Characterisation of cell cycle arrest and terminal differentiation in a maximally proliferative human epithelial tissue: Lessons from the human hair follicle matrix.

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Purba, Talveen S; Brunken, Lars; Peake, Michael; Shahmalak, Asim; Chaves, Asuncion; Poblet, Enrique; Ceballos, Laura; Gandarillas, Alberto; Paus, Ralf

2017-09-01

Human hair follicle (HF) growth and hair shaft formation require terminal differentiation-associated cell cycle arrest of highly proliferative matrix keratinocytes. However, the regulation of this complex event remains unknown. CIP/KIP family member proteins (p21 CIP1 , p27 KIP1 and p57 KIP2 ) regulate cell cycle progression/arrest, endoreplication, differentiation and apoptosis. Since they have not yet been adequately characterized in the human HF, we asked whether and where CIP/KIP proteins localise in the human hair matrix and pre-cortex in relation to cell cycle activity and HF-specific epithelial cell differentiation that is marked by keratin 85 (K85) protein expression. K85 expression coincided with loss or reduction in cell cycle activity markers, including in situ DNA synthesis (EdU incorporation), Ki-67, phospho-histone H3 and cyclins A and B1, affirming a post-mitotic state of pre-cortical HF keratinocytes. Expression of CIP/KIP proteins was found abundantly within the proliferative hair matrix, concomitant with a role in cell cycle checkpoint control. p21 CIP1 , p27 KIP1 and cyclin E persisted within post-mitotic keratinocytes of the pre-cortex, whereas p57 KIP2 protein decreased but became nuclear. These data imply a supportive role for CIP/KIP proteins in maintaining proliferative arrest, differentiation and anti-apoptotic pathways, promoting continuous hair bulb growth and hair shaft formation in anagen VI. Moreover, post-mitotic hair matrix regions contained cells with enlarged nuclei, and DNA in situ hybridisation showed cells that were >2N in the pre-cortex. This suggests that CIP/KIP proteins might counterbalance cyclin E to control further rounds of DNA replication in a cell population that has a propensity to become tetraploid. These data shed new light on the in situ-biography of human hair matrix keratinocytes on their path of active cell cycling, arrest and terminal differentiation, and showcase the human HF as an excellent, clinically

Idas, a Novel Phylogenetically Conserved Geminin-related Protein, Binds to Geminin and Is Required for Cell Cycle Progression*

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Pefani, Dafni-Eleutheria; Dimaki, Maria; Spella, Magda; Karantzelis, Nickolas; Mitsiki, Eirini; Kyrousi, Christina; Symeonidou, Ioanna-Eleni; Perrakis, Anastassis; Taraviras, Stavros; Lygerou, Zoi

2011-01-01

Development and homeostasis of multicellular organisms relies on an intricate balance between cell proliferation and differentiation. Geminin regulates the cell cycle by directly binding and inhibiting the DNA replication licensing factor Cdt1. Geminin also interacts with transcriptional regulators of differentiation and chromatin remodelling factors, and its balanced interactions are implicated in proliferation-differentiation decisions during development. Here, we describe Idas (Idas being a cousin of the Gemini in Ancient Greek Mythology), a previously uncharacterised coiled-coil protein related to Geminin. We show that human Idas localizes to the nucleus, forms a complex with Geminin both in cells and in vitro through coiled-coil mediated interactions, and can change Geminin subcellular localization. Idas does not associate with Cdt1 and prevents Geminin from binding to Cdt1 in vitro. Idas depletion from cells affects cell cycle progression; cells accumulate in S phase and are unable to efficiently progress to mitosis. Idas protein levels decrease in anaphase, whereas its overexpression causes mitotic defects. During development, we show that Idas exhibits high level expression in the choroid plexus and the cortical hem of the mouse telencephalon. Our data highlight Idas as a novel Geminin binding partner, implicated in cell cycle progression, and a putative regulator of proliferation-differentiation decisions during development. PMID:21543332

Linear astrophysical dynamos in rotating spheres: Differential rotation, anisotropic turbulent magnetic diffusivity, and solar-stellar cycle magnetic parity

International Nuclear Information System (INIS)

Yoshimura, H.; Wang, Z.; Wu, F.

1984-01-01

Differential rotation dependence of the selection mechanism for magnetic parity of solar and stellar cycles is studied by assuming various differential rotation profiles inn the dynamo equation. The parity selection depends on propagation direction of oscillating magnetic fields in the form of dynamo waves which propagate along isorotation surfaces. When there is any radial gradient in the differential rotation, dynamo waves propagate either equatorward or poleward. In the former case, field systems of the two hemispheres approach each other and collide at the equator. Then, odd parity is selected. In the latter case, field systems of the two hemispheres recede from each other and do not collide at the equator, an even parity is selected. Thus the equatorial migration of wings of the butterfly iagram of the solar cycle and its odd parity are intrinsically related. In the case of purely latitudibnal differential rotation, dynamo waves propagate purely radially and growth rates of odd and even modes are nearly the same even when dynamo strength is weak when the parity selection mechanism should work most efficiently. In this case, anisotropy of turbulent diffusivity is a decisive factor to separate odd and even modes. Unlike in the case of radial-gradient-dominated differential rotation in which any difference between diffusivities for poloidal and toroidal fields enhancess the parity selection without changing the parity, the parity selection in the case of latitudinal-gradient-dominated differential rotation depends on the difference of diffusivities for poloidal and toroidal fields. When diffusivity for poloidal fields iss larger than that for toroidal fields, odd parity is selected; and when diffusivity for toroidal fields is larger, even parity is selected

Dosage-sensitive function of retinoblastoma related and convergent epigenetic control are required during the Arabidopsis life cycle.

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Amal J Johnston

2010-06-01

Full Text Available The plant life cycle alternates between two distinct multi-cellular generations, the reduced gametophytes and the dominant sporophyte. Little is known about how generation-specific cell fate, differentiation, and development are controlled by the core regulators of the cell cycle. In Arabidopsis, RETINOBLASTOMA RELATED (RBR, an evolutionarily ancient cell cycle regulator, controls cell proliferation, differentiation, and regulation of a subset of Polycomb Repressive Complex 2 (PRC2 genes and METHYLTRANSFERASE 1 (MET1 in the male and female gametophytes, as well as cell fate establishment in the male gametophyte. Here we demonstrate that RBR is also essential for cell fate determination in the female gametophyte, as revealed by loss of cell-specific marker expression in all the gametophytic cells that lack RBR. Maintenance of genome integrity also requires RBR, because diploid plants heterozygous for rbr (rbr/RBR produce an abnormal portion of triploid offspring, likely due to gametic genome duplication. While the sporophyte of the diploid mutant plants phenocopied wild type due to the haplosufficiency of RBR, genetic analysis of tetraploid plants triplex for rbr (rbr/rbr/rbr/RBR revealed that RBR has a dosage-dependent pleiotropic effect on sporophytic development, trichome differentiation, and regulation of PRC2 subunit genes CURLY LEAF (CLF and VERNALIZATION 2 (VRN2, and MET1 in leaves. There were, however, no obvious cell cycle and cell proliferation defects in these plant tissues, suggesting that a single functional RBR copy in tetraploids is capable of maintaining normal cell division but is not sufficient for distinct differentiation and developmental processes. Conversely, in leaves of mutants in sporophytic PRC2 subunits, trichome differentiation was also affected and expression of RBR and MET1 was reduced, providing evidence for a RBR-PRC2-MET1 regulatory feedback loop involved in sporophyte development. Together, dosage-sensitive RBR

CUDC-907 Promotes Bone Marrow Adipocytic Differentiation Through Inhibition of Histone Deacetylase and Regulation of Cell Cycle.

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Ali, Dalia; Alshammari, Hassan; Vishnubalaji, Radhakrishnan; Chalisserry, Elna Paul; Hamam, Rimi; Alfayez, Musaad; Kassem, Moustapha; Aldahmash, Abdullah; Alajez, Nehad M

2017-03-01

The role of bone marrow adipocytes (BMAs) in overall energy metabolism and their effects on bone mass are currently areas of intensive investigation. BMAs differentiate from bone marrow stromal cells (BMSCs); however, the molecular mechanisms regulating BMA differentiation are not fully understood. In this study, we investigated the effect of CUDC-907, identified by screening an epigenetic small-molecule library, on adipocytic differentiation of human BMSCs (hBMSCs) and determined its molecular mechanism of action. Human bone marrow stromal cells exposed to CUDC-907 (500 nM) exhibited enhanced adipocytic differentiation (∼2.9-fold increase, P < 0.005) compared with that of control cells. Global gene expression and signaling pathway analyses of differentially expressed genes revealed a strong enrichment of genes involved in adipogenesis, cell cycle, and DNA replication. Chromatin immune precipitation combined with quantitative polymerase chain reaction showed significant increase in H3K9ac epigenetic marker in the promoter regions of AdipoQ, FABP4, PPARγ, KLF15, and CEBPA in CUDC-907-treated hBMSCs. Follow-up experiments corroborated that the inhibition of histone deacetylase (HDAC) activity enhanced adipocytic differentiation, while the inhibition of PI3K decreased adipocytic differentiation. In addition, CUDC-907 arrested hBMSCs in the G0-G1 phase of the cell cycle and reduced the number of S-phase cells. Our data reveal that HDAC, PI3K, and cell cycle genes are important regulators of BMA formation and demonstrate that adipocyte differentiation of hBMSCs is associated with complex changes in a number of epigenetic and genetic pathways, which can be targeted to regulate BMA formation.

Induction of cell cycle arrest at G1 and S phases and cAMP-dependent differentiation in C6 glioma by low concentration of cycloheximide

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Zhang Samuel S

2010-12-01

Full Text Available Abstract Background Differentiation therapy has been shown effective in treatment of several types of cancer cells and may prove to be effective in treatment of glioblastoma multiforme, the most common and most aggressive primary brain tumor. Although extensively used as a reagent to inhibit protein synthesis in mammalian cells, whether cycloheximide treatment leads to glioma cell differentiation has not been reported. Methods C6 glioma cell was treated with or without cycloheximide at low concentrations (0.5-1 μg/ml for 1, 2 and 3 days. Cell proliferation rate was assessed by direct cell counting and colony formation assays. Apoptosis was assessed by Hoechst 33258 staining and FACS analysis. Changes in several cell cycle regulators such as Cyclins D1 and E, PCNA and Ki67, and several apoptosis-related regulators such as p53, p-JNK, p-AKT, and PARP were determined by Western blot analysis. C6 glioma differentiation was determined by morphological characterization, immunostaining and Western blot analysis on upregulation of GFAP and o p-STAT3 expression, and upregulation of intracellular cAMP. Results Treatment of C6 cell with low concentration of cycloheximide inhibited cell proliferation and depleted cells at both G2 and M phases, suggesting blockade at G1 and S phases. While no cell death was observed, cells underwent profound morphological transformation that indicated cell differentiation. Western blotting and immunostaining analyses further indicated that changes in expression of several cell cycle regulators and the differentiation marker GFAP were accompanied with cycloheximide-induced cell cycle arrest and cell differentiation. Increase in intracellular cAMP, a known promoter for C6 cell differentiation, was found to be elevated and required for cycloheximide-promoted C6 cell differentiation. Conclusion Our results suggest that partial inhibition of protein synthesis in C6 glioma by low concentration of cycloheximide induces cell cycle

Cell cycle sensitivity of HL-60 cells to the differentiation-inducing effects of 1-alpha,25-dihydroxyvitamin D3

International Nuclear Information System (INIS)

Studzinski, G.P.; Bhandal, A.K.; Brelvi, Z.S.

1985-01-01

A recently described system for monocyte-like differentiation of HL-60 cells was utilized to determine if the initiation of this pathway can be linked to a set of replicative cellular events. The standard induction system consisted of a 4-h exposure to 100 nM 1-alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] followed by determination of nonspecific esterase and phagocytic activity 24 h later. The cell cycle status was ascertained by the incorporation of [ 3 H]thymidine and autoradiography. Studies in which cell cycle block in the G1/S phase boundary region was produced by a partial inhibition of DNA synthesis with thymidine, or sodium butyrate, showed that the exposure of such semisynchronous cultures to 1,25(OH)2D3 resulted in an increased proportion of differentiated cells. Conversely, blocking the cell cycle with vinblastine (G2/M block) or theobromine (mid-G1 block) inhibited the initiation of differentiation by 1,25(OH)2D3. Experiments in which the differentiated cells were examined for the cell cycle position at the time of the exposure to 1,25(OH)2D3 by [ 3 H]thymidine labeling and autoradiography confirmed that the late G1 and early S phase cells are those which predominate in the differentiated fraction of 1,25(OH)2D3-treated HL-60 cultures. These results link pre- and early replicative cellular events to the induction of monocytic differentiation by 1,25(OH)2D3

Bounding the number of limit cycles of discontinuous differential systems by using Picard-Fuchs equations

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Yang, Jihua; Zhao, Liqin

2018-05-01

In this paper, by using Picard-Fuchs equations and Chebyshev criterion, we study the upper bounds of the number of limit cycles given by the first order Melnikov function for discontinuous differential systems, which can bifurcate from the periodic orbits of quadratic reversible centers of genus one (r19): x ˙ = y - 12x2 + 16y2, y ˙ = - x - 16 xy, and (r20): x ˙ = y + 4x2, y ˙ = - x + 16 xy, and the periodic orbits of the quadratic isochronous centers (S1) : x ˙ = - y +x2 -y2, y ˙ = x + 2 xy, and (S2) : x ˙ = - y +x2, y ˙ = x + xy. The systems (r19) and (r20) are perturbed inside the class of polynomial differential systems of degree n and the system (S1) and (S2) are perturbed inside the class of quadratic polynomial differential systems. The discontinuity is the line y = 0. It is proved that the upper bounds of the number of limit cycles for systems (r19) and (r20) are respectively 4 n - 3 (n ≥ 4) and 4 n + 3 (n ≥ 3) counting the multiplicity, and the maximum numbers of limit cycles bifurcating from the period annuluses of the isochronous centers (S1) and (S2) are exactly 5 and 6 (counting the multiplicity) on each period annulus respectively.

Limit cycles via higher order perturbations for some piecewise differential systems

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Buzzi, Claudio A.; Lima, Maurício Firmino Silva; Torregrosa, Joan

2018-05-01

A classical perturbation problem is the polynomial perturbation of the harmonic oscillator, (x‧ ,y‧) =(- y + εf(x , y , ε) , x + εg(x , y , ε)) . In this paper we study the limit cycles that bifurcate from the period annulus via piecewise polynomial perturbations in two zones separated by a straight line. We prove that, for polynomial perturbations of degree n , no more than Nn - 1 limit cycles appear up to a study of order N. We also show that this upper bound is reached for orders one and two. Moreover, we study this problem in some classes of piecewise Liénard differential systems providing better upper bounds for higher order perturbation in ε, showing also when they are reached. The Poincaré-Pontryagin-Melnikov theory is the main technique used to prove all the results.

Differential Expression of Proteins Associated with the Hair Follicle Cycle - Proteomics and Bioinformatics Analyses.

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Lei Wang

Full Text Available Hair follicle cycling can be divided into the following three stages: anagen, catagen, and telogen. The molecular signals that orchestrate the follicular transition between phases are still unknown. To better understand the detailed protein networks controlling this process, proteomics and bioinformatics analyses were performed to construct comparative protein profiles of mouse skin at specific time points (0, 8, and 20 days. Ninety-five differentially expressed protein spots were identified by MALDI-TOF/TOF as 44 proteins, which were found to change during hair follicle cycle transition. Proteomics analysis revealed that these changes in protein expression are involved in Ca2+-regulated biological processes, migration, and regulation of signal transduction, among other processes. Subsequently, three proteins were selected to validate the reliability of expression patterns using western blotting. Cluster analysis revealed three expression patterns, and each pattern correlated with specific cell processes that occur during the hair cycle. Furthermore, bioinformatics analysis indicated that the differentially expressed proteins impacted multiple biological networks, after which detailed functional analyses were performed. Taken together, the above data may provide insight into the three stages of mouse hair follicle morphogenesis and provide a solid basis for potential therapeutic molecular targets for this hair disease.

Network-based differential gene expression analysis suggests cell cycle related genes regulated by E2F1 underlie the molecular difference between smoker and non-smoker lung adenocarcinoma

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2013-01-01

Background Differential gene expression (DGE) analysis is commonly used to reveal the deregulated molecular mechanisms of complex diseases. However, traditional DGE analysis (e.g., the t test or the rank sum test) tests each gene independently without considering interactions between them. Top-ranked differentially regulated genes prioritized by the analysis may not directly relate to the coherent molecular changes underlying complex diseases. Joint analyses of co-expression and DGE have been applied to reveal the deregulated molecular modules underlying complex diseases. Most of these methods consist of separate steps: first to identify gene-gene relationships under the studied phenotype then to integrate them with gene expression changes for prioritizing signature genes, or vice versa. It is warrant a method that can simultaneously consider gene-gene co-expression strength and corresponding expression level changes so that both types of information can be leveraged optimally. Results In this paper, we develop a gene module based method for differential gene expression analysis, named network-based differential gene expression (nDGE) analysis, a one-step integrative process for prioritizing deregulated genes and grouping them into gene modules. We demonstrate that nDGE outperforms existing methods in prioritizing deregulated genes and discovering deregulated gene modules using simulated data sets. When tested on a series of smoker and non-smoker lung adenocarcinoma data sets, we show that top differentially regulated genes identified by the rank sum test in different sets are not consistent while top ranked genes defined by nDGE in different data sets significantly overlap. nDGE results suggest that a differentially regulated gene module, which is enriched for cell cycle related genes and E2F1 targeted genes, plays a role in the molecular differences between smoker and non-smoker lung adenocarcinoma. Conclusions In this paper, we develop nDGE to prioritize

Cell cycle, differentiation and tissue-independent expression of ribosomal protein L37.

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Su, S; Bird, R C

1995-09-15

A unique human cDNA (hG1.16) that encodes a mRNA of 450 nucleotides was isolated from a subtractive library derived from HeLa cells. The relative expression level of hG1.16 during different cell-cycle phases was determined by Northern-blot analysis of cells synchronized by double-thymidine block and serum deprivation/refeeding. hG1.16 was constitutively expressed during all phases of the cell cycle, including the quiescent phase when even most constitutively expressed genes experience some suppression of expression. The expression level of hG1.16 did not change during terminal differentiation of myoblasts to myotubes, during which cells become permanently post-mitotic. Examination of other tissues revealed that the relative expression level of hG1.16 was constitutive in all embryonic mouse tissues examined, including brain, eye, heart, kidney, liver, lung and skeletal muscle. This was unusual in that expression was not down-modulated during differentiation and did not vary appreciably between tissue types. Analysis by inter-species Northern-blot analysis revealed that hG1.16 was highly conserved among all vertebrates studied (from fish to humans but not in insects). DNA sequence analysis of hG1.16 revealed a high level of similarity to rat ribosomal protein L37, identifying hG1.16 as a new member of this multigene family. The deduced amino acid sequence of hG1.16 was identical to rat ribosomal protein L37 that contained 97 amino acids, many of which are highly positively charged (15 arginine and 14 lysine residues with a predicted M(r) of 11,065). hG1.16 protein has a single C2-C2 zinc-finger-like motif which is also present in rat ribosomal protein L37. Using primers designed from the sequence of hG1.16, unique bovine and rat cDNAs were also isolated by 5'-rapid-amplification of cDNA ends. DNA sequences of bovine and rat G1.16, clones were 92.8% and 92.2% similar to human G1.16 while the deduced amino acid sequences derived from bovine and rat cDNAs each differed

Differential gene expression during the moult cycle of Antarctic krill (Euphausia superba

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Gaten Edward

2010-10-01

Full Text Available Abstract Background All crustaceans periodically moult to renew their exoskeleton. In krill this involves partial digestion and resorption of the old exoskeleton and synthesis of new cuticle. Molecular events that underlie the moult cycle are poorly understood in calcifying crustaceans and even less so in non-calcifying organisms such as krill. To address this we constructed an Antarctic krill cDNA microarray in order to generate gene expression profiles across the moult cycle and identify possible activation pathways. Results A total of 26 different cuticle genes were identified that showed differential gene expression across the moult cycle. Almost all cuticle genes were up regulated during premoult and down regulated during late intermoult. There were a number of transcripts with significant sequence homology to genes potentially involved in the synthesis, breakdown and resorption of chitin. During early premoult glutamine synthetase, a gene involved in generating an amino acid used in the synthesis of glucosamine, a constituent of chitin, was up regulated more than twofold. Mannosyltransferase 1, a member of the glycosyltransferase family of enzymes that includes chitin synthase was also up regulated during early premoult. Transcripts homologous to a β-N-acetylglucosaminidase (β-NAGase precursor were expressed at a higher level during late intermoult (prior to apolysis than during premoult. This observation coincided with the up regulation during late intermoult, of a coatomer subunit epsilon involved in the production of vesicles that maybe used to transport the β-NAGase precursors into the exuvial cleft. Trypsin, known to activate the β-NAGase precursor, was up regulated more than fourfold during premoult. The up regulation of a predicted oligopeptide transporter during premoult may allow the transport of chitin breakdown products across the newly synthesised epi- and exocuticle layers. Conclusion We have identified many genes

The Effect of Thermal Cycling on Crystal-Liquid Separation During Lunar Magma Ocean Differentiation

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Mills, Ryan D.

2013-01-01

Differentiation of magma oceans likely involves a mixture of fractional and equilibrium crystallization [1]. The existence of: 1) large volumes of anorthosite in the lunar highlands and 2) the incompatible- rich (KREEP) reservoir suggests that fractional crystallization may have dominated during differentiation of the Moon. For this to have occurred, crystal fractionation must have been remarkably efficient. Several authors [e.g. 2, 3] have hypothesized that equilibrium crystallization would have dominated early in differentiation of magma oceans because of crystal entrainment during turbulent convection. However, recent numerical modeling [4] suggests that crystal settling could have occurred throughout the entire solidification history of the lunar magma ocean if crystals were large and crystal fraction was low. These results indicate that the crystal size distribution could have played an important role in differentiation of the lunar magma ocean. Here, I suggest that thermal cycling from tidal heating during lunar magma ocean crystallization caused crystals to coarsen, leading to efficient crystal-liquid separation.

Post-Transcriptional Regulation of KLF4 by High-Risk Human Papillomaviruses Is Necessary for the Differentiation-Dependent Viral Life Cycle.

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Vignesh Kumar Gunasekharan

2016-07-01

Full Text Available Human papillomaviruses (HPVs are epithelial tropic viruses that link their productive life cycles to the differentiation of infected host keratinocytes. A subset of the over 200 HPV types, referred to as high-risk, are the causative agents of most anogenital malignancies. HPVs infect cells in the basal layer, but restrict viral genome amplification, late gene expression, and capsid assembly to highly differentiated cells that are active in the cell cycle. In this study, we demonstrate that HPV proteins regulate the expression and activities of a critical cellular transcription factor, KLF4, through post-transcriptional and post-translational mechanisms. Our studies show that KLF4 regulates differentiation as well as cell cycle progression, and binds to sequences in the upstream regulatory region (URR to regulate viral transcription in cooperation with Blimp1. KLF4 levels are increased in HPV-positive cells through a post-transcriptional mechanism involving E7-mediated suppression of cellular miR-145, as well as at the post-translational level by E6-directed inhibition of its sumoylation and phosphorylation. The alterations in KLF4 levels and functions results in activation and suppression of a subset of KLF4 target genes, including TCHHL1, VIM, ACTN1, and POT1, that is distinct from that seen in normal keratinocytes. Knockdown of KLF4 with shRNAs in cells that maintain HPV episomes blocked genome amplification and abolished late gene expression upon differentiation. While KLF4 is indispensable for the proliferation and differentiation of normal keratinocytes, it is necessary only for differentiation-associated functions of HPV-positive keratinocytes. Increases in KLF4 levels alone do not appear to be sufficient to explain the effects on proliferation and differentiation of HPV-positive cells indicating that additional modifications are important. KLF4 has also been shown to be a critical regulator of lytic Epstein Barr virus (EBV replication

The development of a differential game related to terrorism: Min-Max differential game

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Abd El-Monem A. Megahed

2017-07-01

Full Text Available In this work, we study a differential game related to terrorism: Min-Max differential game taking into account the governmental activities such as the education quality, increasing the chances of labor, social justice, religious awareness and security arrangements. A Min-Max differential game between government and terrorist organizations is considered in this study. To obtain the optimal strategy of solving this problem, we study the analytic form of a Min-Max differential game and the governmental activities. Furthermore, a saddle point of a Min-Max differential game is studied.

Glucose-ABL1-TOR Signaling Modulates Cell Cycle Tuning to Control Terminal Appressorial Cell Differentiation.

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Marroquin-Guzman, Margarita; Sun, Guangchao; Wilson, Richard A

2017-01-01

The conserved target of rapamycin (TOR) pathway integrates growth and development with available nutrients, but how cellular glucose controls TOR function and signaling is poorly understood. Here, we provide functional evidence from the devastating rice blast fungus Magnaporthe oryzae that glucose can mediate TOR activity via the product of a novel carbon-responsive gene, ABL1, in order to tune cell cycle progression during infection-related development. Under nutrient-free conditions, wild type (WT) M. oryzae strains form terminal plant-infecting cells (appressoria) at the tips of germ tubes emerging from three-celled spores (conidia). WT appressorial development is accompanied by one round of mitosis followed by autophagic cell death of the conidium. In contrast, Δabl1 mutant strains undergo multiple rounds of accelerated mitosis in elongated germ tubes, produce few appressoria, and are abolished for autophagy. Treating WT spores with glucose or 2-deoxyglucose phenocopied Δabl1. Inactivating TOR in Δabl1 mutants or glucose-treated WT strains restored appressorium formation by promoting mitotic arrest at G1/G0 via an appressorium- and autophagy-inducing cell cycle delay at G2/M. Collectively, this work uncovers a novel glucose-ABL1-TOR signaling axis and shows it engages two metabolic checkpoints in order to modulate cell cycle tuning and mediate terminal appressorial cell differentiation. We thus provide new molecular insights into TOR regulation and cell development in response to glucose.

The role of cell cycle in retinal development: cyclin-dependent kinase inhibitors co-ordinate cell-cycle inhibition, cell-fate determination and differentiation in the developing retina.

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Bilitou, Aikaterini; Ohnuma, Shin-ichi

2010-03-01

The mature retina is formed through multi-step developmental processes, including eye field specification, optic vesicle evagination, and cell-fate determination. Co-ordination of these developmental events with cell-proliferative activity is essential to achieve formation of proper retinal structure and function. In particular, the molecular and cellular dynamics of the final cell cycle significantly influence the identity that a cell acquires, since cell fate is largely determined at the final cell cycle for the production of postmitotic cells. This review summarizes our current understanding of the cellular mechanisms that underlie the co-ordination of cell-cycle and cell-fate determination, and also describes a molecular role of cyclin-dependent kinase inhibitors (CDKIs) as co-ordinators of cell-cycle arrest, cell-fate determination and differentiation. Copyright (c) 2010 Wiley-Liss, Inc.

Differential forms and the geometry of general relativity

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Dray, Tevian

2015-01-01

Differential Forms and the Geometry of General Relativity provides readers with a coherent path to understanding relativity. Requiring little more than calculus and some linear algebra, it helps readers learn just enough differential geometry to grasp the basics of general relativity.The book contains two intertwined but distinct halves. Designed for advanced undergraduate or beginning graduate students in mathematics or physics, most of the text requires little more than familiarity with calculus and linear algebra. The first half presents an introduction to general relativity that describes

Canthin-6-one induces cell death, cell cycle arrest and differentiation in human myeloid leukemia cells.

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Vieira Torquato, Heron F; Ribeiro-Filho, Antonio C; Buri, Marcus V; Araújo Júnior, Roberto T; Pimenta, Renata; de Oliveira, José Salvador R; Filho, Valdir C; Macho, Antonio; Paredes-Gamero, Edgar J; de Oliveira Martins, Domingos T

2017-04-01

Canthin-6-one is a natural product isolated from various plant genera and from fungi with potential antitumor activity. In the present study, we evaluate the antitumor effects of canthin-6-one in human myeloid leukemia lineages. Kasumi-1 lineage was used as a model for acute myeloid leukemia. Cells were treated with canthin-6-one and cell death, cell cycle and differentiation were evaluated in both total cells (Lin + ) and leukemia stem cell population (CD34 + CD38 - Lin -/low ). Among the human lineages tested, Kasumi-1 was the most sensitive to canthin-6-one. Canthin-6-one induced cell death with apoptotic (caspase activation, decrease of mitochondrial potential) and necrotic (lysosomal permeabilization, double labeling of annexin V/propidium iodide) characteristics. Moreover, canthin-6-one induced cell cycle arrest at G 0 /G 1 (7μM) and G 2 (45μM) evidenced by DNA content, BrdU incorporation and cyclin B1/histone 3 quantification. Canthin-6-one also promoted differentiation of Kasumi-1, evidenced by an increase in the expression of myeloid markers (CD11b and CD15) and the transcription factor PU.1. Furthermore, a reduction of the leukemic stem cell population and clonogenic capability of stem cells were observed. These results show that canthin-6-one can affect Kasumi-1 cells by promoting cell death, cell cycle arrest and cell differentiation depending on concentration used. Canthin-6-one presents an interesting cytotoxic activity against leukemic cells and represents a promising scaffold for the development of molecules for anti-leukemic applications, especially by its anti-leukemic stem cell activity. Copyright © 2017 Elsevier B.V. All rights reserved.

Prevention, Evaluation, and Rehabilitation of Cycling-Related Injury.

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Kotler, Dana H; Babu, Ashwin N; Robidoux, Greg

2016-01-01

The unique quality of the bicycle is its ability to accommodate a wide variety of injuries and disabilities. Cycling for recreation, transportation, and competition is growing nationwide, and has proven health and societal benefits. The demands of each type of cycling dictate the necessary equipment, as well as potential for injury. Prevention of cycling-related injury in both the athlete and the recreational cyclist involves understanding the common mechanisms for both traumatic and overuse injury, and early correction of strength and flexibility imbalances, technique errors, and bicycle fit.

Secreted Frizzled related protein-4 (sFRP4) promotes epidermal differentiation and apoptosis

International Nuclear Information System (INIS)

Maganga, Richard; Giles, Natalie; Adcroft, Katharine; Unni, Ambili; Keeney, Diane; Wood, Fiona; Fear, Mark; Dharmarajan, Arunasalam

2008-01-01

The skin provides vital protection from infection and dehydration. Maintenance of the skin is through a constant program of proliferation, differentiation and apoptosis of epidermal cells, whereby proliferating cells in the basal layer differentiating to form the keratinized, anucleated stratum corneum. The WNT signalling pathway is known to be important in the skin. WNT signalling has been shown to be important both in epidermal development and in the maintenance and cycling of hair follicles and epidermal stem cells. However, the precise role for this pathway in epidermal differentiation remains unknown. We investigated the role of the WNT signalling inhibitor sFRP4 in epidermal differentiation. sFRP4 is expressed in both normal skin and keratinocytes in culture. Expression of sFRP4 mRNA and protein increases with keratinocyte differentiation and apoptosis, whilst exposure of keratinocytes to exogenous sFRP4 promotes apoptosis and expression of the terminal differentiation marker Involucrin. These data suggest sFRP4 promotes epidermal differentiation.

The potential role of ribosomal protein S5 on cell cycle arrest and initiation of murine erythroleukemia cell differentiation.

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Matragkou, Christina N; Papachristou, Eleni T; Tezias, Sotirios S; Tsiftsoglou, Asterios S; Choli-Papadopoulou, Theodora; Vizirianakis, Ioannis S

2008-07-01

Evidence now exists to indicate that some ribosomal proteins besides being structural components of the ribosomal subunits are involved in the regulation of cell differentiation and apoptosis. As we have shown earlier, initiation of erythroid differentiation of murine erythroleukemia (MEL) cells is associated with transcriptional inactivation of genes encoding ribosomal RNAs and ribosomal proteins S5 (RPS5) and L35a. In this study, we extended these observations and investigated whether transfection of MEL cells with RPS5 cDNA affects the onset of initiation of erythroid maturation and their entrance in cell cycle arrest. Stably transfected MEL cloned cells (MEL-C14 and MEL-C56) were established and assessed for their capacity to produce RPS5 RNA transcript and its translated product. The impact of RPS5 cDNA transfection on the RPS5 gene expression patterns and the accumulation of RPS5 protein in inducible transfected MEL cells were correlated with their ability to: (a) initiate differentiation, (b) enter cell cycle arrest at G(1)/G(0) phase, and (c) modulate the level of cyclin-dependent kinases CDK2, CDK4, and CDK6. The data presented indicate that deregulation of RPS5 gene expression (constitutive expression) affects RPS5 protein level and delays both the onset of initiation of erythroid maturation and entrance in cell cycle arrest in inducer-treated MEL cells. 2008 Wiley-Liss, Inc.

Connecting Related Rates and Differential Equations

Science.gov (United States)

Brandt, Keith

2012-01-01

This article points out a simple connection between related rates and differential equations. The connection can be used for in-class examples or homework exercises, and it is accessible to students who are familiar with separation of variables.

OECD/NEA Ongoing activities related to the nuclear fuel cycle

International Nuclear Information System (INIS)

Cornet, S.M.; McCarthy, K.; Chauvin, N.

2013-01-01

As part of its role in encouraging international collaboration, the OECD Nuclear Energy Agency is coordinating a series of projects related to the Nuclear Fuel Cycle. The Nuclear Science Committee (NSC) Working Party on Scientific Issues of the Nuclear Fuel Cycle (WPFC) comprises five different expert groups covering all aspects of the fuel cycle from front to back-end. Activities related to fuels, materials, physics, separation chemistry, and fuel cycles scenarios are being undertaken. By publishing state-of-the-art reports and organizing workshops, the groups are able to disseminate recent research advancements to the international community. Current activities mainly focus on advanced nuclear systems, and experts are working on analyzing results and establishing challenges associated to the adoption of new materials and fuels. By comparing different codes, the Expert Group on Advanced Fuel Cycle Scenarios is aiming at gaining further understanding of the scientific issues and specific national needs associated with the implementation of advanced fuel cycles. At the back end of the fuel cycle, separation technologies (aqueous and pyrochemical processing) are being assessed. Current and future activities comprise studies on minor actinides separation and post Fukushima studies. Regular workshops are also organized to discuss recent developments on Partitioning and Transmutation. In addition, the Nuclear Development Committee (NDC) focuses on the analysis of the economics of nuclear power across the fuel cycle in the context of changes of electricity markets, social acceptance and technological advances and assesses the availability of the nuclear fuel and infrastructure required for the deployment of existing and future nuclear power. The Expert Group on the Economics of the Back End of the Nuclear Fuel Cycle (EBENFC), in particular, is looking at assessing economic and financial issues related to the long term management of spent nuclear fuel. (authors)

Functional cooperation between FACT and MCM is coordinated with cell cycle and differential complex formation

Directory of Open Access Journals (Sweden)

Lin Chih-Li

2010-02-01

Full Text Available Abstract Background Functional cooperation between FACT and the MCM helicase complex constitutes an integral step during DNA replication initiation. However, mode of regulation that underlies the proper functional interaction of FACT and MCM is poorly understood. Methods & Results Here we present evidence indicating that such interaction is coordinated with cell cycle progression and differential complex formation. We first demonstrate the existence of two distinct FACT-MCM subassemblies, FACT-MCM2/4/6/7 and FACT-MCM2/3/4/5. Both complexes possess DNA unwinding activity and are subject to cell cycle-dependent enzymatic regulation. Interestingly, analysis of functional attributes further suggests that they act at distinct, and possibly sequential, steps during origin establishment and replication initiation. Moreover, we show that the phosphorylation profile of the FACT-associated MCM4 undergoes a cell cycle-dependent change, which is directly correlated with the catalytic activity of the FACT-MCM helicase complexes. Finally, at the quaternary structure level, physical interaction between FACT and MCM complexes is generally dependent on persistent cell cycle and further stabilized upon S phase entry. Cessation of mitotic cycle destabilizes the complex formation and likely leads to compromised coordination and activities. Conclusions Together, our results correlate FACT-MCM functionally and temporally with S phase and DNA replication. They further demonstrate that enzymatic activities intrinsically important for DNA replication are tightly controlled at various levels, thereby ensuring proper progression of, as well as exit from, the cell cycle and ultimately euploid gene balance.

Dihydroartemisinin inhibits the human erythroid cell differentiation by altering the cell cycle

International Nuclear Information System (INIS)

Finaurini, Sara; Basilico, Nicoletta; Corbett, Yolanda; D’Alessandro, Sarah; Parapini, Silvia; Olliaro, Piero; Haynes, Richard K.; Taramelli, Donatella

2012-01-01

Artemisinin derivatives such as dihydroartemisinin (DHA) induce significant depletion of early embryonic erythroblasts in animal models. We have reported previously that DHA specifically targets pro-erythroblasts and basophilic erythroblasts, when human CD34+ stem cells are differentiated toward the erythroid lineage, indicating that a window of susceptibility to artemisinins may exist also in human developmental erythropoiesis during pregnancy. To better investigate the toxicity of artemisinin derivatives, the structure–activity relationship was evaluated against the K562 leukaemia cell line, used as a model for differentiating early human erythroblasts. All artemisinins derivatives, except deoxyartemisinin, inhibited both spontaneous and induced erythroid differentiation, confirming that the peroxide bridge is responsible for the erythro-toxicity. On the contrary, cell growth was markedly reduced by DHA, artemisone and artesunate but not by artemisinin, 10-deoxoartemisinin or deoxy-artemisinin. The substituent at position C-10 is responsible only for the anti-proliferative effect, since 10-deoxoartemisinin did not reduce cell growth but arrested the differentiation of K562 cells. In particular, the results showed that DHA resulted the most potent and rapidly acting compound of the drug family, causing (i) the decreased expression of GpA surface receptors and the down regulation the γ-globin gene; (ii) the alteration of S phase of cell cycle and (iii) the induction of programmed cell death of early erythroblasts in a dose dependent manner within 24 h. In conclusion, these findings confirm that the active metabolite DHA is responsible for the erythro-toxicity of most of artemisinins used in therapy. Thus, as long as no further clinical data are available, current WHO recommendations of avoiding malaria treatment with artemisinins during the first trimester of pregnancy remain valid.

TRANSCRIPTOME ANALYSES REVEAL DIFFERENTIAL GENE EXPRESSION PATTERNS BETWEEN THE LIFE-CYCLE STAGES OF EMILIANIA HUXLEYI (HAPTOPHYTA) AND REFLECT SPECIALIZATION TO DIFFERENT ECOLOGICAL NICHES(1).

Science.gov (United States)

Rokitta, Sebastian D; de Nooijer, Lennart J; Trimborn, Scarlett; de Vargas, Colomban; Rost, Björn; John, Uwe

2011-08-01

Coccolithophores, especially the abundant, cosmopolitan species Emiliania huxleyi (Lohmann) W. W. Hay et H. P. Mohler, are one of the main driving forces of the oceanic carbonate pump and contribute significantly to global carbon cycling, due to their ability to calcify. A recent study indicates that termination of diploid blooms by viral infection induces life-cycle transition, and speculation has arisen about the role of the haploid, noncalcifying stage in coccolithophore ecology. To explore gene expression patterns in both life-cycle stages, haploid and diploid cells of E. huxleyi (RCC 1217 and RCC 1216) were acclimated to limiting and saturating photon flux densities. Transcriptome analyses were performed to assess differential genomic expression related to different ploidy levels and acclimation light intensities. Analyses indicated that life-cycle stages exhibit different properties of regulating genome expression (e.g., pronounced gene activation and gene silencing in the diploid stage), proteome maintenance (e.g., increased turnover of proteins in the haploid stage), as well as metabolic processing (e.g., pronounced primary metabolism and motility in the haploid stage and calcification in the diploid stage). Furthermore, higher abundances of transcripts related to endocytotic and digestive machinery were observed in the diploid stage. A qualitative feeding experiment indicated that both life-cycle stages are capable of particle uptake (0.5 μm diameter) in late-stationary growth phase. Results showed that the two life-cycle stages represent functionally distinct entities that are evolutionarily shaped to thrive in the environment they typically inhabit. © 2011 Phycological Society of America.

Life cycle assessment of a wind farm and related externalities

DEFF Research Database (Denmark)

Schleisner, Liselotte

2000-01-01

This paper concentrates on the assessment of energy and emissions related to the production and manufacture of materials for an offshore wind farm as well as a wind farm on land based on a life cycle analysis (LCA) model. In Denmark a model has been developed for life cycle assessments of different...... materials. The model is able to assess the energy use related to the production, transportation and manufacture of 1 kg of material. The energy use is divided into fuels used in order to estimate the emissions through the life cycle. In the paper the model and the attached assumptions are described......, and the model is demonstrated for two wind farms. The externalities for the wind farms are reported, showing the importance of life cycle assessment for renewable energy technologies. (C) 2000 Elsevier Science Ltd. All rights reserved....

Interactions between Genetic and Ecological Effects on the Evolution of Life Cycles.

Science.gov (United States)

Rescan, Marie; Lenormand, Thomas; Roze, Denis

2016-01-01

Sexual reproduction leads to an alternation between haploid and diploid phases, whose relative length varies widely across taxa. Previous genetical models showed that diploid or haploid life cycles may be favored, depending on dominance interactions and on effective recombination rates. By contrast, niche differentiation between haploids and diploids may favor biphasic life cycles, in which development occurs in both phases. In this article, we explore the interplay between genetical and ecological factors, assuming that deleterious mutations affect the competitivity of individuals within their ecological niche and allowing different effects of mutations in haploids and diploids (including antagonistic selection). We show that selection on a modifier gene affecting the relative length of both phases can be decomposed into a direct selection term favoring the phase with the highest mean fitness (due to either ecological differences or differential effects of mutations) and an indirect selection term favoring the phase in which selection is more efficient. When deleterious alleles occur at many loci and in the presence of ecological differentiation between haploids and diploids, evolutionary branching often occurs and leads to the stable coexistence of alleles coding for haploid and diploid cycles, while temporal variations in niche sizes may stabilize biphasic cycles.

Differential biologic effects of CPD and 6-4PP UV-induced DNA damage on the induction of apoptosis and cell-cycle arrest

International Nuclear Information System (INIS)

Lo, Hsin-Lung; Nakajima, Satoshi; Ma, Lisa; Walter, Barbara; Yasui, Akira; Ethell, Douglas W; Owen, Laurie B

2005-01-01

UV-induced damage can induce apoptosis or trigger DNA repair mechanisms. Minor DNA damage is thought to halt the cell cycle to allow effective repair, while more severe damage can induce an apoptotic program. Of the two major types of UV-induced DNA lesions, it has been reported that repair of CPD, but not 6-4PP, abrogates mutation. To address whether the two major forms of UV-induced DNA damage, can induce differential biological effects, NER-deficient cells containing either CPD photolyase or 6-4 PP photolyase were exposed to UV and examined for alterations in cell cycle and apoptosis. In addition, pTpT, a molecular mimic of CPD was tested in vitro and in vivo for the ability to induce cell death and cell cycle alterations. NER-deficient XPA cells were stably transfected with CPD-photolyase or 6-4PP photolyase to specifically repair only CPD or only 6-4PP. After 300 J/m 2 UVB exposure photoreactivation light (PR, UVA 60 kJ/m 2 ) was provided for photolyase activation and DNA repair. Apoptosis was monitored 24 hours later by flow cytometric analysis of DNA content, using sub-G1 staining to indicate apoptotic cells. To confirm the effects observed with CPD lesions, the molecular mimic of CPD, pTpT, was also tested in vitro and in vivo for its effect on cell cycle and apoptosis. The specific repair of 6-4PP lesions after UVB exposure resulted in a dramatic reduction in apoptosis. These findings suggested that 6-4PP lesions may be the primary inducer of UVB-induced apoptosis. Repair of CPD lesions (despite their relative abundance in the UV-damaged cell) had little effect on the induction of apoptosis. Supporting these findings, the molecular mimic of CPD, (dinucleotide pTpT) could mimic the effects of UVB on cell cycle arrest, but were ineffective to induce apoptosis. The primary response of the cell to UV-induced 6-4PP lesions is to trigger an apoptotic program whereas the response of the cell to CPD lesions appears to principally involve cell cycle arrest. These

Parametric Bayesian Estimation of Differential Entropy and Relative Entropy

OpenAIRE

Gupta; Srivastava

2010-01-01

Given iid samples drawn from a distribution with known parametric form, we propose the minimization of expected Bregman divergence to form Bayesian estimates of differential entropy and relative entropy, and derive such estimators for the uniform, Gaussian, Wishart, and inverse Wishart distributions. Additionally, formulas are given for a log gamma Bregman divergence and the differential entropy and relative entropy for the Wishart and inverse Wishart. The results, as always with Bayesian est...

BOOK REVIEW: Partial Differential Equations in General Relativity

Science.gov (United States)

Halburd, Rodney G.

2008-11-01

Although many books on general relativity contain an overview of the relevant background material from differential geometry, very little attention is usually paid to background material from the theory of differential equations. This is understandable in a first course on relativity but it often limits the kinds of problems that can be studied rigorously. Einstein's field equations lie at the heart of general relativity. They are a system of partial differential equations (PDEs) relating the curvature of spacetime to properties of matter. A central part of most problems in general relativity is to extract information about solutions of these equations. Most standard texts achieve this by studying exact solutions or numerical and analytical approximations. In the book under review, Alan Rendall emphasises the role of rigorous qualitative methods in general relativity. There has long been a need for such a book, giving a broad overview of the relevant background from the theory of partial differential equations, and not just from differential geometry. It should be noted that the book also covers the basic theory of ordinary differential equations. Although there are many good books on the rigorous theory of PDEs, methods related to the Einstein equations deserve special attention, not only because of the complexity and importance of these equations, but because these equations do not fit into any of the standard classes of equations (elliptic, parabolic, hyperbolic) that one typically encounters in a course on PDEs. Even specifying exactly what ones means by a Cauchy problem in general relativity requires considerable care. The main problem here is that the manifold on which the solution is defined is determined by the solution itself. This means that one does not simply define data on a submanifold. Rendall's book gives a good overview of applications and results from the qualitative theory of PDEs to general relativity. It would be impossible to give detailed

The relative contribution of genes operating in the S-methylmethionine cycle to methionine metabolism in Arabidopsis seeds.

Science.gov (United States)

Cohen, Hagai; Salmon, Asaf; Tietel, Zipora; Hacham, Yael; Amir, Rachel

2017-05-01

Enzymes operating in the S -methylmethionine cycle make a differential contribution to methionine synthesis in seeds. In addition, mutual effects exist between the S -methylmethionine cycle and the aspartate family pathway in seeds. Methionine, a sulfur-containing amino acid, is a key metabolite in plant cells. The previous lines of evidence proposed that the S-methylmethionine (SMM) cycle contributes to methionine synthesis in seeds where methionine that is produced in non-seed tissues is converted to SMM and then transported via the phloem into the seeds. However, the relative regulatory roles of the S-methyltransferases operating within this cycle in seeds are yet to be fully understood. In the current study, we generated transgenic Arabidopsis seeds with altered expression of three HOMOCYSTEINE S-METHYLTRANSFERASEs (HMTs) and METHIONINE S-METHYLTRANSFERASE (MMT), and profiled them for transcript and metabolic changes. The results revealed that AtHMT1 and AtHMT3, but not AtHMT2 and AtMMT, are the predominant enzymes operating in seeds as altered expression of these two genes affected the levels of methionine and SMM in transgenic seeds. Their manipulations resulted in adapted expression level of genes participating in methionine synthesis through the SMM and aspartate family pathways. Taken together, our findings provide new insights into the regulatory roles of the SMM cycle and the mutual effects existing between the two methionine biosynthesis pathways, highlighting the complexity of the metabolism of methionine and SMM in seeds.

A pilot study differentiating recurrent major depression from bipolar disorder cycling on the depressive pole

OpenAIRE

Hinz, Marty; Stein, Alvin; Uncini, Thomas

2010-01-01

Marty Hinz1, Alvin Stein2, Thomas Uncini31Clinical Research, NeuroResearch Clinics, Inc., Cape Coral, FL, USA; 2Stein Orthopedic Associates, Plantation, FL, USA; 3DBS Labs, Duluth, MN, USAPurpose: A novel method for differentiating and treating bipolar disorder cycling on the depressive pole from patients who are suffering a major depressive episode is explored in this work. To confirm the diagnosis of type 1 or type 2 bipolar disorder, the Diagnostic and Statistical Manual of Mental Disorder...

SOLAR CYCLE VARIABILITY AND SURFACE DIFFERENTIAL ROTATION FROM Ca II K-LINE TIME SERIES DATA

Energy Technology Data Exchange (ETDEWEB)

Scargle, Jeffrey D.; Worden, Simon P. [NASA Ames Research Center, Moffett Field, CA, 94035 (United States); Keil, Stephen L. [National Solar Observatory, P.O. Box 57, Sunspot, NM 88349 (United States)

2013-07-01

Analysis of over 36 yr of time series data from the NSO/AFRL/Sac Peak K-line monitoring program elucidates 5 components of the variation of the 7 measured chromospheric parameters: (a) the solar cycle (period {approx} 11 yr), (b) quasi-periodic variations (periods {approx} 100 days), (c) a broadband stochastic process (wide range of periods), (d) rotational modulation, and (e) random observational errors, independent of (a)-(d). Correlation and power spectrum analyses elucidate periodic and aperiodic variation of these parameters. Time-frequency analysis illuminates periodic and quasi-periodic signals, details of frequency modulation due to differential rotation, and in particular elucidates the rather complex harmonic structure (a) and (b) at timescales in the range {approx}0.1-10 yr. These results using only full-disk data suggest that similar analyses will be useful for detecting and characterizing differential rotation in stars from stellar light curves such as those being produced by NASA's Kepler observatory. Component (c) consists of variations over a range of timescales, in the manner of a 1/f random process with a power-law slope index that varies in a systematic way. A time-dependent Wilson-Bappu effect appears to be present in the solar cycle variations (a), but not in the more rapid variations of the stochastic process (c). Component (d) characterizes differential rotation of the active regions. Component (e) is of course not characteristic of solar variability, but the fact that the observational errors are quite small greatly facilitates the analysis of the other components. The data analyzed in this paper can be found at the National Solar Observatory Web site http://nsosp.nso.edu/cak{sub m}on/, or by file transfer protocol at ftp://ftp.nso.edu/idl/cak.parameters.

Postural reconfiguration and cycle-to-cycle variability in patients with work-related musculoskeletal disorders compared to healthy controls and in relation to pain emerging during a repetitive movement task.

Science.gov (United States)

Longo, Alessia; Meulenbroek, Ruud; Haid, Thomas; Federolf, Peter

2018-05-01

Movement variability in sustained repetitive tasks is an important factor in the context of work-related musculoskeletal disorders. While a popular hypothesis suggests that movement variability can prevent overuse injuries, pain evolving during task execution may also cause variability. The aim of the current study was to investigate, first, differences in movement behavior between volunteers with and without work-related pain and, second, the influence of emerging pain on movement variability. Upper-body 3D kinematics were collected as 22 subjects with musculoskeletal disorders and 19 healthy volunteers performed a bimanual repetitive tapping task with a self-chosen and a given rhythm. Three subgroups were formed within the patient group according to the level of pain the participants experienced during the task. Principal component analysis was applied to 30 joint angle coordinates to characterize in a combined analysis the movement variability associated with reconfigurations of the volunteers' postures and the cycle-to-cycle variability that occurred during the execution of the task. Patients with no task-related pain showed lower cycle-to-cycle variability compared to healthy controls. Findings also indicated an increase in movement variability as pain emerged, manifesting both as frequent postural changes and large cycle-to-cycle variability. The findings suggested a relationship between work-related musculoskeletal disorders and movement variability but further investigation is needed on this issue. Additionally, the findings provided clear evidence that pain increased motor variability. Postural reconfigurations and cycle-to-cycle variability should be considered jointly when investigating movement variability and musculoskeletal disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

IAEA Activities in the Area of Fast Reactors and Related Fuels and Fuel Cycles

International Nuclear Information System (INIS)

Monti, S.; Basak, U.; Dyck, G.; Inozemtsev, V.; Toti, A.; Zeman, A.

2013-01-01

Summary: • The IAEA role to support fast reactors and associated fuel cycle development programmes; • Main IAEA activities on fast reactors and related fuel and fuel cycle technology; • Main IAEA deliverables on fast reactors and related fuel and fuel cycle technology

Two Chimeric Regulators of G-protein Signaling (RGS) Proteins Differentially Modulate Soybean Heterotrimeric G-protein Cycle*

Science.gov (United States)

Roy Choudhury, Swarup; Westfall, Corey S.; Laborde, John P.; Bisht, Naveen C.; Jez, Joseph M.; Pandey, Sona

2012-01-01

Heterotrimeric G-proteins and the regulator of G-protein signaling (RGS) proteins, which accelerate the inherent GTPase activity of Gα proteins, are common in animals and encoded by large gene families; however, in plants G-protein signaling is thought to be more limited in scope. For example, Arabidopsis thaliana contains one Gα, one Gβ, three Gγ, and one RGS protein. Recent examination of the Glycine max (soybean) genome reveals a larger set of G-protein-related genes and raises the possibility of more intricate G-protein networks than previously observed in plants. Stopped-flow analysis of GTP-binding and GDP/GTP exchange for the four soybean Gα proteins (GmGα1–4) reveals differences in their kinetic properties. The soybean genome encodes two chimeric RGS proteins with an N-terminal seven transmembrane domain and a C-terminal RGS box. Both GmRGS interact with each of the four GmGα and regulate their GTPase activity. The GTPase-accelerating activities of GmRGS1 and -2 differ for each GmGα, suggesting more than one possible rate of the G-protein cycle initiated by each of the Gα proteins. The differential effects of GmRGS1 and GmRGS2 on GmGα1–4 result from a single valine versus alanine difference. The emerging picture suggests complex regulation of the G-protein cycle in soybean and in other plants with expanded G-protein networks. PMID:22474294

Relation between Feynman Cycles and Off-Diagonal Long-Range Order

International Nuclear Information System (INIS)

Ueltschi, Daniel

2006-01-01

The usual order parameter for Bose-Einstein condensation involves the off-diagonal correlation function of Penrose and Onsager, but an alternative is Feynman's notion of infinite cycles. We present a formula that relates both order parameters. We discuss its validity with the help of rigorous results and heuristic arguments. The conclusion is that infinite cycles do not always represent the Bose condensate

Determination of the optimum number of cardiac cycles to differentiate intra-pulmonary shunt and patent foramen ovale by saline contrast two- and three-dimensional echocardiography.

Science.gov (United States)

Bhatia, Nirmanmoh; Abushora, Mohannad Y; Donneyong, Macarius M; Stoddard, Marcus F

2014-03-01

Patent foramen ovale (PFO) and intra-pulmonary shunt (IPS) are potential causes of stroke. The most optimum cardiac cycle cutoff for bubbles to appear in the left heart on saline contrast transthoracic echocardiography (TTE) as criteria to differentiate the 2 entities is unknown. Ninety-five adult patients had saline contrast transesophageal echocardiography (TEE), two-dimensional (2D) and 3DTTE. Sensitivity and specificity of each cardiac cycle as cutoff to differentiate a PFO and IPS were obtained. Transesophageal echocardiography showed IPS in 28 and PFO in 15 patients. If bubbles appeared in the left heart within the first 4 cardiac cycles (the 4th cardiac cycle rule) as compared to alternate cutoffs, a PFO was most accurately diagnosed by both 2D and 3DTTE. Bubbles appearing at or after the 5th cardiac cycle most accurately determined an IPS. 3D versus 2DTTE had a trend for a higher sensitivity (61% vs. 36%, P = 0.06), but similar specificity (94% vs. 91%) for IPS. Accuracy of 3DTTE was 84% and 2DTTE was 75% (P = 0.08) for IPS. For PFO, 2DTTE sensitivity (87%) and specificity (98%) did not differ (P = NS) from that of 3DTTE sensitivity (73%) and specificity (100%). This study demonstrates for the first time that the 4th cardiac cycle rule differentiates PFO and IPS most optimally by 2D and 3DTTE. 3DTTE appears to have higher sensitivity for diagnosing IPS. These data suggest that 3DTTE is preferable when IPS is to be diagnosed. Both methods are similar for diagnosing PFO. © 2013, Wiley Periodicals, Inc.

The differential radiological impact of plutonium recycle in the light-water reactor fuel cycle: effluent discharges during normal operation

International Nuclear Information System (INIS)

Bouville, A.; Guetat, P.; Jones, J.A.; Kelly, G.N.; Legrand, J.; White, I.F.

1980-01-01

The radiological impact of a light-water reactor fuel cycle utilizing enriched uranium fuel may be altered by the recycle of plutonium. Differences in impact may arise during various operations in the fuel cycle: those which arise from effluents discharged during normal operation of the various installations comprising the fuel cycle are evaluated in this study. The differential radiological impact on the population of the European Communities (EC) of effluents discharged during the recycling of 10 tonnes of fissile plutonium metal is evaluated. The contributions from each stage of the fuel cycle, i.e. fuel fabrication, reactor operation and fuel reprocessing and conversion, are identified. Separate consideration is given to airborne and liquid effluents and account is taken of a wide range of environmental conditions, representative of the EC, in estimating the radiological impact. The recycle of plutonium is estimated to result in a reduction in the radiological impact from effluents of about 30% of that when using enriched uranium fuel

Age-related decrements in cycling and running performance ...

African Journals Online (AJOL)

South African Journal of Sports Medicine ... This study examined age-related decrements in athletic performance during running and cycling activities. ... These findings establish a trend that there is 'accelerated' aging during running which can perhaps be attributed to the increased weight-bearing stress on the muscles ...

Indirect immobilized Jagged1 suppresses cell cycle progression and induces odonto/osteogenic differentiation in human dental pulp cells.

Science.gov (United States)

Manokawinchoke, Jeeranan; Nattasit, Praphawi; Thongngam, Tanutchaporn; Pavasant, Prasit; Tompkins, Kevin A; Egusa, Hiroshi; Osathanon, Thanaphum

2017-08-31

Notch signaling regulates diverse biological processes in dental pulp tissue. The present study investigated the response of human dental pulp cells (hDPs) to the indirect immobilized Notch ligand Jagged1 in vitro. The indirect immobilized Jagged1 effectively activated Notch signaling in hDPs as confirmed by the upregulation of HES1 and HEY1 expression. Differential gene expression profiling using an RNA sequencing technique revealed that the indirect immobilized Jagged1 upregulated genes were mainly involved in extracellular matrix organization, disease, and signal transduction. Downregulated genes predominantly participated in the cell cycle, DNA replication, and DNA repair. Indirect immobilized Jagged1 significantly reduced cell proliferation, colony forming unit ability, and the number of cells in S phase. Jagged1 treated hDPs exhibited significantly higher ALP enzymatic activity, osteogenic marker gene expression, and mineralization compared with control. Pretreatment with a γ-secretase inhibitor attenuated the Jagged1-induced ALP activity and mineral deposition. NOTCH2 shRNA reduced the Jagged1-induced osteogenic marker gene expression, ALP enzymatic activity, and mineral deposition. In conclusion, indirect immobilized Jagged1 suppresses cell cycle progression and induces the odonto/osteogenic differentiation of hDPs via the canonical Notch signaling pathway.

Cell cycle regulation of hematopoietic stem or progenitor cells.

Science.gov (United States)

Hao, Sha; Chen, Chen; Cheng, Tao

2016-05-01

The highly regulated process of blood production is achieved through the hierarchical organization of hematopoietic stem cell (HSC) subsets and their progenies, which differ in self-renewal and differentiation potential. Genetic studies in mice have demonstrated that cell cycle is tightly controlled by the complex interplay between extrinsic cues and intrinsic regulatory pathways involved in HSC self-renewal and differentiation. Deregulation of these cellular programs may transform HSCs or hematopoietic progenitor cells (HPCs) into disease-initiating stem cells, and can result in hematopoietic malignancies such as leukemia. While previous studies have shown roles for some cell cycle regulators and related signaling pathways in HSCs and HPCs, a more complete picture regarding the molecular mechanisms underlying cell cycle regulation in HSCs or HPCs is lacking. Based on accumulated studies in this field, the present review introduces the basic components of the cell cycle machinery and discusses their major cellular networks that regulate the dormancy and cell cycle progression of HSCs. Knowledge on this topic would help researchers and clinicians to better understand the pathogenesis of relevant blood disorders and to develop new strategies for therapeutic manipulation of HSCs.

Pak3 promotes cell cycle exit and differentiation of β-cells in the embryonic pancreas and is necessary to maintain glucose homeostasis in adult mice.

Science.gov (United States)

Piccand, Julie; Meunier, Aline; Merle, Carole; Jia, Zhengping; Barnier, Jean-Vianney; Gradwohl, Gérard

2014-01-01

The transcription factor neurogenin3 (Ngn3) triggers islet cell differentiation in the developing pancreas. However, little is known about the molecular mechanisms coupling cell cycle exit and differentiation in Ngn3(+) islet progenitors. We identified a novel effector of Ngn3 endocrinogenic function, the p21 protein-activated kinase Pak3, known to control neuronal differentiation and implicated in X-linked intellectual disability in humans. We show that Pak3 expression is initiated in Ngn3(+) endocrine progenitor cells and next maintained in maturing hormone-expressing cells during pancreas development as well as in adult islet cells. In Pak3-deficient embryos, the proliferation of Ngn3(+) progenitors and β-cells is transiently increased concomitantly with an upregulation of Ccnd1. β-Cell differentiation is impaired at E15.5 but resumes at later stages. Pak3-deficient mice do not develop overt diabetes but are glucose intolerant under high-fat diet (HFD). In the intestine, Pak3 is expressed in enteroendocrine cells but is not necessary for their differentiation. Our results indicate that Pak3 is a novel regulator of β-cell differentiation and function. Pak3 acts downstream of Ngn3 to promote cell cycle exit and differentiation in the embryo by a mechanism that might involve repression of Ccnd1. In the adult, Pak3 is required for the proper control of glucose homeostasis under challenging HFD.

Mycelium differentiation and development of Streptomyces coelicolor in lab-scale bioreactors: Programmed cell death, differentiation, and lysis are closely linked to undecylprodigiosin and actinorhodin production

OpenAIRE

Rioseras de Bustos, Beatriz; López García, María Teresa (Bio); Yagüe Menéndez, Paula; Sánchez Martín, Jesús; Manteca Fernández, Ángel

2014-01-01

Streptomycetes are mycelium-forming bacteria that produce two thirds of clinically relevant secondary metabolites. Secondary metabolite production is activated at specific developmental stages of Streptomyces life cycle. Despite this, Streptomyces differentiation in industrial bioreactors tends to be underestimated and the most important parameters managed are only indirectly related to differentiation: modifications to the culture media, optimization of productive strains by random or direct...

Parametric Bayesian Estimation of Differential Entropy and Relative Entropy

Directory of Open Access Journals (Sweden)

Maya Gupta

2010-04-01

Full Text Available Given iid samples drawn from a distribution with known parametric form, we propose the minimization of expected Bregman divergence to form Bayesian estimates of differential entropy and relative entropy, and derive such estimators for the uniform, Gaussian, Wishart, and inverse Wishart distributions. Additionally, formulas are given for a log gamma Bregman divergence and the differential entropy and relative entropy for the Wishart and inverse Wishart. The results, as always with Bayesian estimates, depend on the accuracy of the prior parameters, but example simulations show that the performance can be substantially improved compared to maximum likelihood or state-of-the-art nonparametric estimators.

The expression of apoptosis-related proteins Bcl-2 and Ki67 in endometrium of ovulatory menstrual cycles

NARCIS (Netherlands)

Mertens, HJMM; Heineman, MJ; Evers, JLH

2002-01-01

Background. During the menstrual cycle, a rapid sequence of proliferation, differentiation and cell death occurs in the human endometrium. Mechanisms involved in cell proliferation have been studied extensively. Apoptosis has recently been recognized to be a physiologic phenomenon. The aim of this

The expression of apoptosis-related proteins Bcl-2 and Ki67 in endometrium of ovulatory menstrual cycles

NARCIS (Netherlands)

Mertens, Helena J. M. M.; Heineman, Maas J.; Evers, Johannes L. H.

2002-01-01

BACKGROUND: During the menstrual cycle, a rapid sequence of proliferation, differentiation and cell death occurs in the human endometrium. Mechanisms involved in cell proliferation have been studied extensively. Apoptosis has recently been recognized to be a physiologic phenomenon. The aim of this

Genome-Wide Studies Reveal that H3K4me3 Modification in Bivalent Genes Is Dynamically Regulated during the Pluripotent Cell Cycle and Stabilized upon Differentiation.

Science.gov (United States)

Grandy, Rodrigo A; Whitfield, Troy W; Wu, Hai; Fitzgerald, Mark P; VanOudenhove, Jennifer J; Zaidi, Sayyed K; Montecino, Martin A; Lian, Jane B; van Wijnen, André J; Stein, Janet L; Stein, Gary S

2016-02-15

Stem cell phenotypes are reflected by posttranslational histone modifications, and this chromatin-related memory must be mitotically inherited to maintain cell identity through proliferative expansion. In human embryonic stem cells (hESCs), bivalent genes with both activating (H3K4me3) and repressive (H3K27me3) histone modifications are essential to sustain pluripotency. Yet, the molecular mechanisms by which this epigenetic landscape is transferred to progeny cells remain to be established. By mapping genomic enrichment of H3K4me3/H3K27me3 in pure populations of hESCs in G2, mitotic, and G1 phases of the cell cycle, we found striking variations in the levels of H3K4me3 through the G2-M-G1 transition. Analysis of a representative set of bivalent genes revealed that chromatin modifiers involved in H3K4 methylation/demethylation are recruited to bivalent gene promoters in a cell cycle-dependent fashion. Interestingly, bivalent genes enriched with H3K4me3 exclusively during mitosis undergo the strongest upregulation after induction of differentiation. Furthermore, the histone modification signature of genes that remain bivalent in differentiated cells resolves into a cell cycle-independent pattern after lineage commitment. These results establish a new dimension of chromatin regulation important in the maintenance of pluripotency. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Increasing water cycle extremes in California and in relation to ENSO cycle under global warming

Science.gov (United States)

Yoon, Jin-Ho; Wang, S-Y Simon; Gillies, Robert R.; Kravitz, Ben; Hipps, Lawrence; Rasch, Philip J.

2015-01-01

Since the winter of 2013–2014, California has experienced its most severe drought in recorded history, causing statewide water stress, severe economic loss and an extraordinary increase in wildfires. Identifying the effects of global warming on regional water cycle extremes, such as the ongoing drought in California, remains a challenge. Here we analyse large-ensemble and multi-model simulations that project the future of water cycle extremes in California as well as to understand those associations that pertain to changing climate oscillations under global warming. Both intense drought and excessive flooding are projected to increase by at least 50% towards the end of the twenty-first century; this projected increase in water cycle extremes is associated with a strengthened relation to El Niño and the Southern Oscillation (ENSO)—in particular, extreme El Niño and La Niña events that modulate California's climate not only through its warm and cold phases but also its precursor patterns. PMID:26487088

Nuclear fuel cycle risk assessment: survey and computer compilation of risk-related literature. [Once-through Cycle and Plutonium Recycle

Energy Technology Data Exchange (ETDEWEB)

Yates, K.R.; Schreiber, A.M.; Rudolph, A.W.

1982-10-01

The US Nuclear Regulatory Commission has initiated the Fuel Cycle Risk Assessment Program to provide risk assessment methods for assistance in the regulatory process for nuclear fuel cycle facilities other than reactors. Both the once-through cycle and plutonium recycle are being considered. A previous report generated by this program defines and describes fuel cycle facilities, or elements, considered in the program. This report, the second from the program, describes the survey and computer compilation of fuel cycle risk-related literature. Sources of available information on the design, safety, and risk associated with the defined set of fuel cycle elements were searched and documents obtained were catalogued and characterized with respect to fuel cycle elements and specific risk/safety information. Both US and foreign surveys were conducted. Battelle's computer-based BASIS information management system was used to facilitate the establishment of the literature compilation. A complete listing of the literature compilation and several useful indexes are included. Future updates of the literature compilation will be published periodically. 760 annotated citations are included.

Gametophyte differentiation and imprinting control in plants: Crosstalk between RBR and chromatin.

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Johnston, Amal J; Gruissem, Wilhelm

2009-01-01

The Retinoblastoma (pRb) pathway has been implicated as a convergent regulatory unit in the control of cell cycle and disease. We have shown that a crosstalk between RETINOBLASTOMA RELATED (RBR), the Arabidopsis homologue of pRb, and the genes encoding proteins of the chromatin complexes involved in DNA or histone methylation, controls gametophytic and post-fertilization differentiation events and a subset of imprinting effects. We describe here a plausible model that incorporates several components of the plant Retinoblastoma pathway, thus offering a novel paradigm that merges the traditional cell cycle and the chromatin components in the control of cell differentiation and imprinting.

Differentiation of breast cancer stem cells by knockdown of CD44: promising differentiation therapy

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Pham Phuc V

2011-12-01

Full Text Available Abstract Background Breast cancer stem cells (BCSCs are the source of breast tumors. Compared with other cancer cells, cancer stem cells show high resistance to both chemotherapy and radiotherapy. Targeting of BCSCs is thus a potentially promising and effective strategy for breast cancer treatment. Differentiation therapy represents one type of cancer stem-cell-targeting therapy, aimed at attacking the stemness of cancer stem cells, thus reducing their chemo- and radioresistance. In a previous study, we showed that down-regulation of CD44 sensitized BCSCs to the anti-tumor agent doxorubicin. This study aimed to determine if CD44 knockdown caused BCSCs to differentiate into breast cancer non-stem cells (non-BCSCs. Methods We isolated a breast cancer cell population (CD44+CD24- cells from primary cultures of malignant breast tumors. These cells were sorted into four sub-populations based on their expression of CD44 and CD24 surface markers. CD44 knockdown in the BCSC population was achieved using small hairpin RNA lentivirus particles. The differentiated status of CD44 knock-down BCSCs was evaluated on the basis of changes in CD44+CD24- phenotype, tumorigenesis in NOD/SCID mice, and gene expression in relation to renewal status, metastasis, and cell cycle in comparison with BCSCs and non-BCSCs. Results Knockdown of CD44 caused BCSCs to differentiate into non-BCSCs with lower tumorigenic potential, and altered the cell cycle and expression profiles of some stem cell-related genes, making them more similar to those seen in non-BCSCs. Conclusions Knockdown of CD44 is an effective strategy for attacking the stemness of BCSCs, resulting in a loss of stemness and an increase in susceptibility to chemotherapy or radiation. The results of this study highlight a potential new strategy for breast cancer treatment through the targeting of BCSCs.

Sometimes "Newton's Method" Always "Cycles"

Science.gov (United States)

Latulippe, Joe; Switkes, Jennifer

2012-01-01

Are there functions for which Newton's method cycles for all non-trivial initial guesses? We construct and solve a differential equation whose solution is a real-valued function that two-cycles under Newton iteration. Higher-order cycles of Newton's method iterates are explored in the complex plane using complex powers of "x." We find a class of…

Differential response of cell-cycle and cell-expansion regulators to heat stress in apple (Malus domestica) fruitlets.

Science.gov (United States)

Flaishman, Moshe A; Peles, Yuval; Dahan, Yardena; Milo-Cochavi, Shira; Frieman, Aviad; Naor, Amos

2015-04-01

Temperature is one of the most significant factors affecting physiological and biochemical aspects of fruit development. Current and progressing global warming is expected to change climate in the traditional deciduous fruit tree cultivation regions. In this study, 'Golden Delicious' trees, grown in a controlled environment or commercial orchard, were exposed to different periods of heat treatment. Early fruitlet development was documented by evaluating cell number, cell size and fruit diameter for 5-70 days after full bloom. Normal activities of molecular developmental and growth processes in apple fruitlets were disrupted under daytime air temperatures of 29°C and higher as a result of significant temporary declines in cell-production and cell-expansion rates, respectively. Expression screening of selected cell cycle and cell expansion genes revealed the influence of high temperature on genetic regulation of apple fruitlet development. Several core cell-cycle and cell-expansion genes were differentially expressed under high temperatures. While expression levels of B-type cyclin-dependent kinases and A- and B-type cyclins declined moderately in response to elevated temperatures, expression of several cell-cycle inhibitors, such as Mdwee1, Mdrbr and Mdkrps was sharply enhanced as the temperature rose, blocking the cell-cycle cascade at the G1/S and G2/M transition points. Moreover, expression of several expansin genes was associated with high temperatures, making them potentially useful as molecular platforms to enhance cell-expansion processes under high-temperature regimes. Understanding the molecular mechanisms of heat tolerance associated with genes controlling cell cycle and cell expansion may lead to the development of novel strategies for improving apple fruit productivity under global warming. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Differential rotation of the Sun and the Maunder minimum of solar activity

International Nuclear Information System (INIS)

Ikhsanov, R.N.; Vitinskij, Yu.I.

1980-01-01

Nature of differential rotation of the Sun is discussed. Investigation of long term changes in differential rotation separately for two phase of 11 year cycle of the Sun activity is carried out. Data on heliographic coordinates for every day of all groups of the Sun spots for the years preceding the epoch of the minimum of the 11 year cycle and the Sun groups for the years of maximum from ''Greenwich Photoheliographic Results'' for 1875-1954 are used as initial material. It is shown that differential rotation of the Sun changes in time from one 11 year cycle of the Sun activity to another. This change is connected with the power of 11 year cycle. During the maximum phase of 11 year cycle differentiality of the rotation increases in the cycles where the cycle maximum is higher. Before the minimum of 11 year cycle rotation differentiability is lower in the cycles for which activity maximum is higher in the next 11 year cycle. Equatorial rate of the Sun rotation increases with the decrease in the cycle power when the maximum Wolf number is less than 110. The mentioned regularities took place both during Maunder minimum and before its beginning [ru

CDKL5, a novel MYCN-repressed gene, blocks cell cycle and promotes differentiation of neuronal cells.

Science.gov (United States)

Valli, Emanuele; Trazzi, Stefania; Fuchs, Claudia; Erriquez, Daniela; Bartesaghi, Renata; Perini, Giovanni; Ciani, Elisabetta

2012-01-01

Mutations in the CDKL5 (cyclin-dependent kinase-like 5) gene are associated with a severe epileptic encephalopathy (early infantile epileptic encephalopathy type 2, EIEE2) characterized by early-onset intractable seizures, infantile spasms, severe developmental delay, intellectual disability, and Rett syndrome (RTT)-like features. Despite the clear involvement of CDKL5 mutations in intellectual disability, the function of this protein during brain development and the molecular mechanisms involved in its regulation are still unknown. Using human neuroblastoma cells as a model system we found that an increase in CDKL5 expression caused an arrest of the cell cycle in the G(0)/G(1) phases and induced cellular differentiation. Interestingly, CDKL5 expression was inhibited by MYCN, a transcription factor that promotes cell proliferation during brain development and plays a relevant role in neuroblastoma biology. Through a combination of different and complementary molecular and cellular approaches we could show that MYCN acts as a direct repressor of the CDKL5 promoter. Overall our findings unveil a functional axis between MYCN and CDKL5 governing both neuron proliferation rate and differentiation. The fact that CDKL5 is involved in the control of both neuron proliferation and differentiation may help understand the early appearance of neurological symptoms in patients with mutations in CDKL5. Copyright © 2012 Elsevier B.V. All rights reserved.

Cycles of light and dark co-ordinate reversible colony differentiation in Listeria monocytogenes.

Science.gov (United States)

Tiensuu, Teresa; Andersson, Christopher; Rydén, Patrik; Johansson, Jörgen

2013-02-01

Recently, several light receptors have been identified in non-phototrophic bacteria, but their physiological roles still remain rather elusive. Here we show that colonies of the saprophytic bacterium Listeria monocytogenes undergo synchronized multicellular behaviour on agar plates, in response to oscillating light/dark conditions, giving rise to alternating ring formation (opaque and translucent rings). On agar plates, bacteria from opaque rings survive increased levels of reactive oxygen species (ROS), as well as repeated cycles of light and dark, better than bacteria from translucent rings. The ring formation is strictly dependent on a blue-light receptor, Lmo0799, acting through the stress-sigma factor, σ(B) . A transposon screening identified 48 mutants unable to form rings at alternating light conditions, with several of them showing a decreased σ(B) activity/level. However, some of the tested mutants displayed a varied σ(B) activity depending on which of the two stress conditions tested (light or H(2) O(2) exposure). Intriguingly, the transcriptional regulator PrfA and the virulence factor ActA were shown to be required for ring formation by a mechanism involving activation of σ(B) . All in all, this suggests a distinct pathway for Lmo0799 that converge into a common signalling pathway for σ(B) activation. Our results show that night and day cycles co-ordinate a reversible differentiation of a L. monocytogenes colony at room temperature, by a process synchronized by a blue-light receptor and σ(B) . © 2013 Blackwell Publishing Ltd.

Gene expression profiling of cuticular proteins across the moult cycle of the crab Portunus pelagicus

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Kuballa Anna V

2007-10-01

Full Text Available Abstract Background Crustaceans represent an attractive model to study biomineralization and cuticle matrix formation, as these events are precisely timed to occur at certain stages of the moult cycle. Moulting, the process by which crustaceans shed their exoskeleton, involves the partial breakdown of the old exoskeleton and the synthesis of a new cuticle. This cuticle is subdivided into layers, some of which become calcified while others remain uncalcified. The cuticle matrix consists of many different proteins that confer the physical properties, such as pliability, of the exoskeleton. Results We have used a custom cDNA microarray chip, developed for the blue swimmer crab Portunus pelagicus, to generate expression profiles of genes involved in exoskeletal formation across the moult cycle. A total of 21 distinct moult-cycle related differentially expressed transcripts representing crustacean cuticular proteins were isolated. Of these, 13 contained copies of the cuticle_1 domain previously isolated from calcified regions of the crustacean exoskeleton, four transcripts contained a chitin_bind_4 domain (RR consensus sequence associated with both the calcified and un-calcified cuticle of crustaceans, and four transcripts contained an unannotated domain (PfamB_109992 previously isolated from C. pagurus. Additionally, cryptocyanin, a hemolymph protein involved in cuticle synthesis and structural integrity, also displays differential expression related to the moult cycle. Moult stage-specific expression analysis of these transcripts revealed that differential gene expression occurs both among transcripts containing the same domain and among transcripts containing different domains. Conclusion The large variety of genes associated with cuticle formation, and their differential expression across the crustacean moult cycle, point to the complexity of the processes associated with cuticle formation and hardening. This study provides a molecular entry path

Molecular signature of cell cycle exit induced in human T lymphoblasts by IL-2 withdrawal

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Pfeifer Aleksandra

2009-06-01

Full Text Available Abstract Background The molecular mechanisms of cell cycle exit are poorly understood. Studies on lymphocytes at cell cycle exit after growth factor deprivation have predominantly focused on the initiation of apoptosis. We aimed to study gene expression profile of primary and immortalised IL-2-dependent human T cells forced to exit the cell cycle by growth factor withdrawal, before apoptosis could be evidenced. Results By the Affymetrix microarrays HG-U133 2.0 Plus, 53 genes were distinguished as differentially expressed before and soon after IL-2 deprivation. Among those, PIM1, BCL2, IL-8, HBEGF, DUSP6, OSM, CISH, SOCS2, SOCS3, LIF and IL13 were down-regulated and RPS24, SQSTM1, TMEM1, LRRC8D, ECOP, YY1AP1, C1orf63, ASAH1, SLC25A46 and MIA3 were up-regulated. Genes linked to transcription, cell cycle, cell growth, proliferation and differentiation, cell adhesion, and immune functions were found to be overrepresented within the set of the differentially expressed genes. Conclusion Cell cycle exit of the growth factor-deprived T lymphocytes is characterised by a signature of differentially expressed genes. A coordinate repression of a set of genes known to be induced during T cell activation is observed. However, growth arrest following exit from the cell cycle is actively controlled by several up-regulated genes that enforce the non-dividing state. The identification of genes involved in cell cycle exit and quiescence provides new hints for further studies on the molecular mechanisms regulating the non-dividing state of a cell, the mechanisms closely related to cancer development and to many biological processes.

Playing with the cell cycle to build the spinal cord.

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Molina, Angie; Pituello, Fabienne

2017-12-01

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

Toward the classification of differential calculi on κ-Minkowski space and related field theories

Energy Technology Data Exchange (ETDEWEB)

Jurić, Tajron; Meljanac, Stjepan; Pikutić, Danijel [Ruđer Bošković Institute, Theoretical Physics Division,Bijenička c.54, HR-10002 Zagreb (Croatia); Štrajn, Rina [Dipartimento di Matematica e Informatica, Università di Cagliari,viale Merello 92, I-09123 Cagliari (Italy); INFN, Sezione di Cagliari,Cagliari (Italy)

2015-07-13

Classification of differential forms on κ-Minkowski space, particularly, the classification of all bicovariant differential calculi of classical dimension is presented. By imposing super-Jacobi identities we derive all possible differential algebras compatible with the κ-Minkowski algebra for time-like, space-like and light-like deformations. Embedding into the super-Heisenberg algebra is constructed using non-commutative (NC) coordinates and one-forms. Particularly, a class of differential calculi with an undeformed exterior derivative and one-forms is considered. Corresponding NC differential calculi are elaborated. Related class of new Drinfeld twists is proposed. It contains twist leading to κ-Poincaré Hopf algebra for light-like deformation. Corresponding super-algebra and deformed super-Hopf algebras, as well as the symmetries of differential algebras are presented and elaborated. Using the NC differential calculus, we analyze NC field theory, modified dispersion relations, and discuss further physical applications.

Cell cycle pathway dysregulation in human keratinocytes during chronic exposure to low arsenite.

Science.gov (United States)

Al-Eryani, Laila; Waigel, Sabine; Jala, Venkatakrishna; Jenkins, Samantha F; States, J Christopher

2017-09-15

Arsenic is naturally prevalent in the earth's crust and widely distributed in air and water. Chronic low arsenic exposure is associated with several cancers in vivo, including skin cancer, and with transformation in vitro of cell lines including immortalized human keratinocytes (HaCaT). Arsenic also is associated with cell cycle dysregulation at different exposure levels in multiple cell lines. In this work, we analyzed gene expression in HaCaT cells to gain an understanding of gene expression changes contributing to transformation at an early time point. HaCaT cells were exposed to 0 or 100nM NaAsO 2 for 7weeks. Total RNA was purified and analyzed by microarray hybridization. Differential expression with fold change≥|1.5| and p-value≤0.05 was determined using Partek Genomic Suite™ and pathway and network analyses using MetaCore™ software (FDR≤0.05). Cell cycle analysis was performed using flow cytometry. 644 mRNAs were differentially expressed. Cell cycle/cell cycle regulation pathways predominated in the list of dysregulated pathways. Genes involved in replication origin licensing were enriched in the network. Cell cycle assay analysis showed an increase in G2/M compartment in arsenite-exposed cells. Arsenite exposure induced differential gene expression indicating dysregulation of cell cycle control, which was confirmed by cell cycle analysis. The results suggest that cell cycle dysregulation is an early event in transformation manifested in cells unable to transit G2/M efficiently. Further study at later time points will reveal additional changes in gene expression related to transformation processes. Copyright © 2017 Elsevier Inc. All rights reserved.

GC/MS-based profiling of amino acids and TCA cycle-related molecules in ulcerative colitis.

Science.gov (United States)

Ooi, Makoto; Nishiumi, Shin; Yoshie, Tomoo; Shiomi, Yuuki; Kohashi, Michitaka; Fukunaga, Ken; Nakamura, Shiro; Matsumoto, Takayuki; Hatano, Naoya; Shinohara, Masakazu; Irino, Yasuhiro; Takenawa, Tadaomi; Azuma, Takeshi; Yoshida, Masaru

2011-09-01

The roles that amino acids play in immunity and inflammation are well defined, and the relationship between inflammatory bowel disease (IBD) and certain amino acids has recently attracted attention. In this study, the levels of amino acids and trichloroacetic acid (TCA) cycle-related molecules in the colonic tissues and sera of patients with ulcerative colitis (UC) were profiled by gas chromatography/mass spectrometry (GC/MS), with the aim of evaluating whether the clinical state induced by UC leads to variations in the amino acid profile. Colonic biopsy samples from 22 UC patients were used, as well as serum samples from UC patients (n = 13), Crohn's disease (CD) patients (n = 21), and healthy volunteers (n = 17). In the GC/MS-based profiling of amino acids and TCA cycle-related molecules, lower levels of 16 amino acids and 5 TCA cycle-related molecules were observed in the colonic lesion tissues of the UC patients, and the serum profiles of amino acids and TCA cycle-related molecules of the UC patients were different from those of the CD patients and healthy volunteers. Our study raises the possibility that GC/MS-based profiling of amino acids and TCA cycle-related molecules is a useful early diagnostic tool for UC.

[Effects of biochar on soil nitrogen cycle and related mechanisms: a review].

Science.gov (United States)

Pan, Yi-Fan; Yang, Min; Dong, Da; Wu, Wei-Xiang

2013-09-01

Biochar has its unique physical and chemical properties, playing a significant role in soil amelioration, nutrient retention, fertility improvement, and carbon storage, and being a hotspot in the research areas of soil ecosystem, biogeochemical cycling, and agricultural carbon sequestration. As a kind of anthropogenic materials, biochar has the potential in controlling soil nitrogen (N) cycle directly or indirectly, and thus, has profound effects on soil ecological functions. This paper reviewed the latest literatures regarding the effects of biochar applications on soil N cycle, with the focuses on the nitrogen species adsorption and the biochemical processes (nitrification, denitrification, and nitrogen fixation) , and analyzed the related action mechanisms of biochar. The future research areas for better understanding the interactions between biochar and soil N cycle were proposed.

Electrofishing power requirements in relation to duty cycle

Science.gov (United States)

Miranda, L.E.; Dolan, C.R.

2004-01-01

Under controlled laboratory conditions we measured the electrical peak power required to immobilize (i.e., narcotize or tetanize) fish of various species and sizes with duty cycles (i.e., percentage of time a field is energized) ranging from 1.5% to 100%. Electrofishing effectiveness was closely associated with duty cycle. Duty cycles of 10-50% required the least peak power to immobilize fish; peak power requirements increased gradually above 50% duty cycle and sharply below 10%. Small duty cycles can increase field strength by making possible higher instantaneous peak voltages that allow the threshold power needed to immobilize fish to radiate farther away from the electrodes. Therefore, operating within the 10-50% range of duty cycles would allow a larger radius of immobilization action than operating with higher duty cycles. This 10-50% range of duty cycles also coincided with some of the highest margins of difference between the electrical power required to narcotize and that required to tetanize fish. This observation is worthy of note because proper use of duty cycle could help reduce the mortality associated with tetany documented by some authors. Although electrofishing with intermediate duty cycles can potentially increase effectiveness of electrofishing, our results suggest that immobilization response is not fully accounted for by duty cycle because of a potential interaction between pulse frequency and duration that requires further investigation.

Changes in total and differential white cell counts, total lymphocyte ...

African Journals Online (AJOL)

Background: Published reports on the possible changes in the various immune cell populations, especially the total lymphocyte and CD4 cell counts, during the menstrual cycle in Nigerian female subjects are relatively scarce. Aim: To determine possible changes in the total and differential white blood cell [WBC] counts, ...

Human fibroblasts display a differential focal adhesion phenotype relative to chimpanzee.

Science.gov (United States)

Advani, Alexander S; Chen, Annie Y; Babbitt, Courtney C

2016-01-01

There are a number of documented differences between humans and our closest relatives in responses to wound healing and in disease susceptibilities, suggesting a differential cellular response to certain environmental factors. In this study, we sought to look at a specific cell type, fibroblasts, to examine differences in cellular adhesion between humans and chimpanzees in visualized cells and in gene expression. We have found significant differences in the number of focal adhesions between primary human and chimpanzee fibroblasts. Additionally, we see that adhesion related gene ontology categories are some of the most differentially expressed between human and chimpanzee in normal fibroblast cells. These results suggest that human and chimpanzee fibroblasts may have somewhat different adhesive properties, which could play a role in differential disease phenotypes and responses to external factors. © The Author(s) 2016. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

A central to peripheral progression of cell cycle exit and hair cell differentiation in the developing mouse cristae.

Science.gov (United States)

Slowik, Amber D; Bermingham-McDonogh, Olivia

2016-03-01

The inner ear contains six distinct sensory organs that each maintains some ability to regenerate hair cells into adulthood. In the postnatal cochlea, there appears to be a relationship between the developmental maturity of a region and its ability to regenerate as postnatal regeneration largely occurs in the apical turn, which is the last region to differentiate and mature during development. In the mature cristae there are also regional differences in regenerative ability, which led us to hypothesize that there may be a general relationship between the relative maturity of a region and the regenerative competence of that region in all of the inner ear sensory organs. By analyzing adult mouse cristae labeled embryonically with BrdU, we found that hair cell birth starts in the central region and progresses to the periphery with age. Since the peripheral region of the adult cristae also maintains active Notch signaling and some regenerative competence, these results are consistent with the hypothesis that the last regions to develop retain some of their regenerative ability into adulthood. Further, by analyzing embryonic day 14.5 inner ears we provide evidence for a wave of hair cell birth along the longitudinal axis of the cristae from the central regions to the outer edges. Together with the data from the adult inner ears labeled with BrdU as embryos, these results suggest that hair cell differentiation closely follows cell cycle exit in the cristae, unlike in the cochlea where they are uncoupled. Copyright © 2016 Elsevier Inc. All rights reserved.

Multiaxial Cycle Deformation and Low-Cycle Fatigue Behavior of Mild Carbon Steel and Related Welded-Metal Specimen

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Weilian Qu

2017-01-01

Full Text Available The low-cycle fatigue experiments of mild carbon Q235B steel and its related welded-metal specimens are performed under uniaxial, in-phase, and 90° out-of-phase loading conditions. Significant additional cyclic hardening for 90° out-of-phase loading conditions is observed for both base metal and its related weldment. Besides, welding process produces extra additional hardening under the same loading conditions compared with the base metal. Multiaxial low-cycle fatigue strength under 90° out-of-phase loading conditions is significantly reduced for both base-metal and welded-metal specimens. The weldment has lower fatigue life than the base metal under the given loading conditions, and the fatigue life reduction of weldment increases with the increasing strain amplitude. The KBM, FS, and MKBM critical plane parameters are evaluated for the fatigue data obtained. The FS and MKBM parameters are found to show better correlation with fatigue lives for both base-metal and welded-metal specimens.

Relative boundedness and compactness theory for second-order differential operators

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Don B. Hinton

1997-01-01

Full Text Available The problem considered is to give necessary and sufficient conditions for perturbations of a second-order ordinary differential operator to be either relatively bounded or relatively compact. Such conditions are found for three classes of operators. The conditions are expressed in terms of integral averages of the coefficients of the perturbing operator.

Ambivalent sexism, attitudes towards menstruation and menstrual cycle-related symptoms.

Science.gov (United States)

Marván, Ma Luisa; Vázquez-Toboada, Rocío; Chrisler, Joan C

2014-08-01

The objective of the present study was to investigate the relationship between ambivalent sexism and beliefs and attitudes towards menstruation, and, in turn, to study the influence of these variables on menstrual cycle-related symptoms. One hundred and six Mexican women completed the Ambivalent Sexism Inventory, the Beliefs about and Attitudes toward Menstruation Questionnaire and the Menstrual Distress Questionnaire. The higher scores on benevolent sexism were associated with the most positive attitudes towards menstruation and also with the belief that a menstruating woman should or should not do some activities and that menstruation keeps women from their daily activities. The higher scores on hostile sexism were associated with rejection of menstruation as well as with feelings of embarrassment about it. Beliefs about and attitudes towards menstruation predicted menstrual cycle-related symptoms related to negative affect, impaired concentration and behavioural changes, but did not predict somatic symptoms. These results will be useful to health professionals and advocates who want to change the negative expectations and stereotypes of premenstrual and menstrual women and reduce the sexism and negative attitudes towards women that are evident in Mexican culture. © 2013 International Union of Psychological Science.

Transcriptome-based differentiation of closely-related Miscanthus lines.

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Philippe Chouvarine

Full Text Available BACKGROUND: Distinguishing between individuals is critical to those conducting animal/plant breeding, food safety/quality research, diagnostic and clinical testing, and evolutionary biology studies. Classical genetic identification studies are based on marker polymorphisms, but polymorphism-based techniques are time and labor intensive and often cannot distinguish between closely related individuals. Illumina sequencing technologies provide the detailed sequence data required for rapid and efficient differentiation of related species, lines/cultivars, and individuals in a cost-effective manner. Here we describe the use of Illumina high-throughput exome sequencing, coupled with SNP mapping, as a rapid means of distinguishing between related cultivars of the lignocellulosic bioenergy crop giant miscanthus (Miscanthus × giganteus. We provide the first exome sequence database for Miscanthus species complete with Gene Ontology (GO functional annotations. RESULTS: A SNP comparative analysis of rhizome-derived cDNA sequences was successfully utilized to distinguish three Miscanthus × giganteus cultivars from each other and from other Miscanthus species. Moreover, the resulting phylogenetic tree generated from SNP frequency data parallels the known breeding history of the plants examined. Some of the giant miscanthus plants exhibit considerable sequence divergence. CONCLUSIONS: Here we describe an analysis of Miscanthus in which high-throughput exome sequencing was utilized to differentiate between closely related genotypes despite the current lack of a reference genome sequence. We functionally annotated the exome sequences and provide resources to support Miscanthus systems biology. In addition, we demonstrate the use of the commercial high-performance cloud computing to do computational GO annotation.

Developmental Differentiation and Binding of Mental Processes with g through the Life-Span

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Andreas Demetriou

2017-05-01

Full Text Available Integration/differentiation of mental processes is major mechanism of development. Developmental theories ascribe intellectual development to it. In psychometric theory, Spearman’s law of diminishing returns postulates that increasing g allows increasing differentiation of cognitive abilities, because increased mental power allows variable investment in domain-specific learning. Empirical evidence has been inconsistent so far, with some studies supporting and others contradicting this mechanism. This state of affairs is due to a developmental phenomenon: Both differentiation and strengthening of relations between specific processes and g may happen but these changes are phase-specific and ability-specific, depending upon the developmental priorities in the formation of g in each phase. We present eight studies covering the age span from 4 to 85 years in support of this phenomenon. Using new powerful modeling methods we showed that differentiation and binding of mental processes in g occurs in cycles. Specific processes intertwine with g at the beginning of cycles when they are integrated into it; when well established, these processes may vary with increasing g, reflecting its higher flexibility. Representational knowledge, inductive inference and awareness of it, and grasp of logical constraints framing inference are the major markers of g, first intertwining with in their respective cycles and differentiating later during the periods of 2–6, 7–11, and 11–20 years, respectively. The implications of these findings for an overarching cognitive developmental/differential theory of human mind are discussed.

Nuclear fuel cycle risk assessment: survey and computer compilation of risk-related literature

International Nuclear Information System (INIS)

Yates, K.R.; Schreiber, A.M.; Rudolph, A.W.

1982-10-01

The US Nuclear Regulatory Commission has initiated the Fuel Cycle Risk Assessment Program to provide risk assessment methods for assistance in the regulatory process for nuclear fuel cycle facilities other than reactors. Both the once-through cycle and plutonium recycle are being considered. A previous report generated by this program defines and describes fuel cycle facilities, or elements, considered in the program. This report, the second from the program, describes the survey and computer compilation of fuel cycle risk-related literature. Sources of available information on the design, safety, and risk associated with the defined set of fuel cycle elements were searched and documents obtained were catalogued and characterized with respect to fuel cycle elements and specific risk/safety information. Both US and foreign surveys were conducted. Battelle's computer-based BASIS information management system was used to facilitate the establishment of the literature compilation. A complete listing of the literature compilation and several useful indexes are included. Future updates of the literature compilation will be published periodically. 760 annotated citations are included

Downregulation of rRNA transcription triggers cell differentiation.

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Yuki Hayashi

Full Text Available Responding to various stimuli is indispensable for the maintenance of homeostasis. The downregulation of ribosomal RNA (rRNA transcription is one of the mechanisms involved in the response to stimuli by various cellular processes, such as cell cycle arrest and apoptosis. Cell differentiation is caused by intra- and extracellular stimuli and is associated with the downregulation of rRNA transcription as well as reduced cell growth. The downregulation of rRNA transcription during differentiation is considered to contribute to reduced cell growth. However, the downregulation of rRNA transcription can induce various cellular processes; therefore, it may positively regulate cell differentiation. To test this possibility, we specifically downregulated rRNA transcription using actinomycin D or a siRNA for Pol I-specific transcription factor IA (TIF-IA in HL-60 and THP-1 cells, both of which have differentiation potential. The inhibition of rRNA transcription induced cell differentiation in both cell lines, which was demonstrated by the expression of the common differentiation marker CD11b. Furthermore, TIF-IA knockdown in an ex vivo culture of mouse hematopoietic stem cells increased the percentage of myeloid cells and reduced the percentage of immature cells. We also evaluated whether differentiation was induced via the inhibition of cell cycle progression because rRNA transcription is tightly coupled to cell growth. We found that cell cycle arrest without affecting rRNA transcription did not induce differentiation. To the best of our knowledge, our results demonstrate the first time that the downregulation of rRNA levels could be a trigger for the induction of differentiation in mammalian cells. Furthermore, this phenomenon was not simply a reflection of cell cycle arrest. Our results provide a novel insight into the relationship between rRNA transcription and cell differentiation.

Revisiting the TCA cycle: signaling to tumor formation.

Science.gov (United States)

Raimundo, Nuno; Baysal, Bora E; Shadel, Gerald S

2011-11-01

A role for mitochondria in tumor formation is suggested by mutations in enzymes of the TCA cycle: isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH) and fumarate hydratase (FH). Although they are all components of the TCA cycle, the resulting clinical presentations do not overlap. Activation of the hypoxia pathway can explain SDH phenotypes, but recent data suggest that FH and IDH mutations lead to tumor formation by repressing cellular differentiation. In this review, we discuss recent findings in the context of both mitochondrial and cytoplasmic components of the TCA cycle, and we propose that extrametabolic roles of TCA cycle metabolites result in reduced cellular differentiation. Furthermore, activation of the pseudohypoxia pathway likely promotes the growth of these neoplasias into tumors. Copyright © 2011 Elsevier Ltd. All rights reserved.

Differential Expression of Tyrosine Hydroxylase Protein and Apoptosis-Related Genes in Differentiated and Undifferentiated SH-SY5Y Neuroblastoma Cells Treated with MPP+

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Kawinthra Khwanraj

2015-01-01

Full Text Available The human neuroblastoma SH-SY5Y cell line has been used as a dopaminergic cell model for Parkinson’s disease research. Whether undifferentiated or differentiated SH-SY5Y cells are more suitable remains controversial. This study aims to evaluate the expression of apoptosis-related mRNAs activated by MPP+ and evaluate the differential expression of tyrosine hydroxylase (TH in undifferentiated and retinoic acid- (RA- induced differentiated cells. The western blot results showed a gradual decrease in TH in undifferentiated cells and a gradual increase in TH in differentiated cells from days 4 to 10 after cell plating. Immunostaining revealed a gradual increase in TH along with neuritic outgrowth in differentiated cells on days 4 and 7 of RA treatment. For the study on cell susceptibility to MPP+ and the expression of apoptosis-related genes, MTT assay showed a decrease in cell viability to approximately 50% requiring 500 and 1000 μM of MPP+ for undifferentiated and RA-differentiated cells, respectively. Using real-time RT-PCR, treatment with 500 μM MPP+ led to significant increases in the Bax/Bcl-2 ratio, p53, and caspase-3 in undifferentiated cells but was without significance in differentiated cells. In conclusion, differentiated cells may be more suitable, and the shorter duration of RA differentiation may make the SH-SY5Y cell model more accessible.

The regulation of autophagy differentially affects Trypanosoma cruzi metacyclogenesis.

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María Cristina Vanrell

2017-11-01

Full Text Available Autophagy is a cellular process required for the removal of aged organelles and cytosolic components through lysosomal degradation. All types of eukaryotic cells from yeasts to mammalian cells have the machinery to activate autophagy as a result of many physiological and pathological situations. The most frequent stimulus of autophagy is starvation and the result, in this case, is the fast generation of utilizable food (e.g. amino acids and basic nutrients to maintain the vital biological processes. In some organisms, starvation also triggers other associated processes such as differentiation. The protozoan parasite Trypanosoma cruzi undergoes a series of differentiation processes throughout its complex life cycle. Although not all autophagic genes have been identified in the T. cruzi genome, previous works have demonstrated the presence of essential autophagic-related proteins. Under starvation conditions, TcAtg8, which is the parasite homolog of Atg8/LC3 in other organisms, is located in autophagosome-like vesicles. In this work, we have characterized the autophagic pathway during T. cruzi differentiation from the epimastigote to metacyclic trypomastigote form, a process called metacyclogenesis. We demonstrated that autophagy is stimulated during metacyclogenesis and that the induction of autophagy promotes this process. Moreover, with exception of bafilomycin, other classical autophagy modulators have similar effects on T. cruzi autophagy. We also showed that spermidine and related polyamines can positively regulate parasite autophagy and differentiation. We concluded that both polyamine metabolism and autophagy are key processes during T. cruzi metacyclogenesis that could be exploited as drug targets to avoid the parasite cycle progression.

Differentiating immunoglobulin g4-related sclerosing cholangitis from hilar cholangiocarcinoma.

Science.gov (United States)

Tabata, Taku; Kamisawa, Terumi; Hara, Seiichi; Kuruma, Sawako; Chiba, Kazuro; Kuwata, Go; Fujiwara, Takashi; Egashira, Hideto; Koizumi, Koichi; Fujiwara, Junko; Arakawa, Takeo; Momma, Kumiko; Kurata, Masanao; Honda, Goro; Tsuruta, Koji; Itoi, Takao

2013-03-01

Few studies have differentiated immunoglobulin G (IgG) 4-related sclerosing cholangitis (IgG4-SC) from hilar cholangiocarcinoma (CC). Thus, we sought to investigate useful features for differentiating IgG4-SC from hilar CC. We retrospectively compared clinical, serological, imaging, and histological features of six patients with IgG4-SC and 42 patients with hilar CC. In patients with hilar CC, obstructive jaundice was more frequent (philar CC patients (philar or hepatic duct was completely obstructed in 83% of hilar CC patients (philar bile duct stenosis, was more frequent in IgG4-SC patients (philar CC.

An assessment of twelve- versus eighteen-month cycles for PWRs

International Nuclear Information System (INIS)

Momsen, B.F.; Dale, R.

1983-01-01

This paper discusses the technical and economic factors involved in 18-month cycles for Zion pressurized water reactors (PWRs). The technical factors are divided into the factors that define input to the economic analysis and factors that are combined with the economic results in the final decisionmaking process. The economic analysis was performed by using a Present Value of the Revenue Requirements (PVRR) method and a complementary cash flow examination. The PVRR analysis examined total costs associated with both the 12- and 18-month cycles. The only significant technical problem that was identified was the relatively low new fuel enrichment limit of 3.2 w/o U 235 . The economic analysis demonstrated that 18-month cycles yielded significant PVRR savings over the 15-year study period. The economic benefits of 18-month cycles decreased as the fuel cost increased, the operating capacity factor decreased, the refueling outage length decreased, the differential 18-month cycle outage length increased, the replacement power cost decreased, and the escalation rate decreased

Antisense myb inhibition of purified erythroid progenitors in development and differentiation is linked to cycling activity and expression of DNA polymerase alpha

International Nuclear Information System (INIS)

Valtieri, M.; Venturelli, D.; Care, A.; Fossati, C.; Pelosi, E.; Labbaye, C.; Mattia, G.; Gewirtz, A.M.; Calabretta, B.; Peschle, C.

1991-01-01

These studies aimed to determine the expression and functional role of c-myb in erythroid progenitors with different cycling activities. In the first series of experiments the erythroid burst-forming unit (BFU-E) and colony-forming unit (CFU-E) populations from adult peripheral blood (PB), bone marrow (BM), and embryonic-fetal liver (FL) were treated with either c-myb antisense oligomers or 3H-thymidine (3H-TdR). A direct correlation was always observed between the inhibitory effect of anti-myb oligomers and the level of cycling activity. Thus, the inhibitory effect of antisense c-myb on the number of BFU-E colonies was 28.3% +/- 15.8% in PB, 53.4% +/- 9.3% in BM, and 68.2% +/- 24.5% in FL. Both adult and embryonic CFU-E were markedly inhibited. Using purified PB progenitors, we observed a similar pattern, although with slightly lower inhibitory effects. In the 3H-TdR suicide assay the killing index of BFU-E was 8.9% +/- 4.2% in PB, 29.4% +/- 6.5% in BM, and 40.1% +/- 9.6% in FL. The values for adult and embryonic CFU-E were 55.7% +/- 7.9% and 60.98% +/- 6.6%, respectively. We then investigated the kinetics of c-myb mRNA level during the erythroid differentiation of purified adult PB and FL BFU-E, as evaluated in liquid-phase culture by reverse transcription-polymerase chain reaction. Adult erythroid precursors showed a gradual increase of c-myb mRNA from day 4 through day 8 of culture and a sharp decrease at later times, whereas the expression of c-myb mRNA and protein in differentiation embryonic precursors peaked 2 days earlier. In both cases, c-myb mRNA level peaked at the CFU-E stage of differentiation. Finally, highly purified adult PB BFU-E were stimulated into cycling by a 3-day treatment with interleukin-3 in liquid phase: both the sensitivity to c-myb antisense oligomers and the 3H-TdR suicide index showed a gradual, strictly parallel increase

Characterization of glucose‐related metabolic pathways in differentiated rat oligodendrocyte lineage cells

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Amaral, Ana I.; Hadera, Mussie G.; Tavares, Joana M.

2015-01-01

Although oligodendrocytes constitute a significant proportion of cells in the central nervous system (CNS), little is known about their intermediary metabolism. We have, therefore, characterized metabolic functions of primary oligodendrocyte precursor cell cultures at late stages of differentiation using isotope‐labelled metabolites. We report that differentiated oligodendrocyte lineage cells avidly metabolize glucose in the cytosol and pyruvate derived from glucose in the mitochondria. The labelling patterns of metabolites obtained after incubation with [1,2‐13C]glucose demonstrated that the pentose phosphate pathway (PPP) is highly active in oligodendrocytes (approximately 10% of glucose is metabolized via the PPP as indicated by labelling patterns in phosphoenolpyruvate). Mass spectrometry and magnetic resonance spectroscopy analyses of metabolites after incubation of cells with [1‐13C]lactate or [1,2‐13C]glucose, respectively, demonstrated that anaplerotic pyruvate carboxylation, which was thought to be exclusive to astrocytes, is also active in oligodendrocytes. Using [1,2‐13C]acetate, we show that oligodendrocytes convert acetate into acetyl CoA which is metabolized in the tricarboxylic acid cycle. Analysis of labelling patterns of alanine after incubation of cells with [1,2‐13C]acetate and [1,2‐13C]glucose showed catabolic oxidation of malate or oxaloacetate. In conclusion, we report that oligodendrocyte lineage cells at late differentiation stages are metabolically highly active cells that are likely to contribute considerably to the metabolic activity of the CNS. GLIA 2016;64:21–34 PMID:26352325

Functional studies of TcRjl, a novel GTPase of Trypanosoma cruzi, reveals phenotypes related with MAPK activation during parasite differentiation and after heterologous expression in Drosophila model system

International Nuclear Information System (INIS)

Reis Monteiro dos-Santos, Guilherme Rodrigo; Fontenele, Marcio Ribeiro; Dias, Felipe de Almeida; Oliveira, Pedro Lagerblad de; Nepomuceno-Silva, José Luciano

2015-01-01

The life cycle of the protozoan parasite Trypanosoma cruzi comprises rounds of proliferative cycles and differentiation in distinct host environments. Ras GTPases are molecular switches that play pivotal regulatory functions in cell fate. Rjl is a novel GTPase with unknown function. Herein we show that TcRjl blocks in vivo cell differentiation. The forced expression of TcRjl leads to changes in the overall tyrosine protein phosphorylation profile of parasites. TcRjl expressing parasites sustained DNA synthesis regardless the external stimuli for differentiation. Heterologous expression in the Drosophila melanogaster genetic system strongly suggests a role from TcRjl protein in RTK-dependent pathways and MAPK activation.

Functional studies of TcRjl, a novel GTPase of Trypanosoma cruzi, reveals phenotypes related with MAPK activation during parasite differentiation and after heterologous expression in Drosophila model system

Energy Technology Data Exchange (ETDEWEB)

Reis Monteiro dos-Santos, Guilherme Rodrigo [Laboratório de Parasitologia Molecular, Instituto de Biofísica Carlos Chagas Filho, CCS, UFRJ, Rio de Janeiro (Brazil); Fontenele, Marcio Ribeiro [Laboratório de Biologia Molecular do Desenvolvimento Instituto de Ciências Biomédicas, CCS, UFRJ, Rio de Janeiro (Brazil); Dias, Felipe de Almeida [Laboratório de Bioquímica de Artrópodes Hematófagos, Instituto de Bioquímica Médica, CCS, UFRJ, Rio de Janeiro (Brazil); Oliveira, Pedro Lagerblad de [Laboratório de Bioquímica de Artrópodes Hematófagos, Instituto de Bioquímica Médica, CCS, UFRJ, Rio de Janeiro (Brazil); Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (INCT-EM) (Brazil); Nepomuceno-Silva, José Luciano [Laboratório Integrado de Bioquímica Hatisaburo Masuda, NUPEM/UFRJ, Pólo Barreto, Universidade Federal do Rio de Janeiro, Campus Macaé, Macaé (Brazil); and others

2015-11-06

The life cycle of the protozoan parasite Trypanosoma cruzi comprises rounds of proliferative cycles and differentiation in distinct host environments. Ras GTPases are molecular switches that play pivotal regulatory functions in cell fate. Rjl is a novel GTPase with unknown function. Herein we show that TcRjl blocks in vivo cell differentiation. The forced expression of TcRjl leads to changes in the overall tyrosine protein phosphorylation profile of parasites. TcRjl expressing parasites sustained DNA synthesis regardless the external stimuli for differentiation. Heterologous expression in the Drosophila melanogaster genetic system strongly suggests a role from TcRjl protein in RTK-dependent pathways and MAPK activation.

Distinct regulatory functions of calpain 1 and 2 during neural stem cell self-renewal and differentiation.

Directory of Open Access Journals (Sweden)

Daniela M Santos

Full Text Available Calpains are calcium regulated cysteine proteases that have been described in a wide range of cellular processes, including apoptosis, migration and cell cycle regulation. In addition, calpains have been implicated in differentiation, but their impact on neural differentiation requires further investigation. Here, we addressed the role of calpain 1 and calpain 2 in neural stem cell (NSC self-renewal and differentiation. We found that calpain inhibition using either the chemical inhibitor calpeptin or the endogenous calpain inhibitor calpastatin favored differentiation of NSCs. This effect was associated with significant changes in cell cycle-related proteins and may be regulated by calcium. Interestingly, calpain 1 and calpain 2 were found to play distinct roles in NSC fate decision. Calpain 1 expression levels were higher in self-renewing NSC and decreased with differentiation, while calpain 2 increased throughout differentiation. In addition, calpain 1 silencing resulted in increased levels of both neuronal and glial markers, β-III Tubulin and glial fibrillary acidic protein (GFAP. Calpain 2 silencing elicited decreased levels of GFAP. These results support a role for calpain 1 in repressing differentiation, thus maintaining a proliferative NSC pool, and suggest that calpain 2 is involved in glial differentiation.

Effects of differentiated music on cycling time trial.

Science.gov (United States)

Lim, H B T; Atkinson, G; Karageorghis, C I; Eubank, M R; Eubank, M M

2009-06-01

The aim of this study was to investigate the effects of music introduced and removed during a 10-km cycling time trial with reference to Rejeski's parallel processing theory and Karageorghis, Terry and Lane's conceptual framework for the prediction of responses to asynchronous music during sub-maximal exercise. A range of performance variables, ratings of perceived exertion, positive affect, negative affect, and blood lactate were assessed. Eleven males (mean age=24.9, s=6.1 years) completed a 10-km time trial under three conditions; no music, music played initially then removed between 5-10 km, and music played between 5-10 km only. Variables of time, power, cadence, speed, RPE, blood lactate, positive and negative affect were analysed using a ConditionxDistance ANOVA. There was no significant main effect for music conditions for the performance variables, perceived exertion, blood lactate, and affect (p>0.05). Nevertheless, a significant interaction effect for ConditionxDistance was found for cycling speed, with participants cycling 1-1.25 km/h faster at the start of the music introduced time trial than in both the music removed and no music time trials (pmusic during exercise and this finding can be used to extend current theory as it does not specifically address the periodic use music. The fact that participants exercised harder when they expected music to be introduced at a later stage illustrates the behavioural influences that music can engender during self-paced exercise.

Monitoring Perceived Stress and Recovery in Relation to Cycling Performance in Female Athletes.

Science.gov (United States)

Otter, R T A; Brink, M S; van der Does, H T D; Lemmink, K A P M

2016-01-01

The purpose was to investigate perceived stress and recovery related to cycling performance of female athletes over one full year. 20 female athletes (age, 27±8 years; ˙VO2max, 50.3±4.6 mL·kg(-1)·min(-1)) were measured 8 times in one year to determine perceived stress and recovery (RESTQ-Sport) in relation to cycling performance (Lamberts and Lambert Submaximal Cycle Test (LSCT)). All 19 RESTQ-Sport scales were calculated and scores of the 4 main categories were determined (i. e., general stress, general recovery, sport-specific stress and sport-specific recovery). A balance score of total stress and recovery was calculated by recovery-stress. Power at the second stage (P80), third stage (P90) and heart rate recovery (HRR60 s) of the LSCT were determined as performance parameters. 110 RESTQ-Sports and LSCTs were analysed using a multilevel approach (random intercepts model). Higher self-efficacy was related to improvement of all performance parameters. Higher total recovery stress, and lower emotional stress were related to improvement of P90 and HRR60 s. Higher sport-specific recovery was related to P80, higher general stress, fatigue and physical complaints were related to decreased P90 and higher social stress and injury were related to decreased HRR60 s. Improved perceived recovery and stress contributed to an improved performance. Relevant information could be provided by monitoring changes in perceived stress and recovery of female athletes. © Georg Thieme Verlag KG Stuttgart · New York.

[Expression of ICAT and Wnt signaling-related proteins in the monocytic differentiation of HL-60 cells induced by a new steroidal drug NSC67657].

Science.gov (United States)

Wang, J S; Wang, W J; Wang, T; Zhang, Y

2016-04-01

To investigate the expression of mRNA and proteins of β-catenin, TCF-4 (ICAT) and Wnt signaling pathway-related genes in the monocytic differentiation of acute myeloid leukemia HL-60 cells induced by a new steroidal drug NSC67657. Wright's staining and α-NBE staining were used to observe the differentiation of HL-60 cells after 5 days of 10 μmol/L NSC67657 treatment. Flow cytometry (FCM) was used to detect the differentiation and cell cycles. The expressions of mRNA and proteins of ICAT and Wnt signaling pathway-related factors, including β-catenin, TCF-4, c-myc, cyclin D1 and TCF-1 before and after differentiation, were detected by RT-PCR and Western blot. Morphological observation showed that NSC67657 induced monocytic differentiation of HL-60 cells. At 5 days after 10 μmol/L NSC67657 treatment, the number of CD14(+) HL-60 cells was (94.37±2.84)%, significantly higher than the (1.31±0.09)% in control group (Pcells were of (18.76±0.98)%, significantly lower than that of (34.38±2.61) % in the control group (Pprotein, and down-regulated the expression of β-catenin mRNA and protin (Pprotein and nuclear protein in the HL-60 cells (P>0.05 for all). The target genes of Wnt signaling pathway, including c-myc, cyclinD1 and TCF-1 mRNA and proteins in the HL-60 cells were significantly down-regulated after NSC67657 treatment (Pcells, and down-regulates the expression of β-catenin and target genes of Wnt signaling pathway. These results indicate that Wnt signaling pathway may be directly or indirectly involved in the monocytic differentiation process of HL-60 cells.

Molecular analysis of expansion, differentiation, and growth factor treatment of human chondrocytes identifies differentiation markers and growth-related genes.

Science.gov (United States)

Benz, Karin; Breit, Stephen; Lukoschek, Martin; Mau, Hans; Richter, Wiltrud

2002-04-26

This study is intended to optimise expansion and differentiation of cultured human chondrocytes by growth factor application and to identify molecular markers to monitor their differentiation state. We dissected the molecular consequences of matrix release, monolayer, and 3D-alginate culture, growth factor optimised expansion, and re-differentiation protocols by gene expression analysis. Among 19 common cartilage molecules assessed by cDNA array, six proved best to monitor differentiation. Instant down-regulation at release of cells from the matrix was strongest for COL 2A1, fibromodulin, and PRELP while LUM, CHI3L1, and CHI3L2 were expansion-related. Both gene sets reflected the physiologic effects of the most potent growth-inducing (PDGF-BB) and proteoglycan-inducing (BMP-4) factors. Only CRTAC1 expression correlated with 2D/3D switches while the molecular phenotype of native chondrocytes was not restored. The markers and optimised protocols we suggest can help to improve cell therapy of cartilage defects and chondrocyte differentiation from stem cell sources.

Technical Meeting on Fast Reactors and Related Fuel Cycle Facilities with Improved Economic Characteristics. Presentations

International Nuclear Information System (INIS)

2013-01-01

The objectives of the meeting were: • To identify the main issues and technical features that affect capital and energy production costs of fast reactors and related fuel cycle facilities; • To present fast reactor concepts and designs with enhanced economic characteristics, as well as innovative technical solutions (components, subsystems, etc.) that have the potential to reduce the capital costs of fast reactors and related fuel cycle facilities; • To present energy models and advanced tools for the cost assessment of innovative fast reactors and associated nuclear fuel cycles; • To discuss the results of studies and ongoing R&D activities that address cost reduction and the future economic competitiveness of fast reactors; • To identify research and technology development needs in the field, also in view of new IAEA initiatives to help and support Member States in improving the economic competitiveness of fast reactors and associated nuclear fuel cycles

Differential age-related effects on conjunctive and relational visual short-term memory binding.

Science.gov (United States)

Bastin, Christine

2017-12-28

An age-related associative deficit has been described in visual short-term binding memory tasks. However, separate studies have suggested that ageing disrupts relational binding (to associate distinct items or item and context) more than conjunctive binding (to integrate features within an object). The current study directly compared relational and conjunctive binding with a short-term memory task for object-colour associations in 30 young and 30 older adults. Participants studied a number of object-colour associations corresponding to their individual object span level in a relational task in which objects were associated to colour patches and a conjunctive task where colour was integrated into the object. Memory for individual items and for associations was tested with a recognition memory test. Evidence for an age-related associative deficit was observed in the relational binding task, but not in the conjunctive binding task. This differential impact of ageing on relational and conjunctive short-term binding is discussed by reference to two underlying age-related cognitive difficulties: diminished hippocampally dependent binding and attentional resources.

Effect of resveratrol on proliferation and differentiation of embryonic cardiomyoblasts

International Nuclear Information System (INIS)

Leong, C.-W.; Wong, C.H.; Lao, S.-C.; Leong, Emilia Conceicao; Lao, Iok Fong; Law, Patrick Tik Wan; Fung, Kwok Pui; Tsang, Kam Sze; Waye, Mary Miu-Yee; Tsui, Stephen Kwok-Wing; Wang Yitao; Lee, Simon Ming-Yuen

2007-01-01

Resveratrol (trans-3,5,4'-trihydroxystilbene), a polyphenolic compound found largely in the skins of red grapes, has been used as a nutritional supplement or an investigational new drug for prevention of cardiovascular diseases. Previous reports showed that resveratrol had a protective effect against oxidative agent-induced cell injury. Our studies indicate that resveratrol plays a role in the differentiation of cardiomyoblasts. The cardiomyoblast cell line, H9c2, was exposed to 30-120 μM resveratrol for up to 5 days. Resveratrol inhibits cardiomyoblast proliferation without causing cells injury. Moreover, resveratrol treatment modulated the differentiation of morphological characteristics including elongation and cell fusion in cardiomyoblasts. Proliferation and differentiation of H9c2 cells were further revealed by measurement of the mRNA expression of a cell cycle marker (CDK2), a differentiation marker (myogenin), and a contractile apparatus protein (MLC-2). Gene expression analysis revealed that resveratrol promoted entry into cell cycle arrest but extended the myogenic differentiation progress. These results have implications for the role of resveratrol in modulating cell cycle control and differentiation in cardiomyoblasts

Cell cycle-dependent differentiation dynamics balances growth and endocrine differentiation in the pancreas

DEFF Research Database (Denmark)

Kim, Yung Hae; Larsen, Hjalte List; Rué, Paul

2015-01-01

Organogenesis relies on the spatiotemporal balancing of differentiation and proliferation driven by an expanding pool of progenitor cells. In the mouse pancreas, lineage tracing at the population level has shown that the expanding pancreas progenitors can initially give rise to all endocrine...

Differential gene expression profiling of endometrium during the mid-luteal phase of the estrous cycle between a repeat breeder (RB) and non-RB cows.

Science.gov (United States)

Hayashi, Ken-Go; Hosoe, Misa; Kizaki, Keiichiro; Fujii, Shiori; Kanahara, Hiroko; Takahashi, Toru; Sakumoto, Ryosuke

2017-03-23

Repeat breeding directly affects reproductive efficiency in cattle due to an increase in services per conception and calving interval. This study aimed to investigate whether changes in endometrial gene expression profile are involved in repeat breeding in cows. Differential gene expression profiles of the endometrium were investigated during the mid-luteal phase of the estrous cycle between repeat breeder (RB) and non-RB cows using microarray analysis. The caruncular (CAR) and intercaruncular (ICAR) endometrium of both ipsilateral and contralateral uterine horns to the corpus luteum were collected from RB (inseminated at least three times but not pregnant) and non-RB cows on Day 15 of the estrous cycle (4 cows/group). Global gene expression profiles of these endometrial samples were analyzed with a 15 K custom-made oligo-microarray for cattle. Immunohistochemistry was performed to investigate the cellular localization of proteins of three identified transcripts in the endometrium. Microarray analysis revealed that 405 and 397 genes were differentially expressed in the CAR and ICAR of the ipsilateral uterine horn of RB, respectively when compared with non-RB cows. In the contralateral uterine horn, 443 and 257 differentially expressed genes were identified in the CAR and ICAR of RB, respectively when compared with non-RB cows. Gene ontology analysis revealed that genes involved in development and morphogenesis were mainly up-regulated in the CAR of RB cows. In the ICAR of both the ipsilateral and contralateral uterine horns, genes related to the metabolic process were predominantly enriched in the RB cows when compared with non-RB cows. In the analysis of the whole uterus (combining the data above four endometrial compartments), RB cows showed up-regulation of 37 genes including PRSS2, GSTA3 and PIPOX and down-regulation of 39 genes including CHGA, KRT35 and THBS4 when compared with non-RB cows. Immunohistochemistry revealed that CHGA, GSTA3 and PRSS2 proteins

Constructing general partial differential equations using polynomial and neural networks.

Science.gov (United States)

Zjavka, Ladislav; Pedrycz, Witold

2016-01-01

Sum fraction terms can approximate multi-variable functions on the basis of discrete observations, replacing a partial differential equation definition with polynomial elementary data relation descriptions. Artificial neural networks commonly transform the weighted sum of inputs to describe overall similarity relationships of trained and new testing input patterns. Differential polynomial neural networks form a new class of neural networks, which construct and solve an unknown general partial differential equation of a function of interest with selected substitution relative terms using non-linear multi-variable composite polynomials. The layers of the network generate simple and composite relative substitution terms whose convergent series combinations can describe partial dependent derivative changes of the input variables. This regression is based on trained generalized partial derivative data relations, decomposed into a multi-layer polynomial network structure. The sigmoidal function, commonly used as a nonlinear activation of artificial neurons, may transform some polynomial items together with the parameters with the aim to improve the polynomial derivative term series ability to approximate complicated periodic functions, as simple low order polynomials are not able to fully make up for the complete cycles. The similarity analysis facilitates substitutions for differential equations or can form dimensional units from data samples to describe real-world problems. Copyright © 2015 Elsevier Ltd. All rights reserved.

Vocabulary test format and differential relations to age.

Science.gov (United States)

Bowles, Ryan P; Salthouse, Timothy A

2008-06-01

Although vocabulary tests are generally considered interchangeable, regardless of format, different tests can have different relations to age and to other cognitive abilities. In this study, 4 vocabulary test formats were examined: multiple-choice synonyms, multiple-choice antonyms, produce the definition, and picture identification. Results indicated that, although they form a single coherent vocabulary knowledge factor, the formats have different relations to age. In earlier adulthood, picture identification had the strongest growth, and produce the definition had the weakest. In later adulthood, picture identification had the strongest decline, and multiple-choice synonyms had the least. The formats differed in their relation to other cognitive variables, including reasoning, spatial visualization, memory, and speed. After accounting for the differential relations to other cognitive variables, differences in relation to age were eliminated with the exception of differences for the picture identification test. No theory of the aging of vocabulary knowledge fully explains these findings. These results suggest that using a single indicator of vocabulary may yield incomplete and somewhat misleading results about the aging of vocabulary knowledge.

Kinetics of growth and differentiation of cultured human epidermal keratinocytes

International Nuclear Information System (INIS)

Albers, K.M.

1985-01-01

A study was made of the interrelationship between replication and differentiation in cultures of human epidermal keratinocytes. Measures of both parameters were made using newly developed methods to quantify the rate at which keratinocytes replicate and the rate at which they withdraw from the cell cycle. Keratinocyte replication was measured by determining the cell doubling time, labeling index, and cell cycle duration. Cell cycle length was measured using a double label assay that determines the length of time between two successive phases of DNA synthesis. The first DNA synthesis phase was marked by labeling keratinocytes with 14 C-thymidine. At the next round of DNA synthesis, cells were labeled with bromodeoxyuridine, a heavy analog of thymidine. The cell cycle length is given by the time required for the 14 C-labeled DNA to become double labeled. To measure keratinocyte differentiation, the rate at which cells withdraw from the cell cycle was determined. To measure withdrawal, the percentage of cells labeled by a pulse of 14 C-thymidine that failed to undergo a second cycle of DNA synthesis, as measured by bromodeoxyuridine incorporation, was determined. Cells which failed to undergo a second cycle of synthesis were considered to have differentiated and withdrawn from the cell cycle

The effects and mechanisms of clinorotation on proliferation and differentiation in bone marrow mesenchymal stem cells

International Nuclear Information System (INIS)

Yan, Ming; Wang, Yongchun; Yang, Min; Liu, Yanwu; Qu, Bo; Ye, Zhengxu; Liang, Wei; Sun, Xiqing; Luo, Zhuojing

2015-01-01

Data from human and rodent studies have demonstrated that microgravity induces observed bone loss in real spaceflight or simulated experiments. The decrease of bone formation and block of maturation may play important roles in bone loss induced by microgravity. The aim of this study was to investigate the changes of proliferation and differentiation in bone marrow mesenchymal stem cells (BMSCs) induced by simulated microgravity and the mechanisms underlying it. We report here that clinorotation, a simulated model of microgravity, decreased proliferation and differentiation in BMSCs after exposure to 48 h simulated microgravity. The inhibited proliferation are related with blocking the cell cycle in G2/M and enhancing the apoptosis. While alterations of the osteoblast differentiation due to the decreased SATB2 expression induced by simulated microgravity in BMSCs. - Highlights: • Simulated microgravity inhibited proliferation and differentiation in BMSCs. • The decreased proliferation due to blocked cell cycle and enhanced the apoptosis. • The inhibited differentiation accounts for alteration of SATB2, Hoxa2 and Cbfa1

Differential Expression of Adhesion-Related Proteins and MAPK Pathways Lead to Suitable Osteoblast Differentiation of Human Mesenchymal Stem Cells Subpopulations.

Science.gov (United States)

Leyva-Leyva, Margarita; López-Díaz, Annia; Barrera, Lourdes; Camacho-Morales, Alberto; Hernandez-Aguilar, Felipe; Carrillo-Casas, Erika M; Arriaga-Pizano, Lourdes; Calderón-Pérez, Jaime; García-Álvarez, Jorge; Orozco-Hoyuela, Gabriel; Piña-Barba, Cristina; Rojas-Martínez, Augusto; Romero-Díaz, Víktor; Lara-Arias, Jorge; Rivera-Bolaños, Nancy; López-Camarillo, César; Moncada-Saucedo, Nidia; Galván-De los Santos, Alejandra; Meza-Urzúa, Fátima; Villarreal-Gómez, Luis; Fuentes-Mera, Lizeth

2015-11-01

Cellular adhesion enables communication between cells and their environment. Adhesion can be achieved throughout focal adhesions and its components influence osteoblast differentiation of human mesenchymal stem cells (hMSCs). Because cell adhesion and osteoblast differentiation are closely related, this article aimed to analyze the expression profiles of adhesion-related proteins during osteoblastic differentiation of two hMSCs subpopulations (CD105(+) and CD105(-)) and propose a strategy for assembling bone grafts based on its adhesion ability. In vitro experiments of osteogenic differentiation in CD105(-) cells showed superior adhesion efficiency and 2-fold increase of α-actinin expression compared with CD105(+) cells at the maturation stage. Interestingly, levels of activated β1-integrin increased in CD105(-) cells during the process. Additionally, the CD105(-) subpopulation showed 3-fold increase of phosphorylated FAK(Y397) compared to CD105(+) cells. Results also indicate that ERK1/2 was activated during CD105(-) bone differentiation and participation of mitogen-activated protein kinase (MAPK)-p38 in CD105(+) differentiation through a focal adhesion kinase (FAK)-independent pathway. In vivo trial demonstrated that grafts containing CD105(-) showed osteocytes embedded in a mineralized matrix, promoted adequate graft integration, increased host vascular infiltration, and efficient intramembranous repairing. In contrast, grafts containing CD105(+) showed deficient endochondral ossification and fibrocartilaginous tissue. Based on the expression of α-actinin, FAKy,(397) and ERK1/2 activation, we define maturation stage as critical for bone graft assembling. By in vitro assays, CD105(-) subpopulation showed superior adhesion efficiency compared to CD105(+) cells. Considering in vitro and in vivo assays, this study suggests that integration of a scaffold with CD105(-) subpopulation at the maturation stage represents an attractive strategy for clinical use in

Change in running kinematics after cycling are related to alterations in running economy in triathletes.

Science.gov (United States)

Bonacci, Jason; Green, Daniel; Saunders, Philo U; Blanch, Peter; Franettovich, Melinda; Chapman, Andrew R; Vicenzino, Bill

2010-07-01

Emerging evidence suggests that cycling may influence neuromuscular control during subsequent running but the relationship between altered neuromuscular control and run performance in triathletes is not well understood. The aim of this study was to determine if a 45 min high-intensity cycle influences lower limb movement and muscle recruitment during running and whether changes in limb movement or muscle recruitment are associated with changes in running economy (RE) after cycling. RE, muscle activity (surface electromyography) and limb movement (sagittal plane kinematics) were compared between a control run (no preceding cycle) and a run performed after a 45 min high-intensity cycle in 15 moderately trained triathletes. Muscle recruitment and kinematics during running after cycling were altered in 7 of 15 (46%) triathletes. Changes in kinematics at the knee and ankle were significantly associated with the change in VO(2) after cycling (precruitment in some triathletes and that changes in kinematics, especially at the ankle, are closely related to alterations in running economy after cycling. Copyright 2010 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Auxins differentially regulate root system architecture and cell cycle protein levels in maize seedlings.

Science.gov (United States)

Martínez-de la Cruz, Enrique; García-Ramírez, Elpidio; Vázquez-Ramos, Jorge M; Reyes de la Cruz, Homero; López-Bucio, José

2015-03-15

Maize (Zea mays) root system architecture has a complex organization, with adventitious and lateral roots determining its overall absorptive capacity. To generate basic information about the earlier stages of root development, we compared the post-embryonic growth of maize seedlings germinated in water-embedded cotton beds with that of plants obtained from embryonic axes cultivated in liquid medium. In addition, the effect of four different auxins, namely indole-3-acetic acid (IAA), 1-naphthaleneacetic acid (NAA), indole-3-butyric acid (IBA) and 2,4-dichlorophenoxyacetic acid (2,4-D) on root architecture and levels of the heat shock protein HSP101 and the cell cycle proteins CKS1, CYCA1 and CDKA1 were analyzed. Our data show that during the first days after germination, maize seedlings develop several root types with a simultaneous and/or continuous growth. The post-embryonic root development started with the formation of the primary root (PR) and seminal scutellar roots (SSR) and then continued with the formation of adventitious crown roots (CR), brace roots (BR) and lateral roots (LR). Auxins affected root architecture in a dose-response fashion; whereas NAA and IBA mostly stimulated crown root formation, 2,4-D showed a strong repressing effect on growth. The levels of HSP101, CKS1, CYCA1 and CDKA in root and leaf tissues were differentially affected by auxins and interestingly, HSP101 registered an auxin-inducible and root specific expression pattern. Taken together, our results show the timing of early branching patterns of maize and indicate that auxins regulate root development likely through modulation of the HSP101 and cell cycle proteins. Copyright © 2014 Elsevier GmbH. All rights reserved.

Differential Expression of Tyrosine Hydroxylase Protein and Apoptosis-Related Genes in Differentiated and Undifferentiated SH-SY5Y Neuroblastoma Cells Treated with MPP+

OpenAIRE

Khwanraj, Kawinthra; Phruksaniyom, Chareerut; Madlah, Suriyat; Dharmasaroja, Permphan

2015-01-01

The human neuroblastoma SH-SY5Y cell line has been used as a dopaminergic cell model for Parkinson's disease research. Whether undifferentiated or differentiated SH-SY5Y cells are more suitable remains controversial. This study aims to evaluate the expression of apoptosis-related mRNAs activated by MPP+ and evaluate the differential expression of tyrosine hydroxylase (TH) in undifferentiated and retinoic acid- (RA-) induced differentiated cells. The western blot results showed a gradual decre...

Gender-based differences and menstrual cycle-related changes in specific diseases: implications for pharmacotherapy.

Science.gov (United States)

Ensom, M H

2000-05-01

Pharmacists should be aware of gender-based differences and menstrual cycle-related changes in six diseases: asthma, arthritis, migraine, diabetes, depression, and epilepsy. In general, women report symptoms of physical illness at higher rates, visit physicians more frequently, and make greater use of other health care services than men. Whereas reasons for these gender differences are not fully clear, a combination of biologic, physiologic, social, behavioral, psychologic, and cultural factors most likely contributes. A significant percentage of women with asthma, arthritis, migraine, diabetes, depression, or epilepsy experience worsening of their disease premenstrually. The mechanism is unknown, but is speculated to be multifactorial because of many endogenous and exogenous modulators and mediators of each disease. As part of general therapy for cycle-related exacerbations of any one of these disorders, patients should be encouraged to use a menstrual calendar to track signs and symptoms for two to three cycles; if cyclic trends are identified, the women should anticipate exacerbations and avoid triggering factors. Cyclic modulation with pharmacotherapy may be attempted. If unsuccessful, a trial of medical ovulation suppression with a gonadotropin-releasing hormone (GnRH) analog may be warranted. If that is successful, continuous therapy with a GnRH analog and steroid add-back therapy or less expensive alternatives may be effective. If pharmacotherapy is impractical, hysterectomy and bilateral oophorectomy with estrogen replacement therapy is a last resort. Gender differences and menstrual cycle-related changes are important areas for clinical and mechanistic research.

Failure of sheathed thermocouples due to thermal cycling

International Nuclear Information System (INIS)

Anderson, R.L.; Ludwig, R.L.

1982-03-01

Open circuit failures (up to 100%) in small-diameter thermocouples used in electrically heated nuclear fuel rod simulator prototypes during thermal cycling tests were investigated to determine the cause(s) of the failures. The experiments conducted to determine the relative effects of differential thermal expansion, wire size, grain size, and manufacturing technology are described. It was concluded that the large grain size and embrittlement which result from certain common manufacturing annealing and drawing procedures were a major contributing factor in the breakage of the thermocouple wires

Inactivation of EGFR/AKT signaling enhances TSA-induced ovarian cancer cell differentiation.

Science.gov (United States)

Shao, Genbao; Lai, Wensheng; Wan, Xiaolei; Xue, Jing; Wei, Ye; Jin, Jie; Zhang, Liuping; Lin, Qiong; Shao, Qixiang; Zou, Shengqiang

2017-05-01

Ovarian tumor is one of the most lethal gynecologic cancers, but differentiation therapy for this cancer is poorly characterized. Here, we show that thrichostatin A (TSA), the well known inhibitor of histone deacetylases (HDACs), can induce cell differentiation in HO8910 ovarian cancer cells. TSA-induced cell differentiation is characterized by typical morphological change, increased expression of the differentiation marker FOXA2, decreased expression of the pluripotency markers SOX2 and OCT4, suppressing cell proliferation, and cell cycle arrest in the G1 phase. TSA also induces an elevated expression of cell cycle inhibitory protein p21Cip1 along with a decrease in cell cycle regulatory protein cyclin D1. Significantly, blockage of epidermal growth factor receptor (EGFR) signaling pathway with specific inhibitors of this signaling cascade promotes the TSA-induced differentiation of HO8910 cells. These results imply that the EGFR cascade inhibitors in combination with TSA may represent a promising differentiation therapy strategy for ovarian cancer.

Constructing regional advantage: platform policies based on related variety and differentiated knowledge bases.

NARCIS (Netherlands)

Asheim, B.T.; Boschma, R.A.; Cooke, P.

2011-01-01

Constructing regional advantage: platform policies based on related variety and differentiated knowledge bases, Regional Studies. This paper presents a regional innovation policy model based on the idea of constructing regional advantage. This policy model brings together concepts like related

Partial Differential Equations in General Relativity

International Nuclear Information System (INIS)

Choquet-Bruhat, Yvonne

2008-01-01

General relativity is a physical theory basic in the modeling of the universe at the large and small scales. Its mathematical formulation, the Einstein partial differential equations, are geometrically simple, but intricate for the analyst, involving both hyperbolic and elliptic PDE, with local and global problems. Many problems remain open though remarkable progress has been made recently towards their solutions. Alan Rendall's book states, in a down-to-earth form, fundamental results used to solve different types of equations. In each case he gives applications to special models as well as to general properties of Einsteinian spacetimes. A chapter on ODE contains, in particular, a detailed discussion of Bianchi spacetimes. A chapter entitled 'Elliptic systems' treats the Einstein constraints. A chapter entitled 'Hyperbolic systems' is followed by a chapter on the Cauchy problem and a chapter 'Global results' which contains recently proved theorems. A chapter is dedicated to the Einstein-Vlasov system, of which the author is a specialist. On the whole, the book surveys, in a concise though precise way, many essential results of recent interest in mathematical general relativity, and it is very clearly written. Each chapter is followed by an up to date bibliography. In conclusion, this book will be a valuable asset to relativists who wish to learn clearly-stated mathematical results and to mathematicians who want to penetrate into the subtleties of general relativity, as a mathematical and physical theory. (book review)

Partial Differential Equations in General Relativity

Energy Technology Data Exchange (ETDEWEB)

Choquet-Bruhat, Yvonne

2008-09-07

General relativity is a physical theory basic in the modeling of the universe at the large and small scales. Its mathematical formulation, the Einstein partial differential equations, are geometrically simple, but intricate for the analyst, involving both hyperbolic and elliptic PDE, with local and global problems. Many problems remain open though remarkable progress has been made recently towards their solutions. Alan Rendall's book states, in a down-to-earth form, fundamental results used to solve different types of equations. In each case he gives applications to special models as well as to general properties of Einsteinian spacetimes. A chapter on ODE contains, in particular, a detailed discussion of Bianchi spacetimes. A chapter entitled 'Elliptic systems' treats the Einstein constraints. A chapter entitled 'Hyperbolic systems' is followed by a chapter on the Cauchy problem and a chapter 'Global results' which contains recently proved theorems. A chapter is dedicated to the Einstein-Vlasov system, of which the author is a specialist. On the whole, the book surveys, in a concise though precise way, many essential results of recent interest in mathematical general relativity, and it is very clearly written. Each chapter is followed by an up to date bibliography. In conclusion, this book will be a valuable asset to relativists who wish to learn clearly-stated mathematical results and to mathematicians who want to penetrate into the subtleties of general relativity, as a mathematical and physical theory. (book review)

Technical Meeting on Fast Reactors and Related Fuel Cycle Facilities with Improved Economic Characteristics. Working Material

International Nuclear Information System (INIS)

2013-01-01

The objectives of the meeting were: - To identify the main issues and technical features that affect capital and energy production costs of fast reactors and related fuel cycle facilities; - To present fast reactor concepts and designs with enhanced economic characteristics, as well as innovative technical solutions (components, subsystems, etc.) that have the potential to reduce the capital costs of fast reactors and related fuel cycle facilities; - To present energy models and advanced tools for the cost assessment of innovative fast reactors and associated nuclear fuel cycles; - To discuss the results of studies and on-going R&D activities that address cost reduction and the future economic competitiveness of fast reactors; and - To identify research and technology development needs in the field, also in view of new IAEA initiatives to help and support Member States in improving the economic competitiveness of fast reactors and associated nuclear fuel cycles

Reconstructing the sales and fulfillment cycle to create supply chain differentiation

NARCIS (Netherlands)

Wouters, M.J.F.; Sharman, G.J.; Wortmann, J.C.

1999-01-01

Redesigns of supply chains have been largely limited to the differentiation of delivery processes to offer customers different delivery lead-times on different products. In the future, differentiation will go much deeper, back into the supply chains within and across companies. Companies, together

Topics of differential geometry in hamiltonian and lagrangian mechanics and relativity

International Nuclear Information System (INIS)

Rodrigues, P.R.

1982-01-01

A little introduction to the tensor and exterior algebra just as to the differential geometry is made. Such a geometry is used in order to study the hamiltonian and lagrangian mechanics stressing their geometrical aspects. Some applications are done in relativity theory. (L.C.) [pt

Pulsed feedback defers cellular differentiation.

Directory of Open Access Journals (Sweden)

Joe H Levine

2012-01-01

Full Text Available Environmental signals induce diverse cellular differentiation programs. In certain systems, cells defer differentiation for extended time periods after the signal appears, proliferating through multiple rounds of cell division before committing to a new fate. How can cells set a deferral time much longer than the cell cycle? Here we study Bacillus subtilis cells that respond to sudden nutrient limitation with multiple rounds of growth and division before differentiating into spores. A well-characterized genetic circuit controls the concentration and phosphorylation of the master regulator Spo0A, which rises to a critical concentration to initiate sporulation. However, it remains unclear how this circuit enables cells to defer sporulation for multiple cell cycles. Using quantitative time-lapse fluorescence microscopy of Spo0A dynamics in individual cells, we observed pulses of Spo0A phosphorylation at a characteristic cell cycle phase. Pulse amplitudes grew systematically and cell-autonomously over multiple cell cycles leading up to sporulation. This pulse growth required a key positive feedback loop involving the sporulation kinases, without which the deferral of sporulation became ultrasensitive to kinase expression. Thus, deferral is controlled by a pulsed positive feedback loop in which kinase expression is activated by pulses of Spo0A phosphorylation. This pulsed positive feedback architecture provides a more robust mechanism for setting deferral times than constitutive kinase expression. Finally, using mathematical modeling, we show how pulsing and time delays together enable "polyphasic" positive feedback, in which different parts of a feedback loop are active at different times. Polyphasic feedback can enable more accurate tuning of long deferral times. Together, these results suggest that Bacillus subtilis uses a pulsed positive feedback loop to implement a "timer" that operates over timescales much longer than a cell cycle.

Glutathione maintenance mitigates age-related susceptibility to redox cycling agents

Directory of Open Access Journals (Sweden)

Nicholas O. Thomas

2016-12-01

Full Text Available Isolated hepatocytes from young (4–6 mo and old (24–26 mo F344 rats were exposed to increasing concentrations of menadione, a vitamin K derivative and redox cycling agent, to determine whether the age-related decline in Nrf2-mediated detoxification defenses resulted in heightened susceptibility to xenobiotic insult. An LC50 for each age group was established, which showed that aging resulted in a nearly 2-fold increase in susceptibility to menadione (LC50 for young: 405 μM; LC50 for old: 275 μM. Examination of the known Nrf2-regulated pathways associated with menadione detoxification revealed, surprisingly, that NAD(PH: quinone oxido-reductase 1 (NQO1 protein levels and activity were induced 9-fold and 4-fold with age, respectively (p=0.0019 and p=0.018; N=3, but glutathione peroxidase 4 (GPX4 declined by 70% (p=0.0043; N=3. These results indicate toxicity may stem from vulnerability to lipid peroxidation instead of inadequate reduction of menadione semi-quinone. Lipid peroxidation was 2-fold higher, and GSH declined by a 3-fold greater margin in old versus young rat cells given 300 µM menadione (p2-fold reduction in cell death, suggesting that the age-related increase in menadione susceptibility likely stems from attenuated GSH-dependent defenses. This data identifies cellular targets for intervention in order to limit age-related toxicological insults to menadione and potentially other redox cycling compounds.

Impact of cycling cells and cell cycle regulation on Hydra regeneration.

Science.gov (United States)

Buzgariu, Wanda; Wenger, Yvan; Tcaciuc, Nina; Catunda-Lemos, Ana-Paula; Galliot, Brigitte

2018-01-15

Hydra tissues are made from three distinct populations of stem cells that continuously cycle and pause in G2 instead of G1. To characterize the role of cell proliferation after mid-gastric bisection, we have (i) used flow cytometry and classical markers to monitor cell cycle modulations, (ii) quantified the transcriptomic regulations of 202 genes associated with cell proliferation during head and foot regeneration, and (iii) compared the impact of anti-proliferative treatments on regeneration efficiency. We confirm two previously reported events: an early mitotic wave in head-regenerating tips, when few cell cycle genes are up-regulated, and an early-late wave of proliferation on the second day, preceded by the up-regulation of 17 cell cycle genes. These regulations appear more intense after mid-gastric bisection than after decapitation, suggesting a position-dependent regulation of cell proliferation during head regeneration. Hydroxyurea, which blocks S-phase progression, delays head regeneration when applied before but not after bisection. This result is consistent with the fact that the Hydra central region is enriched in G2-paused adult stem cells, poised to divide upon injury, thus forming a necessary constitutive pro-blastema. However a prolonged exposure to hydroxyurea does not block regeneration as cells can differentiate apical structures without traversing S-phase, and also escape in few days the hydroxyurea-induced S-phase blockade. Thus Hydra head regeneration, which is a fast event, is highly plastic, relying on large stocks of adult stem cells paused in G2 at amputation time, which immediately divide to proliferate and/or differentiate apical structures even when S-phase is blocked. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Calculation of prevalence estimates through differential equations: application to stroke-related disability.

Science.gov (United States)

Mar, Javier; Sainz-Ezkerra, María; Moler-Cuiral, Jose Antonio

2008-01-01

Neurological diseases now make up 6.3% of the global burden of disease mainly because they cause disability. To assess disability, prevalence estimates are needed. The objective of this study is to apply a method based on differential equations to calculate the prevalence of stroke-related disability. On the basis of a flow diagram, a set of differential equations for each age group was constructed. The linear system was solved analytically and numerically. The parameters of the system were obtained from the literature. The model was validated and calibrated by comparison with previous results. The stroke prevalence rate per 100,000 men was 828, and the rate for stroke-related disability was 331. The rates steadily rose with age, but the group between the ages of 65 and 74 years had the highest total number of individuals. Differential equations are useful to represent the natural history of neurological diseases and to make possible the calculation of the prevalence for the various states of disability. In our experience, when compared with the results obtained by Markov models, the benefit of the continuous use of time outweighs the mathematical requirements of our model. (c) 2008 S. Karger AG, Basel.

How to Make Eccentricity Cycles in Stratigraphy: the Role of Compaction

Science.gov (United States)

Liu, W.; Hinnov, L.; Wu, H.; Pas, D.

2017-12-01

Milankovitch cycles from astronomically driven climate variations have been demonstrated as preserved in cyclostratigraphy throughout geologic time. These stratigraphic cycles have been identified in many types of proxies, e.g., gamma ray, magnetic susceptibility, oxygen isotopes, carbonate content, grayscale, etc. However, the commonly prominent spectral power of orbital eccentricity cycles in stratigraphy is paradoxical to insolation, which is dominated by precession index power. How is the spectral power transferred from precession to eccentricity in stratigraphy? Nonlinear sedimentation and bioturbation have long been identified as players in this transference. Here, we propose that in the absence of bioturbation differential compaction can generate the transference. Using insolation time series, we trace the steps by which insolation is transformed into stratigraphy, and how differential compaction of lithology acts to transfer spectral power from precession to eccentricity. Differential compaction is applied to unique values of insolation, which is assumed to control the type of deposited sediment. High compaction is applied to muds, and progressively lower compaction is applied to silts and sands, or carbonate. Linear differential compaction promotes eccentricity spectral power, but nonlinear differential compaction elevates eccentricity spectral power to dominance and precession spectral power to near collapse as is often observed in real stratigraphy. Keywords: differential compaction, cyclostratigraphy, insolation, eccentricity

Review of the IAEA Nuclear Fuel Cycle Materials Section activities related to WWER fuel

International Nuclear Information System (INIS)

Killeen, J.

2003-01-01

The IAEA Nuclear Fuel Cycle Programme, designated as Programme B, has the main objective of supporting Member States in policy making, strategic planning, developing technology and addressing issues with respect to safe, reliable, economically efficient, proliferation resistant and environmentally sound nuclear fuel cycle. This paper is concentrated on describing the work within Sub-programme B.2 'Fuel Performance and Technology'. Two Technical Working Groups assist in the preparation of the IAEA programme in the nuclear fuel cycle area - Technical Working Group on Water Reactor Fuel Performance and Technology and Technical Working Group on Nuclear Fuel Cycle Options. The activities of the Unit within the Nuclear Fuel Cycle and Materials Section working on Fuel Performance and Technology are given, based on the sub-programme structure of the Agency programme and budget for 2002-2003. Within the framework of Co-ordinated Research Projects a study of the delayed hydride cracking (DHC) of the zirconium alloys used in pressurised heavy water reactors (PHWR) involving 10 countries has been completed. It achieved very effective transfer of know-how at the laboratory level in three technologically important areas: 1) Controlled hydriding of samples to predetermined levels; 2) Accurate measurement of hydrogen concentrations at the relatively low levels found in pressure tubes and RBMK channel tubes; and 3) In the determination of DHC rates under various conditions of temperature and stress. A new project has been started on the 'Improvement of Models used for Fuel Behaviour Simulation' (FUMEX II) to assist Member States in improving the predictive capabilities of computer codes used in modelling fuel behaviour for extended burnup. The IAEA also collaborates with organisations in the Member States to support activities and meetings on nuclear fuel cycle related topics

Site-dependent life-cycle impact assessment of acidification

DEFF Research Database (Denmark)

Potting, Josepha Maria Barbara; Schöpp, W.; Blok, Kornelis

1998-01-01

The lack of spatial differentiation in current life-cycle impact assessment (LCIA) affects the relevance of the assessed impact. This article first describes a framework for constructing factors relating the region of emission to the acidifying impact on its deposition areas. Next, these factors...... are established for 44 European regions with the help of the RAINS model, an integrated assessment model that combines information on regional emission levels with information on long-range atmospheric transport to estimate patterns of deposition and concentration for comparison with critical loads and thresholds...

Differential gene expression during Trypanosoma cruzi metacyclogenesis

Directory of Open Access Journals (Sweden)

Marco Aurelio Krieger

1999-09-01

Full Text Available The transformation of epimastigotes into metacyclic trypomastigotes involves changes in the pattern of expressed genes, resulting in important morphological and functional differences between these developmental forms of Trypanosoma cruzi. In order to identify and characterize genes involved in triggering the metacyclogenesis process and in conferring to metacyclic trypomastigotes their stage specific biological properties, we have developed a method allowing the isolation of genes specifically expressed when comparing two close related cell populations (representation of differential expression or RDE. The method is based on the PCR amplification of gene sequences selected by hybridizing and subtracting the populations in such a way that after some cycles of hybridization-amplification genes specific to a given population are highly enriched. The use of this method in the analysis of differential gene expression during T. cruzi metacyclogenesis (6 hr and 24 hr of differentiation and metacyclic trypomastigotes resulted in the isolation of several clones from each time point. Northern blot analysis showed that some genes are transiently expressed (6 hr and 24 hr differentiating cells, while others are present in differentiating cells and in metacyclic trypomastigotes. Nucleotide sequencing of six clones characterized so far showed that they do not display any homology to gene sequences available in the GeneBank.

Single generation cycles and delayed feedback cycles are not separate phenomena.

Science.gov (United States)

Pfaff, T; Brechtel, A; Drossel, B; Guill, C

2014-12-01

We study a simple model for generation cycles, which are oscillations with a period of one or a few generation times of the species. The model is formulated in terms of a single delay-differential equation for the population density of an adult stage, with recruitment to the adult stage depending on the intensity of competition during the juvenile phase. This model is a simplified version of a group of models proposed by Gurney and Nisbet, who were the first to distinguish between single-generation cycles and delayed-feedback cycles. According to these authors, the two oscillation types are caused by different mechanisms and have periods in different intervals, which are one to two generation times for single-generation cycles and two to four generation times for delayed-feedback cycles. By abolishing the strict coupling between the maturation time and the time delay between competition and its effect on the population dynamics, we find that single-generation cycles and delayed-feedback cycles occur in the same model version, with a gradual transition between the two as the model parameters are varied over a sufficiently large range. Furthermore, cycle periods are not bounded to lie within single octaves. This implies that a clear distinction between different types of generation cycles is not possible. Cycles of all periods and even chaos can be generated by varying the parameters that determine the time during which individuals from different cohorts compete with each other. This suggests that life-cycle features in the juvenile stage and during the transition to the adult stage are important determinants of the dynamics of density limited populations. Copyright © 2014 Elsevier Inc. All rights reserved.

Activity of iodine-123 metaiodobenzylguanidine in childhood neuroblastoma: lack of relation to tumour differentiation in vivo

International Nuclear Information System (INIS)

Brans, B.; Wiele, C. van de; Simons, M.; Dierckx, R.A.; Laureys, G.; Dhooge, C.; Schelfhout, V.; Potter, C.R. de

1998-01-01

Neuroblastoma (NB) tumour cells have a remarkable tendency to differentiate spontaneously or under the influence of certain drugs. It is not clear whether metaiodobenzylguanidine (MIBG) uptake correlates with differentiation of NB cells. In 28 tumours of 26 patients, iodine-123 MIBG uptake in primary NBs was studied in relation to tumour differentiation, tumour size, cell density and degree of necrosis in subsequently resected specimens. Genetic features such as the presence of chromosomal aberrations (1p-deletion and MYCN amplification) and/or P-glycoprotein (mdr-1 gene product) were also evaluated in relation to MIBG uptake. A highly variable and unpredictable intensity of MIBG uptake was observed in primary as well as secondary resected tumours. This intensity did not relate to any of the above-mentioned factors except that there was a trend towards more intense uptake with increasing size of the tumour. We conclude from our observations that, in contrast to commonly held opinion, well-differentiated tumours do not a priori show a lower MIBG uptake in vivo, even when there are a low number of viable cells and a high degree of necrosis. The degree of differentiation or tumour viability and necrosis following longstanding chemotherapeutic treatment cannot be predicted by the MIBG scan findings. The observed MIBG uptake may be importantly influenced by factors other than those associated with cellular differentiation. (orig.)

Activity of iodine-123 metaiodobenzylguanidine in childhood neuroblastoma: lack of relation to tumour differentiation in vivo

Energy Technology Data Exchange (ETDEWEB)

Brans, B.; Wiele, C. van de; Simons, M.; Dierckx, R.A. [Division of Nuclear Medicine, University Hospital Gent, Gent (Belgium); Laureys, G.; Dhooge, C. [Department of Pediatric Hemato-oncology, University Hospital Gent, Gent (Belgium); Schelfhout, V.; Potter, C.R. de [Department of Pathology, University Hospital Gent, Gent (Belgium)

1998-02-01

Neuroblastoma (NB) tumour cells have a remarkable tendency to differentiate spontaneously or under the influence of certain drugs. It is not clear whether metaiodobenzylguanidine (MIBG) uptake correlates with differentiation of NB cells. In 28 tumours of 26 patients, iodine-123 MIBG uptake in primary NBs was studied in relation to tumour differentiation, tumour size, cell density and degree of necrosis in subsequently resected specimens. Genetic features such as the presence of chromosomal aberrations (1p-deletion and MYCN amplification) and/or P-glycoprotein (mdr-1 gene product) were also evaluated in relation to MIBG uptake. A highly variable and unpredictable intensity of MIBG uptake was observed in primary as well as secondary resected tumours. This intensity did not relate to any of the above-mentioned factors except that there was a trend towards more intense uptake with increasing size of the tumour. We conclude from our observations that, in contrast to commonly held opinion, well-differentiated tumours do not a priori show a lower MIBG uptake in vivo, even when there are a low number of viable cells and a high degree of necrosis. The degree of differentiation or tumour viability and necrosis following longstanding chemotherapeutic treatment cannot be predicted by the MIBG scan findings. The observed MIBG uptake may be importantly influenced by factors other than those associated with cellular differentiation. (orig.) With 2 figs., 1 tab., 19 refs.

Relative thinking in consumer choice between differentiated goods and services and its implications for business strategy

Directory of Open Access Journals (Sweden)

Ofer H. Azar

2011-02-01

Full Text Available The article shows that when people consider differentiated goods or services that differ in price and quality, they exhibit a decision-making bias of ``relative thinking'': relative price differences affect them even when economic theory suggests that only absolute price differences matter. This result is obtained in four different consumption categories. Sometimes subjects are affected only by relative price differences (``full relative thinking'' and sometimes also by absolute price differences (``partial relative thinking''. This behavior has implications for various disciplines, and it is particularly relevant in models dealing with horizontal or vertical differentiation, optimal pricing, competitive strategy, or advertising.

Fuel cycle related parametric study considering long lived actinide production, decay heat and fuel cycle performances

International Nuclear Information System (INIS)

Raepsaet, X.; Damian, F.; Lenain, R.; Lecomte, M.

2001-01-01

One of the very attractive HTGR reactor characteristics is its highly versatile and flexible core that can fulfil a wide range of diverse fuel cycles. Based on a GTMHR-600 MWth reactor, analyses of several fuel cycles were carried out without taking into account common fuel particle performance limits (burnup, fast fluence, temperature). These values are, however, indicated in each case. Fuel derived from uranium, thorium and a wide variety of plutonium grades has been considered. Long-lived actinide production and total residual decay heat were evaluated for the various types of fuel. The results presented in this papers provide a comparison of the potential and limits of each fuel cycle and allow to define specific cycles offering lowest actinide production and residual heat associated with a long life cycle. (author)

Endothelial cell subpopulations in vitro: cell volume, cell cycle, and radiosensitivity

International Nuclear Information System (INIS)

Rubin, D.B.; Drab, E.A.; Bauer, K.D.

1989-01-01

Vascular endothelial cells (EC) are important clinical targets of radiation and other forms of free radical/oxidant stresses. In this study, we found that the extent of endothelial damage may be determined by the different cytotoxic responses of EC subpopulations. The following characteristics of EC subpopulations were examined: (1) cell volume; (2) cell cycle position; and (3) cytotoxic indexes for both acute cell survival and proliferative capacity after irradiation (137Cs, gamma, 0-10 Gy). EC cultured from bovine aortas were separated by centrifugal elutriation into subpopulations of different cell volumes. Through flow cytometry, we found that cell volume was related to the cell cycle phase distribution. The smallest EC were distributed in G1 phase and the larger cells were distributed in either early S, middle S, or late S + G2M phases. Cell cycle phase at the time of irradiation was not associated with acute cell loss. However, distribution in the cell cycle did relate to cell survival based on proliferative capacity (P less than 0.01). The order of increasing radioresistance was cells in G1 (D0 = 110 cGy), early S (135 cGy), middle S (145 cGy), and late S + G2M phases (180 cGy). These findings (1) suggest an age-related response to radiation in a nonmalignant differentiated cell type and (2) demonstrate EC subpopulations in culture

Relation Between the Cell Volume and the Cell Cycle Dynamics in Mammalian cell

International Nuclear Information System (INIS)

Magno, A.C.G.; Oliveira, I.L.; Hauck, J.V.S.

2016-01-01

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 (paper)

The circle of life: A cross-cultural comparison of children's attribution of life-cycle traits.

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Burdett, Emily R R; Barrett, Justin L

2016-06-01

Do children attribute mortality and other life-cycle traits to all minded beings? The present study examined whether culture influences young children's ability to conceptualize and differentiate human beings from supernatural beings (such as God) in terms of life-cycle traits. Three-to-5-year-old Israeli and British children were questioned whether their mother, a friend, and God would be subject to various life-cycle processes: Birth, death, ageing, existence/longevity, and parentage. Children did not anthropomorphize but differentiated among human and supernatural beings, attributing life-cycle traits to humans, but not to God. Although 3-year-olds differentiated significantly among agents, 5-year-olds attributed correct life-cycle traits more consistently than younger children. The results also indicated some cross-cultural variation in these attributions. Implications for biological conceptual development are discussed. © 2015 The British Psychological Society.

Metabolism: Part II. The Tricarboxylic Acid (TCA), Citric Acid, or Krebs Cycle.

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Bodner, George M.

1986-01-01

Differentiates the tricarboxylic acid (TCA) cycle (or Krebs cycle) from glycolysis, and describes the bridge between the two as being the conversion of pyruvate into acetyl coenzyme A. Discusses the eight steps in the TCA cycle, the results of isotopic labeling experiments, and the net effects of the TCA cycle. (TW)

International Conference on Fast Reactors and Related Fuel Cycles: Safe Technologies and Sustainable Scenarios (FR13). Presentations

International Nuclear Information System (INIS)

2013-01-01

The conference, which was held from 4 to 7 of March 2013 in Paris, provided a forum to exchange information on national and international programmes, and more generally new developments and experience, in the field of fast reactors and related fuel cycle technologies. A first goal was to identify and discuss strategic and technical options that have been proposed by individual countries or companies. Another goal was to promote the development of fast reactors and related fuel cycle technologies in a safe, proliferation resistant and economic way. A third goal was to identify gaps and key issues that need to be addressed in relation to the industrial deployment of fast reactors with a closed fuel cycle. A fourth goal was to engage young scientists and engineers in this field, in particular with sustainability, innovation, simulation, safety, economics and public acceptance

A pilot study differentiating recurrent major depression from bipolar disorder cycling on the depressive pole.

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Hinz, Marty; Stein, Alvin; Uncini, Thomas

2010-11-09

A novel method for differentiating and treating bipolar disorder cycling on the depressive pole from patients who are suffering a major depressive episode is explored in this work. To confirm the diagnosis of type 1 or type 2 bipolar disorder, the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria require that at least one manic or hypomanic episode be identified. History of one or more manic or hypomanic episodes may be impossible to obtain, representing a potential blind spot in the DSM-IV diagnostic criteria. Many bipolar patients who cycle primarily on the depressive side for many years carry a misdiagnosis of recurrent major depression, leading to treatment with antidepressants that achieve little or no relief of symptoms. This article discusses a novel approach for diagnosing and treating patients with bipolar disorder cycling on the depressive pole versus patients with recurrent major depression. Patients involved in this study were formally diagnosed with recurrent major depression under DSM-IV criteria and had no medical history of mania or hypomania to support the diagnosis of bipolar disorder. All patients had suffered multiple depression treatment failures in the past, when evaluated under DSM-IV guidelines, secondary to administration of antidepressant drugs and/or serotonin with dopamine amino acid precursors. This study contained 1600 patients who were diagnosed with recurrent major depression under the DSM-IV criteria. All patients had no medical history of mania or hypomania. All patients experienced no relief of depression symptoms on level 3 amino acid dosing values of the amino acid precursor dosing protocol. Of 1600 patients studied, 117 (7.3%) nonresponder patients were identified who experienced no relief of depression symptoms when the serotonin and dopamine amino acid precursor dosing values were adjusted to establish urinary serotonin and urinary dopamine levels in the Phase III therapeutic ranges. All of the 117

Msx2 alters the timing of retinal ganglion cells fate commitment and differentiation

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Jiang, Shao-Yun, E-mail: jiangshaoyun@yahoo.com [School of Dentistry, Tianjin Medical University, 12 Qi Xiang Tai Street, Tianjin 300070 (China); Wang, Jian-Tao, E-mail: wangjiantao65@hotmail.com [Eye Center, Tianjin Medical University, 64 Tongan Road, Tianjin 300070 (China); Dohney Eye Institute, Keck School of Medicine, University of Southern California, 1355 San Pablo Street, DOH 314, Los Angeles, CA 90033 (United States)

2010-05-14

Timing of cell fate commitment determines distinct retinal cell types, which is believed to be controlled by a tightly coordinated regulatory program of proliferation, cell cycle exit and differentiation. Although homeobox protein Msx2 could induce apoptosis of optic vesicle, it is unclear whether Msx2 regulates differentiation and cell fate commitment of retinal progenitor cells (RPCs) to retinal ganglion cells (RGCs). In this study, we show that overexpression of Msx2 transiently suppressed the expression of Cyclin D1 and blocked cell proliferation. Meanwhile, overexpression of Msx2 delayed the expression of RGC-specific differentiation markers (Math5 and Brn3b), which showed that Msx2 could affect the timing of RGCs fate commitment and differentiation by delaying the timing of cell cycle exit of retinal progenitors. These results indicate Msx2 possesses dual regulatory functions in controlling cell cycle progression of retinal RPCs and timing of RGCs differentiation.

Fungal-induced cell cycle impairment, chromosome instability and apoptosis via differential activation of NF-κB.

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Mariem Ben-Abdallah

Full Text Available Microbial pathogens have developed efficient strategies to compromise host immune responses. Cryptococcus neoformans is a facultative intracellular pathogen, recognised as the most common cause of systemic fungal infections leading to severe meningoencephalitis, mainly in immunocompromised patients. This yeast is characterized by a polysaccharide capsule, which inhibits its phagocytosis. Whereas phagocytosis escape and macrophage intracellular survival have been intensively studied, extracellular survival of this yeast and restraint of host innate immune response are still poorly understood. In this study, we have investigated whether C. neoformans affected macrophage cell viability and whether NF-κB (nuclear factor-κB, a key regulator of cell growth, apoptosis and inflammation, was involved. Using wild-type (WT as well as mutant strains of C. neoformans for the pathogen side, and WT and mutant cell lines with altered NF-κB activity or signalling as well as primary macrophages for the host side, we show that C. neoformans manipulated NF-κB-mediated signalling in a unique way to regulate macrophage cell fate and viability. On the one hand, serotype A strains reduced macrophage proliferation in a capsule-independent fashion. This growth decrease, which required a critical dosage of NF-κB activity, was caused by cell cycle disruption and aneuploidy, relying on fungal-induced modification of expression of several cell cycle checkpoint regulators in S and G2/M phases. On the other hand, C. neoformans infection induced macrophage apoptosis in a capsule-dependent manner with a differential requirement of the classical and alternative NF-κB signalling pathways, the latter one being essential. Together, these findings shed new light on fungal strategies to subvert host response through uncoupling of NF-κB activity in pathogen-controlled apoptosis and impairment of cell cycle progression. They also provide the first demonstration of induction of

THE EFFICIENCY OF PROMOTIONAL INSTRUMENTS RELATED TO THE PRODUCT LIFE CYCLE STAGES

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MIHAELA MARCU

2010-01-01

Full Text Available Regarded as a planning tool, PLC (product life cycle strongly contributes to the identification of the main marketing challenges that may arise throughout the life of a product/service. Thus, the marketing management has the opportunity to develop and implement those solutions designed to optimize each of the 4P of marketing mix: product (quality, price, distribution (placement and promotion. The communication program has an essential role, because the company presents through it its "product" to actual or potential customers in order to convince them of the benefits of purchasing/using it. The efficiency of the promotional instruments involves an appropriate allocation of funds needed to promote the product/service in relation to the stage of its life cycle.

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

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Jarrin, Miguel; Pandit, Tanushree; Gunhaga, Lena

2012-01-01

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

The Wnt Signaling Pathway Is Differentially Expressed during the Bovine Herpesvirus 1 Latency-Reactivation Cycle: Evidence That Two Protein Kinases Associated with Neuronal Survival, Akt3 and BMPR2, Are Expressed at Higher Levels during Latency.

Science.gov (United States)

Workman, Aspen; Zhu, Liqian; Keel, Brittney N; Smith, Timothy P L; Jones, Clinton

2018-04-01

Sensory neurons in trigeminal ganglia (TG) of calves latently infected with bovine herpesvirus 1 (BoHV-1) abundantly express latency-related (LR) gene products, including a protein (ORF2) and two micro-RNAs. Recent studies in mouse neuroblastoma cells (Neuro-2A) demonstrated ORF2 interacts with β-catenin and a β-catenin coactivator, high-mobility group AT-hook 1 (HMGA1) protein, which correlates with increased β-catenin-dependent transcription and cell survival. β-Catenin and HMGA1 are readily detected in a subset of latently infected TG neurons but not TG neurons from uninfected calves or reactivation from latency. Consequently, we hypothesized that the Wnt/β-catenin signaling pathway is differentially expressed during the latency and reactivation cycle and an active Wnt pathway promotes latency. RNA-sequencing studies revealed that 102 genes associated with the Wnt/β-catenin signaling pathway were differentially expressed in TG during the latency-reactivation cycle in calves. Wnt agonists were generally expressed at higher levels during latency, but these levels decreased during dexamethasone-induced reactivation. The Wnt agonist bone morphogenetic protein receptor 2 (BMPR2) was intriguing because it encodes a serine/threonine receptor kinase that promotes neuronal differentiation and inhibits cell death. Another differentially expressed gene encodes a protein kinase (Akt3), which is significant because Akt activity enhances cell survival and is linked to herpes simplex virus 1 latency and neuronal survival. Additional studies demonstrated ORF2 increased Akt3 steady-state protein levels and interacted with Akt3 in transfected Neuro-2A cells, which correlated with Akt3 activation. Conversely, expression of Wnt antagonists increased during reactivation from latency. Collectively, these studies suggest Wnt signaling cooperates with LR gene products, in particular ORF2, to promote latency. IMPORTANCE Lifelong BoHV-1 latency primarily occurs in sensory neurons

Sex-Specific Habitat Utilization and Differential Breeding Investments in Christmas Island Frigatebirds throughout the Breeding Cycle.

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Janos C Hennicke

Full Text Available In seabirds, equal bi-parental care is the rule, as it is considered crucial for raising chicks successfully because seabirds forage in an environment with unpredictable and highly variable food supply. Frigatebirds forage in poor tropical waters, yet males reduce and even stop parental care soon after chick brooding, leaving the female to provision the chick alone for an extended fledging period. Using bird-borne tracking devices, male and female Christmas Island Frigatebirds (Fregata andrewsi were investigated during the brooding, late chick rearing and post-fledging period to examine whether sexes exhibit foraging strategies that may be linked to differential breeding investments. During brooding, males and females showed similar foraging behaviour under average marine productivity of oceanic waters close to the colony, but males shifted to more distant and more productive habitats when conditions deteriorated to continue with reduced chick provisioning. During the late chick rearing period, females progressively increased their foraging range to the more distant but productive marine areas that only males had visited during brooding. Birds spent the non-breeding period roosting in highly productive waters of the Sunda Shelf. The sex-specific utilisation of three different foraging habitats with different primary productivity (oceanic, coastal, and shelf areas allowed for temporal and spatial segregation in the exploitation of favourable habitats which seems to enable each sex to optimise its foraging profitability. In addition, post-fledging foraging movements of females suggest a biennial breeding cycle, while limited information on males suggests the possibility of an annual breeding cycle.

Cell cycle kinetics and radiation therapy

International Nuclear Information System (INIS)

Mendelsohn, M.L.

1975-01-01

Radiation therapy as currently practiced involves the subtle largely empirical art of balancing the recurrence of cancer due to undertreatment against severe damage to local tissues due to overtreatment. Therapeutic results too often fall short of desired success rates; yet, the therapist is continually tantalized to the likelihood that a slight shift of therapeutic ratio favoring normal tissue over cancer would have a profoundly beneficial effect. The application of cell cycle kinetics to radiation therapy is one hope for improving the therapeutic ratio; but, as I will try to show, kinetic approaches are complex, poorly understood, and presently too elusive to elicit confidence or to be used clinically. Their promise lies in their diversity and in the magnitude of our ignorance about how they work and how they should be used. Potentially useful kinetic approaches to therapy can be grouped into three classes. The first class takes advantage of intracyclic differential sensitivity, an effect involving the metabolism and biology of the cell cycle; its strategies are based on synchronization of cells over intervals of hours to days. The second class involves the distinction between cycling and noncycling cells; its strategies are based on the resistance of noncycling cells to cycle-linked radiation sensitizers and chemotherapeutic agents. The third class uses cell repopulation between fractions; its strategies are based on the relative growth rates of tumor and relevant normal tissue before and after perturbation

Stable Density and Dynamics of Dendritic Spines of Cortical Neurons Across the Estrous Cycle While Expressing Differential Levels of Sensory-Evoked Plasticity

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Bailin H. Alexander

2018-03-01

Full Text Available Periodic oscillations of gonadal hormone levels during the estrous cycle exert effects on the female brain, impacting cognition and behavior. While previous research suggests that changes in hormone levels across the cycle affect dendritic spine dynamics in the hippocampus, little is known about the effects on cortical dendritic spines and previous studies showed contradictory results. In this in vivo imaging study, we investigated the impact of the estrous cycle on the density and dynamics of dendritic spines of pyramidal neurons in the primary somatosensory cortex of mice. We also examined if the induction of synaptic plasticity during proestrus, estrus, and metestrus/diestrus had differential effects on the degree of remodeling of synapses in this brain area. We used chronic two-photon excitation (2PE microscopy during steady-state conditions and after evoking synaptic plasticity by whisker stimulation at the different stages of the cycle. We imaged apical dendritic tufts of layer 5 pyramidal neurons of naturally cycling virgin young female mice. Spine density, turnover rate (TOR, survival fraction, morphology, and volume of mushroom spines remained unaltered across the estrous cycle, and the values of these parameters were comparable with those of young male mice. However, while whisker stimulation of female mice during proestrus and estrus resulted in increases in the TOR of spines (74.2 ± 14.9% and 75.1 ± 12.7% vs. baseline, respectively, sensory-evoked plasticity was significantly lower during metestrus/diestrus (32.3 ± 12.8%. In males, whisker stimulation produced 46.5 ± 20% increase in TOR compared with baseline—not significantly different from female mice at any stage of the cycle. These results indicate that, while steady-state density and dynamics of dendritic spines of layer 5 pyramidal neurons in the primary somatosensory cortex of female mice are constant during the estrous cycle, the susceptibility of these neurons to

A novel DLX3-PKC integrated signaling network drives keratinocyte differentiation.

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Palazzo, Elisabetta; Kellett, Meghan D; Cataisson, Christophe; Bible, Paul W; Bhattacharya, Shreya; Sun, Hong-Wei; Gormley, Anna C; Yuspa, Stuart H; Morasso, Maria I

2017-04-01

Epidermal homeostasis relies on a well-defined transcriptional control of keratinocyte proliferation and differentiation, which is critical to prevent skin diseases such as atopic dermatitis, psoriasis or cancer. We have recently shown that the homeobox transcription factor DLX3 and the tumor suppressor p53 co-regulate cell cycle-related signaling and that this mechanism is functionally involved in cutaneous squamous cell carcinoma development. Here we show that DLX3 expression and its downstream signaling depend on protein kinase C α (PKCα) activity in skin. We found that following 12-O-tetradecanoyl-phorbol-13-acetate (TPA) topical treatment, DLX3 expression is significantly upregulated in the epidermis and keratinocytes from mice overexpressing PKCα by transgenic targeting (K5-PKCα), resulting in cell cycle block and terminal differentiation. Epidermis lacking DLX3 (DLX3cKO), which is linked to the development of a DLX3-dependent epidermal hyperplasia with hyperkeratosis and dermal leukocyte recruitment, displays enhanced PKCα activation, suggesting a feedback regulation of DLX3 and PKCα. Of particular significance, transcriptional activation of epidermal barrier, antimicrobial peptide and cytokine genes is significantly increased in DLX3cKO skin and further increased by TPA-dependent PKC activation. Furthermore, when inhibiting PKC activity, we show that epidermal thickness, keratinocyte proliferation and inflammatory cell infiltration are reduced and the PKC-DLX3-dependent gene expression signature is normalized. Independently of PKC, DLX3 expression specifically modulates regulatory networks such as Wnt signaling, phosphatase activity and cell adhesion. Chromatin immunoprecipitation sequencing analysis of primary suprabasal keratinocytes showed binding of DLX3 to the proximal promoter regions of genes associated with cell cycle regulation, and of structural proteins and transcription factors involved in epidermal differentiation. These results indicate

Redistribution of cell cycle by arsenic trioxide is associated with demethylation and expression changes of cell cycle related genes in acute promyelocytic leukemia cell line (NB4).

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Hassani, Saeed; Khaleghian, Ali; Ahmadian, Shahin; Alizadeh, Shaban; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir; Ghaffari, Seyed H

2018-01-01

PML-RARα perturbs the normal epigenetic setting, which is essential to oncogenic transformation in acute promyelocytic leukemia (APL). Transcription induction and recruitment of DNA methyltransferases (DNMTs) by PML-RARα and subsequent hypermethylation are components of this perturbation. Arsenic trioxide (ATO), an important drug in APL therapy, concurrent with degradation of PML-RARα induces cell cycle change and apoptosis. How ATO causes cell cycle alteration has remained largely unexplained. Here, we investigated DNA methylation patterns of cell cycle regulatory genes promoters, the effects of ATO on the methylated genes and cell cycle distribution in an APL cell line, NB4. Analysis of promoter methylation status of 22 cell cycle related genes in NB4 revealed that CCND1, CCNE1, CCNF, CDKN1A, GADD45α, and RBL1 genes were methylated 60.7, 84.6, 58.6, 8.7, 33.4, and 73.7%, respectively, that after treatment with 2 μM ATO for 48 h, turn into 0.6, 13.8, 0.1, 6.6, 10.7, and 54.5% methylated. ATO significantly reduced the expression of DNMT1, 3A, and 3B. ATO induced the expression of CCND1, CCNE1, and GADD45α genes, suppressed the expression of CCNF and CDKN1A genes, which were consistent with decreased number of cells in G1 and S phases and increased number of cells in G2/M phase. In conclusion, demethylation and alteration in the expression level of the cell cycle related genes may be possible mechanisms in ATO-induced cell cycle arrest in APL cells. It may suggest that ATO by demethylation of CCND1 and CCNE1 and their transcriptional activation accelerates G1 and S transition into the G2/M cell cycle arrest.

GRAND MINIMA AND EQUATORWARD PROPAGATION IN A CYCLING STELLAR CONVECTIVE DYNAMO

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Augustson, Kyle; Miesch, Mark [High Altitude Observatory, Center Green 1, Boulder, CO 80301 (United States); Brun, Allan Sacha [Laboratoire AIM Paris-Saclay, CEA/DSM–CNRS–Université Paris Diderot, IRFU/SAp, Gif-sur-Yvette (France); Toomre, Juri [JILA and Department of Astrophysical and Planetary Sciences, University of Colorado, Boulder, CO 80309 (United States)

2015-08-20

The 3D MHD Anelastic Spherical Harmonic code, using slope-limited diffusion, is employed to capture convective and dynamo processes achieved in a global-scale stellar convection simulation for a model solar-mass star rotating at three times the solar rate. The dynamo-generated magnetic fields possesses many timescales, with a prominent polarity cycle occurring roughly every 6.2 years. The magnetic field forms large-scale toroidal wreaths, whose formation is tied to the low Rossby number of the convection in this simulation. The polarity reversals are linked to the weakened differential rotation and a resistive collapse of the large-scale magnetic field. An equatorial migration of the magnetic field is seen, which is due to the strong modulation of the differential rotation rather than a dynamo wave. A poleward migration of magnetic flux from the equator eventually leads to the reversal of the polarity of the high-latitude magnetic field. This simulation also enters an interval with reduced magnetic energy at low latitudes lasting roughly 16 years (about 2.5 polarity cycles), during which the polarity cycles are disrupted and after which the dynamo recovers its regular polarity cycles. An analysis of this grand minimum reveals that it likely arises through the interplay of symmetric and antisymmetric dynamo families. This intermittent dynamo state potentially results from the simulation’s relatively low magnetic Prandtl number. A mean-field-based analysis of this dynamo simulation demonstrates that it is of the α-Ω type. The timescales that appear to be relevant to the magnetic polarity reversal are also identified.

Ovarian matrix metalloproteinases are differentially regulated during the estrous cycle but not during short photoperiod induced regression in Siberian hamsters (Phodopus sungorus

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Vrooman Lisa A

2010-06-01

Full Text Available Abstract Background Matrix metalloproteinases (MMPs are implicated as mediators for ovarian remodeling events, and are involved with ovarian recrudescence during seasonal breeding cycles in Siberian hamsters. However, involvement of these proteases as the photoinhibited ovary undergoes atrophy and regression had not been assessed. We hypothesized that 1 MMPs and their tissue inhibitors, the TIMPs would be present and differentially regulated during the normal estrous cycle in Siberian hamsters, and that 2 MMP/TIMP mRNA and protein levels would increase as inhibitory photoperiod induced ovarian degeneration. Methods MMP-2, -9, -14 and TIMP-1 and -2 mRNA and protein were examined in the stages of estrous (proestrus [P], estrus [E], diestrus I [DI], and diestrus II [DII] in Siberian hamsters, as well as after exposure to 3, 6, 9, and 12 weeks of inhibitory short photoperiod (SD. Results MMP-9 exhibited a 1.6-1.8 fold decrease in mRNA expression in DII (p Conclusions Although MMPs appear to be involved in the normal ovarian estrus cycle at the protein level in hamsters, those examined in the present study are unlikely to be key players in the slow atrophy of tissue as seen in Siberian hamster ovarian regression.

Theory of limit cycles

CERN Document Server

Ye, Yan-Qian; Lo, Chi Y

1986-01-01

Over the past two decades the theory of limit cycles, especially for quadratic differential systems, has progressed dramatically in China as well as in other countries. This monograph, updating the 1964 first edition, includes these recent developments, as revised by eight of the author's colleagues in their own areas of expertise. The first part of the book deals with limit cycles of general plane stationary systems, including their existence, nonexistence, stability, and uniqueness. The second section discusses the global topological structure of limit cycles and phase-portraits of quadratic systems. Finally, the last section collects important results that could not be included under the subject matter of the previous two sections or that have appeared in the literature very recently. The book as a whole serves as a reference for college seniors, graduate students, and researchers in mathematics and physics.

Application of a personal computer relational data base management system to fuel cycle economic scoping

International Nuclear Information System (INIS)

Malone, J.P.; Dooley, G.D.

1986-01-01

A personal computer (PC) relational data base management system (RDBMS) permits large quantities of data to be maintained in a data base composed of structured data sets or files and provides data access through a software environment, procedure, or program language. The features of an RDBMS-based system create an environment on a PC that can provide significant benefits to any fuel cycle economics analysis. The ability to maintain a separate data set for each fuel cycle parameter group and the ability to manipulate the data through a series of independent calculation modules combine to provide the fuel cycle analyst with more time to examine and use the data, because less time is required to manipulate it

Relation between Peak Power Output in Sprint Cycling and Maximum Voluntary Isometric Torque Production.

Science.gov (United States)

Kordi, Mehdi; Goodall, Stuart; Barratt, Paul; Rowley, Nicola; Leeder, Jonathan; Howatson, Glyn

2017-08-01

From a cycling paradigm, little has been done to understand the relationships between maximal isometric strength of different single joint lower body muscle groups and their relation with, and ability to predict PPO and how they compare to an isometric cycling specific task. The aim of this study was to establish relationships between maximal voluntary torque production from isometric single-joint and cycling specific tasks and assess their ability to predict PPO. Twenty male trained cyclists participated in this study. Peak torque was measured by performing maximum voluntary contractions (MVC) of knee extensors, knee flexors, dorsi flexors and hip extensors whilst instrumented cranks measured isometric peak torque from MVC when participants were in their cycling specific position (ISOCYC). A stepwise regression showed that peak torque of the knee extensors was the only significant predictor of PPO when using SJD and accounted for 47% of the variance. However, when compared to ISOCYC, the only significant predictor of PPO was ISOCYC, which accounted for 77% of the variance. This suggests that peak torque of the knee extensors was the best single-joint predictor of PPO in sprint cycling. Furthermore, a stronger prediction can be made from a task specific isometric task. Copyright © 2017 Elsevier Ltd. All rights reserved.

The practical impact of differential item functioning analyses in a health-related quality of life instrument

DEFF Research Database (Denmark)

Scott, Neil W; Fayers, Peter M; Aaronson, Neil K

2009-01-01

Differential item functioning (DIF) analyses are commonly used to evaluate health-related quality of life (HRQoL) instruments. There is, however, a lack of consensus as to how to assess the practical impact of statistically significant DIF results.......Differential item functioning (DIF) analyses are commonly used to evaluate health-related quality of life (HRQoL) instruments. There is, however, a lack of consensus as to how to assess the practical impact of statistically significant DIF results....

The SnSAG merozoite surface antigens of Sarcocystis neurona are expressed differentially during the bradyzoite and sporozoite life cycle stages.

Science.gov (United States)

Gautam, A; Dubey, J P; Saville, W J; Howe, D K

2011-12-29

Sarcocystis neurona is a two-host coccidian parasite whose complex life cycle progresses through multiple developmental stages differing at morphological and molecular levels. The S. neurona merozoite surface is covered by multiple, related glycosylphosphatidylinositol-linked proteins, which are orthologous to the surface antigen (SAG)/SAG1-related sequence (SRS) gene family of Toxoplasma gondii. Expression of the SAG/SRS proteins in T. gondii and another related parasite Neospora caninum is life-cycle stage specific and seems necessary for parasite transmission and persistence of infection. In the present study, the expression of S. neurona merozoite surface antigens (SnSAGs) was evaluated in the sporozoite and bradyzoite stages. Western blot analysis was used to compare SnSAG expression in merozoites versus sporozoites, while immunocytochemistry was performed to examine expression of the SnSAGs in merozoites versus bradyzoites. These analyses revealed that SnSAG2, SnSAG3 and SnSAG4 are expressed in sporozoites, while SnSAG5 was appeared to be downregulated in this life cycle stage. In S. neurona bradyzoites, it was found that SnSAG2, SnSAG3, SnSAG4 and SnSAG5 were either absent or expression was greatly reduced. As shown for T. gondii, stage-specific expression of the SnSAGs may be important for the parasite to progress through its developmental stages and complete its life cycle successfully. Thus, it is possible that the SAG switching mechanism by these parasites could be exploited as a point of intervention. As well, the alterations in surface antigen expression during different life cycle stages may need to be considered when designing prospective approaches for protective vaccination. Copyright © 2011 Elsevier B.V. All rights reserved.

Organic amendment of crop soil and its relation to hotspots of bacterial nitrogen cycling

Science.gov (United States)

Pereg, Lily; McMillan, Mary

2015-04-01

Crop production in Australian soils requires a high use of fertilisers, including N, P and K for continues utilisation of the soil. Growers often grow crops in rotation of summer crop, such as cotton with winter crop, such as wheat in the same field. Growers are getting more and more aware about sustainability of the soil resources and the more adventurous ones use soil amendments, such as organic supplements in addition to the chemical fertilisers. We have collected soil samples from fields that were cultivated in preparation for planting cotton and tested the soil for its bacterial populations with potential to perform different functions, including those related to the nitrogen cycling. One of our aims was to determine whether organic amendments create hotspots for bacterial functions related to bacterial nitrogen cycling. This pan of the project will be discussed in this presentation.

Alternative ORC bottoming cycles FOR combined cycle power plants

International Nuclear Information System (INIS)

Chacartegui, R.; Sanchez, D.; Munoz, J.M.; Sanchez, T.

2009-01-01

In this work, low temperature Organic Rankine Cycles are studied as bottoming cycle in medium and large scale combined cycle power plants. The analysis aims to show the interest of using these alternative cycles with high efficiency heavy duty gas turbines, for example recuperative gas turbines with lower gas turbine exhaust temperatures than in conventional combined cycle gas turbines. The following organic fluids have been considered: R113, R245, isobutene, toluene, cyclohexane and isopentane. Competitive results have been obtained for toluene and cyclohexane ORC combined cycles, with reasonably high global efficiencies. The paper is structured in four main parts. A review of combined cycle and ORC cycle technologies is presented, followed by a thermodynamic analysis of combined cycles with commercial gas turbines and ORC low temperature bottoming cycles. Then, a parametric optimization of an ORC combined cycle plant is performed in order to achieve a better integration between these two technologies. Finally, some economic considerations related to the use of ORC in combined cycles are discussed.

The APC/C Coordinates Retinal Differentiation with G1 Arrest through the Nek2-Dependent Modulation of Wingless Signaling.

Science.gov (United States)

Martins, Torcato; Meghini, Francesco; Florio, Francesca; Kimata, Yuu

2017-01-09

The cell cycle is coordinated with differentiation during animal development. Here we report a cell-cycle-independent developmental role for a master cell-cycle regulator, the anaphase-promoting complex or cyclosome (APC/C), in the regulation of cell fate through modulation of Wingless (Wg) signaling. The APC/C controls both cell-cycle progression and postmitotic processes through ubiquitin-dependent proteolysis. Through an RNAi screen in the developing Drosophila eye, we found that partial APC/C inactivation severely inhibits retinal differentiation independently of cell-cycle defects. The differentiation inhibition coincides with hyperactivation of Wg signaling caused by the accumulation of a Wg modulator, Drosophila Nek2 (dNek2). The APC/C degrades dNek2 upon synchronous G1 arrest prior to differentiation, which allows retinal differentiation through local suppression of Wg signaling. We also provide evidence that decapentaplegic signaling may posttranslationally regulate this APC/C function. Thus, the APC/C coordinates cell-fate determination with the cell cycle through the modulation of developmental signaling pathways. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Identifying and Assessing Life-Cycle-Related Critical Technology Elements (CTEs) for Technology Readiness Assessments (TRAs)

National Research Council Canada - National Science Library

Mandelbaum, Jay

2006-01-01

.... Because these technologies are not emphasized in the current Technology Readiness Assessment (TRA) process this document is intended to improve the focus on life-cycle-related technologies in TRAs...

Quantifying uncertainties of climate signals related to the 11-year solar cycle

Science.gov (United States)

Kruschke, T.; Kunze, M.; Matthes, K. B.; Langematz, U.; Wahl, S.

2017-12-01

Although state-of-the-art reconstructions based on proxies and (semi-)empirical models converge in terms of total solar irradiance, they still significantly differ in terms of spectral solar irradiance (SSI) with respect to the mean spectral distribution of energy input and temporal variability. This study aims at quantifying uncertainties for the Earth's climate related to the 11-year solar cycle by forcing two chemistry-climate models (CCMs) - CESM1(WACCM) and EMAC - with five different SSI reconstructions (NRLSSI1, NRLSSI2, SATIRE-T, SATIRE-S, CMIP6-SSI) and the reference spectrum RSSV1-ATLAS3, derived from observations. We conduct a unique set of timeslice experiments. External forcings and boundary conditions are fixed and identical for all experiments, except for the solar forcing. The set of analyzed simulations consists of one solar minimum simulation, employing RSSV1-ATLAS3 and five solar maximum experiments. The latter are a result of adding the amplitude of solar cycle 22 according to the five reconstructions to RSSV1-ATLAS3. Our results show that the climate response to the 11y solar cycle is generally robust across CCMs and SSI forcings. However, analyzing the variance of the solar maximum ensemble by means of ANOVA-statistics reveals additional information on the uncertainties of the mean climate signals. The annual mean response agrees very well between the two CCMs for most parts of the lower and middle atmosphere. Only the upper mesosphere is subject to significant differences related to the choice of the model. However, the different SSI forcings lead to significant differences in ozone concentrations, shortwave heating rates, and temperature throughout large parts of the mesosphere and upper stratosphere. Regarding the seasonal evolution of the climate signals, our findings for short wave heating rates, and temperature are similar to the annual means with respect to the relative importance of the choice of the model or the SSI forcing for the

A pilot study differentiating recurrent major depression from bipolar disorder cycling on the depressive pole

Directory of Open Access Journals (Sweden)

Marty Hinz

2010-11-01

Full Text Available Marty Hinz1, Alvin Stein2, Thomas Uncini31Clinical Research, NeuroResearch Clinics, Inc., Cape Coral, FL, USA; 2Stein Orthopedic Associates, Plantation, FL, USA; 3DBS Labs, Duluth, MN, USAPurpose: A novel method for differentiating and treating bipolar disorder cycling on the depressive pole from patients who are suffering a major depressive episode is explored in this work. To confirm the diagnosis of type 1 or type 2 bipolar disorder, the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV criteria require that at least one manic or hypomanic episode be identified. History of one or more manic or hypomanic episodes may be impossible to obtain, representing a potential blind spot in the DSM-IV diagnostic criteria. Many bipolar patients who cycle primarily on the depressive side for many years carry a misdiagnosis of recurrent major depression, leading to treatment with antidepressants that achieve little or no relief of symptoms. This article discusses a novel approach for diagnosing and treating patients with bipolar disorder cycling on the depressive pole versus patients with recurrent major depression.Patients and methods: Patients involved in this study were formally diagnosed with recurrent major depression under DSM-IV criteria and had no medical history of mania or hypomania to support the diagnosis of bipolar disorder. All patients had suffered multiple depression treatment failures in the past, when evaluated under DSM-IV guidelines, secondary to administration of antidepressant drugs and/or serotonin with dopamine amino acid precursors.Results: This study contained 1600 patients who were diagnosed with recurrent major depression under the DSM-IV criteria. All patients had no medical history of mania or hypomania. All patients experienced no relief of depression symptoms on level 3 amino acid dosing values of the amino acid precursor dosing protocol. Of 1600 patients studied, 117 (7.3% nonresponder patients were identified

Differentiation in Teaching Science in the First and Second Cycles of Primary Education

Directory of Open Access Journals (Sweden)

Skribe Dimec Darja

2013-09-01

Full Text Available There are differences between pupils with regard to their knowledge, but also their abilities or skills and attitudes. The aim of our research study was to determine whether those differences are taken into account while planning and executing primary science lessons. We looked for evidence of differentiation in primary science curricula and textbooks as well as in conceptions and practices of students who are to be future primary school teachers. We noticed that Slovenian curricula designers were clearly aware of the differentiation, as the curricula specifically defined “minimum” and “basic” standards of knowledge. Based on a questionnaire we established that most students were well aware of the differences in pupils’ level of knowledge. An analysis of the lesson plans that were written by students showed significant shortcomings in differentiation in primary science education. As a rule, over 90 per cent of lesson plans that students had to write at the beginning of natural science didactics did not include either quantitative or qualitative differentiation. We found out that once students had completed the teacher education programme, the concept of differentiation was realized through the elements of the constructivist theory of learning. By analyzing various textbooks and workbooks, we tried to determine how the authors of the respective books perceived differentiation. We came to a conclusion that a majority of teaching materials did not incorporate the elements of differentiation.

Assessment of serum HE4 levels throughout the normal menstrual cycle.

Science.gov (United States)

Moore, Richard G; Plante, Beth; Hartnett, Erin; Mitchel, Jessica; Raker, Christine A; Vitek, Wendy; Eklund, Elizabeth; Lambert-Messerlian, Geralyn

2017-07-01

Human epididymis protein 4 is a serum biomarker to aid in differentiating benign and malignant disease in women with a pelvic mass. Interpretation of human epididymis protein 4 results relies on robust normative data. The purpose of this study was to evaluate whether human epididymis protein 4 levels are variable in women during the normal menstrual cycle. Healthy women, 18-45 years old, with regular menstrual cycles were recruited from community gynecologic practices in Rhode Island. Women consented to enroll and to participate by the donation of blood and urine samples at 5 specific times over the course of each cycle. Levels of reproductive hormones and human epididymis protein 4 were determined. Data were analyzed with the use of linear regression after log transformation. Among 74 enrolled cycles, 53 women had confirmed ovulation during the menstrual cycle and completed all 5 sample collections. Levels of estradiol, progesterone, and luteinizing hormone displayed the expected menstrual cycle patterns. Levels of human epididymis protein 4 in serum were relatively stable across the menstrual cycle, except for a small ovulatory (median, 37.0 pM) increase. Levels of human epididymis protein 4 in urine, after correction for creatinine, displayed the same pattern of secretion observed in serum. Serum human epididymis protein 4 levels are relatively stable across the menstrual cycle of reproductive-aged women and can be determined on any day to evaluate risk of ovarian malignancy. A slight increase is expected at ovulation; but even with this higher human epididymis protein 4 level, results are well within the healthy reference range for women (<120 pM). Levels of human epididymis protein 4 in urine warrant further investigation for use in clinical practice as a simple and convenient sample. Copyright © 2017 Elsevier Inc. All rights reserved.

Triton-3He relative and differential flows as probes of the nuclear symmetry energy at supra-saturation densities

International Nuclear Information System (INIS)

Yong Gaochan; Li Baoan; Chen Liewen; Zhang Xunchao

2009-01-01

Using a transport model coupled with a phase-space coalescence afterburner, we study the triton- 3 He (t- 3 He) ratio with both relative and differential transverse flows in semicentral 132 Sn+ 124 Sn reactions at a beam energy of 400 MeV/nucleon. The neutron-proton ratios with relative and differential flows are also discussed as a reference. We find that similar to the neutron-proton pairs, the t- 3 He pairs also carry interesting information regarding the density dependence of the nuclear symmetry energy. Moreover, the nuclear symmetry energy affects more strongly the t- 3 He relative and differential flows than the π - /π + ratio in the same reaction. The t- 3 He relative flow can be used as a particularly powerful probe of the high-density behavior of the nuclear symmetry energy.

ODE, RDE and SDE models of cell cycle dynamics and clustering in yeast.

Science.gov (United States)

Boczko, Erik M; Gedeon, Tomas; Stowers, Chris C; Young, Todd R

2010-07-01

Biologists have long observed periodic-like oxygen consumption oscillations in yeast populations under certain conditions, and several unsatisfactory explanations for this phenomenon have been proposed. These ‘autonomous oscillations’ have often appeared with periods that are nearly integer divisors of the calculated doubling time of the culture. We hypothesize that these oscillations could be caused by a form of cell cycle synchronization that we call clustering. We develop some novel ordinary differential equation models of the cell cycle. For these models, and for random and stochastic perturbations, we give both rigorous proofs and simulations showing that both positive and negative growth rate feedback within the cell cycle are possible agents that can cause clustering of populations within the cell cycle. It occurs for a variety of models and for a broad selection of parameter values. These results suggest that the clustering phenomenon is robust and is likely to be observed in nature. Since there are necessarily an integer number of clusters, clustering would lead to periodic-like behaviour with periods that are nearly integer divisors of the period of the cell cycle. Related experiments have shown conclusively that cell cycle clustering occurs in some oscillating yeast cultures.

A novel DLX3–PKC integrated signaling network drives keratinocyte differentiation

Science.gov (United States)

Palazzo, Elisabetta; Kellett, Meghan D; Cataisson, Christophe; Bible, Paul W; Bhattacharya, Shreya; Sun, Hong-wei; Gormley, Anna C; Yuspa, Stuart H; Morasso, Maria I

2017-01-01

Epidermal homeostasis relies on a well-defined transcriptional control of keratinocyte proliferation and differentiation, which is critical to prevent skin diseases such as atopic dermatitis, psoriasis or cancer. We have recently shown that the homeobox transcription factor DLX3 and the tumor suppressor p53 co-regulate cell cycle-related signaling and that this mechanism is functionally involved in cutaneous squamous cell carcinoma development. Here we show that DLX3 expression and its downstream signaling depend on protein kinase C α (PKCα) activity in skin. We found that following 12-O-tetradecanoyl-phorbol-13-acetate (TPA) topical treatment, DLX3 expression is significantly upregulated in the epidermis and keratinocytes from mice overexpressing PKCα by transgenic targeting (K5-PKCα), resulting in cell cycle block and terminal differentiation. Epidermis lacking DLX3 (DLX3cKO), which is linked to the development of a DLX3-dependent epidermal hyperplasia with hyperkeratosis and dermal leukocyte recruitment, displays enhanced PKCα activation, suggesting a feedback regulation of DLX3 and PKCα. Of particular significance, transcriptional activation of epidermal barrier, antimicrobial peptide and cytokine genes is significantly increased in DLX3cKO skin and further increased by TPA-dependent PKC activation. Furthermore, when inhibiting PKC activity, we show that epidermal thickness, keratinocyte proliferation and inflammatory cell infiltration are reduced and the PKC-DLX3-dependent gene expression signature is normalized. Independently of PKC, DLX3 expression specifically modulates regulatory networks such as Wnt signaling, phosphatase activity and cell adhesion. Chromatin immunoprecipitation sequencing analysis of primary suprabasal keratinocytes showed binding of DLX3 to the proximal promoter regions of genes associated with cell cycle regulation, and of structural proteins and transcription factors involved in epidermal differentiation. These results indicate

Life cycle characteristics of SME’s

NARCIS (Netherlands)

Masurel, E.; Montfort, van K.

2006-01-01

Our study of professional services firms clearly revealed that firms change over the course of their life cycles. During the first three stages, diversification in sales, the differentiation in labor force, and the level of labor productivity increase. In the last stage, diversification in sales,

Monitoring Perceived Stress and Recovery in Relation to Cycling Performance in Female Athletes

NARCIS (Netherlands)

Otter, R. T. A.; Brink, M. S.; van der Does, H. T. D.; Lemmink, K. A. P. M.

The purpose was to investigate perceived stress and recovery related to cycling performance of female athletes over one full year. 20 female athletes ( age, 27 +/- 8 years; VO2max, 50.3 +/- 4.6 mL center dot kg(-1) center dot min(-1)) were measured 8 times in one year to determine perceived stress

Bach2 is involved in neuronal differentiation of N1E-115 neuroblastoma cells

International Nuclear Information System (INIS)

Shim, Ki Shuk; Rosner, Margit; Freilinger, Angelika; Lubec, Gert; Hengstschlaeger, Markus

2006-01-01

Bach1 and Bach2 are evolutionarily related members of the BTB-basic region leucine zipper transcription factor family. We found that Bach2 downregulates cell proliferation of N1E-115 cells and negatively affects their potential to differentiate. Nuclear localization of the cyclin-dependent kinase inhibitor p21 is known to arrest cell cycle progression, and cytoplasmic p21 has been shown to promote neuronal differentiation of N1E-115 cells. We found that ectopic Bach2 causes upregulation of p21 expression in the nucleus and in the cytoplasm in undifferentiated N1E-115 cells. In differentiated cells, Bach2 specifically triggers upregulation of cytoplasmic p21. Our data suggest that Bach2 expression could represent a switch during the process of neuronal differentiation. Bach2 is not expressed in neuronal precursor cells. It would have negative effects on proliferation and differentiation of these cells. In differentiated neuronal cells Bach2 expression is upregulated, which could allow Bach2 to function as a gatekeeper of the differentiated status

Menstrual cycle pattern and fertility

DEFF Research Database (Denmark)

Kolstad, Henrik A.; Bonde, Jens Peter; Hjøllund, Niels Henrik

1999-01-01

To characterize how the menstrual cycle pattern relates to fertility regardless of potential biases caused by inappropriate coital timing during the menstrual cycle or early embryonal loss.......To characterize how the menstrual cycle pattern relates to fertility regardless of potential biases caused by inappropriate coital timing during the menstrual cycle or early embryonal loss....

Universal relations for differentially rotating relativistic stars at the threshold to collapse

Science.gov (United States)

Bozzola, Gabriele; Stergioulas, Nikolaos; Bauswein, Andreas

2018-03-01

A binary neutron star merger produces a rapidly and differentially rotating compact remnant whose lifespan heavily affects the electromagnetic and gravitational emissions. Its stability depends on both the equation of state (EOS) and the rotation law and it is usually investigated through numerical simulations. Nevertheless, by means of a sufficient criterion for secular instability, equilibrium sequences can be used as a computational inexpensive way to estimate the onset of dynamical instability, which, in general, is close to the secular one. This method works well for uniform rotation and relies on the location of turning points: stellar models that are stationary points in a sequence of equilibrium solutions with constant rest mass or angular momentum. Here, we investigate differentially rotating models (using a large number of EOSs and different rotation laws) and find that several universal relations between properly scaled gravitational mass, rest mass and angular momentum of the turning-point models that are valid for uniform rotation are insensitive to the degree of differential rotation, to high accuracy.

A Natural Light/Dark Cycle Regulation of Carbon-Nitrogen Metabolism and Gene Expression in Rice Shoots.

Science.gov (United States)

Li, Haixing; Liang, Zhijun; Ding, Guangda; Shi, Lei; Xu, Fangsen; Cai, Hongmei

2016-01-01

Light and temperature are two particularly important environmental cues for plant survival. Carbon and nitrogen are two essential macronutrients required for plant growth and development, and cellular carbon and nitrogen metabolism must be tightly coordinated. In order to understand how the natural light/dark cycle regulates carbon and nitrogen metabolism in rice plants, we analyzed the photosynthesis, key carbon-nitrogen metabolites, and enzyme activities, and differentially expressed genes and miRNAs involved in the carbon and nitrogen metabolic pathway in rice shoots at the following times: 2:00, 6:00, 10:00, 14:00, 18:00, and 22:00. Our results indicated that more CO2 was fixed into carbohydrates by a high net photosynthetic rate, respiratory rate, and stomatal conductance in the daytime. Although high levels of the nitrate reductase activity, free ammonium and carbohydrates were exhibited in the daytime, the protein synthesis was not significantly facilitated by the light and temperature. In mRNA sequencing, the carbon and nitrogen metabolism-related differentially expressed genes were obtained, which could be divided into eight groups: photosynthesis, TCA cycle, sugar transport, sugar metabolism, nitrogen transport, nitrogen reduction, amino acid metabolism, and nitrogen regulation. Additionally, a total of 78,306 alternative splicing events have been identified, which primarily belong to alternative 5' donor sites, alternative 3' acceptor sites, intron retention, and exon skipping. In sRNA sequencing, four carbon and nitrogen metabolism-related miRNAs (osa-miR1440b, osa-miR2876-5p, osa-miR1877 and osa-miR5799) were determined to be regulated by natural light/dark cycle. The expression level analysis showed that the four carbon and nitrogen metabolism-related miRNAs negatively regulated their target genes. These results may provide a good strategy to study how natural light/dark cycle regulates carbon and nitrogen metabolism to ensure plant growth and

A natural light/dark cycle regulation of carbon-nitrogen metabolism and gene expression in rice shoots

Directory of Open Access Journals (Sweden)

Haixing Li

2016-08-01

Full Text Available Light and temperature are two particularly important environmental cues for plant survival. Carbon and nitrogen are two essential macronutrients required for plant growth and development, and cellular carbon and nitrogen metabolism must be tightly coordinated. In order to understand how the natural light/dark cycle regulates carbon and nitrogen metabolism in rice plants, we analyzed the photosynthesis, key carbon-nitrogen metabolites and enzyme activities, and differentially expressed genes and miRNAs involved in the carbon and nitrogen metabolic pathway in rice shoots at the following times: 2:00, 6:00, 10:00, 14:00, 18:00 and 22:00. Our results indicated that more CO2 was fixed into carbohydrates by a high net photosynthetic rate, respiratory rate and stomatal conductance in the daytime. Although high levels of the nitrate reductase activity, free ammonium and carbohydrates were exhibited in the daytime, the protein synthesis was not significantly facilitated by the light and temperature. In mRNA sequencing, the carbon and nitrogen metabolism-related differentially expressed genes were obtained, which could be divided into eight groups: photosynthesis, TCA cycle, sugar transport, sugar metabolism, nitrogen transport, nitrogen reduction, amino acid metabolism and nitrogen regulation. Additionally, a total of 78,306 alternative splicing events have been identified, which primarily belong to alternative 5' donor sites, alternative 3' acceptor sites, intron retention and exon skipping. In sRNA sequencing, four carbon and nitrogen metabolism-related miRNAs (osa-miR1440b, osa-miR2876-5p, osa-miR1877 and osa-miR5799 were determined to be regulated by natural light/dark cycle. The expression level analysis showed that the four carbon and nitrogen metabolism-related miRNAs negatively regulated their target genes. These results may provide a good strategy to study how natural light/dark cycle regulates carbon and nitrogen metabolism to ensure plant

Expression of Iron-Related Proteins Differentiate Non-Cancerous and Cancerous Breast Tumors

Directory of Open Access Journals (Sweden)

Sara Pizzamiglio

2017-02-01

Full Text Available We have previously reported hepcidin and ferritin increases in the plasma of breast cancer patients, but not in patients with benign breast disease. We hypothesized that these differences in systemic iron homeostasis may reflect alterations in different iron-related proteins also play a key biochemical and regulatory role in breast cancer. Thus, here we explored the expression of a bundle of molecules involved in both iron homeostasis and tumorigenesis in tissue samples. Enzyme-linked immunosorbent assay (ELISA or reverse-phase protein array (RPPA, were used to measure the expression of 20 proteins linked to iron processes in 24 non-cancerous, and 56 cancerous, breast tumors. We found that cancerous tissues had higher level of hepcidin than benign lesions (p = 0.012. The univariate analysis of RPPA data highlighted the following seven proteins differentially expressed between non-cancerous and cancerous breast tissue: signal transducer and transcriptional activator 5 (STAT5, signal transducer and activator of transcription 3 (STAT3, bone morphogenetic protein 6 (BMP6, cluster of differentiation 74 (CD74, transferrin receptor (TFRC, inhibin alpha (INHA, and STAT5_pY694. These findings were confirmed for STAT5, STAT3, BMP6, CD74 and INHA when adjusting for age. The multivariate statistical analysis indicated an iron-related 10-protein panel effective in separating non-cancerous from cancerous lesions including STAT5, STAT5_pY694, myeloid differentiation factor 88 (MYD88, CD74, iron exporter ferroportin (FPN, high mobility group box 1 (HMGB1, STAT3_pS727, TFRC, ferritin heavy chain (FTH, and ferritin light chain (FTL. Our results showed an association between some iron-related proteins and the type of tumor tissue, which may provide insight in strategies for using iron chelators to treat breast cancer.

Memantine, an antagonist of the NMDA glutamate receptor, affects cell proliferation, differentiation and the intracellular cycle and induces apoptosis in Trypanosoma cruzi.

Directory of Open Access Journals (Sweden)

Flávia Silva Damasceno

2014-02-01

Full Text Available Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi and affects approximately 10 million people in endemic areas of Mexico and Central and South America. Currently available chemotherapies are limited to two compounds: Nifurtimox and Benznidazole. Both drugs reduce the symptoms of the disease and mortality among infected individuals when used during the acute phase, but their efficacy during the chronic phase (during which the majority of cases are diagnosed remains controversial. Moreover, these drugs have several side effects. The aim of this study was to evaluate the effect of Memantine, an antagonist of the glutamate receptor in the CNS of mammals, on the life cycle of T. cruzi. Memantine exhibited a trypanocidal effect, inhibiting the proliferation of epimastigotes (IC50 172.6 µM. Furthermore, this compound interfered with metacyclogenesis (approximately 30% reduction and affected the energy metabolism of the parasite. In addition, Memantine triggered mechanisms that led to the apoptosis-like cell death of epimastigotes, with extracellular exposure of phosphatidylserine, increased production of reactive oxygen species, decreased ATP levels, increased intracellular Ca(2+ and morphological changes. Moreover, Memantine interfered with the intracellular cycle of the parasite, specifically the amastigote stage (IC50 31 µM. Interestingly, the stages of the parasite life cycle that require more energy (epimastigote and amastigote were more affected as were the processes of differentiation and cell invasion.

Life Cycle Management

DEFF Research Database (Denmark)

Bey, Niki

2018-01-01

This chapter gives an overview of Life Cycle Management (LCM)—a discipline that deals with the managerial tasks related to practicing sustainable development in an organisation . Just as Life Cycle Assessment, LCM advocates the life cycle perspective , and it applies this perspective in decision...

Computation techniques and computer programs to analyze Stirling cycle engines using characteristic dynamic energy equations

Science.gov (United States)

Larson, V. H.

1982-01-01

The basic equations that are used to describe the physical phenomena in a Stirling cycle engine are the general energy equations and equations for the conservation of mass and conversion of momentum. These equations, together with the equation of state, an analytical expression for the gas velocity, and an equation for mesh temperature are used in this computer study of Stirling cycle characteristics. The partial differential equations describing the physical phenomena that occurs in a Stirling cycle engine are of the hyperbolic type. The hyperbolic equations have real characteristic lines. By utilizing appropriate points along these curved lines the partial differential equations can be reduced to ordinary differential equations. These equations are solved numerically using a fourth-fifth order Runge-Kutta integration technique.

Cell reprogramming modelled as transitions in a hierarchy of cell cycles

International Nuclear Information System (INIS)

Hannam, Ryan; Annibale, Alessia; Kühn, Reimer

2017-01-01

We construct a model of cell reprogramming (the conversion of fully differentiated cells to a state of pluripotency, known as induced pluripotent stem cells, or iPSCs) which builds on key elements of cell biology viz. cell cycles and cell lineages. Although reprogramming has been demonstrated experimentally, much of the underlying processes governing cell fate decisions remain unknown. This work aims to bridge this gap by modelling cell types as a set of hierarchically related dynamical attractors representing cell cycles. Stages of the cell cycle are characterised by the configuration of gene expression levels, and reprogramming corresponds to triggering transitions between such configurations. Two mechanisms were found for reprogramming in a two level hierarchy: cycle specific perturbations and a noise induced switching. The former corresponds to a directed perturbation that induces a transition into a cycle-state of a different cell type in the potency hierarchy (mainly a stem cell) whilst the latter is a priori undirected and could be induced, e.g. by a (stochastic) change in the cellular environment. These reprogramming protocols were found to be effective in large regimes of the parameter space and make specific predictions concerning reprogramming dynamics which are broadly in line with experimental findings. (paper)

DETECTING ALIEN LIMIT CYCLES NEAR A HAMILTONIAN 2-SADDLE CYCLE

OpenAIRE

LUCA, Stijn; DUMORTIER, Freddy; Caubergh, M.; Roussarie, R.

2009-01-01

This paper aims at providing and example of a cubic Hamiltonian 2-saddle cycle that after bifurcation can give rise to an alien limit cycle; this is a limit cycle that is not controlled by a zero of the related Abelian integral. To guarantee the existence of an alien limit cycle one can verify generic conditions on the Abelian integral and on the transition map associated to the connections of the 2-saddle cycle. In this paper, a general method is developed to compute the first and second der...

Using optical tweezers to relate the chemical and mechanical cross-bridge cycles.

OpenAIRE

Steffen, Walter; Sleep, John

2004-01-01

In most current models of muscle contraction there are two translational steps, the working stroke, whereby an attached myosin cross-bridge moves relative to the actin filament, and the repriming step, in which the cross-bridge returns to its original orientation. The development of single molecule methods has allowed a more detailed investigation of the relationship of these mechanical steps to the underlying biochemistry. In the normal adenosine triphosphate cycle, myosin.adenosine diphosph...

Differential concentration-specific effects of caffeine on cell viability, oxidative stress, and cell cycle in pulmonary oxygen toxicity in vitro

International Nuclear Information System (INIS)

Tiwari, Kirti Kumar; Chu, Chun; Couroucli, Xanthi; Moorthy, Bhagavatula; Lingappan, Krithika

2014-01-01

Highlights: • Caffeine at 0.05 mM decreases oxidative stress in hyperoxia. • Caffeine at 1 mM decreases cell viability, increases oxidative stress in hyperoxia. • Caffeine at 1 but not 0.05 mM, abrogates hyperoxia-induced G2/M arrest. - Abstract: Caffeine is used to prevent bronchopulmonary dysplasia (BPD) in premature neonates. Hyperoxia contributes to the development of BPD, inhibits cell proliferation and decreases cell survival. The mechanisms responsible for the protective effect of caffeine in pulmonary oxygen toxicity remain largely unknown. A549 and MLE 12 pulmonary epithelial cells were exposed to hyperoxia or maintained in room air, in the presence of different concentrations (0, 0.05, 0.1 and 1 mM) of caffeine. Caffeine had a differential concentration-specific effect on cell cycle progression, oxidative stress and viability, with 1 mM concentration being deleterious and 0.05 mM being protective. Reactive oxygen species (ROS) generation during hyperoxia was modulated by caffeine in a similar concentration-specific manner. Caffeine at 1 mM, but not at the 0.05 mM concentration decreased the G2 arrest in these cells. Taken together this study shows the novel funding that caffeine has a concentration-specific effect on cell cycle regulation, ROS generation, and cell survival in hyperoxic conditions

Differential concentration-specific effects of caffeine on cell viability, oxidative stress, and cell cycle in pulmonary oxygen toxicity in vitro

Energy Technology Data Exchange (ETDEWEB)

Tiwari, Kirti Kumar; Chu, Chun; Couroucli, Xanthi; Moorthy, Bhagavatula; Lingappan, Krithika, E-mail: lingappa@bcm.edu

2014-08-08

Highlights: • Caffeine at 0.05 mM decreases oxidative stress in hyperoxia. • Caffeine at 1 mM decreases cell viability, increases oxidative stress in hyperoxia. • Caffeine at 1 but not 0.05 mM, abrogates hyperoxia-induced G2/M arrest. - Abstract: Caffeine is used to prevent bronchopulmonary dysplasia (BPD) in premature neonates. Hyperoxia contributes to the development of BPD, inhibits cell proliferation and decreases cell survival. The mechanisms responsible for the protective effect of caffeine in pulmonary oxygen toxicity remain largely unknown. A549 and MLE 12 pulmonary epithelial cells were exposed to hyperoxia or maintained in room air, in the presence of different concentrations (0, 0.05, 0.1 and 1 mM) of caffeine. Caffeine had a differential concentration-specific effect on cell cycle progression, oxidative stress and viability, with 1 mM concentration being deleterious and 0.05 mM being protective. Reactive oxygen species (ROS) generation during hyperoxia was modulated by caffeine in a similar concentration-specific manner. Caffeine at 1 mM, but not at the 0.05 mM concentration decreased the G2 arrest in these cells. Taken together this study shows the novel funding that caffeine has a concentration-specific effect on cell cycle regulation, ROS generation, and cell survival in hyperoxic conditions.

Differential Rotation via Tracking of Coronal Bright Points.

Science.gov (United States)

McAteer, James; Boucheron, Laura E.; Osorno, Marcy

2016-05-01

The accurate computation of solar differential rotation is important both as a constraint for, and evidence towards, support of models of the solar dynamo. As such, the use of Xray and Extreme Ultraviolet bright points to elucidate differential rotation has been studied in recent years. In this work, we propose the automated detection and tracking of coronal bright points (CBPs) in a large set of SDO data for re-evaluation of solar differential rotation and comparison to other results. The big data aspects, and high cadence, of SDO data mitigate a few issues common to detection and tracking of objects in image sequences and allow us to focus on the use of CBPs to determine differential rotation. The high cadence of the data allows to disambiguate individual CBPs between subsequent images by allowing for significant spatial overlap, i.e., by the fact that the CBPs will rotate a short distance relative to their size. The significant spatial overlap minimizes the effects of incorrectly detected CBPs by reducing the occurrence of outlier values of differential rotation. The big data aspects of the data allows to be more conservative in our detection of CBPs (i.e., to err on the side of missing CBPs rather than detecting extraneous CBPs) while still maintaining statistically larger populations over which to study characteristics. The ability to compute solar differential rotation through the automated detection and tracking of a large population of CBPs will allow for further analyses such as the N-S asymmetry of differential rotation, variation of differential rotation over the solar cycle, and a detailed study of the magnetic flux underlying the CBPs.

The relationship between macroeconomic and industry-specific business cycle indicators and work-related injuris among Danish construction workers

DEFF Research Database (Denmark)

Nielsen, Kent Jacob; Lander, Flemming; Lauritsen, Jens

2015-01-01

Objectives The current study examines and compares the relationship between both macroeconomic and industry-specific business cycle indicators, and work-related injuries among construction workers in Denmark using emergency department (ED) injury data and also officially reported injuries...... (range 0.14–0.20) and WEA injuries (range 0.13–0.36). Furthermore, although there is some variability in the strength of the relationship of the different business cycle indicators, the relationships are generally not stronger for the WEA injuries than for the ED injuries, except for general unemployment....... Similarly, no substantial differences in strength of relation between industry-specific and macroeconomic indicators were identified. Conclusions The study shows that there was no difference in the relationship between business cycle indicators, and WEA and ED injury data. This indicates that changes...

Msx homeobox genes inhibit differentiation through upregulation of cyclin D1.

Science.gov (United States)

Hu, G; Lee, H; Price, S M; Shen, M M; Abate-Shen, C

2001-06-01

During development, patterning and morphogenesis of tissues are intimately coordinated through control of cellular proliferation and differentiation. We describe a mechanism by which vertebrate Msx homeobox genes inhibit cellular differentiation by regulation of the cell cycle. We show that misexpression of Msx1 via retroviral gene transfer inhibits differentiation of multiple mesenchymal and epithelial progenitor cell types in culture. This activity of Msx1 is associated with its ability to upregulate cyclin D1 expression and Cdk4 activity, while Msx1 has minimal effects on cellular proliferation. Transgenic mice that express Msx1 under the control of the mouse mammary tumor virus long terminal repeat (MMTV LTR) display impaired differentiation of the mammary epithelium during pregnancy, which is accompanied by elevated levels of cyclin D1 expression. We propose that Msx1 gene expression maintains cyclin D1 expression and prevents exit from the cell cycle, thereby inhibiting terminal differentiation of progenitor cells. Our model provides a framework for reconciling the mutant phenotypes of Msx and other homeobox genes with their functions as regulators of cellular proliferation and differentiation during embryogenesis.

Optimal cure cycle design of a resin-fiber composite laminate

Science.gov (United States)

Hou, Jean W.; Sheen, Jeenson

1987-01-01

A unified computed aided design method was studied for the cure cycle design that incorporates an optimal design technique with the analytical model of a composite cure process. The preliminary results of using this proposed method for optimal cure cycle design are reported and discussed. The cure process of interest is the compression molding of a polyester which is described by a diffusion reaction system. The finite element method is employed to convert the initial boundary value problem into a set of first order differential equations which are solved simultaneously by the DE program. The equations for thermal design sensitivities are derived by using the direct differentiation method and are solved by the DE program. A recursive quadratic programming algorithm with an active set strategy called a linearization method is used to optimally design the cure cycle, subjected to the given design performance requirements. The difficulty of casting the cure cycle design process into a proper mathematical form is recognized. Various optimal design problems are formulated to address theses aspects. The optimal solutions of these formulations are compared and discussed.

Omega-3 Polyunsaturated Fatty Acids Enhance Neuronal Differentiation in Cultured Rat Neural Stem Cells

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Masanori Katakura

2013-01-01

Full Text Available Polyunsaturated fatty acids (PUFAs can induce neurogenesis and recovery from brain diseases. However, the exact mechanisms of the beneficial effects of PUFAs have not been conclusively described. We recently reported that docosahexaenoic acid (DHA induced neuronal differentiation by decreasing Hes1 expression and increasing p27kip1 expression, which causes cell cycle arrest in neural stem cells (NSCs. In the present study, we examined the effect of eicosapentaenoic acid (EPA and arachidonic acid (AA on differentiation, expression of basic helix-loop-helix transcription factors (Hes1, Hes6, and NeuroD, and the cell cycle of cultured NSCs. EPA also increased mRNA levels of Hes1, an inhibitor of neuronal differentiation, Hes6, an inhibitor of Hes1, NeuroD, and Map2 mRNA and Tuj-1-positive cells (a neuronal marker, indicating that EPA induced neuronal differentiation. EPA increased the mRNA levels of p21cip1 and p27kip1, a cyclin-dependent kinase inhibitor, which indicated that EPA induced cell cycle arrest. Treatment with AA decreased Hes1 mRNA but did not affect NeuroD and Map2 mRNA levels. Furthermore, AA did not affect the number of Tuj-1-positive cells or cell cycle progression. These results indicated that EPA could be involved in neuronal differentiation by mechanisms alternative to those of DHA, whereas AA did not affect neuronal differentiation in NSCs.

Depth of dormancy in tomato seeds is related to the progression of the cell cycle prior to its induction

NARCIS (Netherlands)

Castro, de R.D.; Lammeren, van A.A.M.; Groot, S.P.C.; Bino, R.J.; Hilhorst, H.W.M.

2001-01-01

Cell cycle activities are initiated following imbibition of non-dormant seeds. However, it is not known whether cell cycle related events other than DNA replication also remain suppressed in imbibed dormant seeds. The objective of this study was to demonstrate that the transitions between the

Gene activation by UV light, fungal elicitor or fungal infection in Petroselinum crispum is correlated with repression of cell cycle-related genes

International Nuclear Information System (INIS)

Logemann, E.; Wu ShengCheng; Schröder, J.; Schmelzer, E.; Somssich, I.E.; Hahlbrock, K.

1995-01-01

The effects of UV light or fungal elicitors on plant cells have so far been studied mostly with respect to defense-related gene activation. Here, an inverse correlation of these stimulatory effects with the activities of several cell cycle-related genes is demonstrated. Concomitant with the induction of flavonoid biosynthetic enzymes in UV-irradiated cell suspension cultures of parsley (Petroselinum crispum), total histone synthesis declined to about half the initial rate. A subclass of the histone H3 gene family was selected to demonstrate the close correlation of its expression with cell division, both in intact plants and cultured cells. Using RNA-blot and run-on transcription assays, it was shown that one arbitrarily selected subclass of each of the histone H2A, H2B, H3 and H4 gene families and of the genes encoding a p34cdc2 protein kinase and a mitotic cyclin were transcriptionally repressed in UV-irradiated as well as fungal elicitor-treated parsley cells. The timing and extent of repression differed between the two stimuli; the response to light was more transient and smaller in magnitude. These differential responses to light and elicitor were inversely correlated with the induction of phenylalanine ammonia-lyase, a key enzyme of phenylpropanoid metabolism. Essentially the same result was obtained with a defined oligopeptide elicitor, indicating that the same signaling pathway is responsible for defense-related gene activation and cell cycle-related gene repression. A temporary (UV light) or long-lasting (fungal elicitor) cessation of cell culture growth is most likely due to an arrest of cell division which may be a prerequisite for full commitment of the cells to transcriptional activation of full commitment of the cells to transcriptional activation of pathways involved in UV protection or pathogen defense. This conclusion is corroborated by the observation that the histone H3 mRNA level greatly declined around fungal infection sites in young parsley

Cytoplasmic sequestration of cyclin D1 associated with cell cycle withdrawal of neuroblastoma cells

International Nuclear Information System (INIS)

Sumrejkanchanakij, Piyamas; Eto, Kazuhiro; Ikeda, Masa-Aki

2006-01-01

The regulation of D-type cyclin-dependent kinase activity is critical for neuronal differentiation and apoptosis. We recently showed that cyclin D1 is sequestered in the cytoplasm and that its nuclear localization induces apoptosis in postmitotic primary neurons. Here, we further investigated the role of the subcellular localization of cyclin D1 in cell cycle withdrawal during the differentiation of N1E-115 neuroblastoma cells. We show that cyclin D1 became predominantly cytoplasmic after differentiation. Targeting cyclin D1 expression to the nucleus induced phosphorylation of Rb and cdk2 kinase activity. Furthermore, cyclin D1 nuclear localization promoted differentiated N1E-115 cells to reenter the cell cycle, a process that was inhibited by p16 INK4a , a specific inhibitor of D-type cyclin activity. These results indicate that cytoplasmic sequestration of cyclin D1 plays a role in neuronal cell cycle withdrawal, and suggests that the abrogation of machinery involved in monitoring aberrant nuclear cyclin D1 activity contributes to neuronal tumorigenesis

Investigation of relation between singular points and number of limit cycles for a rotor-AMBs system

International Nuclear Information System (INIS)

Li, J.; Tian, Y.; Zhang, W.

2009-01-01

The relation between singular points and the number of limit cycles is investigated for a rotor-active magnetic bearings system with time-varying stiffness and single-degree-of-freedom. The averaged equation of the system is a perturbed polynomial Hamiltonian system of degree 5. The dynamic characteristics of the unperturbed system are first analyzed for a certain parameter group. The number of limit cycles and their configurations of the perturbed system under eight different parametric groups are obtained and the influence of eight control conditions on the number of limit cycles is studied. The results obtained here will play an important leading role in the study of the properties of nonlinear dynamics and control of the rotor-active magnetic bearings system with time-varying stiffness.

Ethanol induces cell-cycle activity and reduces stem cell diversity to alter both regenerative capacity and differentiation potential of cerebral cortical neuroepithelial precursors

Directory of Open Access Journals (Sweden)

Tingling Joseph D

2005-09-01

Full Text Available Abstract Background The fetal cortical neuroepithelium is a mosaic of distinct progenitor populations that elaborate diverse cellular fates. Ethanol induces apoptosis and interferes with the survival of differentiating neurons. However, we know little about ethanol's effects on neuronal progenitors. We therefore exposed neurosphere cultures from fetal rat cerebral cortex, to varying ethanol concentrations, to examine the impact of ethanol on stem cell fate. Results Ethanol promoted cell cycle progression, increased neurosphere number and increased diversity in neurosphere size, without inducing apoptosis. Unlike controls, dissociated cortical progenitors exposed to ethanol exhibited morphological evidence for asymmetric cell division, and cells derived from ethanol pre-treated neurospheres exhibited decreased proliferation capacity. Ethanol significantly reduced the numbers of cells expressing the stem cell markers CD117, CD133, Sca-1 and ABCG2, without decreasing nestin expression. Furthermore, ethanol-induced neurosphere proliferation was not accompanied by a commensurate increase in telomerase activity. Finally, cells derived from ethanol-pretreated neurospheres exhibited decreased differentiation in response to retinoic acid. Conclusion The reduction in stem cell number along with a transient ethanol-driven increase in cell proliferation, suggests that ethanol promotes stem to blast cell maturation, ultimately depleting the reserve proliferation capacity of neuroepithelial cells. However, the lack of a concomitant change in telomerase activity suggests that neuroepithelial maturation is accompanied by an increased potential for genomic instability. Finally, the cellular phenotype that emerges from ethanol pre-treated, stem cell depleted neurospheres is refractory to additional differentiation stimuli, suggesting that ethanol exposure ablates or delays subsequent neuronal differentiation.

Associations between urban form and cycling

DEFF Research Database (Denmark)

Nielsen, Thomas Alexander Sick; Olafsson, Anton Stahl; Carstensen, Trine Agervig

of National Travel Survey data indicated that established walkability factors such as density, connectivity and diversity are related to cycling, and that access to retail concentrations/centres, public transportation level-of-service, as well as competition between walking and cycling depending...... of cycling and the distance cycled. A high probability of cycling generally implies short cycling distances, which leads to non-uniform, non-monotonous relations between environmental indicators such as walkability and total cycling. Further analysis of primary data allowing a consideration of attitudes...

On generalized de Rham-Hodge complexes, the related characteristic Chern classes and some applications to integrable multi-dimensional differential systems on Riemannian manifolds

International Nuclear Information System (INIS)

Bogolubov, Nikolai N. Jr.; Prykarpatsky, Anatoliy K.

2006-12-01

The differential-geometric aspects of generalized de Rham-Hodge complexes naturally related with integrable multi-dimensional differential systems of M. Gromov type, as well as the geometric structure of Chern characteristic classes are studied. Special differential invariants of the Chern type are constructed, their importance for the integrability of multi-dimensional nonlinear differential systems on Riemannian manifolds is discussed. An example of the three-dimensional Davey-Stewartson type nonlinear strongly integrable differential system is considered, its Cartan type connection mapping and related Chern type differential invariants are analyzed. (author)

Nonlinear operators and nonlinear transformations studied via the differential form of the completeness relation in quantum mechanics

International Nuclear Information System (INIS)

Fan Hongyi; Yu Shenxi

1994-01-01

We show that the differential form of the fundamental completeness relation in quantum mechanics and the technique of differentiation within an ordered product (DWOP) of operators provide a new approach for calculating normal product expansions of some nonlinear operators and study some nonlinear transformations. Their usefulness in perturbative calculations is pointed out. (orig.)

Cyclic mechanical stretch enhances BMP9-induced osteogenic differentiation of mesenchymal stem cells.

Science.gov (United States)

Song, Yang; Tang, Yinhong; Song, Jinlin; Lei, Mingxing; Liang, Panpan; Fu, Tiwei; Su, Xudong; Zhou, Pengfei; Yang, Li; Huang, Enyi

2018-04-01

The purpose of this study was to investigate whether mechanical stretch can enhance the bone morphogenetic protein 9 (BMP9)-induced osteogenic differentiation in MSCs. Recombinant adenoviruses were used to overexpress the BMP9 in C3H10T1/2 MSCs. Cells were seeded onto six-well BioFlex collagen I-coated plates and subjected to cyclic mechanical stretch [6% elongation at 60 cycles/minute (1 Hz)] in a Flexercell FX-4000 strain unit for up to 12 hours. Immunostaining and confocal microscope were used to detect cytoskeleton organization. Cell cycle progression was checked by flow cytometry. Alkaline phosphatase activity was measured with a Chemiluminescence Assay Kit and was quantified with a histochemical staining assay. Matrix mineralization was examined by Alizarin Red S Staining. Mechanical stretch induces cytoskeleton reorganization and inhibits cell proliferation by preventing cells entry into S phase of the cell cycle. Although mechanical stretch alone does not induce the osteogenic differentiation of C3H10T1/2 MSCs, co-stimulation with mechanical stretch and BMP9 enhances alkaline phosphatase activity. The expression of key lineage-specific regulators (e.g., osteocalcin (OCN), SRY-related HMG-box 9, and runt-related transcription factor 2) is also increased after the co-stimulation, compared to the mechanical stretch stimulation along. Furthermore, mechanical stretch augments the BMP9-mediated bone matrix mineralization of C3H10T1/2 MSCs. Our results suggest that mechanical stretch enhances BMP9-induced osteoblastic lineage specification in C3H10T1/2 MSCs.

The KDM5 family is required for activation of pro-proliferative cell cycle genes during adipocyte differentiation

DEFF Research Database (Denmark)

Brier, Ann-Sofie B; Loft, Anne; Madsen, Jesper G S

2017-01-01

The KDM5 family of histone demethylases removes the H3K4 tri-methylation (H3K4me3) mark frequently found at promoter regions of actively transcribed genes and is therefore generally considered to contribute to corepression. In this study, we show that knockdown (KD) of all expressed members...... of the KDM5 family in white and brown preadipocytes leads to deregulated gene expression and blocks differentiation to mature adipocytes. KDM5 KD leads to a considerable increase in H3K4me3 at promoter regions; however, these changes in H3K4me3 have a limited effect on gene expression per se. By contrast......, genome-wide analyses demonstrate that KDM5A is strongly enriched at KDM5-activated promoters, which generally have high levels of H3K4me3 and are associated with highly expressed genes. We show that KDM5-activated genes include a large set of cell cycle regulators and that the KDM5s are necessary...

Proteomes of the Female Genital Tract During the Oestrous Cycle.

Science.gov (United States)

Soleilhavoup, Clement; Riou, Cindy; Tsikis, Guillaume; Labas, Valerie; Harichaux, Gregoire; Kohnke, Philippa; Reynaud, Karine; de Graaf, Simon P; Gerard, Nadine; Druart, Xavier

2016-01-01

The female genital tract includes several anatomical regions whose luminal fluids successively interact with gametes and embryos and are involved in the fertilisation and development processes. The luminal fluids from the inner cervix, the uterus and the oviduct were collected along the oestrous cycle at oestrus (Day 0 of the cycle) and during the luteal phase (Day 10) from adult cyclic ewes. The proteomes were assessed by GeLC-MS/MS and quantified by spectral counting. A set of 940 proteins were identified including 291 proteins differentially present along the cycle in one or several regions. The global analysis of the fluid proteomes revealed a general pattern of endocrine regulation of the tract, with the cervix and the oviduct showing an increased differential proteins abundance mainly at oestrus while the uterus showed an increased abundance mainly during the luteal phase. The proteins more abundant at oestrus included several families such as the heat shock proteins (HSP), the mucins, the complement cascade proteins and several redox enzymes. Other proteins known for their interaction with gametes such as oviductin (OVGP), osteopontin, HSPA8, and the spermadhesin AWN were also overexpressed at oestrus. The proteins more abundant during the luteal phase were associated with the immune system such as ceruloplasmin, lactoferrin, DMBT1, or PIGR, and also with tissue remodeling such as galectin 3 binding protein, alkaline phosphatase, CD9, or fibulin. Several proteins differentially abundant between estrus and the luteal phase, such as myosin 9 and fibronectin, were also validated by immunohistochemistry. The potential roles in sperm transit and uterine receptivity of the proteins differentially regulated along the cycle in the female genital tract are discussed. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The stability problem in the Kaldor-Kalecki business cycle model

International Nuclear Information System (INIS)

SzydIowski, Marek; Krawiec, Adam

2005-01-01

We consider the Kaldor-Kalecki model of the business cycle which is the modified Kaldor model with the Kalecki time delay in investment. The model is formulated in terms of a second-order nonlinear delay differential equation with a negative feedback. We investigate the problem of stability of cycles caused by retarded action. The method of a centre manifold is used to find the conditions for the Hopf bifurcation. The conditions for stability of limit cycles on the centre manifold is given

Developmental regulation of nucleolus size during Drosophila eye differentiation.

Directory of Open Access Journals (Sweden)

Nicholas E Baker

Full Text Available When cell cycle withdrawal accompanies terminal differentiation, biosynthesis and cellular growth are likely to change also. In this study, nucleolus size was monitored during cell fate specification in the Drosophila eye imaginal disc using fibrillarin antibody labeling. Nucleolus size is an indicator of ribosome biogenesis and can correlate with cellular growth rate. Nucleolar size was reduced significantly during cell fate specification and differentiation, predominantly as eye disc cells entered a cell cycle arrest that preceded cell fate specification. This reduction in nucleolus size required Dpp and Hh signaling. A transient enlargement of the nucleolus accompanied cell division in the Second Mitotic Wave. Nucleoli continued to diminish in postmitotic cells following fate specification. These results suggest that cellular growth is regulated early in the transition from proliferating progenitor cells to terminal cell fate specification, contemporary with regulation of the cell cycle, and requiring the same extracellular signals.

Developmental regulation of nucleolus size during Drosophila eye differentiation.

Science.gov (United States)

Baker, Nicholas E

2013-01-01

When cell cycle withdrawal accompanies terminal differentiation, biosynthesis and cellular growth are likely to change also. In this study, nucleolus size was monitored during cell fate specification in the Drosophila eye imaginal disc using fibrillarin antibody labeling. Nucleolus size is an indicator of ribosome biogenesis and can correlate with cellular growth rate. Nucleolar size was reduced significantly during cell fate specification and differentiation, predominantly as eye disc cells entered a cell cycle arrest that preceded cell fate specification. This reduction in nucleolus size required Dpp and Hh signaling. A transient enlargement of the nucleolus accompanied cell division in the Second Mitotic Wave. Nucleoli continued to diminish in postmitotic cells following fate specification. These results suggest that cellular growth is regulated early in the transition from proliferating progenitor cells to terminal cell fate specification, contemporary with regulation of the cell cycle, and requiring the same extracellular signals.

PI3K/AKT and ERK regulate retinoic acid-induced neuroblastoma cellular differentiation

Energy Technology Data Exchange (ETDEWEB)

Qiao, Jingbo [Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Paul, Pritha; Lee, Sora [Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Qiao, Lan; Josifi, Erlena; Tiao, Joshua R. [Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Chung, Dai H., E-mail: dai.chung@vanderbilt.edu [Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States)

2012-08-03

Highlights: Black-Right-Pointing-Pointer Retinoic acid (RA) induces neuroblastoma cells differentiation, which is accompanied by G0/G1 cell cycle arrest. Black-Right-Pointing-Pointer RA resulted in neuroblastoma cell survival and inhibition of DNA fragmentation; this is regulated by PI3K pathway. Black-Right-Pointing-Pointer RA activates PI3K and ERK1/2 pathway; PI3K pathway mediates RA-induced neuroblastoma cell differentiation. Black-Right-Pointing-Pointer Upregulation of p21 is necessary for RA-induced neuroblastoma cell differentiation. -- Abstract: Neuroblastoma, the most common extra-cranial solid tumor in infants and children, is characterized by a high rate of spontaneous remissions in infancy. Retinoic acid (RA) has been known to induce neuroblastoma differentiation; however, the molecular mechanisms and signaling pathways that are responsible for RA-mediated neuroblastoma cell differentiation remain unclear. Here, we sought to determine the cell signaling processes involved in RA-induced cellular differentiation. Upon RA administration, human neuroblastoma cell lines, SK-N-SH and BE(2)-C, demonstrated neurite extensions, which is an indicator of neuronal cell differentiation. Moreover, cell cycle arrest occurred in G1/G0 phase. The protein levels of cyclin-dependent kinase inhibitors, p21 and p27{sup Kip}, which inhibit cell proliferation by blocking cell cycle progression at G1/S phase, increased after RA treatment. Interestingly, RA promoted cell survival during the differentiation process, hence suggesting a potential mechanism for neuroblastoma resistance to RA therapy. Importantly, we found that the PI3K/AKT pathway is required for RA-induced neuroblastoma cell differentiation. Our results elucidated the molecular mechanism of RA-induced neuroblastoma cellular differentiation, which may be important for developing novel therapeutic strategy against poorly differentiated neuroblastoma.

Income-related inequalities in diseases and health conditions over the business cycle

OpenAIRE

Asgeirsdottir, Tinna Laufey; Hildur Margrét, Jóhannsdóttir

2017-01-01

How business cycles affect income-related distribution of diseases and health disorders is largely unknown. We examine how the prevalence of thirty diseases and health conditions is distributed across the income spectrum using survey data collected in Iceland in 2007, 2009 and 2012. Thus, we are able to take advantage of the unusually sharp changes in economic conditions in Iceland during the Great Recession initiated in 2008 and the partial recovery that had already taken place by 2012 to an...

Parametrized overview of CO_2 power cycles for different operation conditions and configurations – An absolute and relative performance analysis

International Nuclear Information System (INIS)

Cardemil, José M.; Silva, Alexandre K. da

2016-01-01

Highlights: • Thermodynamic modeling of CO_2-based power cycles. • A multi-parameter analysis for different cycle configurations. • Performance comparison between CO_2 and four other fluids. • Detailed discussion considering optimized operational parameters (i.e., pressure, HX size). • Overview of the technical applicability of the CO_2. - Abstract: This thermodynamically based study focuses on the thermal performance of power cycles using CO_2 as the working fluid. The work considers numerous aspects that can influence the cycle's performance, such as the type of cycle (i.e., Rankine or Brayton), its configuration (i.e., with and without a recuperator), and different operational conditions (i.e., heat source temperature and the upper and lower operating pressures of the CO_2). To account for all possible scenarios, a thermodynamic routine was especially implemented and linked to a library that contained all the thermodynamics properties of CO_2. The results are mostly presented in terms of the absolute and relative 1st and 2nd Law efficiencies of CO_2 as well as the cycle's scale, here represented by the global conductance (UA) of the heat exchangers used within the cycle. For the relative performance assessment, four other working fluids, commonly used in energy conversion cycles, were considered (i.e., ethane, toluene, D4 siloxane and water). As expected, the absolute performance results indicate a strong dependence of the cycle's efficiencies on the operational conditions. As for the relative performance, the results suggest that while the CO_2's 1st Law efficiency might be lower than other fluids, its exergetic efficiency can be significantly higher. Furthermore, the calculations also indicate that the CO_2's needed global conductance is potentially lower than competing fluids (e.g., toluene) for certain operational conditions, which suggests that CO_2-based power plants can be more compact, since they might require smaller heat exchangers to produce

Deep-Coverage MPS Analysis of Heteroplasmic Variants within the mtGenome Allows for Frequent Differentiation of Maternal Relatives

Directory of Open Access Journals (Sweden)

Mitchell M. Holland

2018-02-01

Full Text Available Distinguishing between maternal relatives through mitochondrial (mt DNA sequence analysis has been a longstanding desire of the forensic community. Using a deep-coverage, massively parallel sequencing (DCMPS approach, we studied the pattern of mtDNA heteroplasmy across the mtgenomes of 39 mother-child pairs of European decent; haplogroups H, J, K, R, T, U, and X. Both shared and differentiating heteroplasmy were observed on a frequent basis in these closely related maternal relatives, with the minor variant often presented as 2–10% of the sequencing reads. A total of 17 pairs exhibited differentiating heteroplasmy (44%, with the majority of sites (76%, 16 of 21 occurring in the coding region, further illustrating the value of conducting sequence analysis on the entire mtgenome. A number of the sites of differentiating heteroplasmy resulted in non-synonymous changes in protein sequence (5 of 21, and to changes in transfer or ribosomal RNA sequences (5 of 21, highlighting the potentially deleterious nature of these heteroplasmic states. Shared heteroplasmy was observed in 12 of the 39 mother-child pairs (31%, with no duplicate sites of either differentiating or shared heteroplasmy observed; a single nucleotide position (16093 was duplicated between the data sets. Finally, rates of heteroplasmy in blood and buccal cells were compared, as it is known that rates can vary across tissue types, with similar observations in the current study. Our data support the view that differentiating heteroplasmy across the mtgenome can be used to frequently distinguish maternal relatives, and could be of interest to both the medical genetics and forensic communities.

Spatial differentiated effect assessment for aquatic eutrophication in Life Cycle Assessment.

NARCIS (Netherlands)

Penailillo, Reinaldo

2005-01-01

The conventional evaluation of aquatic eutrophication in Life Cycle Assessment (LCA) expresses the contribution of nitrogen and/or phosphorus emissions to biomass production in terms of the equivalent emission of a reference substance. This assessment doe

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

Science.gov (United States)

Sukawa, Yumiko; Okamoto, Takashi

2018-03-01

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

EZH2 regulates neuroblastoma cell differentiation via NTRK1 promoter epigenetic modifications.

Science.gov (United States)

Li, Zhenghao; Takenobu, Hisanori; Setyawati, Amallia Nuggetsiana; Akita, Nobuhiro; Haruta, Masayuki; Satoh, Shunpei; Shinno, Yoshitaka; Chikaraishi, Koji; Mukae, Kyosuke; Akter, Jesmin; Sugino, Ryuichi P; Nakazawa, Atsuko; Nakagawara, Akira; Aburatani, Hiroyuki; Ohira, Miki; Kamijo, Takehiko

2018-05-01

The polycomb repressor complex 2 molecule EZH2 is now known to play a role in essential cellular processes, namely, cell fate decisions, cell cycle regulation, senescence, cell differentiation, and cancer development/progression. EZH2 inhibitors have recently been developed; however, their effectiveness and underlying molecular mechanisms in many malignancies have not yet been elucidated in detail. Although the functional role of EZH2 in tumorigenesis in neuroblastoma (NB) has been investigated, mutations of EZH2 have not been reported. A Kaplan-Meier analysis on the event free survival and overall survival of NB patients indicated that the high expression of EZH2 correlated with an unfavorable prognosis. In order to elucidate the functional roles of EZH2 in NB tumorigenesis and its aggressiveness, we knocked down EZH2 in NB cell lines using lentivirus systems. The knockdown of EZH2 significantly induced NB cell differentiation, e.g., neurite extension, and the neuronal differentiation markers, NF68 and GAP43. EZH2 inhibitors also induced NB cell differentiation. We performed a comprehensive transcriptome analysis using Human Gene Expression Microarrays and found that NTRK1 (TrkA) is one of the EZH2-related suppression targets. The depletion of NTRK1 canceled EZH2 knockdown-induced NB cell differentiation. Our integrative methylome, transcriptome, and chromatin immunoprecipitation assays using NB cell lines and clinical samples clarified that the NTRK1 P1 and P2 promoter regions were regulated differently by DNA methylation and EZH2-related histone modifications. The NTRK1 transcript variants 1/2, which were regulated by EZH2-related H3K27me3 modifications at the P1 promoter region, were strongly expressed in favorable, but not unfavorable NB. The depletion and inhibition of EZH2 successfully induced NTRK1 transcripts and functional proteins. Collectively, these results indicate that EZH2 plays important roles in preventing the differentiation of NB cells and also

The Differential-Algebraic Analysis of Symplectic and Lax Structures Related with New Riemann-Type Hydrodynamic Systems

Science.gov (United States)

Prykarpatsky, Yarema A.; Artemovych, Orest D.; Pavlov, Maxim V.; Prykarpatski, Anatolij K.

2013-06-01

A differential-algebraic approach to studying the Lax-type integrability of the generalized Riemann-type hydrodynamic hierarchy, proposed recently by O. D. Artemovych, M. V. Pavlov, Z. Popowicz and A. K. Prykarpatski, is developed. In addition to the Lax-type representation, found before by Z. Popowicz, a closely related representation is constructed in exact form by means of a new differential-functional technique. The bi-Hamiltonian integrability and compatible Poisson structures of the generalized Riemann type hierarchy are analyzed by means of the symplectic and gradient-holonomic methods. An application of the devised differential-algebraic approach to other Riemann and Vakhnenko type hydrodynamic systems is presented.

PARP-2 regulates cell cycle-related genes through histone deacetylation and methylation independently of poly(ADP-ribosyl)ation

International Nuclear Information System (INIS)

Liang, Ya-Chen; Hsu, Chiao-Yu; Yao, Ya-Li; Yang, Wen-Ming

2013-01-01

Highlights: ► PARP-2 acts as a transcription co-repressor independently of PARylation activity. ► PARP-2 recruits HDAC5, 7, and G9a and generates repressive chromatin. ► PARP-2 is recruited to the c-MYC promoter by DNA-binding factor YY1. ► PARP-2 represses cell cycle-related genes and alters cell cycle progression. -- Abstract: Poly(ADP-ribose) polymerase-2 (PARP-2) catalyzes poly(ADP-ribosyl)ation (PARylation) and regulates numerous nuclear processes, including transcription. Depletion of PARP-2 alters the activity of transcription factors and global gene expression. However, the molecular action of how PARP-2 controls the transcription of target promoters remains unclear. Here we report that PARP-2 possesses transcriptional repression activity independently of its enzymatic activity. PARP-2 interacts and recruits histone deacetylases HDAC5 and HDAC7, and histone methyltransferase G9a to the promoters of cell cycle-related genes, generating repressive chromatin signatures. Our findings propose a novel mechanism of PARP-2 in transcriptional regulation involving specific protein–protein interactions and highlight the importance of PARP-2 in the regulation of cell cycle progression

Technical Meeting on Fast Reactors and Related Fuel Cycle Facilities with Improved Economic Characteristics. Working Material

International Nuclear Information System (INIS)

2013-01-01

In recent years, engineering oriented work, rather than basic research and development (R&D), has led to significant progress in improving the economics of innovative fast reactors and associated fuel cycle facilities, while maintaining and even enhancing the safety features of these systems. Optimization of plant size and layout, more compact designs, reduction of the amount of plant materials and the building volumes, higher operating temperatures to attain higher generating efficiencies, improvement of load factor, extended core lifetimes, high fuel burnup, etc. are good examples of achievements to date that have improved the economics of fast neutron systems. The IAEA, through its Technical Working Group on Fast Reactors (TWG-FR) and Technical Working Group on Nuclear Fuel Cycle Options and Spent Fuel Management (TWG-NFCO), devotes many of its initiatives to encouraging technical cooperation and promoting common research and technology development projects among Member States with fast reactor and advanced fuel cycle development programmes, with the general aim of catalysing and accelerating technology advances in these fields. In particular the theme of fast reactor deployment, scenarios and economics has been largely debated during the recent IAEA International Conference on Fast Reactors and Related Fuel Cycles: Safe Technologies and Sustainable Scenarios, held in Paris in March 2013. Several papers presented at this conference discussed the economics of fast reactors from different national and regional perspectives, including business cases, investment scenarios, funding mechanisms and design options that offer significant capital and energy production cost reductions. This Technical Meeting on Fast Reactors and Related Fuel Cycle Facilities with Improved Economic Characteristics addresses Member States’ expressed need for information exchange in the field, with the aim of identifying the main open issues and launching possible initiatives to help and

PPARγ ligand production is tightly linked to clonal expansion during initiation of adipocyte differentiation

DEFF Research Database (Denmark)

Hallenborg, Philip; Petersen, Rasmus Koefoed; Feddersen, Søren

2014-01-01

of differentiation. Concomitant with agonist production, murine fibroblasts undergo two rounds of mitosis referred to as mitotic clonal expansion. Here we show that mouse embryonic fibroblasts deficient in either of two cell cycle inhibitors, the transcription factor p53 or its target gene encoding the cyclin...... cycle inhibitory compounds decreased PPAR ligand production in differentiating 3T3-L1 preadipocytes. Furthermore, these inhibitors abolished the release of arachidonic acid induced by the hormonal cocktail initiating adipogenesis. Collectively, our results suggest that murine fibroblasts require clonal...... expansion for PPAR ligand production at the onset of adipocyte differentiation....

A prospect of fast reactor and related fuel cycle in Japan

Energy Technology Data Exchange (ETDEWEB)

Nagata, Takashi [Japan Atomic Energy Agency, Ibaraki (Japan)

2009-04-15

JAEA has launched a new project 'Fast Reactor Cycle Technology Development'(FaCT) in cooperation with electric utilities. In this FaCT project, a combination of 'the Japanese sodium cooled loop type fast reactor with oxide fuel, the advanced aqueous reprocessing, and the simplified palletizing fuel fabrication systems' is adopted, where many innovative technologies with technical challenging issues are actively used in order to provide significant improvements in economic competitiveness, and enhancement of safety and reliability, sustainability, and nonproliferation. Fast reactor cycle technology will provide harmonic solutions for global issues of energy resources and environments, and is expected to contribute to sustainable development of the future society. Therefore, it was selected as one of key technologies of national importance in the third term (JPY2006-2010) 'Science and Technology Basic Plan' in March 2006 in Japan. The 'Nuclear Energy National Plan' in August 2006 states start up of a demonstration FR by around 2025 and deployment of a commercial FR before 2050, and start operating fuel cycle facilities when these reactors achieve consistency. Accordingly, we will decide about the adoption of innovative technologies by judging their applicability by 2010, and present the conceptual designs of commercial and demonstration FR cycle facilities by 2015 with the R and D plans to realize. In developing the FR cycle, 5 Party council, which consists of MEXt, MITI, electricity utilities, manufacturers, and JAEA, was established in July 2006 for moving forward on the commercialization smoothly. In this framework, users' requirements for the future R and D, a scenario of transition from light water reactor cycle to sodium cooled FR cycle, international collaboration, development schedule, demonstration steps, and so on are discussed. In this presentation, a prospect concerning the system design features of JSFR and a

A prospect of fast reactor and related fuel cycle in Japan

International Nuclear Information System (INIS)

Nagata, Takashi

2009-01-01

JAEA has launched a new project 'Fast Reactor Cycle Technology Development'(FaCT) in cooperation with electric utilities. In this FaCT project, a combination of 'the Japanese sodium cooled loop type fast reactor with oxide fuel, the advanced aqueous reprocessing, and the simplified palletizing fuel fabrication systems' is adopted, where many innovative technologies with technical challenging issues are actively used in order to provide significant improvements in economic competitiveness, and enhancement of safety and reliability, sustainability, and nonproliferation. Fast reactor cycle technology will provide harmonic solutions for global issues of energy resources and environments, and is expected to contribute to sustainable development of the future society. Therefore, it was selected as one of key technologies of national importance in the third term (JPY2006-2010) 'Science and Technology Basic Plan' in March 2006 in Japan. The 'Nuclear Energy National Plan' in August 2006 states start up of a demonstration FR by around 2025 and deployment of a commercial FR before 2050, and start operating fuel cycle facilities when these reactors achieve consistency. Accordingly, we will decide about the adoption of innovative technologies by judging their applicability by 2010, and present the conceptual designs of commercial and demonstration FR cycle facilities by 2015 with the R and D plans to realize. In developing the FR cycle, 5 Party council, which consists of MEXt, MITI, electricity utilities, manufacturers, and JAEA, was established in July 2006 for moving forward on the commercialization smoothly. In this framework, users' requirements for the future R and D, a scenario of transition from light water reactor cycle to sodium cooled FR cycle, international collaboration, development schedule, demonstration steps, and so on are discussed. In this presentation, a prospect concerning the system design features of JSFR and a summary of the above R and D progresses for

Differential effects of x-rays and high-energy 56Fe ions on human mesenchymal stem cells.

Science.gov (United States)

Kurpinski, Kyle; Jang, Deok-Jin; Bhattacharya, Sanchita; Rydberg, Bjorn; Chu, Julia; So, Joanna; Wyrobek, Andy; Li, Song; Wang, Daojing

2009-03-01

Stem cells hold great potential for regenerative medicine, but they have also been implicated in cancer and aging. How different kinds of ionizing radiation affect stem cell biology remains unexplored. This study was designed to compare the biological effects of X-rays and of high-linear energy transfer (LET) (56)Fe ions on human mesenchymal stem cells (hMSC). A multi-functional comparison was carried out to investigate the differential effects of X-rays and (56)Fe ions on hMSC. The end points included modulation of key markers such as p53, cell cycle progression, osteogenic differentiation, and pathway and networks through transcriptomic profiling and bioinformatics analysis. X-rays and (56)Fe ions differentially inhibited the cell cycle progression of hMSC in a p53-dependent manner without impairing their in vitro osteogenic differentiation process. Pathway and network analyses revealed that cytoskeleton and receptor signaling were uniquely enriched for low-dose (0.1 Gy) X-rays. In contrast, DNA/RNA metabolism and cell cycle regulation were enriched for high-dose (1 Gy) X-rays and (56)Fe ions, with more significant effects from (56)Fe ions. Specifically, DNA replication, DNA strand elongation, and DNA binding/transferase activity were perturbed more severely by 1 Gy (56)Fe ions than by 1 Gy X-rays, consistent with the significant G2/M arrest for the former while not for the latter. (56)Fe ions exert more significant effects on hMSC than X-rays. Since hMSC are the progenitors of osteoblasts in vivo, this study provides new mechanistic understandings of the relative health risks associated with low- and high-dose X-rays and high-LET space radiation.

International comparisons of the associations between objective measures of the built environment and transport-related walking and cycling: IPEN Adult Study.

Science.gov (United States)

Christiansen, Lars B; Cerin, Ester; Badland, Hannah; Kerr, Jacqueline; Davey, Rachel; Troelsen, Jens; van Dyck, Delfien; Mitáš, Josef; Schofield, Grant; Sugiyama, Takemi; Salvo, Deborah; Sarmiento, Olga L; Reis, Rodrigo; Adams, Marc; Frank, Larry; Sallis, James F

2016-12-01

Mounting evidence documents the importance of urban form for active travel, but international studies could strengthen the evidence. The aim of the study was to document the strength, shape, and generalizability of relations of objectively measured built environment variables with transport-related walking and cycling. This cross-sectional study maximized variation of environments and demographics by including multiple countries and by selecting adult participants living in neighborhoods based on higher and lower classifications of objectively measured walkability and socioeconomic status. Analyses were conducted on 12,181 adults aged 18-66 years, drawn from 14 cities across 10 countries worldwide. Frequency of transport-related walking and cycling over the last seven days was assessed by questionnaire and four objectively measured built environment variables were calculated. Associations of built environment variables with transport-related walking and cycling variables were estimated using generalized additive mixed models, and were tested for curvilinearity and study site moderation. We found positive associations of walking for transport with all the environmental attributes, but also found that the relationships was only linear for land use mix, but not for residential density, intersection density, and the number of parks. Our findings suggest that there may be optimum values in these attributes, beyond which higher densities or number of parks could have minor or even negative impact. Cycling for transport was associated linearly with residential density, intersection density (only for any cycling), and land use mix, but not with the number of parks. Across 14 diverse cities and countries, living in more densely populated areas, having a well-connected street network, more diverse land uses, and having more parks were positively associated with transport-related walking and/or cycling. Except for land-use-mix, all built environment variables had curvilinear

Expression Profiling of Differentiating Emerin-Null Myogenic Progenitor Identifies Molecular Pathways Implicated in Their Impaired Differentiation

Directory of Open Access Journals (Sweden)

Ashvin Iyer

2017-10-01

Full Text Available Mutations in the gene encoding emerin cause Emery-Dreifuss muscular dystrophy (EDMD, a disorder causing progressive skeletal muscle wasting, irregular heart rhythms and contractures of major tendons. RNA sequencing was performed on differentiating wildtype and emerin-null myogenic progenitors to identify molecular pathways implicated in EDMD, 340 genes were uniquely differentially expressed during the transition from day 0 to day 1 in wildtype cells. 1605 genes were uniquely expressed in emerin-null cells; 1706 genes were shared among both wildtype and emerin-null cells. One thousand and forty-seven transcripts showed differential expression during the transition from day 1 to day 2. Four hundred and thirty-one transcripts showed altered expression in both wildtype and emerin-null cells. Two hundred and ninety-five transcripts were differentially expressed only in emerin-null cells and 321 transcripts were differentially expressed only in wildtype cells. DAVID, STRING and Ingenuity Pathway Analysis identified pathways implicated in impaired emerin-null differentiation, including cell signaling, cell cycle checkpoints, integrin signaling, YAP/TAZ signaling, stem cell differentiation, and multiple muscle development and myogenic differentiation pathways. Functional enrichment analysis showed biological functions associated with the growth of muscle tissue and myogenesis of skeletal muscle were inhibited. The large number of differentially expressed transcripts upon differentiation induction suggests emerin functions during transcriptional reprograming of progenitors to committed myoblasts.

Differential response of carbon cycling to long-term nutrient input and altered hydrological conditions in a continental Canadian peatland

Science.gov (United States)

Berger, Sina; Praetzel, Leandra S. E.; Goebel, Marie; Blodau, Christian; Knorr, Klaus-Holger

2018-02-01

Peatlands play an important role in global carbon cycling, but their responses to long-term anthropogenically changed hydrologic conditions and nutrient infiltration are not well known. While experimental manipulation studies, e.g., fertilization or water table manipulations, exist on the plot scale, only few studies have addressed such factors under in situ conditions. Therefore, an ecological gradient from the center to the periphery of a continental Canadian peatland bordering a eutrophic water reservoir, as reflected by increasing nutrient input, enhanced water level fluctuations, and increasing coverage of vascular plants, was used for a case study of carbon cycling along a sequence of four differently altered sites. We monitored carbon dioxide (CO2) and methane (CH4) surface fluxes and dissolved inorganic carbon (DIC) and CH4 concentrations in peat profiles from April 2014 through September 2015. Moreover, we studied bulk peat and pore-water quality and we applied δ13C-CH4 and δ13C-CO2 stable isotope abundance analyses to examine dominant CH4 production and emission pathways during the growing season of 2015. We observed differential responses of carbon cycling at the four sites, presumably driven by abundances of plant functional types and vicinity to the reservoir. A shrub-dominated site in close vicinity to the reservoir was a comparably weak sink for CO2 (in 1.5 years: -1093 ± 794, in 1 year: +135 ± 281 g CO2 m-2; a net release) as compared to two graminoid-moss-dominated sites and a moss-dominated site (in 1.5 years: -1552 to -2260 g CO2 m-2, in 1 year: -896 to -1282 g CO2 m-2). Also, the shrub-dominated site featured notably low DIC pore-water concentrations and comparably 13C-enriched CH4 (δ13C- CH4: -57.81 ± 7.03 ‰) and depleted CO2 (δ13C-CO2: -15.85 ± 3.61 ‰) in a more decomposed peat, suggesting a higher share of CH4 oxidation and differences in predominant methanogenic pathways. In comparison to all other sites, the graminoid

Periodic solutions and bifurcations of delay-differential equations

International Nuclear Information System (INIS)

He Jihuan

2005-01-01

In this Letter a simple but effective iteration method is proposed to search for limit cycles or bifurcation curves of delay-differential equations. An example is given to illustrate its convenience and effectiveness

Life-cycle assessments in the South African water sector: A review ...

African Journals Online (AJOL)

Therefore, in South Africa it is important to promote the use of LCAs for the water sector in order to improve efficiency of processes and systems, but also to promote life-cycle based water footprinting and to include differentiated water consumption data into life-cycle inventories to make more efficient use of water as a ...

Hypoxia is a key regulator of limbal epithelial stem cell growth and differentiation

DEFF Research Database (Denmark)

Bath, Chris; Yang, Sufang; Muttuvelu, Danson

2013-01-01

The aim of this study was to determine whether the growth and differentiation of limbal epithelial stem cell cultures could be controlled through manipulation of the oxygen tension. Limbal epithelial cells were isolated from corneoscleral disks, and cultured using either feeder cells in a growth......, progression through cell cycle, colony forming efficiency (CFE), and expression of stem cell (ABCG2 and p63α) and differentiation (CK3) markers was determined throughout the culture period of up to 18 days. Low oxygen levels favored a stem cell phenotype with a lower proliferative rate, high CFE......, and a relatively higher expression of ABCG2 and p63α, while higher levels of oxygen led not only to decreased CFE but also to increased proportion of differentiated cells positive for CK3. Hypoxic cultures may thus potentially improve stem cell grafts for cultured limbal epithelial transplantation (CLET)....

Replicon-dependent differentiation of symbiosis-related genes in Sinorhizobium strains nodulating Glycine max.

Science.gov (United States)

Guo, Hui Juan; Wang, En Tao; Zhang, Xing Xing; Li, Qin Qin; Zhang, Yan Ming; Tian, Chang Fu; Chen, Wen Xin

2014-02-01

In order to investigate the genetic differentiation of Sinorhizobium strains nodulating Glycine max and related microevolutionary mechanisms, three housekeeping genes (SMc00019, truA, and thrA) and 16 symbiosis-related genes on the chromosome (7 genes), pSymA (6 genes), and pSymB (3 genes) were analyzed. Five distinct species were identified among the test strains by calculating the average nucleotide identity (ANI) of SMc00019-truA-thrA: Sinorhizobium fredii, Sinorhizobium sojae, Sinorhizobium sp. I, Sinorhizobium sp. II, and Sinorhizobium sp. III. These species assignments were also supported by population genetics and phylogenetic analyses of housekeeping genes and symbiosis-related genes on the chromosome and pSymB. Different levels of genetic differentiation were observed among these species or different replicons. S. sojae was the most divergent from the other test species and was characterized by its low intraspecies diversity and limited geographic distribution. Intergenic recombination dominated the evolution of 19 genes from different replicons. Intraspecies recombination happened frequently in housekeeping genes and symbiosis-related genes on the chromosome and pSymB, whereas pSymA genes showed a clear pattern of lateral-transfer events between different species. Moreover, pSymA genes were characterized by a lower level of polymorphism and recombination than those on the chromosome and pSymB. Taken together, genes from different replicons of rhizobia might be involved in the establishment of symbiosis with legumes, but these symbiosis-related genes might have evolved differently according to their corresponding replicons.

F-actin distribution and function during sexual differentiation in Schizosaccharomyces pombe

DEFF Research Database (Denmark)

Petersen, J; Nielsen, O; Egel, R

1998-01-01

Sexual differentiation in Schizosaccharomyces pombe is induced from the G1 phase of the cell cycle by nitrogen starvation and the presence of mating pheromones. We describe the distribution of F-actin during sexual differentiation. Cortical F-actin dots have previously been shown to be restricted...... to one end of the rod shaped cell during the G1 phase of the cell cycle. Within half an hour of nitrogen starvation the distribution of cortical F-actin dots switched from being monopolar to bipolar. This was then reversed as the F-actin cytoskeleton repolarized so that cortical F-actin dots accumulated...

Galectin-12 in Cellular Differentiation, Apoptosis and Polarization

Directory of Open Access Journals (Sweden)

Lei Wan

2018-01-01

Full Text Available Galectin-12 is a member of a family of mammalian lectins characterized by their affinity for β-galactosides and consensus amino acid sequences. The protein structure consists of a single polypeptide chain containing two carbohydrate-recognition domains joined by a linker region. Galectin-12 is predominantly expressed in adipose tissue, but is also detected in macrophages and other leukocytes. Downregulation of galectin-12 in mouse 3T3-L1 cells impairs their differentiation into adipocytes. Conversely, overexpression of galectin-12 in vitro induces cell cycle arrest in G1 and apoptosis. Upregulation of galectin-12 and initiation of G1 cell cycle arrest are associated with driving pre-adipocytes toward terminal differentiation. Galectin-12 deficiency increases insulin sensitivity and glucose tolerance in obese animals. Galectin-12 inhibits macrophage polarization to the M2 population, enhancing inflammation and decreasing insulin sensitivity in adipocytes. Galectin-12 also affects myeloid differentiation, which is associated with chemotherapy resistance. In addition to highlighting the above-mentioned aspects, this review also discusses the potential clinical applications of modulating the function of galectin-12.

The timing of T cell priming and cycling

Directory of Open Access Journals (Sweden)

Reinhard eObst

2015-11-01

Full Text Available The proliferation of specific lymphocytes is the central tenet of the clonal selection paradigm. Antigen recognition by T cells triggers a series of events that produces expanded clones of differentiated effector cells. TCR signaling events are detectable within seconds and minutes and are likely to continue for hours and days in vivo. Here, I review the work done on the importance of TCR signals in the later part of the expansion phase of the primary T cell response, primarily regarding the regulation of the cell cycle in CD4+ and CD8+ cells. The results suggest a degree of programming by early signals for effector differentiation, particularly in the CD8+ T cell compartment, with optimal expansion supported by persistent antigen presentation later on. Differences to CD4+ T cell expansion and new avenues towards a molecular understanding of cell cycle regulation in lymphocytes are discussed.

Differentiating Writing Instruction: Meeting the Diverse Needs of Authors in a Classroom

Science.gov (United States)

Shea, Mary

2015-01-01

This article outlines a rational for responsive, differentiated writing instruction that targets students' identified needs with respect to various dimensions of the writing process. Discussed is a cycle that requires ongoing assessment, instructional decision-making, responsive, differentiated instruction, guided practice, and assessment.…

Sprint interval and moderate-intensity cycling training differentially affect adiposity and aerobic capacity in overweight young-adult women.

Science.gov (United States)

Higgins, Simon; Fedewa, Michael V; Hathaway, Elizabeth D; Schmidt, Michael D; Evans, Ellen M

2016-11-01

The purpose of the study was to examine the effects of sprint interval training (SIT) and moderate-intensity continuous cycle training (MICT), with equal estimated energy expenditure during training on body composition and aerobic capacity. Body composition measured via dual-energy X-ray absorptiometry and aerobic capacity were assessed following 6 weeks of training in previously inactive overweight/obese young women (n = 52; age, 20.4 ± 1.5 years; body mass index, 30.3 ± 4.5 kg·m -2 , 67.3% white). Training was performed in a group-exercise format that mimicked cycling classes offered by commercial fitness facilities, and included 3 weekly sessions of either 30-s "all-out" sprints followed by 4 min of active recovery (SIT), or continuous cycling at 60%-70% heart rate reserve to expend a similar amount of energy. Participants were randomized to SIT or MICT, attended a similar number of sessions (15.0 ± 1.5 sessions vs. 15.8 ± 1.9 sessions, P = 0.097) and expended a similar amount of energy (541.8 ± 104.6 kJ·session -1 vs. 553.5 ± 138.1 kJ·session -1 , P = 0.250). Without significant changes in body mass (P > 0.05), greater relative reductions occurred in SIT than in MICT in total fat mass (3.6% ± 5.6% vs. 0.6% ± 3.9%, P = 0.007), and android fat mass (6.6% ± 6.9% vs. 0.7% ± 6.5%, P = 0.002). Aerobic capacity (mL·kg -1 ·min -1 ) increased significantly following both interventions (P interval cycling reduces adiposity and increases aerobic capacity more than continuous moderate-intensity cycling of equal estimated energy expenditure in overweight/obese young women.

Cell-cycle phase specificity of chloroethylnitrosoureas

International Nuclear Information System (INIS)

Linfoot, P.A.

1986-01-01

Although the cancer chemotherapeutic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) is considered a non-cell cycle phase specific drug, it has been shown to produce differential cell killing in G 1 , S, and G 2 /M phase cells, with S phase cells appearing relatively resistant. Studies of cell cycle phase specific cell killing produced by nitrosoureas with different chemical reactivities, clearly indicated that the ability of compounds to cross-link DNA was important in determining their phase specificity. Cells that lacked guanine O 6 -alkytransferase activity showed similar patterns of BCNU phase specificity regardless of their intrinsic sensitivity to BCNU. DNA inter-strand cross-linking, as measured by alkaline elution, was similar in cells exposed to BCNU in G 1 or S phase. 3 H [1-chloroethyl-1nitrosourea] binding to DNA was the same in G 1 , S and G 2 /M phase cells indicating that phase-specific differences in drug uptake and intracellular drug dose were not responsible for phase specific cell kill. These studies suggest that cross-link lesions, other than DNA inter-strand cross-links, and/or effects on DNA repair, other than guanine O 6 -alkyltransferase, are additional important determinants of BCNU phase specific cell killing

Neuron-NG2 Cell Synapses: Novel Functions for Regulating NG2 Cell Proliferation and Differentiation

Directory of Open Access Journals (Sweden)

Qian-Kun Yang

2013-01-01

Full Text Available NG2 cells are a population of CNS cells that are distinct from neurons, mature oligodendrocytes, astrocytes, and microglia. These cells can be identified by their NG2 proteoglycan expression. NG2 cells have a highly branched morphology, with abundant processes radiating from the cell body, and express a complex set of voltage-gated channels, AMPA/kainate, and GABA receptors. Neurons notably form classical and nonclassical synapses with NG2 cells, which have varied characteristics and functions. Neuron-NG2 cell synapses could fine-tune NG2 cell activities, including the NG2 cell cycle, differentiation, migration, and myelination, and may be a novel potential therapeutic target for NG2 cell-related diseases, such as hypoxia-ischemia injury and periventricular leukomalacia. Furthermore, neuron-NG2 cell synapses may be correlated with the plasticity of CNS in adulthood with the synaptic contacts passing onto their progenies during proliferation, and synaptic contacts decrease rapidly upon NG2 cell differentiation. In this review, we highlight the characteristics of classical and nonclassical neuron-NG2 cell synapses, the potential functions, and the fate of synaptic contacts during proliferation and differentiation, with the emphasis on the regulation of the NG2 cell cycle by neuron-NG2 cell synapses and their potential underlying mechanisms.

Environmental Impacts, Health and Safety Impacts, and Financial Costs of the Front End of the Nuclear Fuel Cycle

Energy Technology Data Exchange (ETDEWEB)

Brett W Carlsen; Urairisa Phathanapirom; Eric Schneider; John S. Collins; Roderick G. Eggert; Brett Jordan; Bethany L. Smith; Timothy M. Ault; Alan G. Croff; Steven L. Krahn; William G. Halsey; Mark Sutton; Clay E. Easterly; Ryan P. Manger; C. Wilson McGinn; Stephen E. Fisher; Brent W. Dixon; Latif Yacout

2013-07-01

FEFC processes, unlike many of the proposed fuel cycles and technologies under consideration, involve mature operational processes presently in use at a number of facilities worldwide. This report identifies significant impacts resulting from these current FEFC processes and activities. Impacts considered to be significant are those that may be helpful in differentiating between fuel cycle performance and for which the FEFC impact is not negligible relative to those from the remainder of the full fuel cycle. This report: • Defines ‘representative’ processes that typify impacts associated with each step of the FEFC, • Establishes a framework and architecture for rolling up impacts into normalized measures that can be scaled to quantify their contribution to the total impacts associated with various fuel cycles, and • Develops and documents the bases for estimates of the impacts and costs associated with each of the representative FEFC processes.

The Reduction of Chazy Classes and Other Third-Order Differential Equations Related to Boundary Layer Flow Models

International Nuclear Information System (INIS)

Fakhar, K.; Kara, A. H.

2012-01-01

We study the symmetries, conservation laws and reduction of third-order equations that evolve from a prior reduction of models that arise in fluid phenomena. These could be the ordinary differential equations (ODEs) that are reductions of partial differential equations (PDEs) or, alternatively, PDEs related to given ODEs. In this class, the analysis includes the well-known Blasius, Chazy, and other associated third-order ODEs. (general)

Response of an oscillatory differential delay equation to a single stimulus.

Science.gov (United States)

Mackey, Michael C; Tyran-Kamińska, Marta; Walther, Hans-Otto

2017-04-01

Here we analytically examine the response of a limit cycle solution to a simple differential delay equation to a single pulse perturbation of the piecewise linear nonlinearity. We construct the unperturbed limit cycle analytically, and are able to completely characterize the perturbed response to a pulse of positive amplitude and duration with onset at different points in the limit cycle. We determine the perturbed minima and maxima and period of the limit cycle and show how the pulse modifies these from the unperturbed case.

SOLAR CYCLE 24: CURIOUS CHANGES IN THE RELATIVE NUMBERS OF SUNSPOT GROUP TYPES

International Nuclear Information System (INIS)

Kilcik, A.; Yurchyshyn, V. B.; Ozguc, A.; Rozelot, J. P.

2014-01-01

Here, we analyze different sunspot group (SG) behaviors from the points of view of both the sunspot counts (SSCs) and the number of SGs, in four categories, for the time period of 1982 January-2014 May. These categories include data from simple (A and B), medium (C), large (D, E, and F), and decaying (H) SGs. We investigate temporal variations of all data sets used in this study and find the following results. (1) There is a very significant decrease in the large groups' SSCs and the number of SGs in solar cycle 24 (cycle 24) compared to cycles 21-23. (2) There is no strong variation in the decaying groups' data sets for the entire investigated time interval. (3) Medium group data show a gradual decrease for the last three cycles. (4) A significant decrease occurred in the small groups during solar cycle 23, while no strong changes show in the current cycle (cycle 24) compared to the previous ones. We confirm that the temporal behavior of all categories is quite different from cycle to cycle and it is especially flagrant in solar cycle 24. Thus, we argue that the reduced absolute number of the large SGs is largely, if not solely, responsible for the weak cycle 24. These results might be important for long-term space weather predictions to understand the rate of formation of different groups of sunspots during a solar cycle and the possible consequences for the long-term geomagnetic activity

Chloroplast Dysfunction Causes Multiple Defects in Cell Cycle Progression in the Arabidopsis crumpled leaf Mutant

KAUST Repository

Hudik, Elodie

2014-07-18

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

Chromatin plasticity as a differentiation index during muscle differentiation of C2C12 myoblasts

International Nuclear Information System (INIS)

Watanabe, Tomonobu M.; Higuchi, Sayaka; Kawauchi, Keiko; Tsukasaki, Yoshikazu; Ichimura, Taro; Fujita, Hideaki

2012-01-01

Highlights: ► Change in the epigenetic landscape during myogenesis was optically investigated. ► Mobility of nuclear proteins was used to state the epigenetic status of the cell. ► Mobility of nuclear proteins decreased as myogenesis progressed in C2C12. ► Differentiation state diagram was developed using parameters obtained. -- Abstract: Skeletal muscle undergoes complicated differentiation steps that include cell-cycle arrest, cell fusion, and maturation, which are controlled through sequential expression of transcription factors. During muscle differentiation, remodeling of the epigenetic landscape is also known to take place on a large scale, determining cell fate. In an attempt to determine the extent of epigenetic remodeling during muscle differentiation, we characterized the plasticity of the chromatin structure using C2C12 myoblasts. Differentiation of C2C12 cells was induced by lowering the serum concentration after they had reached full confluence, resulting in the formation of multi-nucleated myotubes. Upon induction of differentiation, the nucleus size decreased whereas the aspect ratio increased, indicating the presence of force on the nucleus during differentiation. Movement of the nucleus was also suppressed when differentiation was induced, indicating that the plasticity of chromatin changed upon differentiation. To evaluate the histone dynamics during differentiation, FRAP experiment was performed, which showed an increase in the immobile fraction of histone proteins when differentiation was induced. To further evaluate the change in the histone dynamics during differentiation, FCS was performed, which showed a decrease in histone mobility on differentiation. We here show that the plasticity of chromatin decreases upon differentiation, which takes place in a stepwise manner, and that it can be used as an index for the differentiation stage during myogenesis using the state diagram developed with the parameters obtained in this study.

Cell cycle related /sup 125/IUDR-induced-division delay

International Nuclear Information System (INIS)

Scheniderman, M.H.; Hofer, K.G.

1987-01-01

A series of experiments were run to determine if /sup 125/I-decays, in /sup 125/IUdR labeled DNA, specifically accumulated at 1, 3, 5, 7 and 9 hours after plating labeled mitotic cells caused a change in the rate or time of cell entry into mitosis. To accomplish this, a pool of labeled mitotic cells was selected in mitosis and plated in replicate flasks. /sup 125/I decays were accumulated in groups of cells by cooling (4 0 C) for 2 hours starting at the designated times. After rewarding, colcemid was added to arrest cells in mitosis. The rate of cell progression into mitosis for each cell cycle time of accumulation was determined by scoring the mitotic index of cells sampled as a function of time after addition of the colcemid. The results are summarized: (1) Decays from /sup 125/I in /sup 125/I(UdR) labeled DNA reduced the rate of cell progression into mitosis and delayed the time of initiation of mitosis. (2) The reduced rate of progression and the delayed time of initiation of mitosis were independent of the cell cycle time that /sup 125/I-decays were accumulated. (3) The reduced rate of progression after cell cycle accumulation of /sup 125/I decay was statistically indistinguishable from the corresponding controls. (4) The delayed initiation of mitosis after specific cell cycle accumulation of /sup 125/I- decays was greater than the corresponding control. The relationship of these data to DNA and non-DNA division delay target(s) is emphasized

Establishment of human papillomavirus infection requires cell cycle progression.

Directory of Open Access Journals (Sweden)

Dohun Pyeon

2009-02-01

Full Text Available Human papillomaviruses (HPVs are DNA viruses associated with major human cancers. As such there is a strong interest in developing new means, such as vaccines and microbicides, to prevent HPV infections. Developing the latter requires a better understanding of the infectious life cycle of HPVs. The HPV infectious life cycle is closely linked to the differentiation state of the stratified epithelium it infects, with progeny virus only made in the terminally differentiating suprabasal compartment. It has long been recognized that HPV must first establish its infection within the basal layer of stratified epithelium, but why this is the case has not been understood. In part this restriction might reflect specificity of expression of entry receptors. However, this hypothesis could not fully explain the differentiation restriction of HPV infection, since many cell types can be infected with HPVs in monolayer cell culture. Here, we used chemical biology approaches to reveal that cell cycle progression through mitosis is critical for HPV infection. Using infectious HPV16 particles containing the intact viral genome, G1-synchronized human keratinocytes as hosts, and early viral gene expression as a readout for infection, we learned that the recipient cell must enter M phase (mitosis for HPV infection to take place. Late M phase inhibitors had no effect on infection, whereas G1, S, G2, and early M phase cell cycle inhibitors efficiently prevented infection. We conclude that host cells need to pass through early prophase for successful onset of transcription of the HPV encapsidated genes. These findings provide one reason why HPVs initially establish infections in the basal compartment of stratified epithelia. Only this compartment of the epithelium contains cells progressing through the cell cycle, and therefore it is only in these cells that HPVs can establish their infection. By defining a major condition for cell susceptibility to HPV infection, these

Life Cycle Characteristics of Small Professional Service Firms

NARCIS (Netherlands)

Masurel, E.; van Montfort, C.A.G.M.

2006-01-01

Our study of professional services firms clearly revealed that firms change over the course of their life cycles. During the first three stages, diversification in sales, the differentiation in labor force, and the level of labor productivity increase. In the last stage, diversification in sales,

Vertical patterns of ichthyoplankton at the interface between a temperate estuary and adjacent coastal waters: Seasonal relation to diel and tidal cycles

Science.gov (United States)

Primo, Ana Lígia; Azeiteiro, Ulisses M.; Marques, Sónia C.; Ré, Pedro; Pardal, Miguel A.

2012-07-01

Vertical distribution and migration pattern of ichthyoplankton assemblage in the Mondego estuary were investigated in relation to diel and tidal cycle. Summer and winter communities were sampled, at surface and bottom, over a diel cycle during spring and neap tides at a fixed station at the mouth of the estuary. Summer presented higher larvae density mainly of Pomatoschistus spp., Gobius niger and Parablennius pilicornis. Main species in winter assemblages were Pomatoschistus spp. and Sardina pilchardus. There were no differences between depth stratums across diel or tide cycle. Nevertheless, main species larval densities showed significant periodic variation associated with tide (M2) and diel (K1) cycles presenting generally, higher density at night and around low tide. Conversely, vertical patterns observed could not be related with diel or tidal cycle. Tough, main species presented some extent of vertical migration. Vertical patterns observed appear to be related to seasonal stratification and river flow, increasing amplitude during periods of less stratification and lower water currents. Present study provides a better understanding of ichthyoplankton vertical movement patterns and of small scale dynamics at the interface of two coastal European systems.

Haematological and electrocardiographic variations during menstrual cycle

International Nuclear Information System (INIS)

Rajnee, A.; Binawara, B.K.; Choudhary, S.; Chawla, V.K.; Choudhary, R.

2010-01-01

Menstruation coupled periodic bleeding from the blood vessels, at the time of shedding of the uterine mucosa has directed interest, more especially in the haematological changes during different phases of menstrual cycle. Methods: The present study was carried out on 30 healthy female medical students in the age group of 18 to 23 years with the normal menstrual cycle of 30 +- 3 days. The various haematological parameter and electrocardiography were studied on the second, eleventh, fourteenth and twenty second day of menstrual cycle. Result: The study reveals that the total leukocyte count and total platelet count significantly increased (p<0.001) around mid cycle, however total eosinophil count significantly decreased (p<0.05) during the same period. Differential leukocyte count, bleeding time, clotting time, heart rate, P-R interval and Q-T interval did not show any significant change during different phases of menstrual cycle, although some mild changes were observed. Conclusion: This study was a moderate attempt to determine regular variation in the different haematological parameters and ECG during the different phases of menstrual cycle in normal healthy females and evaluate conflicting reports on the subjects. (author)

Automatic differentiation bibliography

Energy Technology Data Exchange (ETDEWEB)

Corliss, G.F. [comp.

1992-07-01

This is a bibliography of work related to automatic differentiation. Automatic differentiation is a technique for the fast, accurate propagation of derivative values using the chain rule. It is neither symbolic nor numeric. Automatic differentiation is a fundamental tool for scientific computation, with applications in optimization, nonlinear equations, nonlinear least squares approximation, stiff ordinary differential equation, partial differential equations, continuation methods, and sensitivity analysis. This report is an updated version of the bibliography which originally appeared in Automatic Differentiation of Algorithms: Theory, Implementation, and Application.

Proposal of a nuclear cycle research and development plan in Tokai works. The roadmap from LWR cycle to FBR cycle

International Nuclear Information System (INIS)

Nakamura, Hirofumi; Abe, Tomoyuki; Kashimura, Takuo; Nagai, Toshihisa; Maeda, Seichiro; Yamaguchi, Toshiya; Kuroki, Ryoichiro

2003-07-01

The Generation-II Project Task Force Team has investigated a research and development plan of a future nuclear fuel cycle in Tokai works for about three months from December 19, 2002. First we have discussed about the present condition of Japanese nuclear fuel cycle and have recognized it as the following. The relation of the technology between the LWR-cycle and the FBR-cycle is not clear. MOX Fuel Use in Light Water Reactors is important to establish technology of the FBR fuel cycle. Radioactive waste disposal issue is urgent. Next we have proposed the three basic policies on R and D plan of nuclear fuel cycle in consideration of the F.S. on FBR-cycle. Establishment and advancement of 'the tough nuclear fuel cycle'. Early establishment of the FBR cycle technology to be able to supply energy stably for long-term. Establishment of the radioactive waste treatment and disposal technology, and optimization of nuclear fuel cycle technology from the viewpoint of radioactive waste. And we have proposed the Japanese technical holder system to integrate all LWR and FBR cycle technology. (author)

Differential radiosensitivity on a tissue level in Delphinium ajacis

Energy Technology Data Exchange (ETDEWEB)

Mandal, S K; Basu, R K [Bose Research Inst., Calcutta (India). Cryogenetics Lab.

1980-09-01

Root, leaf, pollen mother cell and endosperm of D.ajacis showed differential sensitivity as measured by X-ray-induced chromosomal aberrations at mitotic anaphase and telophase stages of the first and second division cycles after irradiation. These tissues differed significantly in Interphase Chromosome Volume (ICV) values. In all the tissues the percentage of aberrant cells increased linearly with increase in X-ray dose. Though endosperm had the largest ICV value it was the most radioresistant tissue tested. The relative radiosensitivity of the other 3 tissues was positively correlated with ICV value. The radioresistance of endosperm is probably due to factors unique to this tissue which remained obscure.

Why Consumers Misattribute Sponsorships to Non-Sponsor Brands: Differential Roles of Item and Relational Communications.

Science.gov (United States)

Weeks, Clinton S; Humphreys, Michael S; Cornwell, T Bettina

2018-02-01

Brands engaged in sponsorship of events commonly have objectives that depend on consumer memory for the sponsor-event relationship (e.g., sponsorship awareness). Consumers however, often misattribute sponsorships to nonsponsor competitor brands, indicating erroneous memory for these relationships. The current research uses an item and relational memory framework to reveal sponsor brands may inadvertently foster this misattribution when they communicate relational linkages to events. Effects can be explained via differential roles of communicating item information (information that supports processing item distinctiveness) versus relational information (information that supports processing relationships among items) in contributing to memory outcomes. Experiment 1 uses event-cued brand recall to show that correct memory retrieval is best supported by communicating relational information when sponsorship relationships are not obvious (low congruence). In contrast, correct retrieval is best supported by communicating item information when relationships are obvious (high congruence). Experiment 2 uses brand-cued event recall to show that, against conventional marketing recommendations, relational information increases misattribution, whereas item information guards against misattribution. Results suggest sponsor brands must distinguish between item and relational communications to enhance correct retrieval and limit misattribution. Methodologically, the work shows that choice of cueing direction is critical in differentially revealing patterns of correct and incorrect retrieval with pair relationships. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Differential Effects of X-Rays and High-Energy 56Fe Ions on Human Mesenchymal Stem Cells

International Nuclear Information System (INIS)

Kurpinski, Kyle; Jang, Deok-Jin; Bhattacharya, Sanchita; Rydberg, Bjorn; Chu, Julia; So, Joanna; Wyrobek, Andy; Li Song; Wang Daojing

2009-01-01

Purpose: Stem cells hold great potential for regenerative medicine, but they have also been implicated in cancer and aging. How different kinds of ionizing radiation affect stem cell biology remains unexplored. This study was designed to compare the biological effects of X-rays and of high-linear energy transfer (LET) 56 Fe ions on human mesenchymal stem cells (hMSC). Methods and Materials: A multi-functional comparison was carried out to investigate the differential effects of X-rays and 56 Fe ions on hMSC. The end points included modulation of key markers such as p53, cell cycle progression, osteogenic differentiation, and pathway and networks through transcriptomic profiling and bioinformatics analysis. Results: X-rays and 56 Fe ions differentially inhibited the cell cycle progression of hMSC in a p53-dependent manner without impairing their in vitro osteogenic differentiation process. Pathway and network analyses revealed that cytoskeleton and receptor signaling were uniquely enriched for low-dose (0.1 Gy) X-rays. In contrast, DNA/RNA metabolism and cell cycle regulation were enriched for high-dose (1 Gy) X-rays and 56 Fe ions, with more significant effects from 56 Fe ions. Specifically, DNA replication, DNA strand elongation, and DNA binding/transferase activity were perturbed more severely by 1 Gy 56 Fe ions than by 1 Gy X-rays, consistent with the significant G2/M arrest for the former while not for the latter. Conclusions: 56 Fe ions exert more significant effects on hMSC than X-rays. Since hMSC are the progenitors of osteoblasts in vivo, this study provides new mechanistic understandings of the relative health risks associated with low- and high-dose X-rays and high-LET space radiation

Fuel cycle cost uncertainty from nuclear fuel cycle comparison

International Nuclear Information System (INIS)

Li, J.; McNelis, D.; Yim, M.S.

2013-01-01

This paper examined the uncertainty in fuel cycle cost (FCC) calculation by considering both model and parameter uncertainty. Four different fuel cycle options were compared in the analysis including the once-through cycle (OT), the DUPIC cycle, the MOX cycle and a closed fuel cycle with fast reactors (FR). The model uncertainty was addressed by using three different FCC modeling approaches with and without the time value of money consideration. The relative ratios of FCC in comparison to OT did not change much by using different modeling approaches. This observation was consistent with the results of the sensitivity study for the discount rate. Two different sets of data with uncertainty range of unit costs were used to address the parameter uncertainty of the FCC calculation. The sensitivity study showed that the dominating contributor to the total variance of FCC is the uranium price. In general, the FCC of OT was found to be the lowest followed by FR, MOX, and DUPIC. But depending on the uranium price, the FR cycle was found to have lower FCC over OT. The reprocessing cost was also found to have a major impact on FCC

Aspectos nutricionais relacionados ao ciclo menstrual Nutritional aspects related to menstrual cycle

Directory of Open Access Journals (Sweden)

Helena Alves de Carvalho SAMPAIO

2002-09-01

Full Text Available O objetivo da presente revisão é apresentar os principais tópicos discutidos na literatura quanto à associação da nutrição com o ciclo menstrual, contribuindo para a implementação do atendimento nutricional de mulheres. São revisados aspectos referentes à fisiologia da menstruação, alterações metabólicas durante o ciclo menstrual e comportamentos alimentares associados a ele. Considerando-se o ciclo menstrual dividido em duas fases, a folicular e a lútea, é nesta última que são descritas mais alterações, como retenção de água, elevação de peso, aumento de demanda energética, modificações no perfil lipídico e no metabolismo de vitamina D, cálcio, magnésio e ferro, hipersensibilidade emocional, dores generalizadas e mudança do comportamento alimentar. Em relação a este último item, podem ocorrer maior ingestão energética e o desenvolvimento de compulsões alimentares, principalmente por chocolate, doces e alimentos muito salgados. É fundamental que todos os aspectos citados sejam investigados durante a consulta nutricional, a fim de serem adotadas condutas mais específicas.The aim of the present review is to show the most important topics discussed in literature about the association between nutrition and menstrual cycle, contributing to improve the nutritional care for women. Aspects related to physiology of the menstruation, metabolic changes and feeding behavior during the menstrual cycle are reviewed. Considering the menstrual cycle divided in two phases, follicular and luteal, it is in this last one that more alterations are described, like fluid retention, weight gain, increase in caloric needs, modifications in the lipid profile and in the metabolism of vitamin D, calcium, magnesium and iron, emotional hypersensitivity, aches and changes in feeding behavior. In relation to this last item, it can occur a higher caloric intake and the development of food cravings, mainly for chocolate, candies and

Premenstrual dysphoric disorder--review of actual findings about mental disorders related to menstrual cycle and possibilities of their therapy.

Science.gov (United States)

Zukov, I; Ptácek, R; Raboch, J; Domluvilová, D; Kuzelová, H; Fischer, S; Kozelek, P

2010-01-01

It is known that mood disorders in women explicitly relates to estrogen production. Except for these findings phenomenon as Premenstrual Syndrome and Premenstrual Dysphoric Disorder, directly connected to menstrual cycle in women, is widely discussed. Premenstrual dysphoric disorder (PMDD) is a set of subjectively unpleasant mental and somatic symptoms. It appears in luteal phase of ovarian cycle. During menstruation it remits and disappears up to one week from its termination. DSM IV classified PMDD into the category of "Other specific depressive disorders" and further revision DSM IV-TR classifies PMDD as a separate strictly defined psychiatric diagnosis. The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) does not include any specific category as PMDD or similar. The closest category F38.8 does not represent the core of the phenomenon because it relates only to general depressive symptomatology and does not give specific diagnostic criteria to menstrual cycle related mood disorders (Grady-Weliky, 2003). In the presented article, possible effectivity of PMDD treatment with the focus to antidepressants of SSRI type (Serotonin selective reuptake inhibitors) is discussed. In spite of interesting and significant findings, the treatment of PMDD and accordingly PMS is above all multidisciplinary question and it must be treated like that.

An estimator for the relative entropy rate of path measures for stochastic differential equations

Energy Technology Data Exchange (ETDEWEB)

Opper, Manfred, E-mail: manfred.opper@tu-berlin.de

2017-02-01

We address the problem of estimating the relative entropy rate (RER) for two stochastic processes described by stochastic differential equations. For the case where the drift of one process is known analytically, but one has only observations from the second process, we use a variational bound on the RER to construct an estimator.

Numerical simulation of the hair formation -modeling of hair cycle

Science.gov (United States)

Kajihara, Narumichi; Nagayama, Katsuya

2018-01-01

In the recent years, the fields of study of anti-aging, health and beauty, cosmetics, and hair diseases have attracted significant attention. In particular, human hair is considered to be an important aspect with regard to an attractive appearance. To this end, many workers have sought to understand the formation mechanism of the hair root. However, observing growth in the hair root is difficult, and a detailed mechanism of the process has not yet been elucidated. Hair repeats growth, retraction, and pause cycles (hair cycle) in a repetitive process. In the growth phase, hair is formed through processes of cell proliferation and differentiation (keratinization). During the retraction phase, hair growth stops, and during the resting period, hair fall occurs and new hair grows. This hair cycle is believed to affect the elongation rate, thickness, strength, and shape of hair. Therefore, in this study, we introduce a particle model as a new method to elucidate the unknown process of hair formation, and to model the hair formation process accompanying the proliferation and differentiation of the hair root cells in all three dimensions. In addition, to the growth period, the retraction and the resting periods are introduced to realize the hair cycle using this model.

Differentiation of closely related fungi by electronic nose analysis

DEFF Research Database (Denmark)

Karlshøj, Kristian; Nielsen, Per Væggemose; Larsen, Thomas Ostenfeld

2007-01-01

the electronic nose potentially responded to, volatile metabolites were collected, by diffusive sampling overnight onto tubes containing Tenax TA, between the 7th and 8th day of Incubation.Volatiles were analyzed by gas chromatography coupled to mass spectrometry and the results indicated that mail alcohols...... as well as the noacheese ociated P. expansum have been investigated by electronic nose, GC-MS, and LGMS analysis. The isolates were inoculated on yeast extract sucroseagar in 20-mL headspace flasks and electronicnose analysis was performed daily for a-74period. To assess which volatile metabolites...... by high pressure liquid chromatography, coupled-to a diode array detector and a time of flight mass spectrometer. Several mycotoxins were detected in samples from the specles P.nordicum, P.roqueforti, P.paneum, P.carneum, and P.expansum. Differentiation of closely related mycotoxin producing fungi...

Optimum gas turbine cycle for combined cycle power plant

International Nuclear Information System (INIS)

Polyzakis, A.L.; Koroneos, C.; Xydis, G.

2008-01-01

The gas turbine based power plant is characterized by its relatively low capital cost compared with the steam power plant. It has environmental advantages and short construction lead time. However, conventional industrial engines have lower efficiencies, especially at part load. One of the technologies adopted nowadays for efficiency improvement is the 'combined cycle'. The combined cycle technology is now well established and offers superior efficiency to any of the competing gas turbine based systems that are likely to be available in the medium term for large scale power generation applications. This paper has as objective the optimization of a combined cycle power plant describing and comparing four different gas turbine cycles: simple cycle, intercooled cycle, reheated cycle and intercooled and reheated cycle. The proposed combined cycle plant would produce 300 MW of power (200 MW from the gas turbine and 100 MW from the steam turbine). The results showed that the reheated gas turbine is the most desirable overall, mainly because of its high turbine exhaust gas temperature and resulting high thermal efficiency of the bottoming steam cycle. The optimal gas turbine (GT) cycle will lead to a more efficient combined cycle power plant (CCPP), and this will result in great savings. The initial approach adopted is to investigate independently the four theoretically possible configurations of the gas plant. On the basis of combining these with a single pressure Rankine cycle, the optimum gas scheme is found. Once the gas turbine is selected, the next step is to investigate the impact of the steam cycle design and parameters on the overall performance of the plant, in order to choose the combined cycle offering the best fit with the objectives of the work as depicted above. Each alterative cycle was studied, aiming to find the best option from the standpoint of overall efficiency, installation and operational costs, maintainability and reliability for a combined power

Differential item functioning (DIF) analyses of health-related quality of life instruments using logistic regression

DEFF Research Database (Denmark)

Scott, Neil W.; Fayers, Peter M.; Aaronson, Neil K.

2010-01-01

Differential item functioning (DIF) methods can be used to determine whether different subgroups respond differently to particular items within a health-related quality of life (HRQoL) subscale, after allowing for overall subgroup differences in that scale. This article reviews issues that arise...

Solar-cycle period-amplitude relation as evidence of hysteresis of the solar-cycle nonlinear magnetic oscillation and the long-term (55 year) cyclic modulation

International Nuclear Information System (INIS)

Yoshimura, H.

1979-01-01

A new dynamical model of the solar cycle has predicted that the cycle should have a hysteretic nature: the behavior of each 11 year cycle should depend on previous cycles. In the light of this new understanding of the dynamical mechanism of the solar cycle, Waldmeier's (hypothetical) law was examined as a yet unexplained characteristic of the cycle by studying the observed sunspot frequency curve. Contrary to this hypothetical law, however, it was found that sunspot cycle curves did not form a single-parameter family characterized by the maximum amplitude of the cycle. The evolutionary trajectories in period-amplitude phase space verified the hysteretic nature of the observed cycle and revealed long-term (55 year instead of the previously claimed 80 year) periodic modulations, called here 55 year grand cycles. Each 55 year grand cycle forms a loop in the phase space, and the characteristics of each 11 year cycle depend on its position in the ascending or descending phase of the grand cycle. This new law was analyzed by the nonlinear multiple-period dynamo oscillation model which has predicted the hysteretic nature. The era from cycle 11 to cycle 15 turned out to be an anomalous one characterized by alternating amplitudes for odd and even cycles. Cycles 16--20 seem to constitute one grand cycle. If this is true, cycle 21 would be the beginning of another grand maximum and the model predicts that its duration would be short

Transportation life cycle assessment (LCA) synthesis : life cycle assessment learning module series.

Science.gov (United States)

2015-03-12

The Life Cycle Assessment Learning Module Series is a set of narrated, self-advancing slideshows on : various topics related to environmental life cycle assessment (LCA). This research project produced the first 27 of such modules, which : are freely...

Cyclic tensile strain enhances human mesenchymal stem cell Smad 2/3 activation and tenogenic differentiation in anisotropic collagen-glycosaminoglycan scaffolds

Directory of Open Access Journals (Sweden)

WK Grier

2017-03-01

Full Text Available Orthopaedic injuries, particularly those involving ligaments and tendons, are some of the most commonly treated ailments in the United States and are associated with both high costs and poor outcomes. Regenerative medicine strategies for tendon injuries could be enhanced by three-dimensional biomaterials that can promote cell alignment and pro-tenogenic differentiation of patient-derived MSCs. We have previously described a collagen-glycosaminoglycan (CG scaffold possessing aligned structural features able to promote bone marrow MSC differentiation towards a tenogenic lineage, in the absence of growth factor supplementation. We aimed to employ a bioreactor to enhance MSC tenogenic differentiation within the aligned CG scaffold via cyclic tensile strain (CTS, and further to evaluate the relative effects of strain cycle duration and extended application of repeated cycles of CTS on MSC response. Human MSCs were cultured in CG scaffolds for up to 6 d under static (unloaded or cyclic tensile strain (1 Hz for 10 min every 6 h. Time-dependent activation of ERK 1/2 and p38 mechanotransduction pathways was observed within each 6 h strain cycle. MSCs remained viable throughout the experiment and application of CTS robustly upregulated the expression of tendon-specific extracellular matrix proteins and phenotypic markers. Simultaneously, CTS promoted increased phosphorylation of Smad 2/3, suggesting a link between tensile stimulation and TGF-β family growth factor production. Together, we demonstrated the design, fabrication and validation of a high-throughput tensile stimulation bioreactor to increase MSC tenogenic differentiation in porous CG scaffolds.

Differential-associative processing or example elaboration: Which strategy is best for learning the definitions of related and unrelated concepts?

Science.gov (United States)

Hannon, Brenda

2012-10-01

Definitions of related concepts (e.g., genotype - phenotype ) are prevalent in introductory classes. Consequently, it is important that educators and students know which strategy(s) work best for learning them. This study showed that a new comparative elaboration strategy, called differential-associative processing, was better for learning definitions of related concepts than was an integrative elaborative strategy, called example elaboration. This outcome occurred even though example elaboration was administered in a naturalistic way (Experiment 1) and students spent more time in the example elaboration condition learning (Experiments 1, 2, 3), and generating pieces of information about the concepts (Experiments 2 and 3). Further, with unrelated concepts ( morpheme-fluid intelligence ), performance was similar regardless if students used differential-associative processing or example elaboration (Experiment 3). Taken as a whole, these results suggest that differential-associative processing is better than example elaboration for learning definitions of related concepts and is as good as example elaboration for learning definitions of unrelated concepts.

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

Science.gov (United States)

El-Badawy, Ahmed; El-Badri, Nagwa

2016-01-13

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

Methylation of miR-145a-5p promoter mediates adipocytes differentiation

Energy Technology Data Exchange (ETDEWEB)

Du, Jingjing; Cheng, Xiao; Shen, Linyuan; Tan, Zhendong; Luo, Jia; Wu, Xiaoqian; Liu, Chendong [College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130 (China); Yang, Qiong [Department of Animal Husbandry and Veterinary Medicine, Chengdu Agricultural College, Chengdu 611100, Sichuan (China); Jiang, Yanzhi [College of Life and Science, Sichuan Agricultural University, Chengdu 611130 (China); Tang, Guoqing; Li, Xuewei [College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130 (China); Zhang, Shunhua, E-mail: zhangsh1919@163.com [College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130 (China); Zhu, Li, E-mail: zhuli7508@163.com [College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130 (China)

2016-06-17

MicroRNAs (miRNAs, miR) play important roles in adipocyte development. Recent studies showed that the expression of several miRNAs is closely related with promoter methylation. However, it is not known whether miRNA mediates adipocytes differentiation by means of DNA methylation. Here, we showed that miR-145a-5p was poorly expressed in adipose tissue from mice fed a high fat diet (HFD). Overexpression or inhibition of miR-145a-5p was unfavorable or beneficial, respectively, for adipogenesis, and these effects were achieved by regulating adipocyte-specific genes involved in lipogenic transcription, fatty acid synthesis, and fatty acid transportation. Particularly, we first suggested that miR-145a-5p mimics or inhibitors promoted or repressed adipocytes proliferation by regulating p53 and p21, which act as cell cycle regulating factors. Surprisingly, the miR-145a-5p-repressed adipocyte differentiation was enhanced or rescued when cells treated with 5-Aza-dC were transfected with miR-145a-5p mimics or inhibitors, respectively. These data indicated that, as a new mean to positively regulate adipocyte proliferation, the process of miR-145a-5p-inhibited adipogenesis may be regulated by DNA methylation. -- Highlights: •MiR-145a-5p promotes adipocytes proliferation. •MiR-145a-5p is negatively correlated with obesity. •MiR-145a-5p mediates adipocytes differentiation via regulating pathway related adipocytes differentiation. MiR-145a-5p mediating adipocytes differentiation was regulated by DNA methylation.

Some Differential Geometric Relations in the Elastic Shell

Directory of Open Access Journals (Sweden)

Xiaoqin Shen

2016-01-01

Full Text Available The theory of the elastic shells is one of the most important parts of the theory of solid mechanics. The elastic shell can be described with its middle surface; that is, the three-dimensional elastic shell with equal thickness comprises a series of overlying surfaces like middle surface. In this paper, the differential geometric relations between elastic shell and its middle surface are provided under the curvilinear coordinate systems, which are very important for forming two-dimensional linear and nonlinear elastic shell models. Concretely, the metric tensors, the determinant of metric matrix field, the Christoffel symbols, and Riemann tensors on the three-dimensional elasticity are expressed by those on the two-dimensional middle surface, which are featured by the asymptotic expressions with respect to the variable in the direction of thickness of the shell. Thus, the novelty of this work is that we can further split three-dimensional mechanics equations into two-dimensional variation problems. Finally, two kinds of special shells, hemispherical shell and semicylindrical shell, are provided as the examples.

The differentiation potential of adipose tissue-derived mesenchymal stem cells into cell lineage related to male germ cells

Directory of Open Access Journals (Sweden)

P. Bräunig

Full Text Available ABSTRACT The adipose tissue is a reliable source of Mesenchymal stem cells (MSCs showing a higher plasticity and transdifferentiation potential into multilineage cells. In the present study, adipose tissue-derived mesenchymal stem cells (AT-MSCs were isolated from mice omentum and epididymis fat depots. The AT-MSCs were initially compared based on stem cell surface markers and on the mesodermal trilineage differentiation potential. Additionally, AT-MSCs, from both sources, were cultured with differentiation media containing retinoic acid (RA and/or testicular cell-conditioned medium (TCC. The AT-MSCs expressed mesenchymal surface markers and differentiated into adipogenic, chondrogenic and osteogenic lineages. Only omentum-derived AT-MSCs expressed one important gene marker related to male germ cell lineages, after the differentiation treatment with RA. These findings reaffirm the importance of adipose tissue as a source of multipotent stromal-stem cells, as well as, MSCs source regarding differentiation purpose.

The relationship between macroeconomic and industry-specific business cycle indicators and work-related injuries among Danish construction workers.

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Nielsen, Kent Jacob; Lander, F; Lauritsen, J M

2015-04-01

The current study examines and compares the relationship between both macroeconomic and industry-specific business cycle indicators, and work-related injuries among construction workers in Denmark using emergency department (ED) injury data and also officially reported injuries to the Danish Working Environment Authority (WEA). The correlations between ED and WEA injury data from the catchment area of Odense University Hospital during the period 1984-2010 were tested separately for variability and trend with two general macroeconomic indicators (gross domestic product and the Danish unemployment rate) and two construction industry-specific indicators (gross value added and the number of employees). The results show that injury rates increase during economic booms and decrease during recessions. However, the regression coefficients were generally weak for both the ED (range 0.14-0.20) and WEA injuries (range 0.13-0.36). Furthermore, although there is some variability in the strength of the relationship of the different business cycle indicators, the relationships are generally not stronger for the WEA injuries than for the ED injuries, except for general unemployment. Similarly, no substantial differences in strength of relation between industry-specific and macroeconomic indicators were identified. The study shows that there was no difference in the relationship between business cycle indicators, and WEA and ED injury data. This indicates that changes in reporting behaviour do not seem to play a major role in the relation between the business cycle and workplace injuries in a Danish context. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

An approach to quantitative assessment of relative proliferation risks from nuclear fuel cycles

International Nuclear Information System (INIS)

Silvennoinen, P.; Vira, J.

1981-01-01

Feasibility of quantitative assessments of the risk of nuclear weapons proliferation is discussed in this paper. The proliferation risk is defined as a combined utility of the different fuel cycle processes or materials for the proscribed acquisition of a nuclear weapon. Based on a set of selected weighted criteria, the process utilities are calculated employing utility functions or fuzzy expectation values. The methods are compared to each other. The scheme appears feasible in relative comparisons while certain leeway must still be retained for political judgement. (author)

Therapeutic Targeting of Redox Signaling in Myofibroblast Differentiation and Age-Related Fibrotic Disease

Directory of Open Access Journals (Sweden)

Natalie Sampson

2012-01-01

Full Text Available Myofibroblast activation plays a central role during normal wound healing. Whereas insufficient myofibroblast activation impairs wound healing, excessive myofibroblast activation promotes fibrosis in diverse tissues (including benign prostatic hyperplasia, BPH leading to organ dysfunction and also promotes a stromal response that supports tumor progression. The incidence of impaired wound healing, tissue fibrosis, BPH, and certain cancers strongly increases with age. This paper summarizes findings from in vitro fibroblast-to-myofibroblast differentiation systems that serve as cellular models to study fibrogenesis of diverse tissues. Supported by substantial in vivo data, a large body of evidence indicates that myofibroblast differentiation induced by the profibrotic cytokine transforming growth factor beta is driven by a prooxidant shift in redox homeostasis due to elevated production of NADPH oxidase 4 (NOX4-derived hydrogen peroxide and supported by concomitant decreases in nitric oxide/cGMP signaling and reactive oxygen species (ROS scavenging enzymes. Fibroblast-to-myofibroblast differentiation can be inhibited and reversed by restoring redox homeostasis using antioxidants or NOX4 inactivation as well as enhancing nitric oxide/cGMP signaling via activation of soluble guanylyl cyclases or inhibition of phosphodiesterases. Current evidence indicates the therapeutic potential of targeting the prooxidant shift in redox homeostasis for the treatment of age-related diseases associated with myofibroblast dysregulation.

Income-related inequalities in diseases and health conditions over the business cycle.

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Ásgeirsdóttir, Tinna Laufey; Jóhannsdóttir, Hildur Margrét

2017-12-01

How business cycles affect income-related distribution of diseases and health disorders is largely unknown. We examine how the prevalence of thirty diseases and health conditions is distributed across the income spectrum using survey data collected in Iceland in 2007, 2009 and 2012. Thus, we are able to take advantage of the unusually sharp changes in economic conditions in Iceland during the Great Recession initiated in 2008 and the partial recovery that had already taken place by 2012 to analyze how income-related health inequality changed across time periods that can be described as a boom, crisis and recovery. The concentration curve and the concentration index are calculated for each disease, both overall and by gender. In all cases, we find a considerable income-related health inequality favoring higher income individuals, with a slight increase over the study period. Between 2007 and 2009, our results indicate increased inequality for women but decreased inequality for men. Between 2009 and 2012 on the contrary, men's inequality increases but women's decreases. The overarching result is thus that the economic hardship of the crisis temporarily increased female income-related health inequality, but decreased that of men.

Report of 3 Patients With Urea Cycle Defects Treated With Related Living-Donor Liver Transplant.

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Özçay, Figen; Barış, Zeren; Moray, Gökhan; Haberal, Nihan; Torgay, Adnan; Haberal, Mehmet

2015-11-01

Urea cycle defects are a group of metabolic disorders caused by enzymatic disruption of the urea cycle pathway, transforming nitrogen to urea for excretion from the body. Severe cases present in early infancy with life-threatening metabolic decompensation, and these episodes of hyperammonemia can be fatal or result in permanent neurologic damage. Despite the progress in pharmacologic treatment, long-term survival is poor especially for severe cases. Liver transplant is an alternative treatment option, providing sufficient enzymatic activity and decreasing the risk of metabolic decompensation. Three patients with urea cycle defects received related living-donor liver transplants at our hospital. Patients presented with late-onset ornithine transcarbamylase deficiency, argininosuccinate lyase deficiency, and citrullinemia. Maximum pretransplant ammonia levels were between 232 and 400 μmol/L (normal range is 18-72 μmol/L), and maximum posttransplant values were 52 to 94 μmol/L. All patients stopped medical treatment and dietary protein restriction for urea cycle defects after transplant. The patient with late-onset ornithine transcarbamylase deficiency already had motor deficits related to recurrent hyperammonemia attacks pretransplant. A major improvement could not be achieved, and he is wheelchair dependent at the age of 6 years. The other 2 patients had normal motor and mental skills before transplant, which have continued 12 and 14 months after transplant. Hepatic artery thrombosis in the patient with the ornithine transcarbamylase deficiency, intraabdominal infection in the patient with argininosuccinate lyase deficiency, and posterior reversible encephalopathy syndrome in the patient with citrullinemia were early postoperative complications. Histopathologic changes in livers explanted from patients with ornithine transcarbamylase deficiency and citrullinemia were nonspecific. The argininosuccinate lyase-deficient patient had portoportal fibrosis and cirrhotic

Serum uric acid in relation to endogenous reproductive hormones during the menstrual cycle: findings from the BioCycle study

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Mumford, Sunni L.; Dasharathy, Sonya S.; Pollack, Anna Z.; Perkins, Neil J.; Mattison, Donald R.; Cole, Stephen R.; Wactawski-Wende, Jean; Schisterman, Enrique F.

2013-01-01

STUDY QUESTION Do uric acid levels across the menstrual cycle show associations with endogenous estradiol (E2) and reproductive hormone concentrations in regularly menstruating women? SUMMARY ANSWER Mean uric acid concentrations were highest during the follicular phase, and were inversely associated with E2 and progesterone, and positively associated with FSH. WHAT IS KNOWN ALREADY E2 may decrease serum levels of uric acid in post-menopausal women; however, the interplay between endogenous reproductive hormones and uric acid levels among regularly menstruating women has not been elucidated. STUDY DESIGN, SIZE, DURATION The BioCycle study was a prospective cohort study conducted at the University at Buffalo research centre from 2005 to 2007, which followed healthy women for one (n = 9) or 2 (n = 250) menstrual cycle(s). PARTICIPANTS/MATERIALS, SETTING, METHODS Participants were healthy women aged 18–44 years. Hormones and uric acid were measured in serum eight times each cycle for up to two cycles. Marginal structural models with inverse probability of exposure weights were used to evaluate the associations between endogenous hormones and uric acid concentrations. MAIN RESULTS AND THE ROLE OF CHANCE Uric acid levels were observed to vary across the menstrual cycle, with the lowest levels observed during the luteal phase. Every log-unit increase in E2 was associated with a decrease in uric acid of 1.1% (β = −0.011; 95% confidence interval (CI): −0.019, −0.004; persistent-effects model), and for every log-unit increase in progesterone, uric acid decreased by ∼0.8% (β = −0.008; 95% CI: −0.012, −0.004; persistent-effects model). FSH was positively associated with uric acid concentrations, such that each log-unit increase was associated with a 1.6% increase in uric acid (β = 0.016; 95% CI: 0.005, 0.026; persistent-effects model). Progesterone and FSH were also associated with uric acid levels in acute-effects models. Of 509 cycles, 42 were anovulatory

Assessing Differential Item Functioning on the Test of Relational Reasoning

Directory of Open Access Journals (Sweden)

Denis Dumas

2018-03-01

Full Text Available The test of relational reasoning (TORR is designed to assess the ability to identify complex patterns within visuospatial stimuli. The TORR is designed for use in school and university settings, and therefore, its measurement invariance across diverse groups is critical. In this investigation, a large sample, representative of a major university on key demographic variables, was collected, and the resulting data were analyzed using a multi-group, multidimensional item-response theory model-comparison procedure. No significant differential item functioning was found on any of the TORR items across any of the demographic groups of interest. This finding is interpreted as evidence of the cultural fairness of the TORR, and potential test-development choices that may have contributed to that cultural fairness are discussed.

Thermodynamic Modeling for Open Combined Regenerative Brayton and Inverse Brayton Cycles with Regeneration before the Inverse Cycle

Directory of Open Access Journals (Sweden)

Lingen Chen

2012-01-01

Full Text Available A thermodynamic model of an open combined regenerative Brayton and inverse Brayton cycles with regeneration before the inverse cycle is established in this paper by using thermodynamic optimization theory. The flow processes of the working fluid with the pressure drops and the size constraint of the real power plant are modeled. There are 13 flow resistances encountered by the working fluid stream for the cycle model. Four of these, the friction through the blades and vanes of the compressors and the turbines, are related to the isentropic efficiencies. The remaining nine flow resistances are always present because of the changes in flow cross-section at the compressor inlet of the top cycle, regenerator inlet and outlet, combustion chamber inlet and outlet, turbine outlet of the top cycle, turbine outlet of the bottom cycle, heat exchanger inlet, and compressor inlet of the bottom cycle. These resistances associated with the flow through various cross-sectional areas are derived as functions of the compressor inlet relative pressure drop of the top cycle, and control the air flow rate, the net power output and the thermal efficiency. The analytical formulae about the power output, efficiency and other coefficients are derived with 13 pressure drop losses. It is found that the combined cycle with regenerator can reach higher thermal efficiency but smaller power output than those of the base combined cycle at small compressor inlet relative pressure drop of the top cycle.

The relationship between blood potassium, blood lactate, and electromyography signals related to fatigue in a progressive cycling exercise test.

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Tenan, Matthew S; McMurray, Robert G; Blackburn, B Troy; McGrath, Melanie; Leppert, Kyle

2011-02-01

Local muscle fatigue may be related to potassium efflux from the muscle cell and/or lactate accumulation within the muscle. Local fatigue causes a decrease in median frequency (MPF) of the electromyogram's power spectrum during isometric contractions but its relationship to changes in potassium and lactate during dynamic exercise is equivocal. Thus, this investigation evaluated relationships between changes in the MPF from the vastus lateralis and blood levels of lactate and potassium during an incremental cycling test and recovery. Trained cyclists (n=8) completed a discontinuous, graded cycle test to exhaustion under normal and glycogen-reduced conditions. The glycogen reduced condition promoted an environment of lower lactate production while permitting a consistent potassium response. Blood samples and maximal isometric EMG data were collected at the end of each stage and during recovery. Maximal lactate levels were ∼ 60% lower in the glycogen reduced condition; potassium was similar between trials. MPF did not change significantly at volitional fatigue. Further, MPF was not significantly related to lactate (p>0.27) or potassium (p>0.16) in either condition. Though both lactate and potassium have been implicated as factors relating to local muscle fatigue, neither is significantly related to changes in MPF during or after progressive exercise on a cycle ergometer. Copyright © 2010 Elsevier Ltd. All rights reserved.

Neurogenic transdifferentiation of human adipose-derived stem cells? A critical protocol reevaluation with special emphasis on cell proliferation and cell cycle alterations.

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Kompisch, Kai Michael; Lange, Claudia; Steinemann, Doris; Skawran, Britta; Schlegelberger, Brigitte; Müller, Reinhard; Schumacher, Udo

2010-11-01

Adipose-derived stem cells (ASCs) are reported to display multilineage differentiation potential, including neuroectodermal pathways. The aim of the present study was to critically re-evaluate the potential neurogenic (trans-)differentiation capacity of ASCs using a neurogenic induction protocol based on the combination of isobutylmethylxanthine (IBMX), indomethacin and insulin. ASCs isolated from lipo-aspirate samples of five healthy female donors were characterized and potential neurogenic (trans-)differentiation was assessed by means of immunohistochemistry and gene expression analyses. Cell proliferation and cell cycle alterations were studied, and the expression of CREB/ATF transcription factors was analyzed. ASCs expressed CD59, CD90 and CD105, and were tested negative for CD34 and CD45. Under neurogenic induction, ASCs adopted a characteristic morphology comparable to neur(on)al progenitors and expressed musashi1, β-III-tubulin and nestin. Gene expression analyses revealed an increased expression of β-III-tubulin, GFAP, vimentin and BDNF, as well as SOX4 in induced ASCs. Cell proliferation was significantly reduced under neurogenic induction; cell cycle analyses showed a G2-cell cycle arrest accompanied by differential expression of key regulators of cell cycle progression. Differential expression of CREB/ATF transcription factors could be observed on neurogenic induction, pointing to a decisive role of the cAMP-CREB/ATF system. Our findings may point to a potential neurogenic (trans-)differentiation of ASCs into early neur(on)al progenitors, but do not present definite evidence for it. Especially, the adoption of a neural progenitor cell-like morphology must not automatically be misinterpreted as a specific characteristic of a respective (trans-)differentiation process, as this may as well be caused by alterations of cell cycle progression.

T-cell differentiation and CD56+ levels in polypoidal choroidal vasculopathy and neovascular age-related macular degeneration.

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Subhi, Yousif; Nielsen, Marie Krogh; Molbech, Christopher Rue; Oishi, Akio; Singh, Amardeep; Nissen, Mogens Holst; Sørensen, Torben Lykke

2017-11-20

Polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (AMD) are prevalent age-related diseases characterized by exudative changes in the macula. Although they share anatomical and clinical similarities, they are also distinctly characterized by their own features, e.g. vascular abnormalities in PCV and drusen-mediated progression in neovascular AMD. PCV remains etiologically uncharacterized, and ongoing discussion is whether PCV and neovascular AMD share the same etiology or constitute two substantially different diseases. In this study, we investigated T-cell differentiation and aging profile in human patients with PCV, patients with neovascular AMD, and age-matched healthy control individuals. Fresh venous blood was prepared for flow cytometry to investigate CD4 + and CD8 + T-cell differentiation (naïve, central memory, effector memory, effector memory CD45ra + ), loss of differentiation markers CD27 and CD28, and expression of aging marker CD56. Patients with PCV were similar to the healthy controls in all aspects. In patients with neovascular AMD we found significantly accelerated T-cell differentiation (more CD28 - CD27 - cells) and aging (more CD56 + cells) in the CD8 + T-cell compartment. These findings suggest that PCV and neovascular AMD are etiologically different in terms of T cell immunity, and that neovascular AMD is associated with T-cell immunosenescence.

Will Solar Cycles 25 and 26 Be Weaker than Cycle 24?

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Javaraiah, J.

2017-11-01

The study of variations in solar activity is important for understanding the underlying mechanism of solar activity and for predicting the level of activity in view of the activity impact on space weather and global climate. Here we have used the amplitudes (the peak values of the 13-month smoothed international sunspot number) of Solar Cycles 1 - 24 to predict the relative amplitudes of the solar cycles during the rising phase of the upcoming Gleissberg cycle. We fitted a cosine function to the amplitudes and times of the solar cycles after subtracting a linear fit of the amplitudes. The best cosine fit shows overall properties (periods, maxima, minima, etc.) of Gleissberg cycles, but with large uncertainties. We obtain a pattern of the rising phase of the upcoming Gleissberg cycle, but there is considerable ambiguity. Using the epochs of violations of the Gnevyshev-Ohl rule (G-O rule) and the `tentative inverse G-O rule' of solar cycles during the period 1610 - 2015, and also using the epochs where the orbital angular momentum of the Sun is steeply decreased during the period 1600 - 2099, we infer that Solar Cycle 25 will be weaker than Cycle 24. Cycles 25 and 26 will have almost same strength, and their epochs are at the minimum between the current and upcoming Gleissberg cycles. In addition, Cycle 27 is expected to be stronger than Cycle 26 and weaker than Cycle 28, and Cycle 29 is expected to be stronger than both Cycles 28 and 30. The maximum of Cycle 29 is expected to represent the next Gleissberg maximum. Our analysis also suggests a much lower value (30 - 40) for the maximum amplitude of the upcoming Cycle 25.

SUV2, which encodes an ATR-related cell cycle checkpoint and putative plant ATRIP, is required for aluminium-dependent root growth inhibition in Arabidopsis.

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Sjogren, Caroline A; Larsen, Paul B

2017-09-01

A suppressor mutagenesis screen was conducted in order to identify second site mutations that could reverse the extreme hypersensitivity to aluminium (Al) seen for the Arabidopsis mutant, als3-1. From this screen, it was found that a loss-of-function mutation in the previously described SUV2 (SENSITIVE TO UV 2), which encodes a putative plant ATRIP homologue that is a component of the ATR-dependent cell checkpoint response, reversed the als3-1 phenotype. This included prevention of hallmarks associated with als3-1 including Al-dependent terminal differentiation of the root tip and transition to endoreduplication. From this analysis, SUV2 was determined to be required for halting cell cycle progression and triggering loss of the quiescent centre (QC) following exposure to Al. In conjunction with this, SUV2 was found to have a similar role as ATR, ALT2 and SOG1 in Al-dependent stoppage of root growth, all of which are required for promotion of expression of a suite of genes that likely are part of an Al-dependent DNA damage transcriptional response. This work argues that these Al response factors work together to detect Al-dependent damage and subsequently activate a DNA damage response pathway that halts the cell cycle and subsequently promotes QC differentiation and entrance into endocycling. © 2017 John Wiley & Sons Ltd.

Using optical tweezers to relate the chemical and mechanical cross-bridge cycles.

Science.gov (United States)

Steffen, Walter; Sleep, John

2004-12-29

In most current models of muscle contraction there are two translational steps, the working stroke, whereby an attached myosin cross-bridge moves relative to the actin filament, and the repriming step, in which the cross-bridge returns to its original orientation. The development of single molecule methods has allowed a more detailed investigation of the relationship of these mechanical steps to the underlying biochemistry. In the normal adenosine triphosphate cycle, myosin.adenosine diphosphate.phosphate (M.ADP.Pi) binds to actin and moves it by ca. 5 nm on average before the formation of the end product, the rigor actomyosin state. All the other product-like intermediate states tested were found to give no net movement indicating that M.ADP.Pi alone binds in a pre-force state. Myosin states with bound, unhydrolysed nucleoside triphosphates also give no net movement, indicating that these must also bind in a post-force conformation and that the repriming, post- to pre-transition during the forward cycle must take place while the myosin is dissociated from actin. These observations fit in well with the structural model in which the working stroke is aligned to the opening of the switch 2 element of the ATPase site.

Phase space representation of neutron monitor count rate and atmospheric electric field in relation to solar activity in cycles 21 and 22.

Science.gov (United States)

Silva, H G; Lopes, I

Heliospheric modulation of galactic cosmic rays links solar cycle activity with neutron monitor count rate on earth. A less direct relation holds between neutron monitor count rate and atmospheric electric field because different atmospheric processes, including fluctuations in the ionosphere, are involved. Although a full quantitative model is still lacking, this link is supported by solid statistical evidence. Thus, a connection between the solar cycle activity and atmospheric electric field is expected. To gain a deeper insight into these relations, sunspot area (NOAA, USA), neutron monitor count rate (Climax, Colorado, USA), and atmospheric electric field (Lisbon, Portugal) are presented here in a phase space representation. The period considered covers two solar cycles (21, 22) and extends from 1978 to 1990. Two solar maxima were observed in this dataset, one in 1979 and another in 1989, as well as one solar minimum in 1986. Two main observations of the present study were: (1) similar short-term topological features of the phase space representations of the three variables, (2) a long-term phase space radius synchronization between the solar cycle activity, neutron monitor count rate, and potential gradient (confirmed by absolute correlation values above ~0.8). Finally, the methodology proposed here can be used for obtaining the relations between other atmospheric parameters (e.g., solar radiation) and solar cycle activity.

Chemical networks with inflows and outflows: a positive linear differential inclusions approach.

Science.gov (United States)

Angeli, David; De Leenheer, Patrick; Sontag, Eduardo D

2009-01-01

Certain mass-action kinetics models of biochemical reaction networks, although described by nonlinear differential equations, may be partially viewed as state-dependent linear time-varying systems, which in turn may be modeled by convex compact valued positive linear differential inclusions. A result is provided on asymptotic stability of such inclusions, and applied to a ubiquitous biochemical reaction network with inflows and outflows, known as the futile cycle. We also provide a characterization of exponential stability of general homogeneous switched systems which is not only of interest in itself, but also plays a role in the analysis of the futile cycle. 2009 American Institute of Chemical Engineers

Generalization of Coffin-Manson relation in connection with the low-cycle fatigue in the temperature range 20-300 o C

International Nuclear Information System (INIS)

Radu, V.

1992-01-01

The low-cycle fatigue phenomenon in the framework of plastic deformation is studied considering the temperature parameter. The experimental results obtained for the plastic strain Δε p (1-7%), in the temperature range 20-300 o C are examined. The conclusion is that the lifetime, expressed by the number of stress cycles, N f , is given by the relation N f = C exp(-A/T)(Δε p ) β+αΔT , where T is the absolute temperature, Δε p is double of plastic deformation amplitude, and C, A, β, and α are material constants. This relation can be interpreted as being the generalization of a relation, known in literature as the 'Coffin-Manson relation', but which does not include the temperature parameter. The validation of this relation can be done either on the results presented in this paper or an those published in literature. (Author)

Cyclin D1 Expression and Its Correlation with Histopathological Differentiation in Oral Squamous Cell Carcinoma

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Swati Saawarn

2012-01-01

Full Text Available Background. Cyclin D1 regulates the G1 to S transition of cell cycle. Its deregulation or overexpression may lead to disturbance in the normal cell cycle control and tumour formation. Overexpression of cyclin D1 has been reported in various tumors of diverse histogenesis. This case control retrospective study was carried out to study the immunohistochemical reactivity and expression of cyclin D1 and its association with site, clinical staging, and histopathological differentiation of oral squamous cell carcinoma (OSCC. Methods. Forty formalin-fixed paraffin-embedded tissue blocks of biopsy specimens of oral squamous cell carcinoma were immunohistochemically evaluated for expression of cyclin D1. Results. Cyclin D1 expression was seen in 45% cases of OSCC. It did not correlate with site and clinical staging. Highest expression was seen in well-differentiated, followed by moderately differentiated, and poorly differentiated squamous cell carcinomas, with a statistically significant correlation. Conclusion. Cyclin D1 expression significantly increases with increase in differentiation.

Effect of low dose radiation on cell cycle and expression of its related proteins of HCT-8 cells

International Nuclear Information System (INIS)

Xu Ying; Ma Kewei; Li Wei; Wang Guanjun

2009-01-01

Objective: To study the effects of low dose radiation (LDR) on cell cycle and the expression of its related proteins of HCT-8 cells and provide theoretical basis for clinical application of LDR. Methods: Human colon carcinoma cells (HCT-8) cultivated in vitro were divided into seven groups: sham radiation group (0 mGy), LDR groups (25, 50, 75, 100 and 200 mGy) and high dose radiation group (1000 mGy). The proliferation rate was detected with the method of cell count and MTT, the ratios of G 0 /G 1 , S, G 2 /M in cell cycle were determined with flow cytometry after LDR, The cell cycle and expressions of related signal proteins were analyzed with protein assay system. Results: The results of cell count and MTT showed that there were no significant differences of proliferation rate of HCT-8 cells between 25, 50, 75, 100, 200 mGy LDR groups and sham radiation group (P>0.05); compared with high dose radiation group, there were significant differences (P 0 /G 1 phase of HCT-8 cells increased (P>0.05), the ratio of S phase decreased significantly (P 2 /M phase increased obviously (P 0 /G 1 , S, and G 2 /M phases of HCT-8 cells 48 h after radiation compared with sham radiation group (P>0.05). The protein assay result indicated that the expressions of AKt, PCNA, p27, CDK2, cyclin E, EGFR, ERK1/2, p-ERK, p-GSK-32/β in HCT-8 cells after LDR decreased compared with sham radiation group. Conclusion: LDR has no stimulating effect on HCT-8 cells. However, to some extent LDR suppress the expressions of some proteins related to proliferation and cell cycle. (authors)

A differential equation for the transition probability B(E2)↑ and the resulting recursion relations connecting even–even nuclei

Energy Technology Data Exchange (ETDEWEB)

Pattnaik, S. [Taratarini College, Purusottampur, Ganjam, Odisha (India); Nayak, R. C. [Department of Physics, Berhampur University, Brahmapur-760007 (India)

2014-04-15

We obtain here a new relation for the reduced electric quadrupole transition probability B(E2)↑ of a given nucleus in terms of its derivatives with respect to neutron and proton numbers based on a similar local energy relation in the Infinite Nuclear Matter (INM) model of atomic nuclei, which is essentially built on the foundation of the Hugenholtz–Van Hove (HVH) theorem of many-body theory. Obviously, such a relation in the form of a differential equation is expected to be more powerful than the usual algebraic difference equations. Although the relation for B(E2)↑ has been perceived simply on the basis of a corresponding differential equation for the local energy in the INM model, its theoretical foundation otherwise has been clearly demonstrated. We further exploit the differential equation in using the very definitions of the derivatives to obtain two different recursion relations for B(E2)↑, connecting in each case three neighboring even–even nuclei from lower to higher mass numbers and vice versa. We demonstrate their numerical validity using available data throughout the nuclear chart and also explore their possible utility in predicting B(E2)↑ values. (author)

A differential equation for the transition probability B(E2)↑ and the resulting recursion relations connecting even–even nuclei

International Nuclear Information System (INIS)

Pattnaik, S.; Nayak, R.C.

2014-01-01

We obtain here a new relation for the reduced electric quadrupole transition probability B(E2)↑ of a given nucleus in terms of its derivatives with respect to neutron and proton numbers based on a similar local energy relation in the Infinite Nuclear Matter (INM) model of atomic nuclei, which is essentially built on the foundation of the Hugenholtz–Van Hove (HVH) theorem of many-body theory. Obviously, such a relation in the form of a differential equation is expected to be more powerful than the usual algebraic difference equations. Although the relation for B(E2)↑ has been perceived simply on the basis of a corresponding differential equation for the local energy in the INM model, its theoretical foundation otherwise has been clearly demonstrated. We further exploit the differential equation in using the very definitions of the derivatives to obtain two different recursion relations for B(E2)↑, connecting in each case three neighboring even–even nuclei from lower to higher mass numbers and vice versa. We demonstrate their numerical validity using available data throughout the nuclear chart and also explore their possible utility in predicting B(E2)↑ values. (author)

The Current Account and the Interest Differential in Canada

OpenAIRE

Martin Boileau; Michel Normandin

2004-01-01

For post-1975 Canadian data, we document the joint behavior of output, the current account, and the interest differential at the business cycle frequency. We also interpret the joint behavior using a simple small open economy model. Our simple model assumes that agents have access to world international financial markets, but face country-specific interest rate on their holdings of world assets. The interest differential depends negatively on the country’s net foreign asset position. We find ...

Cdk phosphorylation of the Ste11 transcription factor constrains differentiation-specific transcription to G1

DEFF Research Database (Denmark)

Kjaerulff, Søren; Andersen, Nicoline Resen; Borup, Mia Trolle

2007-01-01

Eukaryotic cells normally differentiate from G(1); here we investigate the mechanism preventing expression of differentiation-specific genes outside G(1). In fission yeast, induction of the transcription factor Ste11 triggers sexual differentiation. We find that Ste11 is only active in G(1) when...... Cdk activity is low. In the remaining part of the cell cycle, Ste11 becomes Cdk-phosphorylated at Thr 82 (T82), which inhibits its DNA-binding activity. Since the ste11 gene is autoregulated and the Ste11 protein is highly unstable, this Cdk switch rapidly extinguishes Ste11 activity when cells enter...... S phase. When we mutated T82 to aspartic acid, mimicking constant phosphorylation, cells no longer underwent differentiation. Conversely, changing T82 to alanine rendered Ste11-controlled transcription constitutive through the cell cycle, and allowed mating from S phase with increased frequency...

Consistent Differential Expression Pattern (CDEP) on microarray to identify genes related to metastatic behavior.

Science.gov (United States)

Tsoi, Lam C; Qin, Tingting; Slate, Elizabeth H; Zheng, W Jim

2011-11-11

To utilize the large volume of gene expression information generated from different microarray experiments, several meta-analysis techniques have been developed. Despite these efforts, there remain significant challenges to effectively increasing the statistical power and decreasing the Type I error rate while pooling the heterogeneous datasets from public resources. The objective of this study is to develop a novel meta-analysis approach, Consistent Differential Expression Pattern (CDEP), to identify genes with common differential expression patterns across different datasets. We combined False Discovery Rate (FDR) estimation and the non-parametric RankProd approach to estimate the Type I error rate in each microarray dataset of the meta-analysis. These Type I error rates from all datasets were then used to identify genes with common differential expression patterns. Our simulation study showed that CDEP achieved higher statistical power and maintained low Type I error rate when compared with two recently proposed meta-analysis approaches. We applied CDEP to analyze microarray data from different laboratories that compared transcription profiles between metastatic and primary cancer of different types. Many genes identified as differentially expressed consistently across different cancer types are in pathways related to metastatic behavior, such as ECM-receptor interaction, focal adhesion, and blood vessel development. We also identified novel genes such as AMIGO2, Gem, and CXCL11 that have not been shown to associate with, but may play roles in, metastasis. CDEP is a flexible approach that borrows information from each dataset in a meta-analysis in order to identify genes being differentially expressed consistently. We have shown that CDEP can gain higher statistical power than other existing approaches under a variety of settings considered in the simulation study, suggesting its robustness and insensitivity to data variation commonly associated with microarray

Third-order differential ladder operators and supersymmetric quantum mechanics

International Nuclear Information System (INIS)

Mateo, J; Negro, J

2008-01-01

Hierarchies of one-dimensional Hamiltonians in quantum mechanics admitting third-order differential ladder operators are studied. Each Hamiltonian has associated three-step Darboux (pseudo)-cycles and Painleve IV equations as a closure condition. The whole hierarchy is generated applying some operations on the cycles. These operations are investigated in the frame of supersymmetric quantum mechanics and mainly involve algebraic manipulations. A consistent geometric representation for the hierarchy and cycles is built that also helps in understanding the operations. Three kinds of hierarchies are distinguished and a realization based on the harmonic oscillator Hamiltonian is supplied, giving an interpretation for the spectral properties of the Hamiltonians of each hierarchy

Presenteeism and absenteeism: differentiated understanding of related phenomena.

Science.gov (United States)

Gosselin, Eric; Lemyre, Louise; Corneil, Wayne

2013-01-01

In the past it was assumed that work attendance equated to performance. It now appears that health-related loss of productivity can be traced equally to workers showing up at work as well as to workers choosing not to. Presenteeism in the workplace, showing up for work while sick, seems now more prevalent than absenteeism. These findings are forcing organizations to reconsider their approaches regarding regular work attendance. Given this, and echoing recommendations in the literature, this study seeks to identify the main behavioral correlates of presenteeism and absenteeism in the workplace. Comparative analysis of the data from a representative sample of executives from the Public Service of Canada enables us to draw a unique picture of presenteeism and absenteeism with regards not only to the impacts of health disorders but also to the demographic, organizational, and individual factors involved. Results provide a better understanding of the similarities and differences between these phenomena, and more specifically, of the differentiated influence of certain variables. These findings provide food for thought and may pave the way to the development of new organizational measures designed to manage absenteeism without creating presenteeism.

Rho GTPases in ameloblast differentiation

Directory of Open Access Journals (Sweden)

Keishi Otsu

2016-05-01

Full Text Available During tooth development, ameloblasts differentiate from inner enamel epithelial cells to enamel-forming cells by modulating the signal pathways mediating epithelial–mesenchymal interaction and a cell-autonomous gene network. The differentiation process of epithelial cells is characterized by marked changes in their morphology and polarity, accompanied by dynamic cytoskeletal reorganization and changes in cell–cell and cell–matrix adhesion over time. Functional ameloblasts are tall, columnar, polarized cells that synthesize and secrete enamel-specific proteins. After deposition of the full thickness of enamel matrix, ameloblasts become smaller and regulate enamel maturation. Recent significant advances in the fields of molecular biology and genetics have improved our understanding of the regulatory mechanism of the ameloblast cell life cycle, mediated by the Rho family of small GTPases. They act as intracellular molecular switch that transduce signals from extracellular stimuli to the actin cytoskeleton and the nucleus. In our review, we summarize studies that provide current evidence for Rho GTPases and their involvement in ameloblast differentiation. In addition to the Rho GTPases themselves, their downstream effectors and upstream regulators have also been implicated in ameloblast differentiation.

Growth inhibitory effect of 4-phenyl butyric acid on human gastric cancer cells is associated with cell cycle arrest.

Science.gov (United States)

Li, Long-Zhu; Deng, Hong-Xia; Lou, Wen-Zhu; Sun, Xue-Yan; Song, Meng-Wan; Tao, Jing; Xiao, Bing-Xiu; Guo, Jun-Ming

2012-01-07

To investigate the growth effects of 4-phenyl butyric acid (PBA) on human gastric carcinoma cells and their mechanisms. Moderately-differentiated human gastric carcinoma SGC-7901 and lowly-differentiated MGC-803 cells were treated with 5, 10, 20, 40, and 60 μmol/L PBA for 1-4 d. Cell proliferation was detected using the MTT colorimetric assay. Cell cycle distributions were examined using flow cytometry. The proliferation of gastric carcinoma cells was inhibited by PBA in a dose- and time-dependent fashion. Flow cytometry showed that SGC-7901 cells treated with low concentrations of PBA were arrested at the G₀/G₁ phase, whereas cells treated with high concentrations of PBA were arrested at the G₂/M phase. Although MGC-803 cells treated with low concentrations of PBA were also arrested at the G₀/ G₁ phase, cells treated with high concentrations of PBA were arrested at the S phase. The growth inhibitory effect of PBA on gastric cancer cells is associated with alteration of the cell cycle. For moderately-differentiated gastric cancer cells, the cell cycle was arrested at the G₀ /G₁ and G₂/M phases. For lowly-differentiated gastric cancer cells, the cell cycle was arrested at the G₀/G₁ and S phases.

Hopf bifurcation formula for first order differential-delay equations

Science.gov (United States)

Rand, Richard; Verdugo, Anael

2007-09-01

This work presents an explicit formula for determining the radius of a limit cycle which is born in a Hopf bifurcation in a class of first order constant coefficient differential-delay equations. The derivation is accomplished using Lindstedt's perturbation method.

Role of microphthalmia transcription factor (Mitf) in melanoma differentiation

International Nuclear Information System (INIS)

Lekmine, Fatima; Chang, C.K.; Sethakorn, Nan; Das Gupta, Tapas K.; Salti, George I.

2007-01-01

We transfected the melanocyte-specific Mitf-M isoform into the aggressive melanoma UISO-Mel-6 cell lines. Our data show that Mitf decreases cell proliferation and results in cells which grow in clusters. By analyzing the expression of the markers of differentiation, we demonstrate that Mitf favored increased expression of tyrosinase and tyrosinase-related protein-1. In addition, Mitf induces Bcl-2 expression following transfection of UISO-Mel-6 cells. We also showed that Mitf gene affects cell-cycle distribution by resting cells preferentially in G2/G1 phase, and inducing the expression of p21 and p27. Moreover, we performed in vivo studies using subcutaneous injection of UISO-Mel-6 and UISO-Mel-6-Mitf in Balb/c nude mice. Our data show that Mitf inhibits tumor growth and decreases Ki67 expression. Tumors induced by UISO-Mel-6 cells were ulcerated and resulted in metastases to liver. None of the mice injected with UISO-Mel-6 Mitf+ cells harbored liver metastases. Our results suggest that Mitf is involved in melanoma differentiation and leads to a less aggressive phenotype

The molecular chaperone Hsp90 is required for cell cycle exit in Drosophila melanogaster.

Directory of Open Access Journals (Sweden)

Jennifer L Bandura

Full Text Available The coordination of cell proliferation and differentiation is crucial for proper development. In particular, robust mechanisms exist to ensure that cells permanently exit the cell cycle upon terminal differentiation, and these include restraining the activities of both the E2F/DP transcription factor and Cyclin/Cdk kinases. However, the full complement of mechanisms necessary to restrain E2F/DP and Cyclin/Cdk activities in differentiating cells are not known. Here, we have performed a genetic screen in Drosophila melanogaster, designed to identify genes required for cell cycle exit. This screen utilized a PCNA-miniwhite(+ reporter that is highly E2F-responsive and results in a darker red eye color when crossed into genetic backgrounds that delay cell cycle exit. Mutation of Hsp83, the Drosophila homolog of mammalian Hsp90, results in increased E2F-dependent transcription and ectopic cell proliferation in pupal tissues at a time when neighboring wild-type cells are postmitotic. Further, these Hsp83 mutant cells have increased Cyclin/Cdk activity and accumulate proteins normally targeted for proteolysis by the anaphase-promoting complex/cyclosome (APC/C, suggesting that APC/C function is inhibited. Indeed, reducing the gene dosage of an inhibitor of Cdh1/Fzr, an activating subunit of the APC/C that is required for timely cell cycle exit, can genetically suppress the Hsp83 cell cycle exit phenotype. Based on these data, we propose that Cdh1/Fzr is a client protein of Hsp83. Our results reveal that Hsp83 plays a heretofore unappreciated role in promoting APC/C function during cell cycle exit and suggest a mechanism by which Hsp90 inhibition could promote genomic instability and carcinogenesis.

The molecular chaperone Hsp90 is required for cell cycle exit in Drosophila melanogaster.

Science.gov (United States)

Bandura, Jennifer L; Jiang, Huaqi; Nickerson, Derek W; Edgar, Bruce A

2013-01-01

The coordination of cell proliferation and differentiation is crucial for proper development. In particular, robust mechanisms exist to ensure that cells permanently exit the cell cycle upon terminal differentiation, and these include restraining the activities of both the E2F/DP transcription factor and Cyclin/Cdk kinases. However, the full complement of mechanisms necessary to restrain E2F/DP and Cyclin/Cdk activities in differentiating cells are not known. Here, we have performed a genetic screen in Drosophila melanogaster, designed to identify genes required for cell cycle exit. This screen utilized a PCNA-miniwhite(+) reporter that is highly E2F-responsive and results in a darker red eye color when crossed into genetic backgrounds that delay cell cycle exit. Mutation of Hsp83, the Drosophila homolog of mammalian Hsp90, results in increased E2F-dependent transcription and ectopic cell proliferation in pupal tissues at a time when neighboring wild-type cells are postmitotic. Further, these Hsp83 mutant cells have increased Cyclin/Cdk activity and accumulate proteins normally targeted for proteolysis by the anaphase-promoting complex/cyclosome (APC/C), suggesting that APC/C function is inhibited. Indeed, reducing the gene dosage of an inhibitor of Cdh1/Fzr, an activating subunit of the APC/C that is required for timely cell cycle exit, can genetically suppress the Hsp83 cell cycle exit phenotype. Based on these data, we propose that Cdh1/Fzr is a client protein of Hsp83. Our results reveal that Hsp83 plays a heretofore unappreciated role in promoting APC/C function during cell cycle exit and suggest a mechanism by which Hsp90 inhibition could promote genomic instability and carcinogenesis.

Chaotic Behavior of a Generalized Sprott E Differential System

Science.gov (United States)

Oliveira, Regilene; Valls, Claudia

A chaotic system with only one equilibrium, a stable node-focus, was introduced by Wang and Chen [2012]. This system was found by adding a nonzero constant b to the Sprott E system [Sprott, 1994]. The coexistence of three types of attractors in this autonomous system was also considered by Braga and Mello [2013]. Adding a second parameter to the Sprott E differential system, we get the autonomous system ẋ = ayz + b,ẏ = x2 - y,ż = 1 - 4x, where a,b ∈ ℝ are parameters and a≠0. In this paper, we consider theoretically some global dynamical aspects of this system called here the generalized Sprott E differential system. This polynomial differential system is relevant because it is the first polynomial differential system in ℝ3 with two parameters exhibiting, besides the point attractor and chaotic attractor, coexisting stable limit cycles, demonstrating that this system is truly complicated and interesting. More precisely, we show that for b sufficiently small this system can exhibit two limit cycles emerging from the classical Hopf bifurcation at the equilibrium point p = (1/4, 1/16, 0). We also give a complete description of its dynamics on the Poincaré sphere at infinity by using the Poincaré compactification of a polynomial vector field in ℝ3, and we show that it has no first integrals in the class of Darboux functions.

Remote sensing of wetland parameters related to carbon cycling

Science.gov (United States)

Bartlett, David S.; Johnson, Robert W.

1985-01-01

Measurement of the rates of important biogeochemical fluxes on regional or global scales is vital to understanding the geochemical and climatic consequences of natural biospheric processes and of human intervention in those processes. Remote data gathering and interpretation techniques were used to examine important cycling processes taking place in wetlands over large geographic expanses. Large area estimation of vegetative biomass and productivity depends upon accurate, consistent measurements of canopy spectral reflectance and upon wide applicability of algorithms relating reflectance to biometric parameters. Results of the use of airborne multispectral scanner data to map above-ground biomass in a Delaware salt marsh are shown. The mapping uses an effective algorithm linking biomass to measured spectral reflectance and a means to correct the scanner data for large variations in the angle of observation of the canopy. The consistency of radiometric biomass algorithms for marsh grass when they are applied over large latitudinal and tidal range gradients were also examined. Results of a 1 year study of methane emissions from tidal wetlands along a salinity gradient show marked effects of temperature, season, and pore-water chemistry in mediating flux to the atmosphere.

Some operational tools for solving fractional and higher integer order differential equations: A survey on their mutual relations

Science.gov (United States)

Kiryakova, Virginia S.

2012-11-01

The Laplace Transform (LT) serves as a basis of the Operational Calculus (OC), widely explored by engineers and applied scientists in solving mathematical models for their practical needs. This transform is closely related to the exponential and trigonometric functions (exp, cos, sin) and to the classical differentiation and integration operators, reducing them to simple algebraic operations. Thus, the classical LT and the OC give useful tool to handle differential equations and systems with constant coefficients. Several generalizations of the LT have been introduced to allow solving, in a similar way, of differential equations with variable coefficients and of higher integer orders, as well as of fractional (arbitrary non-integer) orders. Note that fractional order mathematical models are recently widely used to describe better various systems and phenomena of the real world. This paper surveys briefly some of our results on classes of such integral transforms, that can be obtained from the LT by means of "transmutations" which are operators of the generalized fractional calculus (GFC). On the list of these Laplace-type integral transforms, we consider the Borel-Dzrbashjan, Meijer, Krätzel, Obrechkoff, generalized Obrechkoff (multi-index Borel-Dzrbashjan) transforms, etc. All of them are G- and H-integral transforms of convolutional type, having as kernels Meijer's G- or Fox's H-functions. Besides, some special functions (also being G- and H-functions), among them - the generalized Bessel-type and Mittag-Leffler (M-L) type functions, are generating Gel'fond-Leontiev (G-L) operators of generalized differentiation and integration, which happen to be also operators of GFC. Our integral transforms have operational properties analogous to those of the LT - they do algebrize the G-L generalized integrations and differentiations, and thus can serve for solving wide classes of differential equations with variable coefficients of arbitrary, including non-integer order

On the possible relations between solar activities and global seismicity in the solar cycle 20 to 23

Energy Technology Data Exchange (ETDEWEB)

Herdiwijaya, Dhani, E-mail: dhani@as.itb.ac.id [Astronomy Research Division and Bosscha Observatory, Faculty of Mathematics and Natural Sciences, Bandung Institute of Technology, Ganesha 10, Bandung, Indonesia 40132 (Indonesia); Arif, Johan [Geology Research Division, Faculty of Earth Sciences and Technology, Bandung Institute of Technology, Ganesha 10, Bandung, Indonesia 40132 (Indonesia); Nurzaman, Muhamad Zamzam; Astuti, Isna Kusuma Dewi [Astronomy Study Program, Faculty of Mathematics and Natural Sciences, Bandung Institute of Technology, Ganesha 10, Bandung, Indonesia 40132 (Indonesia)

2015-09-30

Solar activities consist of high energetic particle streams, electromagnetic radiation, magnetic and orbital gravitational forces. The well-know solar activity main indicator is the existence of sunspot which has mean variation in 11 years, named by solar cycle, allow for the above fluctuations. Solar activities are also related to the space weather affecting all planetary atmospheric variability, moreover to the Earth’s climate variability. Large extreme space and geophysical events (high magnitude earthquakes, explosive volcanic eruptions, magnetic storms, etc.) are hazards for humankind, infrastructure, economies, technology and the activities of civilization. With a growing world population, and with modern reliance on delicate technological systems, human society is becoming increasingly vulnerable to natural hazardous events. The big question arises to the relation between solar forcing energy to the Earth’s global seismic activities. Estimates are needed for the long term occurrence-rate probabilities of these extreme natural hazardous events. We studied connectivity from yearly seismic activities that refer to and sunspot number within the solar cycle 20 to 23 of year 1960 to 2013 (53 years). We found clear evidences that in general high magnitude earthquake events and their depth were related to the low solar activity.

On the possible relations between solar activities and global seismicity in the solar cycle 20 to 23

Science.gov (United States)

Herdiwijaya, Dhani; Arif, Johan; Nurzaman, Muhamad Zamzam; Astuti, Isna Kusuma Dewi

2015-09-01

Solar activities consist of high energetic particle streams, electromagnetic radiation, magnetic and orbital gravitational forces. The well-know solar activity main indicator is the existence of sunspot which has mean variation in 11 years, named by solar cycle, allow for the above fluctuations. Solar activities are also related to the space weather affecting all planetary atmospheric variability, moreover to the Earth's climate variability. Large extreme space and geophysical events (high magnitude earthquakes, explosive volcanic eruptions, magnetic storms, etc.) are hazards for humankind, infrastructure, economies, technology and the activities of civilization. With a growing world population, and with modern reliance on delicate technological systems, human society is becoming increasingly vulnerable to natural hazardous events. The big question arises to the relation between solar forcing energy to the Earth's global seismic activities. Estimates are needed for the long term occurrence-rate probabilities of these extreme natural hazardous events. We studied connectivity from yearly seismic activities that refer to and sunspot number within the solar cycle 20 to 23 of year 1960 to 2013 (53 years). We found clear evidences that in general high magnitude earthquake events and their depth were related to the low solar activity.

International comparisons of the associations between objective measures of the built environment and transport-related walking and cycling

DEFF Research Database (Denmark)

Christiansen, Lars B; Cerin, Ester; Badland, Hannah

2016-01-01

with transport-related walking and cycling. METHODS: This cross-sectional study maximized variation of environments and demographics by including multiple countries and by selecting adult participants living in neighborhoods based on higher and lower classifications of objectively measured walkability...

The levels of adipokines in relation to hormonal changes during the menstrual cycle in young, normal-weight women

Directory of Open Access Journals (Sweden)

Katarzyna Wyskida

2017-11-01

Full Text Available Context: The aim of this study was to assess the plasma leptin, adiponectin, resistin, visfatin/NAMPT, omentin-1, vaspin, apelin, TNF-α, IL-6 and RBP4 levels in relation to hormonal changes during the menstrual cycle in young, healthy, normal-weight women. Methods: The study involved 52 young, healthy, normal-weight women. Anthropometric parameters, body composition and levels of plasma leptin, adiponectin, resistin, visfatin/NAMPT, omentin-1, vaspin, apelin, TNF-α, IL-6 and RBP4 in addition to serum FSH, LH, estradiol, progesterone, 17-OH progesterone, androgens, SHBG and insulin concentrations were measured during a morning in fasting state three times: between days 2–4, days 12–14 and days 24–26 of the menstrual cycle. Results: Plasma adiponectin, omentin-1, resistin and visfatin/NAMPT, apelin, TNF-α, IL-6 and RBP4 concentrations were stable during the menstrual cycle, while leptin and vaspin levels were significantly higher in both the midcycle and the luteal phases than those in the follicular phase. Multivariate regression analyses revealed that changes in leptin and vaspin levels between the follicular and the luteal phase are strongly related to changes in total testosterone levels. Conclusions: Our results revealed stable levels of adipokines during the phases of the physiological menstrual cycle, except for leptin and vaspin, which showed increased levels in both the midcycle and the luteal phases. This effect was significantly associated with changes in the secretion of testosterone, 17-OH progesterone and insulin in the luteal phase.

Differentiation of endosperm transfer cells of barley: a comprehensive analysis at the micro-scale.

Science.gov (United States)

Thiel, Johannes; Riewe, David; Rutten, Twan; Melzer, Michael; Friedel, Swetlana; Bollenbeck, Felix; Weschke, Winfriede; Weber, Hans

2012-08-01

Barley endosperm cells differentiate into transfer cells (ETCs) opposite the nucellar projection. To comprehensively analyse ETC differentiation, laser microdissection-based transcript and metabolite profiles were obtained from laser microdissected tissues and cell morphology was analysed. Flange-like secondary-wall ingrowths appeared between 5 and 7 days after pollination within the three outermost cell layers. Gene expression analysis indicated that ethylene-signalling pathways initiate ETC morphology. This is accompanied by gene activity related to cell shape control and vesicle transport, with abundant mitochondria and endomembrane structures. Gene expression analyses indicate predominant formation of hemicelluloses, glucuronoxylans and arabinoxylans, and transient formation of callose, together with proline and 4-hydroxyproline biosynthesis. Activation of the methylation cycle is probably required for biosynthesis of phospholipids, pectins and ethylene. Membrane microdomains involving sterols/sphingolipids and remorins are potentially involved in ETC development. The transcriptional activity of assimilate and micronutrient transporters suggests ETCs as the main uptake organs of solutes into the endosperm. Accordingly, the endosperm grows maximally after ETCs are fully developed. Up-regulated gene expression related to amino acid catabolism, C:N balances, carbohydrate oxidation, mitochondrial activity and starch degradation meets high demands for respiratory energy and carbohydrates, required for cell proliferation and wall synthesis. At 10 days after pollination, ETCs undergo further differentiation, potentially initiated by abscisic acid, and metabolism is reprogrammed as shown by activated storage and stress-related processes. Overall, the data provide a comprehensive view of barley ETC differentiation and development, and identify candidate genes and associated pathways. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

Differentiating intolerance of uncertainty from three related but distinct constructs.

Science.gov (United States)

Rosen, Natalie O; Ivanova, Elena; Knäuper, Bärbel

2014-01-01

Individual differences in uncertainty have been associated with heightened anxiety, stress and approach-oriented coping. Intolerance of uncertainty (IU) is a trait characteristic that arises from negative beliefs about uncertainty and its consequences. Researchers have established the central role of IU in the development of problematic worry and maladaptive coping, highlighting the importance of this construct to anxiety disorders. However, there is a need to improve our understanding of the phenomenology of IU. The goal of this paper was to present hypotheses regarding the similarities and differences between IU and three related constructs--intolerance of ambiguity, uncertainty orientation, and need for cognitive closure--and to call for future empirical studies to substantiate these hypotheses. To assist with achieving this goal, we conducted a systematic review of the literature, which also served to identify current gaps in knowledge. This paper differentiates these constructs by outlining each definition and general approaches to assessment, reviewing the existing empirical relations, and proposing theoretical similarities and distinctions. Findings may assist researchers in selecting the appropriate construct to address their research questions. Future research directions for the application of these constructs, particularly within the field of clinical and health psychology, are discussed.

A fourth order spline collocation approach for a business cycle model

Science.gov (United States)

Sayfy, A.; Khoury, S.; Ibdah, H.

2013-10-01

A collocation approach, based on a fourth order cubic B-splines is presented for the numerical solution of a Kaleckian business cycle model formulated by a nonlinear delay differential equation. The equation is approximated and the nonlinearity is handled by employing an iterative scheme arising from Newton's method. It is shown that the model exhibits a conditionally dynamical stable cycle. The fourth-order rate of convergence of the scheme is verified numerically for different special cases.

Measuring Business Cycle Time.

OpenAIRE

Stock, James H

1987-01-01

The business cycle analysis of Arthur F. Burns and Wesley C. Mitchell and the National Bureau of Economic Research presumed that aggregate economic variables evolve on a time scale defined by business cycle turning points rather than by months or quarters. Do macroeconomic variables appear to evolve on an economic rather than a calendar time scale? Evidence presented here suggests that they do. However, the estimated economic time scales are only weakly related to business cycle time scales, ...

Progesterone modulation of alpha5 nAChR subunits influences anxiety-related behavior during estrus cycle.

Science.gov (United States)

Gangitano, D; Salas, R; Teng, Y; Perez, E; De Biasi, M

2009-06-01

Smokers often report an anxiolytic effect of cigarettes. In addition, stress-related disorders such as anxiety, post-traumatic stress syndrome and depression are often associated with chronic nicotine use. To study the role of the alpha5 nicotinic acetylcholine receptor subunit in anxiety-related responses, control and alpha5 subunit null mice (alpha5(-/-)) were subjected to the open field activity (OFA), light-dark box (LDB) and elevated plus maze (EPM) tests. In the OFA and LDB, alpha5(-/-) behaved like wild-type controls. In the EPM, female alpha5(-/-) mice displayed an anxiolytic-like phenotype, while male alpha5(-/-) mice were undistinguishable from littermate controls. We studied the hypothalamus-pituitary-adrenal axis by measuring plasma corticosterone and hypothalamic corticotropin-releasing factor. Consistent with an anxiolytic-like phenotype, female alpha5(-/-) mice displayed lower basal corticosterone levels. To test whether gonadal steroids regulate the expression of alpha5, we treated cultured NTera 2 cells with progesterone and found that alpha5 protein levels were upregulated. In addition, brain levels of alpha5 mRNA increased upon progesterone injection into ovariectomized wild-type females. Finally, we tested anxiety levels in the EPM during the estrous cycle. The estrus phase (when progesterone levels are low) is anxiolytic-like in wild-type mice, but no cycle-dependent fluctuations in anxiety levels were found in alpha5(-/-) females. Thus, alpha5-containing neuronal nicotinic acetylcholine receptors may be mediators of anxiogenic responses, and progesterone-dependent modulation of alpha5 expression may contribute to fluctuations in anxiety levels during the ovarian cycle.

DYNAMIC BEHAVIOR OF A DELAY-DIFFERENTIAL EQUATION MODEL FOR THE HORMONAL REGULATION OF THE MENSTRUAL CYCLE

Science.gov (United States)

During the menstrual cycle, pituitary hormones stimulate the growth and development of ovarian follicles and the release of an ovum to be fertilized. The ovarian follicles secrete hormones during the cycle that regulate the production of the pituitary hormones creating positi...

Triton-3He relative and differential flows and the high density behavior of nuclear symmetry

International Nuclear Information System (INIS)

Yong, Gaochan; Li, Baoan; Chen, Liewen

2010-01-01

Using a transport model coupled with a phase-space coalescence after-burner we study the triton- 3 He relative and differential transverse flows in semi-central 132 Sn + 124 Sn reactions at a beam energy of 400 MeV/nucleon. We find that the triton- 3 He pairs carry interesting information about the density dependence of the nuclear symmetry energy. The t- 3 He relative flow can be used as a particularly powerful probe of the high-density behavior of the nuclear symmetry energy. (author)

Akt1 intramitochondrial cycling is a crucial step in the redox modulation of cell cycle progression.

Directory of Open Access Journals (Sweden)

Valeria Gabriela Antico Arciuch

2009-10-01

Full Text Available Akt is a serine/threonine kinase involved in cell proliferation, apoptosis, and glucose metabolism. Akt is differentially activated by growth factors and oxidative stress by sequential phosphorylation of Ser(473 by mTORC2 and Thr(308 by PDK1. On these bases, we investigated the mechanistic connection of H(2O(2 yield, mitochondrial activation of Akt1 and cell cycle progression in NIH/3T3 cell line with confocal microscopy, in vivo imaging, and directed mutagenesis. We demonstrate that modulation by H(2O(2 entails the entrance of cytosolic P-Akt1 Ser(473 to mitochondria, where it is further phosphorylated at Thr(308 by constitutive PDK1. Phosphorylation of Thr(308 in mitochondria determines Akt1 passage to nuclei and triggers genomic post-translational mechanisms for cell proliferation. At high H(2O(2, Akt1-PDK1 association is disrupted and P-Akt1 Ser(473 accumulates in mitochondria in detriment to nuclear translocation; accordingly, Akt1 T308A is retained in mitochondria. Low Akt1 activity increases cytochrome c release to cytosol leading to apoptosis. As assessed by mass spectra, differential H(2O(2 effects on Akt1-PDK interaction depend on the selective oxidation of Cys(310 to sulfenic or cysteic acids. These results indicate that Akt1 intramitochondrial-cycling is central for redox modulation of cell fate.

Product-related research: how research can contribute to successful life-cycle management.

Science.gov (United States)

Sandner, Peter; Ziegelbauer, Karl

2008-05-01

Declining productivity with decreasing new molecular entity output combined with increased R&D spending is one of the key challenges for the entire pharmaceutical industry. In order to offset decreasing new molecular entity output, life-cycle management activities for established drugs become more and more important to maintain or even expand clinical indication and market opportunities. Life-cycle management covers a whole range of activities from strategic pricing to a next generation product launch. In this communication, we review how research organizations can contribute to successful life-cycle management strategies using phosphodiesterase 5 inhibitors as an example.

Comparative Transcriptome Analysis Identifies Candidate Genes Related to Skin Color Differentiation in Red Tilapia.

Science.gov (United States)

Zhu, Wenbin; Wang, Lanmei; Dong, Zaijie; Chen, Xingting; Song, Feibiao; Liu, Nian; Yang, Hui; Fu, Jianjun

2016-08-11

Red tilapia is becoming more popular for aquaculture production in China in recent years. However, the pigmentation differentiation in genetic breeding is the main problem limiting its development of commercial red tilapia culture and the genetic basis of skin color variation is still unknown. In this study, we conducted Illumina sequencing of transcriptome on three color variety red tilapia. A total of 224,895,758 reads were generated, resulting in 160,762 assembled contigs that were used as reference contigs. The contigs of red tilapia transcriptome had hits in the range of 53.4% to 86.7% of the unique proteins of zebrafish, fugu, medaka, three-spined stickleback and tilapia. And 44,723 contigs containing 77,423 simple sequence repeats (SSRs) were identified, with 16,646 contigs containing more than one SSR. Three skin transcriptomes were compared pairwise and the results revealed that there were 148 common significantly differentially expressed unigenes and several key genes related to pigment synthesis, i.e. tyr, tyrp1, silv, sox10, slc24a5, cbs and slc7a11, were included. The results will facilitate understanding the molecular mechanisms of skin pigmentation differentiation in red tilapia and accelerate the molecular selection of the specific strain with consistent skin colors.

Cell Cycle Regulation of Stem Cells by MicroRNAs.

Science.gov (United States)

Mens, Michelle M J; Ghanbari, Mohsen

2018-06-01

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

Cost of the external MTR-fuel cycle. (Uranium , reprocessing and related services)

International Nuclear Information System (INIS)

Mueller, H.; Gruber, G.

1991-01-01

This paper points out how the RERTR program has affected NUKEM's fuel supplies for MTRs and how the prices in the External MTR Fuel Cycle have developed during this period. In addition other potential fuel sources and services on the External MTR Fuel Cycle are given. (orig.)

Life cycle analysis of kidney gene expression in male F344 rats.

Directory of Open Access Journals (Sweden)

Joshua C Kwekel

Full Text Available Age is a predisposing condition for susceptibility to chronic kidney disease and progression as well as acute kidney injury that may arise due to the adverse effects of some drugs. Age-related differences in kidney biology, therefore, are a key concern in understanding drug safety and disease progression. We hypothesize that the underlying suite of genes expressed in the kidney at various life cycle stages will impact susceptibility to adverse drug reactions. Therefore, establishing changes in baseline expression data between these life stages is the first and necessary step in evaluating this hypothesis. Untreated male F344 rats were sacrificed at 2, 5, 6, 8, 15, 21, 78, and 104 weeks of age. Kidneys were collected for histology and gene expression analysis. Agilent whole-genome rat microarrays were used to query global expression profiles. An ANOVA (p1.5 in relative mRNA expression, was used to identify 3,724 unique differentially expressed genes (DEGs. Principal component analyses of these DEGs revealed three major divisions in life-cycle renal gene expression. K-means cluster analysis identified several groups of genes that shared age-specific patterns of expression. Pathway analysis of these gene groups revealed age-specific gene networks and functions related to renal function and aging, including extracellular matrix turnover, immune cell response, and renal tubular injury. Large age-related changes in expression were also demonstrated for the genes that code for qualified renal injury biomarkers KIM-1, Clu, and Tff3. These results suggest specific groups of genes that may underlie age-specific susceptibilities to adverse drug reactions and disease. This analysis of the basal gene expression patterns of renal genes throughout the life cycle of the rat will improve the use of current and future renal biomarkers and inform our assessments of kidney injury and disease.

Measurements of top quark pair relative differential cross-sections with ATLAS in pp collisions at $\\sqrt{s}$ = 7 TeV

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Aad, Georges; Abbott, Brad; Abdallah, Jalal; Abdel Khalek, Samah; Abdelalim, Ahmed Ali; Abdinov, Ovsat; Aben, Rosemarie; Abi, Babak; Abolins, Maris; AbouZeid, Ossama; Abramowicz, Halina; Abreu, Henso; Acerbi, Emilio; Acharya, Bobby Samir; Adamczyk, Leszek; Adams, David; Addy, Tetteh; Adelman, Jahred; Adomeit, Stefanie; Adragna, Paolo; Adye, Tim; Aefsky, Scott; Aguilar-Saavedra, Juan Antonio; Agustoni, Marco; Aharrouche, Mohamed; Ahlen, Steven; Ahles, Florian; Ahmad, Ashfaq; Ahsan, Mahsana; Aielli, Giulio; Akdogan, Taylan; Åkesson, Torsten Paul Ake; Akimoto, Ginga; Akimov, Andrei; Alam, Mohammad; Alam, Muhammad Aftab; Albert, Justin; Albrand, Solveig; Aleksa, Martin; Aleksandrov, Igor; Alessandria, Franco; Alexa, Calin; Alexander, Gideon; Alexandre, Gauthier; Alexopoulos, Theodoros; Alhroob, Muhammad; Aliev, Malik; Alimonti, Gianluca; Alison, John; Allbrooke, Benedict; Allport, Phillip; Allwood-Spiers, Sarah; Almond, John; Aloisio, Alberto; Alon, Raz; Alonso, Alejandro; Alonso, Francisco; 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Henderson, Robert; Henke, Michael; Henrichs, Anna; Henriques Correia, Ana Maria; Henrot-Versille, Sophie; Hensel, Carsten; Henß, Tobias; Medina Hernandez, Carlos; Hernández Jiménez, Yesenia; Herrberg, Ruth; Herten, Gregor; Hertenberger, Ralf; Hervas, Luis; Hesketh, Gavin Grant; Hessey, Nigel; Higón-Rodriguez, Emilio; Hill, John; Hiller, Karl Heinz; Hillert, Sonja; Hillier, Stephen; Hinchliffe, Ian; Hines, Elizabeth; Hirose, Minoru; Hirsch, Florian; Hirschbuehl, Dominic; Hobbs, John; Hod, Noam; Hodgkinson, Mark; Hodgson, Paul; Hoecker, Andreas; Hoeferkamp, Martin; Hoffman, Julia; Hoffmann, Dirk; Hohlfeld, Marc; Holder, Martin; Holmgren, Sven-Olof; Holy, Tomas; Holzbauer, Jenny; Hong, Tae Min; Hooft van Huysduynen, Loek; Horn, Claus; Horner, Stephan; Hostachy, Jean-Yves; Hou, Suen; Hoummada, Abdeslam; Howard, Jacob; Howarth, James; Hristova, Ivana; Hrivnac, Julius; Hryn'ova, Tetiana; Hsu, Pai-hsien Jennifer; Hsu, Shih-Chieh; Hubacek, Zdenek; Hubaut, Fabrice; Huegging, Fabian; Huettmann, Antje; Huffman, Todd Brian; Hughes, Emlyn; Hughes, Gareth; Huhtinen, Mika; Hurwitz, Martina; Husemann, Ulrich; Huseynov, Nazim; Huston, Joey; Huth, John; Iacobucci, Giuseppe; Iakovidis, Georgios; Ibbotson, Michael; Ibragimov, Iskander; Iconomidou-Fayard, Lydia; Idarraga, John; Iengo, Paolo; Igonkina, Olga; Ikegami, Yoichi; Ikeno, Masahiro; Iliadis, Dimitrios; Ilic, Nikolina; Ince, Tayfun; Inigo-Golfin, Joaquin; Ioannou, Pavlos; Iodice, Mauro; Iordanidou, Kalliopi; Ippolito, Valerio; Irles Quiles, Adrian; Isaksson, Charlie; Ishino, Masaya; Ishitsuka, Masaki; Ishmukhametov, Renat; Issever, Cigdem; Istin, Serhat; Ivashin, Anton; Iwanski, Wieslaw; Iwasaki, Hiroyuki; Izen, Joseph; Izzo, Vincenzo; Jackson, Brett; Jackson, John; Jackson, Paul; Jaekel, Martin; Jain, Vivek; Jakobs, Karl; Jakobsen, Sune; Jakoubek, Tomas; Jakubek, Jan; Jana, Dilip; Jansen, Eric; Jansen, Hendrik; Jantsch, Andreas; Janus, Michel; Jarlskog, Göran; Jeanty, Laura; Jen-La Plante, Imai; Jennens, David; Jenni, Peter; Jež, Pavel; Jézéquel, Stéphane; Jha, Manoj Kumar; Ji, Haoshuang; Ji, Weina; Jia, Jiangyong; Jiang, Yi; Jimenez Belenguer, Marcos; Jin, Shan; Jinnouchi, Osamu; Joergensen, Morten Dam; Joffe, David; Johansen, Marianne; Johansson, Erik; Johansson, Per; Johnert, Sebastian; Johns, Kenneth; Jon-And, Kerstin; Jones, Graham; Jones, Roger; Jones, Tim; Joram, Christian; Jorge, Pedro; Joshi, Kiran Daniel; Jovicevic, Jelena; Jovin, Tatjana; Ju, Xiangyang; Jung, Christian; Jungst, Ralph Markus; Juranek, Vojtech; Jussel, Patrick; Juste Rozas, Aurelio; Kabana, Sonja; Kaci, Mohammed; Kaczmarska, Anna; Kadlecik, Peter; Kado, Marumi; Kagan, Harris; Kagan, Michael; Kajomovitz, Enrique; Kalinin, Sergey; Kalinovskaya, Lidia; Kama, Sami; Kanaya, Naoko; Kaneda, Michiru; Kaneti, Steven; Kanno, Takayuki; Kantserov, Vadim; Kanzaki, Junichi; Kaplan, Benjamin; Kapliy, Anton; Kaplon, Jan; Kar, Deepak; Karagounis, Michael; Karakostas, Konstantinos; Karnevskiy, Mikhail; Kartvelishvili, Vakhtang; Karyukhin, Andrey; Kashif, Lashkar; Kasieczka, Gregor; Kass, Richard; Kastanas, Alex; Kataoka, Mayuko; Kataoka, Yousuke; Katsoufis, Elias; Katzy, Judith; Kaushik, Venkatesh; Kawagoe, Kiyotomo; Kawamoto, Tatsuo; Kawamura, Gen; Kayl, Manuel; Kazanin, Vassili; Kazarinov, Makhail; Keeler, Richard; Kehoe, Robert; Keil, Markus; Kekelidze, George; Keller, John; Kenyon, Mike; Kepka, Oldrich; Kerschen, Nicolas; Kerševan, Borut Paul; Kersten, Susanne; Kessoku, Kohei; Keung, Justin; Khalil-zada, Farkhad; Khandanyan, Hovhannes; Khanov, Alexander; Kharchenko, Dmitri; Khodinov, Alexander; Khomich, Andrei; Khoo, Teng Jian; Khoriauli, Gia; Khoroshilov, Andrey; Khovanskiy, Valery; Khramov, Evgeniy; Khubua, Jemal; Kim, Hyeon Jin; Kim, Shinhong; Kimura, Naoki; Kind, Oliver; King, Barry; King, Matthew; King, Robert Steven Beaufoy; Kirk, Julie; Kiryunin, Andrey; Kishimoto, Tomoe; Kisielewska, Danuta; Kitamura, Takumi; Kittelmann, Thomas; Kladiva, Eduard; Klein, Max; Klein, Uta; Kleinknecht, Konrad; Klemetti, Miika; Klier, Amit; Klimek, Pawel; Klimentov, Alexei; Klingenberg, Reiner; Klinger, Joel Alexander; Klinkby, Esben; Klioutchnikova, Tatiana; Klok, Peter; Klous, Sander; Kluge, Eike-Erik; Kluge, Thomas; Kluit, Peter; Kluth, Stefan; Knecht, Neil; Kneringer, Emmerich; Knoops, Edith; Knue, Andrea; Ko, Byeong Rok; Kobayashi, Tomio; Kobel, Michael; Kocian, Martin; Kodys, Peter; Köneke, Karsten; König, Adriaan; Koenig, Sebastian; Köpke, Lutz; Koetsveld, Folkert; Koevesarki, Peter; Koffas, Thomas; Koffeman, Els; Kogan, Lucy Anne; Kohlmann, Simon; Kohn, Fabian; Kohout, Zdenek; Kohriki, Takashi; Koi, Tatsumi; Kolachev, Guennady; Kolanoski, Hermann; Kolesnikov, Vladimir; Koletsou, Iro; Koll, James; Kollefrath, Michael; Komar, Aston; Komori, Yuto; Kondo, Takahiko; Kono, Takanori; Kononov, Anatoly; Konoplich, Rostislav; Konstantinidis, Nikolaos; Koperny, Stefan; Korcyl, Krzysztof; Kordas, Kostantinos; Korn, Andreas; Korol, Aleksandr; Korolkov, Ilya; Korolkova, Elena; Korotkov, Vladislav; Kortner, Oliver; Kortner, Sandra; Kostyukhin, Vadim; Kotov, Sergey; Kotov, Vladislav; Kotwal, Ashutosh; Kourkoumelis, Christine; Kouskoura, Vasiliki; Koutsman, Alex; Kowalewski, Robert Victor; Kowalski, Tadeusz; Kozanecki, Witold; Kozhin, Anatoly; Kral, Vlastimil; Kramarenko, Viktor; Kramberger, Gregor; Krasny, Mieczyslaw Witold; Krasznahorkay, Attila; Kraus, Jana; Kreiss, Sven; Krejci, Frantisek; Kretzschmar, Jan; Krieger, Nina; Krieger, Peter; Kroeninger, Kevin; Kroha, Hubert; Kroll, Joe; Kroseberg, Juergen; Krstic, Jelena; Kruchonak, Uladzimir; Krüger, Hans; Kruker, Tobias; Krumnack, Nils; Krumshteyn, Zinovii; Kubota, Takashi; Kuday, Sinan; Kuehn, Susanne; Kugel, Andreas; Kuhl, Thorsten; Kuhn, Dietmar; Kukhtin, Victor; Kulchitsky, Yuri; Kuleshov, Sergey; Kummer, Christian; Kuna, Marine; Kunkle, Joshua; Kupco, Alexander; Kurashige, Hisaya; Kurata, Masakazu; Kurochkin, Yurii; Kus, Vlastimil; Kuwertz, Emma Sian; Kuze, Masahiro; Kvita, Jiri; Kwee, Regina; La Rosa, Alessandro; La Rotonda, Laura; Labarga, Luis; Labbe, Julien; Lablak, Said; Lacasta, Carlos; Lacava, Francesco; Lacker, Heiko; Lacour, Didier; Lacuesta, Vicente Ramón; Ladygin, Evgueni; Lafaye, Remi; Laforge, Bertrand; Lagouri, Theodota; Lai, Stanley; Laisne, Emmanuel; Lamanna, Massimo; Lambourne, Luke; Lampen, Caleb; Lampl, Walter; Lancon, Eric; Landgraf, Ulrich; Landon, Murrough; Lane, Jenna; Lang, Valerie Susanne; Lange, Clemens; Lankford, Andrew; Lanni, Francesco; Lantzsch, Kerstin; Laplace, Sandrine; Lapoire, Cecile; Laporte, Jean-Francois; Lari, Tommaso; Larner, Aimee; Lassnig, Mario; Laurelli, Paolo; Lavorini, Vincenzo; Lavrijsen, Wim; Laycock, Paul; Le Dortz, Olivier; Le Guirriec, Emmanuel; Le Maner, Christophe; Le Menedeu, Eve; LeCompte, Thomas; Ledroit-Guillon, Fabienne Agnes Marie; Lee, Hurng-Chun; Lee, Jason; Lee, Shih-Chang; Lee, Lawrence; Lefebvre, Michel; Legendre, Marie; Legger, Federica; Leggett, Charles; Lehmacher, Marc; Lehmann Miotto, Giovanna; Lei, Xiaowen; Leite, Marco Aurelio Lisboa; Leitner, Rupert; Lellouch, Daniel; Lemmer, Boris; Lendermann, Victor; Leney, Katharine; Lenz, Tatiana; Lenzen, Georg; Lenzi, Bruno; Leonhardt, Kathrin; Leontsinis, Stefanos; Lepold, Florian; Leroy, Claude; Lessard, Jean-Raphael; Lester, Christopher; Lester, Christopher Michael; Levêque, Jessica; Levin, Daniel; Levinson, Lorne; Lewis, Adrian; Lewis, George; Leyko, Agnieszka; Leyton, Michael; Li, Bo; Li, Haifeng; Li, Shu; Li, Xuefei; Liang, Zhijun; Liao, Hongbo; Liberti, Barbara; Lichard, Peter; Lichtnecker, Markus; Lie, Ki; Liebig, Wolfgang; Limbach, Christian; Limosani, Antonio; Limper, Maaike; Lin, Simon; Linde, Frank; Linnemann, James; Lipeles, Elliot; Lipniacka, Anna; Liss, Tony; Lissauer, David; Lister, Alison; Litke, Alan; Liu, Chuanlei; Liu, Dong; Liu, Hao; Liu, Jianbei; Liu, Lulu; Liu, Minghui; Liu, Yanwen; Livan, Michele; Livermore, Sarah; Lleres, Annick; Llorente Merino, Javier; Lloyd, Stephen; Lobodzinska, Ewelina; Loch, Peter; Lockman, William; Loddenkoetter, Thomas; Loebinger, Fred; Loginov, Andrey; Loh, Chang Wei; Lohse, Thomas; Lohwasser, Kristin; Lokajicek, Milos; Lombardo, Vincenzo Paolo; Long, Robin Eamonn; Lopes, Lourenco; Lopez Mateos, David; Lorenz, Jeanette; Lorenzo Martinez, Narei; Losada, Marta; Loscutoff, Peter; Lo Sterzo, Francesco; Losty, Michael; Lou, Xinchou; Lounis, Abdenour; Loureiro, Karina; Love, Jeremy; Love, Peter; Lowe, Andrew; Lu, Feng; Lubatti, Henry; Luci, Claudio; Lucotte, Arnaud; Ludwig, Andreas; Ludwig, Dörthe; Ludwig, Inga; Ludwig, Jens; Luehring, Frederick; Luijckx, Guy; Lukas, Wolfgang; Lumb, Debra; Luminari, Lamberto; Lund, Esben; Lund-Jensen, Bengt; Lundberg, Björn; Lundberg, Johan; Lundberg, Olof; Lundquist, Johan; Lungwitz, Matthias; Lynn, David; Lytken, Else; Ma, Hong; Ma, Lian Liang; Maccarrone, Giovanni; Macchiolo, Anna; Maček, Boštjan; Machado Miguens, Joana; Mackeprang, Rasmus; Madaras, Ronald; Maddocks, Harvey Jonathan; Mader, Wolfgang; Maenner, Reinhard; Maeno, Tadashi; Mättig, Peter; Mättig, Stefan; Magnoni, Luca; Magradze, Erekle; Mahboubi, Kambiz; Mahmoud, Sara; Mahout, Gilles; Maiani, Camilla; Maidantchik, Carmen; Maio, Amélia; Majewski, Stephanie; Makida, Yasuhiro; Makovec, Nikola; Mal, Prolay; Malaescu, Bogdan; Malecki, Pawel; Malecki, Piotr; Maleev, Victor; Malek, Fairouz; Mallik, Usha; Malon, David; Malone, Caitlin; Maltezos, Stavros; Malyshev, Vladimir; Malyukov, Sergei; Mameghani, Raphael; Mamuzic, Judita; Manabe, Atsushi; Mandelli, Luciano; Mandić, Igor; Mandrysch, Rocco; Maneira, José; Mangeard, Pierre-Simon; Manhaes de Andrade Filho, Luciano; Manjarres Ramos, Joany Andreina; Mann, Alexander; Manning, Peter; Manousakis-Katsikakis, Arkadios; Mansoulie, Bruno; Mapelli, Alessandro; Mapelli, Livio; March, Luis; Marchand, Jean-Francois; Marchese, Fabrizio; Marchiori, Giovanni; Marcisovsky, Michal; Marino, Christopher; Marroquim, Fernando; Marshall, Zach; Martens, Kalen; Marti, Lukas Fritz; Marti-Garcia, Salvador; Martin, Brian; Martin, Brian Thomas; Martin, Jean-Pierre; Martin, Tim; Martin, Victoria Jane; Martin dit Latour, Bertrand; Martin-Haugh, Stewart; Martinez, Mario; Martinez Outschoorn, Verena; Martyniuk, Alex; Marx, Marilyn; Marzano, Francesco; Marzin, Antoine; Masetti, Lucia; Mashimo, Tetsuro; Mashinistov, Ruslan; Masik, Jiri; Maslennikov, Alexey; Massa, Ignazio; Massaro, Graziano; Massol, Nicolas; Mastrandrea, Paolo; Mastroberardino, Anna; Masubuchi, Tatsuya; Matricon, Pierre; Matsunaga, Hiroyuki; Matsushita, Takashi; Mattravers, Carly; Maurer, Julien; Maxfield, Stephen; Mayne, Anna; Mazini, Rachid; Mazur, Michael; Mazzaferro, Luca; Mazzanti, Marcello; Mc Kee, Shawn Patrick; McCarn, Allison; McCarthy, Robert; McCarthy, Tom; McCubbin, Norman; McFarlane, Kenneth; Mcfayden, Josh; Mchedlidze, Gvantsa; Mclaughlan, Tom; McMahon, Steve; McPherson, Robert; Meade, Andrew; Mechnich, Joerg; Mechtel, Markus; Medinnis, Mike; Meera-Lebbai, Razzak; Meguro, Tatsuma; Mehdiyev, Rashid; Mehlhase, Sascha; Mehta, Andrew; Meier, Karlheinz; Meirose, Bernhard; Melachrinos, Constantinos; Mellado Garcia, Bruce Rafael; Meloni, Federico; Mendoza Navas, Luis; Meng, Zhaoxia; Mengarelli, Alberto; Menke, Sven; Meoni, Evelin; Mercurio, Kevin Michael; Mermod, Philippe; Merola, Leonardo; Meroni, Chiara; Merritt, Frank; Merritt, Hayes; Messina, Andrea; Metcalfe, Jessica; Mete, Alaettin Serhan; Meyer, Carsten; Meyer, Christopher; Meyer, Jean-Pierre; Meyer, Jochen; Meyer, Joerg; Meyer, Thomas Christian; Meyer, W Thomas; Miao, Jiayuan; Michal, Sebastien; Micu, Liliana; Middleton, Robin; Migas, Sylwia; Mijović, Liza; Mikenberg, Giora; Mikestikova, Marcela; Mikuž, Marko; Miller, David; Miller, Robert; Mills, Bill; Mills, Corrinne; Milov, Alexander; Milstead, David; Milstein, Dmitry; Minaenko, Andrey; Miñano Moya, Mercedes; Minashvili, Irakli; Mincer, Allen; Mindur, Bartosz; Mineev, Mikhail; Ming, Yao; Mir, Lluisa-Maria; Mirabelli, Giovanni; Mitrevski, Jovan; Mitsou, Vasiliki A; Mitsui, Shingo; Miyagawa, Paul; Mjörnmark, Jan-Ulf; Moa, Torbjoern; Moeller, Victoria; Mönig, Klaus; Möser, Nicolas; Mohapatra, Soumya; Mohr, Wolfgang; Moles-Valls, Regina; Monk, James; Monnier, Emmanuel; Montejo Berlingen, Javier; Monticelli, Fernando; Monzani, Simone; Moore, Roger; Moorhead, Gareth; Mora Herrera, Clemencia; Moraes, Arthur; Morange, Nicolas; Morel, Julien; Morello, Gianfranco; Moreno, Deywis; Moreno Llácer, María; Morettini, Paolo; Morgenstern, Marcus; Morii, Masahiro; Morley, Anthony Keith; Mornacchi, Giuseppe; Morris, John; Morvaj, Ljiljana; Moser, Hans-Guenther; Mosidze, Maia; Moss, Josh; Mount, Richard; Mountricha, Eleni; Mouraviev, Sergei; Moyse, Edward; Mueller, Felix; Mueller, James; Mueller, Klemens; Müller, Thomas; Mueller, Timo; Muenstermann, Daniel; Munwes, Yonathan; Murray, Bill; Mussche, Ido; Musto, Elisa; Myagkov, Alexey; Myska, Miroslav; Nadal, Jordi; Nagai, Koichi; Nagano, Kunihiro; Nagarkar, Advait; Nagasaka, Yasushi; Nagel, Martin; Nairz, Armin Michael; Nakahama, Yu; Nakamura, Koji; Nakamura, Tomoaki; Nakano, Itsuo; Nanava, Gizo; Napier, Austin; Narayan, Rohin; Nash, Michael; Nattermann, Till; Naumann, Thomas; Navarro, Gabriela; Neal, Homer; Nechaeva, Polina; Neep, Thomas James; Negri, Andrea; Negri, Guido; Negrini, Matteo; Nektarijevic, Snezana; Nelson, Andrew; Nelson, Timothy Knight; Nemecek, Stanislav; Nemethy, Peter; Nepomuceno, Andre Asevedo; Nessi, Marzio; Neubauer, Mark; Neusiedl, Andrea; Neves, Ricardo; Nevski, Pavel; Newman, Paul; Nguyen Thi Hong, Van; Nickerson, Richard; Nicolaidou, Rosy; Nicquevert, Bertrand; Niedercorn, Francois; Nielsen, Jason; Nikiforou, Nikiforos; Nikiforov, Andriy; Nikolaenko, Vladimir; Nikolic-Audit, Irena; Nikolics, Katalin; Nikolopoulos, Konstantinos; Nilsen, Henrik; Nilsson, Paul; Ninomiya, Yoichi; Nisati, Aleandro; Nisius, Richard; Nobe, Takuya; Nodulman, Lawrence; Nomachi, Masaharu; Nomidis, Ioannis; Norberg, Scarlet; Nordberg, Markus; Norton, Peter; Novakova, Jana; Nozaki, Mitsuaki; Nozka, Libor; Nugent, Ian Michael; Nuncio-Quiroz, Adriana-Elizabeth; Nunes Hanninger, Guilherme; Nunnemann, Thomas; Nurse, Emily; O'Brien, Brendan Joseph; O'Neale, Steve; O'Neil, Dugan; O'Shea, Val; Oakes, Louise Beth; Oakham, Gerald; Oberlack, Horst; Ocariz, Jose; Ochi, Atsuhiko; Oda, Susumu; Odaka, Shigeru; Odier, Jerome; Ogren, Harold; Oh, Alexander; Oh, Seog; Ohm, Christian; Ohshima, Takayoshi; Okawa, Hideki; Okumura, Yasuyuki; Okuyama, Toyonobu; Olariu, Albert; Olchevski, Alexander; Olivares Pino, Sebastian Andres; Oliveira, Miguel Alfonso; Oliveira Damazio, Denis; Oliver Garcia, Elena; Olivito, Dominick; Olszewski, Andrzej; Olszowska, Jolanta; Onofre, António; Onyisi, Peter; Oram, Christopher; Oreglia, Mark; Oren, Yona; Orestano, Domizia; Orlando, Nicola; Orlov, Iliya; Oropeza Barrera, Cristina; Orr, Robert; Osculati, Bianca; Ospanov, Rustem; Osuna, Carlos; Otero y Garzon, Gustavo; Ottersbach, John; Ouchrif, Mohamed; Ouellette, Eric; Ould-Saada, Farid; Ouraou, Ahmimed; Ouyang, Qun; Ovcharova, Ana; Owen, Mark; Owen, Simon; Ozcan, Veysi Erkcan; Ozturk, Nurcan; Pacheco Pages, Andres; Padilla Aranda, Cristobal; Pagan Griso, Simone; Paganis, Efstathios; Pahl, Christoph; Paige, Frank; Pais, Preema; Pajchel, Katarina; Palacino, Gabriel; Paleari, Chiara; Palestini, Sandro; Pallin, Dominique; Palma, Alberto; Palmer, Jody; Pan, Yibin; Panagiotopoulou, Evgenia; Pani, Priscilla; Panikashvili, Natalia; Panitkin, Sergey; Pantea, Dan; Papadelis, Aras; Papadopoulou, Theodora; Paramonov, Alexander; Paredes Hernandez, Daniela; Park, Woochun; Parker, Andy; Parodi, Fabrizio; Parsons, John; Parzefall, Ulrich; Pashapour, Shabnaz; Pasqualucci, Enrico; Passaggio, Stefano; Passeri, Antonio; Pastore, Fernanda; Pastore, Francesca; Pásztor, Gabriella; Pataraia, Sophio; Patel, Nikhul; Pater, Joleen; Patricelli, Sergio; Pauly, Thilo; Pecsy, Martin; Pedraza Morales, Maria Isabel; Peleganchuk, Sergey; Pelikan, Daniel; Peng, Haiping; Penning, Bjoern; Penson, Alexander; Penwell, John; Perantoni, Marcelo; Perez, Kerstin; Perez Cavalcanti, Tiago; Perez Codina, Estel; Pérez García-Estañ, María Teresa; Perez Reale, Valeria; Perini, Laura; Pernegger, Heinz; Perrino, Roberto; Perrodo, Pascal; Peshekhonov, Vladimir; Peters, Krisztian; Petersen, Brian; Petersen, Jorgen; Petersen, Troels; Petit, Elisabeth; Petridis, Andreas; Petridou, Chariclia; Petrolo, Emilio; Petrucci, Fabrizio; Petschull, Dennis; Petteni, Michele; Pezoa, Raquel; Phan, Anna; Phillips, Peter William; Piacquadio, Giacinto; Picazio, Attilio; Piccaro, Elisa; Piccinini, Maurizio; Piec, Sebastian Marcin; Piegaia, Ricardo; Pignotti, David; Pilcher, James; Pilkington, Andrew; Pina, João Antonio; Pinamonti, Michele; Pinder, Alex; Pinfold, James; Pinto, Belmiro; Pizio, Caterina; Plamondon, Mathieu; Pleier, Marc-Andre; Plotnikova, Elena; Poblaguev, Andrei; Poddar, Sahill; Podlyski, Fabrice; Poggioli, Luc; Pohl, Martin; Polesello, Giacomo; Policicchio, Antonio; Polini, Alessandro; Poll, James; Polychronakos, Venetios; Pomeroy, Daniel; Pommès, Kathy; Pontecorvo, Ludovico; Pope, Bernard; Popeneciu, Gabriel Alexandru; Popovic, Dragan; Poppleton, Alan; Portell Bueso, Xavier; Pospelov, Guennady; Pospisil, Stanislav; Potrap, Igor; Potter, Christina; Potter, Christopher; Poulard, Gilbert; Poveda, Joaquin; Pozdnyakov, Valery; Prabhu, Robindra; Pralavorio, Pascal; Pranko, Aliaksandr; Prasad, Srivas; Pravahan, Rishiraj; Prell, Soeren; Pretzl, Klaus Peter; Price, Darren; Price, Joe; Price, Lawrence; Prieur, Damien; Primavera, Margherita; Prokofiev, Kirill; Prokoshin, Fedor; Protopopescu, Serban; Proudfoot, James; Prudent, Xavier; Przybycien, Mariusz; Przysiezniak, Helenka; Psoroulas, Serena; Ptacek, Elizabeth; Pueschel, Elisa; Purdham, John; Purohit, Milind; Puzo, Patrick; Pylypchenko, Yuriy; Qian, Jianming; Quadt, Arnulf; Quarrie, David; Quayle, William; Quinonez, Fernando; Raas, Marcel; Radescu, Voica; Radloff, Peter; Rador, Tonguc; Ragusa, Francesco; Rahal, Ghita; Rahimi, Amir; Rahm, David; Rajagopalan, Srinivasan; Rammensee, Michael; Rammes, Marcus; Randle-Conde, Aidan Sean; Randrianarivony, Koloina; Rauscher, Felix; Rave, Tobias Christian; Raymond, Michel; Read, Alexander Lincoln; Rebuzzi, Daniela; Redelbach, Andreas; Redlinger, George; Reece, Ryan; Reeves, Kendall; Reinherz-Aronis, Erez; Reinsch, Andreas; Reisinger, Ingo; Rembser, Christoph; Ren, Zhongliang; Renaud, Adrien; Rescigno, Marco; Resconi, Silvia; Resende, Bernardo; Reznicek, Pavel; Rezvani, Reyhaneh; Richter, Robert; Richter-Was, Elzbieta; Ridel, Melissa; Rijpstra, Manouk; Rijssenbeek, Michael; Rimoldi, Adele; Rinaldi, Lorenzo; Rios, Ryan Randy; Riu, Imma; Rivoltella, Giancesare; Rizatdinova, Flera; Rizvi, Eram; Robertson, Steven; Robichaud-Veronneau, Andree; Robinson, Dave; Robinson, James; Robson, Aidan; Rocha de Lima, Jose Guilherme; Roda, Chiara; Roda Dos Santos, Denis; Roe, Adam; Roe, Shaun; Røhne, Ole; Rolli, Simona; Romaniouk, Anatoli; Romano, Marino; Romeo, Gaston; Romero Adam, Elena; Roos, Lydia; Ros, Eduardo; Rosati, Stefano; Rosbach, Kilian; Rose, Anthony; Rose, Matthew; Rosenbaum, Gabriel; Rosenberg, Eli; Rosendahl, Peter Lundgaard; Rosenthal, Oliver; Rosselet, Laurent; Rossetti, Valerio; Rossi, Elvira; Rossi, Leonardo Paolo; Rotaru, Marina; Roth, Itamar; Rothberg, Joseph; Rousseau, David; Royon, Christophe; Rozanov, Alexander; Rozen, Yoram; Ruan, Xifeng; Rubbo, Francesco; Rubinskiy, Igor; Ruckert, Benjamin; Ruckstuhl, Nicole; Rud, Viacheslav; Rudolph, Christian; Rudolph, Gerald; Rühr, Frederik; Ruiz-Martinez, Aranzazu; Rumyantsev, Leonid; Rurikova, Zuzana; Rusakovich, Nikolai; Rutherfoord, John; Ruwiedel, Christoph; Ruzicka, Pavel; Ryabov, Yury; Ryan, Patrick; Rybar, Martin; Rybkin, Grigori; Ryder, Nick; Saavedra, Aldo; Sadeh, Iftach; Sadrozinski, Hartmut; Sadykov, Renat; Safai Tehrani, Francesco; Sakamoto, Hiroshi; Salamanna, Giuseppe; Salamon, Andrea; Saleem, Muhammad; Salek, David; Salihagic, Denis; Salnikov, Andrei; Salt, José; Salvachua Ferrando, Belén; Salvatore, Daniela; Salvatore, Pasquale Fabrizio; Salvucci, Antonio; Salzburger, Andreas; Sampsonidis, Dimitrios; Samset, Björn Hallvard; Sanchez, Arturo; Sanchez Martinez, Victoria; Sandaker, Heidi; Sander, Heinz Georg; Sanders, Michiel; Sandhoff, Marisa; Sandoval, Tanya; Sandoval, Carlos; Sandstroem, Rikard; Sankey, Dave; Sansoni, Andrea; Santamarina Rios, Cibran; Santoni, Claudio; Santonico, Rinaldo; Santos, Helena; Saraiva, João; Sarangi, Tapas; Sarkisyan-Grinbaum, Edward; Sarri, Francesca; Sartisohn, Georg; Sasaki, Osamu; Sasao, Noboru; Satsounkevitch, Igor; Sauvage, Gilles; Sauvan, Emmanuel; Sauvan, Jean-Baptiste; Savard, Pierre; Savinov, Vladimir; Savu, Dan Octavian; Sawyer, Lee; Saxon, David; Saxon, James; Sbarra, Carla; Sbrizzi, Antonio; Scannicchio, Diana; Scarcella, Mark; Schaarschmidt, Jana; Schacht, Peter; Schaefer, Douglas; Schäfer, Uli; Schaepe, Steffen; Schaetzel, Sebastian; Schaffer, Arthur; Schaile, Dorothee; Schamberger, R. Dean; Schamov, Andrey; Scharf, Veit; Schegelsky, Valery; Scheirich, Daniel; Schernau, Michael; Scherzer, Max; Schiavi, Carlo; Schieck, Jochen; Schioppa, Marco; Schlenker, Stefan; Schmidt, Evelyn; Schmieden, Kristof; Schmitt, Christian; Schmitt, Sebastian; Schmitz, Martin; Schneider, Basil; Schnoor, Ulrike; Schoening, Andre; Schorlemmer, Andre Lukas; Schott, Matthias; Schouten, Doug; Schovancova, Jaroslava; Schram, Malachi; Schroeder, Christian; Schroer, Nicolai; Schultens, Martin Johannes; Schultes, Joachim; Schultz-Coulon, Hans-Christian; Schulz, Holger; Schumacher, Markus; Schumm, Bruce; Schune, Philippe; Schwanenberger, Christian; Schwartzman, Ariel; Schwemling, Philippe; Schwienhorst, Reinhard; Schwierz, Rainer; Schwindling, Jerome; Schwindt, Thomas; Schwoerer, Maud; Sciolla, Gabriella; Scott, Bill; Searcy, Jacob; Sedov, George; Sedykh, Evgeny; Seidel, Sally; Seiden, Abraham; Seifert, Frank; Seixas, José; Sekhniaidze, Givi; Sekula, Stephen; Selbach, Karoline Elfriede; Seliverstov, Dmitry; Sellden, Bjoern; Sellers, Graham; Seman, Michal; Semprini-Cesari, Nicola; Serfon, Cedric; Serin, Laurent; Serkin, Leonid; Seuster, Rolf; Severini, Horst; Sfyrla, Anna; Shabalina, Elizaveta; Shamim, Mansoora; Shan, Lianyou; Shank, James; Shao, Qi Tao; Shapiro, Marjorie; Shatalov, Pavel; Shaw, Kate; Sherman, Daniel; Sherwood, Peter; Shibata, Akira; Shimizu, Shima; Shimojima, Makoto; Shin, Taeksu; Shiyakova, Maria; Shmeleva, Alevtina; Shochet, Mel; Short, Daniel; Shrestha, Suyog; Shulga, Evgeny; Shupe, Michael; Sicho, Petr; Sidoti, Antonio; Siegert, Frank; Sijacki, Djordje; Silbert, Ohad; Silva, José; Silver, Yiftah; Silverstein, Daniel; Silverstein, Samuel; Simak, Vladislav; Simard, Olivier; Simic, Ljiljana; Simion, Stefan; Simioni, Eduard; Simmons, Brinick; Simoniello, Rosa; Simonyan, Margar; Sinervo, Pekka; Sinev, Nikolai; Sipica, Valentin; Siragusa, Giovanni; Sircar, Anirvan; Sisakyan, Alexei; Sivoklokov, Serguei; Sjölin, Jörgen; Sjursen, Therese; Skinnari, Louise Anastasia; Skottowe, Hugh Philip; Skovpen, Kirill; Skubic, Patrick; Slater, Mark; Slavicek, Tomas; Sliwa, Krzysztof; Smakhtin, Vladimir; Smart, Ben; Smirnov, Sergei; Smirnov, Yury; Smirnova, Lidia; Smirnova, Oxana; Smith, Ben Campbell; Smith, Douglas; Smith, Kenway; Smizanska, Maria; Smolek, Karel; Snesarev, Andrei; Snow, Steve; Snow, Joel; Snyder, Scott; Sobie, Randall; Sodomka, Jaromir; Soffer, Abner; Solans, Carlos; Solar, Michael; Solc, Jaroslav; Soldatov, Evgeny; Soldevila, Urmila; Solfaroli Camillocci, Elena; Solodkov, Alexander; Solovyanov, Oleg; Soni, Nitesh; Sopko, Vit; Sopko, Bruno; Sosebee, Mark; Soualah, Rachik; Soukharev, Andrey; Spagnolo, Stefania; Spanò, Francesco; Spighi, Roberto; Spigo, Giancarlo; Spiwoks, Ralf; Spousta, Martin; Spreitzer, Teresa; Spurlock, Barry; St Denis, Richard Dante; Stahlman, Jonathan; Stamen, Rainer; Stanecka, Ewa; Stanek, Robert; Stanescu, Cristian; Stanescu-Bellu, Madalina; Stapnes, Steinar; Starchenko, Evgeny; Stark, Jan; Staroba, Pavel; Starovoitov, Pavel; Staszewski, Rafal; Staude, Arnold; Stavina, Pavel; Steele, Genevieve; Steinbach, Peter; Steinberg, Peter; Stekl, Ivan; Stelzer, Bernd; Stelzer, Harald Joerg; Stelzer-Chilton, Oliver; Stenzel, Hasko; Stern, Sebastian; Stewart, Graeme; Stillings, Jan Andre; Stockton, Mark; Stoerig, Kathrin; Stoicea, Gabriel; Stonjek, Stefan; Strachota, Pavel; Stradling, Alden; Straessner, Arno; Strandberg, Jonas; Strandberg, Sara; Strandlie, Are; Strang, Michael; Strauss, Emanuel; Strauss, Michael; Strizenec, Pavol; Ströhmer, Raimund; Strom, David; Strong, John; Stroynowski, Ryszard; Strube, Jan; Stugu, Bjarne; Stumer, Iuliu; Stupak, John; Sturm, Philipp; Styles, Nicholas Adam; Soh, Dart-yin; Su, Dong; Subramania, Halasya Siva; Succurro, Antonella; Sugaya, Yorihito; Suhr, Chad; Suk, Michal; Sulin, Vladimir; Sultansoy, Saleh; Sumida, Toshi; Sun, Xiaohu; Sundermann, Jan Erik; Suruliz, Kerim; Susinno, Giancarlo; Sutton, Mark; Suzuki, Yu; Suzuki, Yuta; Svatos, Michal; Swedish, Stephen; Sykora, Ivan; Sykora, Tomas; Sánchez, Javier; Ta, Duc; Tackmann, Kerstin; Taffard, Anyes; Tafirout, Reda; Taiblum, Nimrod; Takahashi, Yuta; Takai, Helio; Takashima, Ryuichi; Takeda, Hiroshi; Takeshita, Tohru; Takubo, Yosuke; Talby, Mossadek; Talyshev, Alexey; Tamsett, Matthew; Tanaka, Junichi; Tanaka, Reisaburo; Tanaka, Satoshi; Tanaka, Shuji; Tanasijczuk, Andres Jorge; Tani, Kazutoshi; Tannoury, Nancy; Tapprogge, Stefan; Tardif, Dominique; Tarem, Shlomit; Tarrade, Fabien; Tartarelli, Giuseppe Francesco; Tas, Petr; Tasevsky, Marek; Tassi, Enrico; Tatarkhanov, Mous; Tayalati, Yahya; Taylor, Christopher; Taylor, Frank; Taylor, Geoffrey; Taylor, Wendy; Teinturier, Marthe; Teixeira Dias Castanheira, Matilde; Teixeira-Dias, Pedro; Temming, Kim Katrin; Ten Kate, Herman; Teng, Ping-Kun; Terada, Susumu; Terashi, Koji; Terron, Juan; Testa, Marianna; Teuscher, Richard; Therhaag, Jan; Theveneaux-Pelzer, Timothée; Thoma, Sascha; Thomas, Juergen; Thompson, Emily; Thompson, Paul; Thompson, Peter; Thompson, Stan; Thomsen, Lotte Ansgaard; Thomson, Evelyn; Thomson, Mark; Thong, Wai Meng; Thun, Rudolf; Tian, Feng; Tibbetts, Mark James; Tic, Tomáš; Tikhomirov, Vladimir; Tikhonov, Yury; Timoshenko, Sergey; Tipton, Paul; Tisserant, Sylvain; Todorov, Theodore; Todorova-Nova, Sharka; Toggerson, Brokk; Tojo, Junji; Tokár, Stanislav; Tokushuku, Katsuo; Tollefson, Kirsten; Tomoto, Makoto; Tompkins, Lauren; Toms, Konstantin; Tonoyan, Arshak; Topfel, Cyril; Topilin, Nikolai; Torchiani, Ingo; Torrence, Eric; Torres, Heberth; Torró Pastor, Emma; Toth, Jozsef; Touchard, Francois; Tovey, Daniel; Trefzger, Thomas; Tremblet, Louis; Tricoli, Alesandro; Trigger, Isabel Marian; Trincaz-Duvoid, Sophie; Tripiana, Martin; Triplett, Nathan; Trischuk, William; Trocmé, Benjamin; Troncon, Clara; Trottier-McDonald, Michel; Trzebinski, Maciej; Trzupek, Adam; Tsarouchas, Charilaos; Tseng, Jeffrey; Tsiakiris, Menelaos; Tsiareshka, Pavel; Tsionou, Dimitra; Tsipolitis, Georgios; Tsiskaridze, Shota; Tsiskaridze, Vakhtang; Tskhadadze, Edisher; Tsukerman, Ilya; Tsulaia, Vakhtang; Tsung, Jieh-Wen; Tsuno, Soshi; Tsybychev, Dmitri; Tua, Alan; Tudorache, Alexandra; Tudorache, Valentina; Tuggle, Joseph; Turala, Michal; Turecek, Daniel; Turk Cakir, Ilkay; Turlay, Emmanuel; Turra, Ruggero; Tuts, Michael; Tykhonov, Andrii; Tylmad, Maja; Tyndel, Mike; Tzanakos, George; Uchida, Kirika; Ueda, Ikuo; Ueno, Ryuichi; Ugland, Maren; Uhlenbrock, Mathias; Uhrmacher, Michael; Ukegawa, Fumihiko; Unal, Guillaume; Undrus, Alexander; Unel, Gokhan; Unno, Yoshinobu; Urbaniec, Dustin; Usai, Giulio; Uslenghi, Massimiliano; Vacavant, Laurent; Vacek, Vaclav; Vachon, Brigitte; Vahsen, Sven; Valenta, Jan; Valentinetti, Sara; Valero, Alberto; Valkar, Stefan; Valladolid Gallego, Eva; Vallecorsa, Sofia; Valls Ferrer, Juan Antonio; Van Der Deijl, Pieter; van der Geer, Rogier; van der Graaf, Harry; van der Kraaij, Erik; Van Der Leeuw, Robin; van der Poel, Egge; van der Ster, Daniel; van Eldik, Niels; van Gemmeren, Peter; van Vulpen, Ivo; Vanadia, Marco; Vandelli, Wainer; Vaniachine, Alexandre; Vankov, Peter; Vannucci, Francois; Vari, Riccardo; Varol, Tulin; Varouchas, Dimitris; Vartapetian, Armen; Varvell, Kevin; Vassilakopoulos, Vassilios; Vazeille, Francois; Vazquez Schroeder, Tamara; Vegni, Guido; Veillet, Jean-Jacques; Veloso, Filipe; Veness, Raymond; Veneziano, Stefano; Ventura, Andrea; Ventura, Daniel; Venturi, Manuela; Venturi, Nicola; Vercesi, Valerio; Verducci, Monica; Verkerke, Wouter; Vermeulen, Jos; Vest, Anja; Vetterli, Michel; Vichou, Irene; Vickey, Trevor; Vickey Boeriu, Oana Elena; Viehhauser, Georg; Viel, Simon; Villa, Mauro; Villaplana Perez, Miguel; Vilucchi, Elisabetta; Vincter, Manuella; Vinek, Elisabeth; Vinogradov, Vladimir; Virchaux, Marc; Virzi, Joseph; Vitells, Ofer; Viti, Michele; Vivarelli, Iacopo; Vives Vaque, Francesc; Vlachos, Sotirios; Vladoiu, Dan; Vlasak, Michal; Vogel, Adrian; Vokac, Petr; Volpi, Guido; Volpi, Matteo; Volpini, Giovanni; von der Schmitt, Hans; von Loeben, Joerg; von Radziewski, Holger; von Toerne, Eckhard; Vorobel, Vit; Vorwerk, Volker; Vos, Marcel; Voss, Rudiger; Voss, Thorsten Tobias; Vossebeld, Joost; Vranjes, Nenad; Vranjes Milosavljevic, Marija; Vrba, Vaclav; Vreeswijk, Marcel; Vu Anh, Tuan; Vuillermet, Raphael; Vukotic, Ilija; Wagner, Wolfgang; Wagner, Peter; Wahlen, Helmut; Wahrmund, Sebastian; Wakabayashi, Jun; Walch, Shannon; Walder, James; Walker, Rodney; Walkowiak, Wolfgang; Wall, Richard; Waller, Peter; Walsh, Brian; Wang, Chiho; Wang, Haichen; Wang, Hulin; Wang, Jike; Wang, Jin; Wang, Rui; Wang, Song-Ming; Wang, Tan; Warburton, Andreas; Ward, Patricia; Warsinsky, Markus; Washbrook, Andrew; Wasicki, Christoph; Watanabe, Ippei; Watkins, Peter; Watson, Alan; Watson, Ian; Watson, Miriam; Watts, Gordon; Watts, Stephen; Waugh, Anthony; Waugh, Ben; Weber, Marc; Weber, Michele; Weber, Pavel; Weidberg, Anthony; Weigell, Philipp; Weingarten, Jens; Weiser, Christian; Wellenstein, Hermann; Wells, Phillippa; Wenaus, Torre; Wendland, Dennis; Weng, Zhili; Wengler, Thorsten; Wenig, Siegfried; Wermes, Norbert; Werner, Matthias; Werner, Per; Werth, Michael; Wessels, Martin; Wetter, Jeffrey; Weydert, Carole; Whalen, Kathleen; Wheeler-Ellis, Sarah Jane; White, Andrew; White, Martin; White, Sebastian; Whitehead, Samuel Robert; Whiteson, Daniel; Whittington, Denver; Wicek, Francois; Wicke, Daniel; Wickens, Fred; Wiedenmann, Werner; Wielers, Monika; Wienemann, Peter; Wiglesworth, Craig; Wiik-Fuchs, Liv Antje Mari; Wijeratne, Peter Alexander; Wildauer, Andreas; Wildt, Martin Andre; Wilhelm, Ivan; Wilkens, Henric George; Will, Jonas Zacharias; Williams, Eric; Williams, Hugh; Willis, William; Willocq, Stephane; Wilson, John; Wilson, Michael Galante; Wilson, Alan; Wingerter-Seez, Isabelle; Winkelmann, Stefan; Winklmeier, Frank; Wittgen, Matthias; Wollstadt, Simon Jakob; Wolter, Marcin Wladyslaw; Wolters, Helmut; Wong, Wei-Cheng; Wooden, Gemma; Wosiek, Barbara; Wotschack, Jorg; Woudstra, Martin; Wozniak, Krzysztof; Wraight, Kenneth; Wright, Catherine; Wright, Michael; Wrona, Bozydar; Wu, Sau Lan; Wu, Xin; Wu, Yusheng; Wulf, Evan; Wynne, Benjamin; Xella, Stefania; Xiao, Meng; Xie, Song; Xu, Chao; Xu, Da; Yabsley, Bruce; Yacoob, Sahal; Yamada, Miho; Yamaguchi, Hiroshi; Yamamoto, Akira; Yamamoto, Kyoko; Yamamoto, Shimpei; Yamamura, Taiki; Yamanaka, Takashi; Yamaoka, Jared; Yamazaki, Takayuki; Yamazaki, Yuji; Yan, Zhen; Yang, Haijun; Yang, Un-Ki; Yang, Yi; Yang, Zhaoyu; Yanush, Serguei; Yao, Liwen; Yao, Yushu; Yasu, Yoshiji; Ybeles Smit, Gabriel Valentijn; Ye, Jingbo; Ye, Shuwei; Yilmaz, Metin; Yoosoofmiya, Reza; Yorita, Kohei; Yoshida, Riktura; Young, Charles; Young, Christopher John; Youssef, Saul; Yu, Dantong; Yu, Jaehoon; Yu, Jie; Yuan, Li; Yurkewicz, Adam; Byszewski, Marcin; Zabinski, Bartlomiej; Zaidan, Remi; Zaitsev, Alexander; Zajacova, Zuzana; Zanello, Lucia; Zaytsev, Alexander; Zeitnitz, Christian; Zeman, Martin; Zemla, Andrzej; Zendler, Carolin; Zenin, Oleg; Ženiš, Tibor; Zinonos, Zinonas; Zenz, Seth; Zerwas, Dirk; Zevi della Porta, Giovanni; Zhan, Zhichao; Zhang, Dongliang; Zhang, Huaqiao; Zhang, Jinlong; Zhang, Xueyao; Zhang, Zhiqing; Zhao, Long; Zhao, Tianchi; Zhao, Zhengguo; Zhemchugov, Alexey; Zhong, Jiahang; Zhou, Bing; Zhou, Ning; Zhou, Yue; Zhu, Cheng Guang; Zhu, Hongbo; Zhu, Junjie; Zhu, Yingchun; Zhuang, Xuai; Zhuravlov, Vadym; Zieminska, Daria; Zimin, Nikolai; Zimmermann, Robert; Zimmermann, Simone; Zimmermann, Stephanie; Ziolkowski, Michael; Zitoun, Robert; Živković, Lidija; Zmouchko, Viatcheslav; Zobernig, Georg; Zoccoli, Antonio; zur Nedden, Martin; Zutshi, Vishnu; Zwalinski, Lukasz

2013-01-15

Measurements are presented of differential cross-sections for top quark pair production in pp collisions at $\\sqrt{s}$ = 7 TeV relative to the total inclusive top quark pair production cross-section. A data sample of 2.05/fb recorded by the ATLAS detector at the Large Hadron Collider is used. Relative differential cross-sections are derived as a function of the invariant mass, the transverse momentum and the rapidity of the top quark pair system. Events are selected in the lepton (electron or muon) + jets channel. The background-subtracted differential distributions are corrected for detector effects, normalized to the total inclusive top quark pair production cross-section and compared to theoretical predictions. The measurement uncertainties range typically between 10% and 20% and are generally dominated by systematic effects. No significant deviations from the Standard Model expectations are observed.

How to assess performance in cycling: the multivariate nature of influencing factors and related indicators

Science.gov (United States)

Castronovo, A. Margherita; Conforto, Silvia; Schmid, Maurizio; Bibbo, Daniele; D'Alessio, Tommaso

2013-01-01

Finding an optimum for the cycling performance is not a trivial matter, since the literature shows the presence of many controversial aspects. In order to quantify different levels of performance, several indexes have been defined and used in many studies, reflecting variations in physiological and biomechanical factors. In particular, indexes such as Gross Efficiency (GE), Net Efficiency (NE) and Delta Efficiency (DE) have been referred to changes in metabolic efficiency (EffMet), while the Indexes of Effectiveness (IE), defined over the complete crank revolution or over part of it, have been referred to variations in mechanical effectiveness (EffMech). All these indicators quantify the variations of different factors [i.e., muscle fibers type distribution, pedaling cadence, setup of the bicycle frame, muscular fatigue (MFat), environmental variables, ergogenic aids, psychological traits (PsychTr)], which, moreover, show high mutual correlation. In the attempt of assessing cycling performance, most studies in the literature keep all these factors separated. This may bring to misleading results, leaving unanswered the question of how to improve cycling performance. This work provides an overview on the studies involving indexes and factors usually related to performance monitoring and assessment in cycling. In particular, in order to clarify all those aspects, the mutual interactions among these factors are highlighted, in view of a global performance assessment. Moreover, a proposal is presented advocating for a model-based approach that considers all factors mentioned in the survey, including the mutual interaction effects, for the definition of an objective function E representing the overall effectiveness of a training program in terms of both EffMet and EffMech. PMID:23734130

How to Assess Performance in Cycling: the Multivariate Nature of Influencing Factors and Related Indicators.

Directory of Open Access Journals (Sweden)

Anna Margherita eCastronovo

2013-05-01

Full Text Available Finding an optimum for the cycling performance is not a trivial matter, since the literature shows the presence of many controversial aspects. In order to quantify different levels of performance, several indexes have been defined and used in many studies, reflecting variations in physiological and biomechanical factors. In particular, indexes such as Gross Efficiency (GE, Net Efficiency (NE and Delta Efficiency (DE have been referred to changes in metabolic efficiency (EffMet, while the Indexes of Effectiveness (IE, defined over the complete crank revolution or over part of it, have been referred to variations in mechanical effectiveness (EffMech. All these indicators quantify the variations of different factors (i.e. muscle fibers type distribution, pedaling cadence, setup of the bicycle frame, muscular fatigue, environmental variables, ergogenic aids, psychological traits, which, moreover, show high mutual correlation. In the attempt of assessing cycling performance, most studies in the literature keep all these factors separated. This may bring to misleading results, leaving unanswered the question of how to improve cycling performance. This work provides an overview on the studies involving indexes and factors usually related to performance monitoring and assessment in cycling. In particular, in order to clarify all those aspects, the mutual interactions among these factors are highlighted, in view of a global performance assessment. Moreover, a proposal is presented advocating for a model-based approach that considers all factors mentioned in the survey, including the mutual interaction effects, for the definition of an objective function E representing the overall effectiveness of a training program in terms of both metabolic efficiency and mechanical effectiveness.

Crystal Structure of Borrelia turicatae protein, BTA121, a differentially regulated  gene in the tick-mammalian transmission cycle of relapsing fever spirochetes

Energy Technology Data Exchange (ETDEWEB)

Luo, Zhipu; Kelleher, Alan J.; Darwiche, Rabih; Hudspeth, Elissa M.; Shittu, Oluwatosin K.; Krishnavajhala, Aparna; Schneiter, Roger; Lopez, Job E.; Asojo, Oluwatoyin A. (Baylor); (Fribourg); (NCI)

2017-11-10

Tick-borne relapsing fever (RF) borreliosis is a neglected disease that is often misdiagnosed. RF species circulating in the United States include Borrelia turicatae, which is transmitted by argasid ticks. Environmental adaptation by RF Borrelia is poorly understood, however our previous studies indicated differential regulation of B. turicatae genes localized on the 150 kb linear megaplasmid during the tick-mammalian transmission cycle, including bta121. This gene is up-regulated by B. turicatae in the tick versus the mammal, and the encoded protein (BTA121) is predicted to be surface localized. The structure of BTA121 was solved by single-wavelength anomalous dispersion (SAD) using selenomethionine-derivative protein. The topology of BTA121 is unique with four helical domains organized into two helical bundles. Due to the sequence similarity of several genes on the megaplasmid, BTA121 can serve as a model for their tertiary structures. BTA121 has large interconnected tunnels and cavities that can accommodate ligands, notably long parallel helices, which have a large hydrophobic central pocket. Preliminary in-vitro studies suggest that BTA121 binds lipids, notably palmitate with a similar order of binding affinity as tablysin-15, a known palmitate-binding protein. The reported data will guide mechanistic studies to determine the role of BTA121 in the tick-mammalian transmission cycle of B. turicatae.

A data integration approach for cell cycle analysis oriented to model simulation in systems biology

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Mosca Ettore

2007-08-01

Full Text Available Abstract Background The cell cycle is one of the biological processes most frequently investigated in systems biology studies and it involves the knowledge of a large number of genes and networks of protein interactions. A deep knowledge of the molecular aspect of this biological process can contribute to making cancer research more accurate and innovative. In this context the mathematical modelling of the cell cycle has a relevant role to quantify the behaviour of each component of the systems. The mathematical modelling of a biological process such as the cell cycle allows a systemic description that helps to highlight some features such as emergent properties which could be hidden when the analysis is performed only from a reductionism point of view. Moreover, in modelling complex systems, a complete annotation of all the components is equally important to understand the interaction mechanism inside the network: for this reason data integration of the model components has high relevance in systems biology studies. Description In this work, we present a resource, the Cell Cycle Database, intended to support systems biology analysis on the Cell Cycle process, based on two organisms, yeast and mammalian. The database integrates information about genes and proteins involved in the cell cycle process, stores complete models of the interaction networks and allows the mathematical simulation over time of the quantitative behaviour of each component. To accomplish this task, we developed, a web interface for browsing information related to cell cycle genes, proteins and mathematical models. In this framework, we have implemented a pipeline which allows users to deal with the mathematical part of the models, in order to solve, using different variables, the ordinary differential equation systems that describe the biological process. Conclusion This integrated system is freely available in order to support systems biology research on the cell cycle and

Temporo-mandibular joint kinetics and chewing cycles in children. A 3-year follow-up.

Science.gov (United States)

Bodin, C; Lodetti, G; Marinone, M G

2002-01-01

To report the temporo-mandibular joint (TMJ) kinetics and masticatory function in healthy children. Temporo-mandibular joint palpation and electrognathographic registrations of chewing cycles were repeated for 3 years in order to evaluate changes. Healthy children without systemic pathologies, decayed cavities and previous dental treatment. Electrognathographic (EGN) registration of masticatory cycles and TMJ palpation were carried out on 52 patients (mean age: 5 years 8 months, range: 5 years 1 month, 6 years 8 months), by two university researchers, once a year for 3 consecutive years. TMJ palpation, differentiated TMJ synchronism (simultaneous bilateral opening movement) and TMJ asynchronism (not simultaneous bilateral opening movement), TMJ subluxation and click were observed. Electrognathographic registrations differentiated normal and abnormal jaw chewing cycles, and narrow and large cycles. Temporo-mandibular joint asynchronism was evident in 34 of 52 patients in the primary dentition, in 42 of 52 patients after the eruption of the first permanent molar, and in 31 of 52 patients after the eruption of the permanent incisors. TMJ subluxation increased during the full period of observation. Three temporomandibular clicks appeared after the eruption of the permanent incisors. Altered mastication was not always associated with TMJ disorders. In children, normal chewing cycles can coexist with occlusal discrepancies, cranio-facial growth and TMJ alterations.

Inverse problems in ordinary differential equations and applications

CERN Document Server

Llibre, Jaume

2016-01-01

This book is dedicated to study the inverse problem of ordinary differential equations, that is it focuses in finding all ordinary differential equations that satisfy a given set of properties. The Nambu bracket is the central tool in developing this approach. The authors start characterizing the ordinary differential equations in R^N which have a given set of partial integrals or first integrals. The results obtained are applied first to planar polynomial differential systems with a given set of such integrals, second to solve the 16th Hilbert problem restricted to generic algebraic limit cycles, third for solving the inverse problem for constrained Lagrangian and Hamiltonian mechanical systems, fourth for studying the integrability of a constrained rigid body. Finally the authors conclude with an analysis on nonholonomic mechanics, a generalization of the Hamiltonian principle, and the statement an solution of the inverse problem in vakonomic mechanics.

Altered cell cycle-related gene expression in brain and lymphocytes from a transgenic mouse model of Alzheimer's disease [amyloid precursor protein/presenilin 1 (PS1)].

Science.gov (United States)

Esteras, Noemí; Bartolomé, Fernando; Alquézar, Carolina; Antequera, Desireé; Muñoz, Úrsula; Carro, Eva; Martín-Requero, Ángeles

2012-09-01

Cumulative evidence indicates that aberrant re-expression of many cell cycle-related proteins and inappropriate neuronal cell cycle control are critical events in Alzheimer's disease (AD) pathogenesis. Evidence of cell cycle activation in post-mitotic neurons has also been observed in murine models of AD, despite the fact that most of these mice do not show massive loss of neuronal bodies. Dysfunction of the cell cycle appears to affect cells other than neurons, as peripheral cells, such as lymphocytes and fibroblasts from patients with AD, show an altered response to mitogenic stimulation. We sought to determine whether cell cycle disturbances are present simultaneously in both brain and peripheral cells from the amyloid precursor protein (APP)/presenilin 1 (PS1) mouse model of AD, in order to validate the use of peripheral cells from patients not only to study cell cycle abnormalities as a pathogenic feature of AD, but also as a means to test novel therapeutic approaches. By using cell cycle pathway-specific RT(2)Profiler™ PCR Arrays, we detected changes in a number of cell cycle-related genes in brain as well as in lymphocytes from APP/PS1 mice. Moreover, we found enhanced 5'-bromo-2'-deoxyuridine incorporation into DNA in lymphocytes from APP/PS1 mice, and increased expression of the cell proliferation marker proliferating cell nuclear antigen (PCNA), and the cyclin-dependent kinase (CDK) inhibitor Cdkn2a, as detected by immunohistochemistry in cortical neurons of the APP/PS1 mice. Taken together, the cell cycle-related changes in brain and blood cells reported here support the mitosis failure hypothesis in AD and validate the use of peripheral cells as surrogate tissue to study the molecular basis of AD pathogenesis. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Reproductive cycles in tropical intertidal gastropods are timed around tidal amplitude cycles.

Science.gov (United States)

Collin, Rachel; Kerr, Kecia; Contolini, Gina; Ochoa, Isis

2017-08-01

Reproduction in iteroparous marine organisms is often timed with abiotic cycles and may follow lunar, tidal amplitude, or daily cycles. Among intertidal marine invertebrates, decapods are well known to time larval release to coincide with large amplitude nighttime tides, which minimizes the risk of predation. Such bimonthly cycles have been reported for few other intertidal invertebrates. We documented the reproduction of 6 gastropod species from Panama to determine whether they demonstrate reproductive cycles, whether these cycles follow a 2-week cycle, and whether cycles are timed so that larval release occurs during large amplitude tides. Two of the species ( Crepidula cf. marginalis and Nerita scabricosta ) showed nonuniform reproduction, but without clear peaks in timing relative to tidal or lunar cycles. The other 4 species show clear peaks in reproduction occurring every 2 weeks. In 3 of these species ( Cerithideopsis carlifornica var. valida, Littoraria variegata , and Natica chemnitzi ), hatching occurred within 4 days of the maximum amplitude tides. Siphonaria palmata exhibit strong cycles, but reproduction occurred during the neap tides. Strong differences in the intensity of reproduction of Cerithideopsis carlifornica , and in particular, Littoraria variegata , between the larger and smaller spring tides of a lunar month indicate that these species time reproduction with the tidal amplitude cycle rather than the lunar cycle. For those species that reproduce during both the wet and dry seasons, we found that reproductive timing did not differ between seasons despite strong differences in temperature and precipitation. Overall, we found that most (4/6) species have strong reproductive cycles synchronized with the tidal amplitude cycle and that seasonal differences in abiotic factors do not alter these cycles.

Cell cycle-related genes as modifiers of age of onset of colorectal cancer in Lynch syndrome: a large-scale study in non-Hispanic white patients.

Science.gov (United States)

Chen, Jinyun; Pande, Mala; Huang, Yu-Jing; Wei, Chongjuan; Amos, Christopher I; Talseth-Palmer, Bente A; Meldrum, Cliff J; Chen, Wei V; Gorlov, Ivan P; Lynch, Patrick M; Scott, Rodney J; Frazier, Marsha L

2013-02-01

Heterogeneity in age of onset of colorectal cancer in individuals with mutations in DNA mismatch repair genes (Lynch syndrome) suggests the influence of other lifestyle and genetic modifiers. We hypothesized that genes regulating the cell cycle influence the observed heterogeneity as cell cycle-related genes respond to DNA damage by arresting the cell cycle to provide time for repair and induce transcription of genes that facilitate repair. We examined the association of 1456 single nucleotide polymorphisms (SNPs) in 128 cell cycle-related genes and 31 DNA repair-related genes in 485 non-Hispanic white participants with Lynch syndrome to determine whether there are SNPs associated with age of onset of colorectal cancer. Genotyping was performed on an Illumina GoldenGate platform, and data were analyzed using Kaplan-Meier survival analysis, Cox regression analysis and classification and regression tree (CART) methods. Ten SNPs were independently significant in a multivariable Cox proportional hazards regression model after correcting for multiple comparisons (P Lynch syndrome.

Cell cycle-dependent expression of Dub3, Nanog and the p160 family of nuclear receptor coactivators (NCoAs in mouse embryonic stem cells.

Directory of Open Access Journals (Sweden)

Siem van der Laan

Full Text Available Pluripotency of embryonic stem cells (ESC is tightly regulated by a network of transcription factors among which the estrogen-related receptor β (Esrrb. Esrrb contributes to the relaxation of the G1 to S-phase (G1/S checkpoint in mouse ESCs by transcriptional control of the deubiquitylase Dub3 gene, contributing to Cdc25A persistence after DNA damage. We show that in mESCs, Dub3 gene expression is cell cycle regulated and is maximal prior G1/S transition. In addition, following UV-induced DNA damage in G1, Dub3 expression markedly increases in S-phase also suggesting a role in checkpoint recovery. Unexpectedly, we also observed cell cycle-regulation of Nanog expression, and not Oct4, reaching high levels prior to G1/S transition, finely mirroring Cyclin E1 fluctuations. Curiously, while Esrrb showed only limited cell-cycle oscillations, transcript levels of the p160 family of nuclear receptor coactivators (NCoAs displayed strong cell cycle-dependent fluctuations. Since NCoAs function in concert with Esrrb in transcriptional activation, we focussed on NCoA1 whose levels specifically increase prior onset of Dub3 transcription. Using a reporter assay, we show that NCoA1 potentiates Esrrb-mediated transcription of Dub3 and we present evidence of protein interaction between the SRC1 splice variant NCoA1 and Esrrb. Finally, we show a differential developmental regulation of all members of the p160 family during neural conversion of mESCs. These findings suggest that in mouse ESCs, changes in the relative concentration of a coactivator at a given cell cycle phase, may contribute to modulation of the transcriptional activity of the core transcription factors of the pluripotent network and be implicated in cell fate decisions upon onset of differentiation.

Cell cycle-dependent expression of Dub3, Nanog and the p160 family of nuclear receptor coactivators (NCoAs) in mouse embryonic stem cells.

Science.gov (United States)

van der Laan, Siem; Golfetto, Eleonora; Vanacker, Jean-Marc; Maiorano, Domenico

2014-01-01

Pluripotency of embryonic stem cells (ESC) is tightly regulated by a network of transcription factors among which the estrogen-related receptor β (Esrrb). Esrrb contributes to the relaxation of the G1 to S-phase (G1/S) checkpoint in mouse ESCs by transcriptional control of the deubiquitylase Dub3 gene, contributing to Cdc25A persistence after DNA damage. We show that in mESCs, Dub3 gene expression is cell cycle regulated and is maximal prior G1/S transition. In addition, following UV-induced DNA damage in G1, Dub3 expression markedly increases in S-phase also suggesting a role in checkpoint recovery. Unexpectedly, we also observed cell cycle-regulation of Nanog expression, and not Oct4, reaching high levels prior to G1/S transition, finely mirroring Cyclin E1 fluctuations. Curiously, while Esrrb showed only limited cell-cycle oscillations, transcript levels of the p160 family of nuclear receptor coactivators (NCoAs) displayed strong cell cycle-dependent fluctuations. Since NCoAs function in concert with Esrrb in transcriptional activation, we focussed on NCoA1 whose levels specifically increase prior onset of Dub3 transcription. Using a reporter assay, we show that NCoA1 potentiates Esrrb-mediated transcription of Dub3 and we present evidence of protein interaction between the SRC1 splice variant NCoA1 and Esrrb. Finally, we show a differential developmental regulation of all members of the p160 family during neural conversion of mESCs. These findings suggest that in mouse ESCs, changes in the relative concentration of a coactivator at a given cell cycle phase, may contribute to modulation of the transcriptional activity of the core transcription factors of the pluripotent network and be implicated in cell fate decisions upon onset of differentiation.

Women's preferences for men's beards show no relation to their ovarian cycle phase and sex hormone levels.

Science.gov (United States)

Dixson, Barnaby J W; Lee, Anthony J; Blake, Khandis R; Jasienska, Grazyna; Marcinkowska, Urszula M

2018-01-01

According to the ovulatory shift hypothesis, women's mate preferences for male morphology indicative of competitive ability, social dominance, and/or underlying health are strongest at the peri-ovulatory phase of the menstrual cycle. However, recent meta-analyses are divided on the robustness of such effects and the validity of the often-used indirect estimates of fertility and ovulation has been called into question in methodological studies. In the current study, we test whether women's preferences for men's beardedness, a cue of male sexual maturity, androgenic development and social dominance, are stronger at the peri-ovulatory phase of the menstrual cycle compared to during the early follicular or the luteal phase. We also tested whether levels of estradiol, progesterone, and the estradiol to progesterone ratio at each phase were associated with facial hair preferences. Fifty-two heterosexual women completed a two-alternative forced choice preference test for clean-shaven and bearded male faces during the follicular, peri-ovulatory (validated by the surge in luteinizing hormone or the drop in estradiol levels) and luteal phases. Participants also provided for one entire menstrual cycle daily saliva samples for subsequent assaying of estradiol and progesterone. Results showed an overall preference for bearded over clean-shaven faces at each phase of the menstrual cycle. However, preferences for facial hair were not significantly different over the phases of menstrual cycle and were not significantly associated with levels of reproductive hormones. We conclude that women's preferences for men's beardedness may not be related to changes in their likelihood of conception. Copyright © 2017 Elsevier Inc. All rights reserved.

LIFE CYCLE OF INFORMATION SYSTEMS

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Y. S. Sennik

2015-01-01

Full Text Available This work is a generalization of the theoretical propositions related to the life cycle of information systems. There was given the definition of the life cycle, specify which items you should include every step of the cycle. Describes the methodology division of the life cycle on the main stage, including methodology Rational Unified Process. The description of the fundamental standards in this area. Special attention was paid to the work of the basic life cycle models. It was carried out their comparative characteristics. On the basis of the theoretical propositions, it was concluded that the preferred model of the life cycle for the corporate network is a spiral model and the use of international standards in the life cycle saves a lot of effort, time and material resources.

Radicicol, a heat shock protein 90 inhibitor, inhibits differentiation and adipogenesis in 3T3-L1 preadipocytes

Energy Technology Data Exchange (ETDEWEB)

He, Yonghan [Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Baojian Road, Harbin 150081 (China); Aquatic and Crop Resource Development, Life Sciences Branch, National Research Council Canada, Charlottetown, PE, Canada C1A 4P3 (Canada); State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223 (China); Li, Ying [Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Baojian Road, Harbin 150081 (China); Zhang, Shuocheng [Aquatic and Crop Resource Development, Life Sciences Branch, National Research Council Canada, Charlottetown, PE, Canada C1A 4P3 (Canada); Perry, Ben [Aquatic and Crop Resource Development, Life Sciences Branch, National Research Council Canada, Charlottetown, PE, Canada C1A 4P3 (Canada); Department of Biomedical Sciences, University of Prince Edward Island, 550 University Avenue, Charlottetown, PE, Canada C1A 4P3 (Canada); Zhao, Tiantian [Aquatic and Crop Resource Development, Life Sciences Branch, National Research Council Canada, Charlottetown, PE, Canada C1A 4P3 (Canada); Department of Psychology, University of Toronto, 1265 Military Trail, Toronto, ON, Canada M1C 1A4 (Canada); Wang, Yanwen, E-mail: yanwen.wang@nrc.ca [Aquatic and Crop Resource Development, Life Sciences Branch, National Research Council Canada, Charlottetown, PE, Canada C1A 4P3 (Canada); Department of Biomedical Sciences, University of Prince Edward Island, 550 University Avenue, Charlottetown, PE, Canada C1A 4P3 (Canada); Sun, Changhao, E-mail: sun2002changhao@yahoo.com [Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Baojian Road, Harbin 150081 (China)

2013-06-28

Highlights: •Radicicol suppressed intracellular fat accumulation in 3T3-L1 adipocytes. •Radicicol inhibited the expression of FAS and FABP4. •Radicicol blocked cell cycle at the G1-S phase during cell differentiation. •Radicicol inhibited the PDK1/Akt pathway in adipocyte differentiation. -- Abstract: Heat shock protein 90 (Hsp90) is involved in various cellular processes, such as cell proliferation, differentiation and apoptosis. As adipocyte differentiation plays a critical role in obesity development, the present study investigated the effect of an Hsp90 inhibitor radicicol on the differentiation of 3T3-L1 preadipocytes and potential mechanisms. The cells were treated with different concentrations of radicicol during the first 8 days of cell differentiation. Adipogenesis, the expression of adipogenic transcriptional factors, differentiation makers and cell cycle were determined. It was found that radicicol dose-dependently decreased intracellular fat accumulation through down-regulating the expression of peroxisome proliferator-activated receptor γ (PPAR{sub γ}) and CCAAT element binding protein α (C/EBP{sub α}), fatty acid synthase (FAS) and fatty acid-binding protein 4 (FABP4). Flow cytometry analysis revealed that radicicol blocked cell cycle at G1-S phase. Radicicol redcued the phosphorylation of Akt while showing no effect on β-catenin expression. Radicicol decreased the phosphorylation of phosphoinositide-dependent kinase 1 (PDK1). The results suggest that radicicol inhibited 3T3-L1 preadipocyte differentiation through affecting the PDK1/Akt pathway and subsequent inhibition of mitotic clonal expansion and the expression/activity of adipogenic transcriptional factors and their downstream adipogenic proteins.

Radicicol, a heat shock protein 90 inhibitor, inhibits differentiation and adipogenesis in 3T3-L1 preadipocytes

International Nuclear Information System (INIS)

He, Yonghan; Li, Ying; Zhang, Shuocheng; Perry, Ben; Zhao, Tiantian; Wang, Yanwen; Sun, Changhao

2013-01-01

Highlights: •Radicicol suppressed intracellular fat accumulation in 3T3-L1 adipocytes. •Radicicol inhibited the expression of FAS and FABP4. •Radicicol blocked cell cycle at the G1-S phase during cell differentiation. •Radicicol inhibited the PDK1/Akt pathway in adipocyte differentiation. -- Abstract: Heat shock protein 90 (Hsp90) is involved in various cellular processes, such as cell proliferation, differentiation and apoptosis. As adipocyte differentiation plays a critical role in obesity development, the present study investigated the effect of an Hsp90 inhibitor radicicol on the differentiation of 3T3-L1 preadipocytes and potential mechanisms. The cells were treated with different concentrations of radicicol during the first 8 days of cell differentiation. Adipogenesis, the expression of adipogenic transcriptional factors, differentiation makers and cell cycle were determined. It was found that radicicol dose-dependently decreased intracellular fat accumulation through down-regulating the expression of peroxisome proliferator-activated receptor γ (PPAR γ ) and CCAAT element binding protein α (C/EBP α ), fatty acid synthase (FAS) and fatty acid-binding protein 4 (FABP4). Flow cytometry analysis revealed that radicicol blocked cell cycle at G1-S phase. Radicicol redcued the phosphorylation of Akt while showing no effect on β-catenin expression. Radicicol decreased the phosphorylation of phosphoinositide-dependent kinase 1 (PDK1). The results suggest that radicicol inhibited 3T3-L1 preadipocyte differentiation through affecting the PDK1/Akt pathway and subsequent inhibition of mitotic clonal expansion and the expression/activity of adipogenic transcriptional factors and their downstream adipogenic proteins

Exact Solutions of a Fractional-Type Differential-Difference Equation Related to Discrete MKdV Equation

International Nuclear Information System (INIS)

Aslan İsmail

2014-01-01

The extended simplest equation method is used to solve exactly a new differential-difference equation of fractional-type, proposed by Narita [J. Math. Anal. Appl. 381 (2011) 963] quite recently, related to the discrete MKdV equation. It is shown that the model supports three types of exact solutions with arbitrary parameters: hyperbolic, trigonometric and rational, which have not been reported before. (general)

Social Life Cycle Assessment: An Introduction

DEFF Research Database (Denmark)

Moltesen, Andreas; Bonou, Alexandra; Wangel, Arne

2018-01-01

An expansion of the LCA framework has been going on through the development of ‘social life cycle assessment’—S-LCA. The methodology, still in its infancy, has the goal of assessing social impacts related to a product’s life cycle. This chapter introduces S-LCA framework area and the related...

Multivalued stochastic delay differential equations and related ...

African Journals Online (AJOL)

We study the existence and uniqueness of a solution for the multivalued stochastic differential equation with delay (the multivalued term is of subdifferential type):. dX(t) + aφ (X(t))dt ∍ b(t,X(t), Y(t), Z(t)) dt. ⎨ +σ (t, X (t), Y (t), Z (t)) dW (t), t ∈ (s, T). X(t) = ξ (t - s), t ∈ [s - δ, s]. Specify that in this case the coefficients at time t ...

Metabolic reprogramming during neuronal differentiation.

Science.gov (United States)

Agostini, M; Romeo, F; Inoue, S; Niklison-Chirou, M V; Elia, A J; Dinsdale, D; Morone, N; Knight, R A; Mak, T W; Melino, G

2016-09-01

Newly generated neurons pass through a series of well-defined developmental stages, which allow them to integrate into existing neuronal circuits. After exit from the cell cycle, postmitotic neurons undergo neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. Lack of a global metabolic analysis during early cortical neuronal development led us to explore the role of cellular metabolism and mitochondrial biology during ex vivo differentiation of primary cortical neurons. Unexpectedly, we observed a huge increase in mitochondrial biogenesis. Changes in mitochondrial mass, morphology and function were correlated with the upregulation of the master regulators of mitochondrial biogenesis, TFAM and PGC-1α. Concomitant with mitochondrial biogenesis, we observed an increase in glucose metabolism during neuronal differentiation, which was linked to an increase in glucose uptake and enhanced GLUT3 mRNA expression and platelet isoform of phosphofructokinase 1 (PFKp) protein expression. In addition, glutamate-glutamine metabolism was also increased during the differentiation of cortical neurons. We identified PI3K-Akt-mTOR signalling as a critical regulator role of energy metabolism in neurons. Selective pharmacological inhibition of these metabolic pathways indicate existence of metabolic checkpoint that need to be satisfied in order to allow neuronal differentiation.

Alteration of keratinocyte differentiation and senescence by the tumor promoter dioxin

International Nuclear Information System (INIS)

Ray, Soma S.; Swanson, Hollie I.

2003-01-01

Exposure to the environmental contaminant dioxin, elicits a variety of responses, which includes tumor promotion, embryotoxicity/teratogenesis, and carcinogenesis in both animals and humans. Many of the effects of dioxin are mediated by the aryl hydrocarbon receptor (AHR), a ligand-activated bHLH (basic helix-loop-helix)/PAS transcription factor. We initiated this study to determine whether dioxin's tumor-promoting activities may lie in its ability to alter proliferation, differentiation, and/or senescence using normal human epidermal keratinocytes (HEKs). Here, we report that dioxin appears to accelerate differentiation as measured by flow cytometry and by increased expression of the differentiation markers involucrin and filaggrin. In addition, dioxin appears to increase proliferation as indicated by an increase in NADH/NADPH production and changes in cell cycle. Finally, dioxin decreases SA (senescence associated) β-galactosidase staining, an indicator of senescence, in the differentiating keratinocytes. These changes were accompanied by decreases in the expression levels of key cell cycle regulatory proteins p53, p16 INK4a , and p14 ARF . Our findings support the idea that dioxin may exert its tumor-promoting actions, in part, by downregulating the expression levels of key tumor suppressor proteins, which may impair the cell's ability to maintain its appropriate cellular status

Comparative analysis of Goodwin's business cycle models

Science.gov (United States)

Antonova, A. O.; Reznik, S.; Todorov, M. D.

2016-10-01

We compare the behavior of solutions of Goodwin's business cycle equation in the form of neutral delay differential equation with fixed delay (NDDE model) and in the form of the differential equations of 3rd, 4th and 5th orders (ODE model's). Such ODE model's (Taylor series expansion of NDDE in powers of θ) are proposed in N. Dharmaraj and K. Vela Velupillai [6] for investigation of the short periodic sawthooth oscillations in NDDE. We show that the ODE's of 3rd, 4th and 5th order may approximate the asymptotic behavior of only main Goodwin's mode, but not the sawthooth modes. If the order of the Taylor series expansion exceeds 5, then the approximate ODE becomes unstable independently of time lag θ.

Differential Privacy for Relational Algebra: Improving the Sensitivity Bounds via Constraint Systems

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Catuscia Palamidessi

2012-07-01

Full Text Available Differential privacy is a modern approach in privacy-preserving data analysis to control the amount of information that can be inferred about an individual by querying a database. The most common techniques are based on the introduction of probabilistic noise, often defined as a Laplacian parametric on the sensitivity of the query. In order to maximize the utility of the query, it is crucial to estimate the sensitivity as precisely as possible. In this paper we consider relational algebra, the classical language for queries in relational databases, and we propose a method for computing a bound on the sensitivity of queries in an intuitive and compositional way. We use constraint-based techniques to accumulate the information on the possible values for attributes provided by the various components of the query, thus making it possible to compute tight bounds on the sensitivity.

Function of caspase-14 in trophoblast differentiation

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Charles Adrian K

2009-09-01

Full Text Available Abstract Background Within the human placenta, the cytotrophoblast consists of a proliferative pool of progenitor cells which differentiate to replenish the overlying continuous, multi-nucleated syncytiotrophoblast, which forms the barrier between the maternal and fetal tissues. Disruption to trophoblast differentiation and function may result in impaired fetal development and preeclampsia. Caspase-14 expression is limited to barrier forming tissues. It promotes keratinocyte differentiation by cleaving profilaggrin to stabilise keratin intermediate filaments, and indirectly providing hydration and UV protection. However its role in the trophoblast remains unexplored. Methods Using RNA Interference the reaction of control and differentiating trophoblastic BeWo cells to suppressed caspase-14 was examined for genes pertaining to hormonal, cell cycle and cytoskeletal pathways. Results Transcription of hCG, KLF4 and cytokeratin-18 were increased following caspase-14 suppression suggesting a role for caspase-14 in inhibiting their pathways. Furthermore, hCG, KLF4 and cytokeratin-18 protein levels were disrupted. Conclusion Since expression of these molecules is normally increased with trophoblast differentiation, our results imply that caspase-14 inhibits trophoblast differentiation. This is the first functional study of this unusual member of the caspase family in the trophoblast, where it has a different function than in the epidermis. This knowledge of the molecular underpinnings of trophoblast differentiation may instruct future therapies of trophoblast disease.

RIEGER-TYPE PERIODICITY DURING SOLAR CYCLES 14–24: ESTIMATION OF DYNAMO MAGNETIC FIELD STRENGTH IN THE SOLAR INTERIOR

Energy Technology Data Exchange (ETDEWEB)

Gurgenashvili, Eka; Zaqarashvili, Teimuraz V.; Kukhianidze, Vasil; Ramishvili, Giorgi; Shergelashvili, Bidzina [Abastumani Astrophysical Observatory at Ilia State University, Tbilisi, Georgia (United States); Oliver, Ramon; Ballester, Jose Luis [Departament de Física, Universitat de les Illes Balears, E-07122, Palma de Mallorca (Spain); Hanslmeier, Arnold [IGAM, Institute of Physics, University of Graz, Universitätsplatz 5, A-8010 Graz (Austria); Poedts, Stefaan, E-mail: teimuraz.zaqarashvili@uni-graz.at [Centre for Mathematical Plasma Astrophysics, Department of Mathematics, KU Leuven, Celestijnenlaan 200B, B-3001, Leuven (Belgium)

2016-07-20

Solar activity undergoes a variation over timescales of several months known as Rieger-type periodicity, which usually occurs near maxima of sunspot cycles. An early analysis showed that the periodicity appears only in some cycles and is absent in other cycles. But the appearance/absence during different cycles has not been explained. We performed a wavelet analysis of sunspot data from the Greenwich Royal Observatory and the Royal Observatory of Belgium during cycles 14–24. We found that the Rieger-type periods occur in all cycles, but they are cycle dependent: shorter periods occur during stronger cycles. Our analysis revealed a periodicity of 185–195 days during the weak cycles 14–15 and 24 and a periodicity of 155–165 days during the stronger cycles 16–23. We derived the dispersion relation of the spherical harmonics of the magnetic Rossby waves in the presence of differential rotation and a toroidal magnetic field in the dynamo layer near the base of the convection zone. This showed that the harmonics of fast Rossby waves with m = 1 and n = 4, where m ( n ) indicates the toroidal (poloidal) wavenumbers, perfectly fit with the observed periodicity. The variation of the toroidal field strength from weaker to stronger cycles may lead to the different periods found in those cycles, which explains the observed enigmatic feature of the Rieger-type periodicity. Finally, we used the observed periodicity to estimate the dynamo field strength during cycles 14–24. Our estimations suggest a field strength of ∼40 kG for the stronger cycles and ∼20 kG for the weaker cycles.

Muscle fascicle behavior during eccentric cycling and its relation to muscle soreness.

Science.gov (United States)

Peñailillo, Luis; Blazevich, Anthony J; Nosaka, Kazunori

2015-04-01

A single bout of eccentric exercise confers a protective effect against muscle damage and soreness in subsequent eccentric exercise bouts, but the mechanisms underpinning this effect are unclear. This study compared vastus lateralis (VL) muscle-tendon behavior between two eccentric cycling bouts to test the hypothesis that muscle-tendon behavior would be different between bouts and would be associated with the protective effect. Eleven untrained men (27.1 ± 7.0 yr) performed two bouts of eccentric cycling (ECC1 and ECC2) separated by 2 wk for 10 min at 65% of maximal concentric workload (191.9 ± 44.2 W) each. Muscle soreness (by visual analog scale) and maximal voluntary isometric contraction (MVC) torque of the knee extensors were assessed before and 1-2 d after exercise. Using ultrasonography, VL fascicle length and angle changes during cycling were assessed, and tendinous tissue (TT) length changes were estimated. VL EMG amplitude, crank torque, and knee joint angles were measured during cycling. Soreness was greater (P tendon behavior may be an important mechanism underpinning the protective effect.

Live-Birth Rate Associated With Repeat In Vitro Fertilization Treatment Cycles.

Science.gov (United States)

Smith, Andrew D A C; Tilling, Kate; Nelson, Scott M; Lawlor, Debbie A

were less than 4%. No age differential was observed among women using donor oocytes. Rates were lower for women with untreated male partner-related infertility compared with those with any other cause, but treatment with either intracytoplasmic sperm injection or sperm donation removed this difference. Among women in the United Kingdom undergoing IVF, the cumulative prognosis-adjusted live-birth rate after 6 cycles was 65.3%, with variations by age and treatment type. These findings support the efficacy of extending the number of IVF cycles beyond 3 or 4.

NATO Advanced Research Workshop on Approximation by Solutions of Partial Differential Equations, Quadrature Formulae, and Related Topics

CERN Document Server

Goldstein, M; Haussmann, W; Hayman, W; Rogge, L

1992-01-01

This volume consists of the proceedings of the NATO Advanced Research Workshop on Approximation by Solutions of Partial Differential Equations, Quadrature Formulae, and Related Topics, which was held at Hanstholm, Denmark. These proceedings include the main invited talks and contributed papers given during the workshop. The aim of these lectures was to present a selection of results of the latest research in the field. In addition to covering topics in approximation by solutions of partial differential equations and quadrature formulae, this volume is also concerned with related areas, such as Gaussian quadratures, the Pompelu problem, rational approximation to the Fresnel integral, boundary correspondence of univalent harmonic mappings, the application of the Hilbert transform in two dimensional aerodynamics, finely open sets in the limit set of a finitely generated Kleinian group, scattering theory, harmonic and maximal measures for rational functions and the solution of the classical Dirichlet problem. In ...

Timing of breast cancer surgery in relation to the menstrual cycle the rise and fall of a hypothesis

DEFF Research Database (Denmark)

Kroman, N.

2008-01-01

It has been claimed that the timing of surgery in relation to the menstrual cycle can significantly influence the prognosis among premenopausal women with primary breast cancer. The literature on the subject is reviewed. The results are heterogeneous, and the quality of the studies is in general...

Let7a involves in neural stem cell differentiation relating with TLX level

Energy Technology Data Exchange (ETDEWEB)

Song, Juhyun [Department of Anatomy, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cho, Kyoung Joo; Oh, Yumi [Department of Anatomy, Yonsei University College of Medicine, Seoul (Korea, Republic of); BK21 Plus Project for Medical Sciences, and Brain Research Institute, Yonsei University College of Medicine, Seoul (Korea, Republic of); Lee, Jong Eun, E-mail: jelee@yuhs.ac [Department of Anatomy, Yonsei University College of Medicine, Seoul (Korea, Republic of); BK21 Plus Project for Medical Sciences, and Brain Research Institute, Yonsei University College of Medicine, Seoul (Korea, Republic of)

2015-07-10

Neural stem cells (NSCs) have the potential for differentiation into neurons known as a groundbreaking therapeutic solution for central nervous system (CNS) diseases. To resolve the therapeutic efficiency of NSCs, recent researchers have focused on the study on microRNA's role in CNS. Some micro RNAs have been reported significant functions in NSC self-renewal and differentiation through the post-transcriptional regulation of neurogenesis genes. MicroRNA-Let7a (Let7a) has known as the regulator of diverse cellular mechanisms including cell differentiation and proliferation. In present study, we investigated whether Let7a regulates NSC differentiation by targeting the nuclear receptor TLX, which is an essential regulator of NSC self-renewal, proliferation and differentiation. We performed the following experiments: western blot analysis, TaqMan assay, RT-PCR, and immunocytochemistry to confirm the alteration of NSCs. Our data showed that let7a play important roles in controlling NSC fate determination. Thus, manipulating Let-7A and TLX could be a novel strategy to enhance the efficiency of NSC's neuronal differentiation for CNS disorders. - Highlights: • Let7a influences on NSC differentiation and proliferation. • Let7a involves in mainly NSC differentiation rather than proliferation. • Let7a positively regulates the TLX expression.

Let7a involves in neural stem cell differentiation relating with TLX level

International Nuclear Information System (INIS)

Song, Juhyun; Cho, Kyoung Joo; Oh, Yumi; Lee, Jong Eun

2015-01-01

Neural stem cells (NSCs) have the potential for differentiation into neurons known as a groundbreaking therapeutic solution for central nervous system (CNS) diseases. To resolve the therapeutic efficiency of NSCs, recent researchers have focused on the study on microRNA's role in CNS. Some micro RNAs have been reported significant functions in NSC self-renewal and differentiation through the post-transcriptional regulation of neurogenesis genes. MicroRNA-Let7a (Let7a) has known as the regulator of diverse cellular mechanisms including cell differentiation and proliferation. In present study, we investigated whether Let7a regulates NSC differentiation by targeting the nuclear receptor TLX, which is an essential regulator of NSC self-renewal, proliferation and differentiation. We performed the following experiments: western blot analysis, TaqMan assay, RT-PCR, and immunocytochemistry to confirm the alteration of NSCs. Our data showed that let7a play important roles in controlling NSC fate determination. Thus, manipulating Let-7A and TLX could be a novel strategy to enhance the efficiency of NSC's neuronal differentiation for CNS disorders. - Highlights: • Let7a influences on NSC differentiation and proliferation. • Let7a involves in mainly NSC differentiation rather than proliferation. • Let7a positively regulates the TLX expression

Selection of cDNAs differential fragments related to water stress in Ullucus tuberosus Loz. (Bassellaceae) «olluco»

OpenAIRE

Romero-Carpio, Mariela; Estrada-Jiménez, Rolando

2013-01-01

A partir de la expresión diferencial de ARNm de plántulas in vitro de dos accesiones de Ullucus tuberosus Loz. «olluco» altamente tolerantes a estrés osmótico, fueron seleccionados 31 fragmentos diferenciales de ADNc relacionados con tolerancia a sequía. Thirty-one differential fragments of cDNA related to drought tolerance have been selected from the mRNA differential expression of in vitro plantelets belonging to two accessions of Ullucus tuberosus Loz. «olluco» highly tolerant to osmoti...

Depth of dormancy in tomato (Lycopersicon esculentum Mill.) seeds is related to the progression of the cell cycle prior to the induction of dormancy

NARCIS (Netherlands)

Castro, de R.D.; Bino, R.J.; Jing, H.C.; Hilhorst, H.W.M.

2001-01-01

Cell cycle activities are initiated following imbibition of non-dormant seeds. However, it is not known whether cell cycle related events other than DNA replication also remain suppressed in imbibed dormant seeds. The objective of this study was to demonstrate that the transitions between the

Smooth functors vs. differential forms

NARCIS (Netherlands)

Schreiber, U.; Waldorf, K.

2011-01-01

We establish a relation between smooth 2-functors defined on the path 2-groupoid of a smooth manifold and differential forms on this manifold. This relation can be understood as a part of a dictionary between fundamental notions from category theory and differential geometry. We show that smooth

Tissue remodeling and nonendometrium-like menstrual cycling are hallmarks of peritoneal endometriosis lesions.

Science.gov (United States)

Sohler, Florian; Sommer, Anette; Wachter, David L; Agaimy, Abbas; Fischer, Oliver M; Renner, Stefan P; Burghaus, Stefanie; Fasching, Peter A; Beckmann, Matthias W; Fuhrmann, Ulrike; Strick, Reiner; Strissel, Pamela L

2013-01-01

We identified differentially expressed genes comparing peritoneal endometriosis lesions (n = 18), eutopic endometrium (n = 17), and peritoneum (n = 22) from the same patients with complete menstrual cycles using microarrays (54 675 probe sets) and immunohistochemistry. Peritoneal lesions and peritoneum demonstrated 3901 and 4973 significantly differentially expressed genes compared to eutopic endometrium, respectively. Peritoneal lesions significantly revealed no correlation with a specific menstrual cycle phase by gene expression and histopathology, exhibited low expressed proliferation genes, and constant levels of steroid hormone receptor genes. Tissue remodeling genes in cytoskeleton, smooth muscle contraction, cellular adhesion, tight junctions, and O-glycan biosynthesis were the most significant to lesions, including desmin and smooth muscle myosin heavy chain 11. Protein expression and location of desmin, alpha-actin, and h-caldesmon in peritoneal lesions discriminated between smooth muscle hyperplasia and metaplasia. Peritoneal lesions demonstrate no menstrual cycle phasing but constant steroid hormone receptor expression where a slow but steady growth is linked with tissue remodeling. Our study contributes to the molecular pathology of peritoneal endometriosis and will help to identify clinical targets for treatment and management.

Comprehensive Mass Cytometry Analysis of Cell Cycle, Activation, and Coinhibitory Receptors Expression in CD4 T Cells from Healthy and HIV-Infected Individuals.

Science.gov (United States)

Corneau, Aurélien; Cosma, Antonio; Even, Sophie; Katlama, Christine; Le Grand, Roger; Frachet, Véronique; Blanc, Catherine; Autran, Brigitte

2017-01-01

Mass cytometry allows large multiplex analysis of cell cycle stages together with differentiation, activation, and exhaustion markers, allowing further assessment of the quiescence status of resting CD4 T cells. Peripheral blood CD4 T lymphocytes from 8 individuals, 4 healthy donors, and 4 HIV-infected on antiretroviral treatment (T) were stained with the same 26 monoclonal antibodies and dyes targeting surface and intracellular markers of differentiation, activation, exhaustion, and cell cycle stages. Samples were run on a CYTOF-2. Patterns of naïve [TN] CD4 T cells strongly differed from all other memory subsets central-memory (CM), transitional-memory (TM), effector-memory (EM), and terminally differentiated RA-expressing (TEMRA) subsets, while stem-cell memory (SCM) and T follicular-helper cells (TfH) were close to CM and TM cells with the highest percentages in cell cycle. EM and TEMRA were the most altered by HIV infection, with an increased frequency of activated and cycling cells. Activation markers and coinhibitory receptor expression differed among cell cycle stages, with HLA-DR fitting better than CD25 or CD38 with cycle, and opposite PD-1 gradients along differentiation and cell cycle. "Resting" DR-CD25- CD4+ T cells contained similar amounts of cells in G1 than the activated DR ± CD25± ones but three fold lower cells in S-G2-M. This broad multiplex mass cytometry analysis demonstrates some subsets of the so-called "resting" CD25-DR- CD4+ T cells contain noticeable amounts of cells into cycle or expressing coinhibitory receptors, opening new avenues for a redefinition of resting peripheral blood CD4 T cells harboring the HIV reservoirs. © 2016 International Clinical Cytometry Society. © 2016 International Clinical Cytometry Society.

Life Cycle Assessment for Biofuels

Science.gov (United States)

A presentation based on life cycle assessment (LCA) for biofuels is given. The presentation focuses on energy and biofuels, interesting environmental aspects of biofuels, and how to do a life cycle assessment with some examples related to biofuel systems. The stages of a (biofuel...

Proteomic analysis of osteogenic differentiation of dental follicle precursor cells

DEFF Research Database (Denmark)

Morsczeck, Christian; Petersen, Jørgen; Völlner, Florian

2009-01-01

of differentiation. In the present study we applied 2-DE combined with capillary-LC-MS/MS analysis to profile differentially regulated proteins upon differentiation of dental follicle precursor cells (DFPCs). Out of 115 differentially regulated proteins, glutamine synthetase, lysosomal proteinase cathepsin B....... The bioinformatic analyses suggest that proteins associated with cell cycle progression and protein metabolism were down-regulated and proteins involved in catabolism, cell motility and biological quality were up-regulated. These results display the general physiological state of DFPCs before and after osteogenic...... proteins, plastin 3 T-isoform, beta-actin, superoxide dismutases, and transgelin were found to be highly up-regulated, whereas cofilin-1, pro-alpha 1 collagen, destrin, prolyl 4-hydrolase and dihydrolipoamide dehydrogenase were found to be highly down-regulated. The group of up-regulated proteins...

Menstrual cycle mediates vastus medialis and vastus medialis oblique muscle activity.

Science.gov (United States)

Tenan, Matthew S; Peng, Yi-Ling; Hackney, Anthony C; Griffin, Lisa

2013-11-01

Sports medicine professionals commonly describe two functionally different units of the vastus medialis (VM), the VM, and the vastus medialis oblique (VMO), but the anatomical support is equivocal. The functional difference of the VMO is principle to rehabilitation programs designed to alleviate anterior knee pain, a pathology that is known to have a greater occurrence in women. The purpose of this study was to determine whether the motor units of the VM and VMO are differentially recruited and if this recruitment pattern has an effect of sex or menstrual cycle phase. Single motor unit recordings from the VM and VMO were obtained for men and women during an isometric ramp knee extension. Eleven men were tested once. Seven women were tested during five different phases of the menstrual cycle, determined by basal body temperature mapping. The recruitment threshold and the initial firing rate at recruitment were determined from 510 motor unit recordings. The initial firing rate was lower in the VMO than that in the VM in women (P recruitment thresholds for the VM and VMO in either sex or across the menstrual cycle. There was a main effect of menstrual phase on initial firing rate, showing increases from the early follicular to late luteal phase (P = 0.003). The initial firing rate in the VMO was lower than that in the VM during ovulatory (P = 0.009) and midluteal (P = 0.009) phases. The relative control of the VM and VMO changes across the menstrual cycle. This could influence patellar pathologies that have a higher incidence in women.

Regulation of the demographic structure in isomorphic biphasic life cycles at the spatial fine scale.

Directory of Open Access Journals (Sweden)

Vasco Manuel Nobre de Carvalho da Silva Vieira

Full Text Available Isomorphic biphasic algal life cycles often occur in the environment at ploidy abundance ratios (Haploid:Diploid different from 1. Its spatial variability occurs within populations related to intertidal height and hydrodynamic stress, possibly reflecting the niche partitioning driven by their diverging adaptation to the environment argued necessary for their prevalence (evolutionary stability. Demographic models based in matrix algebra were developed to investigate which vital rates may efficiently generate an H:D variability at a fine spatial resolution. It was also taken into account time variation and type of life strategy. Ploidy dissimilarities in fecundity rates set an H:D spatial structure miss-fitting the ploidy fitness ratio. The same happened with ploidy dissimilarities in ramet growth whenever reproductive output dominated the population demography. Only through ploidy dissimilarities in looping rates (stasis, breakage and clonal growth did the life cycle respond to a spatially heterogeneous environment efficiently creating a niche partition. Marginal locations were more sensitive than central locations. Related results have been obtained experimentally and numerically for widely different life cycles from the plant and animal kingdoms. Spore dispersal smoothed the effects of ploidy dissimilarities in fertility and enhanced the effects of ploidy dissimilarities looping rates. Ploidy dissimilarities in spore dispersal could also create the necessary niche partition, both over the space and time dimensions, even in spatial homogeneous environments and without the need for conditional differentiation of the ramets. Fine scale spatial variability may be the key for the prevalence of isomorphic biphasic life cycles, which has been neglected so far.

Estimates of relative areas for the disposal in bedded salt of LWR wastes from alternative fuel cycles

International Nuclear Information System (INIS)

Lincoln, R.C.; Larson, D.W.; Sisson, C.E.

1978-01-01

The relative mine-level areas (land use requirements) which would be required for the disposal of light-water reactor (LWR) radioactive wastes in a hypothetical bedded-salt formation have been estimated. Five waste types from alternative fuel cycles have been considered. The relative thermal response of each of five different site conditions to each waste type has been determined. The fuel cycles considered are the once-through (no recycle), the uranium-only recycle, and the uranium and plutonium recycle. The waste types which were considered include (1) unreprocessed spent reactor fuel, (2) solidified waste derived from reprocessing uranium oxide fuel, (3) plutonium recovered from reprocessing spent reactor fuel and doped with 1.5% of the accompanying waste from reprocessing uranium oxide fuel, (4) waste derived from reprocessing mixed uranium/plutonium oxide fuel in the third recycle, and (5) unreprocessed spent fuel after three recycles of mixed uranium/plutonium oxide fuels. The relative waste-disposal areas were determined from a calculated value of maximum thermal energy (MTE) content of the geologic formations. Results are presented for each geologic site condition in terms of area ratios. Disposal area requirements for each waste type are expressed as ratios relative to the smallest area requirement (for waste type No. 2 above). For the reference geologic site condition, the estimated mine-level disposal area ratios are 4.9 for waste type No. 1, 4.3 for No. 3, 2.6 for No. 4, and 11 for No. 5

Local p-Adic Differential Equations

NARCIS (Netherlands)

Put, Marius van der; Taelman, Lenny

2006-01-01

This paper studies divergence in solutions of p-adic linear local differential equations. Such divergence is related to the notion of p-adic Liouville numbers. Also, the influence of the divergence on the differential Galois groups of such differential equations is explored. A complete result is

Relative estimates of TCA cycle pool size from 14CO2 production profiles

International Nuclear Information System (INIS)

Kelleher, J.K.; Cesta, M.L.; Holleran, A.L.

1986-01-01

In metabolic and isotopic steady state, the rate of 14 CO 2 production by TCA cycle intermediates labeled at different positions is linear. However, before the system reaches isotopic steady state, the rate of 14 CO 2 production is non-linear. The x-intercept extrapolated from the linear phase indicates the turnover rate of all metabolic pools the tracer must pass through. By exposing identical systems to 14 C succinate labeled in different positions, the contribution of TCA cycle pools to the non-linear phase may be considered. Specifically, the extrapolated x-intercept for [2,3 14 C] succinate will be greater than the x-intercept for [1,4 14 C] succinate if the TCA cycle pools are a contributing factor to the non-linear phase. The authors have used this method to analyze pyruvate oxidation in AS 30D hepatoma cells. They found that the extrapolated x-intercepts for the two tracers were identical. This indicates that the non-linear phase resulted from equilibration of the tracer with pools prior to entering the TCA cycle, i.e. lactate. Using this technique, it may be possible to estimate the variations in TCA cycle pool sizes in vivo

Bifurcation theory for finitely smooth planar autonomous differential systems

Science.gov (United States)

Han, Maoan; Sheng, Lijuan; Zhang, Xiang

2018-03-01

In this paper we establish bifurcation theory of limit cycles for planar Ck smooth autonomous differential systems, with k ∈ N. The key point is to study the smoothness of bifurcation functions which are basic and important tool on the study of Hopf bifurcation at a fine focus or a center, and of Poincaré bifurcation in a period annulus. We especially study the smoothness of the first order Melnikov function in degenerate Hopf bifurcation at an elementary center. As we know, the smoothness problem was solved for analytic and C∞ differential systems, but it was not tackled for finitely smooth differential systems. Here, we present their optimal regularity of these bifurcation functions and their asymptotic expressions in the finite smooth case.

Experimental investigation of air relative humidity (RH) cycling tests on MEA/cell aging in PEMFC. Pt. I. Study of high RH cycling test with air RH at 62%/100%

Energy Technology Data Exchange (ETDEWEB)

Huang, B.T.; Chatillon, Y.; Bonnet, C.; Lapicque, F. [Laboratoire Reactions et Genie des Procedes, CNRS-Nancy University, Nancy (France); Leclerc, S. [Laboratoire d' Energetique et de Mecanique Theorique et Appliquee, CNRS-Nancy University, Vandoeuvre-les-Nancy (France); Hinaje, M.; Rael, S. [Groupe de Recherche en Electrotechnique et Electronique de Nancy, CNRS-Nancy University, Vandoeuvre-les-Nancy (France)

2012-06-15

The effect of high air relative humidity (RH) cycling (RH{sub C} 62%/100%) on the degradation mechanisms of a single (5 x 5 cm{sup 2}) proton exchange membrane fuel cells was investigated. The cell performance was compared to a cell operated at constant humidification (RH{sub C} = 62%). Runs were conducted over approximately 1,500 h at 0.3 A cm{sup -2}. The overall loss in cell performance for the high RH cycling test was 12 {mu}V h{sup -1} whereas it was at 3 {mu}V h{sup -1} under constant humidification. Impedance spectroscopy reveals that the ohmic and charge transfer resistances were little modified in both runs. H{sub 2} crossover measurement indicated that both high RH cycling and constant RH test did not promote serious effect on gas permeability. The electroactive surface loss for anode and cathode during high air RH cycling was more significant than at constant RH operation. The water uptake determined by {sup 1}H nuclear magnetic resonance within the membrane electrode assembly (MEA) after high RH cycling was reduced by 12% in comparison with a fresh MEA. Transmission electron microscopy showed bubbles and pinholes formation in the membrane, catalyst particles agglomeration (also observed by X-ray diffraction), catalyst particles migration in the membrane and thickness reduction of the catalytic layers. Scanning electron microscopy was conducted to observe the changes in morphology of gas diffusion layers after the runs. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

RNA-Seq analysis validates the use of culture-derived Trypanosoma brucei and provides new markers for mammalian and insect life-cycle stages.

Science.gov (United States)

Naguleswaran, Arunasalam; Doiron, Nicholas; Roditi, Isabel

2018-04-02

Trypanosoma brucei brucei, the parasite causing Nagana in domestic animals, is closely related to the parasites causing sleeping sickness, but does not infect humans. In addition to its importance as a pathogen, the relative ease of genetic manipulation and an innate capacity for RNAi extend its use as a model organism in cell and infection biology. During its development in its mammalian and insect (tsetse fly) hosts, T. b. brucei passes through several different life-cycle stages. There are currently four life-cycle stages that can be cultured: slender forms and stumpy forms, which are equivalent to forms found in the mammal, and early and late procyclic forms, which are equivalent to forms in the tsetse midgut. Early procyclic forms show coordinated group movement (social motility) on semi-solid surfaces, whereas late procyclic forms do not. RNA-Seq was performed on biological replicates of each life-cycle stage. These constitute the first datasets for culture-derived slender and stumpy bloodstream forms and early and late procyclic forms. Expression profiles confirmed that genes known to be stage-regulated in the animal and insect hosts were also regulated in culture. Sequence reads of 100-125 bases provided sufficient precision to uncover differential expression of closely related genes. More than 100 transcripts showed peak expression in stumpy forms, including adenylate cyclases and several components of inositol metabolism. Early and late procyclic forms showed differential expression of 73 transcripts, a number of which encoded proteins that were previously shown to be stage-regulated. Moreover, two adenylate cyclases previously shown to reduce social motility are up-regulated in late procyclic forms. This study validates the use of cultured bloodstream forms as alternatives to animal-derived parasites and yields new markers for all four stages. In addition to underpinning recent findings that early and late procyclic forms are distinct life-cycle stages

Yeast three-hybrid screen identifies TgBRADIN/GRA24 as a negative regulator of Toxoplasma gondii bradyzoite differentiation.

Directory of Open Access Journals (Sweden)

Anahi V Odell

Full Text Available Differentiation of the protozoan parasite Toxoplasma gondii into its latent bradyzoite stage is a key event in the parasite's life cycle. Compound 2 is an imidazopyridine that was previously shown to inhibit the parasite lytic cycle, in part through inhibition of parasite cGMP-dependent protein kinase. We show here that Compound 2 can also enhance parasite differentiation, and we use yeast three-hybrid analysis to identify TgBRADIN/GRA24 as a parasite protein that interacts directly or indirectly with the compound. Disruption of the TgBRADIN/GRA24 gene leads to enhanced differentiation of the parasite, and the TgBRADIN/GRA24 knockout parasites show decreased susceptibility to the differentiation-enhancing effects of Compound 2. This study represents the first use of yeast three-hybrid analysis to study small-molecule mechanism of action in any pathogenic microorganism, and it identifies a previously unrecognized inhibitor of differentiation in T. gondii. A better understanding of the proteins and mechanisms regulating T. gondii differentiation will enable new approaches to preventing the establishment of chronic infection in this important human pathogen.

Credit cycles and macro fundamentals

NARCIS (Netherlands)

Koopman, S.J.; Kraeussl, R.G.W.; Lucas, A.; Monteiro, A.

2009-01-01

We use an intensity-based framework to study the relation between macroeconomic fundamentals and cycles in defaults and rating activity. Using Standard and Poor's U.S. corporate rating transition and default data over the period 1980-2005, we directly estimate the default and rating cycle from micro

Limit Cycles in Predator-Prey Models

OpenAIRE

Puchuri Medina, Liliana

2017-01-01

The classic Lotka-Volterra model belongs to a family of differential equations known as “Generalized Lotka-Volterra”, which is part of a classification of four models of quadratic fields with center. These models have been studied to address the Hilbert infinitesimal problem, which consists in determine the number of limit cycles of a perturbed hamiltonian system with center. In this work, we first present an alternative proof of the existence of centers in Lotka-Volterra predator-prey models...

Internal cycle modeling and environmental assessment of multiple cycle consumer products

International Nuclear Information System (INIS)

Tsiliyannis, C.A.

2012-01-01

Highlights: ► Dynamic flow models are presented for remanufactured, reused or recycled products. ► Early loss and stochastic return are included for fast and slow cycling products. ► The reuse-to-input flow ratio (Internal Cycle Factor, ICF) is determined. ► The cycle rate, which is increasing with the ICF, monitors eco-performance. ► Early internal cycle losses diminish the ICF, the cycle rate and performance. - Abstract: Dynamic annual flow models incorporating consumer discard and usage loss and featuring deterministic and stochastic end-of-cycle (EOC) return by the consumer are developed for reused or remanufactured products (multiple cycle products, MCPs), including fast and slow cycling, short and long-lived products. It is shown that internal flows (reuse and overall consumption) increase proportionally to the dimensionless internal cycle factor (ICF) which is related to environmental impact reduction factors. The combined reuse/recycle (or cycle) rate is shown capable for shortcut, albeit effective, monitoring of environmental performance in terms of waste production, virgin material extraction and manufacturing impacts of all MCPs, a task, which physical variables (lifetime, cycling frequency, mean or total number of return trips) and conventional rates, via which environmental policy has been officially implemented (e.g. recycling rate) cannot accomplish. The cycle rate is shown to be an increasing (hyperbolic) function of ICF. The impact of the stochastic EOC return characteristics on total reuse and consumption flows, as well as on eco-performance, is assessed: symmetric EOC return has a small, positive effect on performance compared to deterministic, while early shifted EOC return is more beneficial. In order to be efficient, environmental policy should set higher minimum reuse targets for higher trippage MCPs. The results may serve for monitoring, flow accounting and comparative eco-assessment of MCPs. They may be useful in identifying

Differential item functioning (DIF) analyses of health-related quality of life instruments using logistic regression

DEFF Research Database (Denmark)

Scott, Neil W; Fayers, Peter M; Aaronson, Neil K

2010-01-01

Differential item functioning (DIF) methods can be used to determine whether different subgroups respond differently to particular items within a health-related quality of life (HRQoL) subscale, after allowing for overall subgroup differences in that scale. This article reviews issues that arise ...... when testing for DIF in HRQoL instruments. We focus on logistic regression methods, which are often used because of their efficiency, simplicity and ease of application....

Solar cycle distribution of strong solar proton events and the related solar-terrestrial phenomena

Science.gov (United States)

Le, Guiming; Yang, Xingxing; Ding, Liuguang; Liu, Yonghua; Lu, Yangping; Chen, Minhao

2014-08-01

We investigated the solar cycle distribution of strong solar proton events (SPEs, peak flux ≥1000 pfu) and the solar-terrestrial phenomena associated with the strong SPEs during solar cycles 21-23. The results show that 37 strong SPEs were registered over this period of time, where 20 strong SPEs were originated from the super active regions (SARs) and 28 strong SPEs were accompanied by the X-class flares. Most strong SPEs were not associated with the ground level enhancement (GLE) event. Most strong SPEs occurred in the descending phases of the solar cycles. The weaker the solar cycle, the higher the proportion of strong SPES occurred in the descending phase of the cycle. The number of the strong SPEs that occurred within a solar cycle is poorly associated with the solar cycle size. The intensity of the SPEs is highly dependent of the location of their source regions, with the super SPEs (≥20000 pfu) distributed around solar disk center. A super SPE was always accompanied by a fast shock driven by the associated coronal mass ejection and a great geomagnetic storm. The source location of strongest GLE event is distributed in the well-connected region. The SPEs associated with super GLE events (peak increase rate ≥100%) which have their peak flux much lower than 10000 pfu were not accompanied by an intense geomagnetic storm.

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

Science.gov (United States)

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

2013-03-01

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

Thermodynamic cycles of adsorption desalination system

International Nuclear Information System (INIS)

Wu, Jun W.; Hu, Eric J.; Biggs, Mark J.

2012-01-01

Highlights: ► Thermodynamic cycles of adsorption desalination (AD) system have been identified all possible evaporator temperature scenarios. ► Temperature of evaporator determines the cycle. ► Higher evaporator temperature leads to higher water production if no cooling is required. -- Abstract: The potential to use waste heat to co-generate cooling and fresh water from saline water using adsorption on silica is attracting increasing attention. A variety of different thermodynamic cycles of such an adsorption desalination (AD) system arise as the temperature of the saline water evaporator is varied relative to temperature of the water used to cool the adsorbent as it adsorbs the evaporated water. In this paper, all these possible thermodynamic cycles are enumerated and analysed to determine their relative performances in terms of specific energy consumption and fresh water productivity.

MAGNETIC CYCLES IN A DYNAMO SIMULATION OF FULLY CONVECTIVE M-STAR PROXIMA CENTAURI

Energy Technology Data Exchange (ETDEWEB)

Yadav, Rakesh K.; Wolk, Scott J. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Christensen, Ulrich R. [Max-Planck-Institut für Sonnensystemforschung, Justus-von-Liebig-Weg 3, D-37077 Göttingen (Germany); Poppenhaeger, Katja, E-mail: rakesh.yadav@cfa.harvard.edu [Astrophysics Research Center, Queen’s University Belfast, Belfast BT7 1NN (United Kingdom)

2016-12-20

The recent discovery of an Earth-like exoplanet around Proxima Centauri has shined a spot light on slowly rotating fully convective M-stars. When such stars rotate rapidly (period ≲20 days), they are known to generate very high levels of activity that is powered by a magnetic field much stronger than the solar magnetic field. Recent theoretical efforts are beginning to understand the dynamo process that generates such strong magnetic fields. However, the observational and theoretical landscape remains relatively uncharted for fully convective M-stars that rotate slowly. Here, we present an anelastic dynamo simulation designed to mimic some of the physical characteristics of Proxima Centauri, a representative case for slowly rotating fully convective M-stars. The rotating convection spontaneously generates differential rotation in the convection zone that drives coherent magnetic cycles where the axisymmetric magnetic field repeatedly changes polarity at all latitudes as time progress. The typical length of the “activity” cycle in the simulation is about nine years, in good agreement with the recently proposed activity cycle length of about seven years for Proxima Centauri. Comparing our results with earlier work, we hypothesis that the dynamo mechanism undergoes a fundamental change in nature as fully convective stars spin down with age.

Real-world experience of women using extended-cycle vs monthly-cycle combined oral contraception in the United States: the National Health and Wellness Survey.

Science.gov (United States)

Nappi, Rossella E; Lete, Iñaki; Lee, Lulu K; Flores, Natalia M; Micheletti, Marie-Christine; Tang, Boxiong

2018-01-18

The real-world experience of women receiving extended-cycle combined oral contraception (COC) versus monthly-cycle COC has not been reported. Data were from the United States 2013 National Health and Wellness Survey. Eligible women (18-50 years old, premenopausal, without hysterectomy) currently using extended-cycle COC (3 months between periods) were compared with women using monthly-cycle COC. Treatment satisfaction (1 "extremely dissatisfied" to 7 "extremely satisfied"), adherence (8-item Morisky Medication Adherence Scale © ), menstrual cycle-related symptoms, health-related quality of life (HRQOL) and health state utilities (Medical Outcomes Short Form Survey-36v2®), depression (9-item Patient Health Questionnaire), sleep difficulties, Work Productivity and Activity Impairment-General Health, and healthcare resource use were assessed using one-way analyses of variance, chi-square tests, and generalized linear models (adjusted for covariates). Participants included 260 (6.7%) women using extended-cycle and 3616 (93.3%) using monthly-cycle COC. Women using extended-cycle COC reported significantly higher treatment satisfaction (P = 0.001) and adherence (P = 0.04) and reduced heavy menstrual bleeding (P = 0.029). A non-significant tendency toward reduced menstrual pain (39.5% versus 47.3%) and menstrual cycle-related symptoms (40.0% versus 48.7%) was found in women using extended-cycle versus monthly-cycle COC. Significantly more women using extended-cycle COC reported health-related diagnoses, indicating preferential prescription for extended-cycle COC among women reporting more health problems. Consistent with this poorer health, more women using extended-cycle COC reported fatigue, headache, and activity impairment (P values cycle COC as a valuable treatment option with high satisfaction, high adherence, and reduced heavy menstrual bleeding.

Evolution of high duty cycle echolocation in bats

DEFF Research Database (Denmark)

Fenton, M. B.; Faure, P. A.; Ratcliffe, J. M.

2012-01-01

Duty cycle describes the relative 'on time' of a periodic signal. In bats, we argue that high duty cycle (HDC) echolocation was selected for and evolved from low duty cycle (LDC) echolocation because increasing call duty cycle enhanced the ability of echolocating bats to detect, lock onto and track...... relative to background objects and their prey. HDC echolocators are particularly sensitive to amplitude and frequency glints generated by the wings of fluttering insects. We hypothesize that narrowband/CF calls produced at high duty cycle, and combined with neurobiological specializations for processing....... In contrast, bats using HDC echolocation emit long duration, narrowband calls dominated by a single constant frequency (CF) separated by relatively short periods of silence. HDC bats separate pulse and echo in frequency by exploiting information contained in Doppler-shifted echoes arising from their movements...

Menstrual cycle pattern and fertility

DEFF Research Database (Denmark)

Kolstad, Henrik A.; Bonde, Jens Peter; Hjøllund, Niels Henrik

1999-01-01

OBJECTIVE: To characterize how the menstrual cycle pattern relates to fertility regardless of potential biases caused by inappropriate coital timing during the menstrual cycle or early embryonal loss. DESIGN: Prospective follow-up study. SETTING: Healthy couples recruited throughout Denmark....... PATIENT(S): Two hundred ninety-five couples who were planning their first pregnancy were followed up from the discontinuation of birth control until a pregnancy was recognized within six menstrual cycles. Early embryonal losses were detected by changes in urinary hCG levels. INTERVENTION(S): None. MAIN...... OUTCOME MEASURE(S): The probability of pregnancy occurring within one menstrual cycle (fecundity). RESULT(S): In women who had a cycle length that differed by >10 days from the usual cycle length, fecundity was approximately 25% that of women who had no variation (odds ratio 0.25, 95% confidence interval...

A delay differential equation model of follicle waves in women.

Science.gov (United States)

Panza, Nicole M; Wright, Andrew A; Selgrade, James F

2016-01-01

This article presents a mathematical model for hormonal regulation of the menstrual cycle which predicts the occurrence of follicle waves in normally cycling women. Several follicles of ovulatory size that develop sequentially during one menstrual cycle are referred to as follicle waves. The model consists of 13 nonlinear, delay differential equations with 51 parameters. Model simulations exhibit a unique stable periodic cycle and this menstrual cycle accurately approximates blood levels of ovarian and pituitary hormones found in the biological literature. Numerical experiments illustrate that the number of follicle waves corresponds to the number of rises in pituitary follicle stimulating hormone. Modifications of the model equations result in simulations which predict the possibility of two ovulations at different times during the same menstrual cycle and, hence, the occurrence of dizygotic twins via a phenomenon referred to as superfecundation. Sensitive parameters are identified and bifurcations in model behaviour with respect to parameter changes are discussed. Studying follicle waves may be helpful for improving female fertility and for understanding some aspects of female reproductive ageing.

The retinoblastoma-histone deacetylase 3 complex inhibits PPARgamma and adipocyte differentiation

DEFF Research Database (Denmark)

Fajas, Lluis; Egler, Viviane; Reiter, Raphael

2002-01-01

The retinoblastoma protein (RB) has previously been shown to facilitate adipocyte differentiation by inducing cell cycle arrest and enhancing the transactivation by the adipogenic CCAAT/enhancer binding proteins (C/EBP). We show here that the peroxisome proliferator-activated receptor gamma...

Intrinsic and extrinsic mechanical properties related to the differentiation of mesenchymal stem cells.

Science.gov (United States)

Lee, Jin-Ho; Park, Hun-Kuk; Kim, Kyung Sook

2016-05-06

Diverse intrinsic and extrinsic mechanical factors have a strong influence on the regulation of stem cell fate. In this work, we examined recent literature on the effects of mechanical environments on stem cells, especially on differentiation of mesenchymal stem cells (MSCs). We provide a brief review of intrinsic mechanical properties of single MSC and examined the correlation between the intrinsic mechanical property of MSC and the differentiation ability. The effects of extrinsic mechanical factors relevant to the differentiation of MSCs were considered separately. The effect of nanostructure and elasticity of the matrix on the differentiation of MSCs were summarized. Finally, we consider how the extrinsic mechanical properties transfer to MSCs and then how the effects on the intrinsic mechanical properties affect stem cell differentiation. Copyright © 2015 Elsevier Inc. All rights reserved.

Advanced Fuel Cycle Economic Sensitivity Analysis

Energy Technology Data Exchange (ETDEWEB)

David Shropshire; Kent Williams; J.D. Smith; Brent Boore

2006-12-01

A fuel cycle economic analysis was performed on four fuel cycles to provide a baseline for initial cost comparison using the Gen IV Economic Modeling Work Group G4 ECON spreadsheet model, Decision Programming Language software, the 2006 Advanced Fuel Cycle Cost Basis report, industry cost data, international papers, the nuclear power related cost study from MIT, Harvard, and the University of Chicago. The analysis developed and compared the fuel cycle cost component of the total cost of energy for a wide range of fuel cycles including: once through, thermal with fast recycle, continuous fast recycle, and thermal recycle.

Influence of vitamin D on cell cycle, apoptosis, and some apoptosis related molecules in systemic lupus erythematosus

Directory of Open Access Journals (Sweden)

Nafise Tabasi

2015-11-01

Full Text Available Objective(s:Genetic and environmental factors are involved in the pathogenesis of systemic lupus erythematosus (SLE. Autoreactive lymphocytes are cleared through apoptosis and any disturbance in the apoptosis or clearance of apoptotic cells may disturb tolerance and lead to autoimmunity. Vitamin D has anti-proliferative effects and controls cell cycle progression. In this study we investigated the effects of vitamin D on cell cycle and apoptosis induction in lupus patients. Materials and Methods:Isolated peripheral blood mononuclear cells (PBMCs from 25 SLE patients were cultured in the presence of 50 nM of 1,25(OH2D3; then one part of the cells were stained with FITC labeled Annexin V and PI and were analyzed for apoptosis determination. For gene expression assessment of FasL, Bcl-2 and Bax, RNA was extracted from one another part of the cells, cDNA was synthesized and gene expression analysis was performed using Real time PCR. An additional part of the cells were treated with PI and the cell cycle was analyzed using flowcytometer. Results: The mean number of early apoptotic cells in vitamin D treated cells decreased significantly (18.48±7.9% compared to untreated cells (22.02±9.4% (P=0.008. Cell cycle analysis showed a significant increase in G1 phase in vitamin D treated cells (67.33±5.2% compared to non treated ones (60.77±5.7% (P =0.02. Vitamin D up-regulated the expression levels of Bcl-2 by (18.87 fold increase, and down-regulated expression of Bax (23% and FasL (25%. Conclusion:Vitamin D has regulatory effects on cell cycle progression, apoptosis and apoptosis related molecules in lupus patients.

Cdc6 is a rate-limiting factor for proliferative capacity during HL60 cell differentiation

International Nuclear Information System (INIS)

Barkley, Laura R.; Hong, Hye Kyung; Kingsbury, Sarah R.; James, Michelle; Stoeber, Kai; Williams, Gareth H.

2007-01-01

The DNA replication (or origin) licensing pathway represents a critical step in cell proliferation control downstream of growth signalling pathways. Repression of origin licensing through down-regulation of the MCM licensing factors (Mcm2-7) is emerging as a ubiquitous route for lowering proliferative capacity as metazoan cells exit the cell division cycle into quiescent, terminally differentiated and senescent 'out-of-cycle' states. Using the HL60 monocyte/macrophage differentiation model system and a cell-free DNA replication assay, we have undertaken direct biochemical investigations of the coupling of origin licensing to the differentiation process. Our data show that down-regulation of the MCM loading factor Cdc6 acts as a molecular switch that triggers loss of proliferative capacity during early engagement of the somatic differentiation programme. Consequently, addition of recombinant Cdc6 protein to in vitro replication reactions restores DNA replication competence in nuclei prepared from differentiating cells. Differentiating HL60 cells over-expressing either wild-type Cdc6 or a CDK phosphorylation-resistant Cdc6 mutant protein (Cdc6A4) exhibit an extended period of cell proliferation compared to mock-infected cells. Notably, differentiating HL60 cells over-expressing the Cdc6A4 mutant fail to down-regulate Cdc6 protein levels, suggesting that CDK phosphorylation of Cdc6 is linked to its down-regulation during differentiation and the concomitant decrease in cell proliferation. In this experimental model, Cdc6 therefore plays a key role in the sequential molecular events leading to repression of origin licensing and loss of proliferative capacity during execution of the differentiation programme

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

Science.gov (United States)

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

2016-01-01

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

Gas fired combined cycle plant in Singapore: energy use, GWP and cost-a life cycle approach

International Nuclear Information System (INIS)

Kannan, R.; Leong, K.C.; Osman, Ramli; Ho, H.K.; Tso, C.P.

2005-01-01

A life cycle assessment was performed to quantify the non-renewable (fossil) energy use and global warming potential (GWP) in electricity generation from a typical gas fired combined cycle power plant in Singapore. The cost of electricity generation was estimated using a life cycle cost analysis (LCCA) tool. The life cycle assessment (LCA) of a 367.5 MW gas fired combined cycle power plant operating in Singapore revealed that hidden processes consume about 8% additional energy in addition to the fuel embedded energy, and the hidden GWP is about 18%. The natural gas consumed during the operational phase accounted for 82% of the life cycle cost of electricity generation. An empirical relation between plant efficiency and life cycle energy use and GWP in addition to a scenario for electricity cost with varying gas prices and plant efficiency have been established

Improved Survival and Initiation of Differentiation of Human Induced Pluripotent Stem Cells to Hepatocyte-Like Cells upon Culture in William's E Medium followed by Hepatocyte Differentiation Inducer Treatment.

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Minoru Tomizawa

Full Text Available Hepatocyte differentiation inducer (HDI lacks both glucose and arginine, but is supplemented with galactose and ornithine, and is added together with other reagents such as apoptosis inhibitor and oncostatin M. Although human induced pluripotent stem (iPS cells initiate hepatocyte differentiation, most die within 7 days. In this study, we investigated both HDI and conventional media for their potential to improve cell survival.201B7 iPS cells were cultured in conventional media. This consisted of three cycles of 5-day culture in William's E (WE medium, followed by a 2-day culture in HDI.Expression levels of α-feto protein (AFP were higher in cells cultured in WE and in Dulbecco's Modified Eagle's Medium/Nutrient F-12 Ham (DF12. 201B7 cells expressed the highest AFP and albumin (ALB when cultured in HDI for 2 days following 7-day culture in WE. After three cycles of 5-day culture in WE followed by 2 days in HDI, 201B7 cells expressed AFP and ALB 54 ± 2.3 (average ± standard deviation and 73 ± 15.1 times higher, respectively, than those cultured in ReproFF (feeder-free condition.201B7 cells survived culture in WE for 7 days followed HDI for 2 days. After three cycles of culture under these conditions, hepatocyte differentiation was enhanced, as evidenced by increased AFP and ALB expression.

Differential expression of secretogranin II and chromogranin A genes in the female rat pituitary through sexual maturation and estrous cycle

International Nuclear Information System (INIS)

Anouar, Y.; Duval, J.

1991-01-01

Secretogranin II (SgII) is a protein of pituitary secretory granules released by LHRH-stimulated gonadotrope cells. Estrogens and androgens are modulators of SgII release. Experiments were performed to determine the regulation of expression of the SgII gene in the female rat pituitary, during sexual maturation and according to the estrous cycle. Age- and cycle-related changes in SgII mRNA content were estimated through cytoplasmic slot blot; SgII content was determined by western blotting; maturation of the protein was controlled through [35S]sulfate labeling. Variations in chromogranin A (CgA), another protein of secretory granules, were analyzed in the same experimental conditions to assess the specificity of SgII regulation. The pituitary SgII concentration increased between days 7 and 21 (2.2-fold) and then declined to the initial 7-day-old value. Simultaneously, the CgA concentration went through a maximum between days 14 and 21 and then strongly dropped to barely detectable levels in the adult pituitary. The SgII mRNA concentration followed roughly the same pattern as the protein. Moreover, the sulfation level remained constant between days 14 and 60. These results demonstrated a regulatory mechanism operating, during sexual maturation, on the SgII gene and not on the protein processing or on storage/release steps. In the 4-day cycling females, the pituitary SgII mRNA and protein contents were the lowest during estrus. They then increased to their highest values in diestrus II. Moreover, the sulfation level of SgII was significantly higher during estrus than during any other stage. Due to its low content level, variations in pituitary CgA could not be demonstrated during the cycle

Differential nitrogen cycling in semiarid sub-shrubs with contrasting leaf habit.

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Sara Palacio

Full Text Available Nitrogen (N is, after water, the most limiting resource in semiarid ecosystems. However, knowledge on the N cycling ability of semiarid woody plants is still very rudimentary. This study analyzed the seasonal change in the N concentrations and pools of the leaves and woody organs of two species of semiarid sub-shrubs with contrasting leaf habit. The ability of both species to uptake, remobilize and recycle N, plus the main storage organ for N during summer drought were evaluated. We combined an observational approach in the field with experimental (15N labelling of adult individuals grown in sand culture. Seasonal patterns of N concentrations were different between species and organs and foliar N concentrations of the summer deciduous Lepidium subulatum were almost double those of the evergreen Linum suffruticosum. L. subulatum up took ca. 60% more external N than the evergreen and it also had a higher N resorption efficiency and proficiency. Contrastingly, L. suffruticosum relied more on internal N remobilization for shoot growth. Differently to temperate species, the evergreen stored N preferentially in the main stem and old trunks, while the summer deciduous stored it in the foliage and young stems. The higher ability of L. subulatum to uptake external N can be related to its ability to perform opportunistic growth and exploit the sporadic pulses of N typical of semiarid ecosystems. Such ability may also explain its high foliar N concentrations and its preferential storage of N in leaves and young stems. Finally, L. suffruticosum had a lower ability to recycle N during leaf senescence. These strategies contrast with those of evergreen and deciduous species from temperate and boreal areas, highlighting the need of further studies on semiarid and arid plants.

Gender differences in recreational and transport cycling: a cross-sectional mixed-methods comparison of cycling patterns, motivators, and constraints.

Science.gov (United States)

Heesch, Kristiann C; Sahlqvist, Shannon; Garrard, Jan

2012-09-08

Gender differences in cycling are well-documented. However, most analyses of gender differences make broad comparisons, with few studies modeling male and female cycling patterns separately for recreational and transport cycling. This modeling is important, in order to improve our efforts to promote cycling to women and men in countries like Australia with low rates of transport cycling. The main aim of this study was to examine gender differences in cycling patterns and in motivators and constraints to cycling, separately for recreational and transport cycling. Adult members of a Queensland, Australia, community bicycling organization completed an online survey about their cycling patterns; cycling purposes; and personal, social and perceived environmental motivators and constraints (47% response rate). Closed and open-end questions were completed. Using the quantitative data, multivariable linear, logistic and ordinal regression models were used to examine associations between gender and cycling patterns, motivators and constraints. The qualitative data were thematically analyzed to expand upon the quantitative findings. In this sample of 1862 bicyclists, men were more likely than women to cycle for recreation and for transport, and they cycled for longer. Most transport cycling was for commuting, with men more likely than women to commute by bicycle. Men were more likely to cycle on-road, and women off-road. However, most men and women did not prefer to cycle on-road without designed bicycle lanes, and qualitative data indicated a strong preference by men and women for bicycle-only off-road paths. Both genders reported personal factors (health and enjoyment related) as motivators for cycling, although women were more likely to agree that other personal, social and environmental factors were also motivating. The main constraints for both genders and both cycling purposes were perceived environmental factors related to traffic conditions, motorist aggression and

Lamin A/C Is Required for ChAT-Dependent Neuroblastoma Differentiation.

Science.gov (United States)

Guglielmi, Loredana; Nardella, Marta; Musa, Carla; Iannetti, Ilaria; Arisi, Ivan; D'Onofrio, Mara; Storti, Andrea; Valentini, Alessandra; Cacci, Emanuele; Biagioni, Stefano; Augusti-Tocco, Gabriella; D'Agnano, Igea; Felsani, Armando

2017-07-01

The mouse neuroblastoma N18TG2 clone is unable to differentiate and is defective for the enzymes of the biosynthesis of neurotransmitters. The forced expression of choline acetyltransferase (ChAT) in these cells results in the synthesis and release of acetylcholine (Ach) and hence in the expression of neurospecific features and markers. To understand how the expression of ChAT triggered neuronal differentiation, we studied the differences in genome-wide transcription profiles between the N18TG2 parental cells and its ChAT-expressing 2/4 derived clone. The engagement of the 2/4 cells in the neuronal developmental program was confirmed by the increase of the expression level of several differentiation-related genes and by the reduction of the amount of transcripts of cell cycle genes. At the same time, we observed a massive reorganization of cytoskeletal proteins in terms of gene expression, with the accumulation of the nucleoskeletal lamina component Lamin A/C in differentiating cells. The increase of the Lmna transcripts induced by ChAT expression in 2/4 cells was mimicked treating the parental N18TG2 cells with the acetylcholine receptor agonist carbachol, thus demonstrating the direct role played by this receptor in neuron nuclei maturation. Conversely, a treatment of 2/4 cells with the muscarinic receptor antagonist atropine resulted in the reduction of the amount of Lmna RNA. Finally, the hypothesis that Lmna gene product might play a crucial role in the ChAT-dependent molecular differentiation cascade was strongly supported by Lmna knockdown in 2/4 cells leading to the downregulation of genes involved in differentiation and cytoskeleton formation and to the upregulation of genes known to regulate self-renewal and stemness.

On the relation between elementary partial difference equations and partial differential equations

NARCIS (Netherlands)

van den Berg, I.P.

1998-01-01

The nonstandard stroboscopy method links discrete-time ordinary difference equations of first-order and continuous-time, ordinary differential equations of first order. We extend this method to the second order, and also to an elementary, yet general class of partial difference/differential

Chronic fluoxetine treatment directs energy metabolism towards the citric acid cycle and oxidative phosphorylation in rat hippocampal nonsynaptic mitochondria.

Science.gov (United States)

Filipović, Dragana; Costina, Victor; Perić, Ivana; Stanisavljević, Andrijana; Findeisen, Peter

2017-03-15

Fluoxetine (Flx) is the principal treatment for depression; however, the precise mechanisms of its actions remain elusive. Our aim was to identify protein expression changes within rat hippocampus regulated by chronic Flx treatment versus vehicle-controls using proteomics. Fluoxetine-hydrohloride (15mg/kg) was administered daily to adult male Wistar rats for 3weeks, and cytosolic and nonsynaptic mitochondrial hippocampal proteomes were analyzed. All differentially expressed proteins were functionally annotated according to biological process and molecular function using Uniprot and Blast2GO. Our comparative study revealed that in cytosolic and nonsynaptic mitochondrial fractions, 60 and 3 proteins respectively, were down-regulated, and 23 and 60 proteins, respectively, were up-regulated. Proteins differentially regulated in cytosolic and nonsynaptic mitochondrial fractions were primarily related to cellular and metabolic processes. Of the identified proteins, the expressions of calretinin and parvalbumine were confirmed. The predominant molecular functions of differentially expressed proteins in both cell hippocampal fractions were binding and catalytic activity. Most differentially expressed proteins in nonsynaptic mitochondria were catalytic enzymes involved in the pyruvate metabolism, citric acid cycle, oxidative phosphorylation, ATP synthesis, ATP transduction and glutamate metabolism. Results indicate that chronic Flx treatment may influence proteins involved in calcium signaling, cytoskeletal structure, chaperone system and stimulates energy metabolism via the upregulation of GAPDH expression in cytoplasm, as well as directing energy metabolism toward the citric acid cycle and oxidative phosphorylation in nonsynaptic mitochondria. This approach provides new insight into the chronic effects of Flx treatment on protein expression in a key brain region associated with stress response and memory. Copyright © 2017 Elsevier B.V. All rights reserved.

Environmental physiology: effects of energy-related pollutants on daily cycles of energy metabolism, motor activity, and thermoregulation

International Nuclear Information System (INIS)

Sacher, G.A.; Rosenberg, R.S.; Duffy, P.H.; Obermeyer, W.; Russell, J.J.

1979-01-01

This section contains a summary of research on the effects of energy-related pollutants on daily cycles of energy metabolism, motor activity, and thermoregulation. So far, mice have been exposed to fast neutron-gamma radiation or to the chemical effluents of an atmospheric pressure experimental fluidized-bed combustor. The physiological parameters measured included: O 2 consumption; CO 2 production; motor activity; and deep body temperatures

Mitosis in neurons: Roughex and APC/C maintain cell cycle exit to prevent cytokinetic and axonal defects in Drosophila photoreceptor neurons.

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Robert Ruggiero

Full Text Available The mechanisms of cell cycle exit by neurons remain poorly understood. Through genetic and developmental analysis of Drosophila eye development, we found that the cyclin-dependent kinase-inhibitor Roughex maintains G1 cell cycle exit during differentiation of the R8 class of photoreceptor neurons. The roughex mutant neurons re-enter the mitotic cell cycle and progress without executing cytokinesis, unlike non-neuronal cells in the roughex mutant that perform complete cell divisions. After mitosis, the binucleated R8 neurons usually transport one daughter nucleus away from the cell body into the developing axon towards the brain in a kinesin-dependent manner resembling anterograde axonal trafficking. Similar cell cycle and photoreceptor neuron defects occurred in mutants for components of the Anaphase Promoting Complex/Cyclosome. These findings indicate a neuron-specific defect in cytokinesis and demonstrate a critical role for mitotic cyclin downregulation both to maintain cell cycle exit during neuronal differentiation and to prevent axonal defects following failed cytokinesis.

Coupled effects of light and nitrogen source on the urea cycle and nitrogen metabolism over a diel cycle in the marine diatom Thalassiosira pseudonana.

Science.gov (United States)

Bender, Sara J; Parker, Micaela S; Armbrust, E Virginia

2012-03-01

Diatoms are photoautotrophic organisms capable of growing on a variety of inorganic and organic nitrogen sources. Discovery of a complete urea cycle in diatoms was surprising, as this pathway commonly functions in heterotrophic organisms to rid cells of waste nitrogen. To determine how the urea cycle is integrated into cellular nitrogen metabolism and energy management, the centric diatom Thalassiosira pseudonana was maintained in semi-continuous batch cultures on nitrate, ammonium, or urea as the sole nitrogen source, under a 16: 8 light: dark cycle and at light intensities that were low, saturating, or high for growth. Steady-state transcript levels were determined for genes encoding enzymes linked to the urea cycle, urea hydrolysis, glutamine synthesis, pyrimidine synthesis, photorespiration, and energy storage. Transcript abundances were significantly affected by nitrogen source, light intensity and a diel cycle. The impact of N source on differential transcript accumulation was most apparent under the highest light intensity. Models of cellular metabolism under high light were developed based on changes in transcript abundance and predicted enzyme localizations. We hypothesize that the urea cycle is integrated into nitrogen metabolism through its connection to glutamine and in the eventual production of urea. These findings have important implications for nitrogen flow in the cell over diel cycles at surface ocean irradiances. Copyright © 2011 Elsevier GmbH. All rights reserved.

Parental Involvement, Child Temperament, and Parents' Work Hours: Differential Relations for Mothers and Fathers.

Science.gov (United States)

Brown, Geoffrey L; McBride, Brent A; Bost, Kelly K; Shin, Nana

2011-01-01

This study examined how child temperament was related to parents' time spent accessible to and interacting with their 2-year-olds. Bivariate analyses indicated that both fathers and mothers spent more time with temperamentally challenging children than easier children on workdays, but fathers spent less time with challenging children than easier children on non-workdays. After accounting for work hours, some associations between temperament and fathers' workday involvement dropped to non-significance. For fathers, work hours also moderated the relation between irregular temperament and workday play. For mothers, work hours moderated the relation between both difficult and irregular temperament and workday interaction. Mothers also spent more time with girls (but not boys) who were temperamentally irregular. Results speak to the influence of child temperament on parenting behavior, and the differential construction of parenting roles as a function of child characteristics and patterns of work.

Cultural and Intellectual Openness Differentially Relate to Social Judgments of Potential Work Partners.

Science.gov (United States)

Porter, Caitlin M; Parrigon, Scott E; Woo, Sang Eun; Saef, Rachel M; Tay, Louis

2017-10-01

This study investigates the differential functioning of cultural and intellectual openness (the two aspects of Openness to Experience) in relation to social cognitive processes by examining how they influence people's perceptions and interpretations of social information when deciding to initiate working relationships. Using a policy-capturing design, 681 adult participants were asked to rate their similarity to and preference to work with potential work partners characterized by varying nationalities and levels of work-related competence. Multilevel moderated mediation was conducted to simultaneously evaluate whether the indirect effects of potential work partners' characteristics (i.e., nationalities and levels of work-related competence) on work partner preference through perceived similarity were moderated by cultural and intellectual openness. Perceived similarity mediated the relationships between work partner nationality and work-related competence and participants' work partner preferences. Furthermore, the negative indirect effect of work partner nationality on work partner preference via perceived similarity was attenuated by cultural openness, and the positive indirect effect of work partner work-related competence on work partner preference via perceived similarity was strengthened by intellectual openness. Cultural and intellectual openness may have distinct functions that influence how people perceive, evaluate, and appreciate social information when making social judgments. © 2016 Wiley Periodicals, Inc.

Repressive histone methylation regulates cardiac myocyte cell cycle exit.

Science.gov (United States)

El-Nachef, Danny; Oyama, Kyohei; Wu, Yun-Yu; Freeman, Miles; Zhang, Yiqiang; Robb MacLellan, W

2018-05-22

Mammalian cardiac myocytes (CMs) stop proliferating soon after birth and subsequent heart growth comes from hypertrophy, limiting the adult heart's regenerative potential after injury. The molecular events that mediate CM cell cycle exit are poorly understood. To determine the epigenetic mechanisms limiting CM cycling in adult CMs (ACMs) and whether trimethylation of lysine 9 of histone H3 (H3K9me3), a histone modification associated with repressed chromatin, is required for the silencing of cell cycle genes, we developed a transgenic mouse model where H3K9me3 is specifically removed in CMs by overexpression of histone demethylase, KDM4D. Although H3K9me3 is found across the genome, its loss in CMs preferentially disrupts cell cycle gene silencing. KDM4D binds directly to cell cycle genes and reduces H3K9me3 levels at these promotors. Loss of H3K9me3 preferentially leads to increased cell cycle gene expression resulting in enhanced CM cycling. Heart mass was increased in KDM4D overexpressing mice by postnatal day 14 (P14) and continued to increase until 9-weeks of age. ACM number, but not size, was significantly increased in KDM4D expressing hearts, suggesting CM hyperplasia accounts for the increased heart mass. Inducing KDM4D after normal development specifically in ACMs resulted in increased cell cycle gene expression and cycling. We demonstrated that H3K9me3 is required for CM cell cycle exit and terminal differentiation in ACMs. Depletion of H3K9me3 in adult hearts prevents and reverses permanent cell cycle exit and allows hyperplastic growth in adult hearts in vivo. Copyright © 2017. Published by Elsevier Ltd.

Limit cycles bifurcating from the periodic annulus of cubic homogeneous polynomial centers

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Jaume Llibre

2015-10-01

Full Text Available We obtain an explicit polynomial whose simple positive real roots provide the limit cycles which bifurcate from the periodic orbits of any cubic homogeneous polynomial center when it is perturbed inside the class of all polynomial differential systems of degree n.

The Signaling Pathways Involved in Chondrocyte Differentiation and Hypertrophic Differentiation

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Jianmei Li

2016-01-01

Full Text Available Chondrocytes communicate with each other mainly via diffusible signals rather than direct cell-to-cell contact. The chondrogenic differentiation of mesenchymal stem cells (MSCs is well regulated by the interactions of varieties of growth factors, cytokines, and signaling molecules. A number of critical signaling molecules have been identified to regulate the differentiation of chondrocyte from mesenchymal progenitor cells to their terminal maturation of hypertrophic chondrocytes, including bone morphogenetic proteins (BMPs, SRY-related high-mobility group-box gene 9 (Sox9, parathyroid hormone-related peptide (PTHrP, Indian hedgehog (Ihh, fibroblast growth factor receptor 3 (FGFR3, and β-catenin. Except for these molecules, other factors such as adenosine, O2 tension, and reactive oxygen species (ROS also have a vital role in cartilage formation and chondrocyte maturation. Here, we outlined the complex transcriptional network and the function of key factors in this network that determine and regulate the genetic program of chondrogenesis and chondrocyte differentiation.

Presence of bile acids in human follicular fluid and their relation with embryo development in modified natural cycle IVF

NARCIS (Netherlands)

Nagy, R. A.; van Montfoort, A. P. A.; Dikkers, A.; van Echten-Arends, J.; Homminga, I.; Land, J. A.; Hoek, A.; Tietge, U. J. F.

STUDY QUESTION: Are bile acids (BA) and their respective subspecies present in human follicular fluid (FF) and do they relate to embryo quality in modified natural cycle IVF (MNC-IVF)? SUMMARY ANSWER: BAconcentrations are 2-fold higher in follicular fluid than in serum and ursodeoxycholic acid

National Policy on Nuclear Fuel Cycle

International Nuclear Information System (INIS)

Soedyartomo, S.

1996-01-01

National policy on nuclear fuel cycle is aimed at attaining the expected condition, i.e. being able to support optimality the national energy policy and other related Government policies taking into account current domestic nuclear fuel cycle condition and the trend of international nuclear fuel cycle development, the national strength, weakness, thread and opportunity in the field of energy. This policy has to be followed by the strategy to accomplish covering the optimization of domestic efforts, cooperation with other countries, and or purchasing licences. These policy and strategy have to be broken down into various nuclear fuel cycle programmes covering basically assesment of the whole cycle, performing research and development of the whole cycle without enrichment and reprocessing being able for weapon, as well as programmes for industrialization of the fuel cycle stepwisery commencing with the middle part of the cycle and ending with the edge of the back-end of the cycle

3D facial expression recognition based on histograms of surface differential quantities

KAUST Repository

Li, Huibin; Morvan, Jean-Marie; Chen, Liming

2011-01-01

. To characterize shape information of the local neighborhood of facial landmarks, we calculate the weighted statistical distributions of surface differential quantities, including histogram of mesh gradient (HoG) and histogram of shape index (HoS). Normal cycle

Advanced fuel cycles in CANDU reactors

International Nuclear Information System (INIS)

Green, R.E.; Boczar, P.G.

1990-04-01

This paper re-examines the rationale for advanced nuclear fuel cycles in general, and for CANDU advanced fuel cycles in particular. The traditional resource-related arguments for more uranium nuclear fuel cycles are currently clouded by record-low prices for uranium. However, the total known conventional uranium resources can support projected uranium requirements for only another 50 years or so, less if a major revival of the nuclear option occurs as part of the solution to the world's environmental problems. While the extent of the uranium resource in the earth's crust and oceans is very large, uncertainty in the availability and price of uranium is the prime resource-related motivation for advanced fuel cycles. There are other important reasons for pursuing advanced fuel cycles. The three R's of the environmental movement, reduce, recycle, reuse, can be achieved in nuclear energy production through the employment of advanced fuel cycles. The adoption of more uranium-conserving fuel cycles would reduce the amount of uranium which needs to be mined, and the environmental impact of that mining. Environmental concerns over the back end of the fuel cycle can be mitigated as well. Higher fuel burnup reduces the volume of spent fuels which needs to be disposed of. The transmutation of actinides and long-lived fission products into short-lived fission products would reduce the radiological hazard of the waste from thousands to hundreds of years. Recycling of uranium and/or plutonium in spent fuel reuses valuable fissile material, leaving only true waste to be disposed of. Advanced fuel cycles have an economical benefit as well, enabling a ceiling to be put on fuel cycle costs, which are

Energy security externalities and fuel cycle comparisons

International Nuclear Information System (INIS)

Bohi, D.; Toman, M.

1994-01-01

Externalities related to 'energy security' may be one way in which the full social costs of energy use diverge from the market prices of energy commodities. Such divergences need to be included in reckoning the full costs of different fuel cycles. In this paper we critically examine potential externalities related to energy security and issues related to the measurement of 2 these externalities, in the context of fuel cycle comparisons

Energy security externalities and fuel cycle comparisons

Energy Technology Data Exchange (ETDEWEB)

Bohi, D; Toman, M

1994-07-01

Externalities related to 'energy security' may be one way in which the full social costs of energy use diverge from the market prices of energy commodities. Such divergences need to be included in reckoning the full costs of different fuel cycles. In this paper we critically examine potential externalities related to energy security and issues related to the measurement of 2 these externalities, in the context of fuel cycle comparisons.

Study on the supercritical CO2 power cycles for landfill gas firing gas turbine bottoming cycle

International Nuclear Information System (INIS)

Kim, Min Seok; Ahn, Yoonhan; Kim, Beomjoo; Lee, Jeong Ik

2016-01-01

In this paper, a comparison of nine supercritical carbon dioxide (S-CO 2 ) bottoming power cycles in conjunction with a topping cycle of landfill gas (LFG) fired 5MWe gas turbine is presented. For the comparison purpose, a sensitivity study of the cycle design parameters for nine different cycles was conducted and each cycle thermodynamic performance is evaluated. In addition, the cycle performance evaluation dependency on the compressor inlet temperature variation is performed to investigate how S-CO 2 cycles sensitive to the heat sink temperature variation. Furthermore, the development of new S-CO 2 cycle layouts is reported and the suggested cycles' performances are compared to the existing cycle layouts. It was found that a recompression cycle is not suitable for the bottoming cycle application, but a partial heating cycle has relatively higher net produced work with a simple layout and small number of components. Although a dual heated and flow split cycle has the highest net produced work, it has disadvantages of having numerous components and complex process which requires more sophisticated operational strategies. This study identified that the recuperation process is much more important than the intercooling process to the S-CO 2 cycle design for increasing the thermal efficiency and the net produced work point of view. - Highlights: • Study of nine S-CO 2 power cycle layouts for a small scale landfill gas power generation application. • Development of new S-CO 2 cycle layouts. • Sensitivity analysis of S-CO 2 cycles to evaluate and compare nine cycles' performances.

Let7a involves in neural stem cell differentiation relating with TLX level.

Science.gov (United States)

Song, Juhyun; Cho, Kyoung Joo; Oh, Yumi; Lee, Jong Eun

2015-07-10

Neural stem cells (NSCs) have the potential for differentiation into neurons known as a groundbreaking therapeutic solution for central nervous system (CNS) diseases. To resolve the therapeutic efficiency of NSCs, recent researchers have focused on the study on microRNA's role in CNS. Some micro RNAs have been reported significant functions in NSC self-renewal and differentiation through the post-transcriptional regulation of neurogenesis genes. MicroRNA-Let7a (Let7a) has known as the regulator of diverse cellular mechanisms including cell differentiation and proliferation. In present study, we investigated whether Let7a regulates NSC differentiation by targeting the nuclear receptor TLX, which is an essential regulator of NSC self-renewal, proliferation and differentiation. We performed the following experiments: western blot analysis, TaqMan assay, RT-PCR, and immunocytochemistry to confirm the alteration of NSCs. Our data showed that let7a play important roles in controlling NSC fate determination. Thus, manipulating Let-7A and TLX could be a novel strategy to enhance the efficiency of NSC's neuronal differentiation for CNS disorders. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Problems in complying with regulations related to low activity materials: Nuclear fuel cycle issues

International Nuclear Information System (INIS)

Coates, R.

1997-01-01

The range of issues relating to exemption and clearance within the nuclear fuel cycle is reviewed. It is concluded that current regulatory systems and the underpinning technical criteria are potentially inflexible and over-conservative, resulting in an imbalance in the use of society's resources. Proposals are developed for establishing practical requirements which would ensure that resource allocation is commensurate with the magnitude of the risks and in broad proportion to the other risks affecting society. Such an approach would be consistent with the concept of sustainability and could support wider public acceptance of these issues. Within this approach the practical distinction between exemption and clearance is challenged. (author)

Am80 induces neuronal differentiation via increased tropomyosin-related kinase B expression in a human neuroblastoma SH-SY5Y cell line.

Science.gov (United States)

Shiohira, Hideo; Kitaoka, Akira; Enjoji, Munechika; Uno, Tsukasa; Nakashima, Manabu

2012-01-01

Am80, a synthetic retinoid, has been used in differentiation therapy for acute promyelocytic leukemia (APL). All-trans retinoic acid (ATRA) as one of natural retinoid has been also used to treat APL. ATRA treatment causes neuronal differentiation by inducing tropomyosin-related kinase B (TrkB) expression and increasing the sensitivity to brain-derived neurotrophic factor (BDNF), a TrkB ligand. In the present study, we investigated the effects of Am80 on neuronal differentiation, BDNF sensitivity and TrkB expression in human neuroblastoma SH-SY5Y cells. Treatment with Am80 induced morphological differentiation of neurite outgrowth and increased the expression of GAP43 mRNA, a neuronal differentiation marker. Additionally, TrkB protein was also increased, and exogenous BDNF stimulation after treatment with Am80 induced greater neurite outgrowth than without BDNF treatment. These results suggest that Am80 induced neuronal differentiation by increasing TrkB expression and BDNF sensitivity.

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

Science.gov (United States)

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

2010-01-01

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