P = 0 GPa. The ability of Cr2AlB2 to resist volume changes becomes weaker with increasing temperature and stronger with increasing pressure. Analysis of optical properties of Cr2AlB2 shows that the static dielectric function of Cr2AlB2 is 53.1, and the refractive index n 0 is 7.3. If the incident light has a frequency exceeding 16.09 eV, which is the plasma frequency of Cr2AlB2, Cr2AlB2 changes from metallic to dielectric material.

Immunocytochemical location of pituitary cells containing ACTH, alpha-MSH, and beta-endorphin in Acipenser transmontanus, Lepisosteus spatula, and Amia calva.

PubMed

Joss, J M; Dores, R M; Crim, J W; Beshaw, M

1990-06-01

This immunocytochemical study of the pituitaries of the primitive actinopterygians, Acipenser transmontanus, Lepisosteus spatula, and Amia calva, showed a strict delineation between the hormonal fragments of proopiomelanocorticotropin (POMC) produced by corticotropes of the pars distalis and the melanotropes of the pars intermedia. Corticotropes were immunoreactive only for ACTH and not to either of the further degradation products, alpha-MSH or beta-endorphin. Melanotropes were shown to be immunoreactive to all three antisera but it is argued that immunoreactivity of melanotropes to ACTH antiserum is due to that antiserum's cross-reactivity with the cleavage product corticotropin-like intermediate peptide. The PAS positivity of both the corticotropes and the melanotropes of all three primitive fish argues for an ancient origin of a carbohydrate component of POMC and for its loss or reduction in teleosts where these cells are PAS negative.

Ripple/Carcinoid pattern sebaceoma with apocrine differentiation.

PubMed

Misago, Noriyuki; Narisawa, Yutaka

2011-02-01

Sebaceoma is a benign sebaceous neoplasm, which has been reported to show characteristic growth patterns, such as, ripple, labyrinthine/sinusoidal, and carcinoid-like patterns. Another recent finding regarding in sebaceoma is the observation of apocrine differentiation within the sebaceoma lesion. This report describes a case of carcinoid (a partial ripple and labyrinthine) pattern sebaceoma with apocrine differentiation with a literature review and immunohistochemical studies. The various characteristic growth patterns in sebaceoma were suggested to simply be variations of the same growth pattern arranged in cords, namely, a unified term "ripple/carcinoid pattern." The primitive sebaceous germinative cells in sebaceoma may still have the ability to undergo apocrine differentiation. Most of the reports so far on sebaceoma with apocrine differentiation, including the present case, describe a ripple/carcinoid pattern, thus suggesting that ripple/carcinoid pattern sebaceoma is composed of more primitive sebaceous germinative cells than conventional sebaceoma.

Combination Chemotherapy in Treating Patients With Non-Metastatic Extracranial Ewing Sarcoma

ClinicalTrials.gov

2018-02-09

Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Childhood Supratentorial Primitive Neuroectodermal Tumor; Ewing Sarcoma of Bone; Extraosseous Ewing Sarcoma; Extraosseous Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Peripheral Primitive Neuroectodermal Tumor of the Kidney; Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor

Proceedings of the Midwinter Conference of Immunologists (28th) Held in Pacific Grove, California on 28-31 January 1989 (Lymphocyte Differentiation)

DTIC Science & Technology

1989-02-24

N. Witte Sf-ak-r’." OWEN N. WITTE University of California, Los Angeles, CA "Oncogene Interactions with Primitive Lymphoid Cells" DAVID BALTIMORE The...as Schwann cells, myotubes and astroglial cells. Neurons use different receptors to interact with different cell types. Different neu-ons also differ...controlled by a clock in the progenitor cell that is driven by platelet- derived growth factor (PDGF) secreted by type-i astrocytes. Type-2 astrocyte

Characterization of a Weak Allele of Zebrafish cloche Mutant

PubMed Central

Ma, Ning; Huang, Zhibin; Chen, Xiaohui; He, Fei; Wang, Kun; Liu, Wei; Zhao, Linfeng; Xu, Xiangmin; Liao, Wangjun; Ruan, Hua; Luo, Shenqiu; Zhang, Wenqing

2011-01-01

Hematopoiesis is a complicated and dynamic process about which the molecular mechanisms remain poorly understood. Danio rerio (zebrafish) is an excellent vertebrate system for studying hematopoiesis and developmental mechanisms. In the previous study, we isolated and identified a cloche 172 (clo 172) mutant, a novel allele compared to the original cloche (clo) mutant, through using complementation test and initial mapping. Here, according to whole mount in-situ hybridization, we report that the endothelial cells in clo 172 mutant embryos, although initially developed, failed to form the functional vascular system eventually. In addition, further characterization indicates that the clo 172 mutant exhibited weaker defects instead of completely lost in primitive erythroid cells and definitive hematopoietic cells compared with the clo s5 mutant. In contrast, primitive myeloid cells were totally lost in clo 172 mutant. Furthermore, these reappeared definitive myeloid cells were demonstrated to initiate from the remaining hematopoietic stem cells (HSCs) in clo 172 mutant, confirmed by the dramatic decrease of lyc in clo 172 runx1w84x double mutant. Collectively, the clo 172 mutant is a weak allele compared to the clo s5 mutant, therefore providing a model for studying the early development of hematopoietic and vascular system, as well as an opportunity to further understand the function of the cloche gene. PMID:22132109

Fine-Needle Aspiration of Metastatic Central Type Primitive Neuroectodermal Tumors in Patients with a Germ Cell Tumor.

PubMed

Chen, Shaoxiong; Idrees, Muhammad; Lin, Jingmei; Wu, Howard H

2017-01-01

Central type primitive neuroectodermal tumors (PNET) are some of the most frequent somatic type tumors derived from germ cell tumors and can metastasize. We studied the cytomorphological features of metastatic central type PNET by fine-needle aspiration (FNA). A computerized search of our laboratory information system was performed for the 9-year period from 2005 through 2014 to identify all cytology cases in which a diagnosis of metastatic central type PNET had been rendered. A total of 5 FNA cases were collected and direct smears were reexamined. All patients had a history of testicular or ovarian germ cell tumors. Direct smears displayed single and clusters of atypical round to oval cells with scant to moderate cytoplasm. Abundant naked nuclei were present in Diff-Quik-stained smears with mild to marked crushed artifacts and nuclear molding. Tumor cells showed fine granular chromatin, nuclear size variation (up to 1:3), and one or more small nucleoli. Pseudorosettes (Homer Wright-like rosette) were noticed in 1 case. Tumor cells were commonly positive for synaptophysin. Metastatic PNET can be reliably diagnosed by FNA. Differential diagnoses include Ewing sarcoma/peripheral PNET, alveolar rhabdomyosarcoma, neuroblastoma, etc. It is important to be familiar with this entity to avoid diagnostic pitfalls. © 2017 S. Karger AG, Basel.

Stem cell sources for regenerative medicine.

PubMed

Riazi, Ali M; Kwon, Sarah Y; Stanford, William L

2009-01-01

Tissue-resident stem cells or primitive progenitors play an integral role in homeostasis of most organ systems. Recent developments in methodologies to isolate and culture embryonic and somatic stem cells have many new applications poised for clinical and preclinical trials, which will enable the potential of regenerative medicine to be realized. Here, we overview the current progress in therapeutic applications of various stem cells and discuss technical and social hurdles that must be overcome for their potential to be realized.

Design of a nanocomposite substrate inducing adult stem cell assembly and progression toward an Epiblast-like or Primitive Endoderm-like phenotype via mechanotransduction.

PubMed

Morena, Francesco; Armentano, Ilaria; Montanucci, Pia; Argentati, Chiara; Fortunati, Elena; Montesano, Simona; Bicchi, Ilaria; Pescara, Teresa; Pennoni, Ilaria; Mattioli, Samantha; Torre, Luigi; Latterini, Loredana; Emiliani, Carla; Basta, Giuseppe; Calafiore, Riccardo; Kenny, Josè Maria; Martino, Sabata

2017-11-01

This work shows that the active interaction between human umbilical cord matrix stem cells and Poly (l-lactide)acid (PLLA) and PLLA/Multi Walled Carbon Nanotubes (MWCNTs) nanocomposite films results in the stem cell assembly as a spheroid conformation and affects the stem cell fate transition. We demonstrated that spheroids directly respond to a tunable surface and the bulk properties (electric, dielectric and thermal) of plain and nanocomposite PLLA films by triggering a mechanotransduction axis. This stepwise process starts from tethering of the cells' focal adhesion proteins to the surface, together with the adherens junctions between cells. Both complexes transmit traction forces to F-Actin stress fibres that link Filamin-A and Myosin-IIA proteins, generating a biological scaffold, with increased stiffening conformation from PLLA to PLLA/MWCNTs, and enable the nucleoskeleton proteins to boost chromatin reprogramming processes. Herein, the opposite expression of NANOG and GATA6 transcription factors, together with other lineage specification related proteins, steer spheroids toward an Epiblast-like or Primitive Endoderm-like lineage commitment, depending on the absence or presence of 1 wt% MWCNTs, respectively. This work represents a pioneering effort to create a stem cell/material interface that can model the stem cell fate transition under growth culture conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Integration and long distance axonal regeneration in the central nervous system from transplanted primitive neural stem cells.

PubMed

Zhao, Jiagang; Sun, Woong; Cho, Hyo Min; Ouyang, Hong; Li, Wenlin; Lin, Ying; Do, Jiun; Zhang, Liangfang; Ding, Sheng; Liu, Yizhi; Lu, Paul; Zhang, Kang

2013-01-04

Spinal cord injury (SCI) results in devastating motor and sensory deficits secondary to disrupted neuronal circuits and poor regenerative potential. Efforts to promote regeneration through cell extrinsic and intrinsic manipulations have met with limited success. Stem cells represent an as yet unrealized therapy in SCI. Recently, we identified novel culture methods to induce and maintain primitive neural stem cells (pNSCs) from human embryonic stem cells. We tested whether transplanted human pNSCs can integrate into the CNS of the developing chick neural tube and injured adult rat spinal cord. Following injection of pNSCs into the developing chick CNS, pNSCs integrated into the dorsal aspects of the neural tube, forming cell clusters that spontaneously differentiated into neurons. Furthermore, following transplantation of pNSCs into the lesioned rat spinal cord, grafted pNSCs survived, differentiated into neurons, and extended long distance axons through the scar tissue at the graft-host interface and into the host spinal cord to form terminal-like structures near host spinal neurons. Together, these findings suggest that pNSCs derived from human embryonic stem cells differentiate into neuronal cell types with the potential to extend axons that associate with circuits of the CNS and, more importantly, provide new insights into CNS integration and axonal regeneration, offering hope for repair in SCI.

On Synchronization Primitive Systems.

DTIC Science & Technology

The report studies the question: what synchronization primitive should be used to handle inter-process communication. A formal model is presented...between these synchronization primitives. Although only four synchronization primitives are compared, the general methods can be used to compare other... synchronization primitives. Moreover, in the definitions of these synchronization primitives, conditional branches are explicitly allowed. In addition

Resolving Early Mesoderm Diversification through Single Cell Expression Profiling

PubMed Central

Wilson, Nicola K.; Macaulay, Iain C.; Marioni, John C.; Göttgens, Berthold

2016-01-01

Summary In mammals, specification of the three major germ layers occurs during gastrulation, when cells ingressing through the primitive streak differentiate into the precursor cells of major organ systems. However, the molecular mechanisms underlying this process remain unclear, as numbers of gastrulating cells are very limited. In the E6.5 mouse embryo, cells located at the junction between the extra-embryonic region and the epiblast on the posterior side of the embryo undergo an epithelial-to-mesenchymal transition (EMT) and ingress through the primitive streak (PS). Subsequently, cells migrate, either surrounding the prospective ectoderm contributing to the embryo proper, or into the extra-embryonic region to form the yolk sac (YS), umbilical cord and placenta. Fate mapping has shown that mature tissues such as blood and heart originate from specific regions of the pre-gastrula epiblast1 but the plasticity of cells within the embryo and the function of key cell type-specific transcription factors remain unclear. Here we analyse 1,205 cells from the epiblast and nascent Flk1+ mesoderm of gastrulating mouse embryos using single cell RNA-sequencing, representing the first transcriptome-wide in vivo view of early mesoderm formation during mammalian gastrulation. Additionally, using knock-out mice, we study the function of Tal1, a key hematopoietic transcription factor (TF), and demonstrate, contrary to previous studies performed using retrospective assays2,3, that Tal1 knock out does not immediately bias precursor cells towards a cardiac fate. PMID:27383781

CD34+ Testicular Stromal Cells Support Long-Term Expansion of Embryonic and Adult Stem and Progenitor Cells

PubMed Central

Kim, Jiyeon; Seandel, Marco; Falciatori, Ilaria; Wen, Duancheng; Rafii, Shahin

2010-01-01

Stem cells reside in specialized microenvironments created by supporting stromal cells that orchestrate self-renewal and lineage-specific differentiation. However, the precise identity of the cellular and molecular pathways that support self-renewal of stem cells is not known. For example, long-term culture of prototypical stem cells, such as adult spermatogonial stem and progenitor cells (SPCs), in vitro has been impeded by the lack of an optimal stromal cell line that initiates and sustains proliferation of these cells. Indeed, current methods, including the use of mouse embryonic fibroblasts (MEFs), have not been efficient and have generally led to inconsistent results. Here, we report the establishment of a novel CD34-positive cell line, referred to as JK1, derived from mouse testicular stromal cells that not only facilitated long-term SPC culture but also allowed faithful generation of SPCs and multipotent stem cells. SPCs generated on JK1 maintained key features of germ line stem cells, including expression of PLZF, DAZL, and GCNA. Furthermore, these feeders also promoted the long-term cultivation of other types of primitive cells including multi-potent adult spermatogonial-derived stem cells, pluripotent murine embryonic stem cells, and embryonic germ cells derived from primordial germ cells. Stem cells could be passaged serially and still maintained expression of characteristic markers such as OCT4 and NANOG in vitro, as well as the ability to generate all three germ layers in vivo. These results indicate that the JK1 cell line is capable of promoting long-term culture of primitive cells. As such, this cell line allows for identification of stromal-derived factors that support long-term proliferation of various types of stem cells and constitutes a convenient alternative to other types of feeder layers. PMID:18669907

Clonal analysis identifies hemogenic endothelium as the source of the blood-endothelial common lineage in the mouse embryo

PubMed Central

Padrón-Barthe, Laura; Temiño, Susana; Villa del Campo, Cristina; Carramolino, Laura; Isern, Joan

2014-01-01

The first blood and endothelial cells of amniote embryos appear in close association in the blood islands of the yolk sac (YS). This association and in vitro lineage analyses have suggested a common origin from mesodermal precursors called hemangioblasts, specified in the primitive streak during gastrulation. Fate mapping and chimera studies, however, failed to provide strong evidence for a common origin in the early mouse YS. Additional in vitro studies suggest instead that mesodermal precursors first generate hemogenic endothelium, which then generate blood cells in a linear sequence. We conducted an in vivo clonal analysis to determine the potential of individual cells in the mouse epiblast, primitive streak, and early YS. We found that early YS blood and endothelial lineages mostly derive from independent epiblast populations, specified before gastrulation. Additionally, a subpopulation of the YS endothelium has hemogenic activity and displays characteristics similar to those found later in the embryonic hemogenic endothelium. Our results show that the earliest blood and endothelial cell populations in the mouse embryo are specified independently, and that hemogenic endothelium first appears in the YS and produces blood precursors with markers related to definitive hematopoiesis. PMID:25139355

MiRNA-mediated regulation of cell signaling and homeostasis in the early mouse embryo.

PubMed

Pernaute, Barbara; Spruce, Thomas; Rodriguez, Tristan A; Manzanares, Miguel

2011-02-15

At the time of implantation the mouse embryo is composed of three tissues the epiblast, trophectoderm and primitive endoderm. As development progresses the epiblast goes on to form the foetus whilst the trophectoderm and primitive endoderm give rise to extra-embryonic structures with important roles in embryo patterning and nutrition. Dramatic changes in gene expression occur during early embryo development and these require regulation at different levels. miRNAs are small non coding RNAs that have emerged over the last decade as important post-transcriptional repressors of gene expression. The roles played by miRNAs during early mammalian development are only starting to be elucidated. In order to gain insight into the function of miRNAs in the different lineages of the early mouse embryo we have analysed in depth the phenotype of embryos and extra-embryonic stem cells mutant for the miRNA maturation protein Dicer. This study revealed that miRNAs are involved in regulating cell signaling and homeostasis in the early embryo. Specifically, we identified a role for miRNAs in regulating the Erk signaling pathway in the extra-embryonic endoderm, cell cycle progression in extra-embryonic tissues and apoptosis in the epiblast.

Notochord Morphogenesis in Mice: Current Understanding & Open Questions

PubMed Central

Balmer, Sophie; Nowotschin, Sonja; Hadjantonakis, Anna-Katerina

2016-01-01

The notochord is the structure which defines chordates. It is a rod-like mesodermal structure that runs the anterior-posterior length of the embryo, adjacent to the ventral neural tube. The notochord plays a critical role in embryonic tissue patterning, for example the dorsal-ventral patterning of the neural tube. The cells that will come to form the notochord are specified at gastrulation. Axial mesodermal cells arising at the anterior primitive streak migrate anteriorly as the precursors of the notochord and populate the notochordal plate. Interestingly, even though a lot of interest has centered on investigating the functional and structural roles of the notochord, we still have a very rudimentary understanding of notochord morphogenesis. The events driving the formation of the notochord are rapid, taking place over the period of approximately a day in mice. In this commentary we provide an overview of our current understanding of mouse notochord morphogenesis, from the initial specification of axial mesendodermal cells at the primitive streak, the emergence of these cells at the midline on the surface of the embryo, to their submergence and organization of the stereotypically positioned notochord. We will also discuss some key open questions. PMID:26845388

The physics of cellular synthesis, growth and division

NASA Technical Reports Server (NTRS)

Pollard, E. C.

1974-01-01

Three areas of research in NASA'S University Program are described. Primitive terrestrial living cells were studied as a guide to the kind of cells to look for in extraterrestrial life. Experiments in zero gravity conditions are described with emphasis upon effects on small organisms. The effects of ionizing radiation on cells are studied so that it will be possible to predict dosages which can be tolerated by humans with no permanent damage.

[Clinicopathologic study of sinonasal teratocarcinosarcoma and its contrast with olfactory neuroblastoma].

PubMed

Li, Xue; Liu, Hong-Gang; Xie, Xin-Ji; Han, Yi-Ding; Li, Ming

2008-07-01

To study the clinicopathologic features, diagnosis and differential diagnosis of sinonasal teratocarcinosarcoma (SNTCS) and olfactory neuroblastoma (ONB), and to discuss the histogenesis and possible relationship between SNTCS and ONB. Seven cases of SNTCS and 34 cases of ONB were retrieved from the pathological archives together with one case each of malignant teratoma and immature embryonic tissue at 8 weeks were collected from Beijing Tongren Hospital. The clinicopathologic features were analyzed and immunohistochemical staining was performed on paraffin sections. Six of the SNTCS patients were male and one was female. The patients age range was 25 to 69 years (mean age 46). Four cases were initial presentation and three were recurrences. Histologically, the tumor shows multiple tissue components derived from three germ layers. There were mixture of teratoma-like tissue and carcinosarcoma. The components include fetal clear cell squamous epithelium derived from ectoderm. Glandular and tubular structures and ciliated columnar epithelium derived from endoderm. Fibroblasts, striated muscle, smooth muscle, cartilage and osteoid matrix derived from mesoderm. The carcinoma component exhibited mostly adenocarcinoma and squamous cell carcinoma, whereas the sarcoma component mostly exhibited rhabdomyosarcoma, leiomyosarcoma, and fibrosarcoma. In addition, carcinoid, and primitive mesenchymal tissue and the ONB component were also seen. The morphological characteristics of SNTCS comprised fetal clear cell squamous epithelium, carcinosarcoma and the ONB component. By immunohistochemistry, the epithelial component and cells with epithelium differentiation were positive for cytokeratin (pan) and EMA. The ONB component was positive for Syn, NSE, CD99, NF and CgA to different degrees. Neurofibril bundles were positive for S-100, and Flexner-Wintersteiner rosettes expressed cytokeratin (pan) and EMA. The spindle cells expressed vimentin, SMA, desmin, myosin and myoglobin. The primitive mesenchymal tissue expressed vimentin, and the mucoid materials and glycogen were positive for PAS. GFAP was negative in all cases. The 34 cases of ONB, included 18 men and 16 women, the age ranged from 12 to 72 years (mean 42.8 years). Microscopically, the tumor shows epithelial nests, net of angioma-like fibrous connective tissues, small round and spindle cells, glandular, squamous-like cells, and cells of rhabdomyoblastic differentiation, Homer-Wright and Flexner rosette, bundles of neurofibrils, etc. NSE and CgA were expressed in small cells. S-100 protein was positive in the areas of bunches of neurofibril. Cytokeratin (pan) was positive in epithelial cells. Myoglobin was positive in the cells of rhabdomyoblastic differentiation. The single case of immature malignant teratoma exhibited primitive nerve tissue, but fetal clear cell squamous epithelium was not found. In the immature embryonic tissue, rudimentary organs were formed, with fetal clear cell squamous epithelium lining present on the nasal and oral cavities surface. SNTCS is a rare and aggressive malignant neoplasm. Most of ONB are low-grade malignant tumors. Morphological differences are the most important basis to make differentiate SNTCS from ONB. As SNTCS may demonstrate a multiplicity of structures and pleomorphism, inadequate sampling at biopsy, therefore, may lead to errors in diagnosis. No evidence show that SNTCS are derived from germ cells and sinonasal teratoid carcinosarcoma may be a more proper name. SNTCS probably arises from primitive totipotential cells of olfactory/sinonasal membrane, and the relationship between SNTCS and ONB needs further study.

An Animal Model to Investigate the Potential for Breast Cancer Metastatic Dissemination Following Surgery Intervention on the Primitive Tumor

DTIC Science & Technology

2010-09-01

cancer cells at the plasma membrane level were measured by cell surface biotinylation, using a dedicated kit (cat. #89881) obtained from Pierce...each form of the receptor at the plasma membrane of transfected cells was confirmed by isolation of cell surface proteins obtained by biotinylation...this receptor to interact with both plasma membrane-bound and soluble FKN. Based on our study, it seems reasonable to postulate that the dissemination

Single-lineage transcriptome analysis reveals key regulatory pathways in primitive erythroid progenitors in the mouse embryo

PubMed Central

Isern, Joan; He, Zhiyong; Fraser, Stuart T.; Nowotschin, Sonja; Ferrer-Vaquer, Anna; Moore, Rebecca; Hadjantonakis, Anna-Katerina; Schulz, Vincent; Tuck, David; Gallagher, Patrick G.

2011-01-01

Primitive erythroid (EryP) progenitors are the first cell type specified from the mesoderm late in gastrulation. We used a transgenic reporter to image and purify the earliest blood progenitors and their descendants from developing mouse embryos. EryP progenitors exhibited remarkable proliferative capacity in the yolk sac immediately before the onset of circulation, when these cells comprise nearly half of all cells of the embryo. Global expression profiles generated at 24-hour intervals from embryonic day 7.5 through 2.5 revealed 2 abrupt changes in transcript diversity that coincided with the entry of EryPs into the circulation and with their late maturation and enucleation, respectively. These changes were paralleled by the expression of critical regulatory factors. Experiments designed to test predictions from these data demonstrated that the Wnt-signaling pathway is active in EryP progenitors, which display an aerobic glycolytic profile and the numbers of which are regulated by transforming growth factor-β1 and hypoxia. This is the first transcriptome assembled for a single hematopoietic lineage of the embryo over the course of its differentiation. PMID:21263157

Early Lineage Priming by Trisomy of Erg Leads to Myeloproliferation in a Down Syndrome Model

PubMed Central

Ng, Ashley P.; Hu, Yifang; Metcalf, Donald; Hyland, Craig D.; Ierino, Helen; Phipson, Belinda; Wu, Di; Baldwin, Tracey M.; Kauppi, Maria; Kiu, Hiu; Di Rago, Ladina; Hilton, Douglas J.; Smyth, Gordon K.; Alexander, Warren S.

2015-01-01

Down syndrome (DS), with trisomy of chromosome 21 (HSA21), is the commonest human aneuploidy. Pre-leukemic myeloproliferative changes in DS foetal livers precede the acquisition of GATA1 mutations, transient myeloproliferative disorder (DS-TMD) and acute megakaryocytic leukemia (DS-AMKL). Trisomy of the Erg gene is required for myeloproliferation in the Ts(1716)65Dn DS mouse model. We demonstrate here that genetic changes specifically attributable to trisomy of Erg lead to lineage priming of primitive and early multipotential progenitor cells in Ts(1716)65Dn mice, excess megakaryocyte-erythroid progenitors, and malignant myeloproliferation. Gene expression changes dependent on trisomy of Erg in Ts(1716)65Dn multilineage progenitor cells were correlated with those associated with trisomy of HSA21 in human DS hematopoietic stem and primitive progenitor cells. These data suggest a role for ERG as a regulator of hematopoietic lineage potential, and that trisomy of ERG in the context of DS foetal liver hemopoiesis drives the pre-leukemic changes that predispose to subsequent DS-TMD and DS-AMKL. PMID:25973911

Efficient and rapid derivation of primitive neural stem cells and generation of brain subtype neurons from human pluripotent stem cells.

PubMed

Yan, Yiping; Shin, Soojung; Jha, Balendu Shekhar; Liu, Qiuyue; Sheng, Jianting; Li, Fuhai; Zhan, Ming; Davis, Janine; Bharti, Kapil; Zeng, Xianmin; Rao, Mahendra; Malik, Nasir; Vemuri, Mohan C

2013-11-01

Human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, are unique cell sources for disease modeling, drug discovery screens, and cell therapy applications. The first step in producing neural lineages from hPSCs is the generation of neural stem cells (NSCs). Current methods of NSC derivation involve the time-consuming, labor-intensive steps of an embryoid body generation or coculture with stromal cell lines that result in low-efficiency derivation of NSCs. In this study, we report a highly efficient serum-free pluripotent stem cell neural induction medium that can induce hPSCs into primitive NSCs (pNSCs) in 7 days, obviating the need for time-consuming, laborious embryoid body generation or rosette picking. The pNSCs expressed the neural stem cell markers Pax6, Sox1, Sox2, and Nestin; were negative for Oct4; could be expanded for multiple passages; and could be differentiated into neurons, astrocytes, and oligodendrocytes, in addition to the brain region-specific neuronal subtypes GABAergic, dopaminergic, and motor neurons. Global gene expression of the transcripts of pNSCs was comparable to that of rosette-derived and human fetal-derived NSCs. This work demonstrates an efficient method to generate expandable pNSCs, which can be further differentiated into central nervous system neurons and glia with temporal, spatial, and positional cues of brain regional heterogeneity. This method of pNSC derivation sets the stage for the scalable production of clinically relevant neural cells for cell therapy applications in good manufacturing practice conditions.

Bone marrow-on-a-chip: Long-term culture of human haematopoietic stem cells in a three-dimensional microfluidic environment.

PubMed

Sieber, Stefan; Wirth, Lorenz; Cavak, Nino; Koenigsmark, Marielle; Marx, Uwe; Lauster, Roland; Rosowski, Mark

2018-02-01

Multipotent haematopoietic stem and progenitor cells (HSPCs) are the source for all blood cell types. The bone marrow stem cell niche in which the HSPCs are maintained is known to be vital for their maintenance. Unfortunately, to date, no in vitro model exists that accurately mimics the aspects of the bone marrow niche and simultaneously allows the long-term culture of HSPCs. In this study, a novel three-dimensional coculture model is presented, based on a hydroxyapatite coated zirconium oxide scaffold, comprising of human mesenchymal stromal cells (MSCs) and cord blood derived HSPCs, enabling successful HSPC culture for a time span of 28 days within the microfluidic multiorgan chip. The HSPCs were found to stay in their primitive state (CD34 + CD38 - ) and capable of granulocyte, erythrocyte, macrophage, megakaryocyte colony formation. Furthermore, a microenvironment was formed bearing molecular and structural similarity to the in vivo bone marrow niche containing extracellular matrix and signalling molecules known to play an important role in HSPC homeostasis. Here, a novel human in vitro bone marrow model is presented for the first time, capable of long-term culture of primitive HSPCs in a microfluidic environment. Copyright © 2017 John Wiley & Sons, Ltd.

Humic First Theory: A New Theory on the Origin of Life

NASA Astrophysics Data System (ADS)

Daei, Mohammad Ali; Daei, Manijeh; Daei, Bijan

2017-04-01

In 1953, Miller & Urey through a brilliant experiment demonstrated that the building blocks of life could evolve in primitive earth conditions [1]. During the recent years scientists revealed that organic matters are not very rare compounds in comets, asteroids, and meteorites which have bombarded the ancient earth repeatedly [2]. So simple organic molecules on early earth could be quite enough to start chemical evolution and steadily, proceeded to the very simple form of life. Many theories have tried to explain how life emerged from non life, but failed, largely due to the lack of a distinct methodology. There is a huge gap between the simple building blocks, like amino acid, sugar, and lipid molecules, to a living cell with a very sophisticated structure and organization. It is unacceptable to fill this great distance, only by accidental reactions in a passive media (primitive soap) even, over a very long time. Obviously, manufacturing of a primitive cell required a natural factory with rather firm and resistant basement, plenty of organic and inorganic raw materials and qualified production line, plus some sources of energy. There were plenty of solar energy and water in the early Earth, but what about the other factors? Availability of essential minerals was not guaranteed at all, in primitive earth which covered with bare, dead rocks. While we are not able today, to multiply any microorganisms in ideal conditions of modern laboratory in the absence of only one of essential nutrients or elements, how can we expect primitive cells appear on early earth conditions without the support of soluble minerals and organic matters? Ideal production line must be active and protective, have catalyzing ability, could provide numerous opportunities for interaction between basic bio molecules (mainly RNA and proteins) and above all, have capability to react with different sources of energy. There are strong evidences that show only some form of stable, rich and active organic matter like modern "humic substances" could perform this great and complicated duty. A mass of warm, wet clay mixed with enough humic substances (HS) in suitable PH, could provide all above requirements, and promote biochemical evolution step by step toward a functional primitive cell. HS are fluorescent compounds and could transform UV radiation to usable light. In addition these protective materials could provide chemical energy plus balanced minerals and organic molecules. While everything in non living world is reducing energy, HS can collect more and more material and energy like a living organism. Fortunately, there are reliable evidences that HS could be accessible on ancient Earth. In fact Ziechman et al [7], in 1994 by finding humic material in Miller's experimental vessels proved that humic substances could be generated on early Earth conditions by polymerizing simple organic molecules. Our investigations show elemental selection and also chairal selection for life are proportionately tailored to Humic materials. For example nearly all heavy metals make insoluble compounds with HS, hence omitted from life processes. In contrast all essential elements have appropriate affinity and workability with HS. There is reliable evidence that shows HS prefer left amino acids and right sugars. As you see many signs and symptoms are referring to "humic substances" as the mother of life, at least on this planet.

Homo naledi, a new species of the genus Homo from the Dinaledi Chamber, South Africa

PubMed Central

Berger, Lee R; Hawks, John; de Ruiter, Darryl J; Churchill, Steven E; Schmid, Peter; Delezene, Lucas K; Kivell, Tracy L; Garvin, Heather M; Williams, Scott A; DeSilva, Jeremy M; Skinner, Matthew M; Musiba, Charles M; Cameron, Noel; Holliday, Trenton W; Harcourt-Smith, William; Ackermann, Rebecca R; Bastir, Markus; Bogin, Barry; Bolter, Debra; Brophy, Juliet; Cofran, Zachary D; Congdon, Kimberly A; Deane, Andrew S; Dembo, Mana; Drapeau, Michelle; Elliott, Marina C; Feuerriegel, Elen M; Garcia-Martinez, Daniel; Green, David J; Gurtov, Alia; Irish, Joel D; Kruger, Ashley; Laird, Myra F; Marchi, Damiano; Meyer, Marc R; Nalla, Shahed; Negash, Enquye W; Orr, Caley M; Radovcic, Davorka; Schroeder, Lauren; Scott, Jill E; Throckmorton, Zachary; Tocheri, Matthew W; VanSickle, Caroline; Walker, Christopher S; Wei, Pianpian; Zipfel, Bernhard

2015-01-01

Homo naledi is a previously-unknown species of extinct hominin discovered within the Dinaledi Chamber of the Rising Star cave system, Cradle of Humankind, South Africa. This species is characterized by body mass and stature similar to small-bodied human populations but a small endocranial volume similar to australopiths. Cranial morphology of H. naledi is unique, but most similar to early Homo species including Homo erectus, Homo habilis or Homo rudolfensis. While primitive, the dentition is generally small and simple in occlusal morphology. H. naledi has humanlike manipulatory adaptations of the hand and wrist. It also exhibits a humanlike foot and lower limb. These humanlike aspects are contrasted in the postcrania with a more primitive or australopith-like trunk, shoulder, pelvis and proximal femur. Representing at least 15 individuals with most skeletal elements repeated multiple times, this is the largest assemblage of a single species of hominins yet discovered in Africa. DOI: http://dx.doi.org/10.7554/eLife.09560.001 PMID:26354291

17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Advanced Epithelial Cancer, Malignant Lymphoma, or Sarcoma

ClinicalTrials.gov

2013-02-06

AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Primary CNS Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Chondrosarcoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Nodal Marginal Zone B-cell Lymphoma; Ovarian Sarcoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Osteosarcoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Uterine Sarcoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Stage IV Uterine Sarcoma; Unspecified Adult Solid Tumor, Protocol Specific

Shape-Shifted Red Blood Cells: A Novel Red Blood Cell Stage?

PubMed Central

Chico, Verónica; Puente-Marin, Sara; Ciordia, Sergio; Mena, María Carmen; Carracedo, Begoña; Mercado, Luis; Coll, Julio

2018-01-01

Primitive nucleated erythroid cells in the bloodstream have long been suggested to be more similar to nucleated red cells of fish, amphibians, and birds than the red cells of fetal and adult mammals. Rainbow trout Ficoll-purified red blood cells (RBCs) cultured in vitro undergo morphological changes, especially when exposed to stress, and enter a new cell stage that we have coined shape-shifted RBCs (shRBCs). We have characterized these shRBCs using transmission electron microscopy (TEM) micrographs, Wright–Giemsa staining, cell marker immunostaining, and transcriptomic and proteomic evaluation. shRBCs showed reduced density of the cytoplasm, hemoglobin loss, decondensed chromatin in the nucleus, and striking expression of the B lymphocyte molecular marker IgM. In addition, shRBCs shared some features of mammalian primitive pyrenocytes (extruded nucleus surrounded by a thin rim of cytoplasm and phosphatidylserine (PS) exposure on cell surface). These shRBCs were transiently observed in heat-stressed rainbow trout bloodstream for three days. Functional network analysis of combined transcriptomic and proteomic studies resulted in the identification of proteins involved in pathways related to the regulation of cell morphogenesis involved in differentiation, cellular response to stress, and immune system process. In addition, shRBCs increased interleukin 8 (IL8), interleukin 1 β (IL1β), interferon ɣ (IFNɣ), and natural killer enhancing factor (NKEF) protein production in response to viral hemorrhagic septicemia virus (VHSV). In conclusion, shRBCs may represent a novel cell stage that participates in roles related to immune response mediation, homeostasis, and the differentiation and development of blood cells. PMID:29671811

Shape-Shifted Red Blood Cells: A Novel Red Blood Cell Stage?

PubMed

Chico, Verónica; Puente-Marin, Sara; Nombela, Iván; Ciordia, Sergio; Mena, María Carmen; Carracedo, Begoña; Villena, Alberto; Mercado, Luis; Coll, Julio; Ortega-Villaizan, María Del Mar

2018-04-19

Primitive nucleated erythroid cells in the bloodstream have long been suggested to be more similar to nucleated red cells of fish, amphibians, and birds than the red cells of fetal and adult mammals. Rainbow trout Ficoll-purified red blood cells (RBCs) cultured in vitro undergo morphological changes, especially when exposed to stress, and enter a new cell stage that we have coined shape-shifted RBCs (shRBCs). We have characterized these shRBCs using transmission electron microscopy (TEM) micrographs, Wright⁻Giemsa staining, cell marker immunostaining, and transcriptomic and proteomic evaluation. shRBCs showed reduced density of the cytoplasm, hemoglobin loss, decondensed chromatin in the nucleus, and striking expression of the B lymphocyte molecular marker IgM. In addition, shRBCs shared some features of mammalian primitive pyrenocytes (extruded nucleus surrounded by a thin rim of cytoplasm and phosphatidylserine (PS) exposure on cell surface). These shRBCs were transiently observed in heat-stressed rainbow trout bloodstream for three days. Functional network analysis of combined transcriptomic and proteomic studies resulted in the identification of proteins involved in pathways related to the regulation of cell morphogenesis involved in differentiation, cellular response to stress, and immune system process. In addition, shRBCs increased interleukin 8 (IL8), interleukin 1 β (IL1β), interferon ɣ (IFNɣ), and natural killer enhancing factor (NKEF) protein production in response to viral hemorrhagic septicemia virus (VHSV). In conclusion, shRBCs may represent a novel cell stage that participates in roles related to immune response mediation, homeostasis, and the differentiation and development of blood cells.

Rapid Decimation for Direct Volume Rendering

NASA Technical Reports Server (NTRS)

Gibbs, Jonathan; VanGelder, Allen; Verma, Vivek; Wilhelms, Jane

1997-01-01

An approach for eliminating unnecessary portions of a volume when producing a direct volume rendering is described. This reduction in volume size sacrifices some image quality in the interest of rendering speed. Since volume visualization is often used as an exploratory visualization technique, it is important to reduce rendering times, so the user can effectively explore the volume. The methods presented can speed up rendering by factors of 2 to 3 with minor image degradation. A family of decimation algorithms to reduce the number of primitives in the volume without altering the volume's grid in any way is introduced. This allows the decimation to be computed rapidly, making it easier to change decimation levels on the fly. Further, because very little extra space is required, this method is suitable for the very large volumes that are becoming common. The method is also grid-independent, so it is suitable for multiple overlapping curvilinear and unstructured, as well as regular, grids. The decimation process can proceed automatically, or can be guided by the user so that important regions of the volume are decimated less than unimportant regions. A formal error measure is described based on a three-dimensional analog of the Radon transform. Decimation methods are evaluated based on this metric and on direct comparison with reference images.

Novel Target for Ameliorating Pain and Other Problems after SCI: Spontaneous Activity in Nociceptors

DTIC Science & Technology

2016-06-01

BSCB will permit blood-borne mye- loid and lymphoid immune cells to enter the spinal cord parenchyma and exert direct inflammatory actions on central...primitive innate immune system is the first line of defense against pathogens and toxins; it is always present and it depends upon diverse cell types that...adaptive immune system, the innate immune system does not em- ploy antigen-specific humoral and cell -mediated immunity mecha- nisms. Two innate immune

Using Depth Recovery in Humans

DTIC Science & Technology

1988-07-07

presence of oriented luminance discontinuities or "edges" in the image data (Marr & Poggio, i976; Dey, 1975; Nelson, 1975 & 1977; Marr, Palm & Poggio, 1978...primitives, namely computational expense, is rapidly diminishing as we continue to benefit from dramatic advances in signal processing hardware...dimensional weighting function of simple cells are well fitted by Gabor functions. Pollen & Ronner (1981) demonstrated that simple cells which are tuned to

The molecular characterization of porcine egg precursor cells

PubMed Central

Tsai, Te-Sha; Johnson, Jacqueline; White, Yvonne; John, Justin C.

2017-01-01

Female-factor infertility can be caused by poor oocyte quality and depleted ovarian reserves. Egg precursor cells (EPCs), isolated from the ovarian cortex, have the potential to be used to overcome female infertility. We aimed to define the origins of EPCs by analyzing their gene expression profiles and mtDNA content using a mini-pig model. We characterized FAC-sorted DDX4+-derived porcine EPCs by performing RNA-sequencing and determined that they utilize pathways important for cell cycle and proliferation, which supports the existence of adult mitotically active oogonial cells. Expression of the pluripotent markers Sox2 and Oct4, and the primitive germ cell markers Blimp1 and Stella were not detected. However, Nanog and Ddx4 were expressed, as were the primitive germ cell markers Fragilis, c-Kit and Tert. Moreover, porcine EPCs expressed self-renewal and proliferation markers including Myc, Esrrb, Id2, Klf4, Klf5, Stat3, Fgfr1, Fgfr2 and Il6st. The presence of Zp1, Zp2, Zp3 and Nobox were not detected, indicating that porcine EPCs are not indicative of mature primordial oocytes. We performed mitochondrial DNA Next Generation Sequencing and determined that one mtDNA variant harbored by EPCs was present in oocytes, preimplantation embryos and somatic tissues over three generations in our mini-pig model indicating the potential germline origin of EPCs. PMID:28969006

Primitive neuroectodermal tumor of the cervix uteri. A case report.

PubMed

Horn, L C; Fischer, U; Bilek, K

1997-02-01

Primitive neuroectodermal tumors (PNET) of the female genital tract are rare and more common in the ovary, but uncommon in the cervix uteri. A 26-year-old woman presented with suspect cervical smears. The conization specimen showed a small cell non-keratinised squamous cell carcinoma with involved margins. The patient underwent radical abdominal hysterectomy and pelvic lymphonodectomy. The microscopic examination showed a densely cellular tumor of small neuroendocrine cells with scanty cytoplasm and rosettes. Immunohistochemically, the cells were slightly positive for NSE and negative for S 100, GFAP, neurofilaments, squamous cell cytokeratin 1, vimentin, desmin and leukocyte common antigen. The diagnosis of PNET, stage pT1b1,N0, M0 was made. The patient underwent adjuvant pelvic radiation. Three years later, pulmonary metastases occured. Radiation therapy of the thorax and six courses of combination chemotherapy (5-FU and cis-platinium) could not prevent tumor progression. The patient died 4.2 years after diagnosis. The autopsy showed widespread lymphatic metastases and hepatic, pulmonal and skeletal metastases and a peritoneal carcinosis. The tumors are resistent to radio- and chemotherapy, and the prognosis is generally poor. Up to 15% foci of squamous or glandular differentiation occur in or adjacent to these tumors. So the authors favor the histogenesis from a pluripotent endocervical stem cell. The neuroendocrine component of mixed tumors improve the prognosis. Therefore, it is necessary to recognize this component.

DNase I hypersensitivity and epsilon-globin transcriptional enhancement are separable in locus control region (LCR) HS1 mutant human beta-globin YAC transgenic mice.

PubMed

Shimotsuma, Motoshi; Okamura, Eiichi; Matsuzaki, Hitomi; Fukamizu, Akiyoshi; Tanimoto, Keiji

2010-05-07

Expression of the five beta-like globin genes (epsilon, Ggamma, Agamma, delta, beta) in the human beta-globin locus depends on enhancement by the locus control region, which consists of five DNase I hypersensitive sites (5'HS1 through 5'HS5). We report here a novel enhancer activity in 5'HS1 that appears to be potent in transfected K562 cells. Deletion analyses identified a core activating element that bound to GATA-1, and a two-nucleotide mutation that disrupted GATA-1 binding in vitro abrogated 5'HS1 enhancer activity in transfection experiments. To determine the in vivo role of this GATA site, we generated multiple lines of human beta-globin YAC transgenic mice bearing the same two-nucleotide mutation. In the mutant mice, epsilon-, but not gamma-globin, gene expression in primitive erythroid cells was severely attenuated, while adult beta-globin gene expression in definitive erythroid cells was unaffected. Interestingly, DNaseI hypersensitivity near the 5'HS1 mutant sequence was eliminated in definitive erythroid cells, whereas it was only mildly affected in primitive erythroid cells. We therefore conclude that, although the GATA site in 5'HS1 is critical for efficient epsilon-globin gene expression, hypersensitive site formation per se is independent of 5'HS1 function, if any, in definitive erythroid cells.

Efficacy of 68Ga-DOTATOC Positron Emission Tomography (PET) CT in Children and Young Adults With Brain Tumors

ClinicalTrials.gov

2017-04-27

Acoustic Schwannoma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Supratentorial Ependymoma; Meningeal Melanocytoma; Newly Diagnosed Childhood Ependymoma; Recurrent Adult Brain Tumor; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Diffuse Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Fibrillary Astrocytoma; Recurrent Childhood Gemistocytic Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Oligoastrocytoma; Recurrent Childhood Oligodendroglioma; Recurrent Childhood Pilocytic Astrocytoma; Recurrent Childhood Pilomyxoid Astrocytoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Pleomorphic Xanthoastrocytoma; Recurrent Childhood Protoplasmic Astrocytoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Anaplastic Oligodendroglioma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Cerebellar Astrocytoma; Untreated Childhood Cerebral Astrocytoma; Untreated Childhood Diffuse Astrocytoma; Untreated Childhood Fibrillary Astrocytoma; Untreated Childhood Gemistocytic Astrocytoma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliomatosis Cerebri; Untreated Childhood Gliosarcoma; Untreated Childhood Medulloblastoma; Untreated Childhood Oligoastrocytoma; Untreated Childhood Oligodendroglioma; Untreated Childhood Pilocytic Astrocytoma; Untreated Childhood Pilomyxoid Astrocytoma; Untreated Childhood Pineoblastoma; Untreated Childhood Pleomorphic Xanthoastrocytoma; Untreated Childhood Protoplasmic Astrocytoma; Untreated Childhood Subependymal Giant Cell Astrocytoma; Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor; Untreated Childhood Visual Pathway and Hypothalamic Glioma; Untreated Childhood Visual Pathway Glioma

Niche displacement of human leukemic stem cells uniquely allows their competitive replacement with healthy HSPCs

PubMed Central

Boyd, Allison L.; Campbell, Clinton J.V.; Hopkins, Claudia I.; Fiebig-Comyn, Aline; Russell, Jennifer; Ulemek, Jelena; Foley, Ronan; Leber, Brian; Xenocostas, Anargyros; Collins, Tony J.

2014-01-01

Allogeneic hematopoietic stem cell (HSC) transplantation (HSCT) is currently the leading strategy to manage acute myeloid leukemia (AML). However, treatment-related morbidity limits the patient generalizability of HSCT use, and the survival of leukemic stem cells (LSCs) within protective areas of the bone marrow (BM) continues to lead to high relapse rates. Despite growing appreciation for the significance of the LSC microenvironment, it has remained unresolved whether LSCs preferentially situate within normal HSC niches or whether their niche requirements are more promiscuous. Here, we provide functional evidence that the spatial localization of phenotypically primitive human AML cells is restricted to niche elements shared with their normal counterparts, and that their intrinsic ability to initiate and retain occupancy of these niches can be rivaled by healthy hematopoietic stem and progenitor cells (HSPCs). When challenged in competitive BM repopulation assays, primary human leukemia-initiating cells (L-ICs) can be consistently outperformed by HSPCs for BM niche occupancy in a cell dose-dependent manner that ultimately compromises long-term L-IC renewal and subsequent leukemia-initiating capacity. The effectiveness of this approach could be demonstrated using cytokine-induced mobilization of established leukemia from the BM that facilitated the replacement of BM niches with transplanted HSPCs. These findings identify a functional vulnerability of primitive leukemia cells, and suggest that clinical development of these novel transplantation techniques should focus on the dissociation of L-IC–niche interactions to improve competitive replacement with healthy HSPCs during HSCT toward increased survival of patients. PMID:25180064

An immunohistochemical study of neuropeptides and neuronal cytoskeletal proteins in the neuroepithelial component of a spontaneous murine ovarian teratoma. Primitive neuroepithelium displays immunoreactivity for neuropeptides and neuron-associated beta-tubulin isotype.

PubMed Central

Caccamo, D. V.; Herman, M. M.; Frankfurter, A.; Katsetos, C. D.; Collins, V. P.; Rubinstein, L. J.

1989-01-01

Approximately one third of the female mice of the LTXBO strain develop spontaneous ovarian teratomas. These tumors contain a large neuroepithelial component, which includes primitive neural structures resembling embryonic neural tubes (medulloepithelial rosettes), ependymoblastic and ependymal rosettes, neuroblasts, mature ganglionic neurons, myelinated neurites, and astrocytes. The purpose of this study was to characterize these tumors according to the immunohistochemical location of some well-characterized trophic and regulatory neuropeptides and neurotransmitters, several neuronal-associated cytoskeletal proteins, and other proteins indicative of neuronal and glial differentiation. Medulloepithelial rosettes showed focal serotonin-like, opioid peptide-like and gamma-amino butyric acid-like immunoreactivity, and displayed immunostaining for the neuron-associated class III beta-tubulin isotype. The mature ganglion cells were also immunoreactive for these markers, and, in addition, for somatostatin, cholecystokinin, bombesin, glucagon, vasoactive intestinal peptide, and neuropeptide Y. Mature ganglion cells were also immunoreactive for proteins associated with the neuronal cytoskeleton (including microtubule-associated proteins, MAP2 and tau, and higher molecular weight phosphorylated and non-phosphorylated neurofilament subunits), neuron-specific enolase, and synaptophysin. Undifferentiated stem cells, ependymoblastic and ependymal rosettes, and astroglia all stained with a monoclonal antibody that recognizes all mammalian beta-tubulin isotypes, but did not react with antibodies to neuronal-associated cytoskeletal proteins or neuropeptides. Neuropeptide-like immunoreactivity and demonstration of the class III beta-tubulin isotype indicate early neuronal commitment in neoplastic primitive neuroepithelium. These patterns of immunoreactivity closely follow those encountered in the normal neurocytogenesis of the mammalian and avian forebrain, and increase the precision with which the early stages of progressive neuroepithelial differentiation can be analyzed in human embryonal tumors of the CNS. Images Figure 1 Figure 2 Figure 3 PMID:2817080

Epidermal differentiation in embryos of the tuatara Sphenodon punctatus (Reptilia, Sphenodontidae) in comparison with the epidermis of other reptiles.

PubMed

Alibardi, L; Gill, B J

2007-07-01

Studying the epidermis in primitive reptiles can provide clues regarding evolution of the epidermis during land adaptation in vertebrates. With this aim, the development of the skin of the relatively primitive reptile Sphenodon punctatus in representative embryonic stages was studied by light and electron microscopy and compared with that of other reptiles previously studied. The dermis organizes into a superficial and deep portion when the epidermis starts to form the first layers. At embryonic stages comparable with those of lizards, only one layer of the inner periderm is formed beneath the outer periderm. This also occurs in lizards and snakes so far studied. The outer and inner periderm form the embryonic epidermis and accumulate thick, coarse filaments (25-30 nm thick) and sparse alpha-keratin filaments as in other reptiles. Beneath the embryonic epidermis an oberhautchen and beta-cells form small horny tips that represent overlapping borders along the margin of beta-cells that overlap other beta-cells (in a tile-like arrangement). The tips resemble those of agamine lizards but at a small scale, forming a lamellate-spinulated pattern as previously described in adult epidermis. The embryonic epidermis matures by the dispersion of coarse filaments among keratin at the end of embryonic development and is shed around hatching. The presence of these matrix organelles in the embryonic epidermis of this primitive reptile further indicates that amniote epidermis acquired interkeratin matrix proteins early for land adaptation. Unlike the condition in lizards and snakes, a shedding complex is not formed in the epidermis of embryonic S. punctatus that is like that of the adult. Therefore, as in chelonians and crocodilians, the epidermis of S. punctatus also represents an initial stage that preceded the evolution of the shedding complex for moulting.

Epidermal differentiation in embryos of the tuatara Sphenodon punctatus (Reptilia, Sphenodontidae) in comparison with the epidermis of other reptiles

PubMed Central

Alibardi, L; Gill, B J

2007-01-01

Studying the epidermis in primitive reptiles can provide clues regarding evolution of the epidermis during land adaptation in vertebrates. With this aim, the development of the skin of the relatively primitive reptile Sphenodon punctatus in representative embryonic stages was studied by light and electron microscopy and compared with that of other reptiles previously studied. The dermis organizes into a superficial and deep portion when the epidermis starts to form the first layers. At embryonic stages comparable with those of lizards, only one layer of the inner periderm is formed beneath the outer periderm. This also occurs in lizards and snakes so far studied. The outer and inner periderm form the embryonic epidermis and accumulate thick, coarse filaments (25–30 nm thick) and sparse alpha-keratin filaments as in other reptiles. Beneath the embryonic epidermis an oberhautchen and beta-cells form small horny tips that represent overlapping borders along the margin of beta-cells that overlap other beta-cells (in a tile-like arrangement). The tips resemble those of agamine lizards but at a small scale, forming a lamellate-spinulated pattern as previously described in adult epidermis. The embryonic epidermis matures by the dispersion of coarse filaments among keratin at the end of embryonic development and is shed around hatching. The presence of these matrix organelles in the embryonic epidermis of this primitive reptile further indicates that amniote epidermis acquired interkeratin matrix proteins early for land adaptation. Unlike the condition in lizards and snakes, a shedding complex is not formed in the epidermis of embryonic S. punctatus that is like that of the adult. Therefore, as in chelonians and crocodilians, the epidermis of S. punctatus also represents an initial stage that preceded the evolution of the shedding complex for moulting. PMID:17532799

Secure Heterogeneous Multicore Platform Through Diversity and Redundancy

DTIC Science & Technology

2012-03-31

implementation detects synchronization in this way. If a programmer uses custom synchronization primitives , our approach assumes that such primitives ... synchronization primitives . Primitives such as barriers and spinlocks explicitly enforce a pre- determined ordering among threads. Therefore, the outcome of...these synchronization operations are deterministic. In the discussion, we will refer to these primitives as ordering synchronization operations. On the

Atmospheric model development in support of SEASAT. Volume 2: Analysis models

NASA Technical Reports Server (NTRS)

Langland, R. A.

1977-01-01

As part of the SEASAT program of NASA, two sets of analysis programs were developed for the Jet Propulsion Laboratory. One set of programs produce 63 x 63 horizontal mesh analyses on a polar stereographic grid. The other set produces 187 x 187 third mesh analyses. The parameters analyzed include sea surface temperature, sea level pressure and twelve levels of upper air temperature, height and wind analyses. The analysis output is used to initialize the primitive equation forecast models.

Entropy jump across an inviscid shock wave

NASA Technical Reports Server (NTRS)

Salas, Manuel D.; Iollo, Angelo

1995-01-01

The shock jump conditions for the Euler equations in their primitive form are derived by using generalized functions. The shock profiles for specific volume, speed, and pressure are shown to be the same, however density has a different shock profile. Careful study of the equations that govern the entropy shows that the inviscid entropy profile has a local maximum within the shock layer. We demonstrate that because of this phenomenon, the entropy, propagation equation cannot be used as a conservation law.

HOXB4 overexpression mediates very rapid stem cell regeneration and competitive hematopoietic repopulation.

PubMed

Antonchuk, J; Sauvageau, G; Humphries, R K

2001-09-01

Hox transcription factors have emerged as important regulators of hematopoiesis. In particular, we have shown that overexpression of HOXB4 in mouse bone marrow can greatly enhance the level of hematopoietic stem cell (HSC) regeneration achieved at late times (> 4 months) posttransplantation. The objective of this study was to resolve if HOXB4 increases the rate and/or duration of HSC regeneration, and also to see if this enhancement was associated with impaired production of end cells or would lead to competitive reconstitution of all compartments. Retroviral vectors were generated with the GFP reporter gene +/- HOXB4 to enable the isolation and direct tracking of transduced cells in culture or following transplantation. Stem cell recovery was measured by limit dilution assay for long-term competitive repopulating cells (CRU). HOXB4-overexpressing cells have enhanced growth in vitro, as demonstrated by their rapid dominance in mixed cultures and their shortened population doubling time. Furthermore, HOXB4-transduced cells have a marked competitive repopulating advantage in vivo in both primitive and mature compartments. CRU recovery in HOXB4 recipients was extremely rapid, reaching 25% of normal by 14 days posttransplant or some 80-fold greater than control transplant recipients, and attaining normal numbers by 12 weeks. Mice transplanted with even higher numbers of HOXB4-transduced CRU regenerated up to but not beyond the normal CRU levels. HOXB4 is a potent enhancer of primitive hematopoietic cell growth, likely by increasing self-renewal probability but without impairing homeostatic control of HSC population size or the rate of production and maintenance of mature end cells.

Stereotactic Radiosurgery in Treating Patients With Brain Tumors

ClinicalTrials.gov

2012-03-21

Adult Central Nervous System Germ Cell Tumor; Adult Malignant Meningioma; Adult Medulloblastoma; Adult Noninfiltrating Astrocytoma; Adult Oligodendroglioma; Adult Craniopharyngioma; Adult Meningioma; Brain Metastases; Adult Ependymoma; Adult Pineal Parenchymal Tumor; Adult Brain Stem Glioma; Adult Infiltrating Astrocytoma; Mixed Gliomas; Stage IV Peripheral Primitive Neuroectodermal Tumor

Non-canonical Wnt signalling modulates the endothelial shear stress flow sensor in vascular remodelling

PubMed Central

Franco, Claudio A; Jones, Martin L; Bernabeu, Miguel O; Vion, Anne-Clemence; Barbacena, Pedro; Fan, Jieqing; Mathivet, Thomas; Fonseca, Catarina G; Ragab, Anan; Yamaguchi, Terry P; Coveney, Peter V; Lang, Richard A; Gerhardt, Holger

2016-01-01

Endothelial cells respond to molecular and physical forces in development and vascular homeostasis. Deregulation of endothelial responses to flow-induced shear is believed to contribute to many aspects of cardiovascular diseases including atherosclerosis. However, how molecular signals and shear-mediated physical forces integrate to regulate vascular patterning is poorly understood. Here we show that endothelial non-canonical Wnt signalling regulates endothelial sensitivity to shear forces. Loss of Wnt5a/Wnt11 renders endothelial cells more sensitive to shear, resulting in axial polarization and migration against flow at lower shear levels. Integration of flow modelling and polarity analysis in entire vascular networks demonstrates that polarization against flow is achieved differentially in artery, vein, capillaries and the primitive sprouting front. Collectively our data suggest that non-canonical Wnt signalling stabilizes forming vascular networks by reducing endothelial shear sensitivity, thus keeping vessels open under low flow conditions that prevail in the primitive plexus. DOI: http://dx.doi.org/10.7554/eLife.07727.001 PMID:26845523

A network of epigenetic regulators guides developmental haematopoiesis in vivo.

PubMed

Huang, Hsuan-Ting; Kathrein, Katie L; Barton, Abby; Gitlin, Zachary; Huang, Yue-Hua; Ward, Thomas P; Hofmann, Oliver; Dibiase, Anthony; Song, Anhua; Tyekucheva, Svitlana; Hide, Winston; Zhou, Yi; Zon, Leonard I

2013-12-01

The initiation of cellular programs is orchestrated by key transcription factors and chromatin regulators that activate or inhibit target gene expression. To generate a compendium of chromatin factors that establish the epigenetic code during developmental haematopoiesis, a large-scale reverse genetic screen was conducted targeting orthologues of 425 human chromatin factors in zebrafish. A set of chromatin regulators was identified that target different stages of primitive and definitive blood formation, including factors not previously implicated in haematopoiesis. We identified 15 factors that regulate development of primitive erythroid progenitors and 29 factors that regulate development of definitive haematopoietic stem and progenitor cells. These chromatin factors are associated with SWI/SNF and ISWI chromatin remodelling, SET1 methyltransferase, CBP-p300-HBO1-NuA4 acetyltransferase, HDAC-NuRD deacetylase, and Polycomb repressive complexes. Our work provides a comprehensive view of how specific chromatin factors and their associated complexes play a major role in the establishment of haematopoietic cells in vivo.

Clearance detector and method for motion and distance

DOEpatents

Xavier, Patrick G [Albuquerque, NM

2011-08-09

A method for correct and efficient detection of clearances between three-dimensional bodies in computer-based simulations, where one or both of the volumes is subject to translation and/or rotations. The method conservatively determines of the size of such clearances and whether there is a collision between the bodies. Given two bodies, each of which is undergoing separate motions, the method utilizes bounding-volume hierarchy representations for the two bodies and, mappings and inverse mappings for the motions of the two bodies. The method uses the representations, mappings and direction vectors to determine the directionally furthest locations of points on the convex hulls of the volumes virtually swept by the bodies and hence the clearance between the bodies, without having to calculate the convex hulls of the bodies. The method includes clearance detection for bodies comprising convex geometrical primitives and more specific techniques for bodies comprising convex polyhedra.

Data Management Systems (DMS): Complex data types study. Volume 1: Appendices A-B. Volume 2: Appendices C1-C5. Volume 3: Appendices D1-D3 and E

NASA Technical Reports Server (NTRS)

Leibfried, T. F., Jr.; Davari, Sadegh; Natarajan, Swami; Zhao, Wei

1992-01-01

Two categories were chosen for study: the issue of using a preprocessor on Ada code of Application Programs which would interface with the Run-Time Object Data Base Standard Services (RODB STSV), the intent was to catch and correct any mis-registration errors of the program coder between the user declared Objects, their types, their addresses, and the corresponding RODB definitions; and RODB STSV Performance Issues and Identification of Problems with the planned methods for accessing Primitive Object Attributes, this included the study of an alternate storage scheme to the 'store objects by attribute' scheme in the current design of the RODB. The study resulted in essentially three separate documents, an interpretation of the system requirements, an assessment of the preliminary design, and a detailing of the components of a detailed design.

Development and application of CATIA-GDML geometry builder

NASA Astrophysics Data System (ADS)

Belogurov, S.; Berchun, Yu; Chernogorov, A.; Malzacher, P.; Ovcharenko, E.; Schetinin, V.

2014-06-01

Due to conceptual difference between geometry descriptions in Computer-Aided Design (CAD) systems and particle transport Monte Carlo (MC) codes direct conversion of detector geometry in either direction is not feasible. The paper presents an update on functionality and application practice of the CATIA-GDML geometry builder first introduced at CHEP2010. This set of CATIAv5 tools has been developed for building a MC optimized GEANT4/ROOT compatible geometry based on the existing CAD model. The model can be exported via Geometry Description Markup Language (GDML). The builder allows also import and visualization of GEANT4/ROOT geometries in CATIA. The structure of a GDML file, including replicated volumes, volume assemblies and variables, is mapped into a part specification tree. A dedicated file template, a wide range of primitives, tools for measurement and implicit calculation of parameters, different types of multiple volume instantiation, mirroring, positioning and quality check have been implemented. Several use cases are discussed.

Efficient high-quality volume rendering of SPH data.

PubMed

Fraedrich, Roland; Auer, Stefan; Westermann, Rüdiger

2010-01-01

High quality volume rendering of SPH data requires a complex order-dependent resampling of particle quantities along the view rays. In this paper we present an efficient approach to perform this task using a novel view-space discretization of the simulation domain. Our method draws upon recent work on GPU-based particle voxelization for the efficient resampling of particles into uniform grids. We propose a new technique that leverages a perspective grid to adaptively discretize the view-volume, giving rise to a continuous level-of-detail sampling structure and reducing memory requirements compared to a uniform grid. In combination with a level-of-detail representation of the particle set, the perspective grid allows effectively reducing the amount of primitives to be processed at run-time. We demonstrate the quality and performance of our method for the rendering of fluid and gas dynamics SPH simulations consisting of many millions of particles.

On the Behavior of Eisenstein Series Through Elliptic Degeneration

NASA Astrophysics Data System (ADS)

Garbin, D.; Pippich, A.-M. V.

2009-12-01

Let Γ be a Fuchsian group of the first kind acting on the hyperbolic upper half plane {mathbb{H}}, and let {M = Γbackslash mathbb{H}} be the associated finite volume hyperbolic Riemann surface. If γ is a primitive parabolic, hyperbolic, resp. elliptic element of Γ, there is an associated parabolic, hyperbolic, resp. elliptic Eisenstein series. In this article, we study the limiting behavior of these Eisenstein series on an elliptically degenerating family of finite volume hyperbolic Riemann surfaces. In particular, we prove the following result. The elliptic Eisenstein series associated to a degenerating elliptic element converges up to a factor to the parabolic Eisenstein series associated to the parabolic element which fixes the newly developed cusp on the limit surface.

Zebrafish numb and numblike are involved in primitive erythrocyte differentiation.

PubMed

Bresciani, Erica; Confalonieri, Stefano; Cermenati, Solei; Cimbro, Simona; Foglia, Efrem; Beltrame, Monica; Di Fiore, Pier Paolo; Cotelli, Franco

2010-12-13

Notch signaling is an evolutionarily conserved regulatory circuitry implicated in cell fate determination in various developmental processes including hematopoietic stem cell self-renewal and differentiation of blood lineages. Known endogenous inhibitors of Notch activity are Numb-Nb and Numblike-Nbl, which play partially redundant functions in specifying and maintaining neuronal differentiation. Nb and Nbl are expressed in most tissues including embryonic and adult hematopoietic tissues in mice and humans, suggesting possible roles for these proteins in hematopoiesis. We employed zebrafish to investigate the possible functional role of Numb and Numblike during hematopoiesis, as this system allows a detailed analysis even in embryos with severe defects that would be lethal in other organisms. Here we describe that nb/nbl knockdown results in severe reduction or absence of embryonic erythrocytes in zebrafish. Interestingly, nb/nbl knocked-down embryos present severe downregulation of the erythroid transcription factor gata1. This results in erythroblasts which fail to mature and undergo apoptosis. Our results indicate that Notch activity is increased in embryos injected with nb/nbl morpholino, and we show that inhibition of Notch activation can partially rescue the hematopoietic phenotype. Our results provide the first in vivo evidence of an involvement of Numb and Numblike in zebrafish erythroid differentiation during primitive hematopoiesis. Furthermore, we found that, at least in part, the nb/nbl morphant phenotype is due to enhanced Notch activation within hematopoietic districts, which in turn results in primitive erythroid differentiation defects.

Undifferentiated myxoid lipoblastoma with PLAG1-HAS2 fusion in an infant; morphologically mimicking primitive myxoid mesenchymal tumor of infancy (PMMTI)--diagnostic importance of cytogenetic and molecular testing and literature review.

PubMed

Warren, Mikako; Turpin, Brian K; Mark, Melissa; Smolarek, Teresa A; Li, Xia

2016-01-01

Lipoblastoma is a benign myxoid neoplasm arising in young children that typically demonstrates adipose differentiation. It is often morphologically indistinguishable from primitive myxoid mesenchymal tumor of infancy (PMMTI), which is characterized by a well-circumscribed myxoid mass with a proliferation of primitive mesenchymal cells with mild cytologic atypia. PMMTI occurs in the first year of life and is known to have locally aggressive behavior. No specific genetic rearrangements have been reported to date. In contrast, the presence of PLAG1 (Pleomorphic Adenoma Gene 1) rearrangement is diagnostic for lipoblastoma. We hereby demonstrate the combined application of multiple approaches to tackle the diagnostic challenges of a rapidly growing neck tumor in a 3-month-old female. An incisional tumor biopsy had features of an undifferentiated, myxoid mesenchymal neoplasm mimicking PMMTI. However, tumor cells showed diffuse nuclear expression by immunohistochemical (IHC) stain. Conventional cytogenetic and fluorescence in situ hybridization (FISH) analyses as well as next generation sequencing (NGS) demonstrated evidence of PLAG1 rearrangement, confirming the diagnosis of lipoblastoma. This experience warrants that undifferentiated myxoid lipoblastoma can mimic PMMTI, and the combination of cytogenetic and molecular approaches is essential to distinguish these two myxoid neoplasms. Literature on lipoblastomas with relevant molecular and cytogenetic findings is summarized. Our case is the first lipoblastoma diagnosed with a PLAG1 fusion defined by NGS technology. Copyright © 2016 Elsevier Inc. All rights reserved.

JAK2/STAT5 inhibition by nilotinib with ruxolitinib contributes to the elimination of CML CD34+ cells in vitro and in vivo

PubMed Central

Gallipoli, Paolo; Cook, Amy; Rhodes, Susan; Hopcroft, Lisa; Wheadon, Helen; Whetton, Anthony D.; Jørgensen, Heather G.; Bhatia, Ravi

2014-01-01

Chronic myeloid leukemia (CML) stem cell survival is not dependent on BCR-ABL protein kinase and treatment with ABL tyrosine kinase inhibitors cures only a minority of CML patients, thus highlighting the need for novel therapeutic targets. The Janus kinase (JAK)2/signal transducer and activator of transcription (STAT)5 pathway has recently been explored for providing putative survival signals to CML stem/progenitor cells (SPCs) with contradictory results. We investigated the role of this pathway using the JAK2 inhibitor, ruxolitinib (RUX). We demonstrated that the combination of RUX, at clinically achievable concentrations, with the specific and potent tyrosine kinase inhibitor nilotinib, reduced the activity of the JAK2/STAT5 pathway in vitro relative to either single agent alone. These effects correlated with increased apoptosis of CML SPCs in vitro and a reduction in primitive quiescent CML stem cells, including NOD.Cg-Prkdcscid IL2rgtm1Wjl /SzJ mice repopulating cells, induced by combination treatment. A degree of toxicity toward normal SPCs was observed with the combination treatment, although this related to mature B-cell engraftment in NOD.Cg-Prkdcscid IL2rgtm1Wjl /SzJ mice with minimal effects on primitive CD34+ cells. These results support the JAK2/STAT5 pathway as a relevant therapeutic target in CML SPCs and endorse the current use of nilotinib in combination with RUX in clinical trials to eradicate persistent disease in CML patients. PMID:24957147

IGF-1 Signaling Plays an Important Role in the Formation of Three-Dimensional Laminated Neural Retina and Other Ocular Structures From Human Embryonic Stem Cells.

PubMed

Mellough, Carla B; Collin, Joseph; Khazim, Mahmoud; White, Kathryn; Sernagor, Evelyne; Steel, David H W; Lako, Majlinda

2015-08-01

We and others have previously demonstrated that retinal cells can be derived from human embryonic stem cells (hESCs) and induced pluripotent stem cells under defined culture conditions. While both cell types can give rise to retinal derivatives in the absence of inductive cues, this requires extended culture periods and gives lower overall yield. Further understanding of this innate differentiation ability, the identification of key factors that drive the differentiation process, and the development of clinically compatible culture conditions to reproducibly generate functional neural retina is an important goal for clinical cell based therapies. We now report that insulin-like growth factor 1 (IGF-1) can orchestrate the formation of three-dimensional ocular-like structures from hESCs which, in addition to retinal pigmented epithelium and neural retina, also contain primitive lens and corneal-like structures. Inhibition of IGF-1 receptor signaling significantly reduces the formation of optic vesicle and optic cups, while exogenous IGF-1 treatment enhances the formation of correctly laminated retinal tissue composed of multiple retinal phenotypes that is reminiscent of the developing vertebrate retina. Most importantly, hESC-derived photoreceptors exhibit advanced maturation features such as the presence of primitive rod- and cone-like photoreceptor inner and outer segments and phototransduction-related functional responses as early as 6.5 weeks of differentiation, making these derivatives promising candidates for cell replacement studies and in vitro disease modeling. © 2015 AlphaMed Press.

Spindle Cell Epithelioma of the Vagina Shows Immunohistochemical Staining Supporting Its Origin From a Primitive/Progenitor Cell Population

DTIC Science & Technology

2001-04-01

broader spectrum of immunohistochemical stains is presented that supports the origin of these tumors from a progenitor cell popula- tion. REPORT OF A CASE ...with S100 protein, with coexpression of cytokeratins and vimentin and expression of estrogen and progesterone receptors, as previously reported in...SCEVs. In addition, diffuse expres- sion of CD34, CD99, and Bcl-2 immunohistochemical stains was found, which has not previously been reported . The

Phase transition of a cobalt-free perovskite as a high-performance cathode for intermediate-temperature solid oxide fuel cells.

PubMed

Jiang, Shanshan; Zhou, Wei; Niu, Yingjie; Zhu, Zhonghua; Shao, Zongping

2012-10-01

It is generally recognized that the phase transition of a perovskite may be detrimental to the connection between cathode and electrolyte. Moreover, certain phase transitions may induce the formation of poor electronic and ionic conducting phase(s), thereby lowering the electrochemical performance of the cathode. Here, we present a study on the phase transition of a cobalt-free perovskite (SrNb(0.1)Fe(0.9)O(3-δ), SNF) and evaluate its effect on the electrochemical performance of the fuel cell. SNF exists as a primitive perovskite structure with space group P4mm (99) at room temperature. As evidenced by in situ high-temperature X-ray diffraction measurements over the temperature range of 600 to 1000 °C, SNF undergoes a transformation to a tetragonal structure with a space group I4/m (87). This phase transition is accompanied by a moderate change in the volume, allowing a good cathode/electrolyte interface on thermal cycling. According to the electrochemical impedance spectroscopy evaluation, the I4/m phase exhibits positive effects on the cathode's performance, showing the highest oxygen reduction reaction activity of cobalt-free cathodes reported so far. This activity improvement is attributed to enhanced oxygen surface processes. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interlaminar differences in the pyramidal cell phenotype in parietal cortex of an Indian bat, cynopterus sphinx.

PubMed

Srivastava, U C; Pathak, S V

2010-10-30

To study interlaminar phenotypic variations in the pyramidal neurons of parietal isocortex in bat (Cynopterus sphinx), Golgi and Nissl methods have been employed. The parietal isocortex is relatively thin in the bat as compared to prototheria with layer III, V and VI accounting for more than two—thirds of total cortical thickness. Thick cell free layer I and thinnest accentuated layer II are quite in connotation with other chiropterids. Poor demarcation of layer III/IV in the present study is also in connotation with primitive eutherian mammal (i.e. prototherian) and other chiropterids. Most of the pyramidal cells in the different layers of the parietal isocortex are of typical type as seen in other eutherians but differ significantly in terms of soma shape and size, extent of dendritic arbor, diameter of dendrites and spine density. Percentage of pyramidal neurons, diameter of apical dendrite and spine density on apical dendrite appear to follow an increasing trend from primitive to advanced mammals; but extent of dendrites are probably governed by the specific life patterns of these mammals. It is thus concluded that 'typical' pyramidal neurons in parietal isocortex are similar in therians but different from those in prototherians. It is possible that these cells might have arisen among early eutherians after divergence from prototherian stock.

Notochord morphogenesis in mice: Current understanding & open questions.

PubMed

Balmer, Sophie; Nowotschin, Sonja; Hadjantonakis, Anna-Katerina

2016-05-01

The notochord is a structure common to all chordates, and the feature that the phylum Chordata has been named after. It is a rod-like mesodermal structure that runs the anterior-posterior length of the embryo, adjacent to the ventral neural tube. The notochord plays a critical role in embryonic tissue patterning, for example the dorsal-ventral patterning of the neural tube. The cells that will come to form the notochord are specified at gastrulation. Axial mesodermal cells arising at the anterior primitive streak migrate anteriorly as the precursors of the notochord and populate the notochordal plate. Yet, even though a lot of interest has centered on investigating the functional and structural roles of the notochord, we still have a very rudimentary understanding of notochord morphogenesis. The events driving the formation of the notochord are rapid, taking place over the period of approximately a day in mice. In this commentary, we provide an overview of our current understanding of mouse notochord morphogenesis, from the initial specification of axial mesendodermal cells at the primitive streak, the emergence of these cells at the midline on the surface of the embryo, to their submergence and organization of the stereotypically positioned notochord. We will also discuss some key open questions. Developmental Dynamics 245:547-557, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Amphioxus and lamprey AP-2 genes: implications for neural crest evolution and migration patterns

NASA Technical Reports Server (NTRS)

Meulemans, Daniel; Bronner-Fraser, Marianne

2002-01-01

The neural crest is a uniquely vertebrate cell type present in the most basal vertebrates, but not in cephalochordates. We have studied differences in regulation of the neural crest marker AP-2 across two evolutionary transitions: invertebrate to vertebrate, and agnathan to gnathostome. Isolation and comparison of amphioxus, lamprey and axolotl AP-2 reveals its extensive expansion in the vertebrate dorsal neural tube and pharyngeal arches, implying co-option of AP-2 genes by neural crest cells early in vertebrate evolution. Expression in non-neural ectoderm is a conserved feature in amphioxus and vertebrates, suggesting an ancient role for AP-2 genes in this tissue. There is also common expression in subsets of ventrolateral neurons in the anterior neural tube, consistent with a primitive role in brain development. Comparison of AP-2 expression in axolotl and lamprey suggests an elaboration of cranial neural crest patterning in gnathostomes. However, migration of AP-2-expressing neural crest cells medial to the pharyngeal arch mesoderm appears to be a primitive feature retained in all vertebrates. Because AP-2 has essential roles in cranial neural crest differentiation and proliferation, the co-option of AP-2 by neural crest cells in the vertebrate lineage was a potentially crucial event in vertebrate evolution.

Post-transcriptional regulation in hematopoiesis: RNA binding proteins take control.

PubMed

de Rooij, Laura P M H; Chan, Derek C H; Keyvani Chahi, Ava; Hope, Kristin J

2018-06-13

Normal hematopoiesis is sustained through a carefully orchestrated balance between hematopoietic stem cell (HSC) self-renewal and differentiation. The functional importance of this axis is underscored by the severity of disease phenotypes initiated by abnormal HSC function, including myelodysplastic syndromes and hematopoietic malignancies. Major advances in the understanding of transcriptional regulation of primitive hematopoietic cells have been achieved, however, the post-transcriptional regulatory layer that may impinge on their behavior remains underexplored by comparison. Key players at this level include RNA binding proteins (RBPs), which execute precise and highly coordinated control of gene expression through modulation of RNA properties that include its splicing, polyadenylation, localization, degradation or translation. With the recent identification of RBPs having essential roles in regulating proliferation and cell fate decisions in other systems, there has been an increasing appreciation of the importance of post-transcriptional control at the stem cell level. Here we discuss our current understanding of RBP-driven post-transcriptional regulation in HSC, its implications for normal, perturbed and malignant hematopoiesis, as well as the most recent technological innovations aimed at RBP-RNA network characterization at the systems level. Emerging evidence highlights RBP-driven control as an underappreciated feature of primitive hematopoiesis, the greater understanding of which has important clinical implications.

Dynamic Primitives of Motor Behavior

PubMed Central

Hogan, Neville; Sternad, Dagmar

2013-01-01

We present in outline a theory of sensorimotor control based on dynamic primitives, which we define as attractors. To account for the broad class of human interactive behaviors—especially tool use—we propose three distinct primitives: submovements, oscillations and mechanical impedances, the latter necessary for interaction with objects. Due to fundamental features of the neuromuscular system, most notably its slow response, we argue that encoding in terms of parameterized primitives may be an essential simplification required for learning, performance, and retention of complex skills. Primitives may simultaneously and sequentially be combined to produce observable forces and motions. This may be achieved by defining a virtual trajectory composed of submovements and/or oscillations interacting with impedances. Identifying primitives requires care: in principle, overlapping submovements would be sufficient to compose all observed movements but biological evidence shows that oscillations are a distinct primitive. Conversely, we suggest that kinematic synergies, frequently discussed as primitives of complex actions, may be an emergent consequence of neuromuscular impedance. To illustrate how these dynamic primitives may account for complex actions, we briefly review three types of interactive behaviors: constrained motion, impact tasks, and manipulation of dynamic objects. PMID:23124919

PERIODIC AIR-BREATHING BEHAVIOUR IN A PRIMITIVE FISH REVEALED BY SPECTRAL ANALYSIS

PubMed

Hedrick; Katz; Jones

1994-12-01

The ventilatory patterns of air-breathing fish are commonly described as 'arrhythmic' or 'irregular' because the variable periods of breath-holding are punctuated by seemingly unpredictable air-breathing events (see Shelton et al. 1986). This apparent arrhythmicity contrasts with the perceived periodism or regularity in the gill ventilation patterns of some fish and with lung ventilation in birds and mammals. In this sense, periodism refers to behaviour that occurs with a definite, recurring interval (Bendat and Piersol, 1986). The characterisation of aerial ventilation patterns in fish as 'aperiodic' has been generally accepted on the basis of qualitative examination and it remains to be validated with rigorous testing. The bowfin, Amia calva (L.), is a primitive air-breathing fish that makes intermittent excursions to the air­water interface to gulp air, which is transferred to its well-vascularized gas bladder. Its phylogenetic position as the only extant member of the sister lineage of modern teleosts affords a unique opportunity to examine the evolution of aerial ventilation and provides a model for the examination of ventilatory patterns in primitive fishes. To establish whether Amia calva exhibit a particular pattern of air-breathing, we examined time series records of aerial ventilations from undisturbed fish over long periods (8 h). These records were the same as those used to calculate average ventilation intervals under a variety of experimental conditions (Hedrick and Jones, 1993). Their study also reported the occurrence of two distinct breath types. Type I breaths were characterised by an exhalation followed by an inhalation, whereas type II breaths were characterised by inhalation only. It was also hypothesized that the type I breaths were employed to meet oxygen demands, whereas the type II breaths were used to regulate gas bladder volume. However, they did not investigate the potential presence of a periodic ventilatory pattern. We now report the results of just such an analysis of ventilatory pattern that demonstrates a clear periodism to air-breathing in a primitive fish.

Rosetta/VIRTIS-M spectral data: Comet 67P/CG compared to other primitive small bodies.

NASA Astrophysics Data System (ADS)

De Sanctis, M. C.; Capaccioni, F.; Filacchione, G.; Erard, S.; Tosi, F.; Ciarniello, M.; Raponi, A.; Piccioni, G.; Leyrat, C.; Bockelée-Morvan, D.; Drossart, P.; Fornasier, S.

2014-12-01

VIRTIS-M, the Visible InfraRed Thermal Imaging Spectrometer, onboard the Rosetta Mission orbiter (Coradini et al., 2007) acquired data of the comet 67P/Churyumov-Gerasimenko in the 0.25-5.1 µm spectral range. The initial data, obtained during the first mission phases to the comet, allow us to derive albedo and global spectral properties of the comet nucleus as well as spectra of different areas on the nucleus. The characterization of cometary nuclei surfaces and their comparison with those of related populations such as extinct comet candidates, Centaurs, near-Earth asteroids (NEAs), trans-Neptunian objects (TNOs), and primitive asteroids is critical to understanding the origin and evolution of small solar system bodies. The acquired VIRTIS data are used to compare the global spectral properties of comet 67P/CG to published spectra of other cometary nuclei observed from ground or visited by space mission. Moreover, the spectra of 67P/Churyumov-Gerasimenko are also compared to those of primitive asteroids and centaurs. The comparison can give us clues on the possible common formation and evolutionary environment for primitive asteroids, centaurs and Jupiter-family comets. Authors acknowledge the funding from Italian and French Space Agencies. References: Coradini, A., Capaccioni, F., Drossart, P., Arnold, G., Ammannito, E., Angrilli, F., Barucci, A., Bellucci, G., Benkhoff, J., Bianchini, G., Bibring, J. P., Blecka, M., Bockelee-Morvan, D., Capria, M. T., Carlson, R., Carsenty, U., Cerroni, P., Colangeli, L., Combes, M., Combi, M., Crovisier, J., De Sanctis, M. C., Encrenaz, E. T., Erard, S., Federico, C., Filacchione, G., Fink, U., Fonti, S., Formisano, V., Ip, W. H., Jaumann, R., Kuehrt, E., Langevin, Y., Magni, G., McCord, T., Mennella, V., Mottola, S., Neukum, G., Palumbo, P., Piccioni, G., Rauer, H., Saggin, B., Schmitt, B., Tiphene, D., Tozzi, G., Space Science Reviews, Volume 128, Issue 1-4, 529-559, 2007.

Long-term hematopoietic stem cell damage in a murine model of the hematopoietic syndrome of the acute radiation syndrome.

PubMed

Chua, Hui Lin; Plett, P Artur; Sampson, Carol H; Joshi, Mandar; Tabbey, Rebeka; Katz, Barry P; MacVittie, Thomas J; Orschell, Christie M

2012-10-01

Residual bone marrow damage (RBMD) persists for years following exposure to radiation and is believed to be due to decreased self-renewal potential of radiation-damaged hematopoietic stem cells (HSC). Current literature has examined primarily sublethal doses of radiation and time points within a few months of exposure. In this study, the authors examined RBMD in mice surviving lethal doses of total body ionizing irradiation (TBI) in a murine model of the Hematopoietic Syndrome of the Acute Radiation Syndrome (H-ARS). Survivors were analyzed at various time points up to 19 mo post-TBI for hematopoietic function. The competitive bone marrow (BM) repopulating potential of 150 purified c-Kit+ Sca-1+ lineage- CD150+ cells (KSLCD150+) remained severely deficient throughout the study compared to KSLCD150+ cells from non-TBI age-matched controls. The minimal engraftment from these TBI HSCs is predominantly myeloid, with minimal production of lymphocytes both in vitro and in vivo. All classes of blood cells as well as BM cellularity were significantly decreased in TBI mice, especially at later time points as mice aged. Primitive BM hematopoietic cells (KSLCD150+) displayed significantly increased cell cycling in TBI mice at all time points, which may be a physiological attempt to maintain HSC numbers in the post-irradiation state. Taken together, these data suggest that the increased cycling among primitive hematopoietic cells in survivors of lethal radiation may contribute to long-term HSC exhaustion and subsequent RBMD, exacerbated by the added insult of aging at later time points.

What Everyone Should Know about Archeans

ERIC Educational Resources Information Center

Freeland, Peter

2013-01-01

For many years biologists supposed that one group of microorganisms, which they called archaebacteria, were an ancient and primitive type of bacteria. Following biochemical analysis of their RNA and other cell components, it soon became clear that their distinct features merited classification in a separate domain, the archea. From an evolutionary…

Alisertib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Leukemia

ClinicalTrials.gov

2017-09-21

Hepatoblastoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Kidney Neoplasm; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma

HEPATOBLASTOMAS IN THE MUMMICHOG, FUNDULUS HETEROCLITUS (L.), FROM A CREOSOTE-CONTAMINATED ENVIRONMENT: A HISTOLOGIC, ULTRASTRUCTURAL AND IMMUNOHISTOCHEMICAL STUDY

EPA Science Inventory

A detailed histologic and ultrastructural description of two cases of hepatoblastoma, a primitive liver cell neoplasm, is provided from mummichog, Fundulus heteroclitus(L.), inhabiting a creosote-contaminated site in the Elizabeth River, Virginia, USA. Both neoplasms were multifo...

Postirradiation malignant fibrous histiocytoma of the lung. Demonstration of alpha 1-antitrypsin-like material in neoplastic cells.

PubMed

Chowdhury, L N; Swerdlow, M A; Jao, W; Kathpalia, S; Desser, R K

1980-12-01

A metastasizing fibrous histiocytoma arising in the lung of a patient who received radiation therapy and long-term chemotherapy for malignant lymphoma is presented. Ultrastructural studies revealed fibroblast-like and histiocyte-like cells, cells of intermediate type showing ultrastructural features of both fibroblast-like and histiocyte-like cells, primitive mesenchymal cells, multinucleate tumor cells, and xanthomatous cells. The neoplastic cells showed dilated rough endoplasmic reticula with intracisternal accumulation of electron-dense material forming lattice-like structures. Direct immunofluorescence staining of the neoplastic cells using antihuman alpha 1-antitrypsin showed specific activity, with fluorescent deposits exhibiting interlacing globular formations. These findings and their implications are discussed.

Molecular Features of Neural Stem Cells Enable their Enrichment Using Pharmacological Inhibitors of Survival-Promoting Kinases

PubMed Central

Brazel, Christine Y.; Alaythan, Abdulaziz A.; Felling, Ryan J.; Calderon, Frances; Levison, Steven W.

2013-01-01

Isolating a pure population of neural stem cells (NSCs) has been difficult since no exclusive surface markers have been identified for panning or FACS purification. Moreover, additional refinements for maintaining NSCs in culture are required, since NSCs generate a variety of neural precursors (NPs) as they proliferate. Here, we demonstrate that postnatal rat NPs express low levels of pro-apoptotic molecules and resist PI3K and ERK1/2 inhibition as compared to late oligodendrocyte progenitors. Furthermore, maintaining SVZ precursors in LY294002 and PD98059, inhibitors of PI3K and ERK1/2 signaling, eliminated lineage-restricted precursors as revealed by enrichment for Nestin+/SOX-2+ cells. The cells that survived formed neurospheres and 89% of these neurospheres were tripotential, generating neurons, astrocytes and oligodendrocytes. Without this enrichment step, less than 50% of the NPs were Nestin+/SOX-2+ and 42% of the neurospheres were tripotential. Additionally, neurospheres enriched using this procedure produced 3-times more secondary neurospheres, supporting the conclusion that this procedure enriches for NSCs. A number of genes that enhance survival were more highly expressed in neurospheres compared to late oligodendrocyte progenitors. Altogether, these studies demonstrate that primitive neural precursors can be enriched using a relatively simple and inexpensive means that will facilitate cell replacement strategies using stem cells as well as other studies whose goal is to reveal the fundamental properties of primitive neural precursors. PMID:24032666

Common tree shrews and primates share leukocyte membrane antigens.

PubMed

Palley, L S; Schlossman, S F; Letvin, N L

1984-01-01

Monoclonal antibodies reactive with human peripheral blood lymphocyte and myeloid cell surface antigens were utilized to study the phylogeny of the common tree shrew. Blood cells from the common tree shrew, but not the bat or short-tailed shrew, react with certain of these antibodies. These data strengthen the argument that the Tupaiidae are primitive primates rather than insectivores. They also indicate that this approach should be useful for further work in taxonomic systemization.

Cell lineage allocation in equine blastocysts produced in vitro under varying glucose concentrations.

PubMed

Choi, Young-Ho; Ross, Pablo; Velez, Isabel C; Macías-García, B; Riera, Fernando L; Hinrichs, Katrin

2015-07-01

Equine embryos develop in vitro in the presence of high glucose concentrations, but little is known about their requirements for development. We evaluated the effect of glucose concentrations in medium on blastocyst development after ICSI. In experiment 1, there were no significant differences in rates of blastocyst formation among embryos cultured in our standard medium (DMEM/F-12), which contained >16 mM glucose, and those cultured in a minimal-glucose embryo culture medium (<1 mM; Global medium, GB), with either 0 added glucose for the first 5 days, then 20 mM (0-20) or 20 mM for the entire culture period (20-20). In experiment 2, there were no significant differences in the rates of blastocyst development (31-46%) for embryos cultured in four glucose treatments in GB (0-10, 0-20, 5-10, or 5-20). Blastocysts were evaluated by immunofluorescence for lineage-specific markers. All cells stained positively for POU5F1. An inner cluster of cells was identified that included presumptive primitive endoderm cells (GATA6-positive) and presumptive epiblast (EPI) cells. The 5-20 treatment resulted in a significantly lower number of presumptive EPI-lineage cells than the 0-20 treatment did. GATA6-positive cells appeared to be allocated to the primitive endoderm independent of the formation of an inner cell mass, as was previously hypothesized for equine embryos. These data demonstrate that equine blastocyst development is not dependent on high glucose concentrations during early culture; rather, environmental glucose may affect cell allocation. They also present the first analysis of cell lineage allocation in in vitro-fertilized equine blastocysts. These findings expand our understanding of the factors that affect embryo development in the horse. © 2015 Society for Reproduction and Fertility.

Features and the ‘primal sketch’

PubMed Central

Morgan, Michael J.

2014-01-01

This review is concerned primarily with psychophysical and physiological evidence relevant to the question of the existence of spatial features or spatial primitives in human vision. The review will be almost exclusively confined to features defined in the luminance domain. The emphasis will be on the experimental and computational methods that have been used for revealing features, rather than on a detailed comparison between different models of feature extraction. Color and texture fall largely outside the scope of the review, though the principles may be similar. Stereo matching and motion matching are also largely excluded because they are covered in other contributions to this volume, although both have addressed the question of the spatial primitives involved in matching. Similarities between different psychophysically-based model will be emphasized rather than minor differences. All the models considered in the review are based on the extraction of directional spatial derivatives of the luminance profile, typically the first and second, but in one case the third order, and all have some form of non-linearity, be it rectification or thresholding. PMID:20696182

Combined Molecular Algorithms for the Generation, Equilibration and Topological Analysis of Entangled Polymers: Methodology and Performance

PubMed Central

Karayiannis, Nikos Ch.; Kröger, Martin

2009-01-01

We review the methodology, algorithmic implementation and performance characteristics of a hierarchical modeling scheme for the generation, equilibration and topological analysis of polymer systems at various levels of molecular description: from atomistic polyethylene samples to random packings of freely-jointed chains of tangent hard spheres of uniform size. Our analysis focuses on hitherto less discussed algorithmic details of the implementation of both, the Monte Carlo (MC) procedure for the system generation and equilibration, and a postprocessing step, where we identify the underlying topological structure of the simulated systems in the form of primitive paths. In order to demonstrate our arguments, we study how molecular length and packing density (volume fraction) affect the performance of the MC scheme built around chain-connectivity altering moves. In parallel, we quantify the effect of finite system size, of polydispersity, and of the definition of the number of entanglements (and related entanglement molecular weight) on the results about the primitive path network. Along these lines we approve main concepts which had been previously proposed in the literature. PMID:20087477

Workshop on Evolution of Martian Volatiles. Part 1

NASA Technical Reports Server (NTRS)

Jakosky, B. (Editor); Treiman, A. (Editor)

1996-01-01

This volume contains papers that were presented on February 12-14, 1996 at the Evolution for Martian Volatiles Workshop. Topics in this volume include: returned Martian samples; acidic volatiles and the Mars soil; solar EUV Radiation; the ancient Mars Thermosphere; primitive methane atmospheres on Earth and Mars; the evolution of Martian water; the role of SO2 for the climate history of Mars; impact crater morphology; the formation of the Martian drainage system; atmospheric dust-water ice Interactions; volatiles and volcanos; accretion of interplanetary dust particles; Mars' ionosphere; simulations with the NASA Ames Mars General Circulation Model; modeling the Martian water cycle; the evolution of Martian atmosphere; isotopic composition; solar occultation; magnetic fields; photochemical weathering; NASA's Mars Surveyor Program; iron formations; measurements of Martian atmospheric water vapor; and the thermal evolution Models of Mars.

The Late Devonian Gogo Formation Lägerstatte of Western Australia: Exceptional Early Vertebrate Preservation and Diversity

NASA Astrophysics Data System (ADS)

Long, John A.; Trinajstic, Kate

2010-05-01

The Gogo Formation of Western Australia preserves a unique Late Devonian (Frasnian) reef fauna. The exceptional three-dimensional preservation of macrofossils combined with unprecedented soft-tissue preservation (including muscle bundles, nerve cells, and umbilical structures) has yielded a particularly rich assemblage with almost 50 species of fishes described. The most significant discoveries have contributed to resolving placoderm phylogeny and elucidating their reproductive physiology. Specifically, these discoveries have produced data on the oldest known vertebrate embryos; the anatomy of the primitive actinopterygian neurocranium and phylogeny of the earliest actinopterygians; the histology, radiation, and plasticity of dipnoan (lungfish) dental and cranial structures; the anatomy and functional morphology of the extinct onychodonts; and the anatomy of the primitive tetrapodomorph head and pectoral fin.

Neuromuscular transmission in a primitive insect: modulation by octopamine, and catch-like tension.

PubMed

Hoyle, G

1984-01-01

The third pair of legs of the primitive New Zealand orthopteran insect, the " weta ", has and innervation and muscle cell distribution exactly similar to that of locusts, but wetas do not jump. Neuromuscular transmission to the slow excitatory axon ( SETi ) is potentiated more than 10-fold by the natural modulator octopamine (OCT). A brief burst of SETi impulses following infusion of as little as 10(-8) M OCT is followed by a very long-lasting plateau of catch-like tension (CT). The plateau is abruptly relaxed by a single inhibitory impulse, or even by a single SETi impulse if this arrives no sooner than about 30 sec following excitation. CT is used by wetas in a defense posture. Locusts and grasshoppers have a different type of modulation by OCT.

Hair Cell Heterogeneity in the Goldfish Saccule

NASA Technical Reports Server (NTRS)

Saidel, William M.; Lanford, Pamela J.; Yan, Hong Y.; Popper, Arthur N.

1995-01-01

A set of cytological studies performed in the utricle and saccule of Astronotus ocellatus (Teleostei, Percomorphi, Cichlidae) identified two basic types of hair cells and others with some intermediate characteristics. This paper reports on applying the same techniques to the saccule of Carassius auratus (Teleostei, Otophysi, Cyprinidae) and demonstrates similar types of hair cells to those found in Astronotus. Since Carassius and Astronous are species of extreme taxonomic distance within the Euteteostei, two classes of mechanoreceptive hair cells are likely to represent the primitive condition for sensory receptors in the euteleost inner ear and perhaps in all bony fish ears.

Vorinostat With or Without Isotretinoin in Treating Young Patients With Recurrent or Refractory Solid Tumors, Lymphoma, or Leukemia

ClinicalTrials.gov

2014-06-16

Childhood Acute Promyelocytic Leukemia (M3); Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Juvenile Myelomonocytic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

Cell and molecular biology of marine elasmobranchs: Squalus acanthias and Raja erinacea.

PubMed

Mattingly, Carolyn; Parton, Angela; Dowell, Lori; Rafferty, Jason; Barnes, David

2004-01-01

Elasmobranchs are among the most primitive existing species exhibiting fundamental vertebrate characteristics, such as neural crest, jaws, teeth, and an adaptive immune system. They are also among the earliest-evolved vertebrates with a closed, pressurized circulatory system and related signaling molecules. Although many species are used experimentally, the spiny dogfish shark (Squalus acanthias) and little skate (Raja erinacea) have particular advantages and are the most commonly used elasmobranch biomedical models. These animals display powerful molecular systems for dealing with salt and water homeostasis, cell volume regulation, and environmental and internal osmotic sensing. They have become important unique models in studies of transport-related diseases such as cystic fibrosis and anion or xenobiotic transport. Much of this work has relied on physiological experiments combined with molecular approaches and the advantages of comparative genomic analyses to identify conserved regions representing functional protein domains. Recent work has seen the development of cell cultures and the beginning of expressed sequence tags (EST) and genomic libraries. Other areas in which elasmobranches have played critical roles include immunology and neurobiology. It also appears that sharks have tissue regenerative capability beyond what is commonly seen in mammals. For example, sharks and skates possess a region of renal regeneration, with new tubules being formed continually through adulthood. As comparative functional genomics comes of age, these comparative vertebrate models may play an increasing role in the larger picture of human biomedical research. There is plenty of ocean to share.

Three dimensional thermal pollution models. Volume 1: Review of mathematical formulations. [waste heat discharge from power plants and effects on ecosystems

NASA Technical Reports Server (NTRS)

Lee, S. S.; Sengupta, S.

1978-01-01

A mathematical model package for thermal pollution analyses and prediction is presented. These models, intended as user's manuals, are three dimensional and time dependent using the primitive equation approach. Although they have sufficient generality for application at sites with diverse topographical features; they also present specific instructions regarding data preparation for program execution and sample problems. The mathematical formulation of these models is presented including assumptions, approximations, governing equations, boundary and initial conditions, numerical method of solution, and same results.

Spaceborne computer executive routine functional design specification. Volume 1: Functional design of a flight computer executive program for the reusable shuttle

NASA Technical Reports Server (NTRS)

Curran, R. T.

1971-01-01

A flight computer functional executive design for the reusable shuttle is presented. The design is given in the form of functional flowcharts and prose description. Techniques utilized in the regulation of process flow to accomplish activation, resource allocation, suspension, termination, and error masking based on process primitives are considered. Preliminary estimates of main storage utilization by the Executive are furnished. Conclusions and recommendations for timely, effective software-hardware integration in the reusable shuttle avionics system are proposed.

18F-FLT Positron Emission Tomography and Diffusion-Weighted Magnetic Resonance Imaging in Planning Surgery and Radiation Therapy and Measuring Response in Patients With Newly Diagnosed Ewing Sarcoma

ClinicalTrials.gov

2017-11-16

Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Ewing Sarcoma of Bone; Extraosseous Ewing Sarcoma; Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor

Crystallization and preliminary crystallographic analysis of the cellulose biosynthesis-related protein CMCax from Acetobacter xylinum

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

Kawano, Shin; Yasutake, Yoshiaki; Tajima, Kenji

2005-02-01

The cellulose biosynthesis-related protein CMCax from A. xylinum has been purified and crystallized. The crystals of CMCax belong to the primitive hexagonal space group P6{sub 1} or P6{sub 5}, with unit-cell parameters a = b = 89.1, c = 94.2 Å.

Proton Transports in Pure Liquid Water Characterized by Melted Ice Lattice Model

NASA Astrophysics Data System (ADS)

Jie, Binbin; Sah, Chihtang

Basic water properties have not been understood for 200 years. Our Melted Ice Lattice model accounts for the 2 basic properties of pure water, the ion product (pH) and mobilities. It has HCP primitive unit cells, each with 4H2O, based on the 1933 Bernal-Fowler model, verified by 1935 Pauling residual entropy theory of 1928-1935 Giauque experimental low temperature specific heat measurements. Our 2 ion species are point-mass protons p + and p-, for mass and electricity transport. Three protonic thermal activation energies are obtained from pH and p + and p- mobilities vs T (0-100OC). Proton transport is analyzed in 3 proton-phonon collision steps: proton detrapping by protonic phonon absorption, proton scattering by oxygenic (water) phonons, and proton trapping with protonic phonon emission. Distinction between Potential and Kinetic Energy Bands of protons (Fermions) and phonons (Bosons) is noted. Experimental protonic activation energies are the phonon energies given by the spring-mass vibration frequencies of lattice, wn = (kn/mn)1/2 . n is the proton-mass unit of the synchronized vibrating particles in the primitive unit cells.

Diagnostic Study of Tumor Characteristics in Patients With Ewing's Sarcoma

ClinicalTrials.gov

2013-06-20

Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor

Volumic visual perception: principally novel concept

NASA Astrophysics Data System (ADS)

Petrov, Valery

1996-01-01

The general concept of volumic view (VV) as a universal property of space is introduced. VV exists in every point of the universe where electromagnetic (EM) waves can reach and a point or a quasi-point receiver (detector) of EM waves can be placed. Classification of receivers is given for the first time. They are classified into three main categories: biological, man-made non-biological, and mathematically specified hypothetical receivers. The principally novel concept of volumic perception is introduced. It differs chiefly from the traditional concept which traces back to Euclid and pre-Euclidean times and much later to Leonardo da Vinci and Giovanni Battista della Porta's discoveries and practical stereoscopy as introduced by C. Wheatstone. The basic idea of novel concept is that humans and animals acquire volumic visual data flows in series rather than in parallel. In this case the brain is free from extremely sophisticated real time parallel processing of two volumic visual data flows in order to combine them. Such procedure seems hardly probable even for humans who are unable to combine two primitive static stereoscopic images in one quicker than in a few seconds. Some people are unable to perform this procedure at all.

Collecting and Storing Biological Samples From Patients With Ewing Sarcoma

ClinicalTrials.gov

2017-12-11

Askin Tumor; Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor

Absence of suppressor of cytokine signalling 3 reduces self-renewal and promotes differentiation in murine embryonic stem cells.

PubMed

Forrai, Ariel; Boyle, Kristy; Hart, Adam H; Hartley, Lynne; Rakar, Steven; Willson, Tracy A; Simpson, Ken M; Roberts, Andrew W; Alexander, Warren S; Voss, Anne K; Robb, Lorraine

2006-03-01

Leukemia inhibitory factor (LIF) is required to maintain pluripotency and permit self-renewal of murine embryonic stem (ES) cells. LIF binds to a receptor complex of LIFR-beta and gp130 and signals via the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, with signalling attenuated by suppressor of cytokine signalling (SOCS) proteins. Recent in vivo studies have highlighted the role of SOCS-3 in the negative regulation of signalling via gp130. To determine the role of SOCS-3 in ES cell biology, SOCS-3-null ES cell lines were generated. When cultured in LIF levels that sustain self-renewal of wild-type cells, SOCS-3-null ES cell lines exhibited less self-renewal and greater differentiation into primitive endoderm. The absence of SOCS-3 enhanced JAK-STAT and extracellular signal-related kinase 1/2 (ERK-1/2)-mitogen-activated protein kinase (MAPK) signal transduction via gp130, with higher levels of phosphorylated STAT-1, STAT-3, SH-2 domain-containing cytoplasmic protein tyrosine phosphatase 2 (SHP-2), and ERK-1/2 in steady state and in response to LIF stimulation. Attenuation of ERK signalling by the addition of MAPK/ERK kinase (MEK) inhibitors to SOCS-3-null ES cell cultures rescued the differentiation phenotype, but did not restore proliferation to wild-type levels. In summary, SOCS-3 plays a crucial role in the regulation of the LIF signalling pathway in murine ES cells. Its absence perturbs the balance between activation of the JAK-STAT and SHP-2-ERK-1/2-MAPK pathways, resulting in less self-renewal and a greater potential for differentiation into the primitive endoderm lineage.

Oxaliplatin in Treating Young Patients With Recurrent Solid Tumors That Have Not Responded to Previous Treatment

ClinicalTrials.gov

2013-06-04

Childhood Central Nervous System Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Hepatoblastoma; Childhood Hepatocellular Carcinoma; Childhood High-grade Cerebral Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Childhood Teratoma; Recurrent Adrenocortical Carcinoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Colon Cancer; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Nasopharyngeal Cancer; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Rectal Cancer; Recurrent Renal Cell Cancer

Evaluating structural pattern recognition for handwritten math via primitive label graphs

NASA Astrophysics Data System (ADS)

Zanibbi, Richard; Mouchère, Harold; Viard-Gaudin, Christian

2013-01-01

Currently, structural pattern recognizer evaluations compare graphs of detected structure to target structures (i.e. ground truth) using recognition rates, recall and precision for object segmentation, classification and relationships. In document recognition, these target objects (e.g. symbols) are frequently comprised of multiple primitives (e.g. connected components, or strokes for online handwritten data), but current metrics do not characterize errors at the primitive level, from which object-level structure is obtained. Primitive label graphs are directed graphs defined over primitives and primitive pairs. We define new metrics obtained by Hamming distances over label graphs, which allow classification, segmentation and parsing errors to be characterized separately, or using a single measure. Recall and precision for detected objects may also be computed directly from label graphs. We illustrate the new metrics by comparing a new primitive-level evaluation to the symbol-level evaluation performed for the CROHME 2012 handwritten math recognition competition. A Python-based set of utilities for evaluating, visualizing and translating label graphs is publicly available.

The divergent fates of primitive hydrospheric water on Earth and Mars

NASA Astrophysics Data System (ADS)

Wade, Jon; Dyck, Brendan; Palin, Richard M.; Moore, James D. P.; Smye, Andrew J.

2017-12-01

Despite active transport into Earth’s mantle, water has been present on our planet’s surface for most of geological time. Yet water disappeared from the Martian surface soon after its formation. Although some of the water on Mars was lost to space via photolysis following the collapse of the planet’s magnetic field, the widespread serpentinization of Martian crust suggests that metamorphic hydration reactions played a critical part in the sequestration of the crust. Here we quantify the relative volumes of water that could be removed from each planet’s surface via the burial and metamorphism of hydrated mafic crusts, and calculate mineral transition-induced bulk-density changes at conditions of elevated pressure and temperature for each. The metamorphic mineral assemblages in relatively FeO-rich Martian lavas can hold about 25 per cent more structurally bound water than those in metamorphosed terrestrial basalts, and can retain it at greater depths within Mars. Our calculations suggest that in excess of 9 per cent by volume of the Martian mantle may contain hydrous mineral species as a consequence of surface reactions, compared to about 4 per cent by volume of Earth’s mantle. Furthermore, neither primitive nor evolved hydrated Martian crust show noticeably different bulk densities compared to their anhydrous equivalents, in contrast to hydrous mafic terrestrial crust, which transforms to denser eclogite upon dehydration. This would have allowed efficient overplating and burial of early Martian crust in a stagnant-lid tectonic regime, in which the lithosphere comprised a single tectonic plate, with only the warmer, lower crust involved in mantle convection. This provided an important sink for hydrospheric water and a mechanism for oxidizing the Martian mantle. Conversely, relatively buoyant mafic crust and hotter geothermal gradients on Earth reduced the potential for upper-mantle hydration early in its geological history, leading to water being retained close to its surface, and thus creating conditions conducive for the evolution of complex multicellular life.

The divergent fates of primitive hydrospheric water on Earth and Mars.

PubMed

Wade, Jon; Dyck, Brendan; Palin, Richard M; Moore, James D P; Smye, Andrew J

2017-12-20

Despite active transport into Earth's mantle, water has been present on our planet's surface for most of geological time. Yet water disappeared from the Martian surface soon after its formation. Although some of the water on Mars was lost to space via photolysis following the collapse of the planet's magnetic field, the widespread serpentinization of Martian crust suggests that metamorphic hydration reactions played a critical part in the sequestration of the crust. Here we quantify the relative volumes of water that could be removed from each planet's surface via the burial and metamorphism of hydrated mafic crusts, and calculate mineral transition-induced bulk-density changes at conditions of elevated pressure and temperature for each. The metamorphic mineral assemblages in relatively FeO-rich Martian lavas can hold about 25 per cent more structurally bound water than those in metamorphosed terrestrial basalts, and can retain it at greater depths within Mars. Our calculations suggest that in excess of 9 per cent by volume of the Martian mantle may contain hydrous mineral species as a consequence of surface reactions, compared to about 4 per cent by volume of Earth's mantle. Furthermore, neither primitive nor evolved hydrated Martian crust show noticeably different bulk densities compared to their anhydrous equivalents, in contrast to hydrous mafic terrestrial crust, which transforms to denser eclogite upon dehydration. This would have allowed efficient overplating and burial of early Martian crust in a stagnant-lid tectonic regime, in which the lithosphere comprised a single tectonic plate, with only the warmer, lower crust involved in mantle convection. This provided an important sink for hydrospheric water and a mechanism for oxidizing the Martian mantle. Conversely, relatively buoyant mafic crust and hotter geothermal gradients on Earth reduced the potential for upper-mantle hydration early in its geological history, leading to water being retained close to its surface, and thus creating conditions conducive for the evolution of complex multicellular life.

[Primitive neuroectodermal tumor/Ewing's sarcoma of the penis in children: a case report and review of the literature].

PubMed

Zhang, Da-Wei; Jin, Mei; Zhou, Chun-Ju; Song, Hong-Cheng; Ma, Xiao-Li

2012-12-01

To investigate the clinical manifestations, pathological characteristics and treatment of primitive neuroectodermal tumor/Ewing's sarcoma (PNET/EWS) of the penis in children. We analyzed the clinical data of a case of PNET/EWS and reviewed relevant literature. The patient was a 5-year-old boy, admitted for penis swelling with pain for 11 months. Biopsy showed a small round cell tumor, CD99 positive by immunohistochemical staining, with EWS translocation by fluorescence in situ hybridization on molecular biological examination. The tumor was confirmed to be PNET/EWS of the penis, and disappeared after 45 weeks of chemotherapy and local radiotherapy. PNET/EWS of the penis is an extremely rare disease, with no specific clinical symptoms except penis enlargement with pain. Immunohistochemistry and molecular biological examination contribute to its diagnosis.

Identification of CD56 and CD57 by flow cytometry in Ewing's sarcoma or primitive neuroectodermal tumor.

PubMed

Gardner, L J; Polski, J M; Fallon, R; Dunphy, C H

1998-07-01

CD56 and CD57 are commonly considered as natural killer and neuroectodermal markers, but their expression has been identified in a wide spectrum of neoplasms including some cases of Ewing's sarcoma (ES) and primitive neuroectodermal tumor (PNET). We report two cases of small, round blue cell tumor (SRBCT), in which flow cytometry immunophenotyping (FCI) detected strong expression of CD56 and CD57 (one case). Immunohistochemical staining with Leu-19 and Leu-7 confirmed the FI results. Although CD56 and CD57 expression is consistent with ES/PNET, it can be potentially misleading if results of FCI are interpreted in the absence of other findings. These cases suggest the utility of FCI in undifferentiated SRBCT. The literature on CD56 and CD57 expression in ES/PNET is reviewed and discussed.

Intracardiac heterotopia--mesenchymal and endodermal.

PubMed Central

Ariza, S; Rafel, E; Castillo, J A; Garcia-Canton, J A

1978-01-01

A case is reported of an intracardiac 'epithelial heterotopia' with a predominant mesenchymal component. This is thought to have resulted from the differentiation of aberrant primitive cell(s) displaced into the heart during its development. Though microscopically resembling a myxoma, this lesion is clearly distinguished by the presence of glandular structures. The myxoid component exhibited a startling invasiveness which resulted in occlusion of the superior vena cava, causing symptoms very early in life and death at the age of 6 months. Images PMID:637987

Transitional cell carcinoma of the retrorectal space arisen in tailgut cyst: a case report and review of the literature.

PubMed

Vinciguerra, Gian Luca Rampioni; Mercantini, Paolo; La Torre, Marco; Pilozzi, Emanuela; Ziparo, Vincenzo; Vecchione, Andrea

2014-05-01

Tailgut cysts, also known as retrorectal cystic hamartomas, are congenital lesions derived by an abnormal remnant of the postanal primitive hindgut, consisting of unilocular or multilocular cysts usually lined by squamous, transitional, or glandular epithelium. Malignant transformation is an uncommon event, and it mainly involves the neuroendocrine or glandular epithelium; other histotypes are sporadic. Here, we report, for the first time, the clinicopathological features of a transitional cell carcinoma that arose in a tailgut cyst.

Interpreting the universal phylogenetic tree

NASA Technical Reports Server (NTRS)

Woese, C. R.

2000-01-01

The universal phylogenetic tree not only spans all extant life, but its root and earliest branchings represent stages in the evolutionary process before modern cell types had come into being. The evolution of the cell is an interplay between vertically derived and horizontally acquired variation. Primitive cellular entities were necessarily simpler and more modular in design than are modern cells. Consequently, horizontal gene transfer early on was pervasive, dominating the evolutionary dynamic. The root of the universal phylogenetic tree represents the first stage in cellular evolution when the evolving cell became sufficiently integrated and stable to the erosive effects of horizontal gene transfer that true organismal lineages could exist.

Manipulation of immune system via immortal bone marrow stem cells.

PubMed

Ruedl, Christiane; Khameneh, Hanif Javanmard; Karjalainen, Klaus

2008-09-01

Extensive amplification of hematopoietic stem cells (HSCs) and their multipotent primitive progenitors (MPPs) in culture would greatly benefit not only clinical transplantation but also provide a potential tool to manipulate all cellular lineages derived from these cells for gene therapy and experimental purposes. Here, we demonstrate that mouse bone marrow cultures containing cells engineered to over-express NUP98-HOXB4 fusion protein support self-renewal of physiologically normal HSC and MPP for several weeks leading practically to their unlimited expansion. This allows time consuming and cumulative in vitro experimental manipulations without sacrificing their ability to differentiate in vivo or in vitro to any hematopoietic lineage.

Immune-related zinc finger gene ZFAT is an essential transcriptional regulator for hematopoietic differentiation in blood islands

PubMed Central

Tsunoda, Toshiyuki; Takashima, Yasuo; Tanaka, Yoko; Fujimoto, Takahiro; Doi, Keiko; Hirose, Yumiko; Koyanagi, Midori; Yoshida, Yasuhiro; Okamura, Tadashi; Kuroki, Masahide; Sasazuki, Takehiko; Shirasawa, Senji

2010-01-01

TAL1 plays pivotal roles in vascular and hematopoietic developments through the complex with LMO2 and GATA1. Hemangioblasts, which have a differentiation potential for both endothelial and hematopoietic lineages, arise in the primitive streak and migrate into the yolk sac to form blood islands, where primitive hematopoiesis occurs. ZFAT (a zinc-finger gene in autoimmune thyroid disease susceptibility region / an immune-related transcriptional regulator containing 18 C2H2-type zinc-finger domains and one AT-hook) was originally identified as an immune-related transcriptional regulator containing 18 C2H2-type zinc-finger domains and one AT-hook, and is highly conserved among species. ZFAT is thought to be a critical transcription factor involved in immune-regulation and apoptosis; however, developmental roles for ZFAT remain unknown. Here we show that Zfat-deficient (Zfat−/−) mice are embryonic-lethal, with impaired differentiation of hematopoietic progenitor cells in blood islands, where ZFAT is exactly expressed. Expression levels of Tal1, Lmo2, and Gata1 in Zfat−/− yolk sacs are much reduced compared with those of wild-type mice, and ChIP-PCR analysis revealed that ZFAT binds promoter regions for these genes in vivo. Furthermore, profound reduction in TAL1, LMO2, and GATA1 protein expressions are observed in Zfat−/− blood islands. Taken together, these results suggest that ZFAT is indispensable for mouse embryonic development and functions as a critical transcription factor for primitive hematopoiesis through direct-regulation of Tal1, Lmo2, and Gata1. Elucidation of ZFAT functions in hematopoiesis might lead to a better understanding of transcriptional networks in differentiation and cellular programs of hematopoietic lineage and provide useful information for applied medicine in stem cell therapy. PMID:20660741

Use of Optical Storage Devices as Shared Resources in Local Area Networks

DTIC Science & Technology

1989-09-01

13 3. SERVICE CALLS FOR MS-DOS CD-ROM EXTENSIONS . 14 4. MS-DOS PRIMITIVE GROUPS ....................... 15 5. RAM USAGE FOR VARIOUS LAN...17 2. Service Call Translation to DOS Primitives ............. 19 3. MS-DOS Device Drivers ............................. 21 4. MS-DOS/ROM...directed to I/O devices will be referred to as primitive instruction groups). These primitive instruction groups include keyboard, video, disk, serial

Comparative physiology of body fluid regulation in vertebrates with special reference to thirst regulation.

PubMed

Takei, Y

2000-04-01

The origin of life took place in the ancient sea where the ionic concentration is thought to have been somewhat lower than that of the present day seas. This may partly explain why most vertebrate species have plasma ionic concentrations roughly one-third of seawater. Exceptions are primitive marine cyclostomes whose plasma is almost identical to seawater, and marine cartilaginous fishes that accumulate urea in plasma to increase osmolarity to a seawater level. The mechanisms for regulation of water and electrolyte balance should have evolved from these animals into those of more advanced ones in which plasma ions are regulated to one-third of seawater irrespective of the habitat. Although most extant terrestrial and aquatic animals maintain similar plasma osmolarity and ionic concentrations, the mechanisms of regulation differ greatly among different groups of animals according to their habitat. An outstanding difference is that while plasma Na(+) concentration is a primary factor of regulation in terrestrial mammals and birds, blood volume is most strictly regulated in aquatic teleost fishes. Consistently, while an increase in plasma osmolarity (cellular dehydration) is a major dipsogenic stimulus for birds and mammals, hypovolemia (extracellular dehydration) is a much stronger stimulus for elicitation of drinking in teleost fishes. Furthermore, fish cells in culture are tolerant to changes in environmental osmolarity compared with mammalian cells, further suggesting a secondary role of plasma osmolarity as a target of regulation in fishes. A secondary role of blood volume for body fluid regulation in birds is further assessed by the fact that volume receptors for thirst, salt gland secretion, and vasotocin secretion are localized in the extravascular, interstitial space in some species of birds. All terrestrial animals including mammals have derived from the fishes in phylogeny, during which the mechanisms for body fluid regulation underwent adaptive evolution in the course of transition from aquatic to terrestrial life. Therefore, much can be learned from comparative studies of body fluid regulation that reveals the diversity and uniformity of the mechanisms. In this review, important comparative studies that may contribute to an understanding of body fluid regulation throughout vertebrate species will be summarized.

QCAPUF: QCA-based physically unclonable function as a hardware security primitive

NASA Astrophysics Data System (ADS)

Abutaleb, M. M.

2018-04-01

Physically unclonable functions (PUFs) are increasingly used as innovative security primitives to provide the hardware authentication and identification as well as the secret key generation based on unique and random variations in identically fabricated devices. Security and low power have appeared to become two crucial necessities to modern designs. As an emerging nanoelectronic technology, a quantum-dot cellular automata (QCA) can achieve ultra-low power consumption as well as an extremely small area for implementing digital designs. However, there are various classes of permanent defects that can happen during the manufacture of QCA devices. The recent extensive research has been focused on how to eliminate errors in QCA structures resulting from fabrication variances. By a completely different vision, to turn this disadvantage into an advantage, this paper presents a novel QCA-based PUF (QCAPUF) architecture to exploit the unique physical characteristics of fabricated QCA cells in order to produce different hardware fingerprint instances. This architecture is composed of proposed logic and interconnect blocks that have critical vulnerabilities and perform unexpected logical operations. The behaviour of QCAPUF is thoroughly analysed through physical relations and simulations. Results confirm that the proposed QCAPUF has state of the art PUF characteristics in the QCA technology. This paper will serve as a basis for further research into QCA-based hardware security primitives and applications.

Positron Emission Tomography Using Fluorine F 18 EF5 to Find Oxygen in Tumor Cells of Patients Who Are Undergoing Surgery or Biopsy for Newly Diagnosed Brain Tumors

ClinicalTrials.gov

2013-01-15

Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Central Nervous System Germ Cell Tumor; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Grade III Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Meningeal Melanocytoma

Method for concurrent execution of primitive operations by dynamically assigning operations based upon computational marked graph and availability of data

NASA Technical Reports Server (NTRS)

Mielke, Roland V. (Inventor); Stoughton, John W. (Inventor)

1990-01-01

Computationally complex primitive operations of an algorithm are executed concurrently in a plurality of functional units under the control of an assignment manager. The algorithm is preferably defined as a computationally marked graph contianing data status edges (paths) corresponding to each of the data flow edges. The assignment manager assigns primitive operations to the functional units and monitors completion of the primitive operations to determine data availability using the computational marked graph of the algorithm. All data accessing of the primitive operations is performed by the functional units independently of the assignment manager.

How to Spot a Primitive Black Hole

NASA Image and Video Library

2010-03-17

These two data plots from NASA Spitzer Space Telescope show a primitive supermassive black hole top compared to a typical one; usually, dust tori are missing and only gas disks are observed in primitive black holes.

Functional characterization of individual human hematopoietic stem cells cultured at limiting dilution on supportive marrow stromal layers.

PubMed Central

Sutherland, H J; Lansdorp, P M; Henkelman, D H; Eaves, A C; Eaves, C J

1990-01-01

A major goal of current hematopoiesis research is to develop in vitro methods suitable for the measurement and characterization of stem cells with long-term in vivo repopulating potential. Previous studies from several centers have suggested the presence in normal human or murine marrow of a population of very primitive cells that are biologically, physically, and pharmacologically different from cells detectable by short-term colony assays and that can give rise to the latter in long-term cultures (LTCs) containing a competent stromal cell layer. In this report, we show that such cultures can be used to provide a quantitative assay for human "LTC-initiating cells" based on an assessment of the number of clonogenic cells present after 5-8 weeks. Production of derivative clonogenic cells is shown to be absolutely dependent on the presence of a stromal cell feeder. When this requirement is met, the clonogenic cell output (determined by assessment of 5-week-old cultures) is linearly related to the input cell number over a wide range of cell concentrations. Using limiting dilution analysis techniques, we have established the frequency of LTC-initiating cells in normal human marrow to be approximately 1 per 2 X 10(4) cells and in a highly purified CD34-positive subpopulation to be approximately 1 per 50-100 cells. The proliferative capacity exhibited by individual LTC-initiating cells cultured under apparently identical culture conditions was found to be highly variable. Values for the number of clonogenic cells per LTC-initiating cell in 5-week-old cultures ranged from 1 to 30 (the average being 4) with similar levels being detected in positive 8-week-old cultures. Some LTC-initiating cells are multipotent as evidenced by their generation of erythroid as well as granulopoietic progeny. The availability of a system for quantitative analysis of the proliferative and differentiative behavior of this newly defined compartment of primitive human hematopoietic cells should facilitate future studies of specific genetic or microenvironmental parameters involved in the regulation of these cells. Images PMID:2333304

Versatility of `hemorheologic fitness' according to exercise intensity: emphasis on the "healthy primitive lifestyle"

NASA Astrophysics Data System (ADS)

Brun, Jean-Frédéric; Varlet-Marie, Emmanuelle; Chevance, Guillaume; Pollatz, Marion; Fedou, Christine; de Mauverger, Eric Raynaud

2014-05-01

We recently proposed a unifying hypothesis to reconcile unexpected findings in exercise hemorheology and the classical concepts of "hemorheologic fitness" and the "triphasic effects of exercise", based on the "healthy primitive lifestyle" paradigm. This paradigm assumes that evolution has selected genetic polymorphisms leading to insulin resistance as an adaptative strategy to cope with continuous low intensity physical activity and a special alimentation moderately high in protein, rich in low glycemic index carbohydrates, and poor in saturated fat. According to this protocol the true physiological picture would be that of an individual whose exercise and nutritional habits are close from this lifestyle, both sedentary subjects and trained athletes representing situations on the edge of this model. Unfortunately samples of people truly adhering to this ancestral lifestyle are hard to obtain. In order to address this picture we tried to compare databases obtained with our preceding published studies. As a model of the "healthy primitive lifestyle" we selected patients trained at low intensity (LI) and given an advice of protein intake around 1.2 g/kg/day. Results show a continuum for plasma viscosity which seems to be lower in athletes than LI-trained and even more sedentaries. When sedentary subjects become obese the most obvious characteristic is an increase in red blood cell (RBC) aggregation correlated to the size of fat stores. It is clear that 3 months of LI are not a perfect model of "healthy primitive lifestyle", but these data suggest that the most important effect of LI regular exercise is to decrease plasma viscosity and that sedentarity increases RBC aggregation mostly when it results in increased fat storage.

A key heterogeneous structure of fractal networks based on inverse renormalization scheme

NASA Astrophysics Data System (ADS)

Bai, Yanan; Huang, Ning; Sun, Lina

2018-06-01

Self-similarity property of complex networks was found by the application of renormalization group theory. Based on this theory, network topologies can be classified into universality classes in the space of configurations. In return, through inverse renormalization scheme, a given primitive structure can grow into a pure fractal network, then adding different types of shortcuts, it exhibits different characteristics of complex networks. However, the effect of primitive structure on networks structural property has received less attention. In this paper, we introduce a degree variance index to measure the dispersion of nodes degree in the primitive structure, and investigate the effect of the primitive structure on network structural property quantified by network efficiency. Numerical simulations and theoretical analysis show a primitive structure is a key heterogeneous structure of generated networks based on inverse renormalization scheme, whether or not adding shortcuts, and the network efficiency is positively correlated with degree variance of the primitive structure.

High-Dose Chemotherapy With or Without Total-Body Irradiation Followed by Autologous Stem Cell Transplant in Treating Patients With Hematologic Cancer or Solid Tumors

ClinicalTrials.gov

2018-04-05

Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor (PNET); Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Plasma Cell Neoplasm; Primary Systemic Amyloidosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Neuroblastoma; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Regional Neuroblastoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

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

Scarlatescu, Ioana, E-mail: scarlatescuioana@gmail.com; Avram, Calin N.; Virag, Vasile

In this paper we present one treatment plan for irradiation cases which involve a complex technique with multiple beams, using the 3D conformational technique. As the main purpose of radiotherapy is to administrate a precise dose into the tumor volume and protect as much as possible all the healthy tissues around it, for a case diagnosed with a primitive neuro ectoderm tumor, we have developed a new treatment plan, by controlling one of the two adjacent fields used at spinal field, in a way that avoids the fields superposition. Therefore, the risk of overdose is reduced by eliminating the fieldmore » divergence.« less

Developmental characteristics of somatic cell hybrids between totipotent mouse teratocarcinoma and rat intestinal villus cells.

PubMed

van der Kamp, A W; Roza-de Jongh, E J; Houwen, R H; Magrane, G G; van Dongen, J M; Evans, M J

1984-09-01

Hybrids between mouse PCC4-azal teratocarcinoma cells and rat epithelial intestinal villus cells (PCI hybrids) are phenotypically teratocarcinoma cells. They express several teratocarcinoma-specific traits but do not express functions specific for differentiated cells. Tumour formation is partially or completely suppressed. Some of the hybrids show more extensive differentiation both in vitro and in vivo than the PCC4-azal parental line. The hybrids are capable of endoderm formation in monolayer cultures and of the formation of embryoid bodies in suspension cultures. Two of the tumour-forming hybrids generate derivatives of all three germ layers, whereas differentiation in the PCC4-azal tumours is restricted to the formation of primitive neuronal tissues.

A mutli-technique search for the most primitive CO chondrites

NASA Astrophysics Data System (ADS)

Alexander, C. M. O'D.; Greenwood, R. C.; Bowden, R.; Gibson, J. M.; Howard, K. T.; Franchi, I. A.

2018-01-01

As part of a study to identify the most primitive COs and to look for weakly altered CMs amongst the COs, we have conducted a multi-technique study of 16 Antarctic meteorites that had been classified as primitive COs. For this study, we have determined: (1) the bulk H, C and N abundances and isotopes, (2) bulk O isotopic compositions, (3) bulk modal mineralogies, and (4) for some selected samples the abundances and compositions of their insoluble organic matter (IOM). Two of the 16 meteorites do appear to be CMs - BUC 10943 seems to be a fairly typical CM, while MIL 090073 has probably been heated. Of the COs, DOM 08006 appears to be the most primitive CO identified to date and is quite distinct from the other members of its pairing group. The other COs fall into two groups that are less primitive than DOM 08006 and ALH 77307, the previously most primitive CO. The first group is composed of members of the DOM 08004 pairing group, except DOM 08006. The second group is composed of meteorites belonging to the MIL 03377 and MIL 07099 pairing groups. These two pairing groups should probably be combined. There is a dichotomy in the bulk O isotopes between the primitive (all Antarctic finds) and the more metamorphosed COs (mostly falls). This dichotomy can only partly be explained by the terrestrial weathering experienced by the primitive Antarctic samples. It seems that the more equilibrated samples interacted to a greater extent with 16O-poor material, probably water, than the more primitive meteorites.

Human Pluripotent Stem Cells Differentiated in Fully Defined Medium Generate Hematopoietic CD34+ and CD34− Progenitors with Distinct Characteristics

PubMed Central

Chicha, Laurie; Feki, Anis; Boni, Alessandro; Irion, Olivier; Hovatta, Outi; Jaconi, Marisa

2011-01-01

Background Differentiation of pluripotent stem cells in vitro provides a powerful means to investigate early developmental fates, including hematopoiesis. In particular, the use of a fully defined medium (FDM) would avoid biases induced by unidentified factors contained in serum, and would also allow key molecular mediators involved in such a process to be identified. Our goal was to induce in vitro, the differentiation of human embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) into morphologically and phenotypically mature leukocytes and erythrocytes, in the complete absence of serum and feeder cells. Methodology/Principal Findings ESC and iPSC were sequentially induced in liquid cultures for 4 days with bone morphogenic protein-4, and for 4 days with FLT3-ligand, stem cell factor, thrombopoietin and vascular endothelium growth factor. Cell differentiation status was investigated by both mRNA expression and FACS expression profiles. Cells were further sorted and assayed for their hematopoietic properties in colony-forming unit (CFU) assays. In liquid cultures, cells progressively down-modulated Oct-4 expression while a sizeable cell fraction expressed CD34 de novo. SCL/Tal1 and Runx1 transcripts were exclusively detected in CD34+ cells. In clonal assays, both ESC and iPSC-derived cells generated CFU, albeit with a 150-fold lower efficacy than cord blood (CB) CD34+ cells. ESC-derived CD34+ cells generated myeloid and fully hemoglobinized erythroid cells whereas CD34− cells almost exclusively generated small erythroid colonies. Both ESC and iPSC-derived erythroid cells expressed embryonic and fetal globins but were unable to synthesize adult β-globin in contrast with CB cells, suggesting that they had differentiated from primitive rather than from definitive hematopoietic progenitors. Conclusions/Significance Short-term, animal protein-free culture conditions are sufficient to sustain the differentiation of human ESC and iPSC into primitive hematopoietic progenitors, which, in turn, produce more mature blood cell types. However, additional factors have yet to be identified to allow their differentiation into definitive erythroid cultures. PMID:21364915

Human pluripotent stem cells differentiated in fully defined medium generate hematopoietic CD34- and CD34+ progenitors with distinct characteristics.

PubMed

Chicha, Laurie; Feki, Anis; Boni, Alessandro; Irion, Olivier; Hovatta, Outi; Jaconi, Marisa

2011-02-25

Differentiation of pluripotent stem cells in vitro provides a powerful means to investigate early developmental fates, including hematopoiesis. In particular, the use of a fully defined medium (FDM) would avoid biases induced by unidentified factors contained in serum, and would also allow key molecular mediators involved in such a process to be identified. Our goal was to induce in vitro, the differentiation of human embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) into morphologically and phenotypically mature leukocytes and erythrocytes, in the complete absence of serum and feeder cells. ESC and iPSC were sequentially induced in liquid cultures for 4 days with bone morphogenic protein-4, and for 4 days with FLT3-ligand, stem cell factor, thrombopoietin and vascular endothelium growth factor. Cell differentiation status was investigated by both mRNA expression and FACS expression profiles. Cells were further sorted and assayed for their hematopoietic properties in colony-forming unit (CFU) assays. In liquid cultures, cells progressively down-modulated Oct-4 expression while a sizeable cell fraction expressed CD34 de novo. SCL/Tal1 and Runx1 transcripts were exclusively detected in CD34(+) cells. In clonal assays, both ESC and iPSC-derived cells generated CFU, albeit with a 150-fold lower efficacy than cord blood (CB) CD34(+) cells. ESC-derived CD34(+) cells generated myeloid and fully hemoglobinized erythroid cells whereas CD34(-) cells almost exclusively generated small erythroid colonies. Both ESC and iPSC-derived erythroid cells expressed embryonic and fetal globins but were unable to synthesize adult β-globin in contrast with CB cells, suggesting that they had differentiated from primitive rather than from definitive hematopoietic progenitors. Short-term, animal protein-free culture conditions are sufficient to sustain the differentiation of human ESC and iPSC into primitive hematopoietic progenitors, which, in turn, produce more mature blood cell types. However, additional factors have yet to be identified to allow their differentiation into definitive erythroid cultures.

A monoclonal antibody inhibits calcium accumulation and skeleton formation in cultured embryonic cells of the sea urchin.

PubMed

Carson, D D; Farach, M C; Earles, D S; Decker, G L; Lennarz, W J

1985-06-01

The assembly of the spicules (primitive skeleton) of the sea urchin embryo is being studied in primary mesenchyme cells cultured in vitro. A monoclonal antibody (1223) has been prepared that inhibits the deposition of CaCO3 into the spicules. This antibody reacts with a 130,000 Mr cell-surface protein that is concentrated on the surface of approximately 5% of the cells of dissociated gastrula stage embryos. When primary mesenchyme cells in the embryo or cells cultured in vitro are examined, the 1223 antigen is detected on the surface of the cells and on the extracellular material associated with the spicule. We conclude that the 1223 antibody recognizes a cell-surface protein that plays an essential role in spicule formation.

Spontaneous encapsulation and concentration of biological macromolecules in liposomes: an intriguing phenomenon and its relevance in origins of life.

PubMed

de Souza, Tereza Pereira; Fahr, Alfred; Luisi, Pier Luigi; Stano, Pasquale

2014-12-01

One of the main open questions in origin of life research focuses on the formation, by self-organization, of primitive cells composed by macromolecular compounds enclosed within a semi-permeable membrane. A successful experimental strategy for studying the emergence and the properties of primitive cells relies on a synthetic biology approach, consisting in the laboratory assembly of cell models of minimal complexity (semi-synthetic minimal cells). Despite the recent advancements in the construction and characterization of synthetic cells, an important physical aspect related to their formation is still not well known, namely, the mechanism of solute entrapment inside liposomes (in particular, the entrapment of macromolecules). In the past years, we have investigated this phenomenon and here we shortly review our experimental results. We show how the detailed cryo-transmission electron microscopy analyses of liposome populations created in the presence of ferritin (taken as model protein) or ribosomes have revealed that a small fraction of liposomes contains a high number of solutes, against statistical expectations. The local (intra-liposomal) macromolecule concentration in these liposomes largely exceeds the bulk concentration. A similar behaviour is observed when multi-molecular reaction mixtures are used, whereby the reactions occur effectively only inside those liposomes that have entrapped high number of molecules. If similar mechanisms operated in early times, these intriguing results support a scenario whereby the formation of lipid compartments plays an important role in concentrating the components of proto-metabolic systems-in addition to their well-known functions of confinement and protection.

Evolution of the α-Subunit of Na/K-ATPase from Paramecium to Homo sapiens: Invariance of Transmembrane Helix Topology.

PubMed

Morrill, Gene A; Kostellow, Adele B; Liu, Lijun; Gupta, Raj K; Askari, Amir

2016-05-01

Na/K-ATPase is a key plasma membrane enzyme involved in cell signaling, volume regulation, and maintenance of electrochemical gradients. The α-subunit, central to these functions, belongs to a large family of P-type ATPases. Differences in transmembrane (TM) helix topology, sequence homology, helix-helix contacts, cell signaling, and protein domains of Na/K-ATPase α-subunit were compared in fungi (Beauveria), unicellular organisms (Paramecia), primitive multicellular organisms (Hydra), and vertebrates (Xenopus, Homo sapiens), and correlated with evolution of physiological functions in the α-subunit. All α-subunits are of similar length, with groupings of four and six helices in the N- and C-terminal regions, respectively. Minimal homology was seen for protein domain patterns in Paramecium and Hydra, with high correlation between Hydra and vertebrates. Paramecium α-subunits display extensive disorder, with minimal helix contacts. Increases in helix contacts in Hydra approached vertebrates. Protein motifs known to be associated with membrane lipid rafts and cell signaling reveal significant positional shifts between Paramecium and Hydra vulgaris, indicating that regional membrane fluidity changes occur during evolution. Putative steroid binding sites overlapping TM-3 occurred in all species. Sites associated with G-protein-receptor stimulation occur both in vertebrates and amphibia but not in Hydra or Paramecia. The C-terminus moiety "KETYY," necessary for the Na(+) activation of pump phosphorylation, is not present in unicellular species indicating the absence of classical Na(+)/K(+)-pumps. The basic protein topology evolved earliest, followed by increases in protein domains and ordered helical arrays, correlated with appearance of α-subunit regions known to involve cell signaling, membrane recycling, and ion channel formation.

The Paradox of the Axial Melt Lens: Petrology and Geochemistry of the Upper Plutonics at Hess Deep

NASA Astrophysics Data System (ADS)

Lissenberg, C. J.; Loocke, M. P.; MacLeod, C. J.

2014-12-01

The axial melt lens (AML) is a steady-state magma-rich body located at the dyke-gabbro transition at intermediate- and fast-spreading ridges. It is widely believed to be the reservoir from which mid-ocean ridge basalt (MORB) is erupted. The paradox of the axial melt lens is that the plutonic rocks that occur at this level are far too evolved to be in equilibrium with MORB, which is basaltic by definition; hence, the plutonic and volcanic records do not match. We explore this paradox by study of the first comprehensive sample suite of the uppermost plutonics of a fast-spreading ridge, taken by remotely-operated vehicle from the Hess Deep rift during cruise JC21. 23 samples (8 dolerites, 14 gabbronorites, and 1 gabbro) were collected from a section containing the transition from the uppermost gabbroic section into sheeted dykes. We present the results of a detailed petrographic and microanalytical investigation of these samples. They are dominated by evolved, varitextured (both in hand sample and thin section) oxide gabbronorites; olivine occurs in only one sample. A preponderance of the samples have positive Eu/Eu* and Sr/Sr*, indicating a cumulate origin. However, the minerals have evolved compositions, and are in equilibrium with melts significantly more evolved than East Pacific Rise MORB. Furthermore, the trace element contents of clinopyroxene differ significantly from clinopyroxene in equilibrium with MORB, being more enriched in incompatible elements. To account for both the evidence of derivation of MORB from the AML and the evolved nature of its rock record, we posit that the AML must be fed by melts on two different timescales: continual low-volume feeding by evolved interstitial melt from the cumulus pile below is augmented episodically by delivery of high volumes of more primitive melt. The latter episodes may trigger eruptions; hence the primitive melts are held in the magma chamber for only short periods, and erupt on the seafloor before significant crystallisation in the AML has taken place. This model for the feeding of the AML provides ample opportunity for mixing between the relatively primitive melts and the evolved, trace-element-rich melt, and accounts for the observed over-enrichment in incompatible elements of MORB.

Dynamic primitives in the control of locomotion.

PubMed

Hogan, Neville; Sternad, Dagmar

2013-01-01

Humans achieve locomotor dexterity that far exceeds the capability of modern robots, yet this is achieved despite slower actuators, imprecise sensors, and vastly slower communication. We propose that this spectacular performance arises from encoding motor commands in terms of dynamic primitives. We propose three primitives as a foundation for a comprehensive theoretical framework that can embrace a wide range of upper- and lower-limb behaviors. Building on previous work that suggested discrete and rhythmic movements as elementary dynamic behaviors, we define submovements and oscillations: as discrete movements cannot be combined with sufficient flexibility, we argue that suitably-defined submovements are primitives. As the term "rhythmic" may be ambiguous, we define oscillations as the corresponding class of primitives. We further propose mechanical impedances as a third class of dynamic primitives, necessary for interaction with the physical environment. Combination of these three classes of primitive requires care. One approach is through a generalized equivalent network: a virtual trajectory composed of simultaneous and/or sequential submovements and/or oscillations that interacts with mechanical impedances to produce observable forces and motions. Reliable experimental identification of these dynamic primitives presents challenges: identification of mechanical impedances is exquisitely sensitive to assumptions about their dynamic structure; identification of submovements and oscillations is sensitive to their assumed form and to details of the algorithm used to extract them. Some methods to address these challenges are presented. Some implications of this theoretical framework for locomotor rehabilitation are considered.

Overexpression, crystallization and preliminary X-ray crystallographic analysis of phosphopantetheine adenylyltransferase from Enterococcus faecalis

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

Kang, Ji Yong; Lee, Hyung Ho; Yoon, Hye Jin

2006-11-01

Phosphopantetheine adenylyltransferase from En. faecalis was crystallized and X-ray diffraction data were collected to 2.70 Å resolution. Phosphopantetheine adenylyltransferase, an essential enzyme in the coenzyme A biosynthetic pathway, catalyzes the reversible transfer of an adenylyl group from ATP to 4′-phosphopantetheine, yielding 3′-dephospho-CoA and pyrophosphate. Enterococcus faecalis PPAT has been overexpressed in Escherichia coli as a fusion with a C-terminal purification tag and crystallized at 297 K using a reservoir solution consisting of 0.1 M sodium HEPES pH 7.5, 0.8 M sodium dihydrogen phosphate and 0.8 M potassium dihydrogen phosphate. X-ray diffraction data were collected to 2.70 Å at 100 K.more » The crystals belong to the primitive tetragonal space group P4{sub 1} (or P4{sub 3}), with unit-cell parameters a = b = 160.81, c = 225.68 Å. Four copies of the hexameric molecule are likely to be present in the asymmetric unit, giving a crystal volume per protein weight (V{sub M}) of 3.08 Å{sup 3} Da{sup −1} and a solvent content of 60.1%.« less

How many theories for the origin of /proto/life

NASA Technical Reports Server (NTRS)

Fox, S. W.

1980-01-01

The sequence of primordial chemical events leading to contemporary metabolism is considered, taking into account primordial reactants, amino acids, proteinoid, protocells, ATP, polynucleotides, and protein. The right kind of matter, thermal copolyamino acids, can organize itself into cell-like structures, in the absence of discrete lipid, when triggered to do so by water. Another unpredicted result of examination of the microsystems formed was the step-by-step realization that the component processes of a primitive form of replication were latent in the proteinoid microsystems. At the present time, four modes of primitive replication of proteinoid microsystems have been identified, plus one that has the appearance of protosexual reproduction. Two main conceptual pathways have received attention. One is the proteinoid theory, derived from experiments. The other is the DNA-first theory, for which attempts at conceptual construction and experimental support continue to be sought.

The origin and early evolution of life on earth

NASA Technical Reports Server (NTRS)

Oro, J.; Miller, Stanley L.; Lazcano, Antonio

1990-01-01

Results of the studies that have provided insights into the cosmic and primitive earth environments are reviewed with emphasis on those environments in which life is thought to have originated. The evidence bearing on the antiquity of life on the earth and the prebiotic significance of organic compounds found in interstellar clouds and in primitive solar-system bodies such as comets, dark asteroids, and carbonaceous chondrites are assessed. The environmental models of the Hadean and early Archean earth are discussed, as well as the prebiotic formation of organic monomers and polymers essential to life. The processes that may have led to the appearance in the Archean of the first cells are considered, and possible effects of these processes on the early steps of biological evolution are analyzed. The significance of these results to the study of the distribution of life in the universe is evaluated.

Models of glycolysis: Glyceraldehyde as a source of energy and monomers for prebiotic condensation reactions

NASA Technical Reports Server (NTRS)

Weber, A. L.

1986-01-01

All organisms require energy in a chemical form for maintenance and growth. In contemporary life this chemical energy is obtained by the synthesis of the phosphoanhydride bonds of ATP. Among the biological processes that yield ATP, fermentation is generally considered primitive, because it operates under anaerobic conditions by substrate-level phosphorylation which does not require compartmentation by membranes. Fermentation by the glycolytic pathway, which is found in almost every living cell, is an especially attractive energy source for primitive life. Glycolysis not only produces useful chemical energy (ATP), but intermediates of this pathway are also involved in amino acid synthesis and photosynthetic carbon-fixation. It is believed that energy and substrates needed for the origin of life were provided by nonenzymatic chemical reactions that resemble the enzyme-mediated reactions of glycolysis. These nonenzymatic reactions would have provided a starting point for the evolutionary development of glycolysis.

Inhibiting Low-Frequency Vibrations Explains Exceptionally High Electron Mobility in 2,5-Difluoro-7,7,8,8-tetracyanoquinodimethane (F2-TCNQ) Single Crystals.

PubMed

Chernyshov, Ivan Yu; Vener, Mikhail V; Feldman, Elizaveta V; Paraschuk, Dmitry Yu; Sosorev, Andrey Yu

2017-07-06

Organic electronics requires materials with high charge mobility. Despite decades of intensive research, charge transport in high-mobility organic semiconductors has not been well understood. In this Letter, we address the physical mechanism underlying the exceptionally high band-like electron mobility in F 2 -TCNQ (2,5-difluoro-7,7,8,8-tetracyanoquinodimethane) single crystals among a crystal family of similar compounds F n -TCNQ (n = 0, 2, 4) using a combined experimental and theoretical approach. While electron transfer integrals and reorganization energies did not show outstanding features for F 2 -TCNQ, Raman spectroscopy and solid-state DFT indicated that the frequency of the lowest vibrational mode is nearly twice higher in the F 2 -TCNQ crystal than in TCNQ and F 4 -TCNQ. This phenomenon is explained by the specific packing motif of F 2 -TCNQ with only one molecule per primitive cell so that electron-phonon interaction decreases and the electron mobility increases. We anticipate that our findings will encourage investigators for the search and design of organic semiconductors with one molecule per primitive cell and/or the poor low-frequency vibrational spectrum.

Three-dimensional spiral CT during arterial portography: comparison of three rendering techniques.

PubMed

Heath, D G; Soyer, P A; Kuszyk, B S; Bliss, D F; Calhoun, P S; Bluemke, D A; Choti, M A; Fishman, E K

1995-07-01

The three most common techniques for three-dimensional reconstruction are surface rendering, maximum-intensity projection (MIP), and volume rendering. Surface-rendering algorithms model objects as collections of geometric primitives that are displayed with surface shading. The MIP algorithm renders an image by selecting the voxel with the maximum intensity signal along a line extended from the viewer's eye through the data volume. Volume-rendering algorithms sum the weighted contributions of all voxels along the line. Each technique has advantages and shortcomings that must be considered during selection of one for a specific clinical problem and during interpretation of the resulting images. With surface rendering, sharp-edged, clear three-dimensional reconstruction can be completed on modest computer systems; however, overlapping structures cannot be visualized and artifacts are a problem. MIP is computationally a fast technique, but it does not allow depiction of overlapping structures, and its images are three-dimensionally ambiguous unless depth cues are provided. Both surface rendering and MIP use less than 10% of the image data. In contrast, volume rendering uses nearly all of the data, allows demonstration of overlapping structures, and engenders few artifacts, but it requires substantially more computer power than the other techniques.

Breaking the rules? X-ray examination of hematopoietic stem cell grafts at international airports.

PubMed

Petzer, Andreas L; Speth, Hans-Georg; Hoflehner, Elisabeth; Clausen, Johannes; Nachbaur, David; Gastl, Günther; Gunsilius, Eberhard

2002-06-15

Hematopoietic stem cell grafts from unrelated donors are commonly transported by aircraft. They must not be subjected to x-rays during security checks, which may cause inconvenient discussions between the courier and the airport security staff. We exposed hematopoietic stem cells from mobilized peripheral blood to a widely used x-ray hand-luggage control system. Cell viability as well as growth in vitro of mature progenitor cells (colony-forming cells), primitive progenitor cells (long-term culture-initiating cells), and lymphocytes were not altered even after 10 passages through the hand-luggage control system. Thus, repeated exposure to the low radiation dose of hand-luggage control systems (1.5 +/- 0.6 microSv per exposure) seems to be harmless for hematopoietic stem cells, which should simplify the international transport of stem cell grafts.

Study of stem cell homing & self-renewal marker gene profile of ex vivo expanded human CD34+ cells manipulated with a mixture of cytokines & stromal cell-derived factor 1

PubMed Central

Kode, Jyoti; Khattry, Navin; Bakshi, Ashish; Amrutkar, Vasanti; Bagal, Bhausaheb; Karandikar, Rohini; Rane, Pallavi; Fujii, Nobutaka; Chiplunkar, Shubhada

2017-01-01

Background & objectives: Next generation transplantation medicine aims to develop stimulating cocktail for increased ex vivo expansion of primitive hematopoietic stem and progenitor cells (HSPC). The present study was done to evaluate the cocktail GF (Thrombopoietin + Stem Cell factor + Flt3-ligand) and homing-defining molecule Stromal cell-derived factor 1 (SDF1) for HSPC ex vivo expansion. Methods: Peripheral blood stem cell (n=74) harvests were analysed for CD34hi CD45lo HSPC. Immunomagnetically enriched HSPC were cultured for eight days and assessed for increase in HSPC, colony forming potential in vitro and in vivo engrafting potential by analyzing human CD45+ cells. Expression profile of genes for homing and stemness were studied using microarray analysis. Expression of adhesion/homing markers were validated by flow cytometry/ confocal microscopy. Results: CD34hi CD45lo HSPC expansion cultures with GF+SDF1 demonstrated increased nucleated cells (n=28, P< 0.001), absolute CD34+ cells (n=8, P=0.021) and increased colony forming units (cfu) compared to unstimulated and GF-stimulated HSPC. NOD-SCID mice transplanted with GF+SDF1-HSPC exhibited successful homing/engraftment (n=24, P< 0.001). Microarray analysis of expanded HSPC demonstrated increased telomerase activity and many homing-associated genes (35/49) and transcription factors for stemness/self-renewal (49/56) were significantly upregulated in GF+SDF1 stimulated HSPC when compared to GF-stimulated HSPC. Expression of CD44, CXCR4, CD26, CD14, CD45 and soluble IL-6 in expanded cultures were validated by flow cytometry and confocal microscopy. Interpretation & conclusions: Cocktail of cytokines and SDF1 showed good potential to successfully expand HSPC which exhibited enhanced ability to generate multilineage cells in short-term and long-term repopulation assay. This cocktail-mediated stem cell expansion has potential to obviate the need for longer and large volume apheresis procedure making it convenient for donors. PMID:29168461

Fundamental physical theories: Mathematical structures grounded on a primitive ontology

NASA Astrophysics Data System (ADS)

Allori, Valia

In my dissertation I analyze the structure of fundamental physical theories. I start with an analysis of what an adequate primitive ontology is, discussing the measurement problem in quantum mechanics and theirs solutions. It is commonly said that these theories have little in common. I argue instead that the moral of the measurement problem is that the wave function cannot represent physical objects and a common structure between these solutions can be recognized: each of them is about a clear three-dimensional primitive ontology that evolves according to a law determined by the wave function. The primitive ontology is what matter is made of while the wave function tells the matter how to move. One might think that what is important in the notion of primitive ontology is their three-dimensionality. If so, in a theory like classical electrodynamics electromagnetic fields would be part of the primitive ontology. I argue that, reflecting on what the purpose of a fundamental physical theory is, namely to explain the behavior of objects in three-dimensional space, one can recognize that a fundamental physical theory has a particular architecture. If so, electromagnetic fields play a different role in the theory than the particles and therefore should be considered, like the wave function, as part of the law. Therefore, we can characterize the general structure of a fundamental physical theory as a mathematical structure grounded on a primitive ontology. I explore this idea to better understand theories like classical mechanics and relativity, emphasizing that primitive ontology is crucial in the process of building new theories, being fundamental in identifying the symmetries. Finally, I analyze what it means to explain the word around us in terms of the notion of primitive ontology in the case of regularities of statistical character. Here is where the notion of typicality comes into play: we have explained a phenomenon if the typical histories of the primitive ontology give rise to the statistical regularities we observe.

A novel class sensitive hashing technique for large-scale content-based remote sensing image retrieval

NASA Astrophysics Data System (ADS)

Reato, Thomas; Demir, Begüm; Bruzzone, Lorenzo

2017-10-01

This paper presents a novel class sensitive hashing technique in the framework of large-scale content-based remote sensing (RS) image retrieval. The proposed technique aims at representing each image with multi-hash codes, each of which corresponds to a primitive (i.e., land cover class) present in the image. To this end, the proposed method consists of a three-steps algorithm. The first step is devoted to characterize each image by primitive class descriptors. These descriptors are obtained through a supervised approach, which initially extracts the image regions and their descriptors that are then associated with primitives present in the images. This step requires a set of annotated training regions to define primitive classes. A correspondence between the regions of an image and the primitive classes is built based on the probability of each primitive class to be present at each region. All the regions belonging to the specific primitive class with a probability higher than a given threshold are highly representative of that class. Thus, the average value of the descriptors of these regions is used to characterize that primitive. In the second step, the descriptors of primitive classes are transformed into multi-hash codes to represent each image. This is achieved by adapting the kernel-based supervised locality sensitive hashing method to multi-code hashing problems. The first two steps of the proposed technique, unlike the standard hashing methods, allow one to represent each image by a set of primitive class sensitive descriptors and their hash codes. Then, in the last step, the images in the archive that are very similar to a query image are retrieved based on a multi-hash-code-matching scheme. Experimental results obtained on an archive of aerial images confirm the effectiveness of the proposed technique in terms of retrieval accuracy when compared to the standard hashing methods.

Learning multivariate distributions by competitive assembly of marginals.

PubMed

Sánchez-Vega, Francisco; Younes, Laurent; Geman, Donald

2013-02-01

We present a new framework for learning high-dimensional multivariate probability distributions from estimated marginals. The approach is motivated by compositional models and Bayesian networks, and designed to adapt to small sample sizes. We start with a large, overlapping set of elementary statistical building blocks, or "primitives," which are low-dimensional marginal distributions learned from data. Each variable may appear in many primitives. Subsets of primitives are combined in a Lego-like fashion to construct a probabilistic graphical model; only a small fraction of the primitives will participate in any valid construction. Since primitives can be precomputed, parameter estimation and structure search are separated. Model complexity is controlled by strong biases; we adapt the primitives to the amount of training data and impose rules which restrict the merging of them into allowable compositions. The likelihood of the data decomposes into a sum of local gains, one for each primitive in the final structure. We focus on a specific subclass of networks which are binary forests. Structure optimization corresponds to an integer linear program and the maximizing composition can be computed for reasonably large numbers of variables. Performance is evaluated using both synthetic data and real datasets from natural language processing and computational biology.

Cometary dust: the diversity of primitive refractory grains

PubMed Central

Ishii, H. A.

2017-01-01

Comet dust is primitive and shows significant diversity. Our knowledge of the properties of primitive cometary particles has expanded significantly through microscale investigations of cosmic dust samples (anhydrous interplanetary dust particles (IDPs), chondritic porous (CP) IDPs and UltraCarbonaceous Antarctic micrometeorites, Stardust and Rosetta), as well as through remote sensing (Spitzer IR spectroscopy). Comet dust are aggregate particles of materials unequilibrated at submicrometre scales. We discuss the properties and processes experienced by primitive matter in comets. Primitive particles exhibit a diverse range of: structure and typology; distribution of constituents; concentration and form of carbonaceous and refractory organic matter; Mg- and Fe-contents of the silicate minerals; sulfides; existence/abundance of type II chondrule fragments; high-temperature calcium–aluminium inclusions and ameboid-olivine aggregates; and rarely occurring Mg-carbonates and magnetite, whose explanation requires aqueous alteration on parent bodies. The properties of refractory materials imply there were disc processes that resulted in different comets having particular selections of primitive materials. The diversity of primitive particles has implications for the diversity of materials in the protoplanetary disc present at the time and in the region where the comets formed. This article is part of the themed issue ‘Cometary science after Rosetta’. PMID:28554979

Age-related Deterioration of Hematopoietic Stem Cells.

PubMed

Kim, Mi Jung; Kim, Min Hwan; Kim, Seung Ah; Chang, Jae Suk

2008-11-01

Aging is the process of system deterioration over time in the whole body. Stem cells are self-renewing and therefore have been considered exempt from the aging process. Earlier studies by Hayflick showed that there is an intrinsic limit to the number of divisions that mammalian somatic cells can undergo, and cycling kinetics and ontogeny-related studies strongly suggest that even the most primitive stem cell functions exhibit a certain degree of aging. Despite these findings, studies on the effects of aging on stem cell functions are inconclusive. Here we review the age-related properties of hematopoietic stem cells in terms of intrinsic and extrinsic alterations, proliferative potential, signaling molecules, telomere and telomerase, senescence and cancer issues, regenerative potential and other indications of stem cell aging are discussed in detail.

Age-related Deterioration of Hematopoietic Stem Cells

PubMed Central

Kim, Mi Jung; Kim, Min Hwan; Kim, Seung Ah; Chang, Jae Suk

2008-01-01

Aging is the process of system deterioration over time in the whole body. Stem cells are self-renewing and therefore have been considered exempt from the aging process. Earlier studies by Hayflick showed that there is an intrinsic limit to the number of divisions that mammalian somatic cells can undergo, and cycling kinetics and ontogeny-related studies strongly suggest that even the most primitive stem cell functions exhibit a certain degree of aging. Despite these findings, studies on the effects of aging on stem cell functions are inconclusive. Here we review the age-related properties of hematopoietic stem cells in terms of intrinsic and extrinsic alterations, proliferative potential, signaling molecules, telomere and telomerase, senescence and cancer issues, regenerative potential and other indications of stem cell aging are discussed in detail. PMID:24855509

Round cell sarcomas beyond Ewing: emerging entities.

PubMed

Antonescu, Cristina

2014-01-01

Primitive small blue round cell tumours (SBRCT) of childhood and young adults have been problematic to diagnose and classify. Diagnosis is also complicated in cases with atypical morphology, aberrant immunoprofiles and unusual clinical presentations. Even with the increased use of ancillary techniques in archival material, such as immunohistochemistry and molecular/genetic methods, a proportion of these tumours cannot be subclassified into specific histological types. A subset of tumours resembling microscopically the Ewing sarcoma family of tumours (EFT), being composed of primitive small round cells and occurring in paediatric or young adult age groups, remain unclassified, being negative for EWSR1, SS18(SYT), DDIT3(CHOP) and FOXO1(FKHR) gene rearrangements by FISH/RT-PCR. A small number of cases sharing the undifferentiated EFT appearance have been characterized recently carrying BCOR-CCNB3 or CIC-DUX4 fusions. However, based on the somewhat limited number of cases, it remains unclear if these newly defined genetic entities belong to any of the pre-existing clinicopathological disorders or represent altogether novel conditions. This review presents the latest molecular findings related to these SBRCTs, beyond the common EWSR1-ETS fusions. Specific attention has been paid to morphological features not associated typically with classic EFT, and the value of ancillary tests that can be applied when dealing with EWSR1-negative SBRCTs is discussed. © 2013 John Wiley & Sons Ltd.

Basic primitives for molecular diagram sketching

PubMed Central

2010-01-01

A collection of primitive operations for molecular diagram sketching has been developed. These primitives compose a concise set of operations which can be used to construct publication-quality 2 D coordinates for molecular structures using a bare minimum of input bandwidth. The input requirements for each primitive consist of a small number of discrete choices, which means that these primitives can be used to form the basis of a user interface which does not require an accurate pointing device. This is particularly relevant to software designed for contemporary mobile platforms. The reduction of input bandwidth is accomplished by using algorithmic methods for anticipating probable geometries during the sketching process, and by intelligent use of template grafting. The algorithms and their uses are described in detail. PMID:20923555

AZD2171 in Treating Young Patients With Recurrent, Progressive, or Refractory Primary CNS Tumors

ClinicalTrials.gov

2016-03-04

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Cerebral Anaplastic Astrocytoma; Childhood Cerebral Astrocytoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Oligodendroglioma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Neoplasm; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway Glioma

Dynamic primitives in the control of locomotion

PubMed Central

Hogan, Neville; Sternad, Dagmar

2013-01-01

Humans achieve locomotor dexterity that far exceeds the capability of modern robots, yet this is achieved despite slower actuators, imprecise sensors, and vastly slower communication. We propose that this spectacular performance arises from encoding motor commands in terms of dynamic primitives. We propose three primitives as a foundation for a comprehensive theoretical framework that can embrace a wide range of upper- and lower-limb behaviors. Building on previous work that suggested discrete and rhythmic movements as elementary dynamic behaviors, we define submovements and oscillations: as discrete movements cannot be combined with sufficient flexibility, we argue that suitably-defined submovements are primitives. As the term “rhythmic” may be ambiguous, we define oscillations as the corresponding class of primitives. We further propose mechanical impedances as a third class of dynamic primitives, necessary for interaction with the physical environment. Combination of these three classes of primitive requires care. One approach is through a generalized equivalent network: a virtual trajectory composed of simultaneous and/or sequential submovements and/or oscillations that interacts with mechanical impedances to produce observable forces and motions. Reliable experimental identification of these dynamic primitives presents challenges: identification of mechanical impedances is exquisitely sensitive to assumptions about their dynamic structure; identification of submovements and oscillations is sensitive to their assumed form and to details of the algorithm used to extract them. Some methods to address these challenges are presented. Some implications of this theoretical framework for locomotor rehabilitation are considered. PMID:23801959

Model-Free Primitive-Based Iterative Learning Control Approach to Trajectory Tracking of MIMO Systems With Experimental Validation.

PubMed

Radac, Mircea-Bogdan; Precup, Radu-Emil; Petriu, Emil M

2015-11-01

This paper proposes a novel model-free trajectory tracking of multiple-input multiple-output (MIMO) systems by the combination of iterative learning control (ILC) and primitives. The optimal trajectory tracking solution is obtained in terms of previously learned solutions to simple tasks called primitives. The library of primitives that are stored in memory consists of pairs of reference input/controlled output signals. The reference input primitives are optimized in a model-free ILC framework without using knowledge of the controlled process. The guaranteed convergence of the learning scheme is built upon a model-free virtual reference feedback tuning design of the feedback decoupling controller. Each new complex trajectory to be tracked is decomposed into the output primitives regarded as basis functions. The optimal reference input for the control system to track the desired trajectory is next recomposed from the reference input primitives. This is advantageous because the optimal reference input is computed straightforward without the need to learn from repeated executions of the tracking task. In addition, the optimization problem specific to trajectory tracking of square MIMO systems is decomposed in a set of optimization problems assigned to each separate single-input single-output control channel that ensures a convenient model-free decoupling. The new model-free primitive-based ILC approach is capable of planning, reasoning, and learning. A case study dealing with the model-free control tuning for a nonlinear aerodynamic system is included to validate the new approach. The experimental results are given.

36 CFR 261.21 - National Forest primitive areas.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false National Forest primitive areas. 261.21 Section 261.21 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE PROHIBITIONS General Prohibitions § 261.21 National Forest primitive areas. The following are...

Metabolic reprogramming: a cancer hallmark even warburg did not anticipate.

PubMed

Ward, Patrick S; Thompson, Craig B

2012-03-20

Cancer metabolism has long been equated with aerobic glycolysis, seen by early biochemists as primitive and inefficient. Despite these early beliefs, the metabolic signatures of cancer cells are not passive responses to damaged mitochondria but result from oncogene-directed metabolic reprogramming required to support anabolic growth. Recent evidence suggests that metabolites themselves can be oncogenic by altering cell signaling and blocking cellular differentiation. No longer can cancer-associated alterations in metabolism be viewed as an indirect response to cell proliferation and survival signals. We contend that altered metabolism has attained the status of a core hallmark of cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

Histochemical in situ identification of bovine embryonic blood cells reveals differences to the adult haematopoietic system and suggests a close relationship between haematopoietic stem cells and primordial germ cells.

PubMed

Kritzenberger, Michaela; Wrobel, Karl-Heinz

2004-04-01

Cryostat sections of bovine embryos of exactly known age (obtained from artificial insemination), ranging from 32 to 60 days post-insemination, were treated with a wide range of antibodies directed against cell surface antigens or lineage-specific factors in order to demonstrate different types of fetal blood cells and their precursors. An antibody specific to bovine c-kit (bk-1) stained not only presumptive haematopoietic stem cells in the dorsal aorta and the embryonic liver, but also a subpopulation of putative primordial germ cells in the gonadal anlage, the latter being further characterised by a positive labelling with the lectins STA, WFA and WGA and a histochemical reaction for alkaline phosphatase. The antibody against CD 45, commonly regarded as a pan-leukocyte marker, reacted in the bovine embryo with different types of blood cells, as well as with presumptive vasculogenetic cells and a subpopulation of putative primordial germ cells. CD 61 immunoreaction proved to be a useful tool for demonstrating megakaryocytopoiesis in the embryonic liver, in addition to the lumen of blood vessels and the mesonephros. Staining with BM-2 was restricted to a single population of medium-sized, round to oval cells, forming small groups within the parenchymal strands of the liver. Characterised furthermore by a U-shaped nucleus, this BM-2-positive cell type apparently represents a developmental stage in the granulopoietic lineage. B-lymphocytopoiesis in the bovine liver was detected with antibodies directed against WC-4 and IgM, but not until day 58 post-insemination. Using antibodies to CD 14, no positive results could be obtained in embryonic tissues, although anti-CD 14-positive macrophages were easily recognised in lymph nodes of adult bovines. The antibody against CD 68, however, identified two populations of primitive macrophages in our samples. One population was located in parenchymal strands of the embryonic liver, probably acting as nursing cells for haematopoietic foci, and the other was observed intravasally in the sinusoids of the liver, most probably representing primitive Kupffer cells.

An Adaptively-Refined, Cartesian, Cell-Based Scheme for the Euler and Navier-Stokes Equations. Ph.D. Thesis - Michigan Univ.

NASA Technical Reports Server (NTRS)

Coirier, William John

1994-01-01

A Cartesian, cell-based scheme for solving the Euler and Navier-Stokes equations in two dimensions is developed and tested. Grids about geometrically complicated bodies are generated automatically, by recursive subdivision of a single Cartesian cell encompassing the entire flow domain. Where the resulting cells intersect bodies, polygonal 'cut' cells are created. The geometry of the cut cells is computed using polygon-clipping algorithms. The grid is stored in a binary-tree data structure which provides a natural means of obtaining cell-to-cell connectivity and of carrying out solution-adaptive refinement. The Euler and Navier-Stokes equations are solved on the resulting grids using a finite-volume formulation. The convective terms are upwinded, with a limited linear reconstruction of the primitive variables used to provide input states to an approximate Riemann solver for computing the fluxes between neighboring cells. A multi-stage time-stepping scheme is used to reach a steady-state solution. Validation of the Euler solver with benchmark numerical and exact solutions is presented. An assessment of the accuracy of the approach is made by uniform and adaptive grid refinements for a steady, transonic, exact solution to the Euler equations. The error of the approach is directly compared to a structured solver formulation. A non smooth flow is also assessed for grid convergence, comparing uniform and adaptively refined results. Several formulations of the viscous terms are assessed analytically, both for accuracy and positivity. The two best formulations are used to compute adaptively refined solutions of the Navier-Stokes equations. These solutions are compared to each other, to experimental results and/or theory for a series of low and moderate Reynolds numbers flow fields. The most suitable viscous discretization is demonstrated for geometrically-complicated internal flows. For flows at high Reynolds numbers, both an altered grid-generation procedure and a different formulation of the viscous terms are shown to be necessary. A hybrid Cartesian/body-fitted grid generation approach is demonstrated. In addition, a grid-generation procedure based on body-aligned cell cutting coupled with a viscous stensil-construction procedure based on quadratic programming is presented.

The minimal autopoietic unit.

PubMed

Luisi, Pier Luigi

2014-12-01

It is argued that closed, cell-like compartments, may have existed in prebiotic time, showing a simplified metabolism which was bringing about a primitive form of stationary state- a kind of homeostasis. The autopoietic primitive cell can be taken as an example and there are preliminary experimental data supporting the possible existence of this primitive form of cell activity. The genetic code permits, among other things, the continuous self-reproduction of proteins; enzymic proteins permit the synthesis of nucleic acids, and in this way there is a perfect recycling between the two most important classes of biopolymers in our life. On the other hand, the genetic code is a complex machinery, which cannot be posed at the very early time of the origin of life. And the question then arises, whether some form of alternative beginning, prior to the genetic code, would have been possible: and this is the core of the question asked. Is something with the flavor of early life conceivable, prior to the genetic code? My answer is positive, although I am too well aware that the term "conceivable" does not mean that this something is easily to be performed experimentally. To illustrate my answer, I would first go back to the operational description of cellular life as given by the theory of autopoiesis. Accordingly, a living cell is an open system capable of self-maintenance, due to a process of internal self-regeneration of the components, all within a boundary which is itself product from within. This is a universal code, valid not only for a cell, but for any living macroscopic entity, as no living system exists on Earth which does not obey this principle. In this definition (or better operational description) there is no mention of DNA or genetic code. I added in that definition the term "open system"-which is not present in the primary literature (Varela, et al., 1974) to make clear that every living system is indeed an open system-without this addition, it may seem that with autopoiesis we are dealing with a perpetuum mobile, against the second principle of thermodynamics. Now consider the following figure (Fig. 1). It represents in a very schematic form a cell, as an open system, with a semipermeable membrane constituted by the chemical S, which permits the entrance of the nutrient A and the elimination of the decay product P. A is transformed inside the cell into S by a chemical reaction characterized by kgen, and S can be transformed into P by the reaction kdec. The two reactions actually may represent two entire families of reaction, in the sense that one can envisage several A and several S and several P.

Bacillus cereus strain MCN as a debriding agent

NASA Technical Reports Server (NTRS)

Dalton, H. P.; Haynes, B. W.; Stone, L. L.

1978-01-01

Biologically active means are effective for rapidly removing scar tissue caused by burns or corrosive agents. Specially selected strain of bacteria applied to injury site releases enzymes which are active against eschar. These bacteria tend to locate between eschar and unburned tissue, thus providing optimal cell surface area arrangement for enzyme dispersal. Procedure may prove especially useful in treatment of disaster casualties under relatively primitive conditions.

Mysterious Mycorrhizae? A Field Trip & Classroom Experiment to Demystify the Symbioses Formed between Plants & Fungi

ERIC Educational Resources Information Center

Johnson, Nancy C.; Chaudhary, V. Bala; Hoeksema, Jason D.; Moore, John C.; Pringle, Anne; Umbanhowar, James A.; Wilson, Gail W. T.

2009-01-01

Biology curricula cover fungi in units on bacteria, protists, and primitive plants, but fungi are more closely related to animals than to bacteria or plants. Like animals, fungi are heterotrophs and cannot create their own food; but, like plants, fungi have cell walls, and are for the most part immobile. Most species of fungi have a filamentous…

Primary extraskeletal Ewing sarcoma involving the carotid artery: a case report and review of the current literature

PubMed Central

Nikkhah, D; Nix, P; Woodhead, C

2012-01-01

Extraskeletal Ewing sarcoma (EES) is a rare soft tissue neoplasm of primitive mesenchymal cells. There is a scarcity of data on EES involving the head and neck, with studies being over years or even decades. We are the first to report a case of EES involving the carotid artery and its subsequent surgical excision and reconstruction. PMID:22613280

Use of the Primitive Unit Cell in Understanding Subtle Features of the Cubic Closest-Packed Structure

ERIC Educational Resources Information Center

Hawkins, John A.; Rittenhouse, Jeffrey L.; Soper, Linda M.; Rittenhouse, Robert C.

2008-01-01

One of the most important crystal structures adopted by metals is characterized by the "abcabc"...stacking of close-packed layers. This structure is commonly referred to in textbooks as the cubic close-packed (ccp) or face-centered cubic (fcc) structure, since the entire lattice can be generated by replication of a face-centered cubic unit cell…

Self-recognition and Ca2+-dependent carbohydrate-carbohydrate cell adhesion provide clues to the cambrian explosion.

PubMed

Fernàndez-Busquets, Xavier; Körnig, André; Bucior, Iwona; Burger, Max M; Anselmetti, Dario

2009-11-01

The Cambrian explosion of life was a relatively short period approximately 540 Ma that marked a generalized acceleration in the evolution of most animal phyla, but the trigger of this key biological event remains elusive. Sponges are the oldest extant Precambrian metazoan phylum and thus a valid model to study factors that could have unleashed the rise of multicellular animals. One such factor is the advent of self-/non-self-recognition systems, which would be evolutionarily beneficial to organisms to prevent germ-cell parasitism or the introduction of deleterious mutations resulting from fusion with genetically different individuals. However, the molecules responsible for allorecognition probably evolved gradually before the Cambrian period, and some other (external) factor remains to be identified as the missing triggering event. Sponge cells associate through calcium-dependent, multivalent carbohydrate-carbohydrate interactions of the g200 glycan found on extracellular proteoglycans. Single molecule force spectroscopy analysis of g200-g200 binding indicates that calcium affects the lifetime (+Ca/-Ca: 680 s/3 s) and bond reaction length (+Ca/-Ca: 3.47 A/2.27 A). Calculation of mean g200 dissociation times in low and high calcium within the theoretical framework of a cooperative binding model indicates the nonlinear and divergent characteristics leading to either disaggregated cells or stable multicellular assemblies, respectively. This fundamental phenomenon can explain a switch from weak to strong adhesion between primitive metazoan cells caused by the well-documented rise in ocean calcium levels at the end of Precambrian time. We propose that stronger cell adhesion allowed the integrity of genetically uniform animals composed only of "self" cells, facilitating genetic constitutions to remain within the metazoan individual and be passed down inheritance lines. The Cambrian explosion might have been triggered by the coincidence in time of primitive animals endowed with self-/non-self-recognition and of a surge in seawater calcium that increased the binding forces between their calcium-dependent cell adhesion molecules.

Proliferative status of primitive hematopoietic progenitors from patients with acute myelogenous leukemia (AML).

PubMed

Guan, Y; Hogge, D E

2000-12-01

One possible explanation for the competitive advantage that malignant cells in patients with acute myelogenous leukemia (AML) appear to have over normal hematopoietic elements is that leukemic progenitors proliferate more rapidly than their normal progenitor cell counterparts. To test this hypothesis, an overnight 3H-thymidine (3H-Tdr) suicide assay was used to analyze the proliferative status of malignant progenitors detected in both colony-forming cell (CFC) and long-term culture initiating cell (LTC-IC) assays from the peripheral blood of nine patients with newly diagnosed AML. Culture of AML cells in serum-free medium with 100 ng/ml Steel factor (SF), 20 ng/ml interleukin 3 (IL-3) and 20 ng/ml granulocyte colony-stimulating factor (G-CSF) for 16-24 h maintained the number of AML-CFC and LTC-IC at near input values (mean % input +/- s.d. for CFC and LTC-IC were 78 +/- 33 and 126 +/- 53, respectively). The addition of 20 muCi/ml high specific activity 3H-Tdr to these cultures reduced the numbers of both progenitor cell types from most of the patient samples substantially: mean % kill +/- s.d. for AML-CFC and LTC-IC were 64 +/- 27 and 82 +/- 16, respectively, indicating that a large proportion of both progenitor populations were actively cycling. FISH analysis of colonies from CFC and LTC-IC assays confirmed that most cytogenetically abnormal CFC and LTC-IC were actively cycling (mean % kill +/- s.d.: 68 +/- 26 and 85 +/- 13, respectively). Interestingly, in six patient samples where a significant number of cytogenetically normal LTC-ICs were detected, the % kill of these cells (74 +/- 20) was similar to that of the abnormal progenitors. These data contrast with the predominantly quiescent cell cycle status of CFC and LTC-IC previously observed in steady-state peripheral blood from normal individuals but also provide evidence that a significant proportion of primitive malignant progenitors from AML patients are quiescent and therefore may be resistant to standard chemotherapeutic regimens.

Stem cells--clinical application and perspectives.

PubMed

Brehm, Michael; Zeus, Tobias; Strauer, Bodo Eckehard

2002-11-01

Augmentation of myocardial performance in experimental models of therapeutic infarction and heart failure has been achieved by transplantation of exogenous cells into damaged myocardium. The quest for suitable donor cells has prompted research into the use of both embryonic stem cells and adult somatic stem cells. Recently, there has been a growing body of evidence that multipotent somatic stem cells in adult bone marrow exhibit tremendous functional plasticity and can reprogram in a new environmental tissue niche to give rise to cell lineages specific for new organ site. This phenomenon has made huge impact on myocardial biology, while multipotent adult bone marrow hematopoeitic stem cells and mesechymal stem cells can repopulate infarcted rodent myocardium and differentiate into both cardiomyocytes and new blood vessels. These data, coupled with the identification of a putative primitive cardiac stem cell population in the adult human heart, may open the way for novel therapeutic modalities for enhancing myocardial performance and treating heart failure.

Differentiation stage-specific regulation of primitive human hematopoietic progenitor cycling by exogenous and endogenous inhibitors in an in vivo model.

PubMed

Cashman, J D; Clark-Lewis, I; Eaves, A C; Eaves, C J

1999-12-01

Nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice transplanted with human cord blood or adult marrow cells and injected 6 weeks posttransplant with 2 daily doses of transforming growth factor-beta(1) (TGF-beta(1)), monocyte chemoattractant protein-1 (MCP-1), or a nonaggregating form of macrophage inflammatory protein-1alpha (MIP-1alpha) showed unique patterns of inhibition of human progenitor proliferation 1 day later. TGF-beta(1) was active on long-term culture initiating cells (LTC-IC) and on primitive erythroid and granulopoietic colony-forming cells (HPP-CFC), but had no effect on mature CFC. MCP-1 inhibited the cycling of both types of HPP-CFC but not LTC-IC. MIP-1alpha did not inhibit either LTC-IC or granulopoietic HPP-CFC but was active on erythroid HPP-CFC and mature granulopoietic CFC. All of these responses were independent of the source of human cells transplanted. LTC-IC of either human cord blood or adult marrow origin continue to proliferate in NOD/SCID mice for many weeks, although the turnover of all types of human CFC in mice transplanted with adult human marrow (but not cord blood) is downregulated after 6 weeks. Interestingly, administration of either MIP-1beta, an antagonist of both MIP-1alpha and MCP-1 or MCP-1(9-76), an antagonist of MCP-1 (and MCP-2 and MCP-3), into mice in which human marrow-derived CFC had become quiescent, caused the rapid reactivation of these progenitors in vivo. These results provide the first definition of stage-specific inhibitors of human hematopoietic progenitor cell cycling in vivo. In addition they show that endogenous chemokines can contribute to late graft failure, which can be reversed by the administration of specific antagonists.

LIF supports primitive endoderm expansion during pre-implantation development.

PubMed

Morgani, Sophie M; Brickman, Joshua M

2015-10-15

Embryonic stem cells (ESCs) are pluripotent cell lines that can be maintained indefinitely in an early developmental state. ESC culture conditions almost always require the cytokine LIF to maintain self-renewal. As ESCs are not homogeneous but contain multiple populations reminiscent of the blastocyst, identifying the target cells of LIF is necessary to understand the propagation of pluripotency. We recently found that LIF acts under self-renewing conditions to stimulate the fraction of ESCs that express extraembryonic markers, but has little impact on pluripotent gene expression. Here, we report that LIF has two distinct roles: it blocks early epiblast (Epi) differentiation, and it supports the expansion of primitive endoderm (PrE)-primed ESCs and PrE in vivo. We find that activation of JAK/STAT signalling downstream of LIF occurs initially throughout the pre-implantation embryo, but later marks the PrE. Moreover, the addition of LIF to cultured embryos increases the GATA6(+) PrE population, whereas inhibition of JAK/STAT signalling reduces both NANOG(+) epiblast and GATA6(+) PrE. The reduction of the NANOG(+) Epi might be explained by its precocious differentiation to later Epi derivatives, whereas the increase in PrE is mediated both by an increase in proliferation and inhibition of PrE apoptosis that is normally triggered in embryos with an excess of GATA6(+) cells. Thus, it appears that the relative size of the PrE is determined by the number of LIF-producing cells in the embryo. This suggests a mechanism by which the embryo adjusts the relative ratio of the primary lineages in response to experimental manipulation. © 2015. Published by The Company of Biologists Ltd.

Systematic tracking of altered haematopoiesis during sporozoite-mediated malaria development reveals multiple response points.

PubMed

Vainieri, Maria L; Blagborough, Andrew M; MacLean, Adam L; Haltalli, Myriam L R; Ruivo, Nicola; Fletcher, Helen A; Stumpf, Michael P H; Sinden, Robert E; Celso, Cristina Lo

2016-06-01

Haematopoiesis is the complex developmental process that maintains the turnover of all blood cell lineages. It critically depends on the correct functioning of rare, quiescent haematopoietic stem cells (HSCs) and more numerous, HSC-derived, highly proliferative and differentiating haematopoietic progenitor cells (HPCs). Infection is known to affect HSCs, with severe and chronic inflammatory stimuli leading to stem cell pool depletion, while acute, non-lethal infections exert transient and even potentiating effects. Both whether this paradigm applies to all infections and whether the HSC response is the dominant driver of the changes observed during stressed haematopoiesis remain open questions. We use a mouse model of malaria, based on natural, sporozoite-driven Plasmodium berghei infection, as an experimental platform to gain a global view of haematopoietic perturbations during infection progression. We observe coordinated responses by the most primitive HSCs and multiple HPCs, some starting before blood parasitaemia is detected. We show that, despite highly variable inter-host responses, primitive HSCs become highly proliferative, but mathematical modelling suggests that this alone is not sufficient to significantly impact the whole haematopoietic cascade. We observe that the dramatic expansion of Sca-1(+) progenitors results from combined proliferation of direct HSC progeny and phenotypic changes in downstream populations. We observe that the simultaneous perturbation of HSC/HPC population dynamics is coupled with early signs of anaemia onset. Our data uncover a complex relationship between Plasmodium and its host's haematopoiesis and raise the question whether the variable responses observed may affect the outcome of the infection itself and its long-term consequences on the host. © 2016 The Authors.

Systematic tracking of altered haematopoiesis during sporozoite-mediated malaria development reveals multiple response points

PubMed Central

Vainieri, Maria L.; Blagborough, Andrew M.; MacLean, Adam L.; Haltalli, Myriam L. R.; Ruivo, Nicola; Fletcher, Helen A.; Stumpf, Michael P. H.; Sinden, Robert E.; Lo Celso, Cristina

2016-01-01

Haematopoiesis is the complex developmental process that maintains the turnover of all blood cell lineages. It critically depends on the correct functioning of rare, quiescent haematopoietic stem cells (HSCs) and more numerous, HSC-derived, highly proliferative and differentiating haematopoietic progenitor cells (HPCs). Infection is known to affect HSCs, with severe and chronic inflammatory stimuli leading to stem cell pool depletion, while acute, non-lethal infections exert transient and even potentiating effects. Both whether this paradigm applies to all infections and whether the HSC response is the dominant driver of the changes observed during stressed haematopoiesis remain open questions. We use a mouse model of malaria, based on natural, sporozoite-driven Plasmodium berghei infection, as an experimental platform to gain a global view of haematopoietic perturbations during infection progression. We observe coordinated responses by the most primitive HSCs and multiple HPCs, some starting before blood parasitaemia is detected. We show that, despite highly variable inter-host responses, primitive HSCs become highly proliferative, but mathematical modelling suggests that this alone is not sufficient to significantly impact the whole haematopoietic cascade. We observe that the dramatic expansion of Sca-1+ progenitors results from combined proliferation of direct HSC progeny and phenotypic changes in downstream populations. We observe that the simultaneous perturbation of HSC/HPC population dynamics is coupled with early signs of anaemia onset. Our data uncover a complex relationship between Plasmodium and its host's haematopoiesis and raise the question whether the variable responses observed may affect the outcome of the infection itself and its long-term consequences on the host. PMID:27335321

A practical approach to the clinical diagnosis of Ewing's sarcoma/primitive neuroectodermal tumour and other small round cell tumours sharing EWS rearrangement using new fluorescence in situ hybridisation probes for EWSR1 on formalin fixed, paraffin wax embedded tissue.

PubMed

Yamaguchi, U; Hasegawa, T; Morimoto, Y; Tateishi, U; Endo, M; Nakatani, F; Kawai, A; Chuman, H; Beppu, Y; Endo, M; Kurotaki, H; Furuta, K

2005-10-01

Over 90% of Ewing's sarcoma/primitive neuroectodermal tumour (ES/PNET) cases have the t(11;22) chromosomal rearrangement, which is also found in other small round cell tumours, including desmoplastic small round cell tumour (DSRCT) and clear cell sarcoma (CCS). Although this rearrangement can be analysed by fluorescence in situ hybridisation (FISH) using routinely formalin fixed, paraffin wax embedded (FFPE) tissues when fresh or frozen tissues are not available, a sensitive and convenient detection method is needed for routine clinical diagnosis. To investigate the usefulness of newly developed probes for detecting EWS rearrangement resulting from chromosomal translocations using FISH and FFPE tissue in the clinical diagnosis of ES/PNET, DSRCT, and CCS. Sixteen ES/PNETs, six DSRCTs, and six CCSs were studied. Three poorly differentiated synovial sarcomas, three alveolar rhabdomyosarcomas, and three neuroblastomas served as negative controls. Interphase FISH analysis was performed on FFPE tissue sections with a commercially available EWSR1 (22q12) dual colour, breakapart rearrangement probe. One fused signal and one split signal of orange and green, demonstrating rearrangement of the EWS gene, was detected in 14 of 16 ES/PNETs, all six DRSCTs, and five of six CCSs, but not in the negative controls. Interphase FISH using this newly developed probe is sensitive and specific for detecting the EWS gene on FFPE tissues and is of value in the routine clinical diagnosis of ES/PNET, DSRCT, and CCS.

PECHCV, PECHFV, PEFHCV and PEFHFV: A set of atmospheric, primitive equation forecast models for the Northern Hemisphere, volume 3

NASA Technical Reports Server (NTRS)

Wellck, R. E.; Pearce, M. L.

1976-01-01

As part of the SEASAT program of NASA, a set of four hemispheric, atmospheric prediction models were developed. The models, which use a polar stereographic grid in the horizontal and a sigma coordinate in the vertical, are: (1) PECHCV - five sigma layers and a 63 x 63 horizontal grid, (2) PECHFV - ten sigma layers and a 63 x 63 horizontal grid, (3) PEFHCV - five sigma layers and a 187 x 187 horizontal grid, and (4) PEFHFV - ten sigma layers and a 187 x 187 horizontal grid. The models and associated computer programs are described.

Chemical evolution and the origin of life; Proceedings of the Third International Conference, Pont-a-Mousson, France, April 19-25, 1970. Volume 1 - Molecular evolution.

NASA Technical Reports Server (NTRS)

Buvet, R. (Editor); Ponnamperuma, C.

1971-01-01

The present state of investigations on the origin of life is surveyed together with the current state of molecular paleontology. General and theoretical subjects discussed include an energetic approach to prebiological chemistry, the recognition of description and function in chemical reaction networks, and the origin and development of optical activity of bio-organic compounds on the primordial earth. Other fields considered are the syntheses of small molecules, oligomers and polymers; photochemical processes; the origin of biological structures; primitive biochemistry and biology; and exobiology. Individual items are abstracted in this issue.

Generalized compliant motion primitive

NASA Technical Reports Server (NTRS)

Backes, Paul G. (Inventor)

1994-01-01

This invention relates to a general primitive for controlling a telerobot with a set of input parameters. The primitive includes a trajectory generator; a teleoperation sensor; a joint limit generator; a force setpoint generator; a dither function generator, which produces telerobot motion inputs in a common coordinate frame for simultaneous combination in sensor summers. Virtual return spring motion input is provided by a restoration spring subsystem. The novel features of this invention include use of a single general motion primitive at a remote site to permit the shared and supervisory control of the robot manipulator to perform tasks via a remotely transferred input parameter set.

Primitive neuroectodermal tumors of the central nervous system.

PubMed

Becker, L E; Hinton, D

1983-06-01

Primitive neuroectodermal tumors are morphologically similar malignant tumors arising in intracranial and peripheral sites of the nervous system, showing varying degrees of cellular differentiation with a tendency to disseminate along cerebrospinal fluid pathways. They occur primarily in children and young adults. Under the designation primitive neuroectodermal tumors are included medulloblastomas and tumors that may differentiate in other directions, such as medulloepithelioma, neuroblastoma, polar spongioblastoma, pineoblastoma, ependymoblastoma, retinoblastoma, and olfactory neuroblastoma. From a practical, histologic point of view, these tumors are often indistinguishable from one another and are best thought of as primitive neuroectodermal tumors with or without differentiating features.

Prominin‐1/CD133: Lipid Raft Association, Detergent Resistance, and Immunodetection

PubMed Central

Karbanová, Jana; Lorico, Aurelio; Bornhäuser, Martin; Fargeas, Christine A.

2017-01-01

Summary The cell surface antigen prominin‐1 (alias CD133) has gained enormous interest in the past 2 decades and given rise to debates as to its utility as a biological stem and cancer stem cell marker. Important and yet often overlooked knowledge that is pertinent to its physiological function has been generated in other systems given its more general expression beyond primitive cells. This article briefly discusses the importance of particular biochemical features of CD133 with relation to its association with membrane microdomains (lipid rafts) and proper immunodetection. It also draws attention toward the adequate use of detergents and caveats that may apply to the interpretation of the results generated. Stem Cells Translational Medicine 2018;7:155–160 PMID:29271118

Histogenesis of the epithelial component of rat thymus: an ultrastructural and immunohistological analysis.

PubMed

Vicente, A; Varas, A; Sacedón, R; Zapata, A G

1996-04-01

Despite the assumed importance of thymic cell microenvironments for governing T-cell maturation, little is known about the ontogeny of their cell components. A few studies have analyzed previously the ontogenetical development of rat thymic epithelium (Bogojevic et al. 1990. Period. Biol., 92:126; Kampinga and Aspinall 1990 Harwood Acad. Pub., London, pp. 149-186; Micic et al., 1991 Dev. Comp. Immunol., 15:443-450) and recently we have reported the development of both interdigitating/dendritic cells and macrophages (Vicente et al., 1994 Immunology, 82:75-81, 1995 Immunology, 85:99-105). In the present work we analyze in situ ultrastructural, immunohistochemical, and histoenzymatically the appearance and development of the thymic epithelial cell component in both embryonic and neonatal Wistar rats with special emphasis on the origin of the different epithelial cell types, the occurrence or absence of a common precursor for these, and the expression of MHC molecules. The thymic primordium of 13-day-old embryos is formed by a homogeneous population of primitive epithelial cells differentiating gradually into various epithelial cell subtypes of both the cortex and the medulla. In the cortex, subcapsular and stroma-supporting epithelial cells appear at days 14-15 as two structurally different cell entities. At the same time, stroma-supporting, keratinized, and vacuolated epithelial cells occur in the thymic medulla. These last two cell types differentiate subsequently into Hassall's bodies and hypertrophied cells. Lympho-epithelial cell complexes are identified in the deep cortex around birth, when the cortical parenchyma houses a transitional erythropoiesis. mAbs (His-39, RMC-20) which recognize medullary epithelial cells in the adult thymus stain positively cells of the thymic primordium as early as day 16 of embryonic life. Cortical epithelial cell markers (His-37, RMC-17) appear, however, slightly later and the subcapsulary region is not established until postnatal life. MHC class I and class II molecules can be identified on epithelial cells in the thymus of 15-day-old embryonic rats although they reach the highest expression around birth. Our results confirm the heterogeneity of the thymic epithelial component, the persistence of primitive, non-differentiated epithelial cells morphologically similar to those occurring in the early thymic primordium in adult thymus, and the mutual relevance of epithelial cells and thymocytes for an adequate development of rat thymus gland.

Cancer stem cells and cell size: A causal link?

PubMed

Li, Qiuhui; Rycaj, Kiera; Chen, Xin; Tang, Dean G

2015-12-01

The majority of normal animal cells are 10-20 μm in diameter. Many signaling mechanisms, notably PI3K/Akt/mTOR, Myc, and Hippo pathways, tightly control and coordinate cell growth, cell size, cell division, and cell number during homeostasis. These regulatory mechanisms are frequently deregulated during tumorigenesis resulting in wide variations in cell sizes and increased proliferation in cancer cells. Here, we first review the evidence that primitive stem cells in adult tissues are quiescent and generally smaller than their differentiated progeny, suggesting a correlation between small cell sizes with the stemness. Conversely, increased cell size positively correlates with differentiation phenotypes. We then discuss cancer stem cells (CSCs) and present some evidence that correlates cell sizes with CSC activity. Overall, a causal link between CSCs and cell size is relatively weak and remains to be rigorously assessed. In the future, optimizing methods for isolating cells based on size should help elucidate the connection between cancer cell size and CSC characteristics. Copyright © 2015 Elsevier Ltd. All rights reserved.

Density of Primitive Pythagorean Triples

ERIC Educational Resources Information Center

Killen, Duncan A.

2004-01-01

Based on the properties of a Primitive Pythagorean Triple (PPT), a computer program was written to generate, print, and count all PPTs greater than or equal to I[subscript x], where I[subscript x] is an arbitrarily chosen integer. The Density of Primitive Pythagorean Triples may be defined as the ratio of the number of PPTs whose hypotenuse is…

A Discussion on the Substitution Method for Trigonometric Rational Functions

ERIC Educational Resources Information Center

Ponce-Campuzano, Juan Carlos; Rivera-Figueroa, Antonio

2011-01-01

It is common to see, in the books on calculus, primitives of functions (some authors use the word "antiderivative" instead of primitive). However, the majority of authors pay scant attention to the domains over which the primitives are valid, which could lead to errors in the evaluation of definite integrals. In the teaching of calculus, in…

Scientific Terminology and Minimum Terms in Speech Communication: Some Philosophical Ramblings.

ERIC Educational Resources Information Center

Krivonos, Paul D.; Sussman, Lyle.

Philosophers of science have emphasized the need for primitive terms, or "givens," in the construction of theory for any discipline. While there are inherent dangers regarding the use of primitive terms, they can have great value in serving as the basis for minimum terms, which are primitive terms unique to a discipline. (Borrowed terms are those…

A manual for PARTI runtime primitives

NASA Technical Reports Server (NTRS)

Berryman, Harry; Saltz, Joel

1990-01-01

Primitives are presented that are designed to help users efficiently program irregular problems (e.g., unstructured mesh sweeps, sparse matrix codes, adaptive mesh partial differential equations solvers) on distributed memory machines. These primitives are also designed for use in compilers for distributed memory multiprocessors. Communications patterns are captured at runtime, and the appropriate send and receive messages are automatically generated.

Low oxygen atmosphere facilitates proliferation and maintains undifferentiated state of umbilical cord mesenchymal stem cells in an hypoxia inducible factor-dependent manner.

PubMed

Drela, Katarzyna; Sarnowska, Anna; Siedlecka, Patrycja; Szablowska-Gadomska, Ilona; Wielgos, Miroslaw; Jurga, Marcin; Lukomska, Barbara; Domanska-Janik, Krystyna

2014-07-01

As we approach the era of mesenchymal stem cell (MSC) application in the medical clinic, the standarization of their culture conditions are of the particular importance. We re-evaluated the influences of oxygens concentration on proliferation, stemness and differentiation of human umbilical cord Wharton Jelly-derived MSCs (WJ-MSCs). Primary cultures growing in 21% oxygen were either transferred into 5% O2 or continued to grow under standard 21% oxygen conditions. Cell expansion was estimated by WST1/enzyme-linked immunosorbent assay or cell counting. After 2 or 4 weeks of culture, cell phenotypes were evaluated using microscopic, immunocytochemical, fluorescence-activated cell-sorting and molecular methods. Genes and proteins typical of mesenchymal cells, committed neural cells or more primitive stem/progenitors (Oct4A, Nanog, Rex1, Sox2) and hypoxia inducible factor (HIF)-1α-3α were evaluated. Lowering O2 concentration from 21% to the physiologically relevant 5% level substantially affected cell characteristics, with induction of stemness-related-transcription-factor and stimulation of cell proliferative capacity, with increased colony-forming unit fibroblasts (CFU-F) centers exerting OCT4A, NANOG and HIF-1α and HIF-2α immunoreactivity. Moreover, the spontaneous and time-dependent ability of WJ-MSCs to differentiate into neural lineage under 21% O2 culture was blocked in the reduced oxygen condition. Importantly, treatment with trichostatin A (TSA, a histone deacetylase inhibitor) suppressed HIF-1α and HIF-2α expression, in addition to blockading the cellular effects of reduced oxygen concentration. A physiologically relevant microenvironment of 5% O2 rejuvenates WJ-MSC culture toward less-differentiated, more primitive and faster-growing phenotypes with involvement of HIF-1α and HIF-2α-mediated and TSA-sensitive chromatin modification mechanisms. These observations add to the understanding of MSC responses to defined culture conditions, which is the most critical issue for adult stem cells translational applications. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Emergence of Functional Hierarchy in a Multiple Timescale Neural Network Model: A Humanoid Robot Experiment

PubMed Central

Yamashita, Yuichi; Tani, Jun

2008-01-01

It is generally thought that skilled behavior in human beings results from a functional hierarchy of the motor control system, within which reusable motor primitives are flexibly integrated into various sensori-motor sequence patterns. The underlying neural mechanisms governing the way in which continuous sensori-motor flows are segmented into primitives and the way in which series of primitives are integrated into various behavior sequences have, however, not yet been clarified. In earlier studies, this functional hierarchy has been realized through the use of explicit hierarchical structure, with local modules representing motor primitives in the lower level and a higher module representing sequences of primitives switched via additional mechanisms such as gate-selecting. When sequences contain similarities and overlap, however, a conflict arises in such earlier models between generalization and segmentation, induced by this separated modular structure. To address this issue, we propose a different type of neural network model. The current model neither makes use of separate local modules to represent primitives nor introduces explicit hierarchical structure. Rather than forcing architectural hierarchy onto the system, functional hierarchy emerges through a form of self-organization that is based on two distinct types of neurons, each with different time properties (“multiple timescales”). Through the introduction of multiple timescales, continuous sequences of behavior are segmented into reusable primitives, and the primitives, in turn, are flexibly integrated into novel sequences. In experiments, the proposed network model, coordinating the physical body of a humanoid robot through high-dimensional sensori-motor control, also successfully situated itself within a physical environment. Our results suggest that it is not only the spatial connections between neurons but also the timescales of neural activity that act as important mechanisms leading to functional hierarchy in neural systems. PMID:18989398

Comet Dust: The Diversity of "Primitive" Particles and Implications

NASA Technical Reports Server (NTRS)

Wooden, Diane H.; Ishii, Hope A.; Bradley, John P.; Zolensky, Michael E.

2016-01-01

Comet dust is primitive and shows significant diversity. Our knowledge of the properties of primitive particles has expanded significantly through microscale investigations of cosmic dust samples ( IDP's(Interplanetary Dust Particles) and AMM's (Antarctic Micrometeorites)) and of comet dust samples (Stardust and Rosetta's COSIMA), as well as through remote sensing (spectroscopy and imaging) via Spitzer and via spacecraft encounters with 103P/Hartley 2 and 67P/Churyumov-Gerasimenko. Microscale investigations show that comet dust and cosmic dust are particles of unequilibrated materials, including aggregates of materials unequilibrated at submicron scales. We call unequilibrated materials "primitive" and we deduce they were incorporated into ice-rich (H2O-, CO2-, and CO-ice) parent bodies that remained cold, i.e., into comets, because of the lack of aqueous or thermal alteration since particle aggregation; yet some Stardust olivines suggest mild thermal metamorphism. Primitive particles exhibit a diverse range of: structure and typology; size and size distribution of constituents; concentration and form of carbonaceous and organic matter; D-, N-, and O- isotopic enhancements over solar; Mg-, Fe-contents of the silicate minerals; the compositions and concentrations of sulfides, and of less abundant mineral species such as chondrules, CAIs and carbonates. The uniformity within a group of samples points to: aerodynamic sorting of particles and/or particle constituents; the inclusion of a limited range of oxygen fugacities; the inclusion or exclusion of chondrules; a selection of organics. The properties of primitive particles imply there were disk processes that resulted in different comets having particular selections of primitive materials. The diversity of primitive particles has implications for the diversity of materials in the protoplanetary disk present at the time and in the region where the comets formed.

Comet Dust: The Diversity of Primitive Particles and Implications

NASA Technical Reports Server (NTRS)

John Bradley; Zolensky, Michael E.

2016-01-01

Comet dust is primitive and shows significant diversity. Our knowledge of the properties of primitive particles has expanded significantly through microscale investigations of cosmic dust samples (IDPs and AMMs) and of comet dust samples (Stardust and Rosetta's COSIMA), as well as through remote sensing (spectroscopy and imaging) via Spitzer and via spacecraft encounters with 103P/Hartley 2 and 67P/Churyumov-Gerasimenko. Microscale investigations show that comet dust and cosmic dust are particles of unequilibrated materials, including aggregates of materials unequilibrated at submicron scales. We call unequilibrated materials "primitive" and we deduce they were incorporated into ice-­-rich (H2O-, CO2-, and CO-ice) parent bodies that remained cold, i.e., into comets, because of the lack of aqueous or thermal alteration since particle aggregation; yet some Stardust olivines suggest mild thermal metamorphism. Primitive particles exhibit a diverse range of: structure and typology; size and size distribution of constituents; concentration and form of carbonaceous and organic matter; D-, N-, and O- isotopic enhancements over solar; Mg-, Fe-contentsof thesilicate minerals; the compositions and concentrations of sulfides, and of less abundant mineral species such as chondrules, CAIs and carbonates. The unifomity within a group of samples points to: aerodynamic sorting of particles and/or particle constituents; the inclusion of a limited range of oxygen fugacities; the inclusion or exclusion of chondrules; a selection of organics. The properites of primitive particles imply there were disk processes that resulted in different comets having particular selections of primitive materials. The diversity of primitive particles has implications for the diversity of materials in the protoplanetary disk present at the time and in the region where the comets formed.

Spermatogenesis in mammals: proteomic insights.

PubMed

Chocu, Sophie; Calvel, Pierre; Rolland, Antoine D; Pineau, Charles

2012-08-01

Spermatogenesis is a highly sophisticated process involved in the transmission of genetic heritage. It includes halving ploidy, repackaging of the chromatin for transport, and the equipment of developing spermatids and eventually spermatozoa with the advanced apparatus (e.g., tightly packed mitochondrial sheat in the mid piece, elongating of the tail, reduction of cytoplasmic volume) to elicit motility once they reach the epididymis. Mammalian spermatogenesis is divided into three phases. In the first the primitive germ cells or spermatogonia undergo a series of mitotic divisions. In the second the spermatocytes undergo two consecutive divisions in meiosis to produce haploid spermatids. In the third the spermatids differentiate into spermatozoa in a process called spermiogenesis. Paracrine, autocrine, juxtacrine, and endocrine pathways all contribute to the regulation of the process. The array of structural elements and chemical factors modulating somatic and germ cell activity is such that the network linking the various cellular activities during spermatogenesis is unimaginably complex. Over the past two decades, advances in genomics have greatly improved our knowledge of spermatogenesis, by identifying numerous genes essential for the development of functional male gametes. Large-scale analyses of testicular function have deepened our insight into normal and pathological spermatogenesis. Progress in genome sequencing and microarray technology have been exploited for genome-wide expression studies, leading to the identification of hundreds of genes differentially expressed within the testis. However, although proteomics has now come of age, the proteomics-based investigation of spermatogenesis remains in its infancy. Here, we review the state-of-the-art of large-scale proteomic analyses of spermatogenesis, from germ cell development during sex determination to spermatogenesis in the adult. Indeed, a few laboratories have undertaken differential protein profiling expression studies and/or systematic analyses of testicular proteomes in entire organs or isolated cells from various species. We consider the pros and cons of proteomics for studying the testicular germ cell gene expression program. Finally, we address the use of protein datasets, through integrative genomics (i.e., combining genomics, transcriptomics, and proteomics), bioinformatics, and modelling.

[Influence of mineral matter on sulfur conversion in coal during combustion].

PubMed

Wei, Li-hong; Jiang, Xiu-min; Li, Ai-min

2006-09-01

Three species micro-pulverized coals(Hegang, Tiefa, Zhungeer coal) were studied, the mineral matters (MgO, CaO, Al2O3 and Fe3O4) were respectively added to the coals. The combustion of samples were studied to investigate the effect of mineral matter on transformation of sulfur during combustion by the combined of DTG and GC-MS, the flowmeter 50 mL/min, heating rate 20 degrees C/ min, oxygen volume percentage 20% . The SO2 release curve of primitive micro-pulverized coal appear three peaks during the combustion, but the demineralized sample appear two peaks. The species of coal has effect on temperature of the maximum release rate of SOz, the release rate of SO2 of Hegang coal is even in three temperature ranges, Tiefa coal appear maximum value about 500 degrees C and Zhungeer coal about 200 degrees C which probably due to the different amount of all kinds of sulfur in primitive coal sample. The mineral matter (MgO, CaO, Al2O3 and Fe3O4) have sulfur retention and catalyzing effect on SO2 the combustion of coal. The amount and species of mineral matter and species of coal determine the sulfur retention effect.

The Architectural Organization of Human Stem Cell Cycle Regulatory Machinery

PubMed Central

Stein, Gary S.; Stein, Janet L.; Wijnen, Andre van J; Lian, Jane B.; Montecino, Martin; Medina, Ricardo; Kapinas, Kristie; Ghule, Prachi; Grandy, Rodrigo; Zaidi, Sayyed K.; Becker, Klaus A.

2013-01-01

Two striking features of human embryonic stem cells that support biological activity are an abbreviated cell cycle and reduced complexity to nuclear organization. The potential implications for rapid proliferation of human embryonic stem cells within the context of sustaining pluripotency, suppressing phenotypic gene expression and linkage to simplicity in the architectural compartmentalization of regulatory machinery in nuclear microenvironments is explored. Characterization of the molecular and architectural commitment steps that license human embryonic stem cells to initiate histone gene expression is providing understanding of the principal regulatory mechanisms that control the G1/S phase transition in primitive pluripotent cells. From both fundamental regulatory and clinical perspectives, further understanding of the pluripotent cell cycle in relation to compartmentalization of regulatory machinery in nuclear microenvironments is relevant to applications of stem cells for regenerative medicine and new dimensions to therapy where traditional drug discovery strategies have been minimally effective. PMID:22394165

Anti-Cancer Phytometabolites Targeting Cancer Stem Cells

PubMed Central

Torquato, Heron F.V.; Goettert, Márcia I.; Justo, Giselle Z.; Paredes-Gamero, Edgar J.

2017-01-01

Medicinal plants are a plentiful source of bioactive molecules with much structural diversity. In cancer treatment, molecules obtained from plants represent an attractive alternative to other treatments because several plant-derived compounds have exhibited lower toxicity and higher selectivity against cancer cells. In this review, we focus on the possible application of bioactive molecules obtained from plants against more primitive cell populations in cancers, cancer stem cells. Cancer stem cells are present in several kinds of tumors and are responsible for recurrences and metastases. Common anti-cancer drugs exhibit lower effectiveness against cancer stem cells because of their biological features. However, recently discovered natural phytometabolites exert cytotoxic effects on this rare population of cells in cancers. Therefore, this review presents the latest research on promising compounds from plants that can act as antitumor drugs and that mainly affect stem cell populations in cancers. PMID:28367074

Yoga Therapy in Treating Patients With Malignant Brain Tumors

ClinicalTrials.gov

2017-07-27

Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Recurrent Adult Brain Tumor

Testing a Hypothesis for the Evolution of Sex

NASA Astrophysics Data System (ADS)

Örçal, Bora; Tüzel, Erkan; Sevim, Volkan; Jan, Naeem; Erzan, Ayşe.

An asexual set of primitive bacteria is simulated with a bit-string Penna model with a Fermi function for survival. A recent hypothesis by Jan, Stauffer, and Moseley on the evolution of sex from asexual cells as a strategy for trying to escape the effects of deleterious mutations is checked. This strategy is found to provide a successful scenario for the evolution of a stable macroscopic sexual population.

Circuit design tool. User's manual, revision 2

NASA Technical Reports Server (NTRS)

Miyake, Keith M.; Smith, Donald E.

1992-01-01

The CAM chip design was produced in a UNIX software environment using a design tool that supports definition of digital electronic modules, composition of these modules into higher level circuits, and event-driven simulation of these circuits. Our design tool provides an interface whose goals include straightforward but flexible primitive module definition and circuit composition, efficient simulation, and a debugging environment that facilitates design verification and alteration. The tool provides a set of primitive modules which can be composed into higher level circuits. Each module is a C-language subroutine that uses a set of interface protocols understood by the design tool. Primitives can be altered simply by recoding their C-code image; in addition new primitives can be added allowing higher level circuits to be described in C-code rather than as a composition of primitive modules--this feature can greatly enhance the speed of simulation.

Retention of primitive reflexes and delayed motor development in very low birth weight infants.

PubMed

Marquis, P J; Ruiz, N A; Lundy, M S; Dillard, R G

1984-06-01

Primitive reflexes and motor development were evaluated in 127 very low birth weight (VLBW) infants (birth weight less than 1501 grams) at four months corrected age. The asymmetrical tonic neck reflex, tonic labyrinth reflex, and Moro reflex were assessed for each child. The ability of each child to reach (obtain a red ring) and roll were observed. The child's performance on the gross motor scale of the Denver Development Screening Test was recorded. Thirty-seven term infants were administered identical evaluations at four months of age. The VLBW infants retained stronger primitive reflexes and exhibited a significantly higher incidence of motor delays than term infants. Significant correlations existed between the strength of the primitive reflexes and early motor development for VLBW infants. This study confirms a high incidence of motor delays among VLBW infants and demonstrates a clear association between retained primitive reflexes and delayed motor development in VLBW infants.

RIPE integrity primitives, part 2 (RACE Integrity Primitives Evaluation)

NASA Astrophysics Data System (ADS)

Denboer, B.; Boly, J. P.; Bosselaers, A.; Brandt, J.; Chaum, D.; Damgaard, I.; Dichtl, M.; Fumy, W.; Vanderham, M.; Jansen, C. J. A.

1993-04-01

A manual intended for those seeking to secure information systems by applying modern cryptography is presented. It represents the successful attainment of goals by RIPE (RACE (Research and development of Advanced Communications technology in Europe) Integrity Primitives Evaluation). The recommended portfolio of integrity primitives, which is the main product of the project, forms the heart of the manual. By integrity, is meant the kinds of security that can be achieved through cryptography, apart from keeping messages secret. Thus included are ways to ensure that stored or communicated data is not illicitly modified, that parties exchanging messages are actually present, and that 'signed' electronic messages can be recognized as authentic by anyone. Of particular concern to the project were the high speed requirements of broadband communication. The project also aimed for completeness in its recommendations. As a result, the portfolio contains primitives, that is building blocks, that can meet most of today's perceived needs for integrity.

RIPE integrity primitives, part 1 (RACE Integrity Primitives Evaluation)

NASA Astrophysics Data System (ADS)

Denboer, B.; Boly, J. P.; Bosselaers, A.; Brandt, J.; Chaum, D.; Damgaard, I.; Dichtl, M.; Fumy, W.; Vanderham, M.; Jansen, C. J. A.

1993-04-01

A manual intended for those seeking to secure information systems by applying modern cryptography is presented. It represents the successful attainment of goals by RIPE (RACE (Research and development of Advanced Communication technology in Europe) Integrity Primitives Evaluation). The recommended portfolio of integrity primitives, which is the main product of the project, forms the heart of the manual. By integrity, is meant the kinds of security that can be achieved through cryptography, apart from keeping messages secret. Thus included are ways to ensure that stored or communicated data is not illicitly modified, that parties exchanging messages are actually present, and that 'signed' electronic messages can be recognized as authentic by anyone. Of particular concern to the project were the high speed requirements of broadband communication. The project also aimed for completeness in its recommendations. As a result, the portfolio contains primitives, that is building blocks, that can meet most of today's perceived needs for integrity.

Alkane inducible proteins in Geobacillus thermoleovorans B23

PubMed Central

2009-01-01

Background Initial step of β-oxidation is catalyzed by acyl-CoA dehydrogenase in prokaryotes and mitochondria, while acyl-CoA oxidase primarily functions in the peroxisomes of eukaryotes. Oxidase reaction accompanies emission of toxic by-product reactive oxygen molecules including superoxide anion, and superoxide dismutase and catalase activities are essential to detoxify them in the peroxisomes. Although there is an argument about whether primitive life was born and evolved under high temperature conditions, thermophilic archaea apparently share living systems with both bacteria and eukaryotes. We hypothesized that alkane degradation pathways in thermophilic microorganisms could be premature and useful to understand their evolution. Results An extremely thermophilic and alkane degrading Geobacillus thermoleovorans B23 was previously isolated from a deep subsurface oil reservoir in Japan. In the present study, we identified novel membrane proteins (P16, P21) and superoxide dismutase (P24) whose production levels were significantly increased upon alkane degradation. Unlike other bacteria acyl-CoA oxidase and catalase activities were also increased in strain B23 by addition of alkane. Conclusion We first suggested that peroxisomal β-oxidation system exists in bacteria. This eukaryotic-type alkane degradation pathway in thermophilic bacterial cells might be a vestige of primitive living cell systems that had evolved into eukaryotes. PMID:19320977

Historical Development of Origins Research

PubMed Central

Lazcano, Antonio

2010-01-01

Following the publication of the Origin of Species in 1859, many naturalists adopted the idea that living organisms were the historical outcome of gradual transformation of lifeless matter. These views soon merged with the developments of biochemistry and cell biology and led to proposals in which the origin of protoplasm was equated with the origin of life. The heterotrophic origin of life proposed by Oparin and Haldane in the 1920s was part of this tradition, which Oparin enriched by transforming the discussion of the emergence of the first cells into a workable multidisciplinary research program. On the other hand, the scientific trend toward understanding biological phenomena at the molecular level led authors like Troland, Muller, and others to propose that single molecules or viruses represented primordial living systems. The contrast between these opposing views on the origin of life represents not only contrasting views of the nature of life itself, but also major ideological discussions that reached a surprising intensity in the years following Stanley Miller’s seminal result which showed the ease with which organic compounds of biochemical significance could be synthesized under putative primitive conditions. In fact, during the years following the Miller experiment, attempts to understand the origin of life were strongly influenced by research on DNA replication and protein biosynthesis, and, in socio-political terms, by the atmosphere created by Cold War tensions. The catalytic versatility of RNA molecules clearly merits a critical reappraisal of Muller’s viewpoint. However, the discovery of ribozymes does not imply that autocatalytic nucleic acid molecules ready to be used as primordial genes were floating in the primitive oceans, or that the RNA world emerged completely assembled from simple precursors present in the prebiotic soup. The evidence supporting the presence of a wide range of organic molecules on the primitive Earth, including membrane-forming compounds, suggests that the evolution of membrane-bounded molecular systems preceded cellular life on our planet, and that life is the evolutionary outcome of a process, not of a single, fortuitous event. PMID:20534710

Conservation of species, volume, and belief in patients with Alzheimer's disease: the issue of domain specificity and conceptual impairment.

PubMed

Zaitchik, Deborah; Solomon, Gregg E A

2009-09-01

Two studies investigated whether patients with Alzheimer's disease (AD) suffer high-level and category-specific impairment in the conceptual domain of living things. In Experiment 1, AD patients and healthy young and healthy elderly controls took part in three tasks: the conservation of species, volume, and belief. All 3 tasks required tracking an object's identity in the face of irrelevant but salient transformations. Healthy young and elderly controls performed at or near ceiling on all tasks. AD patients were at or near ceiling on the volume and belief tasks, but only about half succeeded on the species task. Experiment 2 demonstrated that the results were not due to simple task demands. AD patients' failure to conserve species indicates that they are impaired in their theoretical understanding of living things, and their success on the volume and belief tasks suggests that the impairment is domain-specific. Two hypotheses are put forward to explain the phenomenon: The first, a category-specific account, holds that the intuitive theory of biology undergoes pervasive degradation; the second, a hybrid domain-general/domain-specific account, holds that impairment to domain-general processes such as executive function interacts with core cognition, the primitive elements that are the foundation of domain-specific knowledge.

Conservation of species, volume, and belief in patients with Alzheimer’s disease: the issue of domain-specificity and conceptual impairment

PubMed Central

Zaitchik, Deborah; Solomon, Gregg E. A.

2009-01-01

Two studies investigated whether patients with Alzheimer’s disease (AD) suffer high-level and category-specific impairment in the conceptual domain of living things. In Study 1, AD patients and healthy young and healthy elderly controls took part in three tasks: the Conservation of Species, Volume, and Belief. All 3 tasks required tracking an object’s identity in the face of irrelevant but salient transformations. Healthy young and elderly controls performed at or near ceiling on all tasks. AD patients were at or near ceiling on the Volume and Belief tasks, but only about half succeeded on the Species task. Study 2 demonstrated that the results were not due to simple task demands. AD patients’ failure to conserve species indicates that they are impaired in their theoretical understanding of living things, and their success on the Volume and Belief tasks suggests that the impairment is domain-specific. Two hypotheses are put forward to explain the phenomenon: the first, a category-specific account, holds that the intuitive theory of biology undergoes pervasive degradation; the second, a hybrid domain-general/domain-specific account, holds that impairment to domain-general processes such as executive function interacts with core cognition, the primitive elements that are the foundation of domain-specific knowledge. PMID:20043252

RO4929097, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Malignant Glioma

ClinicalTrials.gov

2015-09-28

Acoustic Schwannoma; Adult Anaplastic (Malignant) Meningioma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Brain Stem Glioma; Adult Choroid Plexus Neoplasm; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Primary Melanocytic Lesion of Meninges; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor; Malignant Adult Intracranial Hemangiopericytoma

Ispinesib in Treating Young Patients With Relapsed or Refractory Solid Tumors or Lymphoma

ClinicalTrials.gov

2013-01-15

Childhood Burkitt Lymphoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Unspecified Childhood Solid Tumor, Protocol Specific

Establishment of mouse expanded potential stem cells

PubMed Central

Gao, Xuefei; Antunes, Liliana; Yu, Yong; Zhu, Zhexin; Wang, Juexuan; Kolodziejczyk, Aleksandra A.; Campos, Lia S.; Wang, Cui; Yang, Fengtang; Zhong, Zhen; Fu, Beiyuan; Eckersley-Maslin, Melanie A.; Woods, Michael; Tanaka, Yosuke; Chen, Xi; Wilkinson, Adam C.; Bussell, James; White, Jacqui; Ramirez-Solis, Ramiro; Reik, Wolf; Göttgens, Berthold; Teichmann, Sarah A.; Tam, Patrick P. L.; Nakauchi, Hiromitsu; Zou, Xiangang; Lu, Liming; Liu, Pentao

2018-01-01

Mouse embryonic stem cells derived from the epiblast1 contribute to the somatic lineages and the germline but are excluded from the extra-embryonic tissues that are derived from the trophectoderm and the primitive endoderm2 upon reintroduction to the blastocyst. Here we report that cultures of expanded potential stem cells can be established from individual eight-cell blastomeres, and by direct conversion of mouse embryonic stem cells and induced pluripotent stem cells. Remarkably, a single expanded potential stem cell can contribute both to the embryo proper and to the trophectoderm lineages in a chimaera assay. Bona fide trophoblast stem cell lines and extra-embryonic endoderm stem cells can be directly derived from expanded potential stem cells in vitro. Molecular analyses of the epigenome and single-cell transcriptome reveal enrichment for blastomere-specific signature and a dynamic DNA methylome in expanded potential stem cells. The generation of mouse expanded potential stem cells highlights the feasibility of establishing expanded potential stem cells for other mammalian species. PMID:29019987

Using Abstraction in Explicity Parallel Programs.

DTIC Science & Technology

1991-07-01

However, we only rely on sequential consistency of memory operations. includ- ing reads. writes and any synchronization primitives provided by the...explicit synchronization primitives . This demonstrates the practical power of sequentially consistent memory, as opposed to weaker models of memory that...a small set of synchronization primitives , all pro- cedures have non-waiting specifications. This is in contrast to richer process-oriented

Semantically-Sensitive Macroprocessing

DTIC Science & Technology

1989-12-15

constr uct for protecting critical regions. Given the synchronization primitives P and V, we might implement the following transformation, where...By this we mean that the semantic model for the base language provides a primitive set of concepts, represented by data types and operations...the gener- ation of a (dynamic-) semantically equivalent program fragment ultimately expressible in terms of built-in primitives . Note that static

A manual for PARTI runtime primitives, revision 1

NASA Technical Reports Server (NTRS)

Das, Raja; Saltz, Joel; Berryman, Harry

1991-01-01

Primitives are presented that are designed to help users efficiently program irregular problems (e.g., unstructured mesh sweeps, sparse matrix codes, adaptive mesh partial differential equations solvers) on distributed memory machines. These primitives are also designed for use in compilers for distributed memory multiprocessors. Communications patterns are captured at runtime, and the appropriate send and receive messages are automatically generated.

Fast concurrent array-based stacks, queues and deques using fetch-and-increment-bounded, fetch-and-decrement-bounded and store-on-twin synchronization primitives

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

Chen, Dong; Gara, Alana; Heidelberger, Philip

Implementation primitives for concurrent array-based stacks, queues, double-ended queues (deques) and wrapped deques are provided. In one aspect, each element of the stack, queue, deque or wrapped deque data structure has its own ticket lock, allowing multiple threads to concurrently use multiple elements of the data structure and thus achieving high performance. In another aspect, new synchronization primitives FetchAndIncrementBounded (Counter, Bound) and FetchAndDecrementBounded (Counter, Bound) are implemented. These primitives can be implemented in hardware and thus promise a very fast throughput for queues, stacks and double-ended queues.

Probabilistic structural analysis of a truss typical for space station

NASA Technical Reports Server (NTRS)

Pai, Shantaram S.

1990-01-01

A three-bay, space, cantilever truss is probabilistically evaluated using the computer code NESSUS (Numerical Evaluation of Stochastic Structures Under Stress) to identify and quantify the uncertainties and respective sensitivities associated with corresponding uncertainties in the primitive variables (structural, material, and loads parameters) that defines the truss. The distribution of each of these primitive variables is described in terms of one of several available distributions such as the Weibull, exponential, normal, log-normal, etc. The cumulative distribution function (CDF's) for the response functions considered and sensitivities associated with the primitive variables for given response are investigated. These sensitivities help in determining the dominating primitive variables for that response.

Efficient Agent-Based Models for Non-Genomic Evolution

NASA Technical Reports Server (NTRS)

Gupta, Nachi; Agogino, Adrian; Tumer, Kagan

2006-01-01

Modeling dynamical systems composed of aggregations of primitive proteins is critical to the field of astrobiological science involving early evolutionary structures and the origins of life. Unfortunately traditional non-multi-agent methods either require oversimplified models or are slow to converge to adequate solutions. This paper shows how to address these deficiencies by modeling the protein aggregations through a utility based multi-agent system. In this method each agent controls the properties of a set of proteins assigned to that agent. Some of these properties determine the dynamics of the system, such as the ability for some proteins to join or split other proteins, while additional properties determine the aggregation s fitness as a viable primitive cell. We show that over a wide range of starting conditions, there are mechanisins that allow protein aggregations to achieve high values of overall fitness. In addition through the use of agent-specific utilities that remain aligned with the overall global utility, we are able to reach these conclusions with 50 times fewer learning steps.

Significance of solvated electrons (e(aq)-) as promoters of life on earth.

PubMed

Getoff, Nikola

2014-01-01

Based on the present state of knowledge a new hypothesis concerning the origin of life on Earth is presented, and emphasizes the particular significance of solvated electrons (e(aq)(-)). Solvated electrons are produced in seawater, mainly by (40)K radiation and in atmospheric moisture by VUV light, electrical discharges and cosmic ray. Solvated electrons are involved in primary chemical processes and in biological processes. The conversion of aqueous CO2 and CO into simple organic substances, the generation of ammonia from N2 and water, the formation of amines, amino acids and simple proteins under the action of e(aq)(-) has been experimentally proven. Furthermore, it is supposed that the generation of the primitive cell and equilibria of primitive enzymes are also realized due to the strong reducing property of e(aq)(-). The presented hypothesis is mainly founded on recently obtained experimental results. The involvement of e(aq)(-) in such mechanisms, as well as their action as an initiator of life is also briefly discussed.

A method of plane geometry primitive presentation

NASA Astrophysics Data System (ADS)

Jiao, Anbo; Luo, Haibo; Chang, Zheng; Hui, Bin

2014-11-01

Point feature and line feature are basic elements in object feature sets, and they play an important role in object matching and recognition. On one hand, point feature is sensitive to noise; on the other hand, there are usually a huge number of point features in an image, which makes it complex for matching. Line feature includes straight line segment and curve. One difficulty in straight line segment matching is the uncertainty of endpoint location, the other is straight line segment fracture problem or short straight line segments joined to form long straight line segment. While for the curve, in addition to the above problems, there is another difficulty in how to quantitatively describe the shape difference between curves. Due to the problems of point feature and line feature, the robustness and accuracy of target description will be affected; in this case, a method of plane geometry primitive presentation is proposed to describe the significant structure of an object. Firstly, two types of primitives are constructed, they are intersecting line primitive and blob primitive. Secondly, a line segment detector (LSD) is applied to detect line segment, and then intersecting line primitive is extracted. Finally, robustness and accuracy of the plane geometry primitive presentation method is studied. This method has a good ability to obtain structural information of the object, even if there is rotation or scale change of the object in the image. Experimental results verify the robustness and accuracy of this method.

Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF

PubMed Central

De Kleer, Ismé; Henri, Sandrine; Post, Sijranke; Vanhoutte, Leen; De Prijck, Sofie; Deswarte, Kim; Malissen, Bernard; Hammad, Hamida; Lambrecht, Bart N.

2013-01-01

Tissue-resident macrophages can develop from circulating adult monocytes or from primitive yolk sac–derived macrophages. The precise ontogeny of alveolar macrophages (AMFs) is unknown. By performing BrdU labeling and parabiosis experiments in adult mice, we found that circulating monocytes contributed minimally to the steady-state AMF pool. Mature AMFs were undetectable before birth and only fully colonized the alveolar space by 3 d after birth. Before birth, F4/80hiCD11blo primitive macrophages and Ly6ChiCD11bhi fetal monocytes sequentially colonized the developing lung around E12.5 and E16.5, respectively. The first signs of AMF differentiation appeared around the saccular stage of lung development (E18.5). Adoptive transfer identified fetal monocytes, and not primitive macrophages, as the main precursors of AMFs. Fetal monocytes transferred to the lung of neonatal mice acquired an AMF phenotype via defined developmental stages over the course of one week, and persisted for at least three months. Early AMF commitment from fetal monocytes was absent in GM-CSF–deficient mice, whereas short-term perinatal intrapulmonary GM-CSF therapy rescued AMF development for weeks, although the resulting AMFs displayed an immature phenotype. This demonstrates that tissue-resident macrophages can also develop from fetal monocytes that adopt a stable phenotype shortly after birth in response to instructive cytokines, and then self-maintain throughout life. PMID:24043763

Comparative Anatomy of Maintenance Tasks (CAMT): A Feasibility Study

DTIC Science & Technology

1992-03-01

systems. Methods for task primitive definition were developed, then taken into the field for testing . Task primitives were defined to cover three remove...engine maintenance) and to test whether task primitives developed for one weapon system could have applicability to other weapon systems (Phase 2...requirements, levying MPT constraints and predicting MPT requirements are only ritualistic exercises until the operational test and evaluation of a

Two-dimensional CFD modeling of wave rotor flow dynamics

NASA Technical Reports Server (NTRS)

Welch, Gerard E.; Chima, Rodrick V.

1994-01-01

A two-dimensional Navier-Stokes solver developed for detailed study of wave rotor flow dynamics is described. The CFD model is helping characterize important loss mechanisms within the wave rotor. The wave rotor stationary ports and the moving rotor passages are resolved on multiple computational grid blocks. The finite-volume form of the thin-layer Navier-Stokes equations with laminar viscosity are integrated in time using a four-stage Runge-Kutta scheme. Roe's approximate Riemann solution scheme or the computationally less expensive advection upstream splitting method (AUSM) flux-splitting scheme is used to effect upwind-differencing of the inviscid flux terms, using cell interface primitive variables set by MUSCL-type interpolation. The diffusion terms are central-differenced. The solver is validated using a steady shock/laminar boundary layer interaction problem and an unsteady, inviscid wave rotor passage gradual opening problem. A model inlet port/passage charging problem is simulated and key features of the unsteady wave rotor flow field are identified. Lastly, the medium pressure inlet port and high pressure outlet port portion of the NASA Lewis Research Center experimental divider cycle is simulated and computed results are compared with experimental measurements. The model accurately predicts the wave timing within the rotor passages and the distribution of flow variables in the stationary inlet port region.

Two-dimensional CFD modeling of wave rotor flow dynamics

NASA Technical Reports Server (NTRS)

Welch, Gerard E.; Chima, Rodrick V.

1993-01-01

A two-dimensional Navier-Stokes solver developed for detailed study of wave rotor flow dynamics is described. The CFD model is helping characterize important loss mechanisms within the wave rotor. The wave rotor stationary ports and the moving rotor passages are resolved on multiple computational grid blocks. The finite-volume form of the thin-layer Navier-Stokes equations with laminar viscosity are integrated in time using a four-stage Runge-Kutta scheme. The Roe approximate Riemann solution scheme or the computationally less expensive Advection Upstream Splitting Method (AUSM) flux-splitting scheme are used to effect upwind-differencing of the inviscid flux terms, using cell interface primitive variables set by MUSCL-type interpolation. The diffusion terms are central-differenced. The solver is validated using a steady shock/laminar boundary layer interaction problem and an unsteady, inviscid wave rotor passage gradual opening problem. A model inlet port/passage charging problem is simulated and key features of the unsteady wave rotor flow field are identified. Lastly, the medium pressure inlet port and high pressure outlet port portion of the NASA Lewis Research Center experimental divider cycle is simulated and computed results are compared with experimental measurements. The model accurately predicts the wave timing within the rotor passage and the distribution of flow variables in the stationary inlet port region.

Origin of fatty acid synthesis - Thermodynamics and kinetics of reaction pathways

NASA Technical Reports Server (NTRS)

Weber, Arthur L.

1991-01-01

The primitiveness of contemporary fatty acid biosynthesis was evaluated by using the thermodynamics and kinetics of its component reactions to estimate the extent of its dependence on powerful and selective catalysis by enzymes. Since this analysis indicated that the modern pathway is not primitive because it requires sophisticated enzymatic catalysis, an alternative pathway of primitive fatty acid synthesis is proposed that uses glycolaldehyde as a substrate. In contrast to the modern pathway, this primitive pathway is not dependent on an exogenous source of phosphoanhydride energy. Furthermore, the chemical spontaneity of its reactions suggests that it could have been readily catalyzed by the rudimentary biocatalysts available at an early stage in the origin of life.

Physics of the primitive solar nebula and of giant gaseous protoplanets

NASA Technical Reports Server (NTRS)

Cameron, A. G. W.

1978-01-01

It has been proposed that the supernova responsible for injecting Al-26 into the early solar system was in fact responsible for triggering the collapse of an interstellar cloud in order to produce a system of stars, one of which would be the solar system. Details concerning the mechanism involved in such a process are discussed. Attention is given to the evolution of the primitive solar nebula, the instabilities in the primitive solar nebula, and the giant gaseous protoplanets. The principal conclusion to be drawn from the material presented is that the primitive solar nebula was a rather chaotic place, highly turbulent, with the multiple formation of giant gaseous protoplanets.

Microbioreactor Arrays for Full Factorial Screening of Exogenous and Paracrine Factors in Human Embryonic Stem Cell Differentiation

PubMed Central

Titmarsh, Drew M.; Hudson, James E.; Hidalgo, Alejandro; Elefanty, Andrew G.; Stanley, Edouard G.; Wolvetang, Ernst J.; Cooper-White, Justin J.

2012-01-01

Timed exposure of pluripotent stem cell cultures to exogenous molecules is widely used to drive differentiation towards desired cell lineages. However, screening differentiation conditions in conventional static cultures can become impractical in large parameter spaces, and is intrinsically limited by poor spatiotemporal control of the microenvironment that also makes it impossible to determine whether exogenous factors act directly or through paracrine-dependent mechanisms. We detail here the development of a continuous flow microbioreactor array platform that combines full-factorial multiplexing of input factors with progressive accumulation of paracrine factors through serially-connected culture chambers, and further, the use of this system to explore the combinatorial parameter space of both exogenous and paracrine factors involved in human embryonic stem cell (hESC) differentiation to a MIXL1-GFP+ primitive streak-like population. We show that well known inducers of primitive streak (BMP, Activin and Wnt signals) do not simply act directly on hESC to induce MIXL1 expression, but that this requires accumulation of surplus, endogenous factors; and, that conditioned medium or FGF-2 supplementation is able to offset this. Our approach further reveals the presence of a paracrine, negative feedback loop to the MIXL1-GFP+ population, which can be overcome with GSK-3β inhibitors (BIO or CHIR99021), implicating secreted Wnt inhibitory signals such as DKKs and sFRPs as candidate effectors. Importantly, modulating paracrine effects identified in microbioreactor arrays by supplementing FGF-2 and CHIR in conventional static culture vessels resulted in improved differentiation outcomes. We therefore demonstrate that this microbioreactor array platform uniquely enables the identification and decoding of complex soluble factor signalling hierarchies, and that this not only challenges prevailing strategies for extrinsic control of hESC differentiation, but also is translatable to conventional culture systems. PMID:23300662

O-Fucosylation of Thrombospondin Type 1 Repeats Restricts Epithelial to Mesenchymal Transition (EMT) and Maintains Epiblast Pluripotency During Mouse Gastrulation

PubMed Central

Du, Jianguang; Takeuchi, Hideyuki; Leonhard-Melief, Christina; Shroyer, Kenneth R.; Dlugosz, Malgosia; Haltiwanger, Robert S.; Holdener, Bernadette C.

2010-01-01

Thrombospondin type 1 repeat (TSR) superfamily members regulate diverse biological activities ranging from cell motility to inhibition of angiogenesis. In this study, we verified that mouse protein O-fucosyltransferase-2 (POFUT2) specifically adds O-fucose to TSRs. Using two Pofut2 gene trap lines, we demonstrated that O-fucosylation of TSRs was essential for restricting epithelial to mesenchymal transition in the primitive streak, correct patterning of mesoderm, and localization of the definitive endoderm. Although Pofut2 mutant embryos established anterior/posterior polarity, they underwent extensive mesoderm differentiation at the expense of maintaining epiblast pluripotency. Moreover, mesoderm differentiation was biased towards the vascular endothelial cell lineage. Localization of Foxa2 and Cer1 expressing cells within the interior of Pofut2 mutant embryos suggested that POFUT2 activity was also required for the displacement of the primitive endoderm by definitive endoderm. Notably, Nodal, BMP4, Fgf8, and Wnt3 expression were markedly elevated and expanded in Pofut2 mutants, providing evidence that O-fucose modification of TSRs was essential for modulation of growth factor signaling during gastrulation. The ability of Pofut2 mutant embryos to form teratomas comprised of tissues from all three germ layer origins suggested that defects in Pofut2 mutant embryos resulted from abnormalities in the extracellular environment. This prediction is consistent with the observation that POFUT2 targets are constitutive components of the extracellular matrix (ECM) or associate with the ECM. For this reason, the Pofut2 mutants represent a valuable tool for studying the role of O-fucosylation in ECM synthesis and remodeling, and will be a valuable model to study how post-translational modification of ECM components regulates the formation of tissue boundaries, cell movements, and signaling. PMID:20637190

Cooperation between both Wnt/β-catenin and PTEN/PI3K/Akt signaling promotes primitive hematopoietic stem cell self-renewal and expansion

PubMed Central

Perry, John M.; He, Xi C.; Sugimura, Ryohichi; Grindley, Justin C.; Haug, Jeffrey S.; Ding, Sheng; Li, Linheng

2011-01-01

Although self-renewal is the central property of stem cells, the underlying mechanism remains inadequately defined. Using a hematopoietic stem and progenitor cell (HSPC)-specific conditional induction line, we generated a compound genetic model bearing both Pten deletion and β-catenin activation. These double mutant mice exhibit a novel phenotype, including expansion of phenotypic long-term hematopoietic stem cells (LT-HSCs) without extensive differentiation. Unexpectedly, constitutive activation of β-catenin alone results in apoptosis of HSCs. However, together, the Wnt/β-catenin and PTEN/PI3k/Akt pathways interact to drive phenotypic LT-HSC expansion by inducing proliferation while simultaneously inhibiting apoptosis and blocking differentiation, demonstrating the necessity of complementary cooperation between the two pathways in promoting self-renewal. Mechanistically, β-catenin activation reduces multiple differentiation-inducing transcription factors, blocking differentiation partially through up-regulation of Inhibitor of differentiation 2 (Id2). In double mutants, loss of Pten enhances the HSC anti-apoptotic factor Mcl-1. All of these contribute in a complementary way to HSC self-renewal and expansion. While permanent, genetic alteration of both pathways in double mutant mice leads to expansion of phenotypic HSCs, these HSCs cannot function due to blocked differentiation. We developed a pharmacological approach to expand normal, functional HSCs in culture using factors that reversibly activate both Wnt/β-catenin and PI3K/Akt signaling simultaneously. We show for the first time that activation of either single pathway is insufficient to expand primitive HSCs, but in combination, both pathways drive self-renewal and expansion of HSCs with long-term functional capacity. PMID:21890648

Effects of Spaceflight on Cells of Bone Marrow Origin

PubMed Central

Özçivici, Engin

2013-01-01

Once only a subject for science fiction novels, plans for establishing habitation on space stations, the Moon, and distant planets now appear among the short-term goals of space agencies. This article reviews studies that present biomedical issues that appear to challenge humankind for long-term spaceflights. With particularly focus on cells of bone marrow origin, studies involving changes in bone, immune, and red blood cell populations and their functions due to extended weightlessness were reviewed. Furthermore, effects of mechanical disuse on primitive stem cells that reside in the bone marrow were also included in this review. Novel biomedical solutions using space biotechnology will be required in order to achieve the goal of space exploration without compromising the functions of bone marrow, as spaceflight appears to disrupt homeostasis for all given cell types. Conflict of interest:None declared. PMID:24385745

Orbitotomy for retrobulbar malignant fibrous histiocytoma in a dog.

PubMed

Lassaline, Mary E; Gelatt, Kirk N; Brooks, Dennis E; Ellison, Gary W

2005-01-01

A retrobulbar malignant fibrous histiocytoma was diagnosed in a 12-year-old castrated male Keeshond dog. The mass was excised with a lateral orbitotomy and zygomatic arch resection. Vision was preserved in the affected eye, and no recurrence was noted up to 10 months postoperatively. Malignant fibrous histiocytoma originates from primitive mesenchymal stem cells. The malignant fibrous histiocytoma seen in our patient was most consistent with the storiform-pleomorphic variant, given the storiform arrangement of spindle cells, the presence of histiocytoid cells, and a mixed inflammatory infiltrate, without giant cells. The metastatic potential of malignant fibrous histiocytoma in general, and the storiform variant in particular, is unknown. Seventeen months later the dog was presented to the referring veterinarian with anorexia, diarrhea, weight loss and bilateral purulent nasal exudates. The dog was euthanized without necropsy.

CD22 and Siglec-G in B cell function and tolerance

PubMed Central

Poe, Jonathan C.; Tedder, Thomas F.

2012-01-01

The immune system has evolved into two main arms, the primitive innate arm that is the first line of defense but relatively short-lived and broad acting, and the advanced adaptive arm that generates immunologic “memory” allowing rapid, specific recall responses. T cell-independent type-2 (TI-2) antigens (Ags) invoke innate immune responses. However, due to its “at the ready” nature, how the innate arm of the immune system maintains tolerance to potentially abundant host TI-2 Ags remains elusive. Therefore, it is important to define the mechanisms that establish innate immune tolerance. This review highlights recent insights into B cell tolerance to theoretical self TI-2 Ags, and examines how the B cell-restricted Siglecs, CD22 and Siglec-G, might contribute to this process. PMID:22677186

Possible complex organic compounds on Mars.

PubMed

Kobayashi, K; Sato, T; Kajishima, S; Kaneko, T; Ishikawa, Y; Saito, T

1997-01-01

It is suggested that primitive Mars had somehow similar environments as primitive Earth. If life was born on the primitive earth using organic compounds which were produced from the early Earth environment, the same types of organic compounds were also formed on primitive Mars. Such organic compounds might have been preserved on Mars still now. We are studying possible organic formation on primitive and present Mars. A gaseous mixture of CO2, CO, N2 and H2O with various mixing ratios were irradiated with high energy protons (major components of cosmic rays). Hydrogen cyanide and formaldehyde were detected among volatile products, and yellow-brown-colored water-soluble non-volatile substances were produced, which gave amino acids after acid-hydrolysis. Major part of "amino acid precursors" were not simple molecules like aminonitriles, but complex compounds which eluted earlier than free amino acids in cation-exchange HPLC. These organic compounds should be major targets in the future Mars mission. Strategy for the detection of the complex organics on Mars will be discussed.

Blowing in the Wind: II. Creation and Redistribution of Refractory Inclusions in a Turbulent Protoplanetary Nebula

NASA Technical Reports Server (NTRS)

Cuzzi, Jeffrey N.; Davis, Sanford S.; Dobrovolskis, Anthony R.

2003-01-01

Ca-A1 rich refractory mineral inclusions (CAIs) found at 1-6% mass fraction in primitive chondrites appear to be 1-3 million years older than the dominant (chondrule) components which were accreted into the same parent bodies. A prevalent concern is that it is difficult to retain CAIs for this long against gas-drag-induced radial drift into the sun. We reassess the situation in terms of a hot inner (turbulent) nebula context for CAI formation, using analytical models of nebula evolution and particle diffusion. We show that outward radial diffusion in a weakly turbulent nebula can overwhelm inward drift, and prevent significant numbers of CAI-size particles from being lost into the sun for times on the order of 10(exp 6) years. CAIs can form early, when the inner nebula was hot, and persist in sufficient abundance to be incorporated into primitive planetesimals at a much later time. Small (less than or approximately 0.1 mm diameter) CAIs persist for longer times than large (greater than or approximately 5mm diameter ones. To obtain a quantitative match to the observed volume fractions of CAIs in chondrites, another process must be allowed for: a substantial enhancement of the inner hot nebula in silicate-forming material, which we suggest was caused by rapid inward drift of meter-sized objects. This early in nebula history, the drifting rubble would have a carbon content probably an order of magnitude larger than even the most primitive (CI) carbonaceous chondrites. Abundant carbon in the evaporating material would help keep the nebula oxygen fugacity low, plausibly solar; as inferred for the formation environment of CAIs. The associated production of a larger than canonical amount of CO2 might also play a role in mass-independent fractionation of oxygen isotopes, leaving the gas rich in O-16 as inferred from CAIs and other high temperature condensates.

Blowing in the Wind: II. Creation and Redistribution of Refractory Inclusions in a Turbulent Protoplanetary Nebula

NASA Technical Reports Server (NTRS)

Cuzzi, Jeffrey N.; Davis, Sanford S.; Dobrovolskis, Anthony R.

2003-01-01

Ca-Al rich refractory mineral inclusions (CAIs) found at 1-6% mass fraction in primitive chondrites appear to be 1-3 million years older than the dominant (chondrule) components which were accreted into the same parent bodies. A prevalent concern is that it is difficult to retain CAIs for this long against gas-drag-induced radial drift into the sun. We reassess the situation in terms of a hot inner (turbulent) nebula context for CAI formation, using analytical models of nebula evolution and particle diffusion. We show that outward radial diffusion in a weakly turbulent nebula can overwhelm inward drift, and prevent significant numbers of CAI-size particles from being lost into the sun for times on the order of 10(exp 6) years. CAIs can form early, when the inner nebula was hot, and persist in sufficient abundance to be incorporated into primitive planetesimals at a much later time. Small (less than or approx. equal to 0.1 mm diameter) CAIs persist for longer times than large (greater than or approx. equal to 5mm diameter ones). To obtain a quantitative match t o the observed volume fractions of CAIs in chondrites, another process must be allowed for: a substantial enhancement of the inner hot nebula in silicate-forming material, which we suggest was caused by rapid inward drift of meter-sized objects. This early in nebula history, the drifting rubble would have a carbon content probably an order of magnitude larger than even the most primitive (CI) carbonaceous chondrites. Abundant carbon in the evaporating material would help keep the nebula oxygen fugacity low, plausably solar, as inferred for the formation environment of CAIs. The associated production of a larger than canonical amount of CO2 might also play a role in mass-independent fractionation of oxygen isotopes, leaving the gas rich in l60 as inferred from CAIs and other high temperature condensates.

Will Organic Synthesis Within Icy Grains or on Dust Surfaces in the Primitive Solar Nebula Completely Erase the Effects of Photochemical Self Shielding?

NASA Technical Reports Server (NTRS)

Nuth, Joseph A., III; Johnson, Natasha M.

2012-01-01

There are at least 3 separate photochemical self-shielding models with different degrees of commonality. All of these models rely on the selective absorption of (12))C(16)O dissociative photons as the radiation source penetrates through the gas allowing the production of reactive O-17 and O-18 atoms within a specific volume. Each model also assumes that the undissociated C(16)O is stable and does not participate in the chemistry of nebular dust grains. In what follows we will argue that this last, very important assumption is simply not true despite the very high energy of the CO molecular bond.

Using Parallel Processing for Problem Solving.

DTIC Science & Technology

1979-12-01

are the basic parallel proces- sing primitive . Different goals of the system can be pursued in parallel by placing them in separate activities...Language primitives are provided for manipulating running activities. Viewpoints are a generalization of context FOM -(over "*’ DD I FON 1473 ’EDITION OF I...arc the basic parallel processing primitive . Different goals of the system can be pursued in parallel by placing them in separate activities. Language

Security Primitives for Reconfigurable Hardware-Based Systems

DTIC Science & Technology

2010-05-01

work, we propose security primitives using ideas centered around the notion of “moats and drawbridges .” The primitives encompass four design properties...Santa Bar- bara, CA 93106; email: sherwood@cs.ucsb.edu; R. Kastner, Department of Computer Science and Engineering , University of California, San...fingerprint reader), the other to control the ethernet IP core—and an AES encryption engine used by both of the processor cores. These cores are all implemented

Spectrum Analysis of Inertial and Subinertial Motions Based on Analyzed Winds and Wind-Driven Currents from a Primitive Equation General Ocean Circulation Model.

DTIC Science & Technology

1982-12-01

1Muter.Te Motions Based on Ana lyzed Winds and wind-driven December 1982 Currents from. a Primitive Squat ion General a.OW -love"*..* Oean Circulation...mew se"$ (comeS.... do oISN..u am ae~ 00do OWaor NUN Fourier and Rotary Spc , Analysis Modeled Inertial and Subinrtial Motion 4 Primitive Equation

A Generalized-Compliant-Motion Primitive

NASA Technical Reports Server (NTRS)

Backes, Paul G.

1993-01-01

Computer program bridges gap between planning and execution of compliant robotic motions developed and installed in control system of telerobot. Called "generalized-compliant-motion primitive," one of several task-execution-primitive computer programs, which receives commands from higher-level task-planning programs and executes commands by generating required trajectories and applying appropriate control laws. Program comprises four parts corresponding to nominal motion, compliant motion, ending motion, and monitoring. Written in C language.

Intrapartum synthetic oxytocin reduce the expression of primitive reflexes associated with breastfeeding.

PubMed

Marín Gabriel, Miguel A; Olza Fernández, Ibone; Malalana Martínez, Ana M; González Armengod, Carmen; Costarelli, Valeria; Millán Santos, Isabel; Fernández-Cañadas Morillo, Aurora; Pérez Riveiro, Pilar; López Sánchez, Francisco; García Murillo, Lourdes

2015-05-01

Several synthetic peptide manipulations during the time surrounding birth can alter the specific neurohormonal status in the newborn brain. This study is aimed at assessing whether intrapartum oxytocin administration has any effect on primitive neonatal reflexes and determining whether such an effect is dose-dependent. A cohort prospective study was conducted at a tertiary hospital. Mother-infant dyads who received intrapartum oxytocin (n=53) were compared with mother-infant dyads who did not receive intrapartum oxytocin (n=45). Primitive neonatal reflexes (endogenous, antigravity, motor, and rhythmic reflexes) were quantified by analyzing videotaped breastfeeding sessions in a biological nurturing position. Two observers blind to the group assignment and the oxytocin dose analyzed the videotapes and assesed the newborn's state of consciousness according to the Brazelton scale. The release of all rhythmic reflexes (p=0.01), the antigravity reflex (p=0.04), and total primitive neonatal reflexes (p=0.02) in the group exposed to oxytocin was lower than in the group not exposed to oxytocin. No correlations were observed between the dose of oxytocin administered and the percentage of primitive neonatal reflexes released (r=0.03; p=0.82). Intrapartum oxytocin administration might inhibit the expression of several primitive neonatal reflexes associated with breastfeeding. This correlation does not seem to be dose-dependent.

MACOP modular architecture with control primitives

PubMed Central

Waegeman, Tim; Hermans, Michiel; Schrauwen, Benjamin

2013-01-01

Walking, catching a ball and reaching are all tasks in which humans and animals exhibit advanced motor skills. Findings in biological research concerning motor control suggest a modular control hierarchy which combines movement/motor primitives into complex and natural movements. Engineers inspire their research on these findings in the quest for adaptive and skillful control for robots. In this work we propose a modular architecture with control primitives (MACOP) which uses a set of controllers, where each controller becomes specialized in a subregion of its joint and task-space. Instead of having a single controller being used in this subregion [such as MOSAIC (modular selection and identification for control) on which MACOP is inspired], MACOP relates more to the idea of continuously mixing a limited set of primitive controllers. By enforcing a set of desired properties on the mixing mechanism, a mixture of primitives emerges unsupervised which successfully solves the control task. We evaluate MACOP on a numerical model of a robot arm by training it to generate desired trajectories. We investigate how the tracking performance is affected by the number of controllers in MACOP and examine how the individual controllers and their generated control primitives contribute to solving the task. Furthermore, we show how MACOP compensates for the dynamic effects caused by a fixed control rate and the inertia of the robot. PMID:23888140

A real-time robot arm collision detection system

NASA Technical Reports Server (NTRS)

Shaffer, Clifford A.; Herb, Gregory M.

1990-01-01

A data structure and update algorithm are presented for a prototype real time collision detection safety system for a multi-robot environment. The data structure is a variant of the octree, which serves as a spatial index. An octree recursively decomposes 3-D space into eight equal cubic octants until each octant meets some decomposition criteria. The octree stores cylspheres (cylinders with spheres on each end) and rectangular solids as primitives (other primitives can easily be added as required). These primitives make up the two seven degrees-of-freedom robot arms and environment modeled by the system. Octree nodes containing more than a predetermined number N of primitives are decomposed. This rule keeps the octree small, as the entire environment for the application can be modeled using a few dozen primitives. As robot arms move, the octree is updated to reflect their changed positions. During most update cycles, any given primitive does not change which octree nodes it is in. Thus, modification to the octree is rarely required. Incidents in which one robot arm comes too close to another arm or an object are reported. Cycle time for interpreting current joint angles, updating the octree, and detecting/reporting imminent collisions averages 30 milliseconds on an Intel 80386 processor running at 20 MHz.

Fully automatic segmentation of the femur from 3D-CT images using primitive shape recognition and statistical shape models.

PubMed

Ben Younes, Lassad; Nakajima, Yoshikazu; Saito, Toki

2014-03-01

Femur segmentation is well established and widely used in computer-assisted orthopedic surgery. However, most of the robust segmentation methods such as statistical shape models (SSM) require human intervention to provide an initial position for the SSM. In this paper, we propose to overcome this problem and provide a fully automatic femur segmentation method for CT images based on primitive shape recognition and SSM. Femur segmentation in CT scans was performed using primitive shape recognition based on a robust algorithm such as the Hough transform and RANdom SAmple Consensus. The proposed method is divided into 3 steps: (1) detection of the femoral head as sphere and the femoral shaft as cylinder in the SSM and the CT images, (2) rigid registration between primitives of SSM and CT image to initialize the SSM into the CT image, and (3) fitting of the SSM to the CT image edge using an affine transformation followed by a nonlinear fitting. The automated method provided good results even with a high number of outliers. The difference of segmentation error between the proposed automatic initialization method and a manual initialization method is less than 1 mm. The proposed method detects primitive shape position to initialize the SSM into the target image. Based on primitive shapes, this method overcomes the problem of inter-patient variability. Moreover, the results demonstrate that our method of primitive shape recognition can be used for 3D SSM initialization to achieve fully automatic segmentation of the femur.

The use of a computerized algorithm to determine single cardiac cell volumes.

PubMed

Marino, T A; Cook, L; Cook, P N; Dwyer, S J

1981-04-01

Single cardiac muscles cell volume data have been difficult to obtain, especially because the shape of a cell is quite complex. With the aid of a surface reconstruction method, a cell volume estimation algorithm has been developed that can be used on serial of cells. The cell surface is reconstructed by means of triangular tiles so that the cell is represented as a polyhedron. When this algorithm was tested on computer generated surfaces of a known volume, the difference was less than 1.6%. Serial sections of two phantoms of a known volume were also reconstructed and a comparison of the mathematically derived volumes and the computed volume estimations gave a per cent difference of between 2.8% and 4.1%. Finally cell volumes derived using conventional methods and volumes calculated using the algorithm were compared. The mean atrial muscle cell volume derived using conventional methods was 7752.7 +/- 644.7 micrometers3, while the mean computerized algorithm estimated atrial muscle cell volume was 7110.6 +/- 625.5 micrometers3. For AV bundle cells the mean cell volume obtained by conventional methods was 484.4 +/- 88.8 micrometers3 and the volume derived from the computer algorithm was 506.0 +/- 78.5 micrometers3. The differences between the volumes calculated using conventional methods and the algorithm were not significantly different.

Novel population of small tumour-initiating stem cells in the ovaries of women with borderline ovarian cancer

PubMed Central

Virant-Klun, Irma; Stimpfel, Martin

2016-01-01

Small stem cells with diameters of up to 5 μm previously isolated from adult human ovaries indicated pluripotency and germinal lineage, especially primordial germ cells, and developed into primitive oocyte-like cells in vitro. Here, we show that a comparable population of small stem cells can be found in the ovarian tissue of women with borderline ovarian cancer, which, in contrast to small stem cells in “healthy” ovaries, formed spontaneous tumour-like structures and expressed some markers related to pluripotency and germinal lineage. The gene expression profile of these small putative cancer stem cells differed from similar cells sorted from “healthy” ovaries by 132 upregulated and 97 downregulated genes, including some important forkhead box and homeobox genes related to transcription regulation, developmental processes, embryogenesis, and ovarian cancer. These putative cancer stem cells are suggested to be a novel population of ovarian tumour-initiating cells in humans. PMID:27703207

Flow-cytometric separation and enrichment of hepatic progenitor cells in the developing mouse liver.

PubMed

Suzuki, A; Zheng, Y; Kondo, R; Kusakabe, M; Takada, Y; Fukao, K; Nakauchi, H; Taniguchi, H

2000-12-01

Stem cells responsible for tissue maintenance and repair are found in a number of organs. However, hepatic stem cells assumed to play a key role in liver development and regeneration remain to be well characterized. To address this issue, we set up a culture system in which primitive hepatic progenitor cells formed colonies. By combining this culture system with fluorescence-activated cell sorting (FACS), cells forming colonies containing distinct hepatocytes and cholangiocytes were identified in the fetal mouse liver. These cells express both CD49f and CD29 (alpha6 and beta1 integrin subunits), but do not mark for hematopoietic antigens such as CD45, TER119, and c-Kit. When transplanted into the spleen, these cells migrated to the recipient liver and differentiated into liver parenchymal cells. Our data demonstrate that hepatic progenitor cells are enriched by FACS and suggest approaches to supplanting organ allografting and improving artificial-organ hepatic support.

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

PubMed Central

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

2017-01-01

Cells alter their mechanical properties in response to their local microenvironment; this plays a role in determining cell function and can even influence stem cell fate. Here, we identify a robust and unified relationship between cell stiffness and cell volume. As a cell spreads on a substrate, its volume decreases, while its stiffness concomitantly increases. We find that both cortical and cytoplasmic cell stiffness scale with volume for numerous perturbations, including varying substrate stiffness, cell spread area, and external osmotic pressure. The reduction of cell volume is a result of water efflux, which leads to a corresponding increase in intracellular molecular crowding. Furthermore, we find that changes in cell volume, and hence stiffness, alter stem-cell differentiation, regardless of the method by which these are induced. These observations reveal a surprising, previously unidentified relationship between cell stiffness and cell volume that strongly influences cell biology. PMID:28973866

A Case of Desmoplastic Small Round Cell Tumor.

PubMed

Reisner, David; Brahee, Deborah; Patel, Shweta; Hartman, Matthew

2015-08-01

Desmoplastic small round cell tumor is a rare, aggressive tumor primarily affecting young males. It is considered a childhood cancer, and is characterized by a unique chromosomal translocation which leads to failure to suppress tumor growth. It is classified as a soft tissue sarcoma, sharing some features with other small round cell tumors such as Ewing's Sarcoma and primitive neuroectodermal tumor. Typical imaging findings include multiple heterogeneous, lobular abdominal masses, which can grow very large. Often there is a dominant mass with additional peritoneal, omental, retroperitoneal and retrovesical masses. Prognosis is relatively poor with a 3 year survival rate of 50% in those treated aggressively with surgical resection, chemotherapy, and radiation therapy. The clinical presentation, imaging characteristics and pathology are discussed in regards to a recent case.

Next Generation, 4-D Distributed Modeling and Visualization of Battlefield

DTIC Science & Technology

2006-07-14

accurate. However, the effectiveness of such a view is determined by its usability. If the picture contained all the information that had been...major key to success in such missions is the ability to model real-world urban areas accurately and effectively , so as to support US military mission...primitives (including the standard CG primitives such as plane, cube, wedge, polyhedron, cylinder and sphere, and high-order surface primitives such as

A Guide to FASTGEN Target Geometric Modeling

DTIC Science & Technology

1993-10-01

component part is described in plate mode. These rules apply to all primitives with the exception of rod mode primitives which are always accompanied by a...format. A detailed discussion of the rules for preparing the target description file, where components are described using primitives defined as triangles...NN position is 99, the diameter of a rod mode component is limited to a maximum of 1.98-inches. Theie are several rules and cautions associated with

Hydrostatic calculations of axisymmetric flow and its stability for the AGCE model

NASA Technical Reports Server (NTRS)

Miller, T. L.; Gall, R. L.

1981-01-01

Baroclinic waves in the atmospherics general circulation experiment (AGCE) apparatus by the use of numerical hydrostatic primitive equation models were determined. The calculation is accomplished by using an axisymmetric primitive equation model to compute, for a given set of experimental parameters, a steady state axisymmetric flow and then testing this axisymmetric flow for stability using a linear primitive equation model. Some axisymmetric flows are presented together with preliminary stability calculations.

Cave men: stone tools, Victorian science, and the 'primitive mind' of deep time.

PubMed

Pettitt, Paul B; White, Mark J

2011-03-20

Palaeoanthropology, the study of the evolution of humanity, arose in the nineteenth century. Excavations in Europe uncovered a series of archaeological sediments which provided proof that the antiquity of human life on Earth was far longer than the biblical six thousand years, and by the 1880s authors had constructed a basic paradigm of what 'primitive' human life was like. Here we examine the development of Victorian palaeoanthropology for what it reveals of the development of notions of cognitive evolution. It seems that Victorian specialists rarely addressed cognitive evolution explicitly, although several assumptions were generally made that arose from preconceptions derived from contemporary 'primitive' peoples. We identify three main phases of development of notions of the primitive mind in the period.

Primitive neuroectodermal tumor of the cervix: a case report

PubMed Central

2011-01-01

Introduction Peripheral primitive neuroectodermal tumor of the cervix uteri is extremely rare. Between 1987 and 2010, there were only nine cases reported in the English literature, with considerably different management policies. Case presentation A 45-year-old Iranian woman presented to our facility with a primitive neuroectodermal tumor of the cervix uteri. Her clinical stage IB2 tumor was treated successfully with chemotherapy. Our patient underwent radical hysterectomy. There was no trace of the tumor after four years of follow-up. Conclusions According to current knowledge, primitive neuroectodermal tumors belong to the Ewing's sarcoma family, and the improvement of treatment outcome in our patient was due to dose-intensive neoadjuvant chemotherapy, surgery and consolidation chemotherapy in accordance with the protocol for bony Ewing's sarcoma. PMID:21962148

Insights to primitive replication derived from structures of small oligonucleotides

NASA Technical Reports Server (NTRS)

Smith, G. K.; Fox, G. E.

1995-01-01

Available information on the structure of small oligonucleotides is surveyed. It is observed that even small oligomers typically exhibit defined structures over a wide range of pH and temperature. These structures rely on a plethora of non-standard base-base interactions in addition to the traditional Watson-Crick pairings. Stable duplexes, though typically antiparallel, can be parallel or staggered and perfect complementarity is not essential. These results imply that primitive template directed reactions do not require high fidelity. Hence, the extensive use of Watson-Crick complementarity in genes rather than being a direct consequence of the primitive condensation process, may instead reflect subsequent selection based on the advantage of accuracy in maintaining the primitive genetic machinery once it arose.

Decoding the Regulatory Network for Blood Development from Single-Cell Gene Expression Measurements

PubMed Central

Haghverdi, Laleh; Lilly, Andrew J.; Tanaka, Yosuke; Wilkinson, Adam C.; Buettner, Florian; Macaulay, Iain C.; Jawaid, Wajid; Diamanti, Evangelia; Nishikawa, Shin-Ichi; Piterman, Nir; Kouskoff, Valerie; Theis, Fabian J.; Fisher, Jasmin; Göttgens, Berthold

2015-01-01

Here we report the use of diffusion maps and network synthesis from state transition graphs to better understand developmental pathways from single cell gene expression profiling. We map the progression of mesoderm towards blood in the mouse by single-cell expression analysis of 3,934 cells, capturing cells with blood-forming potential at four sequential developmental stages. By adapting the diffusion plot methodology for dimensionality reduction to single-cell data, we reconstruct the developmental journey to blood at single-cell resolution. Using transitions between individual cellular states as input, we develop a single-cell network synthesis toolkit to generate a computationally executable transcriptional regulatory network model that recapitulates blood development. Model predictions were validated by showing that Sox7 inhibits primitive erythropoiesis, and that Sox and Hox factors control early expression of Erg. We therefore demonstrate that single-cell analysis of a developing organ coupled with computational approaches can reveal the transcriptional programs that control organogenesis. PMID:25664528

Numeric and volumetric changes in Leydig cells during aging of rats.

PubMed

Neves, Bruno Vinicius Duarte; Lorenzini, Fernando; Veronez, Djanira; Miranda, Eduardo Pereira de; Neves, Gabriela Duarte; Fraga, Rogério de

2017-10-01

To analyze the effects of aging in rats on the nuclear volume, cytoplasmic volume, and total volume of Leydig cells, as well as their number. Seventy-two Wistar rats were divided into six subgroups of 12 rats, which underwent right orchiectomy at 3, 6, 9, 12, 18, and 24 months of age. The weight and volume of the resected testicles were assessed. A stereological study of Leydig cells was conducted, which included measurements of cell number and nuclear, cytoplasmic, and total cell volumes. The weight and volume of the resected testicles showed reductions with age. Only the subgroup composed of 24-month old rats showed a decrease in the nuclear volume of Leydig cells. Significant reductions in the cytoplasmic volume and total volume of Leydig cells were observed in 18- and 24-month old rats. The number of Leydig cells did not vary significantly with age. Aging in rats resulted in reduction of the nuclear, cytoplasmic, and total cell volumes of Leydig cells. There was no change in the total number of these cells during aging.

A new genus and species of tettigarctid cicada from the early Miocene of New Zealand: Paratettigarcta zealandica (Hemiptera, Auchenorrhyncha, Tettigarctidae)

PubMed Central

Kaulfuss, Uwe; Moulds, Max

2015-01-01

Abstract A new genus and species of primitive cicada (Hemiptera: Tettigarctidae) is described from the early Miocene of southern New Zealand. Paratettigarcta zealandica gen. et sp. n. is the first cicada (Cicadoidea) fossil from New Zealand and exhibits wing venation patterns typical for the subfamily Tettigarctinae. It differs from other fossil taxa and the extant genus Tettigarcta in the early divergence of CuA2 from the nodal line in the forewing, its parallel-sided subcostal cell, the early bifurcation of vein M and long apical cells of the hindwing, and in wing pigmentation patterns. PMID:25829843

A new genus and species of tettigarctid cicada from the early Miocene of New Zealand: Paratettigarctazealandica (Hemiptera, Auchenorrhyncha, Tettigarctidae).

PubMed

Kaulfuss, Uwe; Moulds, Max

2015-01-01

A new genus and species of primitive cicada (Hemiptera: Tettigarctidae) is described from the early Miocene of southern New Zealand. Paratettigarctazealandica gen. et sp. n. is the first cicada (Cicadoidea) fossil from New Zealand and exhibits wing venation patterns typical for the subfamily Tettigarctinae. It differs from other fossil taxa and the extant genus Tettigarcta in the early divergence of CuA2 from the nodal line in the forewing, its parallel-sided subcostal cell, the early bifurcation of vein M and long apical cells of the hindwing, and in wing pigmentation patterns.

Cilengitide in Treating Children With Refractory Primary Brain Tumors

ClinicalTrials.gov

2013-09-27

Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Temozolomide and O6-Benzylguanine in Treating Children With Recurrent Brain Tumors

ClinicalTrials.gov

2013-09-27

Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Lenalidomide in Treating Young Patients With Recurrent, Progressive, or Refractory CNS Tumors

ClinicalTrials.gov

2013-09-27

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; BRAF NP_004324.2:p.V600X; Ependymoma; Ewing Sarcoma; Hepatoblastoma; Histiocytosis; Langerhans Cell Histiocytosis; Malignant Germ Cell Tumor; Malignant Glioma; Osteosarcoma; Peripheral Primitive Neuroectodermal Tumor; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Refractory Central Nervous System Neoplasm; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Rhabdoid Tumor; Rhabdomyosarcoma; Soft Tissue Sarcoma; Wilms Tumor

Cognitive functions of intracellular mechanisms for contextual amplification.

PubMed

Phillips, William A

2017-03-01

Evidence for the hypothesis that input to the apical tufts of neocortical pyramidal cells plays a central role in cognition by amplifying their responses to feedforward input is reviewed. Apical tufts are electrically remote from the soma, and their inputs come from diverse sources including direct feedback from higher cortical regions, indirect feedback via the thalamus, and long-range lateral connections both within and between cortical regions. This suggests that input to tuft dendrites may amplify the cell's response to basal inputs that they receive via layer 4 and which have synapses closer to the soma. ERP data supporting this inference is noted. Intracellular studies of apical amplification (AA) and of disamplification by inhibitory interneurons targeted only at tufts are reviewed. Cognitive processes that have been related to them by computational, electrophysiological, and psychopathological studies are then outlined. These processes include: figure-ground segregation and Gestalt grouping; contextual disambiguation in perception and sentence comprehension; priming; winner-take-all competition; attention and working memory; setting the level of consciousness; cognitive control; and learning. It is argued that theories in cognitive neuroscience should not assume that all neurons function as integrate-and-fire point processors, but should use the capabilities of cells with distinct sites of integration for driving and modulatory inputs. Potentially 'unifying' theories that depend upon these capabilities are reviewed. It is concluded that evolution of the primitives of AA and disamplification in neocortex may have extended cognitive capabilities beyond those built from the long-established primitives of excitation, inhibition, and disinhibition. Copyright © 2015 Elsevier Inc. All rights reserved.

Intrinsic factors and the embryonic environment influence the formation of extragonadal teratomas during gestation.

PubMed

Economou, Constantinos; Tsakiridis, Anestis; Wymeersch, Filip J; Gordon-Keylock, Sabrina; Dewhurst, Robert E; Fisher, Dawn; Medvinsky, Alexander; Smith, Andrew J H; Wilson, Valerie

2015-10-09

Pluripotent cells are present in early embryos until the levels of the pluripotency regulator Oct4 drop at the beginning of somitogenesis. Elevating Oct4 levels in explanted post-pluripotent cells in vitro restores their pluripotency. Cultured pluripotent cells can participate in normal development when introduced into host embryos up to the end of gastrulation. In contrast, pluripotent cells efficiently seed malignant teratocarcinomas in adult animals. In humans, extragonadal teratomas and teratocarcinomas are most frequently found in the sacrococcygeal region of neonates, suggesting that these tumours originate from cells in the posterior of the embryo that either reactivate or fail to switch off their pluripotent status. However, experimental models for the persistence or reactivation of pluripotency during embryonic development are lacking. We manually injected embryonic stem cells into conceptuses at E9.5 to test whether the presence of pluripotent cells at this stage correlates with teratocarcinoma formation. We then examined the effects of reactivating embryonic Oct4 expression ubiquitously or in combination with Nanog within the primitive streak (PS)/tail bud (TB) using a transgenic mouse line and embryo chimeras carrying a PS/TB-specific heterologous gene expression cassette respectively. Here, we show that pluripotent cells seed teratomas in post-gastrulation embryos. However, at these stages, induced ubiquitous expression of Oct4 does not lead to restoration of pluripotency (indicated by Nanog expression) and tumour formation in utero, but instead causes a severe phenotype in the extending anteroposterior axis. Use of a more restricted T(Bra) promoter transgenic system enabling inducible ectopic expression of Oct4 and Nanog specifically in the posteriorly-located primitive streak (PS) and tail bud (TB) led to similar axial malformations to those induced by Oct4 alone. These cells underwent induction of pluripotency marker expression in Epiblast Stem Cell (EpiSC) explants derived from somitogenesis-stage embryos, but no teratocarcinoma formation was observed in vivo. Our findings show that although pluripotent cells with teratocarcinogenic potential can be produced in vitro by the overexpression of pluripotency regulators in explanted somitogenesis-stage somatic cells, the in vivo induction of these genes does not yield tumours. This suggests a restrictive regulatory role of the embryonic microenvironment in the induction of pluripotency.

ARCGRAPH SYSTEM - AMES RESEARCH GRAPHICS SYSTEM

NASA Technical Reports Server (NTRS)

Hibbard, E. A.

1994-01-01

Ames Research Graphics System, ARCGRAPH, is a collection of libraries and utilities which assist researchers in generating, manipulating, and visualizing graphical data. In addition, ARCGRAPH defines a metafile format that contains device independent graphical data. This file format is used with various computer graphics manipulation and animation packages at Ames, including SURF (COSMIC Program ARC-12381) and GAS (COSMIC Program ARC-12379). In its full configuration, the ARCGRAPH system consists of a two stage pipeline which may be used to output graphical primitives. Stage one is associated with the graphical primitives (i.e. moves, draws, color, etc.) along with the creation and manipulation of the metafiles. Five distinct data filters make up stage one. They are: 1) PLO which handles all 2D vector primitives, 2) POL which handles all 3D polygonal primitives, 3) RAS which handles all 2D raster primitives, 4) VEC which handles all 3D raster primitives, and 5) PO2 which handles all 2D polygonal primitives. Stage two is associated with the process of displaying graphical primitives on a device. To generate the various graphical primitives, create and reprocess ARCGRAPH metafiles, and access the device drivers in the VDI (Video Device Interface) library, users link their applications to ARCGRAPH's GRAFIX library routines. Both FORTRAN and C language versions of the GRAFIX and VDI libraries exist for enhanced portability within these respective programming environments. The ARCGRAPH libraries were developed on a VAX running VMS. Minor documented modification of various routines, however, allows the system to run on the following computers: Cray X-MP running COS (no C version); Cray 2 running UNICOS; DEC VAX running BSD 4.3 UNIX, or Ultrix; SGI IRIS Turbo running GL2-W3.5 and GL2-W3.6; Convex C1 running UNIX; Amhdahl 5840 running UTS; Alliant FX8 running UNIX; Sun 3/160 running UNIX (no native device driver); Stellar GS1000 running Stellex (no native device driver); and an SGI IRIS 4D running IRIX (no native device driver). Currently with version 7.0 of ARCGRAPH, the VDI library supports the following output devices: A VT100 terminal with a RETRO-GRAPHICS board installed, a VT240 using the Tektronix 4010 emulation capability, an SGI IRIS turbo using the native GL2 library, a Tektronix 4010, a Tektronix 4105, and the Tektronix 4014. ARCGRAPH version 7.0 was developed in 1988.

Retroviral envelope syncytin capture in an ancestrally diverged mammalian clade for placentation in the primitive Afrotherian tenrecs

PubMed Central

Cornelis, Guillaume; Vernochet, Cécile; Malicorne, Sébastien; Souquere, Sylvie; Tzika, Athanasia C.; Goodman, Steven M.; Catzeflis, François; Robinson, Terence J.; Milinkovitch, Michel C.; Pierron, Gérard; Heidmann, Odile; Dupressoir, Anne; Heidmann, Thierry

2014-01-01

Syncytins are fusogenic envelope (env) genes of retroviral origin that have been captured for a function in placentation. Syncytins have been identified in Euarchontoglires (primates, rodents, Leporidae) and Laurasiatheria (Carnivora, ruminants) placental mammals. Here, we searched for similar genes in species that retained characteristic features of primitive mammals, namely the Malagasy and mainland African Tenrecidae. They belong to the superorder Afrotheria, an early lineage that diverged from Euarchotonglires and Laurasiatheria 100 Mya, during the Cretaceous terrestrial revolution. An in silico search for env genes with full coding capacity within a Tenrecidae genome identified several candidates, with one displaying placenta-specific expression as revealed by RT-PCR analysis of a large panel of Setifer setosus tissues. Cloning of this endogenous retroviral env gene demonstrated fusogenicity in an ex vivo cell–cell fusion assay on a panel of mammalian cells. Refined analysis of placental architecture and ultrastructure combined with in situ hybridization demonstrated specific expression of the gene in multinucleate cellular masses and layers at the materno–fetal interface, consistent with a role in syncytium formation. This gene, which we named “syncytin-Ten1,” is conserved among Tenrecidae, with evidence of purifying selection and conservation of fusogenic activity. To our knowledge, it is the first syncytin identified to date within the ancestrally diverged Afrotheria superorder. PMID:25267646

Evolutionary and Functional Relationships of B Cells from Fish and Mammals: Insights into their Novel Roles in Phagocytosis and Presentation of Particulate Antigen

PubMed Central

Sunyer, J. Oriol

2012-01-01

The evolutionary origins of Ig-producing B cells appear to be linked to the emergence of fish in this planet. There are three major classes of living fish species, which from most primitive to modern they are referred to as agnathan (e.g., lampreys), Chondrichthyes (e.g., sharks), and teleost fish (e.g., rainbow trout). Agnathans do not have immunoglobulin-producing B cells, however these fish contain a subset of lymphocytes-like cells producing type B variable lymphocyte receptors (VLRBs) that appear to act as functional analogs of immunoglobulins. Chondrichthyes fish represent the most primitive living species containing bona-fide immunoglobulin-producing B cells. Their B cells are known to secrete three types of antibodies, IgM, IgW and IgNAR. Teleost fish are also called bony fish since they represent the most ancient living species containing true bones. Teleost B cells produce three different immunoglobulin isotypes, IgM, IgD and the recently described IgT. While teleost IgM is the principal player in systemic immunity, IgT appears to be a teleost immunoglobulin class specialized in mucosal immune responses. Thus far, three major B cell lineages have been described in teleost, those expressing either IgT or IgD, and the most common lineage which co-expresses IgD and IgM. A few years ago, the study of teleost fish B cells revealed for the first time in vertebrates the existence of B cell subsets with phagocytic and intracellular bactericidal capacities. This finding represented a paradigm shift as professional phagocytosis was believed to be exclusively performed by some cells of the myeloid lineage (i.e., macrophages, monocytes, neutrophils). This phagocytic capacity was also found in amphibians and reptiles, suggesting that this innate capacity was evolutionarily conserved in certain B cell subsets of vertebrates. Recently, the existence of subsets of B cells with phagocytic and bactericidal abilities have also been confirmed in mammals. Moreover, it has been shown that phagocytic B-1 B cells have a potent ability to present particulate antigen to CD4+ T cells. Thus, studies carried out originally on fish B cells have lead to the discovery of new innate and adaptive roles of B cells in mammals. This review will concentrate on the evolutionary and functional relationships of fish and mammalian B cells, focusing mainly on the newly discovered roles of these cells in phagocytosis, intracellular killing and presentation of particulate antigen. PMID:22394174

PRIMitive Asteroids Spectroscopic Survey - PRIMASS: First Results

NASA Astrophysics Data System (ADS)

de Leon, Julia; Pinilla-Alonso, Noemi; Campins, Humberto; Lorenzi, Vania; Licandro, Javier; Morate, David; Tanga, Paolo; Cellino, Alberto; Delbo, Marco

2015-11-01

NASA OSIRIS-REx and JAXA Hayabusa 2 sample-return missions have targeted two near-Earth asteroids: (101955) Bennu and (162173) 1999 JU3, respectively. These are primitive asteroids that are believed to originate in the inner belt, where five distinct sources have been identified: four primitive collisional families (Polana, Erigone, Sulamitis, and Clarissa), and a population of low-albedo and low-inclination background asteroids. Identifying and characterizing the populations from which these two NEAs might originate will enchance the science return of the two missions.With this main objective in mind, we initiated in 2010 a spectroscopic survey in the visible and the near-infrared to characterize the primitive collisional families in the inner belt and the low-albedo background population. This is the PRIMitive Asteroids Spectroscopic Survey - PRIMASS. So far we have obtained more than 200 spectra using telescopes located at different observatories. PRIMASS uses a variety of ground based facilities. Most of the spectra have been obtained using the 10.4m Gran Telescopio Canarias (GTC), and the 3.6m Telescopio Nazionale Galileo (TNG), both located at the El Roque de los Muchachos Observatory (La Palma, Spain), and the 3.0m NASA Infrared Telescope Facility on Mauna Kea (Hawai, USA).We present the first results from our on-going survey (de Leon et al. 2015; Pinilla-Alonso et al. 2015; Morate et al. 2015), focused on the Polana and the Erigone primitive families, with visible and near-infrared spectra of more than 200 objects, most of them with no previous spectroscopic data. Our survey is already the largest database of primitive asteroids spectra, and we keep obtaining data on the Sulamitis and the Clarissa families, as well as on the background low-albedo population.

UNCOMPAHGRE PRIMITIVE AREA, COLORADO.

USGS Publications Warehouse

Luedke, R.G.; Sheridan, M.J.

1984-01-01

A mineral-resource study was made of that part of the Uncompahgre National Forest, Colorado constituting the officially designated primitive area. Because the primitive area and its southern border zone contained operating mines producing gold, silver, copper, lead, zinc, and minor amounts of a few other metals, and had been a part of a highly productive mining region, the area was concluded to have large segments of both probable and substantiated mineral-resource potential. No energy resources were identified in the study.

Primitive myxoid mesenchymal tumor of infancy in a preterm infant.

PubMed

Lam, Joseph; Lara-Corrales, Irene; Cammisuli, Salvatore; Somers, Gino R; Pope, Elena

2010-01-01

Primitive myxoid mesenchymal tumor of infancy is a recently recognized entity that has been added to the differential diagnosis of myxoid tumors of the soft tissue. Few cases have been reported of this entity in the literature, but none presenting in a preterm infant. We present the case and clinical course of a preterm boy with a primitive myxoid mesenchymal tumor of infancy that occurred following excision of a congenital juvenile xanthogranuloma. © 2010 Wiley Periodicals, Inc.

HIGH UINTAS PRIMITIVE AREA, UTAH.

USGS Publications Warehouse

Crittenden, Max D.; Sheridan, Michael J.

1984-01-01

Mineral surveys in the High Uintas Primitive Area, Utah and the additions subsequently proposed concluded that the area has little promise for mineral resources. Of the areas around the fringes, a strip along the north flank fault can be classed as having probable energy-resource potential for oil and gas. The oil and gas potential could be tested by additional seismic studies followed by drilling. Much of the necessary information probably could be obtained without drilling within the primitive area itself.

Intrapartum Synthetic Oxytocin Reduce the Expression of Primitive Reflexes Associated with Breastfeeding

PubMed Central

Olza Fernández, Ibone; Malalana Martínez, Ana M.; González Armengod, Carmen; Costarelli, Valeria; Millán Santos, Isabel; Fernández-Cañadas Morillo, Aurora; Pérez Riveiro, Pilar; López Sánchez, Francisco; García Murillo, Lourdes

2015-01-01

Abstract Aim: Several synthetic peptide manipulations during the time surrounding birth can alter the specific neurohormonal status in the newborn brain. This study is aimed at assessing whether intrapartum oxytocin administration has any effect on primitive neonatal reflexes and determining whether such an effect is dose-dependent. Materials and Methods: A cohort prospective study was conducted at a tertiary hospital. Mother–infant dyads who received intrapartum oxytocin (n=53) were compared with mother–infant dyads who did not receive intrapartum oxytocin (n=45). Primitive neonatal reflexes (endogenous, antigravity, motor, and rhythmic reflexes) were quantified by analyzing videotaped breastfeeding sessions in a biological nurturing position. Two observers blind to the group assignment and the oxytocin dose analyzed the videotapes and assesed the newborn's state of consciousness according to the Brazelton scale. Results: The release of all rhythmic reflexes (p=0.01), the antigravity reflex (p=0.04), and total primitive neonatal reflexes (p=0.02) in the group exposed to oxytocin was lower than in the group not exposed to oxytocin. No correlations were observed between the dose of oxytocin administered and the percentage of primitive neonatal reflexes released (r=0.03; p=0.82). Conclusions: Intrapartum oxytocin administration might inhibit the expression of several primitive neonatal reflexes associated with breastfeeding. This correlation does not seem to be dose-dependent. PMID:25785487

Data management for the internet of things: design primitives and solution.

PubMed

Abu-Elkheir, Mervat; Hayajneh, Mohammad; Ali, Najah Abu

2013-11-14

The Internet of Things (IoT) is a networking paradigm where interconnected, smart objects continuously generate data and transmit it over the Internet. Much of the IoT initiatives are geared towards manufacturing low-cost and energy-efficient hardware for these objects, as well as the communication technologies that provide objects interconnectivity. However, the solutions to manage and utilize the massive volume of data produced by these objects are yet to mature. Traditional database management solutions fall short in satisfying the sophisticated application needs of an IoT network that has a truly global-scale. Current solutions for IoT data management address partial aspects of the IoT environment with special focus on sensor networks. In this paper, we survey the data management solutions that are proposed for IoT or subsystems of the IoT. We highlight the distinctive design primitives that we believe should be addressed in an IoT data management solution, and discuss how they are approached by the proposed solutions. We finally propose a data management framework for IoT that takes into consideration the discussed design elements and acts as a seed to a comprehensive IoT data management solution. The framework we propose adapts a federated, data- and sources-centric approach to link the diverse Things with their abundance of data to the potential applications and services that are envisioned for IoT.

Data Management for the Internet of Things: Design Primitives and Solution

PubMed Central

Abu-Elkheir, Mervat; Hayajneh, Mohammad; Ali, Najah Abu

2013-01-01

The Internet of Things (IoT) is a networking paradigm where interconnected, smart objects continuously generate data and transmit it over the Internet. Much of the IoT initiatives are geared towards manufacturing low-cost and energy-efficient hardware for these objects, as well as the communication technologies that provide objects interconnectivity. However, the solutions to manage and utilize the massive volume of data produced by these objects are yet to mature. Traditional database management solutions fall short in satisfying the sophisticated application needs of an IoT network that has a truly global-scale. Current solutions for IoT data management address partial aspects of the IoT environment with special focus on sensor networks. In this paper, we survey the data management solutions that are proposed for IoT or subsystems of the IoT. We highlight the distinctive design primitives that we believe should be addressed in an IoT data management solution, and discuss how they are approached by the proposed solutions. We finally propose a data management framework for IoT that takes into consideration the discussed design elements and acts as a seed to a comprehensive IoT data management solution. The framework we propose adapts a federated, data- and sources-centric approach to link the diverse Things with their abundance of data to the potential applications and services that are envisioned for IoT. PMID:24240599

Probabilistic Evaluation of Advanced Ceramic Matrix Composite Structures

NASA Technical Reports Server (NTRS)

Abumeri, Galib H.; Chamis, Christos C.

2003-01-01

The objective of this report is to summarize the deterministic and probabilistic structural evaluation results of two structures made with advanced ceramic composites (CMC): internally pressurized tube and uniformly loaded flange. The deterministic structural evaluation includes stress, displacement, and buckling analyses. It is carried out using the finite element code MHOST, developed for the 3-D inelastic analysis of structures that are made with advanced materials. The probabilistic evaluation is performed using the integrated probabilistic assessment of composite structures computer code IPACS. The affects of uncertainties in primitive variables related to the material, fabrication process, and loadings on the material property and structural response behavior are quantified. The primitive variables considered are: thermo-mechanical properties of fiber and matrix, fiber and void volume ratios, use temperature, and pressure. The probabilistic structural analysis and probabilistic strength results are used by IPACS to perform reliability and risk evaluation of the two structures. The results will show that the sensitivity information obtained for the two composite structures from the computational simulation can be used to alter the design process to meet desired service requirements. In addition to detailed probabilistic analysis of the two structures, the following were performed specifically on the CMC tube: (1) predicted the failure load and the buckling load, (2) performed coupled non-deterministic multi-disciplinary structural analysis, and (3) demonstrated that probabilistic sensitivities can be used to select a reduced set of design variables for optimization.

Composition and origin of basaltic magma of the Hawaiian Islands

USGS Publications Warehouse

Powers, H.A.

1955-01-01

Silica-saturated basaltic magma is the source of the voluminous lava flows, erupted frequently and rapidly in the primitive shield-building stage of activity, that form the bulk of each Hawaiian volcano. This magma may be available in batches that differ slightly in free silica content from batch to batch both at the same and at different volcanoes; differentiation by fractionation of olivine does not occur within this primitive magma. Silica-deficient basaltic magma, enriched in alkali, is the source of commonly porphyritic lava flows erupted less frequently and in relatively negligible volume during a declining and decadent stage of activity at some Hawaiian volcanoes. Differentiation by fractionation of olivine, plagioclase and augite is evident among these lavas, but does not account for the silica deficiency or the alkali enrichment. Most of the data of Hawaiian volcanism and petrology can be explained by a hypothesis that batches of magma are melted from crystalline paridotite by a recurrent process (distortion of the equatorial bulge by forced and free nutational stresses) that accomplishes the melting only of the plagioclase and pyroxene component but not the excess olivine and more refractory components within a zone of fixed and limited depth. Eruption exhausts the supply of meltable magma under a given locality and, in the absence of more violent melting processes, leaves a stratum of crystalline refractory components. ?? 1955.

A subjective study and an objective metric to quantify the granularity level of textures

NASA Astrophysics Data System (ADS)

Subedar, Mahesh M.; Karam, Lina J.

2015-03-01

Texture granularity is an important visual characteristic that is useful in a variety of applications, including analysis, recognition, and compression, to name a few. A texture granularity measure can be used to quantify the perceived level of texture granularity. The granularity level of the textures is influenced by the size of the texture primitives. A primitive is defined as the smallest recognizable repetitive object in the texture. If the texture has large primitives then the perceived granularity level tends to be lower as compared to a texture with smaller primitives. In this work we are presenting a texture granularity database referred as GranTEX which consists of 30 textures with varying levels of primitive sizes and granularity levels. The GranTEX database consists of both natural and man-made textures. A subjective study is conducted to measure the perceived granularity level of textures present in the GranTEX database. An objective metric that automatically measures the perceived granularity level of textures is also presented as part of this work. It is shown that the proposed granularity metric correlates well with the subjective granularity scores.

Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women.

PubMed

White, Yvonne A R; Woods, Dori C; Takai, Yasushi; Ishihara, Osamu; Seki, Hiroyuki; Tilly, Jonathan L

2012-02-26

Germline stem cells that produce oocytes in vitro and fertilization-competent eggs in vivo have been identified in and isolated from adult mouse ovaries. Here we describe and validate a fluorescence-activated cell sorting-based protocol that can be used with adult mouse ovaries and human ovarian cortical tissue to purify rare mitotically active cells that have a gene expression profile that is consistent with primitive germ cells. Once established in vitro, these cells can be expanded for months and can spontaneously generate 35- to 50-μm oocytes, as determined by morphology, gene expression and haploid (1n) status. Injection of the human germline cells, engineered to stably express GFP, into human ovarian cortical biopsies leads to formation of follicles containing GFP-positive oocytes 1-2 weeks after xenotransplantation into immunodeficient female mice. Thus, ovaries of reproductive-age women, similar to adult mice, possess rare mitotically active germ cells that can be propagated in vitro as well as generate oocytes in vitro and in vivo.

Melatonin and its precursors in Y79 human retinoblastoma cells - Effect of sodium butyrate

NASA Technical Reports Server (NTRS)

Deng, Mei H.; Lopez G.-Coviella, Ignacio; Lynch, Harry J.; Wurtman, Richard J.

1991-01-01

We studied the release of melatonin and the production of its precursors, 5-hydroxytryptophan and serotonin, in cultured Y79 human retinoblastoma cells. This biosynthetic capability was found to be dependent on cell differentiation, which was initiated by culturing Y79 cells for 7 days in dishes coated with poly-D-lysine to promote cell adhesion to the surface of the culture dishes. Differentiation was further induced by exposing the cell monolayer to sodium butyrate (3 mM) for three days. This protocol dramatically increased the release of melatonin, and the syntheses of 5-hydroxytryptophan and serotonin in response to forskolin stimulation. Exposure to dopamine or L-DOPA markedly diminished the forskolin-stimulated release of melatonin, as well as the production of 5-hydroxytryptophan and serotonin. These observations indicate that Y79 cells represent a primitive cell line which, following appropriate differentiation can display biochemical characteristics similar to those of the human retina. Moreover, serotonin synthesis and melatonin release appear to be coupled in Y79 ceils.

Mammary stem cells: angels or demons in mammary gland?

PubMed

Chen, Xueman; Liu, Qiang; Song, Erwei

2017-01-01

A highly dynamic development process exits within the epithelia of mammary gland, featuring morphogenetic variation during puberty, pregnancy, lactation, and regression. The identification of mammary stem cells (MaSCs) via lineage-tracing studies has substantiated a hierarchical organization of the mammary epithelia. A single MaSC is capable of reconstituting the entirely functional mammary gland upon orthotopic transplantation. Although different mammary cell subpopulations can be candidate cells-of-origin for distinct breast tumor subtypes, it still lacks experimental proofs whether MaSCs, the most primitive cells, are the 'seeds' of malignant transformation during most, if not all, tumorigenesis in the breast. Here, we review current knowledge of mammary epithelial hierarchy, highlighting the roles of mammary stem/progenitor cells and breast cancer stem cells (BCSCs) along with their key molecular regulators in organ development and cancer evolution. Clarifying these issues will pave the way for developing novel interventions toward stem/progenitor cells in either prevention or treatment of breast cancer (BrCa).

Mammary stem cells: angels or demons in mammary gland?

PubMed Central

Chen, Xueman; Liu, Qiang; Song, Erwei

2017-01-01

A highly dynamic development process exits within the epithelia of mammary gland, featuring morphogenetic variation during puberty, pregnancy, lactation, and regression. The identification of mammary stem cells (MaSCs) via lineage-tracing studies has substantiated a hierarchical organization of the mammary epithelia. A single MaSC is capable of reconstituting the entirely functional mammary gland upon orthotopic transplantation. Although different mammary cell subpopulations can be candidate cells-of-origin for distinct breast tumor subtypes, it still lacks experimental proofs whether MaSCs, the most primitive cells, are the ‘seeds’ of malignant transformation during most, if not all, tumorigenesis in the breast. Here, we review current knowledge of mammary epithelial hierarchy, highlighting the roles of mammary stem/progenitor cells and breast cancer stem cells (BCSCs) along with their key molecular regulators in organ development and cancer evolution. Clarifying these issues will pave the way for developing novel interventions toward stem/progenitor cells in either prevention or treatment of breast cancer (BrCa). PMID:29263909

Pluripotent Stem Cells in Research and Treatment of Hemoglobinopathies

PubMed Central

Arora, Natasha; Daley, George Q.

2012-01-01

Pluripotent stem cells (PSCs) hold great promise for research and treatment of hemoglobinopathies. In principle, patient-specific induced pluripotent stem cells could be derived from a blood sample, genetically corrected to repair the disease-causing mutation, differentiated into hematopoietic stem cells (HSCs), and returned to the patient to provide a cure through autologous gene and cell therapy. However, there are many challenges at each step of this complex treatment paradigm. Gene repair is currently inefficient in stem cells, but use of zinc finger nucleases and transcription activator-like effector nucleases appear to be a major advance. To date, no successful protocol exists for differentiating PSCs into definitive HSCs. PSCs can be directly differentiated into primitive red blood cells, but not yet in sufficient numbers to enable treating patients, and the cost of clinical scale differentiation is prohibitively expensive with current differentiation methods and efficiencies. Here we review the progress, promise, and remaining hurdles in realizing the potential of PSCs for cell therapy. PMID:22474618

Human trabecular meshwork cell volume decrease by NO-independent soluble guanylate cyclase activators YC-1 and BAY-58-2667 involves the BKCa ion channel.

PubMed

Dismuke, William M; Sharif, Najam A; Ellis, Dorette Z

2009-07-01

There is a correlation between cell volume changes and changes in the rate of aqueous humor outflow; agents that decrease trabecular meshwork (TM) cell volume increase the rate of aqueous humor outflow. This study investigated the effects of the nitric oxide (NO)-independent activators of soluble guanylate cyclase (sGC), YC-1, and BAY-58-2667 on TM cell volume and the signal transduction pathways and ion channel involved. Cell volume was measured with the use of calcein AM fluorescent dye, detected by confocal microscopy. Inhibitors and activators of sGC, 3',5'-cyclic guanosine monophosphate (cGMP), protein kinase G (PKG), and the BK(Ca) channel were used to characterize their involvement in the YC-1- and BAY-58-2667-induced regulation of TM cell volume. cGMP was assayed by an enzyme immunoassay. YC-1 (10 nM-200 microM) and BAY-58-2667 (10 nM-100 microM) each elicited a biphasic effect on TM cell volume. YC-1 (1 microM) increased TM cell volume, but higher concentrations decreased TM cell volume. Similarly, BAY-58-2667 (100 nM) increased TM cell volume, but higher concentrations decreased cell volume. The YC-1-induced cell volume decrease was mimicked by 8-Br-cGMP and abolished by the sGC inhibitor ODQ, the PKG inhibitor (RP)-8-Br-PET-cGMP-S, and the BK(Ca) channel inhibitor IBTX. The BAY-58-2667-induced cell volume decrease was mimicked by 8-Br-cGMP and was abolished by the PKG inhibitor and the BK(Ca) channel inhibitor. Unlike the YC-1 response, ODQ potentiated the BAY-58-2667-induced decreases in cell volume. These data suggest that the NO-independent decrease in TM cell volume is mediated by the sGC/cGMP/PKG pathway and involves K(+) efflux.

Accurate determination of lattice parameters based on Niggli reduced cell theory by using digitized electron diffraction micrograph.

PubMed

Yang, Yi; Cai, Canying; Lin, Jianguo; Gong, Lunjun; Yang, Qibin

2017-05-01

In this paper, we used Niggli reduced cell theory to determine lattice constants of a micro/nano crystal by using electron diffraction patterns. The Niggli reduced cell method enhanced the accuracy of lattice constant measurement obviously, because the lengths and the angles of lattice vectors of a primitive cell can be measured directly on the electron micrographs instead of a double tilt holder. With the aid of digitized algorithm and least square optimization by using three digitized micrographs, a valid reciprocal Niggli reduced cell number can be obtained. Thus a reciprocal and real Bravais lattices are acquired. The results of three examples, i.e., Mg 4 Zn 7 , an unknown phase (Precipitate phase in nickel-base superalloy) and Ba 4 Ti 13 O 30 showed that the maximum errors are 1.6% for lengths and are 0.3% for angles. Copyright © 2017 Elsevier Ltd. All rights reserved.

Stem cell and peripheral nerve injury and repair.

PubMed

Dong, Ming-min; Yi, Tian-hua

2010-10-01

Peripheral motor nerve injuries are a significant source of morbidity. Neural stem cells (NSCs), a group of relatively primitive cells, possess self-renewal ability and multidifferentiation potential. NSCs may be successfully separated from the human embryo and central nervous system (CNS) and differentiated into mature neurons and gliacytes by in vitro induction or transplantation into the body and may be differentiated into Schwann-like cells under specific conditions. It has been demonstrated that the ability of peripheral nerves to regenerate is mainly attributable to Schwann cells. NSC transplantation can promote peripheral nerve regeneration and provide a new means for treatment of peripheral nerve injury. In recent years, the study of NSCs has become a focus of many laboratories, but the biological characteristics and differentiation regulation mechanisms are not fully clear. In this article, we provide a brief review of NSC characteristics, cultivation, oriented differentiation, and clinical application. © Thieme Medical Publishers.

Eliminating Cancer Stem Cells by Targeting Embryonic Signaling Pathways.

PubMed

Oren, Ohad; Smith, B Douglas

2017-02-01

Dramatic advances have been made in the understanding of cancer over the past decade. Prime among those are better appreciation of the biology of cancer and the development of targeted therapies. Despite these improvements, however, most tumors remain refractory to anti-cancer medications and frequently recur. Cancer Stem Cells (CSCs), which in some cases express markers of pluripotency (e.g., Oct-4), share many of the molecular features of normal stem cells. These cells have been hypothesised to play a role in tumor resistance and relapse. They exhibit dependence on many primitive regulatory pathways and may be best viewed in the context of embryonic signaling pathways. In this article, we review important embryonic signaling cascades and their differential expression in CSCs. We also discuss these pathways as actionable targets for novel therapies in hopes that eliminating cancer stem cells will lead to an improvement in overall survival for patients.

Multiscale Modeling of Cardiac Cellular Energetics

PubMed Central

BASSINGTHWAIGHTE, JAMES B.; CHIZECK, HOWARD J.; ATLAS, LES E.; QIAN, HONG

2010-01-01

Multiscale modeling is essential to integrating knowledge of human physiology starting from genomics, molecular biology, and the environment through the levels of cells, tissues, and organs all the way to integrated systems behavior. The lowest levels concern biophysical and biochemical events. The higher levels of organization in tissues, organs, and organism are complex, representing the dynamically varying behavior of billions of cells interacting together. Models integrating cellular events into tissue and organ behavior are forced to resort to simplifications to minimize computational complexity, thus reducing the model’s ability to respond correctly to dynamic changes in external conditions. Adjustments at protein and gene regulatory levels shortchange the simplified higher-level representations. Our cell primitive is composed of a set of subcellular modules, each defining an intracellular function (action potential, tricarboxylic acid cycle, oxidative phosphorylation, glycolysis, calcium cycling, contraction, etc.), composing what we call the “eternal cell,” which assumes that there is neither proteolysis nor protein synthesis. Within the modules are elements describing each particular component (i.e., enzymatic reactions of assorted types, transporters, ionic channels, binding sites, etc.). Cell subregions are stirred tanks, linked by diffusional or transporter-mediated exchange. The modeling uses ordinary differential equations rather than stochastic or partial differential equations. This basic model is regarded as a primitive upon which to build models encompassing gene regulation, signaling, and long-term adaptations in structure and function. During simulation, simpler forms of the model are used, when possible, to reduce computation. However, when this results in error, the more complex and detailed modules and elements need to be employed to improve model realism. The processes of error recognition and of mapping between different levels of model form complexity are challenging but are essential for successful modeling of large-scale systems in reasonable time. Currently there is to this end no established methodology from computational sciences. PMID:16093514

Primitive African Medical Lore and Witchcraft *

PubMed Central

Thompson, Ethel E.

1965-01-01

This article presents a comprehensive study of the methods, practices, equipment, and paraphernalia of African witch doctors in carrying out primitive medical practices. The chief tribes studied are the Azandes of the Sudan, the Manos of Liberia, the Congo tribes, the Bundas of Angola, and the Zulus and other Bantu tribes of South Africa. Primitive beliefs and customs are discussed only insofar as they have a direct bearing on medical practices. The medical practices considered deal mainly with the application of general remedies for ailments and diseases, but certain specialized fields such as obstetrics, surgery, treatment for fractures, and dentistry are also included. Primitive medicaments are presented with reference to their application for various illnesses. An alphabetical list of these medicaments is given at the end of the article. PMID:14223742

Carotid-vertebrobasilar Anastomoses with Reference to Their Segmental Property.

PubMed

Namba, Katsunari

2017-06-15

The primitive carotid-vertebrobasilar anastomoses are primitive embryonic cerebral vessels that temporarily provide arterial supply from the internal carotid artery to the longitudinal neural artery, the future vertebrobasilar artery in the hindbrain. Four types known are the trigeminal, otic, hypoglossal, and proatlantal intersegmental arteries. The arteries are accompanied by their corresponding nerves and resemble an intersegmental pattern. These vessels exist in the very early period of cerebral arterial development and rapidly involute within a week. Occasionally, persistence of the carotid to vertebrobasilar anastomosis is discovered in the adult period, and is considered as the vestige of the corresponding primitive embryonic vessel. The embryonic development and the segmental property of the primitive carotid-vertebrobasilar anastomoses are discussed. This is followed by a brief description of the persisting anastomoses in adults.

Impact of Discrete Corrections in a Modular Approach for Trajectory Generation in Quadruped Robots

NASA Astrophysics Data System (ADS)

Pinto, Carla M. A.; Santos, Cristina P.; Rocha, Diana; Matos, Vítor

2011-09-01

Online generation of trajectories in robots is a very complex task that involves the combination of different types of movements, i.e., distinct motor primitives. The later are used to model complex behaviors in robots, such as locomotion in irregular terrain and obstacle avoidance. In this paper, we consider two motor primitives: rhythmic and discrete. We study the effect on the robots' gaits of superimposing the two motor primitives, considering two distinct types of coupling. Additionally, we simulate two scenarios, where the discrete primitive is inserted in all of the four limbs, or is inserted in ipsilateral pairs of limbs. Numerical results show that amplitude and frequency of the periodic solutions, corresponding to the gaits trot and pace, are almost constant for diffusive and synaptic couplings.

JAK2 mutation in a patient with CLL with coexistent myeloproliferative neoplasm (MPN).

PubMed

Kodali, Srinivas; Chen, Chi; Rathnasabapathy, Chenthilmurugan; Wang, Jen Chin

2009-12-01

JAK2 mutation has not been described in patients with chronic lymphocytic leukemia (CLL). We found JAK2 mutation in a patient with CLL and coexisting myeloproliferative neoplasm (MPN). In this patient, we demonstrated the presence of the JAK2 mutation in CD34(+) progenitor cells, myeloid lineage cells, megakaryocytes, B lymphocytes but not in T lymphocytes. This case represents the first case report of JAK2 mutation in CLL and may also suggest that, JAK2 mutation most likely represents a secondary event from primary gene mutations involving the primitive stem cells which give rise to MPN and CLL. Furthermore, in this case, we believe that we are the first to demonstrate that JAK2 mutation in myeloid and B lymphoid cells but not T lymphocytes in a case of coexisting CLL and MPN.

The human phosphotyrosine signaling network: Evolution and hotspots of hijacking in cancer

PubMed Central

Li, Lei; Tibiche, Chabane; Fu, Cong; Kaneko, Tomonori; Moran, Michael F.; Schiller, Martin R.; Li, Shawn Shun-Cheng; Wang, Edwin

2012-01-01

Phosphotyrosine (pTyr) signaling, which plays a central role in cell–cell and cell–environment interactions, has been considered to be an evolutionary innovation in multicellular metazoans. However, neither the emergence nor the evolution of the human pTyr signaling system is currently understood. Tyrosine kinase (TK) circuits, each of which consists of a TK writer, a kinase substrate, and a related reader, such as Src homology (SH) 2 domains and pTyr-binding (PTB) domains, comprise the core machinery of the pTyr signaling network. In this study, we analyzed the evolutionary trajectories of 583 literature-derived and 50,000 computationally predicted human TK circuits in 19 representative eukaryotic species and assigned their evolutionary origins. We found that human TK circuits for intracellular pTyr signaling originated largely from primitive organisms, whereas the inter- or extracellular signaling circuits experienced significant expansion in the bilaterian lineage through the “back-wiring” of newly evolved kinases to primitive substrates and SH2/PTB domains. Conversely, the TK circuits that are involved in tissue-specific signaling evolved mainly in vertebrates by the back-wiring of vertebrate substrates to primitive kinases and SH2/PTB domains. Importantly, we found that cancer signaling preferentially employs the pTyr sites, which are linked to more TK circuits. Our work provides insights into the evolutionary paths of the human pTyr signaling circuits and suggests the use of a network approach for cancer intervention through the targeting of key pTyr sites and their associated signaling hubs in the network. PMID:22194470

Quantifying chain reptation in entangled polymer melts: Topological and dynamical mapping of atomistic simulation results onto the tube model

NASA Astrophysics Data System (ADS)

Stephanou, Pavlos S.; Baig, Chunggi; Tsolou, Georgia; Mavrantzas, Vlasis G.; Kröger, Martin

2010-03-01

The topological state of entangled polymers has been analyzed recently in terms of primitive paths which allowed obtaining reliable predictions of the static (statistical) properties of the underlying entanglement network for a number of polymer melts. Through a systematic methodology that first maps atomistic molecular dynamics (MD) trajectories onto time trajectories of primitive chains and then documents primitive chain motion in terms of a curvilinear diffusion in a tubelike region around the coarse-grained chain contour, we are extending these static approaches here even further by computing the most fundamental function of the reptation theory, namely, the probability ψ(s,t) that a segment s of the primitive chain remains inside the initial tube after time t, accounting directly for contour length fluctuations and constraint release. The effective diameter of the tube is independently evaluated by observing tube constraints either on atomistic displacements or on the displacement of primitive chain segments orthogonal to the initial primitive path. Having computed the tube diameter, the tube itself around each primitive path is constructed by visiting each entanglement strand along the primitive path one after the other and approximating it by the space of a small cylinder having the same axis as the entanglement strand itself and a diameter equal to the estimated effective tube diameter. Reptation of the primitive chain longitudinally inside the effective constraining tube as well as local transverse fluctuations of the chain driven mainly from constraint release and regeneration mechanisms are evident in the simulation results; the latter causes parts of the chains to venture outside their average tube surface for certain periods of time. The computed ψ(s,t) curves account directly for both of these phenomena, as well as for contour length fluctuations, since all of them are automatically captured in the atomistic simulations. Linear viscoelastic properties such as the zero shear rate viscosity and the spectra of storage and loss moduli obtained on the basis of the obtained ψ(s,t) curves for three different polymer melts (polyethylene, cis-1,4-polybutadiene, and trans-1,4-polybutadiene) are consistent with experimental rheological data and in qualitative agreement with the double reptation and dual constraint models. The new methodology is general and can be routinely applied to analyze primitive path dynamics and chain reptation in atomistic trajectories (accumulated through long MD simulations) of other model polymers or polymeric systems (e.g., bidisperse, branched, grafted, etc.); it is thus believed to be particularly useful in the future in evaluating proposed tube models and developing more accurate theories for entangled systems.

Distributed Computation and TENEX-Related Activities

DTIC Science & Technology

1978-01-01

IPCF) which provides the inter-job communication functions required by MSG. MSG will be modified to use the IPCF primitives when running under TOPS...mmummi iiiwnrnrtnr’in i^WMBi. ■a^j.i.aiAj.k ■*"-’"’’"— •’ ’■■ BBN Report No. 3752 Bolt Beranek and Newman Inc. . . - . *. - primitive (e.g...from a process to MSG when a communication primitive is executed, and from MSG to a process when a pending event (e.g., outstanding receive operation

Primitive ideals of C q [ SL(3)

NASA Astrophysics Data System (ADS)

Hodges, Timothy J.; Levasseur, Thierry

1993-10-01

The primitive ideals of the Hopf algebra C q [ SL(3)] are classified. In particular it is shown that the orbits in Prim C q [ SL(3)] under the action of the representation group H ≅ C *× C * are parameterized naturally by W×W, where W is the associated Weyl group. It is shown that there is a natural one-to-one correspondence between primitive ideals of C q [ SL(3)] and symplectic leaves of the associated Poisson algebraic group SL(3, C).

A comment on methanogenic bacteria and the primitive ecology

NASA Technical Reports Server (NTRS)

Woese, C. R.

1977-01-01

As the phenotype of methanogenic bacteria is suggested to have been one of the major factors creating a dynamic balance between CO2 and CH4 in the primitive atmosphere, these organisms are thought to be very ancient. Their antiquity may be further postulated by comparative characterization of their ribosomal RNA. Accepting this antiquity, it is concluded that a carbon-dioxide-methane cycle, driven by photosynthesis, was the major carbon cycle in primitive ecology, and that photosynthesis and methanogens were thus contemporaneous.

Defibrotide in combination with granulocyte colony-stimulating factor significantly enhances the mobilization of primitive and committed peripheral blood progenitor cells in mice.

PubMed

Carlo-Stella, Carmelo; Di Nicola, Massimo; Magni, Michele; Longoni, Paolo; Milanesi, Marco; Stucchi, Claudio; Cleris, Loredana; Formelli, Franca; Gianni, Massimo A

2002-11-01

Defibrotide is a polydeoxyribonucleotide, which significantly reduces the expression of adhesion molecules on endothelial cells. We investigated the activity of Defibrotide alone or in combination with recombinant human granulocyte colony-stimulating factor (rhG-CSF) to mobilize peripheral blood progenitor cells (PBPCs) in BALB/c mice. A 5-day treatment with Defibrotide alone (1-15 mg/mouse/day) had no effect on WBC counts, frequencies and absolute numbers of total circulating colony-forming cells (CFCs), i.e., granulocyte-macrophage colony-forming units, erythroid burst-forming units, and multilineage colony-forming units. As compared with mock-injected mice, administration of rhG-CSF alone (5 micro g/mouse/day) for 5 days significantly (P < or = 0.0001) increased WBC counts, CFC frequencies, and CFC absolute numbers by 2-, 13-, and 27-fold, respectively. As compared with control mice, the combined administration of Defibrotide (15 mg/mouse/day) and rhG-CSF significantly (P < or = 0.0001) increased WBC counts, frequencies and absolute numbers of CFCs by 4-, 38-, and 119-fold, respectively. As compared with rhG-CSF alone, administration of Defibrotide plus rhG-CSF resulted in a significant increase (P < or = 0.001) of the frequency of circulating long-term culture-initiating cells. In addition, transplantation of 2 x 10(5) rhG-CSF- or Defibrotide/rhG-CSF-mobilized mononuclear cells rescued 43% and 71% of recipient mice, respectively. Experiments of CFC homing performed in lethally irradiated or nonirradiated recipients showed that marrow homing of transplanted PBPCs was reduced by 3-fold in Defibrotide-treated animals as compared with mock-injected mice (P < or = 0.001), suggesting that the mobilizing effect of Defibrotide might be because of an effect on PBPC trafficking. In conclusion, our data demonstrate that Defibrotide synergizes with rhG-CSF and significantly increases the mobilization of a broad spectrum of PBPCs, including primitive and committed progenitor cells. These data might have relevant implications for autologous and allogeneic anticancer therapy in humans.

High grade primitive neuroectodermal tumor of the uterus: A case report.

PubMed

Dizon, A Mitch; Kilgore, Larry C; Grindstaff, Alan; Winkler, Marcus; Kimball, Kristopher J

2014-01-01

•Primitive neuroectodermal tumor of the uterus is extremely rare.•Diagnosis requires timely evaluation with molecular analysis.•Different combinations of adjuvant chemotherapy have been reported.

Ion channels involved in cell volume regulation: effects on migration, proliferation, and programmed cell death in non adherent EAT cells and adherent ELA cells.

PubMed

Hoffmann, Else Kay

2011-01-01

This mini review outlines studies of cell volume regulation in two closely related mammalian cell lines: nonadherent Ehrlich ascites tumour cells (EATC) and adherent Ehrlich Lettre ascites (ELA) cells. Focus is on the regulatory volume decrease (RVD) that occurs after cell swelling, the volume regulatory ion channels involved, and the mechanisms (cellular signalling pathways) that regulate these channels. Finally, I shall also briefly review current investigations in these two cell lines that focuses on how changes in cell volume can regulate cell functions such as cell migration, proliferation, and programmed cell death. Copyright © 2011 S. Karger AG, Basel.

The origin and early evolution of life on Earth.

PubMed

Oró, J; Miller, S L; Lazcano, A

1990-01-01

We do not have a detailed knowledge of the processes that led to the appearance of life on Earth. In this review we bring together some of the most important results that have provided insights into the cosmic and primitive Earth environments, particularly those environments in which life is thought to have originated. To do so, we first discuss the evidence bearing on the antiquity of life on our planet and the prebiotic significance of organic compounds found in interstellar clouds and in primitive solar system bodies such as comets, dark asteroids, and carbonaceous chondrites. This is followed by a discussion on the environmental models of the Hadean and early Archean Earth, as well as on the prebiotic formation of organic monomers and polymers essential to life. We then consider the processes that may have led to the appearance in the Archean of the first cells, and how these processes may have affected the early steps of biological evolution. Finally, the significance of these results to the study of the distribution of life in the Universe is discussed.

Primary Ewing's sarcoma-primitive neuroectodermal tumor of the uterus: a case report and literature review.

PubMed

Park, Jeong-Yeol; Lee, Sun; Kang, Hyoung Jin; Kim, Hy-Sook; Park, Sang-Yoon

2007-08-01

Primary Ewing's sarcoma-primitive neuroectodermal tumor (ES-PNET) of the uterus is an extremely rare malignancy. A 30-year-old Korean woman presented with abnormal uterine bleeding with uterine enlargement. A computed tomography (CT) scan and magnetic resonance imaging (MRI) of the abdomen and pelvis showed a huge uterine mass measuring 18 x 20 x 21 cm, metastasis to both pelvic and para-aortic lymph nodes, and omental infiltration. The pathology report of the uterine mass described a uniformly hypercellular tumor, which was arranged in diffuse solid sheets of uniform, small, rounded, and sometimes spindle-shaped cells, with scanty cytoplasm. Immunohistochemically, the mass tested positive for vimentin, CD99, and chromogranin. The patient received several courses of combination chemotherapy and radiotherapy but died from tumor progression 16 months after the initial diagnosis. This is a rare case of primary uterine ES-PNET in a woman of reproductive age. A review of the literature indicates that primary uterine ES-PNET requires early diagnosis and multimodality treatment including surgery, chemotherapy, and radiotherapy. The behavior of this tumor is potentially aggressive.

A Hypothesis: Life Initiated from Two Genes, as Deduced from the RNA World Hypothesis and the Characteristics of Life-Like Systems

PubMed Central

Kawamura, Kunio

2016-01-01

RNA played a central role in the emergence of the first life-like system on primitive Earth since RNA molecules contain both genetic information and catalytic activity. However, there are several drawbacks regarding the RNA world hypothesis. Here, I briefly discuss the feasibility of the RNA world hypothesis to deduce the RNA functions that are essential for forming a life-like system. At the same time, I have conducted a conceptual analysis of the characteristics of biosystems as a useful approach to deduce a realistic life-like system in relation to the definition of life. For instance, an RNA-based life-like system should possess enough stability to resist environmental perturbations, by developing a cell-like compartment, for instance. Here, a conceptual viewpoint is summarized to provide a realistic life-like system that is compatible with the primitive Earth environment and the capabilities of RNA molecules. According to the empirical and conceptual analysis, I propose the hypothesis that the first life-like system could have initiated from only two genes. PMID:27490571

Peripheral nervous system neuroimmunology seen by a neuro-pathologist.

PubMed

Vallat, J-M

2014-10-01

In most dysimmune neuropathies, historically the microscopical lesions were described prior to immunological studies. The latter along with neuropathological studies have found some immune, albeit incomplete, explanations of the mechanisms of these lesions which we will describe in two main syndromes: the primitive auto-immune inflammatory peripheral polyneuropathies (GBS and CIDP) and polyneuropathies induced by a monoclonal dysglobulinemia. In some patients who have to be discussed case by case pathology (nerve biopsy) will confirm the diagnosis, may help to delineate the molecular anomalies and identify lesional mechanisms. We will review the high variability of nerve lesions which is characteristic of dysimmune neuropathies. Pathological studies confirm that both humoral and cellular immune reactions against Schwann cell and/or axonal antigens are implicated in primitive dysimmune neuropathies due to a dysfunction or failure of immune tolerance mechanisms. In case of a polyneuropathy associated to a monoclonal dysglobulinemia, pathological and immunological studies have shown that in many patients, the dysglobulinemia did harm the peripheral nerve; knowledge of the pathological lesions and their mechanisms is of major interest for orienting specific treatments. Copyright © 2014. Published by Elsevier Masson SAS.

Predatory stem cells in the non-zebrafish chordate, Botryllus schlosseri.

PubMed

Laird, Diana J; De Tomaso, Anthony W

2005-01-01

Botryllus schlosseri is a primitive marine chordate which provides a new model organism to study stem cell biology for several reasons. First, B. schlosseri is a colonial organism that undergoes continuous and regular asexual development. Botryllus adults regenerate themselves, including all somatic tissues and the germline, every week. Second, under natural conditions the cells responsible can mobilize and transplant between two individuals. Once transplanted, these cells can proliferate, differentiate, and often completely replace the cells of the host in both the germline and/or somatic tissues. These processes are called germ cell parasitism (gcp), or somatic cell parasitism (scp), respectively, and we have shown that there are winners and losers in this process, implying that the competitive ability of stem cells is a genetically-determined trait. Fundamental characteristics of stem cell biology, such as self-renewal capacity, homing, or differentiation kinetics must underlie the ability of a stem cell of one genotype to out-compete a stem cell of another genotype, and we are using this system prospectively to isolate the cells responsible and to analyze the molecular mechanisms underlying gcp and scp phenotypes.

Structure and vascularization of the ventricular myocardium in Holocephali: their evolutionary significance

PubMed Central

Durán, Ana C; López-Unzu, Miguel A; Rodríguez, Cristina; Fernández, Borja; Lorenzale, Miguel; Linares, Andrea; Salmerón, Francisca; Sans-Coma, Valentín

2015-01-01

It was generally assumed that the ventricle of the primitive vertebrate heart was composed of trabeculated, or spongy, myocardium, supplied by oxygen-poor luminal blood. In addition, it was presumed that the mixed ventricular myocardium, consisting of a compacta and a spongiosa, and its supply through coronary arteries appeared several times throughout fish evolution. Recent work has suggested, however, that a fully vascularized, mixed myocardium may be the primitive condition in gnathostomes. The present study of the heart ventricles of four holocephalan species aimed to clarify this controversy. Our observations showed that the ventricular myocardium of Chimaera monstrosa and Harriotta raleighana consists of a very thin compacta overlying a widespread spongiosa. The ventricle of Hydrolagus affinis is composed exclusively of trabeculated myocardium. In these three species there is a well-developed coronary artery system. The main coronary artery trunks run along the outflow tract, giving off subepicardial ventricular arteries. The trabeculae of the spongiosa are irrigated by branches of the subepicardial arteries and by penetrating arterial vessels arising directly from the main coronary trunks at the level of the conoventricular junction. The ventricle of Rhinochimaera atlantica has only spongy myocardium supplied by luminal blood. Small coronary arterial vessels are present in the subepicardium, but they do not enter the myocardial trabeculae. The present findings show for the first time that in a wild living vertebrate species, specifically H. affinis, an extensive coronary artery system supplying the whole cardiac ventricle exists in the absence of a well-developed compact ventricular myocardium. This is consistent with the notion derived from experimental work that myocardial cell proliferation and coronary vascular growth rely on distinct developmental programs. Our observations, together with data in the literature on elasmobranchs, support the view that the mixed ventricular myocardium is primitive for chondrichthyans. The reduction or even lack of compacta in holocephali has to be regarded as a derived anatomical trait. Our findings also fit in with the view that the mixed myocardium was the primitive condition in gnathostomes, and that the absence of compact ventricular myocardium in different actinopterygian groups is the result of a repeated loss of such type of cardiac muscle during fish evolution. PMID:25994124

Structure and vascularization of the ventricular myocardium in Holocephali: their evolutionary significance.

PubMed

Durán, Ana C; López-Unzu, Miguel A; Rodríguez, Cristina; Fernández, Borja; Lorenzale, Miguel; Linares, Andrea; Salmerón, Francisca; Sans-Coma, Valentín

2015-06-01

It was generally assumed that the ventricle of the primitive vertebrate heart was composed of trabeculated, or spongy, myocardium, supplied by oxygen-poor luminal blood. In addition, it was presumed that the mixed ventricular myocardium, consisting of a compacta and a spongiosa, and its supply through coronary arteries appeared several times throughout fish evolution. Recent work has suggested, however, that a fully vascularized, mixed myocardium may be the primitive condition in gnathostomes. The present study of the heart ventricles of four holocephalan species aimed to clarify this controversy. Our observations showed that the ventricular myocardium of Chimaera monstrosa and Harriotta raleighana consists of a very thin compacta overlying a widespread spongiosa. The ventricle of Hydrolagus affinis is composed exclusively of trabeculated myocardium. In these three species there is a well-developed coronary artery system. The main coronary artery trunks run along the outflow tract, giving off subepicardial ventricular arteries. The trabeculae of the spongiosa are irrigated by branches of the subepicardial arteries and by penetrating arterial vessels arising directly from the main coronary trunks at the level of the conoventricular junction. The ventricle of Rhinochimaera atlantica has only spongy myocardium supplied by luminal blood. Small coronary arterial vessels are present in the subepicardium, but they do not enter the myocardial trabeculae. The present findings show for the first time that in a wild living vertebrate species, specifically H. affinis, an extensive coronary artery system supplying the whole cardiac ventricle exists in the absence of a well-developed compact ventricular myocardium. This is consistent with the notion derived from experimental work that myocardial cell proliferation and coronary vascular growth rely on distinct developmental programs. Our observations, together with data in the literature on elasmobranchs, support the view that the mixed ventricular myocardium is primitive for chondrichthyans. The reduction or even lack of compacta in holocephali has to be regarded as a derived anatomical trait. Our findings also fit in with the view that the mixed myocardium was the primitive condition in gnathostomes, and that the absence of compact ventricular myocardium in different actinopterygian groups is the result of a repeated loss of such type of cardiac muscle during fish evolution. © 2015 Anatomical Society.

Oocyte formation by mitotically-active germ cells purified from ovaries of reproductive age women

PubMed Central

White, Yvonne A. R.; Woods, Dori C.; Takai, Yasushi; Ishihara, Osamu; Seki, Hiroyuki; Tilly, Jonathan L.

2012-01-01

Germline stem cells that produce oocytes in vitro and fertilization-competent eggs in vivo have been identified in and isolated from adult mouse ovaries. Here we describe and validate a FACS-based protocol that can be used with adult mouse ovaries and human ovarian cortical tissue to purify rare mitotically-active cells that exhibit a gene expression profile consistent with primitive germ cells. Once established in vitro, these cells can be expanded for months and spontaneously generate 35–50 µm oocytes, as determined by morphology, gene expression and attainment of haploid (1n) status. Injection of the human germline cells, engineered to stably express GFP, into human ovarian cortical biopsies leads to formation of follicles containing GFP-positive oocytes 1–2 weeks after xenotransplantation into immunodeficient female mice. Thus, ovaries of reproductive-age women, like adult mice, possess rare mitotically-active germ cells that can be propagated in vitro as well as generate oocytes in vitro and in vivo. PMID:22366948

Primary Ewing's Sarcoma/Primitive Neuroectodermal Tumor of Kidney with Caval Involvement in a Pregnant Woman.

PubMed

Ding, Yinghui; Huang, Zhenlin; Ding, Yafei; Jia, Zhankui; Gu, Chaohui; Xue, Rui; Yang, Jinjian

2016-01-01

In this article, we report the case of a woman in whom was found an abdominal mass during pregnancy and who underwent nephrectomy and extraction of the emboli after delivery. The kidney had a volume of 15 × 10 × 8 cm and pathological diagnosis was primary Ewing's sarcoma. The patient was treated with conventional chemotherapy for 1 year after surgery, at which time multiple metastases were found. From this case, we surmise that hormonal changes that occur during pregnancy may accelerate the growth of Ewing's sarcoma of the kidney, suggesting that renal tumors in pregnant women demand serious attention and that anti-cancer treatment should begin as soon as possible. © 2016 S. Karger AG, Basel.

Palbociclib Isethionate in Treating Younger Patients With Recurrent, Progressive, or Refractory Central Nervous System Tumors

ClinicalTrials.gov

2017-09-27

Childhood Choroid Plexus Tumor; Childhood Ependymoblastoma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor

Irinotecan in Treating Children With Refractory Solid Tumors

ClinicalTrials.gov

2013-06-13

Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

An unusual presentation of adult Wilms' tumor.

PubMed

Mydlo, J H; Horowitz, M; Del Rosario, C; Cosgrove, J; Macchia, R J

1996-01-01

Wilms' tumor (nephroblastoma), a primary renal neoplasm containing primitive blastema and embryonic glomerulotubular structures, is the most common malignant tumor of the urinary tract in children. There have been about 240 cases of adult Wilms' tumor reported in the world literature, however due to some differences in histologic findings, many cases have been reclassified as rhabdoid or clear cell sarcomas, both of which are recognized as separate entities. We report a case of an adult Wilms' tumor and discuss the clinical, radiographic and histologic features of this tumor.

Design principles of a cooperative robot controller

NASA Technical Reports Server (NTRS)

Hayward, Vincent; Hayati, Samad

1987-01-01

The paper describes the design of a controller for cooperative robots being designed at McGill University in a collaborative effort with the Jet Propulsion Laboratory. The first part of the paper discusses the background and motivation for multiple arm control. Then, a set of programming primitives, which are based on the RCCL system and which permit a programmer to specify cooperative tasks are described. The first group of primitives are motion primitives which specify asynchronous motions, master/slave motions, and cooperative motions. In the context of cooperative robots, trajectory generation issues will be discussed and the implementation described. A second set of primitives provides for the specification of spatial relationships. The relations between programming and control in the case of multiple robot are examined. Finally, the paper describes the allocation of various tasks among a set of microprocessors sharing a common bus.

Physically Unclonable Cryptographic Primitives by Chemical Vapor Deposition of Layered MoS2.

PubMed

Alharbi, Abdullah; Armstrong, Darren; Alharbi, Somayah; Shahrjerdi, Davood

2017-12-26

Physically unclonable cryptographic primitives are promising for securing the rapidly growing number of electronic devices. Here, we introduce physically unclonable primitives from layered molybdenum disulfide (MoS 2 ) by leveraging the natural randomness of their island growth during chemical vapor deposition (CVD). We synthesize a MoS 2 monolayer film covered with speckles of multilayer islands, where the growth process is engineered for an optimal speckle density. Using the Clark-Evans test, we confirm that the distribution of islands on the film exhibits complete spatial randomness, hence indicating the growth of multilayer speckles is a spatial Poisson process. Such a property is highly desirable for constructing unpredictable cryptographic primitives. The security primitive is an array of 2048 pixels fabricated from this film. The complex structure of the pixels makes the physical duplication of the array impossible (i.e., physically unclonable). A unique optical response is generated by applying an optical stimulus to the structure. The basis for this unique response is the dependence of the photoemission on the number of MoS 2 layers, which by design is random throughout the film. Using a threshold value for the photoemission, we convert the optical response into binary cryptographic keys. We show that the proper selection of this threshold is crucial for maximizing combination randomness and that the optimal value of the threshold is linked directly to the growth process. This study reveals an opportunity for generating robust and versatile security primitives from layered transition metal dichalcogenides.

Applications of human umbilical cord blood cells in central nervous system regeneration.

PubMed

Herranz, Antonio S; Gonzalo-Gobernado, Rafael; Reimers, Diana; Asensio, Maria J; Rodríguez-Serrano, Macarena; Bazán, Eulalia

2010-03-01

In recent decades, there has been considerable amount of information about embryonic stem cells (ES). The dilemma facing scientists interested in the development and use of human stem cells in replacement therapies is the source of these cells, i.e. the human embryo. There are many ethical and moral problems related to the use of these cells. Hematopoietic stem cells from umbilical cord blood have been proposed as an alternative source of embryonic stem cells. After exposure to different agents, these cells are able to express antigens of diverse cellular lineages, including the neural type. The In vitro manipulation of human umbilical cord blood (hUCB) cells has shown their stem capacity and plasticity. These cells are easily accessible, In vitro amplifiable, well tolerated by the host, and with more primitive molecular characteristics that give them great flexibility. Overall, these properties open a promising future for the use of hUCB in regenerative therapies for the Central Nervous System (CNS). This review will focus on the available literature concerning umbilical cord blood cells as a therapeutic tool for the treatment of neurodegenerative diseases.

Mapping Human Pluripotent-to-Cardiomyocyte Differentiation: Methylomes, Transcriptomes, and Exon DNA Methylation “Memories”

PubMed Central

Tompkins, Joshua D.; Jung, Marc; Chen, Chang-yi; Lin, Ziguang; Ye, Jingjing; Godatha, Swetha; Lizhar, Elizabeth; Wu, Xiwei; Hsu, David; Couture, Larry A.; Riggs, Arthur D.

2016-01-01

The directed differentiation of human cardiomyocytes (CMs) from pluripotent cells provides an invaluable model for understanding mechanisms of cell fate determination and offers considerable promise in cardiac regenerative medicine. Here, we utilize a human embryonic stem cell suspension bank, produced according to a good manufacturing practice, to generate CMs using a fully defined and small molecule-based differentiation strategy. Primitive and cardiac mesoderm purification was used to remove non-committing and multi-lineage populations and this significantly aided the identification of key transcription factors, lncRNAs, and essential signaling pathways that define cardiomyogenesis. Global methylation profiles reflect CM development and we report on CM exon DNA methylation “memories” persisting beyond transcription repression and marking the expression history of numerous developmentally regulated genes, especially transcription factors. PMID:26981572

A critical role for PDGFRα signaling in medial nasal process development.

PubMed

He, Fenglei; Soriano, Philippe

2013-01-01

The primitive face is composed of neural crest cell (NCC) derived prominences. The medial nasal processes (MNP) give rise to the upper lip and vomeronasal organ, and are essential for normal craniofacial development, but the mechanism of MNP development remains largely unknown. PDGFRα signaling is known to be critical for NCC development and craniofacial morphogenesis. In this study, we show that PDGFRα is required for MNP development by maintaining the migration of progenitor neural crest cells (NCCs) and the proliferation of MNP cells. Further investigations reveal that PI3K/Akt and Rac1 signaling mediate PDGFRα function during MNP development. We thus establish PDGFRα as a novel regulator of MNP development and elucidate the roles of its downstream signaling pathways at cellular and molecular levels.

Neoplastic growth: the consequence of evolutionary malignant resistance to chronic damage for survival of cells (review of a new theory of the origin of cancer).

PubMed

Monceviciūte-Eringiene, E

2005-01-01

In the present review, a new theory that the mechanisms of general evolutionary persistent resistance to damaging factors are closely related to the development of tumour cells is introduced. Evolutionary resistance and its variability have an immense power to drive and control the process of carcinogenesis and the success of microbial and antitumour chemotherapy. First, this phenomenon of adaptation is characteristic of microbial cells whose resistance to antibiotics and other chemotherapeutic drugs is manifested through ATP-dependent transmembrane transporters. The structure and function of some multidrug transporters of resistance are conserved from microorganisms to mammals. When somatic cells are exposed to carcinogens and develop into tumour cells, they also acquire resistance to the toxic effects of carcinogens through these same transmembrane transporters (P-glycoprotein, glutathione S-transferases and other products of evolutionary resistance-related genes arisen for detoxification and exportation of cytotoxic xenobiotics and drugs). Cancerous cells acquire a persistent evolutionary resistance to chemotherapy drugs or irradiation through the same ATP-dependent transporters encountered in prokaryotic and eukaryotic cells. The mechanism of acquired resistance of cells to damaging factors, which becomes manifested during tumorigenic process formation, is a general biological law of primary significance in carcinogenesis. This resistance can be called malignant as, once formed, it does not disappear, as does also a clone of malignant cells. In tumorous cells, the mutagenic processes, morphological and functional modifications are a mechanism of secondary significance in carcinogenesis, contributing to formation of damage-resistant cells. This mechanism characterizes the processes of simplification arising in damage-resistant cells. Such cells acquire parasitic features. To survive under unfavourable conditions, they get adapted as if returning down the evolutionary stairs back to a more primitive stage of atavistic regression, which is characteristic of primitive forms of existence. Therefore they cease obeying the growth-regulating mechanisms in the organism and acquire the potential of unlimited division and accelerated growth (metastases) as do unicellular organisms or their forms resistant to damaging factors in the environment and in the host organism. Thus, cancer is a natural self-protective response of the damaged cells to the biological, physical and chemical damage and oxidative stress. This response has been developed in the process of evolution under the impact of the general biological Darwinian law of nature--to survive through variability and adaptation to the changed environmental conditions. Thus, malignization is the consequence of an evolutionary variety of the general biological resistance of cells to damage and stress in order to survive.

Tholeiitic basalt magmatism of Kilauea and Mauna Loa volcanoes of Hawaii

USGS Publications Warehouse

Murata, K.J.

1970-01-01

The primitive magmas of Kilauca and Mauna Loa are generated by partial melting of mantle peridotite at depths of -60 km or more. Results of high-pressure melting experiments indicate that the primitive melt must contain at least 20% MgO in order to have olivine as a liquidus mineral. The least fractionated lavas of both volcanoes have olivine (Fa13) on the liquidus at 1 atmosphere, suggesting that the only substance lost from the primitive melt, during a rather rapid ascent to the surface, is olivine. This relation allows the primitive composition to be computed by adding olivine to the composition of an erupted lava until total MgO is at least 20 percent. Although roughly similar, historic lavas of the two volcanoes show a consistent difference in composition. The primitive melt of Mauna Loa contains 20% more dissolved orthopyroxene, a high-temperature melting phase in the mantle, and is deficient in elements such as potassium, uranium, and niobium, which presumably occur in minor low-melting phases. Mauna Loa appears to be the older volcano, deriving its magma at higher temperature and greater depth from a more depleted source rock. ?? 1970 Springer-Verlag.

Compositional study of asteroids in the Erigone collisional family using visible spectroscopy at the 10.4 m GTC

NASA Astrophysics Data System (ADS)

Morate, David; de León, Julia; De Prá, Mário; Licandro, Javier; Cabrera-Lavers, Antonio; Campins, Humberto; Pinilla-Alonso, Noemí; Alí-Lagoa, Víctor

2016-02-01

Two primitive near-Earth asteroids, (101955) Bennu and (162173) Ryugu, will be visited by a spacecraft with the aim of returning samples back to Earth. Since these objects are believed to originate in the inner main belt primitive collisional families (Erigone, Polana, Clarissa, and Sulamitis) or in the background of asteroids outside these families, the characterization of these primitive populations will enhance the scientific return of the missions. The main goal of this work is to shed light on the composition of the Erigone collisional family by means of visible spectroscopy. Asteroid (163) Erigone has been classified as a primitive object, and we expect the members of this family to be consistent with the spectral type of the parent body. We have obtained visible spectra (0.5-0.9 μm) for 101 members of the Erigone family, using the OSIRIS instrument at the 10.4 m Gran Telescopio Canarias. We found that 87% of the objects have typically primitive visible spectra consistent with that of (163) Erigone. In addition, we found that a significant fraction of these objects (~50%) present evidence of aqueous alteration.

Developmental Approach for Behavior Learning Using Primitive Motion Skills.

PubMed

Dawood, Farhan; Loo, Chu Kiong

2018-05-01

Imitation learning through self-exploration is essential in developing sensorimotor skills. Most developmental theories emphasize that social interactions, especially understanding of observed actions, could be first achieved through imitation, yet the discussion on the origin of primitive imitative abilities is often neglected, referring instead to the possibility of its innateness. This paper presents a developmental model of imitation learning based on the hypothesis that humanoid robot acquires imitative abilities as induced by sensorimotor associative learning through self-exploration. In designing such learning system, several key issues will be addressed: automatic segmentation of the observed actions into motion primitives using raw images acquired from the camera without requiring any kinematic model; incremental learning of spatio-temporal motion sequences to dynamically generates a topological structure in a self-stabilizing manner; organization of the learned data for easy and efficient retrieval using a dynamic associative memory; and utilizing segmented motion primitives to generate complex behavior by the combining these motion primitives. In our experiment, the self-posture is acquired through observing the image of its own body posture while performing the action in front of a mirror through body babbling. The complete architecture was evaluated by simulation and real robot experiments performed on DARwIn-OP humanoid robot.

The primitive code and repeats of base oligomers as the primordial protein-encoding sequence.

PubMed Central

Ohno, S; Epplen, J T

1983-01-01

Even if the prebiotic self-replication of nucleic acids and the subsequent emergence of primitive, enzyme-independent tRNAs are accepted as plausible, the origin of life by spontaneous generation still appears improbable. This is because the just-emerged primitive translational machinery had to cope with base sequences that were not preselected for their coding potentials. Particularly if the primitive mitochondria-like code with four chain-terminating base triplets preceded the universal code, the translation of long, randomly generated, base sequences at this critical stage would have merely resulted in the production of short oligopeptides instead of long polypeptide chains. We present the base sequence of a mouse transcript containing tetranucleotide repeats conserved during evolution. Even if translated in accordance with the primitive mitochondria-like code, this transcript in its three reading frames can yield 245-, 246-, and 251-residue-long tetrapeptidic periodical polypeptides that are already acquiring longer periodicities. We contend that the first set of base sequences translated at the beginning of life were such oligonucleotide repeats. By quickly acquiring longer periodicities, their products must have soon gained characteristic secondary structures--alpha-helical or beta-sheet or both. PMID:6574491

Capture, Learning, and Classification of Upper Extremity Movement Primitives in Healthy Controls and Stroke Patients

PubMed Central

Guerra, Jorge; Uddin, Jasim; Nilsen, Dawn; Mclnerney, James; Fadoo, Ammarah; Omofuma, Isirame B.; Hughes, Shatif; Agrawal, Sunil; Allen, Peter; Schambra, Heidi M.

2017-01-01

There currently exist no practical tools to identify functional movements in the upper extremities (UEs). This absence has limited the precise therapeutic dosing of patients recovering from stroke. In this proof-of-principle study, we aimed to develop an accurate approach for classifying UE functional movement primitives, which comprise functional movements. Data were generated from inertial measurement units (IMUs) placed on upper body segments of older healthy individuals and chronic stroke patients. Subjects performed activities commonly trained during rehabilitation after stroke. Data processing involved the use of a sliding window to obtain statistical descriptors, and resulting features were processed by a Hidden Markov Model (HMM). The likelihoods of the states, resulting from the HMM, were segmented by a second sliding window and their averages were calculated. The final predictions were mapped to human functional movement primitives using a Logistic Regression algorithm. Algorithm performance was assessed with a leave-one-out analysis, which determined its sensitivity, specificity, and positive and negative predictive values for all classified primitives. In healthy control and stroke participants, our approach identified functional movement primitives embedded in training activities with, on average, 80% precision. This approach may support functional movement dosing in stroke rehabilitation. PMID:28813877

Vorinostat and Bortezomib in Treating Young Patients With Refractory or Recurrent Solid Tumors, Including Central Nervous System Tumors and Lymphoma

ClinicalTrials.gov

2013-07-01

Childhood Burkitt Lymphoma; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Medulloepithelioma; Childhood Meningioma; Childhood Mixed Glioma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Childhood Oligodendroglioma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

Cellular pressure and volume regulation and implications for cell mechanics

NASA Astrophysics Data System (ADS)

Jiang, Hongyuan; Sun, Sean

2013-03-01

In eukaryotic cells, small changes in cell volume can serve as important signals for cell proliferation, death and migration. Volume and shape regulation also directly impacts the mechanics of the cell and multi-cellular tissues. Recent experiments found that during mitosis, eukaryotic cells establish a preferred steady volume and pressure, and the steady volume and pressure can robustly adapt to large osmotic shocks. Here we develop a mathematical model of cellular pressure and volume regulation, incorporating essential elements such as water permeation, mechano-sensitive channels, active ion pumps and active stresses in the actomyosin cortex. The model can fully explain the available experimental data, and predicts the cellular volume and pressure for several models of cell cortical mechanics. Furthermore, we show that when cells are subjected to an externally applied load, such as in an AFM indentation experiment, active regulation of volume and pressure leads to complex cellular response. We found the cell stiffness highly depends on the loading rate, which indicates the transport of water and ions might contribute to the observed viscoelasticity of cells.

On the Primitive Ideal spaces of the C(*) -algebras of graphs

NASA Astrophysics Data System (ADS)

Bates, Teresa

2005-11-01

We characterise the topological spaces which arise as the primitive ideal spaces of the Cuntz-Krieger algebras of graphs satisfying condition (K): directed graphs in which every vertex lying on a loop lies on at least two loops. We deduce that the spaces which arise as Prim;C(*(E)) are precisely the spaces which arise as the primitive ideal spaces of AF-algebras. Finally, we construct a graph wt{E} from E such that C(*(wt{E})) is an AF-algebra and Prim;C(*(E)) and Prim;C(*(wt{E})) are homeomorphic.

Chemical evolution of primitive solar system bodies

NASA Technical Reports Server (NTRS)

Oro, J.; Mills, T.

1989-01-01

Observations on organic molecules and compounds containing biogenic elements in the interstellar medium and in the primitive bodies of the solar system are reviewed. The discovery of phosphorus molecular species in dense interstellar clouds, the existence of organic ions in the dust and gas phase of the comas of Comet Halley, and the presence of presolar, deuterium-hydrogen ratios in the amino acids of carbonaceous chondrites are discussed. The relationships between comets, dark asteroids, and carbonaceous chondrites are examined. Also, consideration is given to the chemical evolution of Titan, the primitive earth, and early Mars.

Origin of eukaryotes from within archaea, archaeal eukaryome and bursts of gene gain: eukaryogenesis just made easier?

PubMed Central

Koonin, Eugene V.

2015-01-01

The origin of eukaryotes is a fundamental, forbidding evolutionary puzzle. Comparative genomic analysis clearly shows that the last eukaryotic common ancestor (LECA) possessed most of the signature complex features of modern eukaryotic cells, in particular the mitochondria, the endomembrane system including the nucleus, an advanced cytoskeleton and the ubiquitin network. Numerous duplications of ancestral genes, e.g. DNA polymerases, RNA polymerases and proteasome subunits, also can be traced back to the LECA. Thus, the LECA was not a primitive organism and its emergence must have resulted from extensive evolution towards cellular complexity. However, the scenario of eukaryogenesis, and in particular the relationship between endosymbiosis and the origin of eukaryotes, is far from being clear. Four recent developments provide new clues to the likely routes of eukaryogenesis. First, evolutionary reconstructions suggest complex ancestors for most of the major groups of archaea, with the subsequent evolution dominated by gene loss. Second, homologues of signature eukaryotic proteins, such as actin and tubulin that form the core of the cytoskeleton or the ubiquitin system, have been detected in diverse archaea. The discovery of this ‘dispersed eukaryome’ implies that the archaeal ancestor of eukaryotes was a complex cell that might have been capable of a primitive form of phagocytosis and thus conducive to endosymbiont capture. Third, phylogenomic analyses converge on the origin of most eukaryotic genes of archaeal descent from within the archaeal evolutionary tree, specifically, the TACK superphylum. Fourth, evidence has been presented that the origin of the major archaeal phyla involved massive acquisition of bacterial genes. Taken together, these findings make the symbiogenetic scenario for the origin of eukaryotes considerably more plausible and the origin of the organizational complexity of eukaryotic cells more readily explainable than they appeared until recently. PMID:26323764

Haematopoietic ESL-1 enables stem cell proliferation in the bone marrow by limiting TGFβ availability.

PubMed

Leiva, Magdalena; Quintana, Juan A; Ligos, José M; Hidalgo, Andrés

2016-01-08

The life-long maintenance of haematopoietic stem and progenitor cells (HSPCs) critically relies on environmental signals produced by cells that constitute the haematopoietic niche. Here we report a cell-intrinsic mechanism whereby haematopoietic cells limit proliferation within the bone marrow, and show that this pathway is repressed by E-selectin ligand 1 (ESL-1). Mice deficient in ESL-1 display aberrant HSPC quiescence, expansion of the immature pool and reduction in niche size. Remarkably, the traits were transplantable and dominant when mutant and wild-type precursors coexisted in the same environment, but were independent of E-selectin, the vascular receptor for ESL-1. Instead, quiescence is generated by unrestrained production of the cytokine TGFβ by mutant HSPC, and in vivo or in vitro blockade of the cytokine completely restores the homeostatic properties of the haematopoietic niche. These findings reveal that haematopoietic cells, including the more primitive compartment, can actively shape their own environment.

Haematopoietic ESL-1 enables stem cell proliferation in the bone marrow by limiting TGFβ availability

PubMed Central

Leiva, Magdalena; Quintana, Juan A.; Ligos, José M.; Hidalgo, Andrés

2016-01-01

The life-long maintenance of haematopoietic stem and progenitor cells (HSPCs) critically relies on environmental signals produced by cells that constitute the haematopoietic niche. Here we report a cell-intrinsic mechanism whereby haematopoietic cells limit proliferation within the bone marrow, and show that this pathway is repressed by E-selectin ligand 1 (ESL-1). Mice deficient in ESL-1 display aberrant HSPC quiescence, expansion of the immature pool and reduction in niche size. Remarkably, the traits were transplantable and dominant when mutant and wild-type precursors coexisted in the same environment, but were independent of E-selectin, the vascular receptor for ESL-1. Instead, quiescence is generated by unrestrained production of the cytokine TGFβ by mutant HSPC, and in vivo or in vitro blockade of the cytokine completely restores the homeostatic properties of the haematopoietic niche. These findings reveal that haematopoietic cells, including the more primitive compartment, can actively shape their own environment. PMID:26742601

Embryonic hematopoiesis in vertebrate somites gives rise to definitive hematopoietic stem cells

PubMed Central

Qiu, Juhui; Fan, Xiaoying; Wang, Yixia; Jin, Hongbin; Song, Yixiao; Han, Yang; Huang, Shenghong; Meng, Yaping; Tang, Fuchou; Meng, Anming

2016-01-01

Hematopoietic stem cells (HSCs) replenish all types of blood cells. It is debating whether HSCs in adults solely originate from the aorta-gonad-mesonephros (AGM) region, more specifically, the dorsal aorta, during embryogenesis. Here, we report that somite hematopoiesis, a previously unwitnessed hematopoiesis, can generate definitive HSCs (dHSCs) in zebrafish. By transgenic lineage tracing, we found that a subset of cells within the forming somites emigrate ventromedially and mix with lateral plate mesoderm-derived primitive hematopoietic cells before the blood circulation starts. These somite-derived hematopoietic precursors and stem cells (sHPSCs) subsequently enter the circulation and colonize the kidney of larvae and adults. RNA-seq analysis reveals that sHPSCs express hematopoietic genes with sustained expression of many muscle/skeletal genes. Embryonic sHPSCs transplanted into wild-type embryos expand during growth and survive for life time with differentiation into various hematopoietic lineages, indicating self-renewal and multipotency features. Therefore, the embryonic origin of dHSCs in adults is not restricted to the AGM. PMID:27252540

Heme deficiency in erythroid lineage causes differentiation arrest and cytoplasmic iron overload.

PubMed Central

Nakajima, O; Takahashi, S; Harigae, H; Furuyama, K; Hayashi, N; Sassa, S; Yamamoto, M

1999-01-01

Erythroid 5-aminolevulinate synthase (ALAS-E) catalyzes the first step of heme biosynthesis in erythroid cells. Mutation of human ALAS-E causes the disorder X-linked sideroblastic anemia. To examine the roles of heme during hematopoiesis, we disrupted the mouse ALAS-E gene. ALAS-E-null embryos showed no hemoglobinized cells and died by embryonic day 11.5, indicating that ALAS-E is the principal isozyme contributing to erythroid heme biosynthesis. In the ALAS-E-null mutant embryos, erythroid differentiation was arrested, and an abnormal hematopoietic cell fraction emerged that accumulated a large amount of iron diffusely in the cytoplasm. In contrast, we found typical ring sideroblasts that accumulated iron mostly in mitochondria in adult mice chimeric for ALAS-E-null mutant cells, indicating that the mode of iron accumulation caused by the lack of ALAS-E is different in primitive and definitive erythroid cells. These results demonstrate that ALAS-E, and hence heme supply, is necessary for differentiation and iron metabolism of erythroid cells. PMID:10562540

Dissecting mitochondrial apoptosis pathways by gain-of-function cell culture screens.

PubMed

Grimm, Stefan

2013-05-01

While more primitive organism such as Caenorhabditis elegans and Drosophila melanogaster feature a limited, and by now probably mostly known, array of basic cell death factors, the mammalian cell is replete with additional regulators of the cell's demise. This abundance of apoptosis mediators has made it imperative to set up a systematic inventory of mammalian cell death genes. Genetic screens in this biological system have recently uncovered the rich diversity of cell death signalling and have in particular highlighted mitochondria as an organelle loaded with apoptosis regulators. Many of the screens that have addressed this utilised the novel technique of RNA interference but some also looked at gain-of-functions with transfected cDNAs. Here we give an overview of the rationale for the latter approach, present the genes discovered by this strategy and in particular describe the involvement of mitochondria and their signalling pathways defined by those genes. Copyright © 2012 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Isolation, molecular cloning and in vitro expression of rhesus monkey (Macaca mulatta) prominin-1.s1 complementary DNA encoding a potential hematopoietic stem cell antigen.

PubMed

Husain, S M; Shou, Y; Sorrentino, B P; Handgretinger, R

2006-10-01

Human prominin-1 (CD133 or AC133) is an important cell surface marker used to isolate primitive hematopoietic stem cells. The commercially available antibody to human prominin-1 does not recognize rhesus prominin-1. Therefore, we isolated, cloned and characterized the complementary DNA (cDNA) of rhesus prominin-1 gene and determined its coding potential. Following the nomenclature of prominin family of genes, we named this cDNA as rhesus prominin-1.s1. The amino acid sequence data of the putative rhesus prominin-1.s1 could be used in designing antigenic peptides to raise antibodies for use in isolation of pure populations of rhesus prominin-1(+) hematopoietic cells. To the best of our knowledge, there has been no previously published report about the isolation of a prominin-1 cDNA from rhesus monkey (Macaca mulatta).

CD22 and Siglec-G in B cell function and tolerance.

PubMed

Poe, Jonathan C; Tedder, Thomas F

2012-08-01

The immune system has evolved into two main arms: the primitive innate arm that is the first line of defense but relatively short-lived and broad acting; and the advanced adaptive arm that generates immunological memory, allowing rapid, specific recall responses. T cell-independent type-2 (TI-2) antigens (Ags) invoke innate immune responses. However, due to its 'at the ready' nature, how the innate arm of the immune system maintains tolerance to potentially abundant host TI-2 Ags remains elusive. Therefore, it is important to define the mechanisms that establish innate immune tolerance. This review highlights recent insights into B cell tolerance to theoretical self TI-2 Ags, and examines how the B cell-restricted sialic acid binding Ig-like lectins (Siglecs), CD22 and Siglec-G, might contribute to this process. Copyright © 2012 Elsevier Ltd. All rights reserved.

Survival of patients with Ewing's sarcoma in Yazd-Iran.

PubMed

Akhavan, Ali; Binesh, Fariba; Shamshiri, Hadi; Ghanadi, Fazllolah

2014-01-01

The Ewing's sarcoma family is a group of small round cell tumors which accounts for 10-15% of all primary bone neoplasms. The aim of this study was to evaluate the survival of Ewing's sarcoma patients in our province and to determine of influencing factors. All patients with documented Ewing's sarcoma/ primitive neuroectodermal tumor(PNET) family pathology were enrolled in this study during a period of eight years. For all of them local and systemic therapy were carried out. Overall and event free survival and prognostic factors were evaluated. Thirty two patients were enrolled in the study. The median age was 17.5 years. Twenty (65.2%) were male and 9 (28.1%) were aged 14 years or less. Mean disease free survival was 26.8 (95%CI; 13.8-39.9) months and five year disease free survival was 26%. Mean overall survival was 38.7 months (95%CI; 25.9-50.6) and median overall survival was 24 months. Five year overall survival was 25%. From the variables evaluated , only presence of metastatic disease at presentation (p value=0. 028) and complete response (p value =0. 006) had significant relations to overall survival. Survival of Ewing's sarcoma in our province is disappointing. It seems to be mostly due to less effective treatment. Administration of adequate chemotherapy dosage, resection of tumor with negative margins and precise assessment of irradiation volume may prove helpful.

Pineal tumors: analysis of treatment results in 20 patients.

PubMed

Amendola, Beatriz E; Wolf, Aizik; Coy, Sammie R; Amendola, Marco A; Eber, Daryl

2005-01-01

The authors evaluate their results when using gamma knife surgery (GKS) in the management of patients with tumors in the pineal region. This is a retrospective clinical evaluation of 20 patients with primary tumors of the pineal region treated with GKS from November 1994 through August 2003. There were 13 germ cell tumors, two pineoblastomas, two low-grade gliomas, one primitive neuroectodermal tumor, one teratoma, and one pineocytoma. There were 10 male and 10 female patients. Their median age was 15.5 years (range 5-71 years). The median margin dose was 11 Gy (range 8-20 Gy). The median target volume was 3.1 cm3 (range 0.1-49.9 cm3). Five patients received sequential systemic chemotherapy and four underwent adjuvant conventional radiation therapy. Seventeen (85%) of 20 patients are alive with a median survival of 30.4 months (range 0-85.7 months). Two patients required retreatment. Three patients died: one of unrelated causes, one who presented with extensive local disease, and the other of meningeal carcinomatosis with local control of the primary tumor. No complications from GKS were noted. This initial experience suggests that GKS is a valuable treatment modality for the management of pineal region tumors. This technique offers excellent local tumor control and minimal patient morbidity, allowing for immediate use of systemic chemotherapy and/or conventional radiation if indicated.

Generic extravehicular (EVA) and telerobot task primitives for analysis, design, and integration. Version 1.0: Reference compilation for the EVA and telerobotics communities

NASA Technical Reports Server (NTRS)

Smith, Jeffrey H.; Drews, Michael

1990-01-01

The results are described of an effort to establish commonality and standardization of generic crew extravehicular (crew-EVA) and telerobotic task analysis primitives used for the study of spaceborne operations. Although direct crew-EVA plans are the most visible output of spaceborne operations, significant ongoing efforts by a wide variety of projects and organizations also require tools for estimation of crew-EVA and telerobotic times. Task analysis tools provide estimates for input to technical and cost tradeoff studies. A workshop was convened to identify the issues and needs to establish a common language and syntax for task analysis primitives. In addition, the importance of such a syntax was shown to have precedence over the level to which such a syntax is applied. The syntax, lists of crew-EVA and telerobotic primitives, and the data base in diskette form are presented.

Small Cofactors May Assist Protein Emergence from RNA World: Clues from RNA-Protein Complexes

PubMed Central

Shen, Liang; Ji, Hong-Fang

2011-01-01

It is now widely accepted that at an early stage in the evolution of life an RNA world arose, in which RNAs both served as the genetic material and catalyzed diverse biochemical reactions. Then, proteins have gradually replaced RNAs because of their superior catalytic properties in catalysis over time. Therefore, it is important to investigate how primitive functional proteins emerged from RNA world, which can shed light on the evolutionary pathway of life from RNA world to the modern world. In this work, we proposed that the emergence of most primitive functional proteins are assisted by the early primitive nucleotide cofactors, while only a minority are induced directly by RNAs based on the analysis of RNA-protein complexes. Furthermore, the present findings have significant implication for exploring the composition of primitive RNA, i.e., adenine base as principal building blocks. PMID:21789260

Clay minerals in primitive meteorites and interplanetary dust 1

NASA Technical Reports Server (NTRS)

Zolensky, M. E.; Keller, L. P.

1991-01-01

Many meteorites and interplanetary dust particles (IDPs) with primitive compositions contain significant amounts of phyllosilicate minerals, which are generally interpreted as evidence of protoplanetary aqueous alteration at an early period of the solar system. These meteorites are chondrites (near solar composition) of the carbonaceous and ordinary varieties. The former are subdivided (according to bulk composition and petrology) into CI, CM, CV, CO, CR, and ungrouped classes. IDPs are extraterrestrial particulates, collected in stratosphere, which have chemical compositions indicative of a primitive origin; they are typically distinct from the primitive meteorites. Characterization of phyllosilicates in these materials is a high priority because of the important physico-chemical information they hold. The most common phyllosilicates present in chondritic extraterrestrial materials are serpentine-group minerals, smectites, and micas. We discuss these phyllosilicates and describe the interpretation of their occurrence in meteorites and IDPs and what this indicates about history of their parent bodies, which are probably the hydrous asteroids.

An Alternative Method for Long-Term Culture of Chicken Embryonic Stem Cell In Vitro.

PubMed

Zhang, Li; Wu, Yenan; Li, Xiang; Wei, Shao; Xing, Yiming; Lian, Zhengxing; Han, Hongbing

2018-01-01

Chicken embryonic stem cells (cESCs) obtained from stage X embryos provide a novel model for the study of avian embryonic development. A new way to maintain cESCs for a long period in vitro still remains unexplored. We found that the cESCs showed stem cell-like properties in vitro for a long term with the support of DF-1 feeder and basic culture medium supplemented with human basic fibroblast growth factor (hbFGF), mouse stem cell factor (mSCF), and human leukemia inhibitory factor (hLIF). During the long culture period, the cESCs showed typical ES cell morphology and expressed primitive stem cell markers with a relatively stable proliferation rate and high telomerase activity. These cells also exhibited the capability to differentiate into cardiac myocytes, smooth muscle cells, neural cells, osteoblast, and adipocyte in vitro . Chimera chickens were produced by cESCs cultured for 25 passages with this new culture system. The experiments showed that DF-1 was the optimal feeder and hbFGF was an important factor for maintaining the pluripotency of cESCs in vitro .

The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt signaling pathway.

PubMed

Chen, Hui-Jye; Lin, Chung-Ming; Lin, Chyuan-Sheng; Perez-Olle, Raul; Leung, Conrad L; Liem, Ronald K H

2006-07-15

MACF1 (microtubule actin cross-linking factor 1) is a multidomain protein that can associate with microfilaments and microtubules. We found that MACF1 was highly expressed in neuronal tissues and the foregut of embryonic day 8.5 (E8.5) embryos and the head fold and primitive streak of E7.5 embryos. MACF1(-/-) mice died at the gastrulation stage and displayed developmental retardation at E7.5 with defects in the formation of the primitive streak, node, and mesoderm. This phenotype was similar to Wnt-3(-/-) and LRP5/6 double-knockout embryos. In the absence of Wnt, MACF1 associated with a complex that contained Axin, beta-catenin, GSK3beta, and APC. Upon Wnt stimulation, MACF1 appeared to be involved in the translocation and subsequent binding of the Axin complex to LRP6 at the cell membrane. Reduction of MACF1 with small interfering RNA decreased the amount of beta-catenin in the nucleus, and led to an inhibition of Wnt-induced TCF/beta-catenin-dependent transcriptional activation. Similar results were obtained with a dominant-negative MACF1 construct that contained the Axin-binding region. Reduction of MACF1 in Wnt-1-expressing P19 cells resulted in decreased T (Brachyury) gene expression, a DNA-binding transcription factor that is a direct target of Wnt/beta-catenin signaling and required for mesoderm formation. These results suggest a new role of MACF1 in the Wnt signaling pathway.

Brief report: a human induced pluripotent stem cell model of cernunnos deficiency reveals an important role for XLF in the survival of the primitive hematopoietic progenitors.

PubMed

Tilgner, Katarzyna; Neganova, Irina; Singhapol, Chatchawan; Saretzki, Gabriele; Al-Aama, Jumana Yousuf; Evans, Jerome; Gorbunova, Vera; Gennery, Andrew; Przyborski, Stefan; Stojkovic, Miodrag; Armstrong, Lyle; Jeggo, Penny; Lako, Majlinda

2013-09-01

Cernunnos (also known as XLF) deficiency syndrome is a rare recessive autosomal disorder caused by mutations in the XLF gene, a key factor involved in the end joining step of DNA during nonhomologous end joining (NHEJ) process. Human patients with XLF mutations display microcephaly, developmental and growth delays, and severe immunodeficiency. While the clinical phenotype of DNA damage disorders, including XLF Syndrome, has been described extensively, the underlying mechanisms of disease onset, are as yet, undefined. We have been able to generate an induced pluripotent stem cell (iPSC) model of XLF deficiency, which accurately replicates the double-strand break repair deficiency observed in XLF patients. XLF patient-specific iPSCs (XLF-iPSC) show typical expression of pluripotency markers, but have altered in vitro differentiation capacity and an inability to generate teratomas comprised of all three germ layers in vivo. Our results demonstrate that XLF-iPSCs possess a weak NHEJ-mediated DNA repair capacity that is incapable of coping with the DNA lesions introduced by physiological stress, normal metabolism, and ionizing radiation. XLF-iPSC lines are capable of hematopoietic differentiation; however, the more primitive subsets of hematopoietic progenitors display increased apoptosis in culture and an inability to repair DNA damage. Together, our findings highlight the importance of NHEJ-mediated-DNA repair in the maintenance of a pristine pool of hematopoietic progenitors during human embryonic development. © AlphaMed Press.

Passive potassium transport in low potassium sheep red cells: dependence upon cell volume and chloride.

PubMed Central

Dunham, P B; Ellory, J C

1981-01-01

The major pathway of passive K influx (ouabain-insensitive) was characterized in low-K type (LK) red cells of sheep. 1. Passive K transport in these cells was highly sensitive to variations in cell volume; it increased threefold or more in cells swollen osmotically by 10%, and decreased up to twofold in cells shrunken 5-10%. Active K influx was insensitive to changes in cell volume. Three different methods for varying cell volume osmotically all gave similar results. 2. The volume-sensitive pathway was specific for K in that Na influx did not vary with changes in cell volume. 3. The volume-sensitive K influx was a saturable function of external K concentration. It was slightly inhibited by Na, whereas K influx in shrunken cells was unaffected by Na. 4. Passive K influx was dependent on the major anion in the medium in that replacement of Cl with any of six other anions resulted in a reduction of K influx by 50-80% (replacement of Cl by Br caused an increase in K influx). The activation of K influx by Cl followed sigmoid kinetics. 5. Passive K influx is inhibited by anti-L antibody. The antibody affected only that portion of influx which was Cl-dependent and volume-sensitve. Of the subfractions of the antibody, it is anti-L1 which inhibits passive K transport. 6. Pretreatment of cells with iodoacetamide reduced the sensitivity of K influx to cell volume in that the influx was reduced in swollen IAA-treated cells and increased in shrunken IAA-cells. 7. Intracellular Ca has no role in altering passive K transport in LK sheep cells. Therefore, the major pathway of passive K transport in LK sheep red cells is sensitive to changes in cell volume, specific for K, dependent on Cl, and inhibited by anti-L1 antibody, The minor pathway, observed in shrunken cells, has none of these properties. PMID:6798197

Evolution of Computational Toxicology-from Primitive ...

EPA Pesticide Factsheets

Presentation at the Health Canada seminar in Ottawa, ON, Canada on Nov. 15. 2016 Presentation at the Health Canada seminar in Ottawa, ON, Canada on Nov. 15. 2016 on the Evolution of Computational Toxicology-from Primitive Beginnings to Sophisticated Application

Relation Between the Cell Volume and the Cell Cycle Dynamics in Mammalian cell

NASA Astrophysics Data System (ADS)

Magno, A. C. G.; Oliveira, I. L.; Hauck, J. V. S.

2016-08-01

The main goal of this work is to add and analyze an equation that represents the volume in a dynamical model of the mammalian cell cycle proposed by Gérard and Goldbeter (2011) [1]. The cell division occurs when the cyclinB/Cdkl complex is totally degraded (Tyson and Novak, 2011)[2] and it reaches a minimum value. At this point, the cell is divided into two newborn daughter cells and each one will contain the half of the cytoplasmic content of the mother cell. The equations of our base model are only valid if the cell volume, where the reactions occur, is constant. Whether the cell volume is not constant, that is, the rate of change of its volume with respect to time is explicitly taken into account in the mathematical model, then the equations of the original model are no longer valid. Therefore, every equations were modified from the mass conservation principle for considering a volume that changes with time. Through this approach, the cell volume affects all model variables. Two different dynamic simulation methods were accomplished: deterministic and stochastic. In the stochastic simulation, the volume affects every model's parameters which have molar unit, whereas in the deterministic one, it is incorporated into the differential equations. In deterministic simulation, the biochemical species may be in concentration units, while in stochastic simulation such species must be converted to number of molecules which are directly proportional to the cell volume. In an effort to understand the influence of the new equation a stability analysis was performed. This elucidates how the growth factor impacts the stability of the model's limit cycles. In conclusion, a more precise model, in comparison to the base model, was created for the cell cycle as it now takes into consideration the cell volume variation

Updates to Multi-Dimensional Flux Reconstruction for Hypersonic Simulations on Tetrahedral Grids

NASA Technical Reports Server (NTRS)

Gnoffo, Peter A.

2010-01-01

The quality of simulated hypersonic stagnation region heating with tetrahedral meshes is investigated by using an updated three-dimensional, upwind reconstruction algorithm for the inviscid flux vector. An earlier implementation of this algorithm provided improved symmetry characteristics on tetrahedral grids compared to conventional reconstruction methods. The original formulation however displayed quantitative differences in heating and shear that were as large as 25% compared to a benchmark, structured-grid solution. The primary cause of this discrepancy is found to be an inherent inconsistency in the formulation of the flux limiter. The inconsistency is removed by employing a Green-Gauss formulation of primitive gradients at nodes to replace the previous Gram-Schmidt algorithm. Current results are now in good agreement with benchmark solutions for two challenge problems: (1) hypersonic flow over a three-dimensional cylindrical section with special attention to the uniformity of the solution in the spanwise direction and (2) hypersonic flow over a three-dimensional sphere. The tetrahedral cells used in the simulation are derived from a structured grid where cell faces are bisected across the diagonal resulting in a consistent pattern of diagonals running in a biased direction across the otherwise symmetric domain. This grid is known to accentuate problems in both shock capturing and stagnation region heating encountered with conventional, quasi-one-dimensional inviscid flux reconstruction algorithms. Therefore the test problems provide a sensitive indicator for algorithmic effects on heating. Additional simulations on a sharp, double cone and the shuttle orbiter are then presented to demonstrate the capabilities of the new algorithm on more geometrically complex flows with tetrahedral grids. These results provide the first indication that pure tetrahedral elements utilizing the updated, three-dimensional, upwind reconstruction algorithm may be used for the simulation of heating and shear in hypersonic flows in upwind, finite volume formulations.

Severe Leukopenia and Dysregulated Erythropoiesis in SCID Mice Persistently Infected with the Parvovirus Minute Virus of Mice

PubMed Central

Segovia, José C.; Gallego, Jesús M.; Bueren, Juan A.; Almendral, José M.

1999-01-01

Parvovirus minute virus of mice strain i (MVMi) infects committed granulocyte-macrophage CFU and erythroid burst-forming unit (CFU-GM and BFU-E, respectively) and pluripotent (CFU-S) mouse hematopoietic progenitors in vitro. To study the effects of MVMi infection on mouse hemopoiesis in the absence of a specific immune response, adult SCID mice were inoculated by the natural intranasal route of infection and monitored for hematopoietic and viral multiplication parameters. Infected animals developed a very severe viral-dose-dependent leukopenia by 30 days postinfection (d.p.i.) that led to death within 100 days, even though the number of circulating platelets and erythrocytes remained unaltered throughout the disease. In the bone marrow of every lethally inoculated mouse, a deep suppression of CFU-GM and BFU-E clonogenic progenitors occurring during the 20- to 35-d.p.i. interval corresponded with the maximal MVMi production, as determined by the accumulation of virus DNA replicative intermediates and the yield of infectious virus. Viral productive infection was limited to a small subset of primitive cells expressing the major replicative viral antigen (NS-1 protein), the numbers of which declined with the disease. However, the infection induced a sharp and lasting unbalance of the marrow hemopoiesis, denoted by a marked depletion of granulomacrophagic cells (GR-1+ and MAC-1+) concomitant with a twofold absolute increase in erythroid cells (TER-119+). A stimulated definitive erythropoiesis in the infected mice was further evidenced by a 12-fold increase per femur of recognizable proerythroblasts, a quantitative apoptosis confined to uninfected TER-119+ cells, as well as by a 4-fold elevation in the number of circulating reticulocytes. Therefore, MVMi targets and suppresses primitive hemopoietic progenitors leading to a very severe leukopenia, but compensatory mechanisms are mounted specifically by the erythroid lineage that maintain an effective erythropoiesis. The results show that infection of SCID mice with the parvovirus MVMi causes a novel dysregulation of murine hemopoiesis in vivo. PMID:9971754

Low-Resolution Spectroscopy of Primitive Asteroids: Progress Report for SARA/VSU Survey

NASA Technical Reports Server (NTRS)

Leake, M. A.; Nogues, J. P.; Gaines, J. K.; Looper, J. K.; Freitas, K. A.

2001-01-01

Progress on a low-resolution survey of primitive C-class asteroids continues using new equipment (and its associated problems) to understand aqueous alteration in the solar system. Additional information is contained in the original extended abstract.

Design of Quasi-Terminator Orbits near Primitive Bodies

NASA Technical Reports Server (NTRS)

Lantoine, Gregory; Broschart, Stephen B.; Grebow, Daniel J.

2013-01-01

Quasi-terminator orbits are a class of quasi-periodic orbits around a primitive body that exist in the vicinity of the well-known terminator orbits. The inherent stability of quasi-terminator trajectories and their wide variety of viewing geometries make them a very compelling option for primitive body mapping missions. In this paper, we discuss orbit design methodologies for selection of an appropriate quasi-terminator orbit that would meet the needs of a specific mission. Convergence of these orbits in an eccentric, higher-fidelity model is also discussed with an example case at Bennu, the target of the upcoming NASA's OSIRIS-REx mission.