Stable SREBP-1a knockdown decreases the cell proliferation rate in human preadipocyte cells without inducing senescence

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Alvarez, María Soledad [Instituto de Biomedicina de Valencia (IBV-CSIC), Jaime Roig 11, E-46010 Valencia (Spain); Fernandez-Alvarez, Ana [Fundación Instituto Leloir, IIBBA-CONICET, Av. Patricias Argentinas 435, Ciudad Autónoma de Buenos Aires C1405BWE (Argentina); Cucarella, Carme [Instituto de Biomedicina de Valencia (IBV-CSIC), Jaime Roig 11, E-46010 Valencia (Spain); Casado, Marta, E-mail: mcasado@ibv.csic.es [Instituto de Biomedicina de Valencia (IBV-CSIC), Jaime Roig 11, E-46010 Valencia (Spain)

2014-04-25

Highlights: • SGBS cells mostly expressed SREBP-1a variant. • SREBP-1a knockdown decreased the proliferation of SGBS cells without inducing senescence. • We have identified RBBP8 and CDKN3 genes as potential SREBP-1a targets. - Abstract: Sterol regulatory element binding proteins (SREBP), encoded by the Srebf1 and Srebf2 genes, are important regulators of genes involved in cholesterol and fatty acid metabolism. Whereas SREBP-2 controls the cholesterol synthesis, SREBP-1 proteins (-1a and -1c) function as the central hubs in lipid metabolism. Despite the key function of these transcription factors to promote adipocyte differentiation, the roles of SREBP-1 proteins during the preadipocyte state remain unknown. Here, we evaluate the role of SREBP-1 in preadipocyte proliferation using RNA interference technology. Knockdown of the SREBP-1a gene decreased the proliferation rate in human SGBS preadipocyte cell strain without inducing senescence. Furthermore, our data identified retinoblastoma binding protein 8 and cyclin-dependent kinase inhibitor 3 genes as new potential SREBP-1 targets, in addition to cyclin-dependent kinase inhibitor 1A which had already been described as a gene regulated by SREBP-1a. These data suggested a new role of SREBP-1 in adipogenesis via regulation of preadipocyte proliferation.

Influence of the dose rate on the proliferation capacity of haematopoietic elementary cells in vivo after partial body irradiation

International Nuclear Information System (INIS)

Sauer, R.

1977-01-01

During direct irradiation of the bone marrow, the dose rate effect was so paradoxical that a temporally protracted exposure has a stronger influence on the proliferation capacity of the elementary cells than one with high dose performance. During the recreation process, the elementary cells proliferated in the sense of a rebound-phaenomenon. This was also referred to the observation that in the non-irradiated bone marrow of animals exposed to partial body irradiation, an activation of the elementary cells started. The results have consequences for the oncological radiotherapy. (orig.) [de

Specific proliferation rates of human osteoblasts on calcium phosphate surfaces with variable concentrations of α-TCP

International Nuclear Information System (INIS)

Santos, Euler A. dos; Farina, Marcos; Soares, Gloria A.

2007-01-01

Ideally, ceramics used in the repair of bone defects need to be resorbed and replaced by newly formed bone in vivo. Tricalcium phosphate (TCP) has been widely used in association with hydroxyapatite (HA) due to its higher resorption kinetics when compared with HA alone. The aim of our study was to quantitatively investigate the effect of α-tricalcium phosphate (α-TCP) on human osteoblasts' adhesion and proliferation. Ceramic samples with variable concentrations of α-TCP and HA were produced by the calcination of calcium-deficient and stoichiometric HA. Human osteoblasts were cultured on the materials in three distinct experiments with different concentrations of cells. Numerical evaluation of cellular growth along time in culture was performed for each condition. The quantity of cells seeded onto the ceramics seems to influence the osteoblast behavior once proliferation was lower when more cells were seeded onto the samples. However, a smaller content of α-TCP in relation to that of HA did not significantly modify the specific proliferation rates of the osteoblasts. Only after a long time in culture, the increasing of the α-TCP content seems to change the cells' behavior

Intermittent pressure decreases human keratinocyte proliferation in vitro.

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Nasca, Maria R; Shih, Alan T; West, Dennis P; Martinez, Wanda M; Micali, Giuseppe; Landsman, Adam S

2007-01-01

The aim of this study was to investigate the correlation between pressure changes and keratinocyte proliferation by determining whether keratinocytes exposed to altered mechanical pressures would proliferate at different rates compared to control cells not subjected to pressure changes. Tissue culture flasks of human keratinocytes plated at an approximate density of 15,000 cells/cm(2) undergoing an intermittent cyclic pressure of 362 mm Hg at a frequency of 2.28 or 5.16 cycles/min (0.038 or 0.086 Hz) for 8 h were compared to control flasks grown at ambient room pressure. An in-line pressure transducer was used to monitor and adjust pressure within the cell chambers, using a solenoid valve. A thymidine incorporation assay assessed the amount of cell proliferation in each set of experiments. Differences in proliferation between keratinocytes subjected to cyclic pressure changes and control cells were found to be statistically significant (p < 0.05) in 4 out of 5 proliferation assays. Also, a higher frequency of pressure changes consistently generated a reduced proliferation rate compared to that seen in cells exposed to a lower frequency of pressure changes. These data indicate that keratinocytes undergoing intermittent pressure changes exhibit decreased proliferation rates compared to controls. Furthermore, an increased frequency rate seems to have a greater effect on proliferation than low-frequency rate pressure changes, suggesting that the stress caused by frequently changed pressure may play a greater role in reducing keratinocyte proliferation than the actual magnitude of load applied to the cells. Our results support the current treatment protocol of reducing speed and duration of walking on the site of the wound to promote healing of foot ulcers. (c) 2007 S. Karger AG, Basel.

An Advanced Deep Learning Approach for Ki-67 Stained Hotspot Detection and Proliferation Rate Scoring for Prognostic Evaluation of Breast Cancer.

Science.gov (United States)

Saha, Monjoy; Chakraborty, Chandan; Arun, Indu; Ahmed, Rosina; Chatterjee, Sanjoy

2017-06-12

Being a non-histone protein, Ki-67 is one of the essential biomarkers for the immunohistochemical assessment of proliferation rate in breast cancer screening and grading. The Ki-67 signature is always sensitive to radiotherapy and chemotherapy. Due to random morphological, color and intensity variations of cell nuclei (immunopositive and immunonegative), manual/subjective assessment of Ki-67 scoring is error-prone and time-consuming. Hence, several machine learning approaches have been reported; nevertheless, none of them had worked on deep learning based hotspots detection and proliferation scoring. In this article, we suggest an advanced deep learning model for computerized recognition of candidate hotspots and subsequent proliferation rate scoring by quantifying Ki-67 appearance in breast cancer immunohistochemical images. Unlike existing Ki-67 scoring techniques, our methodology uses Gamma mixture model (GMM) with Expectation-Maximization for seed point detection and patch selection and deep learning, comprises with decision layer, for hotspots detection and proliferation scoring. Experimental results provide 93% precision, 0.88% recall and 0.91% F-score value. The model performance has also been compared with the pathologists' manual annotations and recently published articles. In future, the proposed deep learning framework will be highly reliable and beneficial to the junior and senior pathologists for fast and efficient Ki-67 scoring.

A secreted factor represses cell proliferation in Dictyostelium

OpenAIRE

Brock, Debra A.; Gomer, Richard H.

2005-01-01

Many cells appear to secrete factors called chalones that limit their proliferation, but in most cases the factors have not been identified. We found that growing Dictyostelium cells secrete a 60 kDa protein called AprA for autocrine proliferation repressor. AprA has similarity to putative bacterial proteins of unknown function. Compared with wild-type cells, aprA-null cells proliferate faster, while AprA overexpressing cells proliferate slower. Growing wild-type cells secrete a factor that i...

When the World Changes in Your Hands: Similarity Ratings of Objects Morphing during Active Exploration

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Haemy Lee

2012-10-01

Full Text Available View-based theories of object recognition posit that coherent object representations are formed by linking together successive views of an actively explored object. This linking process relies on the assumption that the object does not change during exploration. Here, we test how object representations might be influenced when the shape of the object changes slowly during exploration. In our experiment, participants rated the similarity of two novel, 3D objects, whose shape was parametrically defined. Seventeen participants explored each object for 10 sec on an iPad which afforded natural and efficient interaction. The experiment contained a baseline condition, in which two objects of varying parameter-differences were presented, and a morphing condition, in which the first of the two objects slowly morphed during active exploration, making the objects more similar. Interestingly, no participant was aware of this morphing manipulation. Comparing baseline and morph trials, however, we found significantly higher similarity ratings during morphing [F(1,16 = 84.79, p < .001]. Furthermore, correlations between similarity ratings and differences in object parameters were high for the baseline condition (r = −.64, with smaller parameter differences being perceived as more similar. Interestingly, in the morphing condition correlations were lower for parameter differences after the morph (r = −.22, but remained high for differences before (r = −.47 and during morphing (r = −.50. In conclusion, similarity ratings in the baseline condition captured the complex parameter space well. Although participants did not notice the changing shape, morphing did systematically bias the ratings. Interestingly, similarity judgments correlated better in the initial exploration phase, suggesting a capacity limit for view integration of complex shapes.

Neural control of colonic cell proliferation.

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Tutton, P J; Barkla, D H

1980-03-15

The mitotic rate in rat colonic crypts and in dimethylhydrazine-induced colonic carcinomas was measured using a stathmokinetic technique. In sympathectomized animals cell proliferation was retarded in the crypts but not in the tumors, whereas in animals treated with Metaraminol, a drug which releases norepinephrine from nerve terminals, crypt cell but not tumor cell proliferation was accelerated. Blockade of alpha-adrenoceptors also inhibited crypt cell proliferation. However, stimulation of beta-adrenoceptors inhibited and blockade of beta-adrenoceptors accelerated tumor cell proliferation without influencing crypt cell proliferation. Injection of either serotonin or histamine stimulated tumor but not crypt cell proliferation and blockade or serotonin receptors or histamine H2-receptors inhibited tumor cell proliferation. It is postulated that cell proliferation in the colonic crypts, like that in the jejunal crypts, is under both endocrine and autonomic neural control whereas colonic tumor cell division is subject to endocrine regulation alone.

Complexities in gauging time-dependency of proliferation resistance

International Nuclear Information System (INIS)

Avens, L.R.; Eller, P.G.; Stanbro, W.D.

2004-01-01

To a considerable extent, policy decisions on nuclear fuel cycle issues depend upon how decision makers recognize and weigh 'long-term' and 'short-term' nuclear proliferation risk factors. Priorities and structures of advanced fuel cycle and safeguards research and development programs are affected similarly. Unfortunately, there is a diversity of understanding of the precise meanings of these proliferation risk terms, leading to lack of precision in their usage. In addition, proliferation risk evaluation fundamentally involves value judgments on the relative importance of time-dependent risks. Poor communication and diverse conclusions often result. This paper explores some complexities in gauging 'long-term' and 'short-term' proliferation risk in the context of advanced nuclear fuel cycles. A convenient vehicle for this purpose is a commonly used notional plot of some proliferation resistance attribute of spent fuel or separated plutonium versus years from reactor discharge, often overlain with similar notional curves denoting multiple fuel irradiation and recycle. A common basis for misuse of such plots is failure to clearly define the range of proliferation threats being evaluated, as illustrated by several common examples of such omissions. Partial arguments of this type can be misleading and provide a disservice to policy makers who must have a clear picture of the tradeoffs being made. This paper concludes with a call for much greater care to avoid overly simplistic interpretations of notional proliferation-related concepts and greater precision in general in use of proliferation-related terminology.

31P NMR spectroscopy studies of phospholipid metabolism in human melanoma xenograft lines differing in rate of tumour cell proliferation.

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Lyng, H; Olsen, D R; Petersen, S B; Rofstad, E K

1995-04-01

The concentration of phospholipid metabolites in tumours has been hypothesized to be related to rate of cell membrane turnover and may reflect rate of cell proliferation. The purpose of the study reported here was to investigate whether 31P NMR resonance ratios involving the phosphomonoester (PME) or phosphodiester (PDE) resonance are correlated to fraction of cells in S-phase or volume-doubling time in experimental tumours. Four human melanoma xenograft lines (BEX-t, HUX-t, SAX-t, WIX-t) were included in the study. The tumours were grown subcutaneously in male BALB/c-nu/nu mice. 31P NMR spectroscopy was performed at a magnetic field strength of 4.7 T. Fraction of cells in S-phase was measured by flow cytometry. Tumour volume-doubling time was determined by Gompertzian analysis of volumetric growth data. BEX-t and SAX-t tumours differed in fraction of cells in S-phase and volume-doubling time, but showed similar 31P NMR resonance ratios. BEX-t and WIX-t tumours showed significantly different 31P NMR resonance ratios but similar fractions of cells in S-phase. The 31P NMR resonance ratios were significantly different for small and large HUX-t tumours even though fraction of cells in S-phase and volume-doubling time did not differ with tumour volume. None of the 31P NMR resonance ratios showed significant increase with increasing fraction of cells in S-phase or significant decrease with increasing tumour volume-doubling time across the four xenograft lines.(ABSTRACT TRUNCATED AT 250 WORDS)

Dedifferentiation, Proliferation, and Redifferentiation of Adult Mammalian Cardiomyocytes After Ischemic Injury.

Science.gov (United States)

Wang, Wei Eric; Li, Liangpeng; Xia, Xuewei; Fu, Wenbin; Liao, Qiao; Lan, Cong; Yang, Dezhong; Chen, Hongmei; Yue, Rongchuan; Zeng, Cindy; Zhou, Lin; Zhou, Bin; Duan, Dayue Darrel; Chen, Xiongwen; Houser, Steven R; Zeng, Chunyu

2017-08-29

Adult mammalian hearts have a limited ability to generate new cardiomyocytes. Proliferation of existing adult cardiomyocytes (ACMs) is a potential source of new cardiomyocytes. Understanding the fundamental biology of ACM proliferation could be of great clinical significance for treating myocardial infarction (MI). We aim to understand the process and regulation of ACM proliferation and its role in new cardiomyocyte formation of post-MI mouse hearts. β-Actin-green fluorescent protein transgenic mice and fate-mapping Myh6-MerCreMer-tdTomato/lacZ mice were used to trace the fate of ACMs. In a coculture system with neonatal rat ventricular myocytes, ACM proliferation was documented with clear evidence of cytokinesis observed with time-lapse imaging. Cardiomyocyte proliferation in the adult mouse post-MI heart was detected by cell cycle markers and 5-ethynyl-2-deoxyuridine incorporation analysis. Echocardiography was used to measure cardiac function, and histology was performed to determine infarction size. In vitro, mononucleated and bi/multinucleated ACMs were able to proliferate at a similar rate (7.0%) in the coculture. Dedifferentiation proceeded ACM proliferation, which was followed by redifferentiation. Redifferentiation was essential to endow the daughter cells with cardiomyocyte contractile function. Intercellular propagation of Ca 2+ from contracting neonatal rat ventricular myocytes into ACM daughter cells was required to activate the Ca 2+ -dependent calcineurin-nuclear factor of activated T-cell signaling pathway to induce ACM redifferentiation. The properties of neonatal rat ventricular myocyte Ca 2+ transients influenced the rate of ACM redifferentiation. Hypoxia impaired the function of gap junctions by dephosphorylating its component protein connexin 43, the major mediator of intercellular Ca 2+ propagation between cardiomyocytes, thereby impairing ACM redifferentiation. In vivo, ACM proliferation was found primarily in the MI border zone. An ischemia

Human tumor cell proliferation evaluated using manganese-enhanced MRI.

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Rod D Braun

Full Text Available Tumor cell proliferation can depend on calcium entry across the cell membrane. As a first step toward the development of a non-invasive test of the extent of tumor cell proliferation in vivo, we tested the hypothesis that tumor cell uptake of a calcium surrogate, Mn(2+ [measured with manganese-enhanced MRI (MEMRI], is linked to proliferation rate in vitro.Proliferation rates were determined in vitro in three different human tumor cell lines: C918 and OCM-1 human uveal melanomas and PC-3 prostate carcinoma. Cells growing at different average proliferation rates were exposed to 1 mM MnCl(2 for one hour and then thoroughly washed. MEMRI R(1 values (longitudinal relaxation rates, which have a positive linear relationship with Mn(2+ concentration, were then determined from cell pellets. Cell cycle distributions were determined using propidium iodide staining and flow cytometry. All three lines showed Mn(2+-induced increases in R(1 compared to cells not exposed to Mn(2+. C918 and PC-3 cells each showed a significant, positive correlation between MEMRI R(1 values and proliferation rate (p≤0.005, while OCM-1 cells showed no significant correlation. Preliminary, general modeling of these positive relationships suggested that pellet R(1 for the PC-3 cells, but not for the C918 cells, could be adequately described by simply accounting for changes in the distribution of the cell cycle-dependent subpopulations in the pellet.These data clearly demonstrate the tumor-cell dependent nature of the relationship between proliferation and calcium influx, and underscore the usefulness of MEMRI as a non-invasive method for investigating this link. MEMRI is applicable to study tumors in vivo, and the present results raise the possibility of evaluating proliferation parameters of some tumor types in vivo using MEMRI.

Molecular imaging of proliferation with [{sup 18}F]FLT-PET; Molekulare Bildgebung der Proliferation mit [{sup 18}F]FLT-PET

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Buck, A.K.; Herrmann, K.; Schwaiger, M.; Wester, H.J. [Klinikum rechts der Isar, Technische Univ. Muenchen (Germany). Nuklearmedizinische Klinik und Poliklinik; Dechow, T.; Graf, N. [Klinikum rechts der Isar, Technische Univ. Muenchen (Germany). Medizinische Klinik III, Haematologi/Onkologie

2009-06-15

An increased proliferation fraction is a hallmark of malignant cells and a specific feature of malignant tumors which potentially allows more specific tumor imaging compared to increased glucose consumption (FDG-PET). The majority of therapeutic approaches aim at inhibition of proliferation or induction of apoptosis. Accordingly, non-invasive assessment of the proliferation fraction is also of interest for monitoring response to treatment and to early detect resistance to a specific kind of therapy. In clinical studies it has been demonstrated that the radiotracer 3'-deoxy-3'-[{sup 18}F]fluorothymidine (FLT) accumulates specifically in malignant tumors. Regression analysis of tumoral FLT-uptake and immunohistochemically detected proliferation fraction (PCNA, Ki-67) resulted in a significant correlation (e.g., in lung cancer, correlation coefficient r=0.87, p<0.0001). The possibility to non-invasively assess the proliferation fraction with FLT-PET has been shown in a variety of solid cancers. Compared to the standard radiotracer FDG, superior demonstration of the proliferative activity using FLT as the tracer has been demonstrated. On the other hand, accumulation of FLT was significantly lower compared to FDG. Malignant tumors with low proliferation rates did not present with increased FLT-uptake resulting in a reduced sensitivity. In lung cancer for example, the sensitivity was 86% of FLT-PET compared to 100% of FDG-PET. Also, regarding detection of locoregional lymph node metastases or distant metastases, FDG-PET was shown to have a higher sensitivity. Due to the reduced sensitivity, there is no advantage of specific imaging of tumor proliferation regarding tumor staging. In malignant lymphoma, FLT was similar effective for tumor staging as compared to FDG-PET. In a pilot study comprising 34 patients, both tracers showed a similar sensitivity regarding detection of lymphoma. An observed specificity of 100% indicates that FLT-PET represents a diagnostic

Recall of short word lists presented visually at fast rates: effects of phonological similarity and word length.

Science.gov (United States)

Coltheart, V; Langdon, R

1998-03-01

Phonological similarity of visually presented list items impairs short-term serial recall. Lists of long words are also recalled less accurately than are lists of short words. These results have been attributed to phonological recoding and rehearsal. If subjects articulate irrelevant words during list presentation, both phonological similarity and word length effects are abolished. Experiments 1 and 2 examined effects of phonological similarity and recall instructions on recall of lists shown at fast rates (from one item per 0.114-0.50 sec), which might not permit phonological encoding and rehearsal. In Experiment 3, recall instructions and word length were manipulated using fast presentation rates. Both phonological similarity and word length effects were observed, and they were not dependent on recall instructions. Experiments 4 and 5 investigated the effects of irrelevant concurrent articulation on lists shown at fast rates. Both phonological similarity and word length effects were removed by concurrent articulation, as they were with slow presentation rates.

Adrenergic factors involved in the control of crypt cell proliferation in jejunum and descending colon of mouse.

Science.gov (United States)

Kennedy, M F; Tutton, P J; Barkla, D H

1983-01-01

The mitotic rates in the crypts of Lieberkühn of the proximal jejunum and descending colon of mouse, following different treatments, were measured using a stathmokinetic technique. Regression coefficients, representing mitotic rates, were then calculated by the method of least squares. Treatment with adrenaline, isoprenaline, phenylephrine, phentolamine, and yohimbine all resulted in decreased mitotic rate of jejunal and colonic crypt cells. Chemical sympathectomy and cryosympathectomy had a similar effect, and chemical sympathectomy was followed by a supersensitivity to clonidine. Intraperitoneal injection of metaraminol, clonidine, propranolol, prazosin, labetolol and simultaneous injection of propranolol and adrenaline all resulted in an increased rate of crypt cell proliferation in both jejunum and colon. A significant increase in mitotic rate was observed in both tissues at night. The amplitude of this diurnal variation was decreased in both jejunum and colon following chemical sympathectomy. In addition, the amplitude of this variation in jejunum was decreased after treatment with yohimbine or phentolamine. The results of the study suggest that the sympathetic nervous system stimulates epithelial cell proliferation in both the small and large intestine and that this effect is mediated by an alpha 2-adrenoceptor. By contrast, stimulation of alpha 1- and beta-adrenoceptors is inhibitory to cell proliferation in these tissues.

Laser isotope separation and proliferation risks

Energy Technology Data Exchange (ETDEWEB)

Fuss, Werner

2015-02-15

There is an ongoing discussion on the proliferation danger of laser enrichment of uranium by the Silex process. Here this risk is compared to that of other processes, in particular centrifuges. The two methods need a similar size of the plant for a comparable production rate (in separative work units per year) and the time and costs for their construction do not differ much. This conclusion from published material does not depend on technical details of Silex. But enough details are known to allow for additional conclusions: Whereas the selectivity (enrichment factor) in the Silex process seems higher, the energy consumption is probably larger. Due to the laser's repetition rate being insufficient for the molecular beam, the method has probably a low depletion factor; this is a serious disadvantage for cascading for high enrichment such as for bomb uranium, although it may be acceptable for low enrichment without cascading for reactor purposes.

MicroRNA-2400 promotes bovine preadipocyte proliferation

International Nuclear Information System (INIS)

Wei, Yao; Cui, Ya Feng; Tong, Hui Li; Zhang, Wei Wei; Yan, Yun Qin

2016-01-01

MicroRNAs (miRNAs) play critical roles in the proliferation of bovine preadipocytes. miR-2400 is a novel and unique miRNA from bovines. In the present study, we separated and identified preadipocytes from bovine samples. miR-2400 overexpression increased the rate of preadipocyte proliferation, which was analyzed with a combination of EdU and flow cytometry. Simultaneously, functional genes related to proliferation (PCNA, CCND2, CCNB1) were also increased, which was detected by real-time PCR. Furthermore, luciferase reporter assays showed that miR-2400 bound directly to the 3'untranslated regions (3′UTRs) of PRDM11 mRNA. These data suggested that miR-2400 could promote preadipocyte proliferation by targeting PRDM11. - Highlights: • miRNAs are important in bovine preadipocyte proliferation. • miR-2400 is a novel miRNA from bovines. • miR-2400 overexpression increased preadipocyte proliferation. • Functional genes related to preadipocyte proliferation were upregulated. • Preadipocyte proliferation was promoted by targeting PRDM11.

Polybrene inhibits human mesenchymal stem cell proliferation during lentiviral transduction.

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Paul Lin

Full Text Available Human mesenchymal stem cells (hMSCs can be engineered to express specific genes, either for their use in cell-based therapies or to track them in vivo over long periods of time. To obtain long-term expression of these genes, a lentivirus- or retrovirus-mediated cell transduction is often used. However, given that the efficiency with these viruses is typically low in primary cells, additives such as polybrene are always used for efficient viral transduction. Unfortunately, as presented here, exposure to polybrene alone at commonly used concentratons (1-8 µg/mL negatively impacts hMSC proliferation in a dose-dependent manner as measured by CyQUANT, EdU incorporation, and cell cycle analysis. This inhibition of proliferation was observable in culture even 3 weeks after exposure. Culturing the cells in the presence of FGF-2, a potent mitogen, did not abrogate this negative effect of polybrene. In fact, the normally sharp increase in hMSC proliferation that occurs during the first days of exposure to FGF-2 was absent at 4 µg/mL or higher concentrations of polybrene. Similarly, the effect of stimulating cell proliferation under simulated hypoxic conditions was also decreased when cells were exposed to polybrene, though overall proliferation rates were higher. The negative influence of polybrene was, however, reduced when the cells were exposed to polybrene for a shorter period of time (6 hr vs 24 hr. Thus, careful evaluation should be done when using polybrene to aid in lentiviral transduction of human MSCs or other primary cells, especially when cell number is critical.

Mixed effects modeling of proliferation rates in cell-based models: consequence for pharmacogenomics and cancer.

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Hae Kyung Im

2012-02-01

Full Text Available The International HapMap project has made publicly available extensive genotypic data on a number of lymphoblastoid cell lines (LCLs. Building on this resource, many research groups have generated a large amount of phenotypic data on these cell lines to facilitate genetic studies of disease risk or drug response. However, one problem that may reduce the usefulness of these resources is the biological noise inherent to cellular phenotypes. We developed a novel method, termed Mixed Effects Model Averaging (MEM, which pools data from multiple sources and generates an intrinsic cellular growth rate phenotype. This intrinsic growth rate was estimated for each of over 500 HapMap cell lines. We then examined the association of this intrinsic growth rate with gene expression levels and found that almost 30% (2,967 out of 10,748 of the genes tested were significant with FDR less than 10%. We probed further to demonstrate evidence of a genetic effect on intrinsic growth rate by determining a significant enrichment in growth-associated genes among genes targeted by top growth-associated SNPs (as eQTLs. The estimated intrinsic growth rate as well as the strength of the association with genetic variants and gene expression traits are made publicly available through a cell-based pharmacogenomics database, PACdb. This resource should enable researchers to explore the mediating effects of proliferation rate on other phenotypes.

Diseased muscles that lack dystrophin or laminin-α2 have altered compositions and proliferation of mononuclear cell populations

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Miller Jeffrey

2005-04-01

Full Text Available Abstract Background Multiple types of mononucleate cells reside among the multinucleate myofibers in skeletal muscles and these mononucleate cells function in muscle maintenance and repair. How neuromuscular disease might affect different types of muscle mononucleate cells had not been determined. In this study, therefore, we examined how two neuromuscular diseases, dystrophin-deficiency and laminin-α2-deficiency, altered the proliferation and composition of different subsets of muscle-derived mononucleate cells. Methods We used fluorescence-activated cell sorting combined with bromodeoxyuridine labeling to examine proliferation rates and compositions of mononuclear cells in diseased and healthy mouse skeletal muscle. We prepared mononucleate cells from muscles of mdx (dystrophin-deficient or Lama2-/- (laminin-α2-deficient mice and compared them to cells from healthy control muscles. We enumerated subsets of resident muscle cells based on Sca-1 and CD45 expression patterns and determined the proliferation of each cell subset in vivo by BrdU incorporation. Results We found that the proliferation and composition of the mononucleate cells in dystrophin-deficient and laminin-α2-deficient diseased muscles are different than in healthy muscle. The mdx and Lama2-/- muscles showed similar significant increases in CD45+ cells compared to healthy muscle. Changes in proliferation, however, differed between the two diseases with proliferation increased in mdx and decreased in Lama2-/- muscles compared to healthy muscles. In particular, the most abundant Sca-1-/CD45- subset, which contains muscle precursor cells, had increased proliferation in mdx muscle but decreased proliferation in Lama2-/- muscles. Conclusion The similar increases in CD45+ cells, but opposite changes in proliferation of muscle precursor cells, may underlie aspects of the distinct pathologies in the two diseases.

Harmine stimulates proliferation of human neural progenitors

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Vanja Dakic

2016-12-01

Full Text Available Harmine is the β-carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 71.5%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A, which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY, and an irreversible selective inhibitor of monoamine oxidase (MAO but not DYRK1A (pargyline. INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of DYRK1A is a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo.

Modification of cell growth rate by irradiation

International Nuclear Information System (INIS)

Itoh, Hisao; Takemasa, Kazuhiko; Nishiguchi, Iku; Ka, Wei-Jei; Kutsuki, Shoji; Hashimoto, Shozo

1993-01-01

The effect of irradiation on the proliferation kinetics of the monolayer cells has been studied. Two human cell lines with different doubling times (HeLa-P and RMUG) and two clones that have the same radiosensitivity but different doubling times (HeLa-R and HeLa-S) were irradiated with a daily dose of 2 Gy for 6 days. The number of the clonogenic cells/dish was calculated by multiplying the number of total cell/dish by the survival fraction. In the rapidly growing cells (HeLa-P, HeLa-R), the number of the clonogenic cells was not decreased by the first two fractionated irradiations, but decreased thereafter at a similar rate as by single-dose fractionation, whereas the clonogenic cell number decreased from the first fractionated irradiation in the slowly growing cells (RMUG, HeLa-S). When the proliferation of clonogenic cell number increased along with a similar growth rates that was seen in all other types of cells. Further, no correlation was seen between the growth rates of cells without irradiation and cells that received irradiation. This latter result suggests that the slow growth rate of non-irradiated cells may not be the predictive factor of the tumor cure and the interruption of radiotherapy may reduce the beneficial effect of this treatment even in slow growing tumors. (author)

Proliferation of the Golgi apparatus in tobacco BY-2 cells during cell proliferation after release from the stationary phase of growth.

Science.gov (United States)

Abiodun, Moses; Matsuoka, Ken

2013-08-01

We have recently developed a new method aimed at mass photo-conversion of photo-convertible fluorescence protein (PFP) fluorescence in transformed tobacco BY-2 cells. Using this method we reported recently that the Golgi apparatus is generated by the de novo formation from ER and the division of pre-existing Golgi stacks with similar extents In this work we report that the proliferation of the Golgi apparatus in tobacco cells that enter the growing cycle from the non-dividing cycle is quite similar to that in rapidly growing cells and that de novo formation from the ER and division of pre-existing stacks seems to contribute almost equally to the proliferation.

Non-proliferation and security: synergy and differences

International Nuclear Information System (INIS)

Joly, J.

2013-01-01

Operators of nuclear facilities put in place both physical and organisational means to meet in a comprehensive way the requirements associated with Nuclear Non-Proliferation, Safety and Security. The common aim is to protect man and the environment from ionising radiation. The approaches for meeting these requirements have real similarities, but also differences which need to be respected in order to develop an appropriate synergy for obtaining the best possible level of safety, security and non-proliferation. This article aims to show the provisions that have been taken with regard to non-proliferation, security and safety which complement and reinforce each other.The paper is followed by the slides of the presentation. (author)

Sustaining non-proliferation in the 1980s

International Nuclear Information System (INIS)

Nye, J.S.

1984-01-01

The subject is discussed as follows: introduction; the non-proliferation regime - 1950s to 1970s (IAEA safeguards; Non-proliferation Treaty; oil crisis; proposed sale of facilities for producing weapons-usable materials; USA position); the Carter Administration approach; INFCE (International Nuclear Fuel Cycle Evaluation); incentives (USA); export legislation (USA); domestic breeder policy (USA); maintaining the regime in the 1980s (safeguards; Pu and highly enriched uranium management; international spent fuel storage; fuel assurances); the problem of priority; rate vs. degree of proliferation; relations among regimes (international regimes); conclusion. (U.K.)

Acellular dermal matrix loading with bFGF achieves similar acceleration of bone regeneration to BMP-2 via differential effects on recruitment, proliferation and sustained osteodifferentiation of mesenchymal stem cells

International Nuclear Information System (INIS)

Du, Mi; Zhu, Ting; Duan, Xiaoqi; Ge, Shaohua; Li, Ning; Sun, Qinfeng; Yang, Pishan

2017-01-01

New generation of barrier membranes has been developed, which not only act as barriers but also as delivery devices to release specific growth factors. This study observed biological behaviors of bone morrow mesenchymal stem cells (BMMSCs) pretreated by bFGF or BMP-2 in vitro and evaluated differential bone regeneration process induced by bFGF and BMP-2 loaded acellular dermal matrix (ADM) membrane using critical-size rat calvarial defect model in vivo. The results showed that the proliferation capability of BMMSCs pretreated by bFGF was stronger than that by BMP-2, while there was temporally differential effect of bFGF and BMP-2 pretreatment on MSC osteogenic differentiation potentials. During healing process of rat calvarial defects, 2-fold more CD34 −/CD90 + MSCs in group of bFGF-ADM was observed than in any other treatment group at 2 weeks. However, there were similar amount of new bone formation and expression of osteopotin in newly-formed bone tissue in groups of bFGF- and BMP-2-ADM at 8 weeks, which were more than those in ADM alone and blank control. Taken together, bFGF-ADM guided similar bone regeneration to BMP-2 through more efficient recruitment of MSCs, and moreover, BMMSCs pretreated by bFGF showed stronger proliferation at 1–5 days and osteogenic differentiation potentials at 14 days compared with BMP-2 pretreatment. - Highlights: • An improved barrier membrane used in the field of bone tissue engineering was proposed, which is acellular dermal matrix (ADM) loaded with growth factors. • It is generally agreed that BMP-2 and -7 provide the greatest bone regeneration potentials, however, we found that ADM loading with bFGF could guide similar bone regeneration to BMP-2. • Compared with BMP-2, bFGF could more effectively recruit MSCs and moreover, BMMSCs pretreated by bFGF showed out stronger proliferation at 1-5 days and osteogenic differentiation potentials at 14 days.

A secreted factor represses cell proliferation in Dictyostelium.

Science.gov (United States)

Brock, Debra A; Gomer, Richard H

2005-10-01

Many cells appear to secrete factors called chalones that limit their proliferation, but in most cases the factors have not been identified. We found that growing Dictyostelium cells secrete a 60 kDa protein called AprA for autocrine proliferation repressor. AprA has similarity to putative bacterial proteins of unknown function. Compared with wild-type cells, aprA-null cells proliferate faster, while AprA overexpressing cells proliferate slower. Growing wild-type cells secrete a factor that inhibits the proliferation of wild-type and aprA- cells; this activity is not secreted by aprA- cells. AprA purified by immunoprecipitation also slows the proliferation of wild-type and aprA- cells. Compared with wild type, there is a higher percentage of multinucleate cells in the aprA- population, and when starved, aprA- cells form abnormal structures that contain fewer spores. AprA may thus decrease the number of multinucleate cells and increase spore production. Together, the data suggest that AprA functions as part of a Dictyostelium chalone.

EDA-containing fibronectin increases proliferation of embryonic stem cells.

Directory of Open Access Journals (Sweden)

Noelia Losino

Full Text Available Embryonic stem cells (ESC need a set of specific factors to be propagated. They can also grow in conditioned medium (CM derived from a bovine granulosa cell line BGC (BGC-CM, a medium that not only preserves their main features but also increases ESC´s proliferation rate. The mitogenic properties of this medium were previously reported, ascribing this effect to an alternative spliced generated fibronectin isoform that contains the extra domain A (FN EDA(+. Here, we investigated if the FN EDA(+ isoform increased proliferation of mouse and human ES cells. We analyzed cell proliferation using conditioned media produced by different mouse embryonic fibroblast (MEF lines genetically engineered to express FN constitutively including or excluding the EDA domain (FN EDA(-, and in media supplemented with recombinant peptides containing or not the EDA. We found that the presence of EDA in the medium increased mouse and human ESC's proliferation rate. Here we showed for the first time that this FN isoform enhances ESC's proliferation. These findings suggest a possible conserved behavior for regulation of ES cells proliferation by this FN isoform and could contribute to improve their culturing conditions both for research and cell therapy.

WE-D-BRE-05: Prediction of Late Radiation-Induced Proctitis in Prostate Cancer Patients Using Chromosome Aberration and Cell Proliferation Rate

Energy Technology Data Exchange (ETDEWEB)

Oh, J; Deasy, J [Memorial Sloan Kettering Cancer Center, New York, NY (United States)

2014-06-15

Purpose: Chromosome damage and cell proliferation rate have been investigated as potential biomarkers for the early prediction of late radiationinduced toxicity. Incorporating these endpoints, we explored the predictive power for late radiation proctitis using a machine learning method. Methods: Recently, Beaton et al. showed that chromosome aberration and cell proliferation rate could be used as biomarkers to predict late radiation proctitis (Beaton et al. (2013) Int J Rad Onc Biol Phys, 85:1346–1352). For the identification of radiosensitive biomarkers, blood samples were collected from 10 patients with grade 3 late proctitis along with 20 control patients with grade 0 proctitis. After irradiation at 6 Gy, statistically significant difference was observed between the two groups, using the number of dicentrics and excess fragments, and the number of cells in metaphase 2 (M2). However, Beaton et al. did not show the usefulness of combining these endpoints. We reanalyzed the dataset to investigate whether incorporating these endpoints can increase the predictive power of radiation proctitis, using a support vector machine (SVM). Results: Using the SVM method with the number of fragments and M2 endpoints, perfect classification was achieved. In addition, to avoid biased estimate of the classification method, leave-one-out cross-validation (LOO-CV) was performed. The best performance was achieved when all three endpoints were used with 87% accuracy, 90% sensitivity, 85% specificity, and 0.85 AUC (the area under the receiver operating characteristic (ROC) curve). The most significant endpoint was the number of fragments that obtained 83% accuracy, 70% sensitivity, 90% specificity, and 0.82 AUC. Conclusion: We demonstrated that chromosome damage and cell proliferation rate could be significant biomarkers to predict late radiation proctitis. When these endpoints were used together in conjunction with a machine learning method, the better performance was obtained

Lipogems Product Treatment Increases the Proliferation Rate of Human Tendon Stem Cells without Affecting Their Stemness and Differentiation Capability.

Science.gov (United States)

Randelli, Pietro; Menon, Alessandra; Ragone, Vincenza; Creo, Pasquale; Bergante, Sonia; Randelli, Filippo; De Girolamo, Laura; Alfieri Montrasio, Umberto; Banfi, Giuseppe; Cabitza, Paolo; Tettamanti, Guido; Anastasia, Luigi

2016-01-01

Increasing the success rate of rotator cuff healing remains tremendous challenge. Among many approaches, the possibility of activating resident stem cells in situ, without the need to isolate them from biopsies, could represent valuable therapeutic strategy. Along this line, it has been recently demonstrated that lipoaspirate product, Lipogems, contains and produces growth-factors that may activate resident stem cells. In this study, human tendon stem cells (hTSCs) from the rotator cuff were cocultured in a transwell system with the Lipogems lipoaspirate product and compared to control untreated cells in terms of cell proliferation, morphology, stem cell marker and VEGF expression, and differentiation and migration capabilities. Results showed that the Lipogems product significantly increases the proliferation rate of hTSCs without altering their stemness and differentiation capability. Moreover, treated cells increase the expression of VEGF, which is crucial for the neovascularization of the tissue during the healing process. Overall, this study supports that directly activating hTSCs with the Lipogems lipoaspirate could represent a new practical therapeutic approach. In fact, obtaining a lipoaspirate is easier, safer, and more cost-effective than harvesting cells from tendon or bone marrow biopsies, expanding them in GMP facility and then reinjecting them in the patient.

Lipogems Product Treatment Increases the Proliferation Rate of Human Tendon Stem Cells without Affecting Their Stemness and Differentiation Capability

Directory of Open Access Journals (Sweden)

Pietro Randelli

2016-01-01

Full Text Available Increasing the success rate of rotator cuff healing remains tremendous challenge. Among many approaches, the possibility of activating resident stem cells in situ, without the need to isolate them from biopsies, could represent valuable therapeutic strategy. Along this line, it has been recently demonstrated that lipoaspirate product, Lipogems, contains and produces growth-factors that may activate resident stem cells. In this study, human tendon stem cells (hTSCs from the rotator cuff were cocultured in a transwell system with the Lipogems lipoaspirate product and compared to control untreated cells in terms of cell proliferation, morphology, stem cell marker and VEGF expression, and differentiation and migration capabilities. Results showed that the Lipogems product significantly increases the proliferation rate of hTSCs without altering their stemness and differentiation capability. Moreover, treated cells increase the expression of VEGF, which is crucial for the neovascularization of the tissue during the healing process. Overall, this study supports that directly activating hTSCs with the Lipogems lipoaspirate could represent a new practical therapeutic approach. In fact, obtaining a lipoaspirate is easier, safer, and more cost-effective than harvesting cells from tendon or bone marrow biopsies, expanding them in GMP facility and then reinjecting them in the patient.

Nanoscale crystallinity modulates cell proliferation on plasma sprayed surfaces

Energy Technology Data Exchange (ETDEWEB)

Smith, Alan M. [School of Applied Sciences, University of Huddersfield, Huddersfield HD1 3DH (United Kingdom); Paxton, Jennifer Z.; Hung, Yi-Pei; Hadley, Martin J.; Bowen, James; Williams, Richard L. [School of Chemical Engineering, University of Birmingham, Edgbaston, B15 2TT (United Kingdom); Grover, Liam M., E-mail: l.m.grover@bham.ac.uk [School of Chemical Engineering, University of Birmingham, Edgbaston, B15 2TT (United Kingdom)

2015-03-01

Calcium phosphate coatings have been applied to the surface of metallic prostheses to mediate hard and soft tissue attachment for more than 40 years. Most coatings are formed of high purity hydroxyapatite, and coating methods are often designed to produce highly crystalline surfaces. It is likely however, that coatings of lower crystallinity can facilitate more rapid tissue attachment since the surface will exhibit a higher specific surface area and will be considerably more reactive than a comparable highly crystalline surface. Here we test this hypothesis by growing a population of MC3T3 osteoblast-like cells on the surface of two types of hip prosthesis with similar composition, but with differing crystallinity. The surfaces with lower crystallinity facilitated more rapid cell attachment and increased proliferation rate, despite having a less heterogeneous surface topography. This work highlights that the influence of the crystallinity of HA at the nano-scale is dominant over macro-scale topography for cell adhesion and growth. Furthermore, crystallinity could be easily adjusted by without compromising coating purity. These findings could facilitate designing novel coated calcium phosphate surfaces that more rapidly bond tissue following implantation. - Highlights: • Crystallinity of HA at the nano-scale was dominant over macro-scale topography. • Lower crystallinity caused rapid cell attachment and proliferation rate. • Crystallinity could be easily adjusted by without compromising coating purity.

Nanoscale crystallinity modulates cell proliferation on plasma sprayed surfaces

International Nuclear Information System (INIS)

Smith, Alan M.; Paxton, Jennifer Z.; Hung, Yi-Pei; Hadley, Martin J.; Bowen, James; Williams, Richard L.; Grover, Liam M.

2015-01-01

Calcium phosphate coatings have been applied to the surface of metallic prostheses to mediate hard and soft tissue attachment for more than 40 years. Most coatings are formed of high purity hydroxyapatite, and coating methods are often designed to produce highly crystalline surfaces. It is likely however, that coatings of lower crystallinity can facilitate more rapid tissue attachment since the surface will exhibit a higher specific surface area and will be considerably more reactive than a comparable highly crystalline surface. Here we test this hypothesis by growing a population of MC3T3 osteoblast-like cells on the surface of two types of hip prosthesis with similar composition, but with differing crystallinity. The surfaces with lower crystallinity facilitated more rapid cell attachment and increased proliferation rate, despite having a less heterogeneous surface topography. This work highlights that the influence of the crystallinity of HA at the nano-scale is dominant over macro-scale topography for cell adhesion and growth. Furthermore, crystallinity could be easily adjusted by without compromising coating purity. These findings could facilitate designing novel coated calcium phosphate surfaces that more rapidly bond tissue following implantation. - Highlights: • Crystallinity of HA at the nano-scale was dominant over macro-scale topography. • Lower crystallinity caused rapid cell attachment and proliferation rate. • Crystallinity could be easily adjusted by without compromising coating purity

Training of tonal similarity ratings in non-musicians: a "rapid learning" approach.

Science.gov (United States)

Oechslin, Mathias S; Läge, Damian; Vitouch, Oliver

2012-01-01

Although cognitive music psychology has a long tradition of expert-novice comparisons, experimental training studies are rare. Studies on the learning progress of trained novices in hearing harmonic relationships are still largely lacking. This paper presents a simple training concept using the example of tone/triad similarity ratings, demonstrating the gradual progress of non-musicians compared to musical experts: In a feedback-based "rapid learning" paradigm, participants had to decide for single tones and chords whether paired sounds matched each other well. Before and after the training sessions, they provided similarity judgments for a complete set of sound pairs. From these similarity matrices, individual relational sound maps, intended to display mental representations, were calculated by means of non-metric multidimensional scaling (NMDS), and were compared to an expert model through procrustean transformation. Approximately half of the novices showed substantial learning success, with some participants even reaching the level of professional musicians. Results speak for a fundamental ability to quickly train an understanding of harmony, show inter-individual differences in learning success, and demonstrate the suitability of the scaling method used for learning research in music and other domains. Results are discussed in the context of the "giftedness" debate.

Training of tonal similarity ratings in non-musicians: a rapid learning approach

Directory of Open Access Journals (Sweden)

Mathias S Oechslin

2012-05-01

Full Text Available Although music psychology has a long tradition of expert-novice comparisons, experimental training studies are rare. Studies on the learning progress of trained novices in hearing harmonic relationships are still largely lacking. This paper presents a simple training concept using the example of tone/triad similarity ratings, demonstrating the gradual progress of non-musicians compared to musical experts: In a feedback-based rapid learning paradigm, participants had to decide for single tones and chords whether paired sounds matched each other well. Before and after the training sessions, they provided similarity judgments for a complete set of sound pairs. From these similarity matrices, individual relational sound maps, aiming to map the mental representations, were calculated by means of non-metric multidimensional scaling (NMDS, which were compared to an expert model through procrustean transformation. Approximately half of the novices showed substantial learning success, with some participants even reaching the level of professional musicians. Results speak for a fundamental ability to quickly train an understanding of harmony, show inter-individual differences in learning success, and demonstrate the suitability of the scaling method used for music psychological research. Results are discussed in the context of the giftedness debate.

MM-MDS: a multidimensional scaling database with similarity ratings for 240 object categories from the Massive Memory picture database.

Directory of Open Access Journals (Sweden)

Michael C Hout

Full Text Available Cognitive theories in visual attention and perception, categorization, and memory often critically rely on concepts of similarity among objects, and empirically require measures of "sameness" among their stimuli. For instance, a researcher may require similarity estimates among multiple exemplars of a target category in visual search, or targets and lures in recognition memory. Quantifying similarity, however, is challenging when everyday items are the desired stimulus set, particularly when researchers require several different pictures from the same category. In this article, we document a new multidimensional scaling database with similarity ratings for 240 categories, each containing color photographs of 16-17 exemplar objects. We collected similarity ratings using the spatial arrangement method. Reports include: the multidimensional scaling solutions for each category, up to five dimensions, stress and fit measures, coordinate locations for each stimulus, and two new classifications. For each picture, we categorized the item's prototypicality, indexed by its proximity to other items in the space. We also classified pairs of images along a continuum of similarity, by assessing the overall arrangement of each MDS space. These similarity ratings will be useful to any researcher that wishes to control the similarity of experimental stimuli according to an objective quantification of "sameness."

MM-MDS: a multidimensional scaling database with similarity ratings for 240 object categories from the Massive Memory picture database.

Science.gov (United States)

Hout, Michael C; Goldinger, Stephen D; Brady, Kyle J

2014-01-01

Cognitive theories in visual attention and perception, categorization, and memory often critically rely on concepts of similarity among objects, and empirically require measures of "sameness" among their stimuli. For instance, a researcher may require similarity estimates among multiple exemplars of a target category in visual search, or targets and lures in recognition memory. Quantifying similarity, however, is challenging when everyday items are the desired stimulus set, particularly when researchers require several different pictures from the same category. In this article, we document a new multidimensional scaling database with similarity ratings for 240 categories, each containing color photographs of 16-17 exemplar objects. We collected similarity ratings using the spatial arrangement method. Reports include: the multidimensional scaling solutions for each category, up to five dimensions, stress and fit measures, coordinate locations for each stimulus, and two new classifications. For each picture, we categorized the item's prototypicality, indexed by its proximity to other items in the space. We also classified pairs of images along a continuum of similarity, by assessing the overall arrangement of each MDS space. These similarity ratings will be useful to any researcher that wishes to control the similarity of experimental stimuli according to an objective quantification of "sameness."

Effect of irradiance and spectral composition of radiation on in vitro shoot proliferation in Malus domestica

International Nuclear Information System (INIS)

Noè, N.; Eccher, T.; Bonini, L.

1997-01-01

Four clones of Malus domestica cv. Golden Delicious - namely Smoothee, Crielaard, Reinders and Golden B - were cultured in vitro from single-node microcuttings placed on solid medium under irradiance (PPFD) of 50 micromol m -2 s -1 . After 9 months an average shoot proliferation of 5.3 was achieved; Crielaard showed the highest rate (7.1), followed Golden B (5.4), Smoothee and Reinders (4.4). Proliferating shoots were then exposed to higher PPFD (80 micromol m -2 s -1 ) and different spectral composition of radiation using PMMA-B and PMMA-R/FR filters. High PPFD decreased the average proliferation rate to 4.5, in particular in Crielaard and Golden B, while it increased proliferation in Reinders. When a PMMA-R/FR filter was interposed, the mean proliferation rate slightly increased. PMMA-B filters decreased the overall proliferation rate to 3.0; only in Crielaard it was increased, but shoots were very small. Thus PPFD and spectral composition influenced in vitro shoot proliferation and growth and the responses were different among the clones. (author)

Infrasonic measurements of the Non-Proliferation Experiment

Energy Technology Data Exchange (ETDEWEB)

Whitaker, R.W.; Noel, S.; Meadows, W. [Los Alamos National Laboratory, NM (United States)

1994-12-31

Two infrasonic arrays were operated for the Non-Proliferation Experiment (NPE). The arrays were located at the Nevada Test Site and at St. George, UT. The results were consistent with experience on underground tests, and therefore close to underground nuclear tests of similar size.

Effect of 103Pd on proliferation and apoptosis of vascular smooth muscle cells

International Nuclear Information System (INIS)

Luo Quanyong; Zhu Jun; Lu Hankui; Zhu Ruisen

2003-01-01

This study aimed at the effect of γ-emitting radionuclide 103 Pd on the proliferation and apoptosis of vascular SMCs (smooth muscle cells) in vitro. The cavy aortic SMCs were cultured with culture medium M-199. The experiments were carried out in two groups, one for proliferation test and the other for apoptosis test. In each group, 103 Pd solutions with various radioactivities were respectively added to the culture solution to irradiate SMCs for 72 h, while non-radioactive palladium solution was added to the control. 3 H-thymidine incorporation test and liquid scintillator were used to detect the effect of 103 Pd on the proliferation of SMCs. Flow cytometer was used to detect the apoptotic SMCs. The inhibition rate of SMCs proliferation by 1.85 MBq 103 Pd solution was 2.3%, which was not significant, while the inhibition rate increased from 41.6% to 91.3% as the 103 Pd activity increased from 7.40 MBq to 37 MBq. The apoptosis rate of SMCs was extremely low (less than 4.0%) by 103 Pd with activity from 1.85 MBq to 37 MBq. The results suggest that the proliferation of SMCs can be repressed effectively in a dose-dependent fashion by 103 Pd in vitro. The mechanism of its inhibiting over neointima proliferation is likely to inhibit SMCs proliferation rather than to induce its apoptosis by 103 Pd. 103 Pd can be used as a γ-emitting intravascular brachytherapy radionuclide to inhibit SMCs proliferation

Exploring similarities and differences in hospital adverse event rates between Norway and Sweden using Global Trigger Tool.

Science.gov (United States)

Deilkås, Ellen Tveter; Risberg, Madeleine Borgstedt; Haugen, Marion; Lindstrøm, Jonas Christoffer; Nylén, Urban; Rutberg, Hans; Michael, Soop

2017-03-20

In this paper, we explore similarities and differences in hospital adverse event (AE) rates between Norway and Sweden by reviewing medical records with the Global Trigger Tool (GTT). All acute care hospitals in both countries performed medical record reviews, except one in Norway. Records were randomly selected from all eligible admissions in 2013. Eligible admissions were patients 18 years of age or older, undergoing care with an in-hospital stay of at least 24 hours, excluding psychiatric and care and rehabilitation. Reviews were done according to GTT methodology. Similar contexts for healthcare and similar socioeconomic and demographic characteristics have inspired the Nordic countries to exchange experiences from measuring and monitoring quality and patient safety in healthcare. The co-operation has promoted the use of GTT to monitor national and local rates of AEs in hospital care. 10 986 medical records were reviewed in Norway and 19 141 medical records in Sweden. No significant difference between overall AE rates was found between the two countries. The rate was 13.0% (95% CI 11.7% to 14.3%) in Norway and 14.4% (95% CI 12.6% to 16.3%) in Sweden. There were significantly higher AE rates of surgical complications in Norwegian hospitals compared with Swedish hospitals. Swedish hospitals had significantly higher rates of pressure ulcers, falls and 'other' AEs. Among more severe AEs, Norwegian hospitals had significantly higher rates of surgical complications than Swedish hospitals. Swedish hospitals had significantly higher rates of postpartum AEs. The level of patient safety in acute care hospitals, as assessed by GTT, was essentially the same in both countries. The differences between the countries in the rates of several types of AEs provide new incentives for Norwegian and Swedish governing bodies to address patient safety issues. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please

Phosphorylation at tyrosine 114 of Proliferating Cell Nuclear Antigen (PCNA) is required for adipogenesis in response to high fat diet

Energy Technology Data Exchange (ETDEWEB)

Lo, Yuan-Hung; Ho, Po-Chun; Chen, Min-Shan; Hugo, Eric; Ben-Jonathan, Nira [Department of Cancer Biology, University of Cincinnati College of Medicine, 3125 Eden Avenue, Cincinnati, OH 45267-0521 (United States); Department of Environmental Health, University of Cincinnati College of Medicine, 3223 Eden Avenue, Kettering Laboratory, Cincinnati, OH 45267-0056 (United States); Wang, Shao-Chun, E-mail: shao-chun.wang@uc.edu [Department of Cancer Biology, University of Cincinnati College of Medicine, 3125 Eden Avenue, Cincinnati, OH 45267-0521 (United States); Department of Environmental Health, University of Cincinnati College of Medicine, 3223 Eden Avenue, Kettering Laboratory, Cincinnati, OH 45267-0056 (United States)

2013-01-04

Highlights: Black-Right-Pointing-Pointer Proliferating Cell Nuclear Antigen (PCNA) is phosphorylated at Y114. Black-Right-Pointing-Pointer Phospho-Y114 of PCNA is not required for cell proliferation for normal growth. Black-Right-Pointing-Pointer MCE during adipogenesis is abolished in the lack of the phosphorylation. Black-Right-Pointing-Pointer Homozygous Y114F mice are resistant to high fat diet induced obesity. Black-Right-Pointing-Pointer Our results shed light on the interface between proliferation and differentiation. -- Abstract: Clonal proliferation is an obligatory component of adipogenesis. Although several cell cycle regulators are known to participate in the transition between pre-adipocyte proliferation and terminal adipocyte differentiation, how the core DNA synthesis machinery is coordinately regulated in adipogenesis remains elusive. PCNA (Proliferating Cell Nuclear Antigen) is an indispensable component for DNA synthesis during proliferation. Here we show that PCNA is subject to phosphorylation at the highly conserved tyrosine residue 114 (Y114). Replacing the Y114 residue with phenylalanine (Y114F), which is structurally similar to tyrosine but cannot be phosphorylated, does not affect normal animal development. However, when challenged with high fat diet, mice carrying homozygous Y114F alleles (PCNA{sup F/F}) are resistant to adipose tissue enlargement in comparison to wild-type (WT) mice. Mouse embryonic fibroblasts (MEFs) harboring WT or Y114F mutant PCNA proliferate at similar rates. However, when subjected to adipogenesis induction in culture, PCNA{sup F/F} MEFs are not able to re-enter the cell cycle and fail to form mature adipocytes, while WT MEFs undergo mitotic clonal expansion in response to the adipogenic stimulation, accompanied by enhanced Y114 phosphorylation of PCNA, and differentiate to mature adipocytes. Consistent with the function of Y114 phosphorylation in clonal proliferation in adipogenesis, fat tissues isolated from WT

Effects of RF-EMF Exposure from GSM Mobile Phones on Proliferation Rate of Human Adipose-derived Stem Cells: An In-vitro Study

Directory of Open Access Journals (Sweden)

Shahbazi-Gahrouei D

2016-12-01

Full Text Available Background: As the use of mobile phones is increasing, public concern about the harmful effects of radiation emitted by these devices is also growing. In addition, protection questions and biological effects are among growing concerns which have remained largely unanswered. Stem cells are useful models to assess the effects of radiofrequency electromagnetic fields (RF-EMF on other cell lines. Stem cells are undifferentiated biological cells that can differentiate into specialized cells. Adipose tissue represents an abundant and accessible source of adult stem cells. The aim of this study is to investigate the effects of GSM 900 MHz on growth and proliferation of mesenchymal stem cells derived from adipose tissue within the specific distance and intensity. Materials and Methods: ADSCs were exposed to GSM mobile phones 900 MHz with intensity of 354.6 µW/cm2 square waves (217 Hz pulse frequency, 50% duty cycle, during different exposure times ranging from 6 to 21 min/day for 5 days at 20 cm distance from the antenna. MTT assay was used to determine the growth and metabolism of cells and trypan blue test was also done for cell viability. Statistical analyses were carried out using analysis of one way ANOVA. P<0.05 was considered to be statistically significant. Results: The proliferation rates of human ADSCs in all exposure groups were significantly lower than control groups (P<0.05 except in the group of 6 minutes/day which did not show any significant difference with control groups. Conclusion: The results show that 900 MHz RF signal radiation from antenna can reduce cell viability and proliferation rates of human ADSCs regarding the duration of exposure.

Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress

Science.gov (United States)

Gould, Elizabeth; Tanapat, Patima; McEwen, Bruce S.; Flügge, Gabriele; Fuchs, Eberhard

1998-01-01

Although granule cells continue to be added to the dentate gyrus of adult rats and tree shrews, this phenomenon has not been demonstrated in the dentate gyrus of adult primates. To determine whether neurons are produced in the dentate gyrus of adult primates, adult marmoset monkeys (Callithrix jacchus) were injected with BrdU and perfused 2 hr or 3 weeks later. BrdU is a thymidine analog that is incorporated into proliferating cells during S phase. A substantial number of cells in the dentate gyrus of adult monkeys incorporated BrdU and ≈80% of these cells had morphological characteristics of granule neurons and expressed a neuronal marker by the 3-week time point. Previous studies suggest that the proliferation of granule cell precursors in the adult dentate gyrus can be inhibited by stress in rats and tree shrews. To test whether an aversive experience has a similar effect on cell proliferation in the primate brain, adult marmoset monkeys were exposed to a resident-intruder model of stress. After 1 hr in this condition, the intruder monkeys were injected with BrdU and perfused 2 hr later. The number of proliferating cells in the dentate gyrus of the intruder monkeys was compared with that of unstressed control monkeys. We found that a single exposure to this stressful experience resulted in a significant reduction in the number of these proliferating cells. Our results suggest that neurons are produced in the dentate gyrus of adult monkeys and that the rate of precursor cell proliferation can be affected by a stressful experience. PMID:9501234

DAF-18/PTEN signals through AAK-1/AMPK to inhibit MPK-1/MAPK in feedback control of germline stem cell proliferation.

Directory of Open Access Journals (Sweden)

Patrick Narbonne

2017-04-01

Full Text Available Under replete growth conditions, abundant nutrient uptake leads to the systemic activation of insulin/IGF-1 signalling (IIS and the promotion of stem cell growth/proliferation. Activated IIS can stimulate the ERK/MAPK pathway, the activation of which also supports optimal stem cell proliferation in various systems. Stem cell proliferation rates can further be locally refined to meet the resident tissue's need for differentiated progeny. We have recently shown that the accumulation of mature oocytes in the C. elegans germ line, through DAF-18/PTEN, inhibits adult germline stem cell (GSC proliferation, despite high systemic IIS activation. We show here that this feedback occurs through a novel cryptic signalling pathway that requires PAR-4/LKB1, AAK-1/AMPK and PAR-5/14-3-3 to inhibit the activity of MPK-1/MAPK, antagonize IIS, and inhibit both GSC proliferation and the production of additional oocytes. Interestingly, our results imply that DAF-18/PTEN, through PAR-4/LKB1, can activate AAK-1/AMPK in the absence of apparent energy stress. As all components are conserved, similar signalling cascades may regulate stem cell activities in other organisms and be widely implicated in cancer.

Modelling the interplay between hypoxia and proliferation in radiotherapy tumour response

International Nuclear Information System (INIS)

Jeong, J; Deasy, J O; Shoghi, K I

2013-01-01

A tumour control probability computational model for fractionated radiotherapy was developed, with the goal of incorporating the fundamental interplay between hypoxia and proliferation, including reoxygenation over a course of radiotherapy. The fundamental idea is that the local delivery of oxygen and glucose limits the amount of proliferation and metabolically-supported cell survival a tumour sub-volume can support. The model has three compartments: a proliferating compartment of cells receiving oxygen and glucose; an intermediate, metabolically-active compartment receiving glucose; and a highly hypoxic compartment of starving cells. Following the post-mitotic cell death of proliferating cells, intermediate cells move into the proliferative compartment and hypoxic cells move into the intermediate compartment. A key advantage of the proposed model is that the initial compartmental cell distribution is uniquely determined from the assumed local growth fraction (GF) and volume doubling time (T D ) values. Varying initial cell state distributions, based on the local (voxel) GF and T D , were simulated. Tumour response was simulated for head and neck squamous cell carcinoma using relevant parameter values based on published sources. The tumour dose required to achieve a 50% local control rate (TCD 50 ) was found for various GFs and T D ’s, and the effect of fraction size on TCD 50 was also evaluated. Due to the advantage of reoxygenation over a course of radiotherapy, conventional fraction sizes (2–2.4 Gy fx −1 ) were predicted to result in smaller TCD 50 's than larger fraction sizes (4–5 Gy fx –1 ) for a 10 cc tumour with GFs of around 0.15. The time to eliminate hypoxic cells (the reoxygenation time) was estimated for a given GF and decreased as GF increased. The extra dose required to overcome accelerated stem cell accumulation in longer treatment schedules was estimated to be 0.68 Gy/day (in EQD2 6.6 ), similar to published values derived from clinical

Carry-over effect of Thidiazuron on banana in vitro proliferation at ...

African Journals Online (AJOL)

USER

2010-05-24

May 24, 2010 ... proliferation at different culture cycles and light incubation conditions ... The results further showed dark conditions enhanced higher proliferation rates than light conditions in some ... the equatorial belt of Africa stretching from East to West. (Hallam ..... working on eastern black walnut (Juglans nigra) cotyle-.

In vitro effect of lysophosphatidic acid on proliferation, invasion and ...

African Journals Online (AJOL)

Purpose: To evaluate the effect of lysophosphatidic acid (LPA) on the proliferation, invasion and migration ability of 3AO, SKOV3 and CAOV3 human ovarian cancer cell lines. Methods: SKOV3, 3AO and CAOV3 cell lines were respectively treated with LPA. Changes in the proliferation rate of these cell lines were observed ...

Examining the relationship between free recall and immediate serial recall: Similar patterns of rehearsal and similar effects of word length, presentation rate, and articulatory suppression.

Science.gov (United States)

Bhatarah, Parveen; Ward, Geoff; Smith, Jessica; Hayes, Louise

2009-07-01

In five experiments, rehearsal and recall phenomena were examined using the free recall and immediate serial recall (ISR) tasks. In Experiment 1, participants were presented with lists of eight words, were precued or postcued to respond using free recall or ISR, and rehearsed out loud during presentation. The patterns of rehearsal were similar in all the conditions, and there was little difference between recall in the precued and postcued conditions. In Experiment 2, both free recall and ISR were sensitive to word length and presentation rate and showed similar patterns of rehearsal. In Experiment 3, both tasks were sensitive to word length and articulatory suppression. The word length effects generalized to 6-item (Experiment 4) and 12-item (Experiment 5) lists. These findings suggest that the two tasks are underpinned by highly similar rehearsal and recall processes.

Cell proliferation of Paramecium tetraurelia on a slow rotating clinostat

Science.gov (United States)

Sawai, Satoe; Mogami, Yoshihiro; Baba, Shoji A.

Paramecium is known to proliferate faster under microgravity conditions, and slower under hypergravity. Experiments using axenic culture medium have demonstrated that hypergravity affected directly on the proliferation of Paramecium itself. In order to assess the mechanisms underlying the physiological effects of gravity on cell proliferation, Paramecium tetraurelia was grown under clinorotation (2.5 rpm) and the time course of the proliferation was investigated in detail on the basis of the logistic analysis. On the basis of the mechanical properties of Paramecium, this slow rate of the rotation appears to be enough to simulate microgravity in terms of the randomization of the cell orientation with respect to gravity. P. tetraurelia was cultivated in a closed chamber in which cells were confined without air bubbles, reducing the shear forces and turbulences under clinorotation. The chamber is made of quartz and silicone rubber film; the former is for the optically-flat walls for the measurement of cell density by means of a non-invasive laser optical-slice method, and the latter for gas exchange. Because of the small dimension for culture space, Paramecium does not accumulate at the top of the chamber in spite of its known negative gravitactic behavior. We measured the cell density at regular time intervals without breaking the configuration of the chamber, and analyzed the proliferation parameters by fitting the data to a logistic equation. As a result, P. tetraurelia showed reduced proliferation under slow clinorotation. The saturation of the cell density as well as the maximum proliferation rate decreased, although we found no significant changes on the half maximal time for proliferation. We also found that the mean swimming velocity decreased under slow clinorotation. These results were not consistent with those under microgravity and fast rotating clinostat. This may suggest that randomization of the cell orientation performed by slow rotating clinostat has

Training of Tonal Similarity Ratings in Non-Musicians: A “Rapid Learning” Approach

Science.gov (United States)

Oechslin, Mathias S.; Läge, Damian; Vitouch, Oliver

2012-01-01

Although cognitive music psychology has a long tradition of expert–novice comparisons, experimental training studies are rare. Studies on the learning progress of trained novices in hearing harmonic relationships are still largely lacking. This paper presents a simple training concept using the example of tone/triad similarity ratings, demonstrating the gradual progress of non-musicians compared to musical experts: In a feedback-based “rapid learning” paradigm, participants had to decide for single tones and chords whether paired sounds matched each other well. Before and after the training sessions, they provided similarity judgments for a complete set of sound pairs. From these similarity matrices, individual relational sound maps, intended to display mental representations, were calculated by means of non-metric multidimensional scaling (NMDS), and were compared to an expert model through procrustean transformation. Approximately half of the novices showed substantial learning success, with some participants even reaching the level of professional musicians. Results speak for a fundamental ability to quickly train an understanding of harmony, show inter-individual differences in learning success, and demonstrate the suitability of the scaling method used for learning research in music and other domains. Results are discussed in the context of the “giftedness” debate. PMID:22629252

Cell proliferation of Paramecium tetraurelia under simulated microgravity

Science.gov (United States)

Sawai, S.; Mogami, Y.; Baba, S. A.

Paramecium is known to proliferate faster under microgravity in space and slower under hypergravity Experiments using axenic culture medium have demonstrated that the hypergravity affected directly on the proliferation of Paramecium itself Kato et al 2003 In order to assess the mechanisms underlying the physiological effects of gravity on cell proliferation Paramecium tetraurelia was grown under simulated microgravity performed by clinorotation and the time course of the proliferation was investigated in detail on the basis of the logistic analysis P tetraurelia was cultivated in a closed chamber in which cells were confined without air babbles reducing the shear stresses and turbulence under the rotation The chamber is made of quartz and silicone rubber film the former is for the optically-flat walls for the measurement of cell density by means of a non-invasive laser optical-slice method and the latter for gas exchange Because the closed chamber has an inner dimension of 3 times 3 times 60 mm Paramecium does not accumulate at the top of the chamber despite its negative gravitactic behavior We measured the cell density at regular time intervals without breaking the configuration of the chamber and analyzed the proliferation parameters by fitting the data to a logistic equation Clinorotation had the effects of reducing the proliferation of P tetraurelia It reduced both the saturation cell density and the maximum proliferation rate although it had little effect on the

Effect of hydroxyurea and vinblastine on the proliferation of the pluripotential stem cells

International Nuclear Information System (INIS)

Necas, E.; Neuwirt, J.

1977-01-01

The population of the pluripotential hemopoietic stem cells in mice, i.e., cells forming colonies in the spleens of lethally irradiated mice (colony forming cells CFc) proliferates relatively slowly. After partial damage the population regenerates which is achieved by an increased proliferation rate. The effect of damage caused by different doses of hydroxyurea or vinblastine to the proliferation of the CFc was investigated. CFc population was measured in femur bone marrow after the grafting of a bone marrow sample into lethally irradiated mice recipients (spleen colony method). The proliferation rate was estimated either according to the magnitude of the fraction of cells synthesizing DNA in the S phase of the cell cycle, or according to the sensitivity of the population to repeated injections of vinblastine. Data showed that even after very minute damage by hydroxyurea the stem cells started to proliferate intensively. The effect was dose dependent. The comparable damage caused by vinblastine had a significantly weaker effect on the proliferation of the stem cells. It is concluded from the results that the proliferation response of the pluripotential stem cells depends on two factors: the extent of the damage caused to the hemopoietic tissue and the position of the killed cells in the cell cycle. (author)

Excessive Cellular Proliferation Negatively Impacts Reprogramming Efficiency of Human Fibroblasts.

Science.gov (United States)

Gupta, Manoj K; Teo, Adrian Kee Keong; Rao, Tata Nageswara; Bhatt, Shweta; Kleinridders, Andre; Shirakawa, Jun; Takatani, Tomozumi; Hu, Jiang; De Jesus, Dario F; Windmueller, Rebecca; Wagers, Amy J; Kulkarni, Rohit N

2015-10-01

The impact of somatic cell proliferation rate on induction of pluripotent stem cells remains controversial. Herein, we report that rapid proliferation of human somatic fibroblasts is detrimental to reprogramming efficiency when reprogrammed using a lentiviral vector expressing OCT4, SOX2, KLF4, and cMYC in insulin-rich defined medium. Human fibroblasts grown in this medium showed higher proliferation, enhanced expression of insulin signaling and cell cycle genes, and a switch from glycolytic to oxidative phosphorylation metabolism, but they displayed poor reprogramming efficiency compared with cells grown in normal medium. Thus, in contrast to previous studies, our work reveals an inverse correlation between the proliferation rate of somatic cells and reprogramming efficiency, and also suggests that upregulation of proteins in the growth factor signaling pathway limits the ability to induce pluripotency in human somatic fibroblasts. The efficiency with which human cells can be reprogrammed is of interest to stem cell biology. In this study, human fibroblasts cultured in media containing different concentrations of growth factors such as insulin and insulin-like growth factor-1 exhibited variable abilities to proliferate, with consequences on pluripotency. This occurred in part because of changes in the expression of proteins involved in the growth factor signaling pathway, glycolysis, and oxidative phosphorylation. These findings have implications for efficient reprogramming of human cells. ©AlphaMed Press.

Proliferation: myth or reality?; La proliferation: mythe ou realite?

Energy Technology Data Exchange (ETDEWEB)

NONE

2005-07-01

This article analyzes the proliferation approach, its technical condition and political motivation, and the share between the myth (political deception, assumptions and extrapolations) and the reality of proliferation. Its appreciation is complicated by the irrational behaviour of some political actors and by the significant loss of the non-use taboo. The control of technologies is an important element for proliferation slowing down but an efficient and autonomous intelligence system remains indispensable. (J.S.)

Functional similarities between the dictyostelium protein AprA and the human protein dipeptidyl-peptidase IV.

Science.gov (United States)

Herlihy, Sarah E; Tang, Yu; Phillips, Jonathan E; Gomer, Richard H

2017-03-01

Autocrine proliferation repressor protein A (AprA) is a protein secreted by Dictyostelium discoideum cells. Although there is very little sequence similarity between AprA and any human protein, AprA has a predicted structural similarity to the human protein dipeptidyl peptidase IV (DPPIV). AprA is a chemorepellent for Dictyostelium cells, and DPPIV is a chemorepellent for neutrophils. This led us to investigate if AprA and DPPIV have additional functional similarities. We find that like AprA, DPPIV is a chemorepellent for, and inhibits the proliferation of, D. discoideum cells, and that AprA binds some DPPIV binding partners such as fibronectin. Conversely, rAprA has DPPIV-like protease activity. These results indicate a functional similarity between two eukaryotic chemorepellent proteins with very little sequence similarity, and emphasize the usefulness of using a predicted protein structure to search a protein structure database, in addition to searching for proteins with similar sequences. © 2016 The Protein Society.

Functional similarities between the dictyostelium protein AprA and the human protein dipeptidyl‐peptidase IV

Science.gov (United States)

Herlihy, Sarah E.; Tang, Yu; Phillips, Jonathan E.

2017-01-01

Abstract Autocrine proliferation repressor protein A (AprA) is a protein secreted by Dictyostelium discoideum cells. Although there is very little sequence similarity between AprA and any human protein, AprA has a predicted structural similarity to the human protein dipeptidyl peptidase IV (DPPIV). AprA is a chemorepellent for Dictyostelium cells, and DPPIV is a chemorepellent for neutrophils. This led us to investigate if AprA and DPPIV have additional functional similarities. We find that like AprA, DPPIV is a chemorepellent for, and inhibits the proliferation of, D. discoideum cells, and that AprA binds some DPPIV binding partners such as fibronectin. Conversely, rAprA has DPPIV‐like protease activity. These results indicate a functional similarity between two eukaryotic chemorepellent proteins with very little sequence similarity, and emphasize the usefulness of using a predicted protein structure to search a protein structure database, in addition to searching for proteins with similar sequences. PMID:28028841

Prospective and retrospective ECG-gating for CT coronary angiography perform similarly accurate at low heart rates

Energy Technology Data Exchange (ETDEWEB)

Stolzmann, Paul, E-mail: paul.stolzmann@usz.ch [Institute of Diagnostic Radiology, University Hospital Zurich, Raemistrasse 100, 8091 Zurich (Switzerland); Goetti, Robert; Baumueller, Stephan [Institute of Diagnostic Radiology, University Hospital Zurich, Raemistrasse 100, 8091 Zurich (Switzerland); Plass, Andre; Falk, Volkmar [Clinic for Cardiovascular Surgery, University Hospital Zurich (Switzerland); Scheffel, Hans; Feuchtner, Gudrun; Marincek, Borut [Institute of Diagnostic Radiology, University Hospital Zurich, Raemistrasse 100, 8091 Zurich (Switzerland); Alkadhi, Hatem [Institute of Diagnostic Radiology, University Hospital Zurich, Raemistrasse 100, 8091 Zurich (Switzerland); Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Leschka, Sebastian [Institute of Diagnostic Radiology, University Hospital Zurich, Raemistrasse 100, 8091 Zurich (Switzerland)

2011-07-15

Objective: To compare, in patients with suspicion of coronary artery disease (CAD) and low heart rates, image quality, diagnostic performance, and radiation dose values of prospectively and retrospectively electrocardiography (ECG)-gated dual-source computed tomography coronary angiography (CTCA) for the diagnosis of significant coronary stenoses. Materials and methods: Two-hundred consecutive patients with heart rates {<=}70 bpm were retrospectively enrolled; 100 patients undergoing prospectively ECG-gated CTCA (group 1) and 100 patients undergoing retrospectively-gated CTCA (group 2). Coronary artery segments were assessed for image quality and significant luminal diameter narrowing. Sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and accuracy of both CTCA groups were determined using conventional catheter angiography (CCA) as reference standard. Radiation dose values were calculated. Results: Both groups were comparable regarding gender, body weight, cardiovascular risk profile, severity of CAD, mean heart rate, heart rate variability, and Agatston score (all p > 0.05). There was no significant difference in the rate of non-assessable coronary segments between group 1 (1.6%, 24/1404) and group 2 (1.4%, 19/1385; p = 0.77); non-diagnostic image quality was significantly (p < 0.001) more often attributed to stair step artifacts in group 1. Segment-based sensitivity, specificity, PPV, NPV, and accuracy were 98%, 98%, 88%, 100%, and 100% among group 1; 96%, 99%, 90%, 100%, and 98% among group 2, respectively. Parameters of diagnostic performance were similar (all p > 0.05). Mean effective radiation dose of prospectively ECG-gated CTCA (2.2 {+-} 0.4 mSv) was significantly (p < 0.0001) smaller than that of retrospectively ECG-gated CTCA (8.1 {+-} 0.6 mSv). Conclusion: Prospectively ECG-gated CTCA yields similar image quality, performs as accurately as retrospectively ECG-gated CTCA in patients having heart rates {<=}70 bpm

n-Order and maximum fuzzy similarity entropy for discrimination of signals of different complexity: Application to fetal heart rate signals.

Science.gov (United States)

Zaylaa, Amira; Oudjemia, Souad; Charara, Jamal; Girault, Jean-Marc

2015-09-01

This paper presents two new concepts for discrimination of signals of different complexity. The first focused initially on solving the problem of setting entropy descriptors by varying the pattern size instead of the tolerance. This led to the search for the optimal pattern size that maximized the similarity entropy. The second paradigm was based on the n-order similarity entropy that encompasses the 1-order similarity entropy. To improve the statistical stability, n-order fuzzy similarity entropy was proposed. Fractional Brownian motion was simulated to validate the different methods proposed, and fetal heart rate signals were used to discriminate normal from abnormal fetuses. In all cases, it was found that it was possible to discriminate time series of different complexity such as fractional Brownian motion and fetal heart rate signals. The best levels of performance in terms of sensitivity (90%) and specificity (90%) were obtained with the n-order fuzzy similarity entropy. However, it was shown that the optimal pattern size and the maximum similarity measurement were related to intrinsic features of the time series. Copyright © 2015 Elsevier Ltd. All rights reserved.

Non-proliferation

International Nuclear Information System (INIS)

Manley, I.T.

1981-01-01

Proliferation is a problem that can only be solved when the political problems which lead countries to contemplate, the possession of nuclear weapons are solved; in the meantime it can only be managed. Non-proliferation policy has to deal both with the political and the technical aspects of proliferation. It must seek to buy time by addressing the reasons why nations feel the political need to construct nuclear weapons, as well as delaying the moment when such nations feel capable of doing so. The subject is examined and proposals made. (author)

Estimation of Cell Proliferation Dynamics Using CFSE Data

Science.gov (United States)

Banks, H.T.; Sutton, Karyn L.; Thompson, W. Clayton; Bocharov, Gennady; Roose, Dirk; Schenkel, Tim; Meyerhans, Andreas

2010-01-01

Advances in fluorescent labeling of cells as measured by flow cytometry have allowed for quantitative studies of proliferating populations of cells. The investigations (Luzyanina et al. in J. Math. Biol. 54:57–89, 2007; J. Math. Biol., 2009; Theor. Biol. Med. Model. 4:1–26, 2007) contain a mathematical model with fluorescence intensity as a structure variable to describe the evolution in time of proliferating cells labeled by carboxyfluorescein succinimidyl ester (CFSE). Here, this model and several extensions/modifications are discussed. Suggestions for improvements are presented and analyzed with respect to statistical significance for better agreement between model solutions and experimental data. These investigations suggest that the new decay/label loss and time dependent effective proliferation and death rates do indeed provide improved fits of the model to data. Statistical models for the observed variability/noise in the data are discussed with implications for uncertainty quantification. The resulting new cell dynamics model should prove useful in proliferation assay tracking and modeling, with numerous applications in the biomedical sciences. PMID:20195910

Molecular analysis of peroxisome proliferation in the hamster.

Science.gov (United States)

Choudhury, Agharul I; Sims, Helen M; Horley, Neill J; Roberts, Ruth A; Tomlinson, Simon R; Salter, Andrew M; Bruce, Mary; Shaw, P Nicholas; Kendall, David; Barrett, David A; Bell, David R

2004-05-15

Three novel P450 members of the cytochrome P450 4A family were cloned as partial cDNAs from hamster liver, characterised as novel members of the CYP4A subfamily, and designated CYP4A17, 18, and 19. Hamsters were treated with the peroxisome proliferator-activated receptor alpha (PPARalpha) agonists, methylclofenapate (MCP) or Wy-14,643, and shown to develop hepatomegaly and induction of CYP4A17 RNA, and concomitant induction of lauric acid 12- hydroxylase. This treatment also resulted in hypolipidaemia, which was most pronounced in the VLDL fraction, with up to 50% reduction in VLDL-triglycerides; by contrast, blood cholesterol concentration was unaffected by this treatment. These data show that hamster is highly responsive to induction of CYP4A by peroxisome proliferators. To characterise the molecular basis of peroxisome proliferation, the hamster PPARalpha was cloned and shown to encode a 468-amino-acid protein, which is highly similar to rat and mouse PPARalpha proteins. The level of expression of hamster PPARalpha in liver is intermediate between mouse and guinea pig. These results fail to support the hypothesis that the level of PPARalpha in liver is directly responsible for species differences in peroxisome proliferation.

Evolution of cultural traits occurs at similar relative rates in different world regions.

Science.gov (United States)

Currie, Thomas E; Mace, Ruth

2014-11-22

A fundamental issue in understanding human diversity is whether or not there are regular patterns and processes involved in cultural change. Theoretical and mathematical models of cultural evolution have been developed and are increasingly being used and assessed in empirical analyses. Here, we test the hypothesis that the rates of change of features of human socio-cultural organization are governed by general rules. One prediction of this hypothesis is that different cultural traits will tend to evolve at similar relative rates in different world regions, despite the unique historical backgrounds of groups inhabiting these regions. We used phylogenetic comparative methods and systematic cross-cultural data to assess how different socio-cultural traits changed in (i) island southeast Asia and the Pacific, and (ii) sub-Saharan Africa. The relative rates of change in these two regions are significantly correlated. Furthermore, cultural traits that are more directly related to external environmental conditions evolve more slowly than traits related to social structures. This is consistent with the idea that a form of purifying selection is acting with greater strength on these more environmentally linked traits. These results suggest that despite contingent historical events and the role of humans as active agents in the historical process, culture does indeed evolve in ways that can be predicted from general principles.

Asiaticoside induces cell proliferation and collagen synthesis in human dermal fibroblasts

Directory of Open Access Journals (Sweden)

Linda Yuliati

2015-12-01

Asiaticoside induces HDF proliferation and type I and III collagen synthesis in a time- and dose-dependent pattern. Asiaticoside has a similar effect as retinoic acid on type I and type III collagen synthesis.

Bio-active molecules modified surfaces enhanced mesenchymal stem cell adhesion and proliferation

International Nuclear Information System (INIS)

Mobasseri, Rezvan; Tian, Lingling; Soleimani, Masoud; Ramakrishna, Seeram; Naderi-Manesh, Hossein

2017-01-01

Surface modification of the substrate as a component of in vitro cell culture and tissue engineering, using bio-active molecules including extracellular matrix (ECM) proteins or peptides derived ECM proteins can modulate the surface properties and thereby induce the desired signaling pathways in cells. The aim of this study was to evaluate the behavior of human bone marrow mesenchymal stem cells (hBM-MSCs) on glass substrates modified with fibronectin (Fn), collagen (Coll), RGD peptides (RGD) and designed peptide (R-pept) as bio-active molecules. The glass coverslips were coated with fibronectin, collagen, RGD peptide and R-peptide. Bone marrow mesenchymal stem cells were cultured on different substrates and the adhesion behavior in early incubation times was investigated using scanning electron microscopy (SEM) and confocal microscopy. The MTT assay was performed to evaluate the effect of different bio-active molecules on MSCs proliferation rate during 24 and 72 h. Formation of filopodia and focal adhesion (FA) complexes, two steps of cell adhesion process, were observed in MSCs cultured on bio-active molecules modified coverslips, specifically in Fn coated and R-pept coated groups. SEM image showed well adhesion pattern for MSCs cultured on Fn and R-pept after 2 h incubation, while the shape of cells cultured on Coll and RGD substrates indicated that they might experience stress condition in early hours of culture. Investigation of adhesion behavior, as well as proliferation pattern, suggests R-peptide as a promising bio-active molecule to be used for surface modification of substrate in supporting and inducing cell adhesion and proliferation. - Highlights: • Bioactive molecules modified surface is a strategy to design biomimicry scaffold. • Bi-functional Tat-derived peptide (R-pept) enhanced MSCs adhesion and proliferation. • R-pept showed similar influences to fibronectin on FA formation and attachment.

Fissile material proliferation risk

International Nuclear Information System (INIS)

Dreicer, J.S.; Rutherford, D.A.

1996-01-01

The proliferation risk of a facility depends on the material attractiveness, level of safeguards, and physical protection applied to the material in conjunction with an assessment of the impact of the socioeconomic circumstances and threat environment. Proliferation risk is a complementary extension of proliferation resistance. The authors believe a better determination of nuclear proliferation can be achieved by establishing the proliferation risk for facilities that contain nuclear material. Developing a method that incorporates the socioeconomic circumstances and threat environment inherent to each country enables a global proliferation assessment. To effectively reduce the nuclear danger, a broadly based set of criteria is needed that provides the capability to relatively assess a wide range of nuclear related sites and facilities in different countries and still ensure a global decrease in proliferation risk for fissile material (plutonium and highly enriched uranium)

Proliferation and the Civilian Nuclear Fuel Cycle. Towards a Simplified Recipe to Measure Proliferation Risk

Energy Technology Data Exchange (ETDEWEB)

Brogli, R.; Krakowski, R.A

2001-08-01

-protection metrics; b) a highly aggregated 'cost-equal-effort' or comparative-value method was applied to an array of commercial nuclear fuel forms in an effort to rank the attractiveness (to a proliferating agent) in terms of required effort as gauged through commercial costs; and c) the extension, if not actual application, of the system of Attractiveness Levels recommended by the USDOE as an extension and refinement of related IAEA protection-category guidelines. The Attractiveness-Level methodology, when compared to similar protection categories suggested by the IAEA, highlighted differences in required protection of specific source materials, with the IAEA being more conservative. From the viewpoint of a utility or research institute dealing with potential source materials, these differences can be important in budgetary terms. Both the 'cost-equal-effort' and the Attractiveness-Level methodologies were pursued to deal with conceptual and evaluation impasses encountered with the 'four-factor' formulation that were related primarily to the material-protection term necessary for its evaluation. The development, analyses, and evaluations performed to date on all three, inter-related approaches to simplified proliferation-risk metrics, as applied to the commercial nuclear fuel cycle, is reported. Key questions are discussed that must be resolved before a useful and simplified evaluation 'recipe' with which to evaluate proliferation risk and required protection levels (and cost) to nullify that risk is made available to the operator of a nuclear power plant and the total fuel cycle supporting it. (author)

Proliferation and the Civilian Nuclear Fuel Cycle. Towards a Simplified Recipe to Measure Proliferation Risk

International Nuclear Information System (INIS)

Brogli, R.; Krakowski, R.A.

2001-08-01

) a highly aggregated 'cost-equal-effort' or comparative-value method was applied to an array of commercial nuclear fuel forms in an effort to rank the attractiveness (to a proliferating agent) in terms of required effort as gauged through commercial costs; and c) the extension, if not actual application, of the system of Attractiveness Levels recommended by the USDOE as an extension and refinement of related IAEA protection-category guidelines. The Attractiveness-Level methodology, when compared to similar protection categories suggested by the IAEA, highlighted differences in required protection of specific source materials, with the IAEA being more conservative. From the viewpoint of a utility or research institute dealing with potential source materials, these differences can be important in budgetary terms. Both the 'cost-equal-effort' and the Attractiveness-Level methodologies were pursued to deal with conceptual and evaluation impasses encountered with the 'four-factor' formulation that were related primarily to the material-protection term necessary for its evaluation. The development, analyses, and evaluations performed to date on all three, inter-related approaches to simplified proliferation-risk metrics, as applied to the commercial nuclear fuel cycle, is reported. Key questions are discussed that must be resolved before a useful and simplified evaluation 'recipe' with which to evaluate proliferation risk and required protection levels (and cost) to nullify that risk is made available to the operator of a nuclear power plant and the total fuel cycle supporting it. (author)

Expression of Nanog gene promotes NIH3T3 cell proliferation

International Nuclear Information System (INIS)

Zhang Jingyu; Wang Xia; Chen Bing; Suo Guangli; Zhao Yanhong; Duan Ziyuan; Dai Jianwu

2005-01-01

Cells are the functional elements in tissue engineering and regenerative medicine. A large number of cells are usually needed for these purposes. However, there are numbers of limitations for in vitro cell proliferation. Nanog is an important self-renewal determinant in embryonic stem cells. However, it remains unknown whether Nanog will influence the cell cycle and cell proliferation of mature cells. In this study, we expressed Nanog in NIH3T3 cells and showed that expression of Nanog in NIH3T3 promoted cells to enter into S phase and enhanced cell proliferation. This suggests that Nanog gene might function in a similar fashion in mature cells as in ES cells. In addition, it may provide an approach for in vitro cell expansion

Primary non-transecting bulbar urethroplasty long-term success rates are similar to transecting urethroplasty.

Science.gov (United States)

Anderson, Kirk M; Blakely, Stephen A; O'Donnell, Colin I; Nikolavsky, Dmitriy; Flynn, Brian J

2017-01-01

To review the long-term outcomes of transecting versus non-transecting urethroplasty to repair bulbar urethral strictures. A retrospective review was conducted of 342 patients who underwent anterior urethroplasty performed by a single surgeon from 2003 to 2014. Patients were excluded from further analysis if there had been prior urethroplasty, stricture location outside the bulbous urethra, or age urethroplasty. In the non-transecting group, surgical techniques used included non-transecting anastomotic urethroplasty and dorsal and/or ventral buccal grafting. The primary endpoint was stricture resolution in transecting vs. non-transecting bulbar urethroplasty. Success was defined as freedom from secondary procedures including dilation, urethrotomy, or repeat urethroplasty. One hundred and fifty-two patients met inclusion criteria. At a mean follow-up of 65 months (range: 10-138 months), stricture-free recurrence in the transecting and non-transecting groups was similar, 83% (n = 85/102) and 82% (n = 41/50), respectively (p = 0.84). Surgical technique (p = 0.91), stricture length (p = 0.8), and etiology (p = 0.6) did not affect stricture recurrence rate on multivariate analysis. There was no difference detected in time to stricture recurrence (p = 0.21). In this retrospective series, transecting and non-transecting primary bulbar urethroplasty resulted in similar long-term stricture resolution rate. Prospective studies are needed to determine what differences may present in outcomes related to sexual function and long-term success.

Cell proliferation in dimethylhydrazine-induced colonic adenocarcinomata following cytotoxic drug treatment.

Science.gov (United States)

Tutton, P J; Barkla, D H

1978-08-25

A stathmokinetic technique was used to study cell proliferation in dimethylhydrazine-induced adenocarcinomata of rat colon following treatment with cytotoxic drugs. The rate of cell division was significantly increased three days after treatment with 5,7-dihydroxytryptamine and seven days after treatment with 5-fluorouracil. Acceleration of tumour cell proliferation following 5,7-dihydroxytryptamine treatment was inhibited by treating animals with the antiseritoninergic drug Xylamidine Tosylate. Acceleration of tumour cell proliferation following 5-fluorouracil treatment was inhibited by treating animals either with the antiseritoninergic drug BW501 or with the histamine H2-receptor blocking drug Cimetidine.

Effect of IL-2 on recovery of proliferation ability of irradiated T lymphocytes

International Nuclear Information System (INIS)

Wang Ninghai; Zhang Lansheng

1989-01-01

3 H-thymidine incorporation assay was used to evaluated the proliferation ability of normal human peripheral blood T lymphocytes irradiated with or without exogenous IL-2 by 60 Co γ-ray at various doses after exposure to 1, 2.5, 5, 10, 20 and 40 Gy γ-ray, the DNA synthesis is blocked. It indicated IL-2 has damage effect on the proliferation ability of T cells. 3 H-thymidine incorporation rate in cells decreases with increasing dose of irradiation. Incorporation of 3 H-Tdk in irradiated groups in the dose range of 1 to 40 Gy was compared with that in the control group. The incorporation rate 3 H-TdR in these irradiated groups is 27 to 82 % of that in control group. The inhibition of lymphocyte proliferation was partially enhanced by adding IL-2, but the inhibiting effect on proliferation of human peripheral blood lymphocytes exposed to irradiation at more than 10 Gy is not reversible

Role of CYP2B in Phenobarbital-Induced Hepatocyte Proliferation in Mice.

Science.gov (United States)

Li, Lei; Bao, Xiaochen; Zhang, Qing-Yu; Negishi, Masahiko; Ding, Xinxin

2017-08-01

Phenobarbital (PB) promotes liver tumorigenesis in rodents, in part through activation of the constitutive androstane receptor (CAR) and the consequent changes in hepatic gene expression and increases in hepatocyte proliferation. A typical effect of CAR activation by PB is a marked induction of Cyp2b10 expression in the liver; the latter has been suspected to be vital for PB-induced hepatocellular proliferation. This hypothesis was tested here by using a Cyp2a(4/5)bgs -null (null) mouse model in which all Cyp2b genes are deleted. Adult male and female wild-type (WT) and null mice were treated intraperitoneally with PB at 50 mg/kg once daily for 5 successive days and tested on day 6. The liver-to-body weight ratio, an indicator of liver hypertrophy, was increased by 47% in male WT mice, but by only 22% in male Cyp2a(4/5)bgs -null mice, by the PB treatment. The fractions of bromodeoxyuridine-positive hepatocyte nuclei, assessed as a measure of the rate of hepatocyte proliferation, were also significantly lower in PB-treated male null mice compared with PB-treated male WT mice. However, whereas few proliferating hepatocytes were detected in saline-treated mice, many proliferating hepatocytes were still detected in PB-treated male null mice. In contrast, female WT mice were much less sensitive than male WT mice to PB-induced hepatocyte proliferation, and PB-treated female WT and PB-treated female null mice did not show significant difference in rates of hepatocyte proliferation. These results indicate that CYP2B induction plays a significant, but partial, role in PB-induced hepatocyte proliferation in male mice. U.S. Government work not protected by U.S. copyright.

Analysis of Mammalian Cell Proliferation and Macromolecule Synthesis Using Deuterated Water and Gas Chromatography-Mass Spectrometry

Directory of Open Access Journals (Sweden)

Victoria C. Foletta

2016-10-01

Full Text Available Deuterated water (2H2O, a stable isotopic tracer, provides a convenient and reliable way to label multiple cellular biomass components (macromolecules, thus permitting the calculation of their synthesis rates. Here, we have combined 2H2O labelling, GC-MS analysis and a novel cell fractionation method to extract multiple biomass components (DNA, protein and lipids from the one biological sample, thus permitting the simultaneous measurement of DNA (cell proliferation, protein and lipid synthesis rates. We have used this approach to characterize the turnover rates and metabolism of a panel of mammalian cells in vitro (muscle C2C12 and colon cancer cell lines. Our data show that in actively-proliferating cells, biomass synthesis rates are strongly linked to the rate of cell division. Furthermore, in both proliferating and non-proliferating cells, it is the lipid pool that undergoes the most rapid turnover when compared to DNA and protein. Finally, our data in human colon cancer cell lines reveal a marked heterogeneity in the reliance on the de novo lipogenic pathway, with the cells being dependent on both ‘self-made’ and exogenously-derived fatty acid.

Arsenic and urinary bladder cell proliferation

International Nuclear Information System (INIS)

Luster, Michael I.; Simeonova, Petia P.

2004-01-01

Epidemiologic studies have demonstrated that a close association exists between the elevated levels of arsenic in drinking water and the incidence of certain cancers, including transitional cell carcinomas of the urinary bladder. We have employed in vitro and in vivo models to examine the effects of sodium arsenite on the urinary bladder epithelium. Mice exposed to 0.01% sodium arsenite in drinking water demonstrated hyperproliferation of the bladder uroepithelium within 4 weeks after initiating treatment. This occurred in the absence of amorphous precipitates and was accompanied by the accumulation of trivalent arsenite (iAs 3+ ), and to a lesser extent dimethylarsenic (DMA), arsenate (iAs 5+ ), and monomethylarsenic (MMA) in bladder tissue. In contrast to the bladder, urinary secretion was primarily in the form of DMA and MMA. Arsenic-induced cell proliferation in the bladder epithelium was correlated with activation of the MAP kinase pathway, leading to extracellular signal-regulated kinase (ERK) kinase activity, AP-1 activation, and expression of AP-1-associated genes involved in cell proliferation. Activation of the MAP kinase pathway involved both epidermal growth factor (EGF) receptor-dependent and -independent events, the latter involving Src activation. Studies summarized in this review suggest that arsenic accumulates in urinary bladder epithelium causing activation of specific signaling pathways that lead to chronic increased cell proliferation. This may play a non-epigenetic role in carcinogenesis by increasing the proliferation of initiated cells or increasing the mutational rate

Nuclear proliferation: motivations, capabilities, and strategies for control

International Nuclear Information System (INIS)

Greenwood, T.; Feiveson, H.A.; Taylor, T.B.

1977-01-01

Two possible patterns of proliferation appear to involve the greatest risks for nuclear use or war. The first is proliferation to particular categories of states and the second dangerous possibility is proliferation at a rapid rate. But rapid proliferation could cause instabilities that might be too great for political systems and institutions to handle, making nuclear use of nuclear war more likely. Thus, any strategy for nonproliferation should especially attempt to prevent a rapid spread of nuclear weapons and to avert acquisition by states in the high-risk categories. Nuclear proliferation will also have important effects on world and regional stability for reasons not directly related to nuclear use. The mere possession of nuclear weapons by certain states could radically alter international perceptions and threaten global arrangements. The main concern in this discussion is to analyze the various incentives and disincentives--involving both security and political considerations--that will affect states' decisions about whether or not to acquire nuclear weapons. The discussion then turns to the means by which individual states and the international community can influence nuclear incentives and disincentives. The particularly important subject of the management of the international nuclear industry is addressed separately, followed by an analysis of nuclear acquisition, use, and threat by non-state entities. Finally, a general strategy for decreasing incentives and increasing disincentives is proposed and applied to four special categories of states

A Dictyostelium chalone uses G proteins to regulate proliferation.

Science.gov (United States)

Bakthavatsalam, Deenadayalan; Choe, Jonathan M; Hanson, Nana E; Gomer, Richard H

2009-07-27

Several studies have shown that organ size, and the proliferation of tumor metastases, may be regulated by negative feedback loops in which autocrine secreted factors called chalones inhibit proliferation. However, very little is known about chalones, and how cells sense them. We previously identified two secreted proteins, AprA and CfaD, which act as chalones in Dictyostelium. Cells lacking AprA or CfaD proliferate faster than wild-type cells, and adding recombinant AprA or CfaD to cells slows their proliferation. We show here that cells lacking the G protein components Galpha8, Galpha9, and Gbeta proliferate faster than wild-type cells despite secreting normal or high levels of AprA and CfaD. Compared with wild-type cells, the proliferation of galpha8-, galpha9- and gbeta- cells are only weakly inhibited by recombinant AprA (rAprA). Like AprA and CfaD, Galpha8 and Gbeta inhibit cell proliferation but not cell growth (the rate of increase in mass and protein per nucleus), whereas Galpha9 inhibits both proliferation and growth. galpha8- cells show normal cell-surface binding of rAprA, whereas galpha9- and gbeta- cells have fewer cell-surface rAprA binding sites, suggesting that Galpha9 and Gbeta regulate the synthesis or processing of the AprA receptor. Like other ligands that activate G proteins, rAprA induces the binding of [3H]GTP to membranes, and GTPgammaS inhibits the binding of rAprA to membranes. Both AprA-induced [3H]GTP binding and the GTPgammaS inhibition of rAprA binding require Galpha8 and Gbeta but not Galpha9. Like aprA- cells, galpha8- cells have reduced spore viability. This study shows that Galpha8 and Gbeta are part of the signal transduction pathway used by AprA to inhibit proliferation but not growth in Dictyostelium, whereas Galpha9 is part of a differealnt pathway that regulates both proliferation and growth, and that a chalone signal transduction pathway uses G proteins.

Hepatocellular proliferation in response to agonists of peroxisome proliferator-activated receptor alpha: a role for kupffer cells?

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Cunningham Michael

2006-01-01

Full Text Available Abstract Background It has been proposed that PPARα agonists stimulate Kupffer cells in rodents which in turn, release mitogenic factors leading to hepatic hyperplasia, and eventually cancer. However, Kupffer cells do not express PPARα receptors, and PPARα agonists stimulate hepatocellular proliferation in both TNFα- and TNFα receptor-null mice, casting doubt on the involvement of Kupffer cells in the mitogenic response to PPARα agonists. This study was therefore designed to investigate whether the PPARα agonist PFOA and the Kupffer cell inhibitor methylpalmitate produce opposing effects on hepatocellular proliferation and Kupffer cell activity in vivo, in a manner that would implicate these cells in the mitogenic effects of PPARα agonists. Methods Male Sprague-Dawley rats were treated intravenously via the tail vein with methylpalmitate 24 hrs prior to perfluorooctanoic acid (PFOA, and were sacrificed 24 hrs later, one hr after an intraperitoneal injection of bromodeoxyuridine (BrdU. Sera were analyzed for TNFα and IL-1β. Liver sections were stained immunohistochemically and quantified for BrdU incorporated into DNA. Results Data show that PFOA remarkably stimulated hepatocellular proliferation in the absence of significant changes in the serum levels of either TNFα or IL-1β. In addition, methylpalmitate did not alter the levels of these mitogens in PFOA-treated animals, despite the fact that it significantly blocked the hepatocellular proliferative effect of PFOA. Correlation between hepatocellular proliferation and serum levels of TNFα or IL-1β was extremely poor. Conclusion It is unlikely that mechanisms involving Kupffer cells play an eminent role in the hepatic hyperplasia, and consequently hepatocarcinogenicity attributed to PPARα agonists. This conclusion is based on the above mentioned published data and the current findings showing animals treated with PFOA alone or in combination with methylpalmitate to have similar

Experimental study of the effect of 103Pd on the proliferation and apoptosis of vascular smooth muscle cells

International Nuclear Information System (INIS)

Luo Quanyong; Zhu Jun; Chen Libo; Lu Hankui; Zhu Ruisen

2002-01-01

Objective: To investigate the ability of γ emitting radionuclide 103 Pd to inhibit the vascular smooth muscle cell (SMC) proliferation and to induce its apoptosis in vitro. Methods: 103 Pd solution was added to the culture medium to irradiate SMCs for 72 h and non-radioactive Pd solution was added as control. 3 H-TdR incorporation test was used to detect the effect of 103 Pd on the proliferation of SMCs. Flow cytometer was used to detect the apoptotic SMCs. Results: The results showed that inhibition of SMC proliferation was evident and the effects were dose-dependant. Inhibition rate of SMC proliferation by 1.85 MBq 103 Pd was 2.3% , which was not significant. The inhibition rate increased from 41.6% to 91.2% as the dose of 103 Pd increased from 7.4 to 37.0 MBq, and the proliferation of SMCs was repressed significantly then. The apoptosis rate was extremely low (less than 4.0% ) with the 103 pd dose escalating from 1.85 to 37.0 MBq. Conclusions: This study suggests that proliferation of SMCs can be repressed effectively in vitro by 103 pd. 103 Pd can be used to inhibit the neointimal proliferation. 103 Pd radioactive stent implantation can be employed as a possible novel means to prevent restenosis

Nuclear non proliferation and disarmament; Non-proliferation nucleaire et desarmement

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-07-01

In the framework of the publication of a document on the ''weapons mastership, disarmament and non proliferation: the french action'', by the ministry of Foreign Affairs and the ministry of Defense, the French Documentation organization presents a whole document. This document describes and details the following topics: the conference on the treaty of non proliferation of nuclear weapons, the France, Usa and Non Governmental Organizations position, the threats of the proliferation, the french actions towards the disarmament, the disarmament in the world, a chronology and some bibliographic resources. (A.L.B.)

Nicotine as a mitogenic stimulus for pancreatic acinar cell proliferation

Institute of Scientific and Technical Information of China (English)

Parimal Chowdhury; Kodetthoor B Udupa

2006-01-01

Cell proliferation is an important process in life for growth of normal and cancer cells. The signal transduction pathways activated during this process are strictly regulated. This editorial focuses on the role of nicotine,a mitogen, in the induction of signaling pathways resulting in proliferation of pancreatic tumor cells and compares these events with those in normal acinar cells isolated from the rat pancreas. The data shows striking similarities between these two cellular systems.In addition, the editorial reviews very recent literature of the contribution of MAPK signaling in cell lines associated with human diseases. A prospective cellular model of nicotine induced activation of MAPK cascade is presented.

Different effects of 25-kDa amelogenin on the proliferation, attachment and migration of various periodontal cells

International Nuclear Information System (INIS)

Li, Xiting; Shu, Rong; Liu, Dali; Jiang, Shaoyun

2010-01-01

Previous studies have assumed that amelogenin is responsible for the therapeutic effect of the enamel matrix derivative (EMD) in periodontal tissue healing and regeneration. However, it is difficult to confirm this hypothesis because both the EMD and the amelogenins are complex mixtures of multiple proteins. Further adding to the difficulties is the fact that periodontal tissue regeneration involves various types of cells and a sequence of associated cellular events including the attachment, migration and proliferation of various cells. In this study, we investigated the potential effect of a 25-kDa recombinant porcine amelogenin (rPAm) on primarily cultured periodontal ligament fibroblasts (PDLF), gingival fibroblasts (GF) and gingival epithelial cells (GEC). The cells were treated with 25-kDa recombinant porcine amelogenin at a concentration of 10 μg/mL. We found that rPAm significantly promoted the proliferation and migration of PDLF, but not their adhesion. Similarly, the proliferation and adhesion of GF were significantly enhanced by treatment with rPAm, while migration was greatly inhibited. Interestingly, this recombinant protein inhibited the growth rate, cell adhesion and migration of GEC. These data suggest that rPAm may play an essential role in periodontal regeneration through the activation of periodontal fibroblasts and inhibition of the cellular behaviors of gingival epithelial cells.

Lymphocyte Proliferation Response in Patients with Acute and Chronic Brucellosis

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Khadijeh Khosravi

2016-05-01

Full Text Available Abstract Background: Brucella is an intracellular bacterium that causes chronic infection in humans and domestic animals. The underlying mechanisms that cause prolonged illness are complex and not fully understood. Immune responses may have an important role in the chronicity of infection. Here, we evaluated the lymphocyte proliferation responses in patients with chronic and acute brucellosis. Materials and Methods: This descriptive - analytical study was performed on 22 patients with acute brucellosis, 21 patients with chronic brucellosis and 21 healthy people with the similar age, sex and genetic background as control group. Peripheral lymphocytes were isolated using Ficoll and the cellular proliferation was quantified in presence of antigen and phytohemaglutinin-A by MTT method. Results: The brucella antigen-specific stimulation index in patients with chronic brucellosis was significantly lower than the acute brucellosis patients (p=0.001. Also, stimulating the lymphocytes with phytohemaglutinin-A has shown that proliferative response in patients with chronic brucellosis was lower than the other groups (p=0.04. Conclusion: The results indicated that chronic brucellosis inhibits lymphocyte proliferation. This inhibition of lymphocyte proliferation may be due to the induction of anergy.

Proliferation of differentiated glial cells in the brain stem

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P.C. Barradas

1998-02-01

Full Text Available Classical studies of macroglial proliferation in muride rodents have provided conflicting evidence concerning the proliferating capabilities of oligodendrocytes and microglia. Furthermore, little information has been obtained in other mammalian orders and very little is known about glial cell proliferation and differentiation in the subclass Metatheria although valuable knowledge may be obtained from the protracted period of central nervous system maturation in these forms. Thus, we have studied the proliferative capacity of phenotypically identified brain stem oligodendrocytes by tritiated thymidine radioautography and have compared it with known features of oligodendroglial differentiation as well as with proliferation of microglia in the opossum Didelphis marsupialis. We have detected a previously undescribed ephemeral, regionally heterogeneous proliferation of oligodendrocytes expressing the actin-binding, ensheathment-related protein 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNPase, that is not necessarily related to the known regional and temporal heterogeneity of expression of CNPase in cell bodies. On the other hand, proliferation of microglia tagged by the binding of Griffonia simplicifolia B4 isolectin, which recognizes an alpha-D-galactosyl-bearing glycoprotein of the plasma membrane of macrophages/microglia, is known to be long lasting, showing no regional heterogeneity and being found amongst both ameboid and differentiated ramified cells, although at different rates. The functional significance of the proliferative behavior of these differentiated cells is unknown but may provide a low-grade cell renewal in the normal brain and may be augmented under pathological conditions.

NoRC Recruitment by H2A.X Deposition at rRNA Gene Promoter Limits Embryonic Stem Cell Proliferation

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Boris Eleuteri

2018-05-01

Full Text Available Summary: Embryonic stem cells (ESCs display an abbreviated cell cycle, resulting in a short doubling time and rapid proliferation. The histone variant H2A.X is critical for proliferation of stem cells, although mechanistic insights have remained obscure. Here, we show that H2A.X defines the rate of mouse ESC proliferation independently of the DNA damage response pathway, and it associates with three major chromatin-modifying complexes. Our functional and biochemical analyses demonstrate that H2A.X-associated factors mediate the H2A.X-dependent effect on ESC proliferation and involve the nucleolar remodeling complex (NoRC. A specific H2A.X deposition at rDNA promoters determines the chromatin recruitment of the NoRC, histone modifications, the rRNA transcription, and the rate of proliferation. Collectively, our results suggest that NoRC assembly by H2A.X deposition at rRNA promoters silences transcription, and this represents an important regulatory component for ESC proliferation. : Histone variant H2A.X defines the rate of embryonic stem cell proliferation. Eleuteri et al. identify H2A.X-interacting proteins, and they show that H2A.X deposition at rDNA promoters assembles the NoRC, which represses rRNA transcription and determines the rate of self-renewal. Keywords: ribosomal biogenesis, rRNA, rDNA, stem cells, TIP5, SNF2H, SPT16, BRG1, H2A.X, G1, cell cycle, cell cycle arrest, proliferation

The threat of proliferation

International Nuclear Information System (INIS)

Palme, Olof.

1986-01-01

The paper on the threat of proliferation, is a keynote speech delivered to the Colloquium on Nuclear War, Nuclear Proliferation and their Consequences, Geneva, 1985. Topics discussed in the address include: nuclear weapons, nuclear war, terrorists, Non-Proliferation Treaty, nuclear disarmament, and leadership in world affairs. (UK)

Dose-dependent dual effects of cholesterol and desmosterol on J774 macrophage proliferation

International Nuclear Information System (INIS)

Rodriguez-Acebes, Sara; Cueva, Paloma de la; Ferruelo, Antonio J.; Fernandez-Hernando, Carlos; Lasuncion, Miguel A.; Martinez-Botas, Javier; Gomez-Coronado, Diego

2008-01-01

We addressed the ability of native, oxidized and acetylated low-density lipoproteins (nLDL, oxLDL and acLDL, respectively) and desmosterol to act as sources of sterol for the proliferation of J774A.1 macrophages. Treatment with 0.5 μM lovastatin and lipoprotein-deficient serum suppressed cell proliferation. This inhibition was effectively prevented by nLDL, but only to a lesser extent by oxLDL. AcLDL, despite its ability to deliver a higher amount of cholesterol to J774 macrophages than the other LDLs, was dependent on mevalonate supply to sustain cell proliferation. Similarly, exogenous desmosterol, which is not converted into cholesterol in J774 cells, required the simultaneous addition of mevalonate to support optimal cell growth. Expression of hydroxymethyl glutaryl coenzyme A reductase mRNA was potently down-regulated by acLDL and exogenous desmosterol, but the effect was weaker with other sterol sources. We conclude that nLDL is more efficient than modified LDL in sustaining macrophage proliferation. Despite the requirement of cholesterol or desmosterol for J774 cell proliferation, excessive provision of either sterol limits mevalonate availability, thus suppressing cell proliferation.

Dose-dependent dual effects of cholesterol and desmosterol on J774 macrophage proliferation

Energy Technology Data Exchange (ETDEWEB)

Rodriguez-Acebes, Sara [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain); Cueva, Paloma de la; Ferruelo, Antonio J; Fernandez-Hernando, Carlos [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); Lasuncion, Miguel A [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain); Departamento de Bioquimica y Biologia Molecular, Universidad de Alcala, Alcala de Henares (Spain); Martinez-Botas, Javier [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain); Gomez-Coronado, Diego [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain)], E-mail: diego.gomez@hrc.es

2008-12-12

We addressed the ability of native, oxidized and acetylated low-density lipoproteins (nLDL, oxLDL and acLDL, respectively) and desmosterol to act as sources of sterol for the proliferation of J774A.1 macrophages. Treatment with 0.5 {mu}M lovastatin and lipoprotein-deficient serum suppressed cell proliferation. This inhibition was effectively prevented by nLDL, but only to a lesser extent by oxLDL. AcLDL, despite its ability to deliver a higher amount of cholesterol to J774 macrophages than the other LDLs, was dependent on mevalonate supply to sustain cell proliferation. Similarly, exogenous desmosterol, which is not converted into cholesterol in J774 cells, required the simultaneous addition of mevalonate to support optimal cell growth. Expression of hydroxymethyl glutaryl coenzyme A reductase mRNA was potently down-regulated by acLDL and exogenous desmosterol, but the effect was weaker with other sterol sources. We conclude that nLDL is more efficient than modified LDL in sustaining macrophage proliferation. Despite the requirement of cholesterol or desmosterol for J774 cell proliferation, excessive provision of either sterol limits mevalonate availability, thus suppressing cell proliferation.

Effect of leptin on proliferation and apoptosis of cholangiocarcinoma QBC939 cells

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DAI Kai

2013-03-01

Full Text Available ObjectiveTo determine whether leptin can exert anti-proliferative and pro-apoptotic effects on human cholangiocarcinoma cells and to investigate the underlying molecular mechanisms. MethodsHuman cholangiocarcinoma QBC939 cells were cultured and treated with different concentrations of leptin. Changes in the proliferation rate were measured by the MTT assay. Changes in cell cycle and in the apoptosis incidence rate were detected by flow cytometry. Changes in cyclin D1, bax and bcl-2 gene expression were detected by measuring mRNA levels by real-time quantitative reverse transcription-polymerase chain reaction (qPCR. Changes in caspase-3 protease activity were detected by fluorometric assay. ResultsLeptin treatment significantly increased the proliferation rate of QBC939 cells in a dose- and time-dependent manner. Compared to untreated QBC939 cells, leptin treatment led to significantly more G0/G1 to S phase transition and significantly lower apoptosis rate. In addition, leptin-treated QBC939 cells showed enhanced mRNA expression of cyclin D1 and bcl-2, but decreased mRNA expression of bax. The leptin treatment also led to decreased caspase-3 activity. ConclusionLeptin promotes S to G0/G1 phase transition and proliferation, but inhibits apoptosis, of human cholangiocarcinoma cells in vitro.

Chromosome Damage and Cell Proliferation Rates in In Vitro Irradiated Whole Blood as Markers of Late Radiation Toxicity After Radiation Therapy to the Prostate

Energy Technology Data Exchange (ETDEWEB)

Beaton, Lindsay A., E-mail: Lindsay.Beaton@hc-sc.gc.ca [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, ON (Canada); Ferrarotto, Catherine; Marro, Leonora [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, ON (Canada); Samiee, Sara; Malone, Shawn; Grimes, Scott; Malone, Kyle [The Ottawa Hospital, Ottawa Hospital Research Institute, University of Ottawa, 501 Smyth Rd, Ottawa, ON (Canada); Wilkins, Ruth C. [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, ON (Canada)

2013-04-01

Purpose: In vitro irradiated blood samples from prostate cancer patients showing late normal tissue damage were examined for lymphocyte response by measuring chromosomal aberrations and proliferation rate. Methods and Materials: Patients were selected from a randomized trial evaluating the optimal timing of dose-escalated radiation and short-course androgen deprivation therapy. Of 438 patients, 3% experienced grade 3 late radiation proctitis and were considered to be radiosensitive. Blood samples were taken from 10 of these patients along with 20 matched samples from patients with grade 0 proctitis. The samples were irradiated at 6 Gy and, along with control samples, were analyzed for dicentric chromosomes and excess fragments per cell. Cells in first and second metaphase were also enumerated to determine the lymphocyte proliferation rate. Results: At 6 Gy, there were statistically significant differences between the radiosensitive and control cohorts for 3 endpoints: the mean number of dicentric chromosomes per cell (3.26 ± 0.31, 2.91 ± 0.32; P=.0258), the mean number of excess fragments per cell (2.27 ± 0.23, 1.43 ± 0.37; P<.0001), and the proportion of cells in second metaphase (0.27 ± 0.10, 0.46 ± 0.09; P=.0007). Conclusions: These results may be a valuable indicator for identifying radiosensitive patients and for tailoring radiation therapy.

Proliferation after the Iraq war; La proliferation apres la guerre d'Irak

Energy Technology Data Exchange (ETDEWEB)

Daguzan, J.F

2004-09-15

This article uses the Iraq war major event to analyze the approach used by the US to fight against proliferation. It questions the decision and analysis process which has led to the US-British intervention and analyzes the consequences of the war on the proliferation of other countries and on the expected perspectives. Finally, the future of proliferation itself is questioned: do we have to fear more threat or is the virtuous circle of non-proliferation well started? (J.S.)

Effect of chronic aspirin ingestion on epithelial proliferation in rat fundus, antrum, and duodenum

International Nuclear Information System (INIS)

Eastwood, G.L.; Quimby, G.F.

1972-01-01

We studied the effect of chronic aspirin ingestion on gastroduodenal epithelial proliferation by feeding rats aspirin in the drinking water. A control group of rats received plain water. At the end of 4 wk, [3H]-thymidine was given intravenously to label proliferating cells, and the rats were killed 1 h later. Sections of fundus, antrum, and proximal duodenum were processed for light autoradiography. We found that chronic aspirin ingestion stimulated epithelial proliferation in fundic mucosa but had no effect in the antrum. In the duodenum, aspirin increased proliferation in the lowest four crypt-cell positions, which most likely indicates an increase in stem-cell production. None of the tissues contained evidence of inflammation or ulceration. The proliferative effects of aspirin may help explain the previously observed phenomenon of mucosal adaptation in the rat after repeated exposure to aspirin. Further, if human gastroduodenal epithelium responds in a similar manner to chronic aspirin exposure, the effects on proliferation may explain in part the distribution of aspirin-associated ulcers

Meta-analysis shows similar re-bleeding rates among Western and Eastern populations after index video capsule endoscopy.

Science.gov (United States)

Tziatzios, Georgios; Gkolfakis, Paraskevas; Hassan, Cesare; Toth, Ervin; Zullo, Angelo; Koulaouzidis, Anastasios; Dimitriadis, George D; Triantafyllou, Konstantinos

2018-03-01

Video capsule endoscopy (VCE) is the first-line diagnostic procedure for investigating obscure gastrointestinal bleeding (OGIB). Different re-bleeding rates following index VCE have been reported among Western and Eastern studies. We conducted a comprehensive literature search to identify studies examining re-bleeding rates after VCE for OGIB. Meta-analysis assessed the pooled proportion of re-bleeding events after VCE for OGIB according to study's origin (Western vs. Eastern) and according to the length of follow-up (≥24 months vs. Western and 16 Eastern) studies with 5796 patients. Significant heterogeneity was detected among meta-analyzed studies. Overall, the pooled re-bleeding rate was similar between Western (29%; 95% CI: 23-34) and Eastern (21%; 95% CI: 15-27) populations, irrespective of the length of follow-up. The odds of re-bleeding was significantly higher after positive as compared to negative index VCE in Eastern studies (OR: 1.77; 95% CI: 1.07-2.94). Application of specific treatment after positive index VCE was associated with lower re-bleeding odds in both Western (OR: 0.37; 95% CI: 0.16-0.87) and Eastern (OR: 0.39; 95% CI: 0.21-0.72) populations. Patients undergoing VCE for OGIB have similar re-bleeding rates in the East and the West, regardless of the length of follow-up. However, increased re-bleeding odds after positive index VCE is observed in Eastern studies. Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Serotonin regulates osteoblast proliferation and function in vitro

Energy Technology Data Exchange (ETDEWEB)

Dai, S.Q.; Yu, L.P. [Department of Orthopedic Surgery, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu (China); Shi, X. [Department of Obstetrics and Gynecology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu (China); Wu, H. [Emergency Department, The First Affiliated Hospital, Soochow University, Suzhou (China); Shao, P.; Yin, G.Y.; Wei, Y.Z. [Department of Orthopedic Surgery, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu (China)

2014-08-01

The monoamine serotonin (5-hydroxytryptamine, 5-HT), a well-known neurotransmitter, also has important functions outside the central nervous system. The objective of this study was to investigate the role of 5-HT in the proliferation, differentiation, and function of osteoblasts in vitro. We treated rat primary calvarial osteoblasts with various concentrations of 5-HT (1 nM to 10 µM) and assessed the rate of osteoblast proliferation, expression levels of osteoblast-specific proteins and genes, and the ability to form mineralized nodules. Next, we detected which 5-HT receptor subtypes were expressed in rat osteoblasts at different stages of osteoblast differentiation. We found that 5-HT could inhibit osteoblast proliferation, differentiation, and mineralization at low concentrations, but this inhibitory effect was mitigated at relatively high concentrations. Six of the 5-HT receptor subtypes (5-HT{sub 1A}, 5-HT{sub 1B}, 5-HT{sub 1D}, 5-HT{sub 2A}, 5-HT{sub 2B}, and 5-HT{sub 2C}) were found to exist in rat osteoblasts. Of these, 5-HT{sub 2A} and 5-HT{sub 1B} receptors had the highest expression levels, at both early and late stages of differentiation. Our results indicated that 5-HT can regulate osteoblast proliferation and function in vitro.

TWEAK induces liver progenitor cell proliferation

Science.gov (United States)

Jakubowski, Aniela; Ambrose, Christine; Parr, Michael; Lincecum, John M.; Wang, Monica Z.; Zheng, Timothy S.; Browning, Beth; Michaelson, Jennifer S.; Baestcher, Manfred; Wang, Bruce; Bissell, D. Montgomery; Burkly, Linda C.

2005-01-01

Progenitor (“oval”) cell expansion accompanies many forms of liver injury, including alcohol toxicity and submassive parenchymal necrosis as well as experimental injury models featuring blocked hepatocyte replication. Oval cells can potentially become either hepatocytes or biliary epithelial cells and may be critical to liver regeneration, particularly when hepatocyte replication is impaired. The regulation of oval cell proliferation is incompletely understood. Herein we present evidence that a TNF family member called TWEAK (TNF-like weak inducer of apoptosis) stimulates oval cell proliferation in mouse liver through its receptor Fn14. TWEAK has no effect on mature hepatocytes and thus appears to be selective for oval cells. Transgenic mice overexpressing TWEAK in hepatocytes exhibit periportal oval cell hyperplasia. A similar phenotype was obtained in adult wild-type mice, but not Fn14-null mice, by administering TWEAK-expressing adenovirus. Oval cell expansion induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) was significantly reduced in Fn14-null mice as well as in adult wild-type mice with a blocking anti-TWEAK mAb. Importantly, TWEAK stimulated the proliferation of an oval cell culture model. Finally, we show increased Fn14 expression in chronic hepatitis C and other human liver diseases relative to its expression in normal liver, which suggests a role for the TWEAK/Fn14 pathway in human liver injury. We conclude that TWEAK has a selective mitogenic effect for liver oval cells that distinguishes it from other previously described growth factors. PMID:16110324

A Dictyostelium chalone uses G proteins to regulate proliferation

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Hanson Nana E

2009-07-01

Full Text Available Abstract Background Several studies have shown that organ size, and the proliferation of tumor metastases, may be regulated by negative feedback loops in which autocrine secreted factors called chalones inhibit proliferation. However, very little is known about chalones, and how cells sense them. We previously identified two secreted proteins, AprA and CfaD, which act as chalones in Dictyostelium. Cells lacking AprA or CfaD proliferate faster than wild-type cells, and adding recombinant AprA or CfaD to cells slows their proliferation. Results We show here that cells lacking the G protein components Galpha8, Galpha9, and Gbeta proliferate faster than wild-type cells despite secreting normal or high levels of AprA and CfaD. Compared with wild-type cells, the proliferation of galpha8-, galpha9- and gbeta- cells are only weakly inhibited by recombinant AprA (rAprA. Like AprA and CfaD, Galpha8 and Gbeta inhibit cell proliferation but not cell growth (the rate of increase in mass and protein per nucleus, whereas Galpha9 inhibits both proliferation and growth. galpha8- cells show normal cell-surface binding of rAprA, whereas galpha9- and gbeta- cells have fewer cell-surface rAprA binding sites, suggesting that Galpha9 and Gbeta regulate the synthesis or processing of the AprA receptor. Like other ligands that activate G proteins, rAprA induces the binding of [3H]GTP to membranes, and GTPgammaS inhibits the binding of rAprA to membranes. Both AprA-induced [3H]GTP binding and the GTPgammaS inhibition of rAprA binding require Galpha8 and Gbeta but not Galpha9. Like aprA- cells, galpha8- cells have reduced spore viability. Conclusion This study shows that Galpha8 and Gbeta are part of the signal transduction pathway used by AprA to inhibit proliferation but not growth in Dictyostelium, whereas Galpha9 is part of a differealnt pathway that regulates both proliferation and growth, and that a chalone signal transduction pathway uses G proteins.

Cell proliferation and ageing in mouse colon

International Nuclear Information System (INIS)

Hamilton, E.; Franks, L.M.

1980-01-01

Cell kinetic parameters in the descending colon of unirradiated mice, 3-30-months-old were compared with those in mice irradiated repeatedly from the age of 6 or 24 months. The latter animals were given 1250 rad local X-irradiation to the colon every 6 weeks. Dose-survival curves showed the colon crypts of 6 and 24-months-old mice were similarly radiosensitive. In unirradiated mice the number of crypts per colon section decreased significantly at 30 months, but no significant age-related changes were seen in crypt size or labelling index (LI). Cell proliferation returned to control levels within 6 weeks of each X-ray dose and remained at this level for 20 weeks after the final dose. Later, cell proliferation in the irradiated colon fell significantly below control. A total of 6 or 7 doses each of 1250 rad produced only 1 colon carcinoma amongst 50 mice kept until they died. (author)

Effect of molecular weight and concentration of hyaluronan on cell proliferation and osteogenic differentiation in vitro

Energy Technology Data Exchange (ETDEWEB)

Zhao, Ningbo, E-mail: curl-zhao@163.com; Wang, Xin, E-mail: 394041230@qq.com; Qin, Lei, E-mail: qinlei30@126.com; Guo, Zhengze, E-mail: zhzeguo@163.com; Li, Dehua, E-mail: lidehuafmmu@163.com

2015-09-25

Hyaluronan (HA), the simplest glycosaminoglycan and a major component of the extracellular matrix, exists in various tissues. It is involved in some critical biological procedures, including cellular signaling, cell adhesion and proliferation, and cell differentiation. The effect of molecular weight (MW) and concentration of HA on cell proliferation and differentiation was controversial. In this study, we investigated the effect of MW and concentration of HA on the proliferation and osteogenic differentiation of rabbit bone marrow-derived stem cells in vitro. Results showed that high MW HA decreased the cell adhesion rate in a concentration-dependant manner. The cell adhesion rate was decreased by increasing MW of HA. Cell proliferation was significantly enhanced by low MW HA (P < 0.05). The factorial analysis indicated that MW and concentration had an interactive effect on the cell adhesion rate and cell proliferation (P < 0.05). High MW HA increased the mRNA expressions of ALP, RUNX-2 and OCN. The higher the MW was, the higher the mRNA expressions were. The factorial analysis indicated that MW and concentration had an interactive effect on ALP mRNA expression (P < 0.05). HA of higher MW and higher concentration promoted bone formation. These findings provide some useful information in understanding the mechanism underlying the effect of MW and concentration of HA on cell proliferation and differentiation. - Highlights: • Effect of hyaluronan on cell proliferation and differentiation is evaluated in vitro. • Hyaluronan of low molecular weight increases cell proliferation. • Hyaluronan of high molecular weight promotes cell osteogenic differentiation. • Molecular weight and concentration of hyaluronan show interactive effect.

Uncertainties in Nuclear Proliferation Modeling

International Nuclear Information System (INIS)

Kim, Chul Min; Yim, Man-Sung; Park, Hyeon Seok

2015-01-01

There have been various efforts in the research community to understand the determinants of nuclear proliferation and develop quantitative tools to predict nuclear proliferation events. Such systematic approaches have shown the possibility to provide warning for the international community to prevent nuclear proliferation activities. However, there are still large debates for the robustness of the actual effect of determinants and projection results. Some studies have shown that several factors can cause uncertainties in previous quantitative nuclear proliferation modeling works. This paper analyzes the uncertainties in the past approaches and suggests future works in the view of proliferation history, analysis methods, and variable selection. The research community still lacks the knowledge for the source of uncertainty in current models. Fundamental problems in modeling will remain even other advanced modeling method is developed. Before starting to develop fancy model based on the time dependent proliferation determinants' hypothesis, using graph theory, etc., it is important to analyze the uncertainty of current model to solve the fundamental problems of nuclear proliferation modeling. The uncertainty from different proliferation history coding is small. Serious problems are from limited analysis methods and correlation among the variables. Problems in regression analysis and survival analysis cause huge uncertainties when using the same dataset, which decreases the robustness of the result. Inaccurate variables for nuclear proliferation also increase the uncertainty. To overcome these problems, further quantitative research should focus on analyzing the knowledge suggested on the qualitative nuclear proliferation studies

Proliferation Networks and Financing

International Nuclear Information System (INIS)

Gruselle, Bruno

2007-01-01

The objective of this study is to propose practical solutions aimed at completing and strengthening the existing arrangement for the control of nuclear proliferation through a control of financial as well as material or immaterial flows. In a first part, the author proposes a systemic analysis of networks of suppliers and demanders. He notably evokes the Khan's network and the Iraqi acquisition network during the 1993-2001 period. He also proposes a modelling of proliferation networks (supplier networks and acquisition networks) and of their interactions. In a second part, the author examines possible means and policies aimed at neutralising proliferation networks: organisation, adaptation and improvement of intelligence tools in front of proliferation networks, and means, limitations and perspectives of network neutralisation. He also briefly addresses the possibility of military action to contain proliferation flows

Can we predict nuclear proliferation

International Nuclear Information System (INIS)

Tertrais, Bruno

2011-01-01

The author aims at improving nuclear proliferation prediction capacities, i.e. the capacities to identify countries susceptible to acquire nuclear weapons, to interpret sensitive activities, and to assess nuclear program modalities. He first proposes a retrospective assessment of counter-proliferation actions since 1945. Then, based on academic studies, he analyzes what causes and motivates proliferation, with notably the possibility of existence of a chain phenomenon (mechanisms driving from one program to another). He makes recommendations for a global approach to proliferation prediction, and proposes proliferation indices and indicators

Commonly used bowel preparations have significant and different effects upon cell proliferation in the colon: a pilot study

Directory of Open Access Journals (Sweden)

Riley Stuart A

2008-11-01

Full Text Available Abstract Background Markers of crypt cell proliferation are frequently employed in studies of the impact of genetic and exogenous factors on human colonic physiology. Human studies often rely on the assessment of tissue acquired at endoscopy. Modulation of cell proliferation by bowel preparation with oral laxatives may confound the findings of such studies, but there is little data on the impact of commonly used bowel preparations on markers of cell proliferation. Methods Crypt length, crypt cellularity and crypt cell proliferation were assessed in biopsies acquired after preparation with either Klean-Prep or Picolax. Crypt cell proliferation was assessed by whole-mount mitotic figure count, and by two different immunohistochemical (IHC labelling methods (Ki-67 and pHH3. Subsequent biopsies were obtained from the same patients without bowel preparation and similarly assessed. Parameters were compared between groups using analysis of variance and paired t-tests. Results There were significant differences in labelling indices (LI between biopsies taken after Klean-prep and those taken after Picolax preparation, for both Ki67 (p = 0.019 and pHH3 (p = 0.017. A similar trend was seen for whole-mount mitotic figure counts. Suppression or elevation of proliferation parameters by bowel preparation may mask any effect due to an intervention or disease. Conclusion Commonly used bowel preparations may have significant and different effects on crypt cell proliferation. This should be taken into account when designing studies and when considering the findings of existing studies.

Phenolic Compounds in Extra Virgin Olive Oil Stimulate Human Osteoblastic Cell Proliferation.

Science.gov (United States)

García-Martínez, Olga; De Luna-Bertos, Elvira; Ramos-Torrecillas, Javier; Ruiz, Concepción; Milia, Egle; Lorenzo, María Luisa; Jimenez, Brigida; Sánchez-Ortiz, Araceli; Rivas, Ana

2016-01-01

In this study, we aimed to clarify the effects of phenolic compounds and extracts from different extra virgin olive oil (EVOO) varieties obtained from fruits of different ripening stages on osteoblast cells (MG-63) proliferation. Cell proliferation was increased by hydroxytyrosol, luteolin, apigenin, p-coumaric, caffeic, and ferulic acids by approximately 11-16%, as compared with controls that were treated with one vehicle alone, while (+)-pinoresinol, oleuropein, sinapic, vanillic acid and derivative (vanillin) did not affect cell proliferation. All phenolic extracts stimulated MG-63 cell growth, and they induced higher cell proliferation rates than individual compounds. The most effective EVOO phenolic extracts were those obtained from the Picual variety, as they significantly increased cell proliferation by 18-22%. Conversely, Arbequina phenolic extracts increased cell proliferation by 9-13%. A decline in osteoblast proliferation was observed in oils obtained from olive fruits collected at the end of the harvest period, as their total phenolic content decreases at this late stage. Further research on the signaling pathways of olive oil phenolic compounds involved in the processes and their metabolism should be carried out to develop new interventions and adjuvant therapies using EVOO for bone health (i.e.osteoporosis) in adulthood and the elderly.

Phenolic Compounds in Extra Virgin Olive Oil Stimulate Human Osteoblastic Cell Proliferation

Science.gov (United States)

García-Martínez, Olga; De Luna-Bertos, Elvira; Ramos-Torrecillas, Javier; Ruiz, Concepción; Milia, Egle; Lorenzo, María Luisa; Jimenez, Brigida; Sánchez-Ortiz, Araceli; Rivas, Ana

2016-01-01

In this study, we aimed to clarify the effects of phenolic compounds and extracts from different extra virgin olive oil (EVOO) varieties obtained from fruits of different ripening stages on osteoblast cells (MG-63) proliferation. Cell proliferation was increased by hydroxytyrosol, luteolin, apigenin, p-coumaric, caffeic, and ferulic acids by approximately 11–16%, as compared with controls that were treated with one vehicle alone, while (+)-pinoresinol, oleuropein, sinapic, vanillic acid and derivative (vanillin) did not affect cell proliferation. All phenolic extracts stimulated MG-63 cell growth, and they induced higher cell proliferation rates than individual compounds. The most effective EVOO phenolic extracts were those obtained from the Picual variety, as they significantly increased cell proliferation by 18–22%. Conversely, Arbequina phenolic extracts increased cell proliferation by 9–13%. A decline in osteoblast proliferation was observed in oils obtained from olive fruits collected at the end of the harvest period, as their total phenolic content decreases at this late stage. Further research on the signaling pathways of olive oil phenolic compounds involved in the processes and their metabolism should be carried out to develop new interventions and adjuvant therapies using EVOO for bone health (i.e.osteoporosis) in adulthood and the elderly. PMID:26930190

Indirubin inhibits cell proliferation, migration, invasion and angiogenesis in tumor-derived endothelial cells

Directory of Open Access Journals (Sweden)

Li Z

2018-05-01

Full Text Available Zhuohong Li, Chaofu Zhu, Baiping An, Yu Chen, Xiuyun He, Lin Qian, Lan Lan, Shijie Li Department of Oncology, The Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China Purpose: Hepatocellular carcinoma is one of the most predominant malignancies with high fatality rate and its incidence is rising at an alarming rate because of its resistance to radio- and chemotherapy. Indirubin is the major active anti-tumor ingredient of a traditional Chinese herbal medicine. The present study aimed to analyze the effects of indirubin on cell proliferation, migration, invasion, and angiogenesis of tumor-derived endothelial cells (Td-EC. Methods: Td-EC were derived from human umbilical vein endothelial cells (HUVEC by treating HUVEC with the conditioned medium of human liver cancer cell line HepG2. Cell proliferation, migration, invasion, and angiogenesis were assessed by MTT, wound healing, in vitro cell invasion, and in vitro tube formation assay. Results: Td-EC were successfully obtained from HUVEC cultured with 50% culture supernatant from serum-starved HepG2 cells. Indirubin significantly inhibited Td-EC proliferation in a dose- and time-dependent manner. Indirubin also inhibited Td-EC migration, invasion, and angiogenesis. However, indirubin’s effects were weaker on HUVEC than Td-EC. Conclusion: Indirubin significantly inhibited Td-EC proliferation, migration, invasion, and angiogenesis. Keywords: indirubin, Td-EC, proliferation, migration, invasion, angiogenesis

Differential proliferation rhythm of neural progenitor and oligodendrocyte precursor cells in the young adult hippocampus.

Directory of Open Access Journals (Sweden)

Yoko Matsumoto

Full Text Available Oligodendrocyte precursor cells (OPCs are a unique type of glial cells that function as oligodendrocyte progenitors while constantly proliferating in the normal condition from rodents to humans. However, the functional roles they play in the adult brain are largely unknown. In this study, we focus on the manner of OPC proliferation in the hippocampus of the young adult mice. Here we report that there are oscillatory dynamics in OPC proliferation that differ from neurogenesis in the subgranular zone (SGZ; the former showed S-phase and M-phase peaks in the resting and active periods, respectively, while the latter only exhibited M-phase peak in the active period. There is coincidence between different modes of proliferation and expression of cyclin proteins that are crucial for cell cycle; cyclin D1 is expressed in OPCs, while cyclin D2 is observed in neural stem cells. Similar to neurogenesis, the proliferation of hippocampal OPCs was enhanced by voluntary exercise that leads to an increase in neuronal activity in the hippocampus. These data suggest an intriguing control of OPC proliferation in the hippocampus.

Future non-proliferation challenges

International Nuclear Information System (INIS)

Yelchenko, Volodymyr

2008-01-01

Having chaired the Second Session of the Preparatory Committee Mr. Volodymyr Yelchenko noted that the NPT States parties reaffirmed the important role of the Treaty as the cornerstone of the global non-proliferation regime. They stressed that non-compliance with the Treaty provisions by States parties undermined non-proliferation and placed emphasis on the mutually reinforcing nature of disarmament and non-proliferation, and due respect for the right of States parties to the peaceful use of nuclear energy in conformity with the treaty. They reaffirmed the importance of promoting the peaceful uses of nuclear energy and international nuclear cooperation for peaceful purposes in ways consistent with the non-proliferation goal of the Treaty. The universality aspect was brought to the front with the lack of progress in this area. States parties called upon India, Israel and Pakistan to accede to the Treaty as non-nuclear-weapons states, promptly and without conditions and to bring into force comprehensive safeguards agreements, together with Additional Protocols, for ensuring non-proliferation. There is concern that non-States actors could gain access to weapons of mass destruction. One of the underlying themes at the Second Prepcom was the total elimination of nuclear weapons as the only absolute guarantee against their proliferation. Negative consequences to nuclear non-proliferation were also mentioned in the context of the abrogation of the Anti-Ballistic Missile Treaty and the development of missile defense systems, with the risk of a new arms race on Earth and in outer space. The importance of the immediate commencement of negotiations in the Conference of Disarmament on a treaty concerning fissile material for nuclear weapons or other nuclear explosive devices and the urgent conclusion of such a treaty as a beneficial step towards non-proliferation was stressed. The NPT states parties reaffirmed the role of the IAEA as the sole competent authority responsible for

Black cohosh inhibits 17β-estradiol-induced cell proliferation of endometrial adenocarcinoma cells.

Science.gov (United States)

Park, So Yun; Kim, Hee Ja; Lee, Sa Ra; Choi, Youn-Hee; Jeong, Kyungah; Chung, Hyewon

2016-10-01

This study was conducted to investigate the effect of black cohosh (BC) extract on the proliferation and apoptosis of Ishikawa cells. Ishikawa human endometrial adenocarcinoma cells were treated with or without BC (1, 5, 10 and 25 μM) and cell proliferation and cytotoxicity were measured by CCK-8 assays and flow cytometry analysis. Additionally, Ishikawa cells were treated with 17β-estradiol (E2), E2 + progesterone and E2 + BC (5 and 10 μM) and the effect of BC and progesterone on E2-induced cell proliferation was analyzed. BC decreased the proliferation of Ishikawa cells at a dose-dependent rate compared with the control group (p < 0.05). The proliferation of Ishikawa cells increased in the presence of E2, whereas the subsequent addition of progesterone or BC decreased proliferation to the level of the control group (p < 0.05). The inhibitory effect of BC on E2-induced cell proliferation was greater than the inhibitory effect of progesterone. In conclusion, BC induces apoptosis in Ishikawa cells and suppresses E2-induced cell proliferation in Ishikawa cells. BC could be considered a candidate co-treatment agent of estrogen-dependent tumors, especially those involving endometrial cells.

Investigation of psychophysical similarity measures for selection of similar images in the diagnosis of clustered microcalcifications on mammograms

International Nuclear Information System (INIS)

Muramatsu, Chisako; Li Qiang; Schmidt, Robert; Shiraishi, Junji; Doi, Kunio

2008-01-01

The presentation of images with lesions of known pathology that are similar to an unknown lesion may be helpful to radiologists in the diagnosis of challenging cases for improving the diagnostic accuracy and also for reducing variation among different radiologists. The authors have been developing a computerized scheme for automatically selecting similar images with clustered microcalcifications on mammograms from a large database. For similar images to be useful, they must be similar from the point of view of the diagnosing radiologists. In order to select such images, subjective similarity ratings were obtained for a number of pairs of clustered microcalcifications by breast radiologists for establishment of a ''gold standard'' of image similarity, and the gold standard was employed for determination and evaluation of the selection of similar images. The images used in this study were obtained from the Digital Database for Screening Mammography developed by the University of South Florida. The subjective similarity ratings for 300 pairs of images with clustered microcalcifications were determined by ten breast radiologists. The authors determined a number of image features which represent the characteristics of clustered microcalcifications that radiologists would use in their diagnosis. For determination of objective similarity measures, an artificial neural network (ANN) was employed. The ANN was trained with the average subjective similarity ratings as teacher and selected image features as input data. The ANN was trained to learn the relationship between the image features and the radiologists' similarity ratings; therefore, once the training was completed, the ANN was able to determine the similarity, called a psychophysical similarity measure, which was expected to be close to radiologists' impressions, for an unknown pair of clustered microcalcifications. By use of a leave-one-out test method, the best combination of features was selected. The correlation

Investigation of psychophysical similarity measures for selection of similar images in the diagnosis of clustered microcalcifications on mammograms

Energy Technology Data Exchange (ETDEWEB)

Muramatsu, Chisako; Li Qiang; Schmidt, Robert; Shiraishi, Junji; Doi, Kunio [Department of Radiology, University of Chicago, 5841 South Maryland Avenue, Chicago, Illinois 60637 (United States) and Department of Intelligent Image Information, Gifu University, 1-1 Yanagido, Gifu (Japan); Department of Radiology, Duke Advanced Imaging Labs, Duke University, 2424 Erwin Road, Suite 302, Durham, North Carolina 27705 (United States); Department of Radiology, University of Chicago, 5841 South Maryland Avenue, Chicago, Illinois 60637 (United States)

2008-12-15

The presentation of images with lesions of known pathology that are similar to an unknown lesion may be helpful to radiologists in the diagnosis of challenging cases for improving the diagnostic accuracy and also for reducing variation among different radiologists. The authors have been developing a computerized scheme for automatically selecting similar images with clustered microcalcifications on mammograms from a large database. For similar images to be useful, they must be similar from the point of view of the diagnosing radiologists. In order to select such images, subjective similarity ratings were obtained for a number of pairs of clustered microcalcifications by breast radiologists for establishment of a ''gold standard'' of image similarity, and the gold standard was employed for determination and evaluation of the selection of similar images. The images used in this study were obtained from the Digital Database for Screening Mammography developed by the University of South Florida. The subjective similarity ratings for 300 pairs of images with clustered microcalcifications were determined by ten breast radiologists. The authors determined a number of image features which represent the characteristics of clustered microcalcifications that radiologists would use in their diagnosis. For determination of objective similarity measures, an artificial neural network (ANN) was employed. The ANN was trained with the average subjective similarity ratings as teacher and selected image features as input data. The ANN was trained to learn the relationship between the image features and the radiologists' similarity ratings; therefore, once the training was completed, the ANN was able to determine the similarity, called a psychophysical similarity measure, which was expected to be close to radiologists' impressions, for an unknown pair of clustered microcalcifications. By use of a leave-one-out test method, the best combination of features

Which future for nuclear counter-proliferation?; Quel avenir pour la contre-proliferation nucleaire?

Energy Technology Data Exchange (ETDEWEB)

Duval, M.

2010-07-15

Dealing with the case of nuclear weapons possessed by nuclear states (but not eventually by terrorists), the author first identifies the constants of counter-proliferation: it is linked to interest conflicts between those who try to preserve their monopoly and those who try to acquire a new weapon either because of a threat or for reasons of regional prestige, the evolution from use to deterrence, the appearance of new actors after the USA and Russia, the role of nuclear tactical weapons, and the future of Russian weapons and know-how. He presents the international counter-proliferation context: the Non Proliferation Treaty (NPT), the IAEA and its controls, the Nuclear Supplier Group (NSG), the nuclear-free zones, the Comprehensive Test Ban Treaty (CTBT), the Missile Technology Control Regime (MTCR). He describes how and why proliferation occurs: uranium enrichment and plutonium technology, political reasons in different parts of the world. Then, he gives an overview of the proliferation status by commenting the cases of Israel, Iraq, India, Pakistan, North Korea, and Iran. He discusses the future of proliferation (involved countries, existence of a nuclear black market) and of counter-proliferation as far as Middle-East and North Korea are concerned. He tries finally to anticipate the consequences for nuclear deterrence strategy, and more particularly for Europe and France

Effect of 60Co γ-ray radiation on bud proliferation of oriental lily scales cultured in vitro

International Nuclear Information System (INIS)

Wang Dan; Zhang Zhiwei; Zhang Dongxue

2009-01-01

The effects of 60 Co γ-ray radiation on the bud proliferation of the oriental lily scales cultured in vitro were studied. The results show that the irradiation significantly inhibits bud proliferation, but the effects of radiation on the number of bud proliferation and the bud proliferation rate are obviously depressed along with the increasing of times of bud proliferation. The effect of radiation on the bud proliferation is repressive during the first time of bud proliferation and the effect is more significant in the higher radiation dosage treatment. The repressive effect of radiation on the bud proliferation disappears during the third time of bud proliferation, but the physiologic status is in the telophase of the damage repair action. The contents of protein and MDA of the bud were influenced differently depending on the radiation dosage and on the types of medium and positions of scales. (authors)

Interaction of LY171883 and other peroxisome proliferators with fatty-acid-binding protein isolated from rat liver.

Science.gov (United States)

Cannon, J R; Eacho, P I

1991-01-01

Fatty-acid-binding protein (FABP) is a 14 kDa protein found in hepatic cytosol which binds and transports fatty acids and other hydrophobic ligands throughout the cell. The purpose of this investigation was to determine whether LY171883, a leukotriene D4 antagonist, and other peroxisome proliferators bind to FABP and displace an endogenous fatty acid. [3H]Oleic acid was used to monitor the elution of FABP during chromatographic purification. [14C]LY171883 had a similar elution profile when substituted in the purification, indicating a common interaction with FABP. LY171883 and its structural analogue, LY189585, as well as the hypolipidaemic peroxisome proliferators clofibric acid, ciprofibrate, bezafibrate and WY14,643, displaced [3H]oleic acid binding to FABP. Analogues of LY171883 that do not induce peroxisome proliferation only weakly displaced oleate binding. [3H]Ly171883 bound directly to FABP with a Kd of 10.8 microM, compared with a Kd of 0.96 microM for [3H]oleate. LY171883 binding was inhibited by LY189585, clofibric acid, ciprofibrate and bezafibrate. These findings demonstrate that peroxisome proliferators, presumably due to their structural similarity to fatty acids, are able to bind to FABP and displace an endogenous ligand from its binding site. Interaction of peroxisome proliferators with FABP may be involved in perturbations of fatty acid metabolism caused by these agents as well as in the development of the pleiotropic response of peroxisome proliferation. Images Fig. 2. PMID:1747111

Dafachronic acid inhibits C. elegans germ cell proliferation in a DAF-12-dependent manner.

Science.gov (United States)

Mukherjee, Madhumati; Chaudhari, Snehal N; Balachandran, Riju S; Vagasi, Alexandra S; Kipreos, Edward T

2017-12-15

Dafachronic acid (DA) is a bile acid-like steroid hormone that regulates dauer formation, heterochrony, and lifespan in C. elegans. Here, we describe that DA is an inhibitor of C. elegans germ stem cell proliferation in adult hermaphrodites. Using a C. elegans germ cell primary culture system, we show that DA inhibits the proliferation of germ cells in vitro. Exogenous DA reduces the frequency of large tumors in adult tumorous germline mutants and decreases the proliferation of wild-type germ stem cells in adult hermaphrodites. In contrast, DA has no appreciable effect on the proliferation of larval-stage germ cells in wild type. The inhibition of adult germ cell proliferation by DA requires its canonical receptor DAF-12. Blocking DA production by inactivating the cytochrome P450 DAF-9 increases germ cell proliferation in wild-type adult hermaphrodites and the frequency of large tumors in germline tumorous mutants, suggesting that DA inhibits the rate of germ cell proliferation under normal growth conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

In vitro PROLIFERATION ABILITY OF AXILLARY BUDS IN Musa spp

African Journals Online (AJOL)

AISA

The proliferation rate of Axillary and apical buds and other growth parameters ... types of buds after four to five sub cultures in all the varieties except for CRBP 39 where the axillary bud exhibits ..... propagation, conservation and exchange.

Non-proliferation and nuclear data

International Nuclear Information System (INIS)

Sowerby, M.G.

1978-01-01

A review is made of the problem of the proliferation of nuclear weapons with particular emphasis on proliferation and nuclear power. Some indications of the nuclear data requirements associated with methods of reducing proliferation risks are presented

Toward translational incremental similarity-based reasoning in breast cancer grading

Science.gov (United States)

Tutac, Adina E.; Racoceanu, Daniel; Leow, Wee-Keng; Müller, Henning; Putti, Thomas; Cretu, Vladimir

2009-02-01

One of the fundamental issues in bridging the gap between the proliferation of Content-Based Image Retrieval (CBIR) systems in the scientific literature and the deficiency of their usage in medical community is based on the characteristic of CBIR to access information by images or/and text only. Yet, the way physicians are reasoning about patients leads intuitively to a case representation. Hence, a proper solution to overcome this gap is to consider a CBIR approach inspired by Case-Based Reasoning (CBR), which naturally introduces medical knowledge structured by cases. Moreover, in a CBR system, the knowledge is incrementally added and learned. The purpose of this study is to initiate a translational solution from CBIR algorithms to clinical practice, using a CBIR/CBR hybrid approach. Therefore, we advance the idea of a translational incremental similarity-based reasoning (TISBR), using combined CBIR and CBR characteristics: incremental learning of medical knowledge, medical case-based structure of the knowledge (CBR), image usage to retrieve similar cases (CBIR), similarity concept (central for both paradigms). For this purpose, three major axes are explored: the indexing, the cases retrieval and the search refinement, applied to Breast Cancer Grading (BCG), a powerful breast cancer prognosis exam. The effectiveness of this strategy is currently evaluated over cases provided by the Pathology Department of Singapore National University Hospital, for the indexing. With its current accuracy, TISBR launches interesting perspectives for complex reasoning in future medical research, opening the way to a better knowledge traceability and a better acceptance rate of computer-aided diagnosis assistance among practitioners.

Proliferation: myth or reality?

International Nuclear Information System (INIS)

2005-01-01

This article analyzes the proliferation approach, its technical condition and political motivation, and the share between the myth (political deception, assumptions and extrapolations) and the reality of proliferation. Its appreciation is complicated by the irrational behaviour of some political actors and by the significant loss of the non-use taboo. The control of technologies is an important element for proliferation slowing down but an efficient and autonomous intelligence system remains indispensable. (J.S.)

Dictyostelium cells bind a secreted autocrine factor that represses cell proliferation.

Science.gov (United States)

Choe, Jonathan M; Bakthavatsalam, Deenadayalan; Phillips, Jonathan E; Gomer, Richard H

2009-02-02

Dictyostelium cells secrete the proteins AprA and CfaD. Cells lacking either AprA or CfaD proliferate faster than wild type, while AprA or CfaD overexpressor cells proliferate slowly, indicating that AprA and CfaD are autocrine factors that repress proliferation. CfaD interacts with AprA and requires the presence of AprA to slow proliferation. To determine if CfaD is necessary for the ability of AprA to slow proliferation, whether AprA binds to cells, and if so whether the binding requires the presence of CfaD, we examined the binding and effect on proliferation of recombinant AprA. We find that the extracellular accumulation of AprA increases with cell density and reaches a concentration of 0.3 microg/ml near a stationary cell density. When added to wild-type or aprA- cells, recombinant AprA (rAprA) significantly slows proliferation at 0.1 microg/ml and higher concentrations. From 4 to 64 microg/ml, the effect of rAprA is at a plateau, slowing but not stopping proliferation. The proliferation-inhibiting activity of rAprA is roughly the same as that of native AprA in conditioned growth medium. Proliferating aprA- cells show saturable binding of rAprA to 92,000 +/- 11,000 cell-surface receptors with a KD of 0.03 +/- 0.02 microg/ml. There appears to be one class of binding site, and no apparent cooperativity. Native AprA inhibits the binding of rAprA to aprA- cells with a Ki of 0.03 mug/ml, suggesting that the binding kinetics of rAprA are similar to those of native AprA. The proliferation of cells lacking CrlA, a cAMP receptor-like protein, or cells lacking CfaD are not affected by rAprA. Surprisingly, both cell types still bind rAprA. Together, the data suggest that AprA functions as an autocrine proliferation-inhibiting factor by binding to cell surface receptors. Although AprA requires CfaD for activity, it does not require CfaD to bind to cells, suggesting the possibility that cells have an AprA receptor and a CfaD receptor, and activation of both receptors is

Controlling nuclear proliferation

International Nuclear Information System (INIS)

Sweet, W.

1981-01-01

Nuclear non-proliferation policy depends on the 1968 Non-Proliferation Treaty, in which countries promise not to acquire nuclear weapons in exchange for open access to peaceful nuclear technology, and a system of international safeguards that are imposed on exported nuclear equipment and facilities operated by parties to the treaty. Critics have feared all along that non-nuclear countries might circumvent or exploit the system to obtain nuclear weapons and that the Atoms for Peace plan would spread the very technology it sought to control. The nuclear weapons states would like everyone else to believe that atomic bombs are undesirable, but they continue to rely on the bombs for their own defense. Israel's raid on Iraq's nuclear reactor focused world attention on the proliferation problem and helped to broaden and sterengthen its prospects. It also highlighted the weakness that there are no effective sanctions against violators. Until the international community can ageee on enforcement measures powerful enough to prevent nuclear proliferation, individual countries may be tempted to follow Israel's example, 19 references

Proliferation risks

International Nuclear Information System (INIS)

Carchon, R.

1998-09-01

The report gives an overview of different aspects related to safeguards of fissile materials. Existing treaties including the Non-Proliferation Treaty, and the Tlatelolco and the Rarotonga Treaties are discussed. An overview of safeguards systems for the control of fissile materials as well as the role of various authorities is given. An overall overview of proliferation risks, the physical protection of fissile materials and the trade in fissile materials is given. Finally, the status in problem countries and de facto nuclear weapon states is discussed

Proliferation after the Iraq war

International Nuclear Information System (INIS)

Daguzan, J.F.

2004-09-01

This article uses the Iraq war major event to analyze the approach used by the US to fight against proliferation. It questions the decision and analysis process which has led to the US-British intervention and analyzes the consequences of the war on the proliferation of other countries and on the expected perspectives. Finally, the future of proliferation itself is questioned: do we have to fear more threat or is the virtuous circle of non-proliferation well started? (J.S.)

Unicystic ameloblastoma with diverse mural proliferation - a hybrid lesion

International Nuclear Information System (INIS)

Mahadesh, Jyothi; Rayapati, Dilip Kumar; Maligi, Prathima M; Ramachandra, Prashanth

2011-01-01

A 46-year-old man was referred to our hospital for treatment, complaining of swelling on the right mandibular molar region. Radiographic examination revealed a well defined multilocular radiolucent lesion with root resorption of right lower anteriors and molars. Following biopsy, a diagnosis of unicystic ameloblastoma of mural type was made and hemimandibulectomy was performed under general anesthesia. Histopathological examination of the surgical specimen exhibited a unicystic ameloblastoma of luminal, intraluminal, and mural type. Intraluminal proliferation was of plexiform pattern and mural proliferation showed unusual histopathological findings, which revealed follicular, acanthomatous areas coexisted with desmoplastic areas. This mural picture was similar to the so-called 'hybrid lesion of ameloblastoma', whose biological profile is not elicited due to the lack of adequate published reports. Two years follow up till date has not revealed any signs of recurrence.

Unicystic ameloblastoma with diverse mural proliferation - a hybrid lesion

Energy Technology Data Exchange (ETDEWEB)

Mahadesh, Jyothi [Sri Siddhartha Dental College and Hospital, (India); Rayapati, Dilip Kumar; Maligi, Prathima M; Ramachandra, Prashanth [Dayananda Sagar College of Dental Sciences, Bengaluru (India)

2011-03-15

A 46-year-old man was referred to our hospital for treatment, complaining of swelling on the right mandibular molar region. Radiographic examination revealed a well defined multilocular radiolucent lesion with root resorption of right lower anteriors and molars. Following biopsy, a diagnosis of unicystic ameloblastoma of mural type was made and hemimandibulectomy was performed under general anesthesia. Histopathological examination of the surgical specimen exhibited a unicystic ameloblastoma of luminal, intraluminal, and mural type. Intraluminal proliferation was of plexiform pattern and mural proliferation showed unusual histopathological findings, which revealed follicular, acanthomatous areas coexisted with desmoplastic areas. This mural picture was similar to the so-called 'hybrid lesion of ameloblastoma', whose biological profile is not elicited due to the lack of adequate published reports. Two years follow up till date has not revealed any signs of recurrence.

Proliferation-dependent changes in amino acid transport and glucose metabolism in glioma cell lines

International Nuclear Information System (INIS)

Sasajima, Toshio; Miyagawa, Tadashi; Oku, Takamitsu; Gelovani, Juri G.; Finn, Ronald; Blasberg, Ronald

2004-01-01

Amino acid imaging is increasingly being used for assessment of brain tumor malignancy, extent of disease, and prognosis. This study explores the relationship between proliferative activity, amino acid transport, and glucose metabolism in three glioma cell lines (U87, Hs683, C6) at different phases of growth in culture. Growth phase was characterized by direct cell counting, proliferation index determined by flow cytometry, and [ 3 H]thymidine (TdR) accumulation, and was compared with the uptake of two non-metabolized amino acids ([ 14 C]aminocyclopentane carboxylic acid (ACPC) and [ 14 C]aminoisobutyric acid (AIB)), and [ 18 F]fluorodeoxyglucose (FDG). Highly significant relationships between cell number (density), proliferation index, and TdR accumulation rate were observed in all cell lines (r>0.99). Influx (K 1 ) of both ACPC and AIB was directly related to cell density, and inversely related to the proliferation index and TdR accumulation in all cell lines. The volume of distribution (V d ) for ACPC and AIB was lowest during rapid growth and highest during the near-plateau growth phase in all cell lines. FDG accumulation in Hs683 and C6 cells was unaffected by proliferation rate, growth phase, and cell density, whereas FDG accumulation was correlated with TdR accumulation, growth phase, and cell density in U87 cells. This study demonstrates that proliferation rate and glucose metabolism are not necessarily co-related in all glioma cell lines. The values of K 1 and V d for ACPC and AIB under different growth conditions suggest that these tumor cell lines can up-regulate amino acid transporters in their cell membranes when their growth conditions become adverse and less than optimal. (orig.)

Regulation of proliferation of embryonic heart mesenchyme: Role of transforming growth factor-beta 1 and the interstitial matrix

International Nuclear Information System (INIS)

Choy, M.; Armstrong, M.T.; Armstrong, P.B.

1990-01-01

Proliferation of atrioventricular cushion mesenchyme of the embryonic avian heart maintained in three-dimensional aggregate culture is stimulated by interaction with the interstitial matrix. Chicken serum or transforming growth factor-beta 1, which stimulates proliferation, induces matrix deposition in regions of the aggregate showing high labeling indices with tritiated thymidine. Dispersed heart mesenchyme interstitial matrix introduced into serum-free culture is incorporated into the aggregate and stimulates cellular proliferation similar to serum or transforming growth factor-beta 1. Proliferation is reversibly inhibited by the peptide Gly-Arg-Gly-Asp-Ser-Pro. It is suggested that transforming growth factor-beta 1 stimulates the production of interstitial matrix and that a sufficient stimulus for proliferation in this system is the presence of the matrix, which acts as the adhesive support for cellular anchorage

Fissile material disposition and proliferation risk

Energy Technology Data Exchange (ETDEWEB)

Dreicer, J.S.; Rutherford, D.A. [Los Alamos National Lab., NM (United States). NIS Div.

1996-05-01

The proliferation risk of a facility is dependent on the material attractiveness, level of safeguards, and physical protection applied to the material in conjunction with an assessment of the impact of the socioeconomic circumstances and threat environment. Proliferation risk is a complementary extension of proliferation resistance. The authors believe a better determination of nuclear material proliferation can be achieved by establishing the proliferation risk for facilities that contain nuclear material. Developing a method that incorporates the socioeconomic circumstances and threat environment inherent to each country enables a global proliferation assessment. In order to effectively reduce the nuclear danger, a broadly based set of criteria is needed that provides the capability to relatively assess a wide range of disposition options/facilities in different countries and still ensure a global decrease in proliferation risk for plutonium.

Fissile material disposition and proliferation risk

International Nuclear Information System (INIS)

Dreicer, J.S.; Rutherford, D.A.

1996-01-01

The proliferation risk of a facility is dependent on the material attractiveness, level of safeguards, and physical protection applied to the material in conjunction with an assessment of the impact of the socioeconomic circumstances and threat environment. Proliferation risk is a complementary extension of proliferation resistance. The authors believe a better determination of nuclear material proliferation can be achieved by establishing the proliferation risk for facilities that contain nuclear material. Developing a method that incorporates the socioeconomic circumstances and threat environment inherent to each country enables a global proliferation assessment. In order to effectively reduce the nuclear danger, a broadly based set of criteria is needed that provides the capability to relatively assess a wide range of disposition options/facilities in different countries and still ensure a global decrease in proliferation risk for plutonium

Efectos del entrenamiento continuo e interválico de carga externa similar sobre la frecuencia cardiaca Effects of continuous and interval training similar external load on heart rate

Directory of Open Access Journals (Sweden)

J. L. Tuimil

2010-09-01

Full Text Available

Los objetivos de este estudio fueron comparar la frecuencia cardíaca (FC media entre dos tipos de entrenamiento de carga externa equiparada basados en la carrera, la relación de la velocidad aeróbica máxima (VAM con la F.C. de reserva (FCR y los efectos de estos dos tipos de entrenamiento sobre la F.C. basal (FCB. El estudio se llevó a cabo con ocho estudiantes de educación física (23,25 años; VAM: 17,93 Km.h-1 que realizaron dos tipos de entrenamiento: CC =8 km al 70%VAM y CI= 4x(1000m al 90%VAM+1000m al 50% VAM. Se registró la FC durante el entrenamiento y la FCB antes y después del mismo. La diferencia de la FC media entre ambos métodos no fue estadísticamente significativa, sin embargo las medias del CC (FCCC (Z=2,240; p<0,05 y CI (FCCI (Z=2,380; p<0,05 fueron significativamente más elevadas que la calculada al 70% de FCR. La FCB se elevó de forma significativa (Z=2,319; p=0.020 solamente después del entrenamiento CI. En conclusión, dos métodos de entrenamiento distintos, pero de intensidad media similar, pueden dar lugar a una FC media también similar. La intensidad de carrera programada en función de la VAM es significativamente superior a la programada en función de la FCR. El entrenamiento interválico puede tener un mayor efecto sobre el incremento de la FCB.
PALABRAS CLAVE: Frecuencia cardíaca media, frecuencia cardíaca de reserva, frecuencia cardíaca basal, VAM, carrera continua, carrera interválica.

The aims of this study were to compare the mean heart rate response in two training methods of equal average intensity based on running, the relationship of the maximal aerobic speed (VAM with the reserve heart rate (FCR and the effects of these modes of training on the basal heart rate (FCB. The study was carried out with eight physical activity students (23,25 years old; VAM: 17,93 Km.h^-1

Intelligence and Nuclear Proliferation: Lessons Learned

International Nuclear Information System (INIS)

Hansen, Keith A.

2011-09-01

Intelligence agencies play a fundamental role in the prevention of nuclear proliferation, as they help to understand other countries' intentions and assess their technical capabilities and the nature of their nuclear activities. The challenges in this area remain, however, formidable. Past experiences and the discoveries of Iraq's WMD programs, of North Korean nuclear weapon program, and of Iranian activities, have put into question the ability of intelligence to monitor small, clandestine proliferation activities from either states or non-state entities. This Proliferation Paper analyzes the complex challenges intelligence faces and the various roles it plays in supporting national and international nuclear non-proliferation efforts, and reviews its track record. In an effort to shed light on the role and contribution of intelligence in national and international efforts to halt, if not prevent, further nuclear weapon proliferation, this paper first analyzes the challenges intelligence faces in monitoring small, clandestine proliferation activities and the role it plays in supporting non-proliferation efforts. It then reviews the intelligence track record in monitoring proliferation including the lessons learned from Iraq. Finally, it addresses whether it is possible for intelligence to accurately monitor future clandestine proliferation efforts. (author)

Getting serious about proliferation

International Nuclear Information System (INIS)

Leventhal, P.

1984-01-01

The US needs to give a higher priority to nuclear non-proliferation, but Reagan's policies assume that proliferation is inevitable and that it is more important to be a reliable supplier than to cause trade frictions by trading only with those nations which sign the non-proliferation treaty (NPT). This undercuts US leadership and the intent of the agreement. Several bills now before Congress could help to restore US leadership by tightening export restrictions and the use of plutonium from the US

Gait in ducks (Anas platyrhynchos and chickens (Gallus gallus – similarities in adaptation to high growth rate

Directory of Open Access Journals (Sweden)

B. M. Duggan

2016-08-01

Full Text Available Genetic selection for increased growth rate and muscle mass in broiler chickens has been accompanied by mobility issues and poor gait. There are concerns that the Pekin duck, which is on a similar selection trajectory (for production traits to the broiler chicken, may encounter gait problems in the future. In order to understand how gait has been altered by selection, the walking ability of divergent lines of high- and low-growth chickens and ducks was objectively measured using a pressure platform, which recorded various components of their gait. In both species, lines which had been selected for large breast muscle mass moved at a slower velocity and with a greater step width than their lighter conspecifics. These high-growth lines also spent more time supported by two feet in order to improve balance when compared with their lighter, low-growth conspecifics. We demonstrate that chicken and duck lines which have been subjected to intense selection for high growth rates and meat yields have adapted their gait in similar ways. A greater understanding of which components of gait have been altered in selected lines with impaired walking ability may lead to more effective breeding strategies to improve gait in poultry.

Differential migration and proliferation of geometrical ensembles of cell clusters

International Nuclear Information System (INIS)

Kumar, Girish; Chen, Bo; Co, Carlos C.; Ho, Chia-Chi

2011-01-01

Differential cell migration and growth drives the organization of specific tissue forms and plays a critical role in embryonic development, tissue morphogenesis, and tumor invasion. Localized gradients of soluble factors and extracellular matrix have been shown to modulate cell migration and proliferation. Here we show that in addition to these factors, initial tissue geometry can feedback to generate differential proliferation, cell polarity, and migration patterns. We apply layer by layer polyelectrolyte assembly to confine multicellular organization and subsequently release cells to demonstrate the spatial patterns of cell migration and growth. The cell shapes, spreading areas, and cell-cell contacts are influenced strongly by the confining geometry. Cells within geometric ensembles are morphologically polarized. Symmetry breaking was observed for cells on the circular pattern and cells migrate toward the corners and in the direction parallel to the longest dimension of the geometric shapes. This migration pattern is disrupted when actomyosin based tension was inhibited. Cells near the edge or corner of geometric shapes proliferate while cells within do not. Regions of higher rate of cell migration corresponded to regions of concentrated growth. These findings demonstrate that multicellular organization can result in spatial patterns of migration and proliferation.

A stimulator of proliferation of spleen colony-forming cells (CFU-S) in the bone marrow of irradiated rats

Energy Technology Data Exchange (ETDEWEB)

Ivanovic, Z.; Milenkovic, P.; Stojanovic, N.; Lukic, M.; Kataranovski, M.

1993-07-01

The presence and activity of a spleen colony - forming cell (CFU-S) proliferation stimulator was investigated in rat bone marrow after irradiation. The dose dependent increase in cytosine arabinoside induced cell dealth of normal mouse bone marrow. The results demonstrate the existence of a CFU-S proliferation stimulator in rat bone marrow similar to that originally found as a macrophage product in regenarating mouse bone marrow. The CFU-S proliferation stimulator activity was not associated with the presence of interleukin - 1,2, or 6 like activities in the material tested.

Albumin Suppresses Human Hepatocellular Carcinoma Proliferation and the Cell Cycle

Directory of Open Access Journals (Sweden)

Shunsuke Nojiri

2014-03-01

Full Text Available Many investigations have revealed that a low recurrence rate of hepatocellular carcinoma (HCC is associated with high serum albumin levels in patients; therefore, high levels of serum albumin are a major indicator of a favorable prognosis. However, the mechanism inhibiting the proliferation of HCC has not yet been elucidated, so we investigated the effect of serum albumin on HCC cell proliferation. Hep3B was cultured in MEM with no serum or containing 5 g/dL human albumin. As control samples, Prionex was added to generate the same osmotic pressure as albumin. After 24-h incubation, the expressions of α-fetoprotein (AFP, p53, p21, and p57 were evaluated with real-time PCR using total RNA extracted from the liver. Protein expressions and the phosphorylation of Rb (retinoblastoma were determined by Western blot analysis using total protein extracted from the liver. For flow cytometric analysis of the cell cycle, FACS analysis was performed. The percentages of cell cycle distribution were evaluated by PI staining, and all samples were analyzed employing FACScalibur (BD with appropriate software (ModFit LT; BD. The cell proliferation assay was performed by counting cells with using a Scepter handy automated cell counter (Millipore. The mRNA levels of AFP relative to Alb(−: Alb(−, Alb(+, and Prionex, were 1, 0.7 ± 0.2 (p < 0.001 for Alb(−, and 1 ± 0.3, respectively. The mRNA levels of p21 were 1, 1.58 ± 0.4 (p = 0.007 for Alb(− and p = 0.004 for Prionex, and 0.8 ± 0.2, respectively. The mRNA levels of p57 were 1, 4.4 ± 1.4 (p = 0.002 for Alb(− and Prionex, and 1.0 ± 0.1, respectively. The protein expression levels of Rb were similar in all culture media. The phosphorylation of P807/811 and P780 of Rb protein was reduced in Alb(+. More cells in the G0/G1 phase and fewer cells in S and G2/M phases were obtained in Alb(+ than in Alb(− (G0/G1: 60.9%, 67.7%, 61.5%; G2/M: 16.5%, 13.1%, 15.6%; S: 22.6%, 19.2%, 23.0%, Alb(−, Alb

Nuclear proliferation: linkages and solutions

International Nuclear Information System (INIS)

Quester, G.H.

1979-01-01

Nuclear proliferation must be periodically re-examined as a moral as well as a practical foreign policy dilemma. The question is asked whether proliferation precludes a safe and peaceful world, or if a halt to proliferation is adequate without other arms control. The moral dilemma in foreign policy arises over the need to make practical choices which often serve one goal while sacrificing another. The ramifications of nuclear proliferation are examined and the conclusions reached that it is not an acceptable option. It is also decided that, because general disarmament steps will be more difficult to achieve, the world may have to accept a small number of nuclear arsenals as the price of state sovereignties. A high priority for making the effort to prevent proliferation is advised. 8 references

miR-99 inhibits cervical carcinoma cell proliferation by targeting TRIB2.

Science.gov (United States)

Xin, Jia-Xuan; Yue, Zhen; Zhang, Shuai; Jiang, Zhong-Hua; Wang, Ping-Yu; Li, You-Jie; Pang, Min; Xie, Shu-Yang

2013-10-01

MicroRNAs (miRNAs) have significant roles in cell processes, including proliferation, apoptosis and stress responses. To investigate the involvement of miR-99 in the inhibition of HeLa cell proliferation, an miR-99 gene expression vector (pU6.1/miR-99), which overexpressed miR-99 in HeLa cells after transient transfection, was constructed. The expression of miR-99 was detected by qPCR. Cell proliferation and apoptosis were analyzed by cell viability, proliferation and apoptosis assays, as well as by electron microscopy. The results showed that overexpression of miR-99 in HeLa cells increased the HeLa cell mortality rate. Moreover, miR-99 overexpression was able to markedly inhibit HeLa cell proliferation according to the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The cell apoptosis rate was significantly higher in pU6.1/miR-99-treated cells compared with that in the control cultures. Increases in intracellular electron density, as well as the proportion of nuclear plasma, blebbing phenomena and apoptotic bodies were observed in pU6.1/miR-99-treated cells compared with control cultures according to electron microscopy analysis. The Tribbles 2 (TRIB2) 3'-untranslated region was also observed to be targeted by miR-99 and the results further demonstrated that miR-99 was able to negatively regulate TRIB2 expression in HeLa cells The results indicate that miR-99 acts as a tumor suppressor gene in HeLa cells, establishing a theoretical basis for its application in cancer therapeutics.

Pooled human platelet lysate versus fetal bovine serum—investigating the proliferation rate, chromosome stability and angiogenic potential of human adipose tissue-derived stem cells intended for clinical use

DEFF Research Database (Denmark)

Trojahn Kølle, Stig-Frederik; Oliveri, Roberto S; Glovinski, Peter V

2013-01-01

Because of an increasing focus on the use of adipose-derived stem cells (ASCs) in clinical trials, the culture conditions for these cells are being optimized. We compared the proliferation rates and chromosomal stability of ASCs that had been cultured in Dulbecco's modified Eagle's Medium (DMEM) ......) supplemented with either pooled human platelet lysate (pHPL) or clinical-grade fetal bovine serum (FBS) (DMEM(pHPL) versus DMEM(FBS))....

Improved collaborative filtering recommendation algorithm of similarity measure

Science.gov (United States)

Zhang, Baofu; Yuan, Baoping

2017-05-01

The Collaborative filtering recommendation algorithm is one of the most widely used recommendation algorithm in personalized recommender systems. The key is to find the nearest neighbor set of the active user by using similarity measure. However, the methods of traditional similarity measure mainly focus on the similarity of user common rating items, but ignore the relationship between the user common rating items and all items the user rates. And because rating matrix is very sparse, traditional collaborative filtering recommendation algorithm is not high efficiency. In order to obtain better accuracy, based on the consideration of common preference between users, the difference of rating scale and score of common items, this paper presents an improved similarity measure method, and based on this method, a collaborative filtering recommendation algorithm based on similarity improvement is proposed. Experimental results show that the algorithm can effectively improve the quality of recommendation, thus alleviate the impact of data sparseness.

Dictyostelium cells bind a secreted autocrine factor that represses cell proliferation

Directory of Open Access Journals (Sweden)

Phillips Jonathan E

2009-02-01

Full Text Available Abstract Background Dictyostelium cells secrete the proteins AprA and CfaD. Cells lacking either AprA or CfaD proliferate faster than wild type, while AprA or CfaD overexpressor cells proliferate slowly, indicating that AprA and CfaD are autocrine factors that repress proliferation. CfaD interacts with AprA and requires the presence of AprA to slow proliferation. To determine if CfaD is necessary for the ability of AprA to slow proliferation, whether AprA binds to cells, and if so whether the binding requires the presence of CfaD, we examined the binding and effect on proliferation of recombinant AprA. Results We find that the extracellular accumulation of AprA increases with cell density and reaches a concentration of 0.3 μg/ml near a stationary cell density. When added to wild-type or aprA- cells, recombinant AprA (rAprA significantly slows proliferation at 0.1 μg/ml and higher concentrations. From 4 to 64 μg/ml, the effect of rAprA is at a plateau, slowing but not stopping proliferation. The proliferation-inhibiting activity of rAprA is roughly the same as that of native AprA in conditioned growth medium. Proliferating aprA- cells show saturable binding of rAprA to 92,000 ± 11,000 cell-surface receptors with a KD of 0.03 ± 0.02 μg/ml. There appears to be one class of binding site, and no apparent cooperativity. Native AprA inhibits the binding of rAprA to aprA- cells with a Ki of 0.03 μg/ml, suggesting that the binding kinetics of rAprA are similar to those of native AprA. The proliferation of cells lacking CrlA, a cAMP receptor-like protein, or cells lacking CfaD are not affected by rAprA. Surprisingly, both cell types still bind rAprA. Conclusion Together, the data suggest that AprA functions as an autocrine proliferation-inhibiting factor by binding to cell surface receptors. Although AprA requires CfaD for activity, it does not require CfaD to bind to cells, suggesting the possibility that cells have an AprA receptor and a Cfa

Protein synthesis rate measured with l-[1-11C]tyrosine positron emission tomography correlates with mitotic activity and MIB-1 antibody-detected proliferation in human soft tissue sarcomas

International Nuclear Information System (INIS)

Plaat, B.; Mastik, M.; Molenaar, W.; Kole, A.; Vaalburg, W.; Hoekstra, H.

1999-01-01

Protein synthesis rate (PSR) can be assessed in vivo using positron emission tomography with l-[1- 11 C]tyrosine (TYR-PET). Biological activity of soft tissue sarcomas (STS) can be measured in vitro by the mitotic rate and number of proliferating cells. In STS the grade of malignancy, in which the mitotic index plays a major role, is considered to be the major standard in predicting biological tumour behaviour. This study was designed to test the validity of TYR-PET in relation to different histopathological features. In 21 patients with untreated STS, the PSR was measured using TYR-PET. The number of mitoses was counted and tumours were graded according to the grading system of Coindre et al. (Cancer 1986; 58:306-309). Proliferative activity was assessed by immunohistological detection of the Ki-67 nuclear antigen using MIB-1 monoclonal antibody. To test the association between the PSR and these tumour parameters, a correlation analysis was performed. A significant (P<0.05) correlation was found between PSR and the Ki-67 proliferation index (R = 0.54), and between PSR and mitotic rate (R = 0.64). There was no correlation between PSR and tumour grade. The present study in malignant soft tissue tumours relates in vivo tumour metabolism as established with TYR-PET to tumour activity measured in vitro and indicates that the non-invasive method of TYR-PET can estimate the mitotic and proliferative activity in STS. (orig.)

The European dimension in non-proliferation

International Nuclear Information System (INIS)

Krause, J.

1996-01-01

Europe was for decades the focal point of efforts to prevent or constrain nuclear proliferation and the first region in which non-proliferation efforts failed. Paper deals with current proliferation problems in Europe, namely, diversion of weapons, diversion from dismantling, production over-capacity, security concerns. Legal instruments against proliferation in Europe described here include development of international norms; instruments of security assurance and cooperation; disarmament assistance; fissile material management; assistance in creating export control systems; improving and harmonizing export controls for dual-purpose items. Problems in implementing non-proliferation instruments are described separately

Serum from plasma rich in growth factors regenerates rabbit corneas by promoting cell proliferation, migration, differentiation, adhesion and limbal stemness.

Science.gov (United States)

Etxebarria, Jaime; Sanz-Lázaro, Sara; Hernáez-Moya, Raquel; Freire, Vanesa; Durán, Juan A; Morales, María-Celia; Andollo, Noelia

2017-12-01

To evaluate the regenerating potential and the mechanisms through which the autologous serum derived from plasma rich in growth factors (s-PRGF) favours corneal wound healing in vitro and in vivo. We compared the effect of various concentrations of s-PRGF versus fetal bovine serum (FBS) and control treatment in rabbit primary corneal epithelial and stromal cells and wounded rabbit corneas. Cell proliferation was measured using an enzymatic colorimetric assay. In vitro and in vivo wound-healing progression was assessed by image-analysis software. Migration and invasion were evaluated using transfilter assays. Histological structure was analysed in stained sections. Protein expression was evaluated by immunohistochemistry. s-PRGF promoted the robust proliferation of epithelial cultures at any concentration, similar to FBS. Likewise, s-PRGF and FBS produced similar re-epithelialization rates in in vitro wound-healing assays. In vivo, s-PRGF treatment accelerated corneal wound healing in comparison with control treatment. This difference was significant only for 100% s-PRGF treatment in our healthy rabbit model. Histological analysis confirmed normal epithelialization in all cases. Immunohistochemistry showed a higher expression of cytokeratins 3/76 and 15, zonula occludens-1 and alpha-smooth muscle actin proteins as a function of s-PRGF concentration. Notably, keratocyte density in the anterior third of the stroma increased with increase in s-PRGF concentration, suggesting an in vivo chemotactic effect of s-PRGF on keratocytes that was further confirmed in vitro. s-PRGF promotes proliferation and migration and influences limbal stemness, adhesion and fibrosis during corneal healing. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Proliferation resistance modeling

International Nuclear Information System (INIS)

Bari, R.; Peterson, P.; Roglans, J.; Mladineo, S.; Nuclear Engineering Division; BNL; Univ. of California at Berkely; PNNL

2004-01-01

The National Nuclear Security Administration is developing methods for nonproliferation assessments. A working group on Nonproliferation Assessment Methodology (NPAM) assembled a toolbox of methods for various applications in the nonproliferation arena. One application of this methodology is to the evaluation of the proliferation resistance of Generation IV nuclear energy systems. This paper first summarizes the key results of the NPAM program and then provides results obtained thus far in the ongoing application, which is co-sponsored by the DOE Office of Nuclear Energy Science and Technology. In NPAM, a top-level measure of proliferation resistance for a fuel cycle system is developed from a hierarchy of metrics. The problem is decomposed into: metrics to be computed, barriers to proliferation, and a finite set of threats. The analyst models the process undertaken by the proliferant to overcome barriers to proliferation and evaluates the outcomes. In addition to proliferation resistance (PR) evaluation, the application also addresses physical protection (PP) evaluation against sabotage and theft. The Generation IV goal for future nuclear energy systems is to assure that they are very unattractive and the least desirable route for diversion or theft of weapons-usable materials, and provide increased physical protection against terrorism. An Expert Group, addressing this application, has identified six high-level measures for the PR goals (six measures have also been identified for the PP goals). Combined together, the complete set of measures provides information for program policy makers and system designers to compare specific system design features and integral system characteristics and to make choices among alternative options. The Group has developed a framework for a phased evaluation approach to analyzing PR and PP of system characteristics and to quantifying metrics and measures. This approach allows evaluations to become more detailed and representative

Theoretical Approaches to Nuclear Proliferation

Directory of Open Access Journals (Sweden)

Konstantin S. Tarasov

2015-01-01

Full Text Available This article analyses discussions between representatives of three schools in the theory of international relations - realism, liberalism and constructivism - on the driving factors of nuclear proliferation. The paper examines major theoretical approaches, outlined in the studies of Russian and foreign scientists, to the causes of nuclear weapons development, while unveiling their advantages and limitations. Much of the article has been devoted to alternative approaches, particularly, the role of mathematical modeling in assessing proliferation risks. The analysis also reveals a variety of different approaches to nuclear weapons acquisition, as well as the absence of a comprehensive proliferation theory. Based on the research results the study uncovers major factors both favoring and impeding nuclear proliferation. The author shows that the lack of consensus between realists, liberals and constructivists on the nature of proliferation led a number of scientists to an attempt to explain nuclear rationale by drawing from the insights of more than one school in the theory of IR. Detailed study of the proliferation puzzle contributes to a greater understating of contemporary international realities, helps to identify mechanisms that are most likely to deter states from obtaining nuclear weapons and is of the outmost importance in predicting short- and long-term security environment. Furthermore, analysis of the existing scientific literature on nuclear proliferation helps to determine future research agenda of the subject at hand.

Trans-Uranium Doping Utilization for Increasing Protected Plutonium Proliferation of Small Long Life Reactor

Energy Technology Data Exchange (ETDEWEB)

Permana, Sidik [Research Laboratory for Nuclear Reactors, Tokyo Institute of Technology 2-12-1-N1-17, O-okayama, Meguro-ku, Tokyo 152-8550 (Japan); Nuclear and Biophysics Research Group, Department of Physics, Bandung Institute of Technology, Gedung Fisika, Jl. Ganesha 10, Bandung 40132 (Indonesia); Suud, Zaki [Nuclear and Biophysics Research Group, Department of Physics, Bandung Institute of Technology, Gedung Fisika, Jl. Ganesha 10, Bandung 40132 (Indonesia); Suzuki, Mitsutoshi [Japan Atomic Energy Agency, Nuclear Non-proliferation Science and Technology Center, 2-4 Shirane Shirakata, Tokai-mura, Ibaraki, 319-1195 (Japan)

2009-06-15

Scientific approaches are performed by adopting some methodologies in order to increase a material 'barrier' in plutonium isotope composition by increasing the even mass number of plutonium isotope such as Pu-238, Pu-240 and Pu-242. Higher difficulties (barrier) or more complex requirement for peaceful use of nuclear materials, material fabrication and handling and isotopic enrichment can be achieved by a higher isotopic barrier. Higher barrier which related to intrinsic properties of plutonium isotopes with even mass number (Pu-238, Pu-240 and Pu-242), in regard to their intense decay heat (DH) and high spontaneous fission neutron (SFN) rates were used as a parameter for improving the proliferation resistance of plutonium itself. Pu-238 has relatively high intrinsic characteristics of DH (567 W/kg) and SFN rate of 2660 n/g/s can be used for making a plutonium characteristics analysis. Similar characteristics with Pu-238, other even mass number of plutonium isotopes such as Pu-240 and Pu-242 have been shown in regard to SFN values. Those even number mass of plutonium isotope contribute to some criteria of plutonium characterization which will be adopted for present study such as IAEA, Pellaud and Kessler criteria (IAEA, 1972; Pellaud, 2002; and Kessler, 2004). The study intends to evaluate the trans-uranium doping effect for increasing protected plutonium proliferation in long-life small reactors. The development of small and medium reactor (SMR) is one of the options which have been adopted by IAEA as future utilization of nuclear energy especially for less developed countries (Kuznetsov, 2008). The preferable feature for small reactors (SMR) is long life operation time without on-site refueling and in the same time, it includes high proliferation resistance feature. The reactor uses MOX fuel as driver fuel for two different core types (inner and outer core) with blanket fuel arrangement. Several trans-uranium doping and some doping rates are evaluated

Exploring similarities and differences in hospital adverse event rates between Norway and Sweden using Global Trigger Tool

OpenAIRE

Deilk?s, Ellen Tveter; Risberg, Madeleine Borgstedt; Haugen, Marion; Lindstr?m, Jonas Christoffer; Nyl?n, Urban; Rutberg, Hans; Michael, Soop

2017-01-01

Objectives: In this paper, we explore similarities and differences in hospital adverse event (AE) rates between Norway and Sweden by reviewing medical records with the Global Trigger Tool (GTT). Design: All acute care hospitals in both countries performed medical record reviews, except one in Norway. Records were randomly selected from all eligible admissions in 2013. Eligible admissions were patients 18 years of age or older, undergoing care with an in-hospital stay of at least 24 hours, exc...

Proliferation resistance design of a plutonium cycle (Proliferation Resistance Engineering Program: PREP)

Energy Technology Data Exchange (ETDEWEB)

Sorenson, R.J.; Roberts, F.P.; Clark, R.G.

1979-01-19

This document describes the proliferation resistance engineering concepts developed to counter the threat of proliferation of nuclear weapons in an International Fuel Service Center (IFSC). The basic elements of an International Fuel Service Center are described. Possible methods for resisting proliferation such as processing alternatives, close-coupling of facilities, process equipment layout, maintenance philosophy, process control, and process monitoring are discussed. Political and institutional issues in providing proliferation resistance for an International Fuel Service Center are analyzed. The conclusions drawn are (1) use-denial can provide time for international response in the event of a host nation takeover. Passive use-denial is more acceptable than active use-denial, and acceptability of active-denial concepts is highly dependent on sovereignty, energy dependence and economic considerations; (2) multinational presence can enhance proliferation resistance; and (3) use-denial must be nonprejudicial with balanced interests for governments and/or private corporations being served. Comparisons between an IFSC as a national facility, an IFSC with minimum multinational effect, and an IFSC with maximum multinational effect show incremental design costs to be less than 2% of total cost of the baseline non-PRE concept facility. The total equipment acquisition cost increment is estimated to be less than 2% of total baseline facility costs. Personnel costs are estimated to increase by less than 10% due to maximum international presence. 46 figures, 9 tables.

Proliferation resistance design of a plutonium cycle (Proliferation Resistance Engineering Program: PREP)

International Nuclear Information System (INIS)

Sorenson, R.J.; Roberts, F.P.; Clark, R.G.

1979-01-01

This document describes the proliferation resistance engineering concepts developed to counter the threat of proliferation of nuclear weapons in an International Fuel Service Center (IFSC). The basic elements of an International Fuel Service Center are described. Possible methods for resisting proliferation such as processing alternatives, close-coupling of facilities, process equipment layout, maintenance philosophy, process control, and process monitoring are discussed. Political and institutional issues in providing proliferation resistance for an International Fuel Service Center are analyzed. The conclusions drawn are (1) use-denial can provide time for international response in the event of a host nation takeover. Passive use-denial is more acceptable than active use-denial, and acceptability of active-denial concepts is highly dependent on sovereignty, energy dependence and economic considerations; (2) multinational presence can enhance proliferation resistance; and (3) use-denial must be nonprejudicial with balanced interests for governments and/or private corporations being served. Comparisons between an IFSC as a national facility, an IFSC with minimum multinational effect, and an IFSC with maximum multinational effect show incremental design costs to be less than 2% of total cost of the baseline non-PRE concept facility. The total equipment acquisition cost increment is estimated to be less than 2% of total baseline facility costs. Personnel costs are estimated to increase by less than 10% due to maximum international presence. 46 figures, 9 tables

Proliferating cell nuclear antigen (PCNA): a new marker to study human colonic cell proliferation.

OpenAIRE

Kubben, F J; Peeters-Haesevoets, A; Engels, L G; Baeten, C G; Schutte, B; Arends, J W; Stockbrügger, R W; Blijham, G H

1994-01-01

Immunohistochemistry of the S phase related proliferating cell nuclear antigen (PCNA) was studied as an alternative to ex-vivo bromodeoxyuridine (BrdU) immunohistochemistry for assessment of human colonic cell proliferation. From 16 subjects without colonic disease biopsy specimens were collected from five different sites along the colorectum and processed for BrdU and PCNA immunohistochemistry. The mean proliferation index of PCNA was significantly higher at 133% of the value obtained with B...

The international nuclear non-proliferation system

International Nuclear Information System (INIS)

Simpson, J.; McGrew, T.

1985-01-01

This volume focuses upon the issues raised at this Conference, and attempts to address the international diplomatic, political and trading, rather than technical, questions which surround nuclear non-proliferation policies. It does so by bringing together chapters contributed by participants in non-proliferation diplomacy, those with experience in shaping International Atomic Energy Agency and national policies and academic observers of non-proliferation activities and the international nuclear industry. An analysis is provided of past non-proliferation policies and activities and current issues, and an attempt is made to offer ideas for new initiatives which may sustain the non-proliferation system in the future

Flexible bactericidal graphene oxide-chitosan layers for stem cell proliferation

Science.gov (United States)

Mazaheri, M.; Akhavan, O.; Simchi, A.

2014-05-01

Graphene oxide (GO)-chitosan composite layers with stacked layer structures were synthesized using chemically exfoliated GO sheets (with lateral dimensions of ˜1 μm and thickness of ˜1 nm), and applied as antibacterial and flexible nanostructured templates for stem cell proliferation. By increasing the GO content from zero to 6 wt%, the strength and elastic modulus of the layers increased ˜80% and 45%, respectively. Similar to the chitosan layer, the GO-chitosan composite layers showed significant antibacterial activity (>77% inactivation after only 3 h) against Staphylococcus aureus bacteria. Surface density of the actin cytoskeleton fibers of human mesenchymal stem cells (hMSCs) cultured on the chitosan and GO(1.5 wt%)-chitosan composite layers was found nearly the same, while it significantly decreased by increasing the GO content to 3 and 6 wt%. Our results indicated that although a high concentration of GO in the chitosan layer (here, 6 wt%) could decelerate the proliferation of the hMSCs on the flexible layer, a low concentration of GO (i.e., 1.5 wt%) not only resulted in biocompatibility but also kept the mechanical flexibility of the self-sterilized layers for high proliferation of hMSCs.

Effects of mercury on the proliferation of human peripheral lymphocytes in vitro

International Nuclear Information System (INIS)

Piwecka, K.; Poniedzialek, B.; Rzymski, P.; Karczewski, J.; Zurawski, J.; Wiktorowicz, K.

2011-01-01

Our project aimed to investigate the effects of mercury on the proliferation of human peripheral lymphocytes in vitro. The lymphocytes were isolated from the blood collected from healthy donors at Regionalne Centrum Krwiodawstwa i Krwiolecznictwa in Poznan, Poland. For the purpose of cell culture, the lymphocyte suspension (25 · 10 4 cells/ml) in Eagle's medium supplemented with 10% fetal calf serum was prepared. Phytohaemagglutinin-L (PHA-L) was used in a concentration of 2.5 mg/ml to stimulate cell proliferation. Mercuric chloride (HgCl 2 ) in four different concentrations (1 μM, 10 μM, 50 μM, 100 μM) and [3H]-thymidine were added after 48 hours of incubation and the cell culture was continued for the next 24 hours. The rate of lymphocyte proliferation was measured by [3H]-thymidine incorporation method with a liquid scintillation counter. Results indicate that higher concentrations of mercury (50 μM, 100 μM) inhibit the [3H]-thymidine incorporation of human peripheral lymphocytes in vitro. The incorporation was lower than the control sample by 65% at a concentration of 50 μM, while at a concentration of 100 μM it fell to virtually zero. Moreover, the phase of lymphocyte proliferation cycle affected by mercuric chloride was also investigated. For this purpose HgCl 2 in 2 concentrations (10 μM, 50 μM) was added to the cell culture in 4 different time points: at the start of the cell culture and after 4, 24, and 48 hours of incubation. After 48 hours, [3H]-thymidine was added and the cell culture was continued for an additional 24 hours. The rate of cell proliferation was estimated by [3H]-thymidine incorporation using a liquid scintillation counter. The inhibition effect was observed in samples with metal added at the start of the cell culture and after 4 h of incubation, i.e. at the initial phase of the lymphocyte proliferation cycle. (authors)

Comparison of the effect of activated or non-activated PRP in various concentrations on osteoblast and fibroblast cell line proliferation.

Science.gov (United States)

Vahabi, Surena; Yadegari, Zahra; Mohammad-Rahimi, Hossein

2017-09-01

Platelet-rich plasma (PRP) contains growth factors which positively affect cell proliferation, cell differentiation, chemotaxis and intracellular matrix synthesis. All these processes are involved in wound healing and tissue regeneration; thus, PRP as a source of growth factors can be used in periodontal regenerative therapies. The purpose of the present study was to assess the effect of various concentrations of activated and non-activated PRP on proliferation of osteoblasts and fibroblasts in vitro. PRP was obtained from three healthy volunteers. 75, 50, 25, and 10% concentrations of f PRP were prepared by dilution in Dulbecco's modified Eagle's medium. In activated PRP groups, PRP concentrations were activated by adding calcium gluconate. Human gingival fibroblast (HGF) cell line and MG-63 (osteosarcoma) human osteoblast-like cell line were used in the study. The MTT proliferation assay was used to assess the effect of different types of PRP concentrates on proliferation of HGF and MG-63 cells, in 24, 48 and 72 h. After 24, 48, and 72 h, the proliferation rate of both cell lines was higher in the positive control group, except in 72 h in HGF cell lines, that 10% non-activated PRP group and 10 and 25% activated PRP groups has higher proliferation rate than the positive control group, which it was not significant. Proliferation rate in cells with 10% activated PRP was highest among samples containing PRP. The current study failed to show the significant effect of activated or non-activated PRP on proliferation of HGFs or MG-63 osteoblast-like cells. However, our results showed that activated PRP had a greater effect than non-activated PRP.

MiR-223 suppresses cell proliferation by targeting IGF-1R.

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Cheng You Jia

Full Text Available To study the roles of microRNA-223 (miR-223 in regulation of cell growth, we established a miR-223 over-expression model in HeLa cells infected with miR-223 by Lentivirus pLL3.7 system. We observed in this model that miR-223 significantly suppressed the proliferation, growth rate, colony formation of HeLa cells in vitro, and in vivo tumorigenicity or tumor formation in nude mice. To investigate the mechanisms involved, we scanned and examined the potential and putative target molecules of miR-223 by informatics, quantitative PCR and Western blot, and found that insulin-like growth factor-1 receptor (IGF-1R was the functional target of miR-223 inhibition of cell proliferation. Targeting IGF-1R by miR-223 was not only seen in HeLa cells, but also in leukemia and hepatoma cells. The downstream pathway, Akt/mTOR/p70S6K, to which the signal was mediated by IGF-1R, was inhibited as well. The relative luciferase activity of the reporter containing wild-type 3'UTR(3'untranslated region of IGF-1R was significantly suppressed, but the mutant not. Silence of IGF-1R expression by vector-based short hairpin RNA resulted in the similar inhibition with miR-223. Contrarily, rescued IGF-1R expression in the cells that over-expressed miR-223, reversed the inhibition caused by miR-223 via introducing IGF-1R cDNA that didn't contain the 3'UTR. Meanwhile, we also noted that miR-223 targeted Rasa1, but the downstream molecules mediated by Rasa1 was neither targeted nor regulated. Therefore we believed that IGF-1R was the functional target for miR-223 suppression of cell proliferation and its downstream PI3K/Akt/mTOR/p70S6K pathway suppressed by miR-223 was by targeting IGF-1R.

Asiaticoside induces cell proliferation and collagen synthesis in human dermal fibroblasts

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Linda Yulianti

2015-08-01

Full Text Available Asiatiocoside, a saponin component isolated from Centella asiatica can improve wound healing by promoting the proliferation of human dermal fibroblasts (HDF and synthesis of collagen. The skin-renewing cells and type I and III collagen synthesis decrease with aging, resulting in the reduction of skin elasticity and delayed wound healing. Usage of natural active compounds from plants in wound healing should be evaluated and compared to retinoic acid as an active agent that regulates wound healing. The aim of this study was to compare and evaluate the effect of asiaticoside and retinoic acid to induce greater cell proliferation and type I and III collagen synthesis in human dermal fibroblast. Methods Laboratory experiments were conducted using human dermal fibroblasts (HDF isolated from human foreskin explants. Seven passages of HDF were treated with asiaticoside and retinoic acid at several doses and incubated for 24 and 48 hours. Cell viability in all groups was tested with the MTT assay to assess HDF proliferation. Type I and III collagen synthesis was examined using the respective ELISA kits. Analysis of variance was performed to compare the treatment groups. Results Asiaticoside had significantly stronger effects on HDF proliferation than retinoic acid (p<0.05. The type III collagen production was significantly greater induction with asiaticoside compared to retinoic acid (p<0.05. Conclusion Asiaticoside induces HDF proliferation and type I and III collagen synthesis in a time- and dose-dependent pattern. Asiaticoside has a similar effect as retinoic acid on type I and type III collagen synthesis.

Synthesis and biological activity of M6-P and M6-P analogs on fibroblast and keratinocyte proliferation.

Science.gov (United States)

Clavel, Caroline; Barragan-Montero, Véronique; Garric, Xavier; Molès, Jean-Pierre; Montero, Jean-Louis

2005-09-01

A new synthetic route to obtain the carboxylate analog of mannose 6-phosphate (M6-P) is presented. The effects of the M6-P, the carboxylate and two other analogs (the phosphonate and the alpha,beta ethylenic carboxylate) on the proliferation of human keratinocytes and dermal fibroblasts as well as on the proliferation of a murine fibroblast cell line, 3T3-J2 are tested. We observed that M6-P is a potent inhibitor of proliferation of both fibroblasts and keratinocytes. Among its analogs, the phosphonate showed a similar effect on human dermal fibroblasts but not on keratinocytes.

Flexible bactericidal graphene oxide–chitosan layers for stem cell proliferation

International Nuclear Information System (INIS)

Mazaheri, M.; Akhavan, O.; Simchi, A.

2014-01-01

Highlights: • Fabrication of flexible graphene oxide–chitosan nanocomposite layers was reported. • The flexibility of the chitosan layers were improved by adding graphene oxide sheets. • The nanocomposite layers with 1.5 wt% graphene oxide content showed yielded flexible and antibacterial surfaces for stem cell proliferation. - Abstract: Graphene oxide (GO)–chitosan composite layers with stacked layer structures were synthesized using chemically exfoliated GO sheets (with lateral dimensions of ∼1 μm and thickness of ∼1 nm), and applied as antibacterial and flexible nanostructured templates for stem cell proliferation. By increasing the GO content from zero to 6 wt%, the strength and elastic modulus of the layers increased ∼80% and 45%, respectively. Similar to the chitosan layer, the GO–chitosan composite layers showed significant antibacterial activity (>77% inactivation after only 3 h) against Staphylococcus aureus bacteria. Surface density of the actin cytoskeleton fibers of human mesenchymal stem cells (hMSCs) cultured on the chitosan and GO(1.5 wt%)–chitosan composite layers was found nearly the same, while it significantly decreased by increasing the GO content to 3 and 6 wt%. Our results indicated that although a high concentration of GO in the chitosan layer (here, 6 wt%) could decelerate the proliferation of the hMSCs on the flexible layer, a low concentration of GO (i.e., 1.5 wt%) not only resulted in biocompatibility but also kept the mechanical flexibility of the self-sterilized layers for high proliferation of hMSCs

Flexible bactericidal graphene oxide–chitosan layers for stem cell proliferation

Energy Technology Data Exchange (ETDEWEB)

Mazaheri, M. [Department of Materials Science and Engineering, Sharif University of Technology, PO Box 11365-9466, Tehran (Iran, Islamic Republic of); Akhavan, O., E-mail: oakhavan@sharif.edu [Department of Physics, Sharif University of Technology, PO Box 11155-9161, Tehran (Iran, Islamic Republic of); Institute for Nanoscience and Nanotechnology, Sharif University of Technology, PO Box 14588-89694, Tehran (Iran, Islamic Republic of); Simchi, A. [Department of Materials Science and Engineering, Sharif University of Technology, PO Box 11365-9466, Tehran (Iran, Islamic Republic of); Institute for Nanoscience and Nanotechnology, Sharif University of Technology, PO Box 14588-89694, Tehran (Iran, Islamic Republic of)

2014-05-01

Highlights: • Fabrication of flexible graphene oxide–chitosan nanocomposite layers was reported. • The flexibility of the chitosan layers were improved by adding graphene oxide sheets. • The nanocomposite layers with 1.5 wt% graphene oxide content showed yielded flexible and antibacterial surfaces for stem cell proliferation. - Abstract: Graphene oxide (GO)–chitosan composite layers with stacked layer structures were synthesized using chemically exfoliated GO sheets (with lateral dimensions of ∼1 μm and thickness of ∼1 nm), and applied as antibacterial and flexible nanostructured templates for stem cell proliferation. By increasing the GO content from zero to 6 wt%, the strength and elastic modulus of the layers increased ∼80% and 45%, respectively. Similar to the chitosan layer, the GO–chitosan composite layers showed significant antibacterial activity (>77% inactivation after only 3 h) against Staphylococcus aureus bacteria. Surface density of the actin cytoskeleton fibers of human mesenchymal stem cells (hMSCs) cultured on the chitosan and GO(1.5 wt%)–chitosan composite layers was found nearly the same, while it significantly decreased by increasing the GO content to 3 and 6 wt%. Our results indicated that although a high concentration of GO in the chitosan layer (here, 6 wt%) could decelerate the proliferation of the hMSCs on the flexible layer, a low concentration of GO (i.e., 1.5 wt%) not only resulted in biocompatibility but also kept the mechanical flexibility of the self-sterilized layers for high proliferation of hMSCs.

Decreased tumor cell proliferation as an indicator of the effect of preoperative radiotherapy of rectal cancer

International Nuclear Information System (INIS)

Adell, Gunnar; Zhang Hong; Jansson, Agneta; Sun Xiaofeng; Staal, Olle; Nordenskjoeld, Bo

2001-01-01

Background: Rectal cancer is a common malignancy, with significant local recurrence and death rates. Preoperative radiotherapy and refined surgical technique can improve local control rates and disease-free survival. Purpose: To investigate the relationship between the tumor growth fraction in rectal cancer measured with Ki-67 and the outcome, with and without short-term preoperative radiotherapy. Method: Ki-67 (MIB-1) immunohistochemistry was used to measure tumor cell proliferation in the preoperative biopsy and the surgical specimen. Materials: Specimens from 152 patients from the Southeast Swedish Health Care region were included in the Swedish rectal cancer trial 1987-1990. Results: Tumors with low proliferation treated with preoperative radiotherapy had a significantly reduced recurrence rate. The influence on death from rectal cancer was shown only in the univariate analysis. Preoperative radiotherapy of tumors with high proliferation did not significantly improve local control and disease-free survival. The interaction between Ki-67 status and the benefit of radiotherapy was significant for the reduced recurrence rate (p=0.03), with a trend toward improved disease-free survival (p=0.08). In the surgery-alone group, Ki-67 staining did not significantly correlate with local recurrence or survival rates. Conclusion: Many Ki-67 stained tumor cells in the preoperative biopsy predicts an increased treatment failure rate after preoperative radiotherapy of rectal cancer

Peroxisome proliferation due to di(2-ethylhexyl) phthalate (DEHP): species differences and possible mechanisms

International Nuclear Information System (INIS)

Elcombe, C.R.; Mitchell, A.M.

1986-01-01

The exposure of cultured rat hepatocytes to mono(2-ethyhexyl)phthalate (MEHP) for 72 hr resulted in marked induction of peroxisomal enzyme activity (β-oxidation; cyanide-insensitive palmitoyl CoA oxidase) and concomitant increases in the number of peroxisomes. Similar treatment of cultured guinea pig, marmoset, or human hepatocytes revealed little or no effect of MEHP. In order to eliminate possible confounding influences of biotransformation, the proximate peroxisome proliferator(s) derived from MEHP have been identified. Using cultured hepatocytes these agents were found to be metabolite VI [mono(2-ethyl-5-oxohexyl) phthalate] and metabolite IX [mono(2-ethyl-5-hydroxyhexyl) phthalate]. The addition of these active metabolites to cultured guinea pig, marmoset, or human hepatocytes again revealed little effect upon peroxisomes or related enzyme activities (peroxisomal β-oxidation or microsomal lauric acid hydroxylation). These studies demonstrate a marked species difference in the response of hepatocytes to MEHP-elicited peroxisome proliferation. Preliminary studies have also suggested that peroxisome proliferation due to MEHP may be due to an initial biochemical lesion of fatty acid metabolism

Handbook for nuclear non-proliferation

International Nuclear Information System (INIS)

Lee, Byung Wook; Oh, Keun Bae; Lee, Kwang Seok; Lee, Dong Jin; Ko, Han Seok.

1997-05-01

This book analyzed international non-proliferation regime preventing from spread of nuclear weapon. This book took review from the historical background of non-proliferation regime to the recent changes and status. The regime, here, is divided into multilateral and bilateral regime. First of all, this book reports four multilateral treaties concluded for non-proliferation such as NPT, NWFZ, CTBT and others. Secondly, international organization and regimes concerned with non-proliferation are analyzed with emphasis of UN, IAEA, ZC and NSG, Regional Safeguards System and international conference. Finally, this book report the current circumstances of nuclear cooperation agreement related with Korea which is an important means for bilateral regime. (author). 13 tabs., 2 figs

Handbook for nuclear non-proliferation

Energy Technology Data Exchange (ETDEWEB)

Lee, Byung Wook; Oh, Keun Bae; Lee, Kwang Seok; Lee, Dong Jin; Ko, Han Seok

1997-05-01

This book analyzed international non-proliferation regime preventing from spread of nuclear weapon. This book took review from the historical background of non-proliferation regime to the recent changes and status. The regime, here, is divided into multilateral and bilateral regime. First of all, this book reports four multilateral treaties concluded for non-proliferation such as NPT, NWFZ, CTBT and others. Secondly, international organization and regimes concerned with non-proliferation are analyzed with emphasis of UN, IAEA, ZC and NSG, Regional Safeguards System and international conference. Finally, this book report the current circumstances of nuclear cooperation agreement related with Korea which is an important means for bilateral regime. (author). 13 tabs., 2 figs.

Memory phenotype CD4 T cells undergoing rapid, nonburst-like, cytokine-driven proliferation can be distinguished from antigen-experienced memory cells.

Directory of Open Access Journals (Sweden)

Souheil-Antoine Younes

2011-10-01

Full Text Available Memory phenotype (CD44(bright, CD25(negative CD4 spleen and lymph node T cells (MP cells proliferate rapidly in normal or germ-free donors, with BrdU uptake rates of 6% to 10% per day and Ki-67 positivity of 18% to 35%. The rapid proliferation of MP cells stands in contrast to the much slower proliferation of lymphocytic choriomeningitis virus (LCMV-specific memory cells that divide at rates ranging from <1% to 2% per day over the period from 15 to 60 days after LCMV infection. Anti-MHC class II antibodies fail to inhibit the in situ proliferation of MP cells, implying a non-T-cell receptor (TCR-driven proliferation. Such proliferation is partially inhibited by anti-IL-7Rα antibody. The sequence diversity of TCRβ CDR3 gene segments is comparable among the proliferating and quiescent MP cells from conventional and germ-free mice, implying that the majority of proliferating MP cells have not recently derived from a small cohort of cells that expand through multiple continuous rounds of cell division. We propose that MP cells constitute a diverse cell population, containing a subpopulation of slowly dividing authentic antigen-primed memory cells and a majority population of rapidly proliferating cells that did not arise from naïve cells through conventional antigen-driven clonal expansion.

Collagen Promotes Higher Adhesion, Survival and Proliferation of Mesenchymal Stem Cells.

Directory of Open Access Journals (Sweden)

Chinnapaka Somaiah

Full Text Available Mesenchymal stem cells (MSC can differentiate into several cell types and are desirable candidates for cell therapy and tissue engineering. However, due to poor cell survival, proliferation and differentiation in the patient, the therapy outcomes have not been satisfactory. Although several studies have been done to understand the conditions that promote proliferation, differentiation and migration of MSC in vitro and in vivo, still there is no clear understanding on the effect of non-cellular bio molecules. Of the many factors that influence the cell behavior, the immediate cell microenvironment plays a major role. In this context, we studied the effect of extracellular matrix (ECM proteins in controlling cell survival, proliferation, migration and directed MSC differentiation. We found that collagen promoted cell proliferation, cell survival under stress and promoted high cell adhesion to the cell culture surface. Increased osteogenic differentiation accompanied by high active RHOA (Ras homology gene family member A levels was exhibited by MSC cultured on collagen. In conclusion, our study shows that collagen will be a suitable matrix for large scale production of MSC with high survival rate and to obtain high osteogenic differentiation for therapy.

SU-F-J-38: Dose Rates and Preliminary Evaluation of Contouring Similarity Metrics Using 4D Cone Beam CT

Energy Technology Data Exchange (ETDEWEB)

Santoso, A [Wayne State University School of Medicine, Detroit, Michigan (United States); Song, K; Qin, Y; Gardner, S; Liu, C; Cattaneo, R; Chetty, I; Movsas, B; Aljouni, M; Wen, N [Henry Ford Health System, Detroit, MI (United States)

2016-06-15

Purpose: 4D imaging modalities require detailed characterization for clinical optimization. The On-Board Imager mounted on the linear accelerator was used to investigate dose rates in a tissue mimicking phantom using 4D-CBCT and assess variability of contouring similarity metrics between 4D-CT and 4D-CBCT retrospective reconstructions. Methods: A 125 kVp thoracic protocol was used. A phantom placed on a motion platform simulated a patient’s breathing cycle. An ion chamber was affixed inside the phantom’s tissue mimicking cavities (i.e. bone, lung, and soft tissue). A sinusoidal motion waveform was executed with a five second period and superior-inferior motion. Dose rates were measured at six ion chamber positions. A preliminary workflow for contouring similarity between 4D-CT and 4D-CBCT was established using a single lung SBRT patient’s historical data. Average intensity projection (Ave-IP) and maximum intensity projection (MIP) reconstructions generated offline were compared between the 4D modalities. Similarity metrics included Dice similarity coefficient (DSC), Hausdorff distance, and center of mass (COM) deviation. Two isolated lesions were evaluated in the patient’s scans: one located in the right lower lobe (ITVRLL) and one located in the left lower lobe (ITVLLL). Results: Dose rates ranged from 2.30 (lung) to 5.18 (bone) E-3 cGy/mAs. For fixed acquisition parameters, cumulative dose is inversely proportional to gantry speed. For ITVRLL, DSC were 0.70 and 0.68, Hausdorff distances were 6.11 and 5.69 mm, and COM deviations were 1.24 and 4.77 mm, for Ave-IP and MIP respectively. For ITVLLL, DSC were 0.64 and 0.75, Hausdorff distances were 10.74 and 8.00 mm, and COM deviations were 7.55 and 4.3 mm, for Ave-IP and MIP respectively. Conclusion: While the dosimetric output of 4D-CBCT is low, characterization is necessary to assure clinical optimization. A basic workflow for comparison of simulation and treatment 4D image-based contours was established

Protein synthesis rate measured with l-[1-{sup 11}C]tyrosine positron emission tomography correlates with mitotic activity and MIB-1 antibody-detected proliferation in human soft tissue sarcomas

Energy Technology Data Exchange (ETDEWEB)

Plaat, B.; Mastik, M.; Molenaar, W. [Department of Pathology, University Hospital Groningen (Netherlands); Kole, A.; Vaalburg, W. [PET Centre, University Hospital Groningen (Netherlands); Hoekstra, H. [Department of Surgical Oncology, University Hospital Groningen (Netherlands)

1999-04-29

Protein synthesis rate (PSR) can be assessed in vivo using positron emission tomography with l-[1-{sup 11}C]tyrosine (TYR-PET). Biological activity of soft tissue sarcomas (STS) can be measured in vitro by the mitotic rate and number of proliferating cells. In STS the grade of malignancy, in which the mitotic index plays a major role, is considered to be the major standard in predicting biological tumour behaviour. This study was designed to test the validity of TYR-PET in relation to different histopathological features. In 21 patients with untreated STS, the PSR was measured using TYR-PET. The number of mitoses was counted and tumours were graded according to the grading system of Coindre et al. (Cancer 1986; 58:306-309). Proliferative activity was assessed by immunohistological detection of the Ki-67 nuclear antigen using MIB-1 monoclonal antibody. To test the association between the PSR and these tumour parameters, a correlation analysis was performed. A significant (P<0.05) correlation was found between PSR and the Ki-67 proliferation index (R = 0.54), and between PSR and mitotic rate (R = 0.64). There was no correlation between PSR and tumour grade. The present study in malignant soft tissue tumours relates in vivo tumour metabolism as established with TYR-PET to tumour activity measured in vitro and indicates that the non-invasive method of TYR-PET can estimate the mitotic and proliferative activity in STS. (orig.) With 2 figs., 2 tabs., 30 refs.

C. elegans FOG-3/Tob can either promote or inhibit germline proliferation, depending on gene dosage and genetic context.

Science.gov (United States)

Snow, J J; Lee, M-H; Verheyden, J; Kroll-Conner, P L; Kimble, J

2013-05-23

Vertebrate Tob/BTG proteins inhibit cell proliferation when overexpressed in tissue-culture cells, and they can function as tumor suppressors in mice. The single Caenorhabditis elegans Tob/BTG ortholog, FOG-3, by contrast, was identified from its loss-of-function phenotype as a regulator of sperm fate specification. Here we report that FOG-3 also regulates proliferation in the germline tissue. We first demonstrate that FOG-3 is a positive regulator of germline proliferation. Thus, fog-3 null mutants possess fewer germ cells than normal, a modest but reproducible decrease observed for each of two distinct fog-3 null alleles. A similar decrease also occurred in fog-3/+ heterozygotes, again for both fog-3 alleles, revealing a haplo-insufficient effect on proliferation. Therefore, FOG-3 normally promotes proliferation, and two copies of the fog-3 gene are required for this function. We next overexpressed FOG-3 by removal of FBF, the collective term for FBF-1 and FBF-2, two nearly identical PUF RNA-binding proteins. We find that overexpressed FOG-3 blocks proliferation in fbf-1 fbf-2 mutants; whereas germ cells stop dividing and instead differentiate in fbf-1 fbf-2 double mutants, they continue to proliferate in fog-3; fbf-1 fbf-2 triple mutants. Therefore, like its vertebrate Tob/BTG cousins, overexpressed FOG-3 is 'antiproliferative'. Indeed, some fog-3; fbf-1 fbf-2 mutants possess small tumors, suggesting that FOG-3 can act as a tumor suppressor. Finally, we show that FOG-3 and FBF work together to promote tumor formation in animals carrying oncogenic Notch mutations. A similar effect was not observed when germline tumors were induced by manipulation of other regulators; therefore, this FOG-3 tumor-promoting effect is context dependent. We conclude that FOG-3 can either promote or inhibit proliferation in a manner that is sensitive to both genetic context and gene dosage. The discovery of these FOG-3 effects on proliferation has implications for our understanding of

Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation

International Nuclear Information System (INIS)

Brady, Robert T.; O'Brien, Fergal J.; Hoey, David A.

2015-01-01

Bone formation requires the recruitment, proliferation and osteogenic differentiation of mesenchymal progenitors. A potent stimulus driving this process is mechanical loading, yet the signalling mechanisms underpinning this are incompletely understood. The objective of this study was to investigate the role of the mechanically-stimulated osteocyte and osteoblast secretome in coordinating progenitor contributions to bone formation. Initially osteocytes (MLO-Y4) and osteoblasts (MC3T3) were mechanically stimulated for 24hrs and secreted factors within the conditioned media were collected and used to evaluate mesenchymal stem cell (MSC) and osteoblast recruitment, proliferation and osteogenesis. Paracrine factors secreted by mechanically stimulated osteocytes significantly enhanced MSC migration, proliferation and osteogenesis and furthermore significantly increased osteoblast migration and proliferation when compared to factors secreted by statically cultured osteocytes. Secondly, paracrine factors secreted by mechanically stimulated osteoblasts significantly enhanced MSC migration but surprisingly, in contrast to the osteocyte secretome, inhibited MSC proliferation when compared to factors secreted by statically cultured osteoblasts. A similar trend was observed in osteoblasts. This study provides new information on mechanically driven signalling mechanisms in bone and highlights a contrasting secretome between cells at different stages in the bone lineage, furthering our understanding of loading-induced bone formation and indirect biophysical regulation of osteoprogenitors. - Highlights: • Physically stimulated osteocytes secrete factors that regulate osteoprogenitors. • These factors enhance recruitment, proliferation and osteogenic differentiation. • Physically stimulated osteoblasts secrete factors that also regulate progenitors. • These factors enhance recruitment but inhibit proliferation of osteoprogenitors. • This study highlights a contrasting

Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation

Energy Technology Data Exchange (ETDEWEB)

Brady, Robert T. [Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (Ireland); Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland (Ireland); Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick (Ireland); O' Brien, Fergal J. [Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (Ireland); Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland (Ireland); Hoey, David A., E-mail: david.hoey@ul.ie [Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick (Ireland); The Centre for Applied Biomedical Engineering Research, University of Limerick (Ireland); Materials & Surface Science Institute, University of Limerick (Ireland)

2015-03-27

Bone formation requires the recruitment, proliferation and osteogenic differentiation of mesenchymal progenitors. A potent stimulus driving this process is mechanical loading, yet the signalling mechanisms underpinning this are incompletely understood. The objective of this study was to investigate the role of the mechanically-stimulated osteocyte and osteoblast secretome in coordinating progenitor contributions to bone formation. Initially osteocytes (MLO-Y4) and osteoblasts (MC3T3) were mechanically stimulated for 24hrs and secreted factors within the conditioned media were collected and used to evaluate mesenchymal stem cell (MSC) and osteoblast recruitment, proliferation and osteogenesis. Paracrine factors secreted by mechanically stimulated osteocytes significantly enhanced MSC migration, proliferation and osteogenesis and furthermore significantly increased osteoblast migration and proliferation when compared to factors secreted by statically cultured osteocytes. Secondly, paracrine factors secreted by mechanically stimulated osteoblasts significantly enhanced MSC migration but surprisingly, in contrast to the osteocyte secretome, inhibited MSC proliferation when compared to factors secreted by statically cultured osteoblasts. A similar trend was observed in osteoblasts. This study provides new information on mechanically driven signalling mechanisms in bone and highlights a contrasting secretome between cells at different stages in the bone lineage, furthering our understanding of loading-induced bone formation and indirect biophysical regulation of osteoprogenitors. - Highlights: • Physically stimulated osteocytes secrete factors that regulate osteoprogenitors. • These factors enhance recruitment, proliferation and osteogenic differentiation. • Physically stimulated osteoblasts secrete factors that also regulate progenitors. • These factors enhance recruitment but inhibit proliferation of osteoprogenitors. • This study highlights a contrasting

Plutonium Proliferation: The Achilles Heel of Disarmament

International Nuclear Information System (INIS)

Leventhal, Paul

2001-01-01

Plutonium is a byproduct of nuclear fission, and it is produced at the rate of about 70 metric tons a year in the world's nuclear power reactors. Concerns about civilian plutonium ran high in the 1970s and prompted enactment of the Nuclear Non-Proliferation Act of 1978 to give the United States a veto over separating plutonium from U.S.-supplied uranium fuel. Over the years, however, so-called reactor-grade plutonium has become the orphan issue of nuclear non-proliferation, largely as a consequence of pressures from plutonium-separating countries. The demise of the fast breeder reactor and the reluctance of utilities to introduce plutonium fuel in light-water reactors have resulted in large surpluses of civilian, weapons-usable plutonium, which now approach in size the 250 tons of military plutonium in the world. Yet reprocessing of spent fuel for recovery and use of plutonium proceeds apace outside the United States and threatens to overwhelm safeguards and security measures for keeping this material out of the hands of nations and terrorists for weapons. A number of historical and current developments are reviewed to demonstrate that plutonium commerce is undercutting efforts both to stop the spread of nuclear weapons and to work toward eliminating existing nuclear arsenals. These developments include the breakdown of U.S. anti-plutonium policy, the production of nuclear weapons by India with Atoms-for-Peace plutonium, the U.S.-Russian plan to introduce excess military plutonium as fuel in civilian power reactors, the failure to include civilian plutonium and bomb-grade uranium in the proposed Fissile Material Cutoff Treaty, and the perception of emerging proliferation threats as the rationale for development of a ballistic missile defense system. Finally, immobilization of separated plutonium in high-level waste is explored as a proliferation-resistant and disarmament-friendly solution for eliminating excess stocks of civilian and military plutonium.

Radiation-induced changes in cellularity and proliferation in human oral mucosa

International Nuclear Information System (INIS)

Doerr, Wolfgang; Hamilton, Christopher S.; Boyd, Teresa; Reed, Barry; Denham, James W.

2002-01-01

Purpose: To quantify the oral mucosal cell density and proliferation rate during conventional radiotherapy of head-and-neck tumors and to compare these parameters with clinical scoring of oral mucositis. Methods and Materials: Between 1996 and 1999, 22 patients were included in this study. Mucosal biopsies were taken before or during the radiotherapy course (5 x 2 Gy/wk). Biopsies were incubated in vitro with tritiated thymidine immediately after excision to label DNA-synthesizing cells. Results: Epithelial cell density followed a biphasic radiation response. A steep decrease to about 50% of the preirradiation value (1000 cells/mm epithelium) during Week 1 was followed by a more gradual loss to about 400 cells at the end of treatment. The initial phase was based on the depression of proliferation, with 5-10 labeled cells/mm at the end of Week 1 vs. 60 labeled cells/mm in controls. Subsequently, proliferation was partially restituted at 20 labeled cells/mm. A significant difference in cell numbers was seen between Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Grade 0 (∼850 cell/mm) and Grade 2 (325/mm) or Grade 3 (370/mm). No significant differences were observed between reaction grades 1, 2, and 3. Conclusion: Conventionally fractionated radiotherapy induces a rapid suppression in cell production in Week 1, which results in a prompt reduction in cell numbers. Subsequently, a partial restoration of proliferation significantly reduces the rate of cell loss. These processes clearly precede the clinical response. Regeneration, defined as restoration of cellularity, is already under way when the maximal clinical response is observed. Clinical reaction grading corresponds poorly to cellular density measures during conventional fractionation

The USA and proliferation in Northeast Asia

International Nuclear Information System (INIS)

Weeks, S.B.

1995-01-01

United States policy on proliferation in Northeast Asia poses a test of balance between general US global non-proliferation goals and specific US regional security goals for Northeast Asia. US policy on proliferation in Northeast Asia further poses a test of priorities for US bilateral relations with the key Northeast Asian states, as non-proliferation and regional security goals must be weighed against other (e.g., economic, human rights) declared US policy goals. The result is a US policy equation for Northeast Asia proliferation that is considerably more complex in execution than might be expected from the simple statement of the US goal to avoid nuclear proliferation in Northeast Asia. The question of security assurances - both negative and positive - may be closely related to US policies to avoid proliferation in Northeast Asia

Incorporation of p-53 mutation status and Ki-67 proliferating index in ...

African Journals Online (AJOL)

Ayesha Ahmed

2018-04-26

Apr 26, 2018 ... gastric cancer. p-53 mutation status and Ki-67 proliferation index are established prognostic ... could not only be predictive in patientLs prognostics but could also form a basis of molecular ... a similar status to Her2-neu in gastric cancer, yet no ..... HER2-based biology in 1,006 cases of gastric cancer in.

Podoplanin as Key Player of Tumor Progression and Lymph Vessel Proliferation in Ovarian Cancer.

Science.gov (United States)

Cobec, Ionut Marcel; Sas, Ioan; Pirtea, Laurențiu; Cimpean, Anca Maria; Moatar, Aurica Elisabeta; Ceaușu, Raluca Amalia; Raica, Marius

2016-10-01

Podoplanin plays a key role in tumor progression and metastasis. We evaluated lymphatics proliferation rate and podoplanin expression in tumor cells of ovarian carcinoma. Seventy-five paraffin-embedded specimens of ovarian cancer were immunohistochemically assessed in order to quantify peritumoral (LMVDP) and intratumoral (LMVDT) lymphatic microvessel density of proliferating lymphatics and for podoplanin variability in tumor cells. LMVDT correlated with proliferating tumor vessels located in the peritumoral area (p=0.024) and with the number of mature vessels located in the intratumoral area (p<0.0001), while LMVDP correlated with peritumoral mature vessels (p<0.000l). Proliferating tumor cells at the invasive front were highly positive for podoplanin. To the best of our knowledge, this study represents the first assessment of lymphatic endothelial cell proliferation correlated with podoplanin expression in tumor cells from ovarian cancer. Our data support podoplanin as a potential target that may help reduce ovarian cancer dissemination and lymphatic metastasis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Strengthening the non proliferation regime: French views

International Nuclear Information System (INIS)

Delaune, P.

2013-01-01

3 main issues can be identified in the French policy concerning the backing of non proliferation: 1) responding resolutely to proliferation crises, 2) reinforcing substantive efforts to prevent and impede proliferation, and 3) strengthening the non-proliferation regime. The first issue is very important because combating proliferation is vital to the security of all. Concerning the second issue, France attaches particular importance to strengthening specific measures to prevent and check proliferation. Let me mention a few proposals that we put forward: exports need to be controlled more effectively, proliferation activities have to be criminalized, or the development of proliferation-resistant technologies should be supported. Concerning the third issue it means the strengthening of the non-proliferation regime, France proposes several means: -) aiming at the universalization of the additional protocol; -) ensuring that the Agency continues to have sufficient human, financial and technical resources to fulfill its verification mission effectively; -) encouraging the IAEA to make full use of the authority available to it; -) enhancing the use of information relevant to the delivery of the IAEA mandate; and -) sharing more accurate information concerning the breaches of commitments that happen. The paper is followed by the slides of the presentation. (A.C.)

Nuclear proliferation

International Nuclear Information System (INIS)

Stencel, S.

1978-01-01

The terms and reactions to President Carter's nuclear policy, culminating in the 1978 Nuclear Non-Proliferation Act, are reviewed and analyzed. The new law increases restrictions on nuclear exports, encourages continued use of light water reactors in preference to plutonium-fueled reactors, and emphasizes technical solutions to proliferation problems. Critics of the law point out that it will hurt U.S. trade unfairly, that other countries do not have as many fuel options as the U.S. has, and that nuclear sales have as many political and economic as technical solutions. Compromise areas include new international safety guidelines, the possibility of an international nuclear fuel bank, and a willingness to consider each case on its merits. 21 references

Zinc Promotes Adipose-Derived Mesenchymal Stem Cell Proliferation and Differentiation towards a Neuronal Fate.

Science.gov (United States)

Moon, Mi-Young; Kim, Hyun Jung; Choi, Bo Young; Sohn, Min; Chung, Tae Nyoung; Suh, Sang Won

2018-01-01

Zinc is an essential element required for cell division, migration, and proliferation. Under zinc-deficient conditions, proliferation and differentiation of neural progenitors are significantly impaired. Adipose-derived mesenchymal stem cells (AD-MSCs) are multipotent stem cells that can differentiate into neurons. The aim of this study was to evaluate the effect of zinc on AD-MSC proliferation and differentiation. We initially examined the effect of zinc on stem cell proliferation at the undifferentiated stage. AD-MSCs showed high proliferation rates on day 6 in 30  μ M and 100  μ M of ZnCl 2 . Zinc chelation inhibited AD-MSC proliferation via downregulation of ERK1/2 activity. We then assessed whether zinc was involved in cell migration and neurite outgrowth during differentiation. After three days of neuronal differentiation, TUJ-1-positive cells were observed, implying that AD-MSCs had differentiated into early neuron or neuron-like cells. Neurite outgrowth was increased in the zinc-treated group, while the CaEDTA-treated group showed diminished, shrunken neurites. Furthermore, we showed that zinc promoted neurite outgrowth via the inactivation of RhoA and led to the induction of neuronal gene expression (MAP2 and nestin) in differentiated stem cells. Taken together, zinc promoted AD-MSC proliferation and affected neuronal differentiation, mainly by increasing neurite outgrowth.

Zinc Promotes Adipose-Derived Mesenchymal Stem Cell Proliferation and Differentiation towards a Neuronal Fate

Directory of Open Access Journals (Sweden)

Mi-Young Moon

2018-01-01

Full Text Available Zinc is an essential element required for cell division, migration, and proliferation. Under zinc-deficient conditions, proliferation and differentiation of neural progenitors are significantly impaired. Adipose-derived mesenchymal stem cells (AD-MSCs are multipotent stem cells that can differentiate into neurons. The aim of this study was to evaluate the effect of zinc on AD-MSC proliferation and differentiation. We initially examined the effect of zinc on stem cell proliferation at the undifferentiated stage. AD-MSCs showed high proliferation rates on day 6 in 30 μM and 100 μM of ZnCl2. Zinc chelation inhibited AD-MSC proliferation via downregulation of ERK1/2 activity. We then assessed whether zinc was involved in cell migration and neurite outgrowth during differentiation. After three days of neuronal differentiation, TUJ-1-positive cells were observed, implying that AD-MSCs had differentiated into early neuron or neuron-like cells. Neurite outgrowth was increased in the zinc-treated group, while the CaEDTA-treated group showed diminished, shrunken neurites. Furthermore, we showed that zinc promoted neurite outgrowth via the inactivation of RhoA and led to the induction of neuronal gene expression (MAP2 and nestin in differentiated stem cells. Taken together, zinc promoted AD-MSC proliferation and affected neuronal differentiation, mainly by increasing neurite outgrowth.

Framework for Proliferation Resistance and Physical Protection for Nonproliferation Impact Assessments

International Nuclear Information System (INIS)

Bari, R.

2008-01-01

This report describes a framework for proliferation resistance and physical protection evaluation for the fuel cycle systems envisioned in the expansion of nuclear power for electricity generation. The methodology is based on an approach developed as part of the Generation IV technical evaluation framework and on a qualitative evaluation approach to policy factors similar to those that were introduced in previous Nonproliferation Impact Assessments performed by DOE

Biomimetic alginate/polyacrylamide porous scaffold supports human mesenchymal stem cell proliferation and chondrogenesis

Energy Technology Data Exchange (ETDEWEB)

Guo, Peng [Department of ENT-Head and Neck Surgery, EENT Hospital, Shanghai 200031 (China); Shanghai Medical School, Fudan University, 210029 (China); Yuan, Yasheng, E-mail: yuanyasheng@163.com [Department of ENT-Head and Neck Surgery, EENT Hospital, Shanghai 200031 (China); Shanghai Medical School, Fudan University, 210029 (China); Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114 (United States); Chi, Fanglu [Department of ENT-Head and Neck Surgery, EENT Hospital, Shanghai 200031 (China); Shanghai Medical School, Fudan University, 210029 (China)

2014-09-01

We describe the development of alginate/polyacrylamide (ALG/PAAm) porous hydrogels based on interpenetrating polymer network structure for human mesenchymal stem cell proliferation and chondrogenesis. Three ALG/PAAm hydrogels at molar ratios of 10/90, 20/80, and 30/70 were prepared and characterized with enhanced elastic and rubbery mechanical properties, which are similar to native human cartilage tissues. Their elasticity and swelling properties were also studied under different physiological pH conditions. Finally, in vitro tests demonstrated that human mesenchymal stem cells could proliferate on the as-synthesized hydrogels with improved alkaline phosphatase activities. These results suggest that ALG/PAAm hydrogels may be a promising biomaterial for cartilage tissue engineering. - Highlights: • ALG/PAAm hydrogels were prepared at different molar ratios for cartilage tissue engineering. • ALG/PAAm hydrogels feature an interpenetrating polymer network structure. • ALG/PAAm hydrogels demonstrate strengthened elastic and rubbery mechanical properties. • hMSCs could be cultured on the ALG/PAAm hydrogels for proliferation and chondrogenesis.

Biomimetic alginate/polyacrylamide porous scaffold supports human mesenchymal stem cell proliferation and chondrogenesis

International Nuclear Information System (INIS)

Guo, Peng; Yuan, Yasheng; Chi, Fanglu

2014-01-01

We describe the development of alginate/polyacrylamide (ALG/PAAm) porous hydrogels based on interpenetrating polymer network structure for human mesenchymal stem cell proliferation and chondrogenesis. Three ALG/PAAm hydrogels at molar ratios of 10/90, 20/80, and 30/70 were prepared and characterized with enhanced elastic and rubbery mechanical properties, which are similar to native human cartilage tissues. Their elasticity and swelling properties were also studied under different physiological pH conditions. Finally, in vitro tests demonstrated that human mesenchymal stem cells could proliferate on the as-synthesized hydrogels with improved alkaline phosphatase activities. These results suggest that ALG/PAAm hydrogels may be a promising biomaterial for cartilage tissue engineering. - Highlights: • ALG/PAAm hydrogels were prepared at different molar ratios for cartilage tissue engineering. • ALG/PAAm hydrogels feature an interpenetrating polymer network structure. • ALG/PAAm hydrogels demonstrate strengthened elastic and rubbery mechanical properties. • hMSCs could be cultured on the ALG/PAAm hydrogels for proliferation and chondrogenesis

Adhesion and Proliferation of Human Periodontal Ligament Cells on Poly(2-methoxyethyl acrylate

Directory of Open Access Journals (Sweden)

Erika Kitakami

2014-01-01

Full Text Available Human periodontal ligament (PDL cells obtained from extracted teeth are a potential cell source for tissue engineering. We previously reported that poly(2-methoxyethyl acrylate (PMEA is highly biocompatible with human blood cells. In this study, we investigated the adhesion, morphology, and proliferation of PDL cells on PMEA and other types of polymers to design an appropriate scaffold for tissue engineering. PDL cells adhered and proliferated on all investigated polymer surfaces except for poly(2-hydroxyethyl methacrylate and poly[(2-methacryloyloxyethyl phosphorylcholine-co-(n-butyl methacrylate]. The initial adhesion of the PDL cells on PMEA was comparable with that on polyethylene terephthalate (PET. In addition, the PDL cells on PMEA spread well and exhibited proliferation behavior similar to that observed on PET. In contrast, platelets hardly adhered to PMEA. PMEA is therefore expected to be an excellent scaffold for tissue engineering and for culturing tissue-derived cells in a blood-rich environment.

Director's series on proliferation

International Nuclear Information System (INIS)

Bailey, K.C.; Price, M.E.

1995-01-01

This is an occasional publication of essays on the topics of nuclear, chemical, biological, and missile proliferation. The views represented are those of the author's. Essay topics include: Nuclear Proliferation: Myth and Reality; Problems of Enforcing Compliance with Arms Control Agreements; The Unreliability of the Russian Officer Corps: Reluctant Domestic Warriors; and Russia's Nuclear Legacy

FLAX OIL FROM TRANSGENIC LINUM USITATISSIMUM SELECTIVELY INHIBITS IN VITRO PROLIFERATION OF HUMAN CANCER CELL LINES.

Science.gov (United States)

Gebarowski, Tomasz; Gebczak, Katarzyna; Wiatrak, Benita; Kulma, Anna; Pelc, Katarzyna; Czuj, Tadeusz; Szopa, Jan; Gasiorowski, Kazimierz

2017-03-01

Emulsions made of oils from transgenic flaxseeds significantly decreased in vitro proliferation of six tested human cancer cell lines in 48-h cultures, as assessed with the standard sulforhodamine assay. However, the emulsions also increased proliferation rate of normal human dermal fibroblasts and, to a lower extend, of keratinocytes. Both inhibition of in vitro proliferation of human cancer cell lines and stimulation of proliferation of normal dermal fibroblasts and keratinocytes were especially strong with the emulsion type B and with emulsion type M. Oils from seeds of transgenic flax type B and M should be considered as valuable adjunct to standard cytostatic therapy of human cancers and also could be applied to improve the treatment of skin lesions in wound healing.

Nuclear non-proliferation

International Nuclear Information System (INIS)

Anon.

1984-01-01

DOE's nuclear non-proliferation responsibilities are defined by the provisions of the Atomic Energy Act of 1954, as amended, and of the Nuclear Non-Proliferation Act of 1978 (NNPA). The Department's major responsibilities in this area are to: (1) provide technical assistance to the Department of State in negotiating agreements for civil cooperation in the peaceful uses of nuclear energy with other countries and international organizations; (2) join with other agencies to reach executive branch judgments with respect to the issuance of export licenses by the Nuclear Regulatory Commission; (3) be responsible for processing subsequent arrangements with other agencies as required by the Nuclear Non-Proliferation Act; (4) control the distribution of special nuclear materials, components, equipment, and nuclear technology exports; (5) participate in bilateral and multilateral cooperation with foreign governments and organizations to promote the peaceful uses of nuclear energy; and (6) act as a primary technical resource with respect to US participation in the International Atomic Energy Agency

miR-198 Represses the Proliferation of HaCaT Cells by Targeting Cyclin D2

Directory of Open Access Journals (Sweden)

Jian Wang

2015-07-01

Full Text Available Background: MiR-198 has been considered as an inhibitor of cell proliferation, invasion, migration and a promoter of apoptosis in most cancer cells, while its effect on non-cancer cells is poorly understood. Methods: The effect of miR-198 transfection on HaCaT cell proliferation was firstly detected using Cell Count Kit-8 and the cell cycle progression was analyzed by flow cytometry. Using bioinformatics analyses and luciferase assay, a new target of miR-198 was searched and identified. Then, the effect of the new target gene of miR-198 on cell proliferation and cell cycle was also detected. Results: Here we showed that miR-198 directly bound to the 3′-UTR of CCND2 mRNA, which was a key regulator in cell cycle progression. Overexpressed miR-198 repressed CCND2 expression at mRNA and protein levels and subsequently led to cell proliferation inhibition and cell cycle arrest in the G1 phase. Transfection ofSiCCND2 in HaCaT cells showed similar inhibitory effects on cell proliferation and cell cycle progression. Conclusion: In conclusion, we have identified that miR-198 inhibited HaCaT cell proliferation by directly targeting CCND2.

Cell Proliferation during Lymphopoiesis in the Thymus of Normal and Continuously Irradiated Mice

Energy Technology Data Exchange (ETDEWEB)

Fabrikant, J. I. [Department of Radiological Science, Johns Hopkins University, Baltimore, MD (United States)

1968-08-15

The patterns of lymphoid cell proliferation in the thymus and spleen in normal and continuously irradiated young C57BL mice have been examined with techniques of flash and repeated labelling with tritiated thymidine and high resolution autoradiography. Changes in percentage labelling indices and labelled mitoses data have provided information on sites and rates of lymphoid cell proliferation in the thymus cortex (reticular cells, large, medium and small lymphocytes) and the spleen white pulp (germinal centre cells, large, medium and small lymphocytes). Labelling rates were fastest in the more primitive cell forms; in both lymphoid organs, the stem-cell labelling - reticular cells and germinal centre cells - reached 100% rapidly, whereas this was not the case for the different lymphocyte populations, and thymic lymphopoiesis was more rapid than splenic lymphopoiesis. Mean cycle times for thymus lymphoid cells were {approx} 12.5 hours for reticular cells, {approx} 9.5 hours for large lymphocytes, and {approx} 10.0 hours for medium and small lymphocytes; in the spleen, representative cycle times were significantly longer. Small lymphocytes were replaced at a greater rate in the thymus than in the spleen. Under continuous {gamma}-irradiation (caesium-137) at 45 rad/day and 75 rad/day for 15 days, there was a progressive depopulation of all lymphoid cell classes, an increase in the relative proportion of the more primitive forms, and a marked decrease in the numbers of small lymphocytes in both tissues. In the thymus and in the spleen, there was an increase in proliferation rates in both stem-cell populations and in all lymphoid cell forms, a decrease in mean cell cycle times to shorter values and a possible reduction in the spread of cell cycle times. In irradiated tissues, there was little evidence for lymphoid cell emigration. Tentative patterns of lymphopoiesis in the normal thymus and spleen based on the autoradiographic data aredescribed and changes in the

Hepatocellular proliferation and hepatocarcinogen bioactivation in mice with diet-induced fatty liver and obesity.

Science.gov (United States)

Iatropoulos, M J; Duan, J-D; Jeffrey, A M; Leach, M W; Hayes, A N; Stedman, N L; Williams, G M

2013-05-01

Human liver cancer is in part associated with obesity and related metabolic diseases. The present study was undertaken in a mouse model of diet-induced obesity (DIO) and hepatic steatosis, conditions which can be associated with hepatic neoplasia, to determine whether the rates of cell proliferation or hepatocarcinogen bioactivation were altered in ways which could facilitate hepatocarcinogenesis. DIO mice were generated by feeding C57BL/6 (B6) male mice a high-fat diet beginning at 4 weeks of age; age-matched conventional lean (LEAN) B6 mice fed a low fat diet (10% Kcal from fat) were used for comparison. Groups of 28 week old DIO and LEAN mice were dosed with the bioactivation-dependent DNA-reactive hepatocarcinogen 2-acetylaminofluorene (AAF), at 2.24 or 22.4 mg/kg, given by gavage 3 times per week for 31 days, or received no treatment (DIO and LEAN control groups). Compared with the LEAN control group, the DIO control group had a higher mean body weight (16.5 g), higher mean absolute (1.4 g) and mean relative (25.5%) liver weights, higher (394%) liver triglyceride concentrations, and an increased incidence and severity of hepatocellular steatosis at the end of the dosing phase. The DIO control group also had a higher mean hepatocellular replicating fraction (31% increase, determined by proliferating cell nuclear antigen immunohistochemistry). Hepatocarcinogen bioactivation, based on formation of AAF DNA adducts as measured by nucleotide (32)P-postlabeling, was similar in both DIO and LEAN AAF-dosed groups. Thus, hepatocellular proliferation, but not hepatocarcinogen bioactivation, was identified as an alteration in livers of DIO mice which could contribute to their susceptibility to hepatocarcinogenesis. Copyright © 2012 Elsevier GmbH. All rights reserved.

Akt1 deficiency diminishes skeletal muscle hypertrophy by reducing satellite cell proliferation.

Science.gov (United States)

Moriya, Nobuki; Miyazaki, Mitsunori

2018-02-14

Skeletal muscle mass is determined by the net dynamic balance between protein synthesis and degradation. Although the Akt/mechanistic target of rapamycin (mTOR)-dependent pathway plays an important role in promoting protein synthesis and subsequent skeletal muscle hypertrophy, the precise molecular regulation of mTOR activity by the upstream protein kinase Akt is largely unknown. In addition, the activation of satellite cells has been indicated as a key regulator of muscle mass. However, the requirement of satellite cells for load-induced skeletal muscle hypertrophy is still under intense debate. In this study, female germline Akt1 knockout (KO) mice were used to examine whether Akt1 deficiency attenuates load-induced skeletal muscle hypertrophy through suppressing mTOR-dependent signaling and satellite cell proliferation. Akt1 KO mice showed a blunted hypertrophic response of skeletal muscle, with a diminished rate of satellite cell proliferation following mechanical overload. In contrast, Akt1 deficiency did not affect the load-induced activation of mTOR signaling and the subsequent enhanced rate of protein synthesis in skeletal muscle. These observations suggest that the load-induced activation of mTOR signaling occurs independently of Akt1 regulation and that Akt1 plays a critical role in regulating satellite cell proliferation during load-induced muscle hypertrophy.

Nuclear arbitration: Interpreting non-proliferation agreements

International Nuclear Information System (INIS)

Tzeng, Peter

2015-01-01

At the core of the nuclear non-proliferation regime lie international agreements. These agreements include, inter alia, the Nuclear Non-proliferation Treaty, nuclear co-operation agreements and nuclear export control agreements.1 States, however, do not always comply with their obligations under these agreements. In response, commentators have proposed various enforcement mechanisms to promote compliance. The inconvenient truth, however, is that states are generally unwilling to consent to enforcement mechanisms concerning issues as critical to national security as nuclear non-proliferation.3 This article suggests an alternative solution to the non-compliance problem: interpretation mechanisms. Although an interpretation mechanism does not have the teeth of an enforcement mechanism, it can induce compliance by providing an authoritative interpretation of a legal obligation. Interpretation mechanisms would help solve the non-compliance problem because, as this article shows, in many cases of alleged non-compliance with a non-proliferation agreement, the fundamental problem has been the lack of an authoritative interpretation of the agreement, not the lack of an enforcement mechanism. Specifically, this article proposes arbitration as the proper interpretation mechanism for non-proliferation agreements. It advocates the establishment of a 'Nuclear Arbitration Centre' as an independent branch of the International Atomic Energy Agency (IAEA), and recommends the gradual introduction of arbitration clauses into the texts of non-proliferation agreements. Section I begins with a discussion of international agreements in general and the importance of interpretation and enforcement mechanisms. Section II then discusses nuclear non-proliferation agreements and their lack of interpretation and enforcement mechanisms. Section III examines seven case studies of alleged non-compliance with non-proliferation agreements in order to show that the main problem in many cases

Cell proliferation is a key determinant of the outcome of FOXO3a activation

International Nuclear Information System (INIS)

Poulsen, Raewyn C.; Carr, Andrew J.; Hulley, Philippa A.

2015-01-01

The FOXO family of forkhead transcription factors have a pivotal role in determining cell fate in response to oxidative stress. FOXO activity can either promote cell survival or induce cell death. Increased FOXO-mediated cell death has been implicated in the pathogenesis of degenerative diseases affecting musculoskeletal tissues. The aim of this study was to determine the conditions under which one member of the FOXO family, FOXO3a, promotes cell survival as opposed to cell death. Treatment of primary human tenocytes with 1 pM hydrogen peroxide for 18 h resulted in increased protein levels of FOXO3a. In peroxide-treated cells cultured in low serum media, FOXO3a inhibited cell proliferation and protected against apoptosis. However in peroxide treated cells cultured in high serum media, cell proliferation was unchanged but level of apoptosis significantly increased. Similarly, in tenocytes transduced to over-express FOXO3a, cell proliferation was inhibited and level of apoptosis unchanged in cells cultured in low serum. However there was a robust increase in cell death in FOXO3a-expressing cells cultured in high serum. Inhibition of cell proliferation in either peroxide-treated or FOXO3a-expressing cells cultured in high serum protected against apoptosis induction. Conversely, addition of a Chk2 inhibitor to peroxide-treated or FOXO3a-expressing cells overrode the inhibitory effect of FOXO3a on cell proliferation and led to increased apoptosis in cells cultured in low serum. This study demonstrates that proliferating cells may be particularly susceptible to the apoptosis-inducing actions of FOXO3a. Inhibition of cell proliferation by FOXO3a may be a critical event in allowing the pro-survival rather than the pro-apoptotic activity of FOXO3a to prevail. - Highlights: • FOXO3a activity can result in either promotion of cell survival or apoptosis. • The outcome of FOXO3a activation differs in proliferating compared to non-proliferating cells. • Proliferating

Cell proliferation is a key determinant of the outcome of FOXO3a activation

Energy Technology Data Exchange (ETDEWEB)

Poulsen, Raewyn C., E-mail: raewyn.poulsen@gmail.com; Carr, Andrew J.; Hulley, Philippa A.

2015-06-19

The FOXO family of forkhead transcription factors have a pivotal role in determining cell fate in response to oxidative stress. FOXO activity can either promote cell survival or induce cell death. Increased FOXO-mediated cell death has been implicated in the pathogenesis of degenerative diseases affecting musculoskeletal tissues. The aim of this study was to determine the conditions under which one member of the FOXO family, FOXO3a, promotes cell survival as opposed to cell death. Treatment of primary human tenocytes with 1 pM hydrogen peroxide for 18 h resulted in increased protein levels of FOXO3a. In peroxide-treated cells cultured in low serum media, FOXO3a inhibited cell proliferation and protected against apoptosis. However in peroxide treated cells cultured in high serum media, cell proliferation was unchanged but level of apoptosis significantly increased. Similarly, in tenocytes transduced to over-express FOXO3a, cell proliferation was inhibited and level of apoptosis unchanged in cells cultured in low serum. However there was a robust increase in cell death in FOXO3a-expressing cells cultured in high serum. Inhibition of cell proliferation in either peroxide-treated or FOXO3a-expressing cells cultured in high serum protected against apoptosis induction. Conversely, addition of a Chk2 inhibitor to peroxide-treated or FOXO3a-expressing cells overrode the inhibitory effect of FOXO3a on cell proliferation and led to increased apoptosis in cells cultured in low serum. This study demonstrates that proliferating cells may be particularly susceptible to the apoptosis-inducing actions of FOXO3a. Inhibition of cell proliferation by FOXO3a may be a critical event in allowing the pro-survival rather than the pro-apoptotic activity of FOXO3a to prevail. - Highlights: • FOXO3a activity can result in either promotion of cell survival or apoptosis. • The outcome of FOXO3a activation differs in proliferating compared to non-proliferating cells. • Proliferating

Canada's nuclear non-proliferation policy

International Nuclear Information System (INIS)

1982-05-01

Canada's non-proliferation safeguards policy has two objectives: 1) to promote a more effective and comprehensive international non-proliferation regime; and 2) to ensure that Canadian nuclear exports will not be used for any nuclear explosive purpose. By emphasizing the key role of the Non-Proliferation Treaty, promoting reliance upon and improvements in the IAEA safeguards system, treating nuclear weapon and non-weapon states alike, and working for new approaches covering reprocessing, Canada promotes attainment of the first objective. The second is served through the network of bilateral nuclear agreements that Canada has put into place with its partners. The Canadian objective in post-INFCE forums is to persuade the international community to devise a more effective and comprehensive non-proliferation regime into which Canada and other suppliers may subsume their national requirements

GMP-grade platelet lysate enhances proliferation and migration of tenon fibroblasts.

Science.gov (United States)

Carducci, Augusto; Scafetta, Gaia; Siciliano, Camilla; Carnevale, Roberto; Rosa, Paolo; Coccia, Andrea; Mangino, Giorgio; Bordin, Antonella; Vingolo, Enzo Maria; Pierelli, Luca; Lendaro, Eugenio; Ragona, Giuseppe; Frati, Giacomo; De Falco, Elena

2016-01-01

Tenon's fibroblasts (TFs), widely employed as in vitro model for many ophthalmological studies, are routinely cultured with FBS. Platelet Lysate (PL), a hemoderivate enriched with growth factors and cytokines has been largely tested in several clinical applications and as substitute of FBS in culture. Here, we investigate whether PL can exert biological effects on TF populations similarly to other cell types. Results show that PL significantly enhances cell proliferation and migration vs. FBS, without influencing cell size/granularity. Upregulation of EGF, VEGF, KDR, MMP2-9, FAK mRNA levels also occurs and phosphorylation of AKT but not of ERK1/2 is significantly enhanced. The inhibition of the PI3kinase/AKT pathway with the specific inhibitor wortmannin, decreases PL-induced cell migration but not proliferation. Condition supernatants containing PL show increased bioavailability of Nitric Oxide and reduced levels of 8-Iso-PGF2-alpha, correlating with cell proliferation and migration. Pro-angiogenic/inflammatory soluble factors (GRO, Angiogenin, EGF, I-309, PARC) are exclusively or greater expressed in media containing PL than FBS. GMP-grade PL preparations positively influence in vitro biological effects of TFs representing a suitable and safer alternative to FBS.

Regenerative responses after mild heart injuries for cardiomyocyte proliferation in zebrafish

Science.gov (United States)

Itou, Junji; Akiyama, Ryutaro; Pehoski, Steve; Yu, Xiaodan; Kawakami, Hiroko; Kawakami, Yasuhiko

2014-01-01

Background The zebrafish heart regenerates after various severe injuries. Common processes of heart regeneration are cardiomyocyte proliferation, activation of epicardial tissue and neovascularization. In order to further characterize heart regeneration processes, we introduced milder injuries and compared responses to those induced by ventricular apex resection, a widely used injury method. We used scratching of the ventricular surface and puncturing of the ventricle with a fine tungsten needle as injury inducing techniques. Results Scratching the ventricular surface induced subtle cardiomyocyte proliferation and responses of the epicardium. Endothelial cell accumulation was limited to the surface of the heart. Ventricular puncture induced cardiomyocyte proliferation, endocardial and epicardial activation and neo-vascularization, similar to the resection method. However, the degree of the responses was milder, correlating with milder injury. Sham operation induced epicardial aldh1a2 expression but not tbx18 and WT1. Conclusions Puncturing the ventricle induces responses equivalent to resection at milder degrees in a shorter time frame and would be used as simple injury model. Scratching the ventricle did not induce heart regeneration and would be used for studying wound responses to epicardium. PMID:25074230

Knockdown of E2f1 by RNA interference impairs proliferation of rat cells in vitro

Directory of Open Access Journals (Sweden)

Luciana dos Reis Vasques

2010-01-01

Full Text Available E2F1 plays a key role in cell-cycle regulation in mammals, since its transcription factor activity controls genes required for DNA synthesis and apoptosis. E2F1 deregulation is a common feature among different tumor types and can be a major cause of cell proliferation. Thus, blocking E2F1 expression by RNA interference represents a promising therapeutic approach. In this study, the introduction of specific short hairpin RNAs (shRNAs reduced E2f1 expression by up to 77%, and impaired rat glioma cell proliferation by approximately 70%, as compared to control cells. Furthermore, we investigated the expression of E2f1 target genes, Cyclin A and Cyclin E. Cyclin A was found to be down-regulated, whereas Cyclin E had similar expression to control cells, indicating that gene(s other than E2f1 control its transcription. Other E2f family members, E2f2 and E2f3, which have been classified in the same subgroup of transcriptional activators, were also analyzed. Expression of both E2f2 and E2f3 was similar to control cells, showing no cross-inactivation or up-regulation to compensate for the absence of E2f1. Nevertheless, their expression was insufficient to maintain the initial proliferation potential. Taken together, our results suggest that shE2f1 is a promising therapy to control tumor cell proliferation.

Strengthening the nuclear non-proliferation regime

International Nuclear Information System (INIS)

Carlson, J.

2003-01-01

Although the nuclear non-proliferation regime has enjoyed considerable success, today the regime has never been under greater threat. Three states have challenged the objectives of the NPT, and there is a technology challenge - the spread of centrifuge enrichment technology and know-how. A major issue confronting the international community is, how to deal with a determined proliferator? Despite this gloomy scenario, however, the non-proliferation regime has considerable strengths - many of which can be developed further. The regime comprises complex interacting and mutually reinforcing elements. At its centre is the NPT - with IAEA safeguards as the Treaty's verification mechanism. Important complementary elements include: restraint in the supply and the acquisition of sensitive technologies; multilateral regimes such as the CTBT and proposed FMCT; various regional and bilateral regimes; the range of security and arms control arrangements outside the nuclear area (including other WMD regimes); and the development of proliferation-resistant technologies. Especially important are political incentives and sanctions in support of non-proliferation objectives. This paper outlines some of the key issues facing the non-proliferation regime

In vitro Proliferation Ability of Axillary Buds in Musa spp | Youmbi ...

African Journals Online (AJOL)

from : Pisang Mas (AA), Grande Naine (AAA), Batard and French Clair (AAB), CRBP 39 (AAAB) and Pelipita (ABB) varieties were used as explants. The proliferation rate of Axillary and apical buds and other growth parameters were measured. Results showed that no significant differences were observed between the two ...

Dynamics of nuclear proliferation

International Nuclear Information System (INIS)

Meyer, S.M.

1984-01-01

This book looks beyond policy disputes to make a systematic examination of the assumptions and contending hypotheses that constitute contemporary thinking on nuclear proliferation. Rather than determine who is right or wrong, the intent is to develop a better picture by using the various schools of thought as analytic windows. A better understanding of how the process operates should offer better guidance for predicting future nuclear proliferation and, ultimately, for controlling it. Separate chapters deal with the contending views, the technological and motivational bases of nuclear proliferation, the presence of a technological imperative, testing the motivational hypothesis, the dynamics of the process, and forecasting. Four appendices present historical decisions, the technical model, cost-estimating procedures, and procedures for estimating nuclear propensities. 288 references, 17 figures, 26 tables

Discovery of rapid whistlers close to Jupiter implying lightning rates similar to those on Earth

Science.gov (United States)

Kolmašová, Ivana; Imai, Masafumi; Santolík, Ondřej; Kurth, William S.; Hospodarsky, George B.; Gurnett, Donald A.; Connerney, John E. P.; Bolton, Scott J.

2018-06-01

Electrical currents in atmospheric lightning strokes generate impulsive radio waves in a broad range of frequencies, called atmospherics. These waves can be modified by their passage through the plasma environment of a planet into the form of dispersed whistlers1. In the Io plasma torus around Jupiter, Voyager 1 detected whistlers as several-seconds-long slowly falling tones at audible frequencies2. These measurements were the first evidence of lightning at Jupiter. Subsequently, Jovian lightning was observed by optical cameras on board several spacecraft in the form of localized flashes of light3-7. Here, we show measurements by the Waves instrument8 on board the Juno spacecraft9-11 that indicate observations of Jovian rapid whistlers: a form of dispersed atmospherics at extremely short timescales of several milliseconds to several tens of milliseconds. On the basis of these measurements, we report over 1,600 lightning detections, the largest set obtained to date. The data were acquired during close approaches to Jupiter between August 2016 and September 2017, at radial distances below 5 Jovian radii. We detected up to four lightning strokes per second, similar to rates in thunderstorms on Earth12 and six times the peak rates from the Voyager 1 observations13.

Proliferation resistance of small modular reactors fuels

Energy Technology Data Exchange (ETDEWEB)

Polidoro, F.; Parozzi, F. [RSE - Ricerca sul Sistema Energetico,Via Rubattino 54, 20134, Milano (Italy); Fassnacht, F.; Kuett, M.; Englert, M. [IANUS, Darmstadt University of Technology, Alexanderstr. 35, D-64283 Darmstadt (Germany)

2013-07-01

In this paper the proliferation resistance of different types of Small Modular Reactors (SMRs) has been examined and classified with criteria available in the literature. In the first part of the study, the level of proliferation attractiveness of traditional low-enriched UO{sub 2} and MOX fuels to be used in SMRs based on pressurized water technology has been analyzed. On the basis of numerical simulations both cores show significant proliferation risks. Although the MOX core is less proliferation prone in comparison to the UO{sub 2} core, it still can be highly attractive for diversion or undeclared production of nuclear material. In the second part of the paper, calculations to assess the proliferation attractiveness of fuel in typical small sodium cooled fast reactor show that proliferation risks from spent fuel cannot be neglected. The core contains a highly attractive plutonium composition during the whole life cycle. Despite some aspects of the design like the sealed core that enables easy detection of unauthorized withdrawal of fissile material and enhances proliferation resistance, in case of open Non-Proliferation Treaty break-out, weapon-grade plutonium in sufficient quantities could be extracted from the reactor core.

Impact of scaffold micro and macro architecture on Schwann cell proliferation under dynamic conditions in a rotating wall vessel bioreactor

International Nuclear Information System (INIS)

Valmikinathan, Chandra M.; Hoffman, John; Yu, Xiaojun

2011-01-01

Over the last decade tissue engineering has emerged as a powerful alternative to regenerate lost tissues owing to trauma or tumor. Evidence shows that Schwann cell containing scaffolds have improved performance in vivo as compared to scaffolds that depend on cellularization post implantation. However, owing to limited supply of cells from the patients themselves, several approaches have been taken to enhance cell proliferation rates to produce complete and uniform cellularization of scaffolds. The most common approach is the application of a bioreactor to enhance cell proliferation rate and therefore reduce the time needed to obtain sufficiently significant number of glial cells, prior to implantation. In this study, we show the application of a rotating wall bioreactor system for studying Schwann cell proliferation on nanofibrous spiral shaped scaffolds, prepared by solvent casting and salt leaching techniques. The scaffolds were fabricated from polycaprolactone (PCL), which has ideal mechanical properties and upon degradation does not produce acidic byproducts. The spiral scaffolds were coated with aligned or random nanofibers, produced by electrospinning, to provide a substrate that mimics the native extracellular matrix and the essential contact guidance cues. At the 4 day time point, an enhanced rate of cell proliferation was observed on the open structured nanofibrous spiral scaffolds in a rotating wall bioreactor, as compared to static culture conditions. However, the cell proliferation rate on the other contemporary scaffolds architectures such as the tubular and cylindrical scaffolds show reduced cell proliferation in the bioreactor as compared to static conditions, at the same time point. Moreover, the rotating wall bioreactor does not alter the orientation or the phenotype of the Schwann cells on the aligned nanofiber containing scaffolds, wherein, the cells remain aligned along the length of the scaffolds. Therefore, these open structured spiral

Non-proliferation and multinational enterprises

International Nuclear Information System (INIS)

1979-04-01

The paper supplements CC/WG.2/9 in presenting the Japanese delegation's contribution in the areas of non-proliferation and multi-national enterprises. The paper questions whether multinational enrichment enterprises would constitute a significant non-proliferation factor, noting that the nature of the venture might create a potential for the dissemination of sensitive information. The paper also argues that a multi-national venture which was not economically competitive (with national facilities) would have questionable viability. The conclusion is that non-proliferation advantages, if any, would be a result, not an objective of such a venture

Nuclear non proliferation and disarmament

International Nuclear Information System (INIS)

2000-01-01

In the framework of the publication of a document on the ''weapons mastership, disarmament and non proliferation: the french action'', by the ministry of Foreign Affairs and the ministry of Defense, the French Documentation organization presents a whole document. This document describes and details the following topics: the conference on the treaty of non proliferation of nuclear weapons, the France, Usa and Non Governmental Organizations position, the threats of the proliferation, the french actions towards the disarmament, the disarmament in the world, a chronology and some bibliographic resources. (A.L.B.)

Which future for nuclear counter-proliferation?

International Nuclear Information System (INIS)

Duval, M.

2010-01-01

Dealing with the case of nuclear weapons possessed by nuclear states (but not eventually by terrorists), the author first identifies the constants of counter-proliferation: it is linked to interest conflicts between those who try to preserve their monopoly and those who try to acquire a new weapon either because of a threat or for reasons of regional prestige, the evolution from use to deterrence, the appearance of new actors after the USA and Russia, the role of nuclear tactical weapons, and the future of Russian weapons and know-how. He presents the international counter-proliferation context: the Non Proliferation Treaty (NPT), the IAEA and its controls, the Nuclear Supplier Group (NSG), the nuclear-free zones, the Comprehensive Test Ban Treaty (CTBT), the Missile Technology Control Regime (MTCR). He describes how and why proliferation occurs: uranium enrichment and plutonium technology, political reasons in different parts of the world. Then, he gives an overview of the proliferation status by commenting the cases of Israel, Iraq, India, Pakistan, North Korea, and Iran. He discusses the future of proliferation (involved countries, existence of a nuclear black market) and of counter-proliferation as far as Middle-East and North Korea are concerned. He tries finally to anticipate the consequences for nuclear deterrence strategy, and more particularly for Europe and France

Proliferation of maize (Zea mays L.) roots in response to localized supply of nitrate

Science.gov (United States)

Granato, T. C.; Raper, C. D. Jr; Raper CD, J. r. (Principal Investigator)

1989-01-01

Maize (Zea mays L.) plants with two primary nodal root axes were grown for 8 d in flowing nutrient culture with each axis independently supplied with NO3-. Dry matter accumulation by roots was similar whether 1.0 mol m-3 NO3- was supplied to one or both axes. When NO3- was supplied to only one axis, however, accumulation of dry matter within the root system was significantly greater in the axis supplied with NO3-. The increased dry matter accumulation by the +N-treated axis was attributable entirely to increased density and growth of lateral branches and not to a difference in growth of the primary axis. Proliferation of lateral branches for the +N axis was associated with the capacity for in situ reduction and utilization of a portion of the absorbed NO3-, especially in the apical region where lateral primordia are initiated. Although reduced nitrogen was translocated to the -N axis, concentrations in the -N axis remained significantly lower than in the +N axis. The concentration of reduced nitrogen, as well as in vitro NO3- reductase activity, was greater in apical than in more basal regions of the +N axis. The enhanced proliferation of lateral branches in the +N axis was accompanied by an increase in total respiration rate of the axis. Part of the increased respiration was attributable to increased mass of roots. The specific respiration rate (micromoles CO2 evolved per hour per gram root dry weight) was also greater for the +N than for the -N axis. If respiration rate is taken as representative of sink demand, stimulation of initiation and growth of laterals by in situ utilization of a localized exogenous supply of NO3- establishes an increased sink demand through enhanced metabolic activity and the increased partitioning of assimilates to the +N axis responds to the difference in sink demand between +N and -N axes.

Impact toughness and microstructure relationship in niobium- and vanadium-microalloyed steels processed with varied cooling rates to similar yield strength

Energy Technology Data Exchange (ETDEWEB)

Shanmugam, S. [Center for Structural and Functional Materials and Department of Chemical Engineering, University of Louisiana at Lafayette, LA 70504-4130 (United States); Misra, R.D.K. [Center for Structural and Functional Materials and Department of Chemical Engineering, University of Louisiana at Lafayette, LA 70504-4130 (United States)]. E-mail: dmisra@louisiana.edu; Mannering, T. [Nucor-Yamato Steel, P.O. Box 1228, 5929 East State Highway 18, Blytheville, AR 72316 (United States); Panda, D. [Nucor-Yamato Steel, P.O. Box 1228, 5929 East State Highway 18, Blytheville, AR 72316 (United States); Jansto, S.G. [Reference Metals, 1000 Old Pond Road, Bridgeville, PA 15017 (United States)

2006-11-15

We describe here the relationship between microstructure and impact toughness behavior as a function of cooling rate for industrially processed Nb- and V-microalloyed steels of almost similar yield strength ({approx}60 ksi). Both Nb- and V-microalloyed steels exhibited increase in toughness with increase in cooling rates during processing. However, Nb-microalloyed steels were characterized by relatively higher toughness than the V-microalloyed steels under identical processing conditions. The microstructure of Nb- and V-microalloyed steels processed at conventional cooling rate, primarily consisted of polygonal ferrite-pearlite microconstituents, while Nb-microalloyed steels besides polygonal ferrite and pearlite contained significant fraction of degenerated pearlite. The microstructure of Nb- and V-microalloyed steels processed at relatively higher cooling rate contained degenerated pearlite and lath-type (acicular) ferrite in addition to the primary ferrite-pearlite constituents. The fraction of degenerated pearlite was higher in Nb-microalloyed steels than in the V-microalloyed steels. In both Nb- and V-microalloyed steels the precipitation characteristics were similar with precipitation occurring at grain boundaries, dislocations, and in the ferrite matrix. Fine-scale ({approx}5-10 nm) precipitation was observed in the ferrite matrix of both the steels. The selected area diffraction (SAD) pattern analysis revealed that these fine precipitates were MC type of niobium and vanadium carbides in the respective steels and followed Baker-Nutting orientation relationship with the ferrite matrix. The microstructural studies suggest that the increase in toughness of Nb-microalloyed steels is attributed to higher fraction of degenerated pearlite in the steel.

Impact toughness and microstructure relationship in niobium- and vanadium-microalloyed steels processed with varied cooling rates to similar yield strength

International Nuclear Information System (INIS)

Shanmugam, S.; Misra, R.D.K.; Mannering, T.; Panda, D.; Jansto, S.G.

2006-01-01

We describe here the relationship between microstructure and impact toughness behavior as a function of cooling rate for industrially processed Nb- and V-microalloyed steels of almost similar yield strength (∼60 ksi). Both Nb- and V-microalloyed steels exhibited increase in toughness with increase in cooling rates during processing. However, Nb-microalloyed steels were characterized by relatively higher toughness than the V-microalloyed steels under identical processing conditions. The microstructure of Nb- and V-microalloyed steels processed at conventional cooling rate, primarily consisted of polygonal ferrite-pearlite microconstituents, while Nb-microalloyed steels besides polygonal ferrite and pearlite contained significant fraction of degenerated pearlite. The microstructure of Nb- and V-microalloyed steels processed at relatively higher cooling rate contained degenerated pearlite and lath-type (acicular) ferrite in addition to the primary ferrite-pearlite constituents. The fraction of degenerated pearlite was higher in Nb-microalloyed steels than in the V-microalloyed steels. In both Nb- and V-microalloyed steels the precipitation characteristics were similar with precipitation occurring at grain boundaries, dislocations, and in the ferrite matrix. Fine-scale (∼5-10 nm) precipitation was observed in the ferrite matrix of both the steels. The selected area diffraction (SAD) pattern analysis revealed that these fine precipitates were MC type of niobium and vanadium carbides in the respective steels and followed Baker-Nutting orientation relationship with the ferrite matrix. The microstructural studies suggest that the increase in toughness of Nb-microalloyed steels is attributed to higher fraction of degenerated pearlite in the steel

Fibroblast response to initial attachment and proliferation on titanium and zirconium surfaces.

Directory of Open Access Journals (Sweden)

Araceli Meza-Rodríguez

2016-08-01

Full Text Available Introduction: In recent decades, dental implants have become one of the best options for comprehensive dental restoration; their placement is a multidisciplinary task that requires a solid understanding of biological, periodontal, surgical and prosthetic principles. Objective: The aim of this study was to quantify in vitro the adhesion and proliferation of human gingival fibroblasts (HGF response on titanium (Ti and zirconia (Zr surfaces. Methodology: Samples of Ti and Zr were observed under atomic force microscopy (AFM. HGFs were inoculated in each sample to determine adhesion and cell proliferation. The reagent MTT was mixed with medium DMEM and inoculated in each plate; formazan was dissolved with dimethyl sulfoxide and analyzed at 540nm in a microplate spectrophotometer. The test was performed with three independent experiments. Data were analyzed with Kolmogorov-Smirnov tests (Lilliefors, Kruskal-Wallis tests and Mann-Whitney test comparisons. Results: Topography of the Zr plates showed greater roughness (Ra=0.39μm than Ti (Ra=0.049μm. Quantification of HGF adhesion was significantly higher (p<0.05 in Ti, while proliferation showed no statistically significant differences between the groups. Conclusion: It is noteworthy that, even though Ti initially showed increased cell adhesion on the surface, after 24h Zr samples showed similar proliferation; this demonstrates that both surfaces have a comparable biological response.

Inhibition of LPS-induced splenocyte proliferation by ortho-substituted polychlorinated biphenyl congeners

International Nuclear Information System (INIS)

Smithwick, L. Ashley; Smith, Andrew; Quensen, John F.; Stack, Allison; London, Lucille; Morris, Pamela J.

2003-01-01

Polychlorinated biphenyls (PCBs) are persistent environmental contaminants, and their ubiquitous nature has prompted studies of their potential health hazards. As a result of their lipophilic nature, PCBs accumulate in breast milk and subsequently affect the health of offspring of exposed individuals. Biological effects of PCBs in animals have mostly been attributed to coplanar congeners, although effects of ortho congeners also have been demonstrated. To investigate the relationship of immunotoxicity and chlorine substitution pattern, the effects of PCB congeners and mixtures of ortho and non-ortho-substituted constituents of Aroclor 1242 on splenocytes from C57B1/6 mice were examined. The immunotoxic endpoints investigated included splenocyte viability, lipopolysaccharide (LPS)-induced splenocyte proliferation, and LPS-induced antibody secretion. Congeners with multiple ortho chlorines preferentially inhibited splenocyte proliferation as compared with non- or mono-ortho-substituted congeners. However, mixtures of non- and mono-ortho-substituted congeners and multi-ortho-substituted congeners inhibited LPS-induced splenocyte proliferation and antibody secretion at similar concentrations. Exposure of splenocytes to these mixtures did not activate the aryl hydrocarbon receptor (AhR) signal transduction pathway. These results suggest individual multi-ortho-substituted congeners preferentially inhibit LPS-induced splenocyte proliferation, while congeners not exhibiting an effect individually may have additive effects in a mixture to produce an immunotoxic response through an AhR-independent pathway

Heparin modulates human intestinal smooth muscle (HISM) cell proliferation and matrix production

International Nuclear Information System (INIS)

Graham, M.; Perr, H.; Drucker, D.E.; Diegelmann, R.F.

1986-01-01

(HISM) cell proliferation and collagen production may play a role in the pathogenesis of intestinal stricture in Crohn's disease. The present studies were performed to evaluate the effects of heparin, a known modulator of vascular smooth muscle cells, on HISM cell proliferation and collagen production. Heparin (100 μg/ml) was added daily to HISM cell cultures for cell proliferation studies and for 24 hours at various time points during culture for collagen synthesis studies. Collagen synthesis was determined by the uptake of 3 H proline into collagenase-sensitive protein. Heparin completely inhibited cell proliferation for 7 days, after which cell numbers increased but at a slower rate than controls. Cells released from heparin inhibition demonstrated catch-up growth to control levels. Collagen production was significantly inhibited by 24 hours exposure to heparin but only at those times during culture when collagen synthesis was maximal (8 to 12 days). Non-collagen protein synthesis was inhibited by heparin at all time points during culture. Heparin through its modulation of HISM cells may play an important role in the control of the extracellular matrix of the intestinal wall

A general native-state method for determination of proliferation capacity of human normal and tumor tissues in vitro

International Nuclear Information System (INIS)

Hoffman, R.M.; Connors, K.M.; Meerson-Monosov, A.Z.; Herrera, H.; Price, J.H.

1989-01-01

An important need in cancer research and treatment is a physiological means in vitro by which to assess the proliferation capacity of human tumors and corresponding normal tissue for comparison. The authors have recently developed a native-state, three-dimensional, gel-supported primary culture system that allows every type of human cancer to grow in vitro at more than 90% frequency, with maintenance of tissue architecture, tumor-stromal interaction, and differentiated functions. Here they demonstrate that the native-state culture system allows proliferation indices to be determined for all solid cancer types explanted directly from surgery into long-term culture. Normal tissues also proliferate readily in this system. The degree of resolution of measurement of cell proliferation by histological autoradiography within the cultured tissues is greatly enhanced with the use of epi-illumination polarization microscopy. The histological status of the cultured tissues can be assessed simultaneously with the proliferation status. Carcinomas generally have areas of high epithelial proliferation with quiescent stromal cells. Sarcomas have high proliferation of cells of mesenchymal organ. Normal tissues can also proliferate at high rates. An image analysis system has been developed to automate proliferation determination. The high-resolution physiological means described here to measure the proliferation capacity of tissues will be important in further understanding of the deregulation of cell proliferation in cancer as well as in cancer prognosis and treatment

Growth and proliferation in vitro of Vaccinium corymbosum under different irradiance and radiation spectral composition

International Nuclear Information System (INIS)

Noe, N.; Eccher, T.; Signore, E. del; Montoldi, A.

1998-01-01

Plantlets of highbush blueberry (Vaccinium corymbosum) cvs. Atlantic, Barkeley and Elizabeth, were exposed in vitro to radiation of different spectral compositions obtained by filtering the cool-white light. Red colour of leaves was the first response to the light treatments. On average, cv. Atlantic yielded the highest number of shoots per explant (10.4), followed by cv. Elizabeth (9.1) and Berkeley (6.5). No-B-PMMA increased the proliferation rate in all the 3 genotypes, especially in cv. Atlantic. Cutting wavelengths between 650 and 760 nm (no-R-PMMA filter) generally depressed the proliferation rate. No-B-PMMA induced remarkable changes in the morphology of the shoots - more elongate leaves and longer internodes - especially in cv. Atlantic

Cell Cycle Phase Abnormalities Do Not Account for Disordered Proliferation in Barrett's Carcinogenesis

Directory of Open Access Journals (Sweden)

Pierre Lao-Sirieix

2004-11-01

Full Text Available Barrett's esophagus (BE epithelium is the precursor lesion for esophageal adenocarcinoma. Cell cycle proteins have been advocated as biomarkers to predict the malignant potential in BE. However, whether disruption of the cell cycle plays a causal role in Barrett's carcinogenesis is not clear. Specimens from the Barrett's dysplasia—carcinoma sequence were immunostained for cell cycle phase markers (cyclin D1 for G1; cyclin A for S, G2, and M; cytoplasmic cyclin B1 for G2; and phosphorylated histone 3 for M phase and expressed as a proportion of proliferating cells. Flow cytometric analysis of the cell cycle phase of prospective biopsies was also performed. The proliferation status of nondysplastic BE was similar to gastric antrum and D2, but the proliferative compartment extended to the luminal surface. In dysplastic samples, the number of proliferating cells correlated with the degree of dysplasia (P < .001. The overall levels of cyclins A and B1 correlated with the degree of dysplasia (P < .001. However, the cell cycle phase distribution measured with both immunostaining and flow cytometry was conserved during all stages of BE, dysplasia, and cancer. Hence, the increased proliferation seen in Barrett's carcinogenesis is due to abnormal cell cycle entry or exit, rather than a primary abnormality within the cell cycle.

Dual effect of LPS on murine myeloid leukemia cells: Pro-proliferation and anti-proliferation

International Nuclear Information System (INIS)

Yu, Lingling; Zhao, Yingmin; Gu, Xin; Wang, Jijun; Pang, Lei; Zhang, Yanqing; Li, Yaoyao; Jia, Xiaoqin; Wang, Xin; Gu, Jian; Yu, Duonan

2016-01-01

Modification of the bone marrow microenvironment is considered as a promising strategy to control leukemic cell proliferation, diseases progression and relapse after treatment. However, due to the diversity and complexity of the cellular and molecular compartments in the leukemic microenvironment, it is extremely difficult to dissect the role of each individual molecule or cell type in vivo. Here we established an in vitro system to dissect the role of lipopolysaccharide (LPS), stromal cells and endothelial cells in the growth of mouse myeloid tumor cells and B-lymphoma cells. We found that either LPS or bone marrow stromal cells as a feeder layer in culture is required for the proliferation of myeloid tumor cells. Surprisingly, the growth of myeloid leukemic cells on stromal cells is strongly inhibited when coupled with LPS in culture. This opposing effect of LPS, a complete switch from pro-proliferation to antitumor growth is due, at least in part, to the rapidly increased production of interleukin 12, Fas ligand and tissue inhibitor of metalloproteinases-2 from stromal cells stimulated by LPS. These results demonstrate that LPS can either facilitate or attenuate tumor cell proliferation, thus changing the disease course of myeloid leukemias through its direct effect or modulation of the tumor microenvironment. - Highlights: • LPS alone in culture is required for the proliferation of murine myeloid tumor cells. • Bone marrow stromal cells as a feeder layer is also required for the proliferation of myeloid tumor cells. • However, the growth of myeloid tumor cells is inhibited when LPS and stromal cells are both available in culture. • Thus LPS can either facilitate or attenuate tumor growth through its direct effect or modulation of tumor microenvironment.

Dual effect of LPS on murine myeloid leukemia cells: Pro-proliferation and anti-proliferation

Energy Technology Data Exchange (ETDEWEB)

Yu, Lingling [Department of Pediatrics, Jingjiang People' s Hospital, Yangzhou University, Jingjiang 214500 (China); Noncoding RNA Center, Yangzhou University, Yangzhou 225001 (China); Zhao, Yingmin [Department of Pediatrics, Jingjiang People' s Hospital, Yangzhou University, Jingjiang 214500 (China); Gu, Xin; Wang, Jijun; Pang, Lei; Zhang, Yanqing; Li, Yaoyao; Jia, Xiaoqin; Wang, Xin [Noncoding RNA Center, Yangzhou University, Yangzhou 225001 (China); Gu, Jian [Department of Hematology, Yangzhou University School of Clinical Medicine, Yangzhou 225001 (China); Yu, Duonan, E-mail: duonan@yahoo.com [Department of Pediatrics, Jingjiang People' s Hospital, Yangzhou University, Jingjiang 214500 (China); Noncoding RNA Center, Yangzhou University, Yangzhou 225001 (China); Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Disease, Yangzhou 225001 (China); Institute of Comparative Medicine, Yangzhou University, Yangzhou 225001 (China); Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonosis, Yangzhou 225001 (China)

2016-06-10

Modification of the bone marrow microenvironment is considered as a promising strategy to control leukemic cell proliferation, diseases progression and relapse after treatment. However, due to the diversity and complexity of the cellular and molecular compartments in the leukemic microenvironment, it is extremely difficult to dissect the role of each individual molecule or cell type in vivo. Here we established an in vitro system to dissect the role of lipopolysaccharide (LPS), stromal cells and endothelial cells in the growth of mouse myeloid tumor cells and B-lymphoma cells. We found that either LPS or bone marrow stromal cells as a feeder layer in culture is required for the proliferation of myeloid tumor cells. Surprisingly, the growth of myeloid leukemic cells on stromal cells is strongly inhibited when coupled with LPS in culture. This opposing effect of LPS, a complete switch from pro-proliferation to antitumor growth is due, at least in part, to the rapidly increased production of interleukin 12, Fas ligand and tissue inhibitor of metalloproteinases-2 from stromal cells stimulated by LPS. These results demonstrate that LPS can either facilitate or attenuate tumor cell proliferation, thus changing the disease course of myeloid leukemias through its direct effect or modulation of the tumor microenvironment. - Highlights: • LPS alone in culture is required for the proliferation of murine myeloid tumor cells. • Bone marrow stromal cells as a feeder layer is also required for the proliferation of myeloid tumor cells. • However, the growth of myeloid tumor cells is inhibited when LPS and stromal cells are both available in culture. • Thus LPS can either facilitate or attenuate tumor growth through its direct effect or modulation of tumor microenvironment.

ASC deficiency suppresses proliferation and prevents medulloblastoma incidence.

Science.gov (United States)

Knight, E R W; Patel, E Y; Flowers, C A; Crowther, A J; Ting, J P; Miller, C R; Gershon, T R; Deshmukh, M

2015-01-15

Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is silenced by promoter methylation in many types of tumors, yet ASC's role in most cancers remains unknown. Here, we show that ASC is highly expressed in a model of medulloblastoma, the most common malignant pediatric brain cancer; ASC is also expressed in human medulloblastomas. Importantly, while ASC deficiency did not affect normal cerebellar development, ASC knockout mice on the Smoothened (ND2:SmoA1) transgenic model of medulloblastoma exhibited a profound reduction in medulloblastoma incidence and a delayed tumor onset. A similar decrease in tumorigenesis with ASC deficiency was also seen in the hGFAP-Cre:SmoM2 mouse model of medulloblastoma. Interestingly, hyperproliferation of the external granule layer (EGL) was comparable at P20 in both wild-type and ASC-deficient SmoA1 mice. However, while the apoptosis and differentiation markers remained unchanged at this age, proliferation makers were decreased, and the EGL was reduced in thickness and area by P60. This reduction in proliferation with ASC deficiency was also seen in isolated SmoA1 cerebellar granule precursor cells in vitro, indicating that the effect of ASC deletion on proliferation was cell autonomous. Interestingly, ASC-deficient SmoA1 cerebella exhibited disrupted expression of genes in the transforming growth factor-β pathway and increased level of nuclear Smad3. Taken together, these results demonstrate an unexpected role for ASC in Sonic hedgehog-driven medulloblastoma tumorigenesis, thus identifying ASC as a promising novel target for antitumor therapy.

IPSN and the mastery of proliferation risks; L'IPSN et la maitrise des risques de proliferation

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-04-14

Since 20 years, the French Institute of Nuclear Protection and Safety (IPSN) works for the reinforcement of the efficiency of the actions against nuclear proliferation. This dossier takes stock of the means and action developed by the IPSN in this domain: nuclear and chemical proliferation: towards a reinforced mastery of risks (status of proliferation during the last 10 years, the aim of the international and national controls, the role of IPSN); nuclear proliferation: the technical control means of the IPSN (inspection, containment/surveillance of nuclear materials (PLUM and FUNE apparatuses), the cooperation between the IPSN and the Kurchatov institute (Russia)); the action of the IPSN in the application of international controls: example of chemistry (conventions, negotiations and expertise, inspections); appendixes: nuclear materials (declaration and permission thresholds), the different steps of the nuclear weapons non-proliferation policy. (J.S.)

The effects of a cyclooxygenase-2 (COX-2 expression and inhibition on human uveal melanoma cell proliferation and macrophage nitric oxide production

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Marshall Jean-Claude

2007-01-01

Full Text Available Abstract Background Cyclooxygenase-2 (COX-2 expression has previously been identified in uveal melanoma although the biological role of COX-2 in this intraocular malignancy has not been elucidated. This study aimed to investigate the effect of a COX-2 inhibitor on the proliferation rate of human uveal melanoma cells, as well as its effect on the cytotoxic response of macrophages. Methods Human uveal melanoma cell lines were transfected to constitutively express COX-2 and the proliferative rate of these cells using two different methods, with and without the addition of Amfenac, was measured. Nitric oxide production by macrophages was measured after exposure to melanoma-conditioned medium from both groups of cells as well as with and without Amfenac, the active metabolite of Nepafenac. Results Cells transfected to express COX-2 had a higher proliferation rate than those that did not. The addition of Amfenac significantly decreased the proliferation rate of all cell lines. Nitric oxide production by macrophages was inhibited by the addition of melanoma conditioned medium, the addition of Amfenac partially overcame this inhibition. Conclusion Amfenac affected both COX-2 transfected and non-transfected uveal melanoma cells in terms of their proliferation rates as well as their suppressive effects on macrophage cytotoxic activity.

Luteolin Inhibits Angiotensin II-Stimulated VSMC Proliferation and Migration through Downregulation of Akt Phosphorylation

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Tongda Xu

2015-01-01

Full Text Available Luteolin is a naturally occurring flavonoid found in many plants that possesses cardioprotective properties. The purpose of this study was to elucidate the effect of luteolin on vascular smooth muscle cells (VSMCs proliferation and migration induced by Angiotensin II (Ang II and to investigate the mechanism(s of action of this compound. Rat VSMCs were cultured in vitro, and the proliferation and migration of these cells following Ang II stimulation were monitored. Different doses of luteolin were added to VSMC cultures, and the proliferation and migration rate were observed by MTT and Transwell chamber assays, respectively. In addition, the expressions of p-Akt (308, p-Akt (473, and proliferative cell nuclear antigen (PCNA in VSMCs were monitored by Western blotting. This study demonstrated that luteolin has an inhibitory effect on Ang II-induced VSMC proliferation and migration. Further, the levels of p-Akt (308, p-Akt (473, and PCNA were reduced in VSMCs treated with both Ang II and luteolin compared to VSMCs treated with only Ang II. These findings strongly suggest that luteolin inhibits Ang II-stimulated proliferation and migration of VSMCs, which is partially due to downregulation of the Akt signaling pathway.

The handbook of nuclear non-proliferation

International Nuclear Information System (INIS)

Yang, M. H.; Lee, B. W.; Oh, K. B.; Lee, H. M.; Ko, H. S.; Ryu, J. S.; Lee, K. S.

2003-07-01

This report analyzed international non-proliferation regime preventing from spread of nuclear weapon. This report took review from the historical background of non-proliferation regime to the recent changes and current status. It is here divided into multilateral and bilateral regime. First of all, this report dealt four multilateral treaties concluded for international non-proliferation such as NPT, NWFZ, CTBT and others. And international organization and regimes concerned with non-proliferation are also analyzed focused on UN, IAEA, ZC and NSG, regional safeguards system and international conferences. In addition, this report reviewed the nuclear cooperation agreement related with Korea which is a important tool for bilateral regime

[Notochord cells enhance proliferation and phenotype-keeping of intervertebral disc chondroid cells].

Science.gov (United States)

Zhao, Xianfeng; Liu, Hao; Feng, Ganjun; Deng, Li; Li, Xiuqun; Liang, Tao

2008-08-01

To isolate and culture the chondroid cells and notochord cells from New Zealand rabbit immature nucleus pulposus (NP) in monolayer, and to evaluate the responsiveness of rabbit disc-derived chondroid cells to notochord cells with respect to cell proliferation and phenotype. The NP cells were released from the minced immature NP of 6 New Zealand rabbits (4-week-old) by 0.2% collagenase II digestion. The chondroid cells and notochord cells were purified by discontinuous gradient density centrifugation. The chondroid cells were cultured alone (group A) and co-cultured with notochord cells (group B) (1:1), and cell proliferation and phenotype including proteoglycan and collagen II were evaluated. The cells in both groups were observed by the inverted microscope, and the survival rates of the primary and passage cells were detected by toluidine blue staining. The growth curves of the second passage cells in both groups were determined by MTT. Besides, the expressions of proteoglycan and collagen II of the primary and passage cells were examined by toluidine blue and immunocytochemistry staining. The notochord cells and chondroid cells were isolated and purified. With the diameter of 10-15 microm, the notochord cell had abundant intracytoplasmic vesicles, while the chondroid cell, with the diameter of 4-6 microm, had no intracytoplasmic vesicle. The cell survival rate was 89.0%-95.3% in group A and 91.3%-96.3% in group B. There was no significant difference between the same passages in both groups (P > 0.05). The co-cultured cells (group B) increased in cell proliferation compared with the chondroid cells alone (group A) in repeated experiments. The cells in group A reached their logarithmic growth phase after 3-4 days of culture, while the cells in group B did after 2 days of culture. The cell proliferation in group B was more than that in group A after 4-day culture (P notochord cells are conducive for the proliferation and phenotype-keeping of the chondroid cells and

EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion

International Nuclear Information System (INIS)

Huang, Er-Wen; Xue, Sheng-Jiang; Li, Xiao-Yan; Xu, Suo-Wen; Cheng, Jian-Ding; Zheng, Jin-Xiang; Shi, He; Lv, Guo-Li; Li, Zhi-Gang; Li, Yue; Liu, Chang-Hui; Chen, Xiao-Hui; Liu, Hong; Li, Jie; Liu, Chao

2014-01-01

Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation, facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma

EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion

Energy Technology Data Exchange (ETDEWEB)

Huang, Er-Wen [Guangzhou Institute of Forensic Science, Guangzhou (China); Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Xue, Sheng-Jiang [Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Li, Xiao-Yan [Department of Pharmacy, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Xu, Suo-Wen [Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou (China); Cheng, Jian-Ding; Zheng, Jin-Xiang [Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Shi, He; Lv, Guo-Li; Li, Zhi-Gang; Li, Yue; Liu, Chang-Hui; Chen, Xiao-Hui; Liu, Hong [Guangzhou Institute of Forensic Science, Guangzhou (China); Li, Jie, E-mail: mdlijie@sina.com [Department of Anaesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Liu, Chao, E-mail: liuchaogaj@21cn.com [Guangzhou Institute of Forensic Science, Guangzhou (China)

2014-05-02

Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation, facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma.

Perspectives of the nuclear non-proliferation regime

International Nuclear Information System (INIS)

Koungou, Leon

2004-01-01

To join traditional methods and new approaches of 'non-proliferation'. This is a technical method and the best way to fight against 'non-proliferation' which is facing few preoccupations: knowledge's disseminations; technologies; equipments and weapons that should be stopped. As it's important to note the return of nuclear danger as the end of confrontation between west-east which should be reduce. As the adaptation of mechanisms is necessary today, as it is important to react about states' incitations to violate international engagement of non-proliferation. Areas control allows finding out change and evolution, but more insufficient. Functional difficulties show that the IAEA (International Agency of Atomic Energy) does not work good. Safeguard system does not allow to respect 'non-proliferation' engagements; for instance 'junkies states' that they cannot dissuade traditional methods. The fight of 'non-proliferation' shows new progresses with fearing methods of prevention actions and heaviest international controls of exportation. The target of this is very ambitious. This new method is self-successful because it contributes to re-enforce international security when defeating acquisition of nuclear and mass destruction weapons by non-states factors. Therefore non-proliferation regime and especially 'non-proliferation treaty' remains delicate as long as some militaries state such USA will reject their 'non-proliferation' engagement. (author) [fr

Comparison of the value of PCNA and Ki-67 as markers of cell proliferation in ameloblastic tumor

Science.gov (United States)

Mosqueda-Taylor, Adalberto; Molina-Frechero, Nelly; Mori-Estevez, Ana D.; Sánchez-Acuña, Guillermo

2013-01-01

Objectives: The aim of this study was to compare among PCNAand Ki-67 as the most reliable immunohistochemical marker for evaluating cell proliferation in ameloblastic tumors. Study Design: Observational, retrospective, and descriptive study of a large series of ameloblastic tumors, composed of 161 ameloblastomas and four ameloblastic carcinomas, to determine and compare PCNA and Ki-67 expression using immunohistochemistry techniques. Results: When analyzing Ki-67 positivity, the desmoplastic ameloblastoma demonstrated a significantly lower proliferation rate (1.9%) compared with the solid/multicystic and unicystic ameloblastomas and ameloblastic carcinomas (p<0.05), whereas the ameloblastic carcinomas displayed a significantly higher rate compared with all of the other ameloblastomas (48.7%) (p<0.05). When analyzing cell proliferation with PCNA, we found significant differences only between the ameloblastic carcinomas (93.3%) and the desmoplastic ameloblastomas (p<0.05). When differences between the immunopositivity for PCNA and Ki-67 were compared, the percentages were higher for PCNA in all types of ameloblastomas and ameloblastic carcinomas. In all cases, the percentages were greater than 80%, whereas the immunopositivity for Ki-67 was significantly lower; for example, the ameloblastic carcinoma expressed the highest positivity and only reached 48.7%, compared to 93.3% when we used PCNA. Conclusions: In the present study, when we used the proliferation cell marker Ki-67, the percentages of positivity were more specific and varied among the different types of ameloblastomas, suggesting that Ki-67 is a more specific marker for the proliferation of ameloblastic tumor cells. Key words:Ameloblastomas, ameloblastic carcinoma, PCNA, Ki-67, cell proliferation markers. PMID:23229269

Evaluation of proliferation potential in thyroid normo-/hypofunctioning and hyperfunctioning nodules.

Science.gov (United States)

Cornianu, Marioara; Stan, V; Lazăr, Elena; Dema, Alis; Golu, Ioana; Tăban, Sorina; Vlad, Mihaela; Faur, Alexandra; Vărcuş, F; Babău, F

2011-01-01

Thyroid follicular adenomas (FA) and adenomatous thyroid nodules (AN) - lesions that are frequently found in areas with iodine deficiency, can be normo-/hypofunctioning (scintigraphically cold - SCN) or hyperfunctioning (scintigraphically hot - SHN) nodules. Evaluation of proliferation potential in thyroid nodules on tissue samples obtained at surgery from euthyroid patients clinically diagnosed with SCN and from patients with thyroid hyperfunction and SHN. We investigated the proliferation activity estimated by assessing PCNA and Ki-67 proliferation markers in 20 SCN (eight FA and 12 AN) and 16 toxic nodules (six hyperfunctioning FA and 10 toxic multinodular goiters), on formalin-fixed and paraffin-embedded tissue samples, 4-5 μm thick; we used the immunohistochemical technique in LSAB system (DAB visualization) with anti-PCNA (PC10) and anti-Ki-67 (MIB-1) monoclonal antibodies. For each case, we calculated the proliferation index PI-PCNA and PI-Ki-67. The dates were statistically evaluated using the t-unpaired test. We observed a higher PI-PCNA in thyroid nodules than in the normal surrounding thyroid tissue, with statistically significant values for FA (14.3% vs. 3.8%; pnodules vs. surrounding thyroid tissue was 1.64% vs. 1.10% in FA (p0.05). We also noted: (1) significantly higher PI-PCNA values (p 0.05); (2) increased proliferation rate (pthyroid nodules with aspects of lymphocytic thyroiditis (LT) (PI-Ki-67 was 1.21%) as compared to nodules without LT (PI-Ki-67 was 0.12%); (3) a mean PI-PCNA of 8.5% and PI-Ki-67 of 4.61% in toxic thyroid nodules (TTN) vs. 3.01% and 1.5% in normal surrounding thyroid, respectively. The clinical expression of SCN is the consequence of increased thyrocyte proliferation in the nodules; the increased proliferative potential of TTN thyrocytes is a common feature of nodules, independent of their histopathological characteristics.

Andrographolide reduces proliferation and migration of lens epithelial cells by modulating PI3K/Akt pathway.

Science.gov (United States)

Kayastha, Forum; Madhu, Hardik; Vasavada, Abhay; Johar, Kaid

2014-11-01

Lens epithelial cell proliferation, migration, and transdifferentiation are involved in the development of subcapsular cataracts and postoperative capsular opacification (PCO). PI3K/Akt pathway is involved in the proliferation and migration of lens epithelial cells. Andrographolide is the main bioactive component of Andrographis paniculata and is known to possess anti-proliferative and anti-migratory activities. The purpose of this study is to evaluate the effect of andrographolide on proliferation and migration induced by growth factors (TGF-β and bFGF) in the lens epithelial cell line, FHL 124. We have also evaluated the role of the PI3K/Akt pathway and its alteration by andrographolide during proliferation and migration of lens epithelial cells. The results showed that andrographolide significantly inhibited proliferation in a dose and time dependent manner. The growth factors, TGF-β and bFGF, induced migration of lens epithelial cells, which was lowered by andrographolide. The growth factors also up regulated phosphorylated Akt (Ser473) and Akt (Thr308), which was abolished by simultaneous treatment of andrographolide. Similar changes were also observed with the PI3K inhibitor, LY290042. Our findings suggest that andrographolide reduces proliferation, migration, and phosphorylated Akt levels in lens epithelial cells. Hence andrographolide can be utilized for the prevention of PCO. Copyright © 2014 Elsevier Ltd. All rights reserved.

Nuclear proliferation: prospects, problems, and proposals

International Nuclear Information System (INIS)

Anon.

1977-01-01

This issue of the ANNALS addresses itself to three aspects of nuclear proliferation: the prospect that new nuclear powers will come on the scene, the problems that their arrival may create, and ways of coping with those problems. In an introductory paper, ''Quo Vadimus,'' Joseph I. Coffey investigates the pros and cons of proliferation, concluding that it is not a question of whether there will be nuclear proliferation, but in what countries. Part I, Where We Are, contains five papers preceded by introductory comments by Joseph I. Coffey. The papers and their authors are: Why States Go--and Don't Go--Nuclear, William Epstein; How States Can ''Go Nuclear,'' Frank C. Barnaby; What Happens If. . .Terrorists, Revolutionaries, and Nuclear Weapons, David Kreiger; Safeguards Against Diversion of Nuclear Material: An Overview, Ryukichi Imai; and Reducing the Incentives to Proliferation, George H. Quester. Part II, And Where We May Go, again includes some introductory remarks by Joseph I. Coffey. The seven succeeding papers are: Nth Powers of the Future, Ashok Kapur; Nuclear Proliferation and World Politics, Lewis A. Dunn; Arms Control in a Nuclear Armed World, Colin Gray; The United Nations, the Superpowers, and Proliferation, Abraham Bargman; Proliferation and the Future: Destruction or Transformation, Frederick C. Thayer; Decision Making in a Nuclear Armed World, Michael Brenner; and The United States in a World of Nuclear Powers, Michael Nacht. This special report is concluded with a glossary

A Rare Cutaneous Adnexal Tumor: Malignant Proliferating Trichilemmal Tumor

Directory of Open Access Journals (Sweden)

Omer Alici

2015-01-01

Full Text Available Proliferating trichilemmal tumors (PTTs are neoplasms derived from the outer root sheath of the hair follicle. These tumors, which commonly affect the scalp of elderly women, rarely demonstrate malignant transformation. Although invasion of the tumors into neighboring tissues and being accompanied with anaplasia and necrosis are accepted as findings of malignancy, histological features may not always be sufficient to identify these tumors. The clinical behavior of the tumor may be incompatible with its histological characteristics. Squamous-cell carcinoma should certainly be considered in differential diagnosis because of its similarity in morphological appearance with PTT. Immunostaining for CD34, P53, and Ki-67 is a useful adjuvant diagnostic method that can be used in differential diagnosis aside from morphological findings. In this study, we aimed to present the case of a 52-year-old female patient with clinicopathological features. We reported a low-grade malignant proliferating trichilemmal tumor in this patient and detected no relapse or metastasis in a 24-month period of follow-up.

Monin-Obukhov Similarity Functions of the Structure Parameter of Temperature and Turbulent Kinetic Energy Dissipation Rate in the Stable Boundary Layer

NARCIS (Netherlands)

Hartogensis, O.K.; Debruin, H.A.R.

2005-01-01

The Monin-Obukhov similarity theory (MOST) functions fepsi; and fT, of the dissipation rate of turbulent kinetic energy (TKE), ¿, and the structure parameter of temperature, CT2, were determined for the stable atmospheric surface layer using data gathered in the context of CASES-99. These data cover

The technical potential for proliferation in Northeast Asian states

International Nuclear Information System (INIS)

Joeck, N.; Kramer, R.

1995-01-01

This is a review of the technical capabilities of the states in Northeast Asia - principally Japan, South Korea, and North Korea - to develop nuclear weapons. At the outset, however, it should be emphasised that nuclear proliferation is primarily a political and security problem, rather than a technical challenge. The technical challenge is substantial, but if one looks at states with the technical capacity to develop nuclear weapons, it might be surprising to find that most of them have chosen not to do so. Even with access to fissile material and the technical and scientific infrastructure necessary to produce nuclear weapons, such states as Canada, Switzerland, Norway, Germany, Argentina, Brazil, Japan and many others, have not done so. All three non-nuclear weapon states in Northeast Asia have the technical capability to develop nuclear weapons. Japan and South Korea have intrusive safeguards and inspection arrangements on their nuclear programs, which allow their neighbours and the rest of the world to verify that they have not changed that status, and that they are living up to their NPT commitments. Despite its original commitment to the NPT, North Korea has yet to establish similar arrangements. It is ironic that the country with the smallest and technically least sophisticated nuclear program is the one creating the greatest concern about nuclear proliferation in the region. This irony illustrates the point made in the introduction, however. Nuclear proliferation is more a function of political decision-making than of technical capability

Functional similarities between pigeon 'milk' and mammalian milk: induction of immune gene expression and modification of the microbiota.

Directory of Open Access Journals (Sweden)

Meagan J Gillespie

Full Text Available Pigeon 'milk' and mammalian milk have functional similarities in terms of nutritional benefit and delivery of immunoglobulins to the young. Mammalian milk has been clearly shown to aid in the development of the immune system and microbiota of the young, but similar effects have not yet been attributed to pigeon 'milk'. Therefore, using a chicken model, we investigated the effect of pigeon 'milk' on immune gene expression in the Gut Associated Lymphoid Tissue (GALT and on the composition of the caecal microbiota. Chickens fed pigeon 'milk' had a faster rate of growth and a better feed conversion ratio than control chickens. There was significantly enhanced expression of immune-related gene pathways and interferon-stimulated genes in the GALT of pigeon 'milk'-fed chickens. These pathways include the innate immune response, regulation of cytokine production and regulation of B cell activation and proliferation. The caecal microbiota of pigeon 'milk'-fed chickens was significantly more diverse than control chickens, and appears to be affected by prebiotics in pigeon 'milk', as well as being directly seeded by bacteria present in pigeon 'milk'. Our results demonstrate that pigeon 'milk' has further modes of action which make it functionally similar to mammalian milk. We hypothesise that pigeon 'lactation' and mammalian lactation evolved independently but resulted in similarly functional products.

[Inhibition effects of black rice pericarp extracts on cell proliferation of PC-3 cells].

Science.gov (United States)

Jiang, Weiwei; Yu, Xudong; Ren, Guofeng

2013-05-01

To observe the inhibitive effects of black rice pericarp extracts on cell proliferation of human prostate cancer cell PC-3 and to explore its effecting mechanism. The black rice pericarp extract was used to treat the PC-3 cells. The inhibitory effect of black rice pericarp extract on cells proliferation of PC-3 was tested by MTT method. Cell apoptosis rates and cell cycle were measured by flow cytometric assay (FCM). Western blot was used to study the protein expression levels of p38, p-p38, JNK, p-JNK. A dose-dependent and time-dependent proliferation inhibition of black rice pericarp extract was demonstrated in PC-3. The most prominent experiment condition was inhibitory concentration with 300microg/ml and treated for 72 h. The experiment result of flow cytometry analysis demonstrates that the apoptosis rate of PC-3 cells increased along with the increasing of black rice pericarp extract concentration, and a G1-S cell cycle arrest was induced in a dose-dependent manner. After PC-3 cell was treated with black rice pericarp extract for 72 h, the expressions of p-p38, p-JNK protein increased. Black rice pericarp extract could inhibit proliferation, change the cell cycle distributions and induce apoptosis in human prostatic cancer cell PC-3. Its inhibitory effect may be through promoting activation of the JNK, p38 signaling pathway. These results suggest that black rice pericarp extract maybe has an inhibitory effect on prostatic cancer.

Proliferation: does the peaceful use of nuclear energy have to lead to proliferation of nuclear weapons

International Nuclear Information System (INIS)

Muench, E.; Stein, G.

The question of whether the proliferation of nuclear weapons is promoted by an increasing use of peaceful nuclear energy can be answered with a well-founded no. Even a regional renouncing of the peaceful use of nuclear energy would not reduce the worldwide problem of nuclear weapons' proliferation. Therefore, joint efforts must be aimed at promoting trust between peoples in the nuclear sphere and the political reasons for the proliferation of nuclear weapons must be reduced in order also to promote international harmony

A Novel Hybrid Similarity Calculation Model

Directory of Open Access Journals (Sweden)

Xiaoping Fan

2017-01-01

Full Text Available This paper addresses the problems of similarity calculation in the traditional recommendation algorithms of nearest neighbor collaborative filtering, especially the failure in describing dynamic user preference. Proceeding from the perspective of solving the problem of user interest drift, a new hybrid similarity calculation model is proposed in this paper. This model consists of two parts, on the one hand the model uses the function fitting to describe users’ rating behaviors and their rating preferences, and on the other hand it employs the Random Forest algorithm to take user attribute features into account. Furthermore, the paper combines the two parts to build a new hybrid similarity calculation model for user recommendation. Experimental results show that, for data sets of different size, the model’s prediction precision is higher than the traditional recommendation algorithms.

Prognostic value of proliferating cell nuclear antigen in parotid gland cancer.

Science.gov (United States)

Stenner, Markus; Demgensky, Ariane; Molls, Christoph; Hardt, Aline; Luers, Jan C; Grosheva, Maria; Huebbers, Christian U; Klussmann, Jens P

2012-04-01

Although cell proliferation is related to tumour aggressiveness and prognosis, there are few studies describing the expression of proliferative markers in salivary gland cancer. Our aim was to assess the long-term prognostic value of the proliferating cell nuclear antigen (PCNA) in a large group of histologically different salivary gland cancers. We analysed the expression of PCNA in 159 patients with parotid gland cancer by means of immunohistochemistry. The mean follow-up time was 56.6 months. A high expression of PCNA showed a significant correlation to the patients' pathological lymph node stage (p = 0.004). A high PCNA expression significantly indicated a poor 5-year disease-free (p = 0.046) and overall survival rate (p = 0.018). The PCNA expression was the only prognostic factor for a worse 5-year disease-free and overall survival in acinic cell carcinomas (p = 0.004, p = 0.022). The correlation between PCNA expression and survival probabilities of salivary gland cancer might make proliferation markers helpful tools in patient follow-up, prognosis and targeted therapy in salivary gland cancer in future.

Influence of prostaglandin analogues on epithelial cell proliferation and xenograft growth.

Science.gov (United States)

Tutton, P J; Barkla, D H

1980-01-01

The influence of two prostaglandin (PG) analogues, 16,16-dimethyl PG E2 and 16,16-dimethyl PG F2 alpha and of the cyclo-oxygenase inhibitor, flurbiprofen, on epithelial cell proliferation was assessed using a stathmokinetic technique. The epithelia examined were those of the jejunal crypts, the colonic crypts and that of dimethylhydrazine-induced adenocarcinomas of rat colon. The influence of the two prostaglandin analogues, and of flurbiprofen, on the growth of a human colorectal tumour propagated as xenografts in immune-deprived mice was also assessed. The PG E2 analogue transiently inhibited xenograft growth, but was without effect on the mitotic rate in the rat tissues. The PG F2 alpha analogue was also found to inhibit xenograft growth but, unlike the PG E2 analogue, it was found to be a strong inhibitor of cell proliferation in rat colonic tumours, and an accelerator of proliferation in jejunal-crypt cells. The only statistically significant effect of flurbiprofen was to accelerate cell division in the rat colonic tumours.

Glucose Induces Mouse β-Cell Proliferation via IRS2, MTOR, and Cyclin D2 but Not the Insulin Receptor

Science.gov (United States)

Stamateris, Rachel E.; Sharma, Rohit B.; Kong, Yahui; Ebrahimpour, Pantea; Panday, Deepika; Ranganath, Pavana; Zou, Baobo; Levitt, Helena; Parambil, Nisha Abraham; O’Donnell, Christopher P.; García-Ocaña, Adolfo

2016-01-01

An important goal in diabetes research is to understand the processes that trigger endogenous β-cell proliferation. Hyperglycemia induces β-cell replication, but the mechanism remains debated. A prime candidate is insulin, which acts locally through the insulin receptor. Having previously developed an in vivo mouse hyperglycemia model, we tested whether glucose induces β-cell proliferation through insulin signaling. By using mice lacking insulin signaling intermediate insulin receptor substrate 2 (IRS2), we confirmed that hyperglycemia-induced β-cell proliferation requires IRS2 both in vivo and ex vivo. Of note, insulin receptor activation was not required for glucose-induced proliferation, and insulin itself was not sufficient to drive replication. Glucose and insulin caused similar acute signaling in mouse islets, but chronic signaling differed markedly, with mammalian target of rapamycin (MTOR) and extracellular signal–related kinase (ERK) activation by glucose and AKT activation by insulin. MTOR but not ERK activation was required for glucose-induced proliferation. Cyclin D2 was necessary for glucose-induced β-cell proliferation. Cyclin D2 expression was reduced when either IRS2 or MTOR signaling was lost, and restoring cyclin D2 expression rescued the proliferation defect. Human islets shared many of these regulatory pathways. Taken together, these results support a model in which IRS2, MTOR, and cyclin D2, but not the insulin receptor, mediate glucose-induced proliferation. PMID:26740601

Framework of Comprehensive Proliferation Resistance Evaluation Methodology

International Nuclear Information System (INIS)

Kim, Min Su; Jo, Seong Youn; Kim, Min Soo; Kim, Jae San; Lee, Hyun Kyung

2007-01-01

Civilian nuclear programs can be used as a pretext to acquire technologies, materials, equipment for military weapon programs. Consequently, international society has a strong incentive to develop a nuclear system more proliferation resistant to assure that the civilian nuclear energy system is an unattractive and least desirable route for diversion of weapon usable material. The First step developing a more proliferation resistant nuclear energy system is to develop a systematic and standardized evaluation methodology to ensure that any future nuclear energy system satisfies the proliferation resistance goals. Many attempts to develop systematic evaluation methodology have been proposed and many systems for assessing proliferation resistance have been previously studied. However, a comprehensive proliferation resistance evaluation can not be achieved by simply applying one method since complicated proliferation resistance characteristics, including inherent features and extrinsic features, should be completely evaluated. Therefore, it is necessary to develop one incorporated evaluation methodology to make up for weak points of each evaluation method. The objective of this study is to provide a framework of comprehensive proliferation resistance evaluation methodology by incorporating two generally used evaluation methods, attribute and scenario analysis

Nifedipine promotes the proliferation and migration of breast cancer cells.

Directory of Open Access Journals (Sweden)

Dong-Qing Guo

Full Text Available Nifedipine is widely used as a calcium channel blocker (CCB to treat angina and hypertension,but it is controversial with respect the risk of stimulation of cancers. In this study, we demonstrated that nifedipine promoted the proliferation and migration of breast cancer cells both invivo and invitro. However, verapamil, another calcium channel blocker, didn't exert the similar effects. Nifedipine and high concentration KCl failed to alter the [Ca2+]i in MDA-MB-231 cells, suggesting that such nifedipine effect was not related with calcium channel. Moreover, nifedipine decreased miRNA-524-5p, resulting in the up-regulation of brain protein I3 (BRI3. Erk pathway was consequently activated and led to the proliferation and migration of breast cancer cells. Silencing BRI3 reversed the promoting effect of nifedipine on the breast cancer. In a summary, nifedipine stimulated the proliferation and migration of breast cancer cells via the axis of miRNA-524-5p-BRI3-Erk pathway independently of its calcium channel-blocking activity. Our findings highlight that nifedipine but not verapamil is conducive for breast cancer growth and metastasis, urging that the caution should be taken in clinic to prescribe nifedipine to women who suffering both hypertension and breast cancer, and hypertension with a tendency in breast cancers.

Cerium oxide nanoparticles stimulate proliferation of primary mouse embryonic fibroblasts in vitro

Energy Technology Data Exchange (ETDEWEB)

Popov, Anton L., E-mail: antonpopovleonid@gmail.com [Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow region (Russian Federation); Popova, Nelly R. [Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow region (Russian Federation); Selezneva, Irina I. [Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow region (Russian Federation); Pushchino State Institute of Natural sciences, Pushchino, Moscow region (Russian Federation); Akkizov, Azamat Y. [Kabardino-Balkarian State University, Nalchik (Russian Federation); Ivanov, Vladimir K. [Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, Moscow (Russian Federation); National Research Tomsk State University, Tomsk (Russian Federation)

2016-11-01

The increasing application of cell therapy technologies in the treatment of various diseases requires the development of new effective methods for culturing primary cells. The major limitation for the efficient use of autologous cell material is the low rate of cell proliferation. Successful cell therapy requires sufficient amounts of cell material over a short period of time with the preservation of their differentiation and proliferative potential. In this regard, the development of novel, highly efficient stimulators of proliferative activity in stem cells is a truly urgent task. In this paper we have demonstrated that citrate-stabilized cerium oxide nanoparticles (nanoceria) enhance the proliferative activity of primary mouse embryonic fibroblasts in vitro. Cerium oxide nanoparticles stimulate cell proliferation in a wide range of concentrations (10{sup −3} M–10{sup −9} M) through reduction of intracellular levels of reactive oxygen species (ROS) during the lag phase of cell growth and by modulating the expression level of the major antioxidant enzymes. We found the optimal concentration of nanoceria, which provides the greatest acceleration of cell proliferation in vitro, while maintaining the levels of intracellular ROS and mRNA of antioxidant enzymes in the physiological range. Our results confirm that nanocrystalline ceria can be considered as a basis for effective and inexpensive supplements in cell culturing. - Highlights: • Citrate-stabilized cerium oxide nanoparticles are shown to stimulate proliferation of primary embryonic cells in vitro. • Some of mechanisms involved in stimulating of the proliferation by CeO{sub 2} have been uncovered. • The most effective (optimal) concentration of CeO{sub 2} nanoparticles for stimulation of proliferation was determined.

Prevalence and proliferation of antibiotic resistance genes in two municipal wastewater treatment plants.

Science.gov (United States)

Mao, Daqing; Yu, Shuai; Rysz, Michal; Luo, Yi; Yang, Fengxia; Li, Fengxiang; Hou, Jie; Mu, Quanhua; Alvarez, P J J

2015-11-15

The propagation of antibiotic resistance genes (ARGs) is an emerging health concern worldwide. Thus, it is important to understand and mitigate their occurrence in different systems. In this study, 30 ARGs that confer resistance to tetracyclines, sulfonamides, quinolones or macrolides were detected in two activated sludge wastewater treatment plants (WWTPs) in northern China. Bacteria harboring ARGs persisted through all treatment units, and survived disinfection by chlorination in greater percentages than total Bacteria (assessed by 16S rRNA genes). Although the absolute abundances of ARGs were reduced from the raw influent to the effluent by 89.0%-99.8%, considerable ARG levels [(1.0 ± 0.2) × 10(3) to (9.5 ± 1.8) × 10(5) copies/mL)] were found in WWTP effluent samples. ARGs were concentrated in the waste sludge (through settling of bacteria and sludge dewatering) at (1.5 ± 2.3) × 10(9) to (2.2 ± 2.8) × 10(11) copies/g dry weight. Twelve ARGs (tetA, tetB, tetE, tetG, tetH, tetS, tetT, tetX, sul1, sul2, qnrB, ermC) were discharged through the dewatered sludge and plant effluent at higher rates than influent values, indicating overall proliferation of resistant bacteria. Significant antibiotic concentrations (2%-50% of raw influent concentrations) remained throughout all treatment units. This apparently contributed selective pressure for ARG replication since the relative abundance of resistant bacteria (assessed by ARG/16S rRNA gene ratios) was significantly correlated to the corresponding effluent antibiotic concentrations. Similarly, the concentrations of various heavy metals (which induce a similar bacterial resistance mechanism as antibiotics - efflux pumps) were also correlated to the enrichment of some ARGs. Thus, curtailing the release of antibiotics and heavy metals to sewage systems (or enhancing their removal in pre-treatment units) may alleviate their selective pressure and mitigate ARG proliferation in WWTPs. Copyright © 2015 Elsevier Ltd. All

MARKOV Model Application to Proliferation Risk Reduction of an Advanced Nuclear System

International Nuclear Information System (INIS)

Bari, R.A.

2008-01-01

The Generation IV International Forum (GIF) emphasizes proliferation resistance and physical protection (PR and PP) as a main goal for future nuclear energy systems. The GIF PR and PP Working Group has developed a methodology for the evaluation of these systems. As an application of the methodology, Markov model has been developed for the evaluation of proliferation resistance and is demonstrated for a hypothetical Example Sodium Fast Reactor (ESFR) system. This paper presents the case of diversion by the facility owner/operator to obtain material that could be used in a nuclear weapon. The Markov model is applied to evaluate material diversion strategies. The following features of the Markov model are presented here: (1) An effective detection rate has been introduced to account for the implementation of multiple safeguards approaches at a given strategic point; (2) Technical failure to divert material is modeled as intrinsic barriers related to the design of the facility or the properties of the material in the facility; and (3) Concealment to defeat or degrade the performance of safeguards is recognized in the Markov model. Three proliferation risk measures are calculated directly by the Markov model: the detection probability, technical failure probability, and proliferation time. The material type is indicated by an index that is based on the quality of material diverted. Sensitivity cases have been done to demonstrate the effects of different modeling features on the measures of proliferation resistance

Similar speaker recognition using nonlinear analysis

International Nuclear Information System (INIS)

Seo, J.P.; Kim, M.S.; Baek, I.C.; Kwon, Y.H.; Lee, K.S.; Chang, S.W.; Yang, S.I.

2004-01-01

Speech features of the conventional speaker identification system, are usually obtained by linear methods in spectral space. However, these methods have the drawback that speakers with similar voices cannot be distinguished, because the characteristics of their voices are also similar in spectral space. To overcome the difficulty in linear methods, we propose to use the correlation exponent in the nonlinear space as a new feature vector for speaker identification among persons with similar voices. We show that our proposed method surprisingly reduces the error rate of speaker identification system to speakers with similar voices

The effect of stem cell factor on proliferation of human endometrial CD146+ cells

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Mehri Fayazi

2016-07-01

Full Text Available Background: Stem cell factor (SCF is a transcriptional factor which plays crucial roles in normal proliferation, differentiation and survival in a range of stem cells. Objective: The aim of the present study was to examine the proliferation effect of different concentrations of SCF on expansion of human endometrial CD146+ cells. Materials and Methods: In this experimental study, total populations of isolated human endometrial suspensions after fourth passage were isolated by magnetic activated cell sorting (MACS into CD146+ cells. Human endometrial CD146+ cells were karyotyped and tested for the effect of SCF on proliferation of CD146+ cells, then different concentrations of 0, 12.5, 25, 50 and 100 ng/ml was carried out and mitogens-stimulated endometrial CD146+ cells proliferation was assessed by MTT assay. Results: Chromosomal analysis showed a normal metaphase spread and 46XX karyotype. The proliferation rate of endometrial CD146P + P cells in the presence of 0, 12.5, 25, 50 and 100 ng/ml SCF were 0.945±0.094, 0.962±0.151, 0.988±0.028, 1.679±0.012 and 1.129±0.145 respectively. There was a significant increase in stem/ stromal cell proliferation following in vitro treatment by 50 ng/ml than other concentrations of SCF (p=0.01. Conclusion: The present study suggests that SCF could have effect on the proliferation and cell survival of human endometrial CD146P+P cells and it has important implications for medical sciences and cell therapies

International proliferation on nuclear weapons

International Nuclear Information System (INIS)

Hill, J.

1977-01-01

The subject is dealt with under the following headings: introduction; routes to proliferation (preparation of U 235 , Pu 239 , U 233 ); nuclear power fuel cycles and proliferation; the fast reactor fuel cycle; security aspects of the existing fuel cycle; the IAEA and the nuclear non-proliferation treaty. It is concluded that 'the basis for sound international control exists, and taken together with the further technical steps which will be taken to make the existing fuel cycles more robust against the diversion of materials by terrorists and the abuse of civil nuclear power programmes by governments, we have good reason to proceed now with the orderly exploitation of ...nuclear energy...'. (U.K.)

North-East Asia: a risk of nuclear proliferation; Un risque de proliferation nucleaire en Asie du Nord-Est?

Energy Technology Data Exchange (ETDEWEB)

Courmont, B. [Centre d' Etudes Transatlantiques, 75 - Paris (France)

2009-04-15

North-East Asia is distinguished by being potentially one of the world's most nuclearised regions. It includes two nuclear powers recognised by the Non-Proliferation Treaty (Russia and China), a proliferating state (North Korea) and three countries that could very quickly complete nuclear programmes (Japan, South Korea and Taiwan). Now that the question of nuclear proliferation has again surfaced on the international strategic scene, and that North Korea's test of October 2006 has introduced a new security paradigm into the region, how real is the risk of nuclear proliferation in North-East Asia? (author)

3H-thymidine autoradiographic study of cell proliferation and the influence of isoproterenol and kallikrein in various cell populations of the gastrointestinal tract in animal experiments

International Nuclear Information System (INIS)

Albrecht, S.

1981-01-01

Morphological studies were carried out with the aim of studying cell proliferation in various tissues (stable and epithelial tissues) of the gastrointestinal tract. The cells were studied by 3 H thymidine autoradiography in the normal age cycle and under the influence of kallikrein or isoproterenol. Epithelial cells and smooth muscle cells of the forestomach, stomach, small intestine and colon were investigated and, in the case of the stomach, also connective-tissue cells of the mucotic stroma. Counts across the total epithelial thickness yielded similar results for the oesophagus and the forestomach. A count of 1000 cells per animal was found to yield representative information on a defined type of cell. Kallikrein was not found to have a constant mitosis-promoting effect. Isoproterenol caused the labelling index to increase or to decrease; in higher concentrations, it increased the proliferation rate in all cell types. In male animals, the labelling indices of connective-tissue cells of the gastric mucosa were significantly higher than in female animals. (orig./MG) [de

Influence of electrospun scaffolds prepared from distinct polymers on proliferation and viability of endothelial cells

Energy Technology Data Exchange (ETDEWEB)

Matveeva, V. G., E-mail: matveeva-vg@mail.ru; Antonova, L. V., E-mail: antonova.la@mail.ru; Velikanova, E. A.; Sergeeva, E. A.; Krivkina, E. O.; Glushkova, T. V.; Kudryavtseva, Yu. A.; Barbarash, O. L.; Barbarash, L. S. [Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, 650002 (Russian Federation)

2015-10-27

We compared electrospun nonwoven scaffolds from polylactic acid (PLA), polycaprolactone (PCL), and polyhydroxybutyrate/valerate (PHBV)/polycaprolactone (PHBV/PCL). The surface of PHBV/PCL and PCL scaffolds was highly porous and consisted of randomly distributed fibers, whilst the surface of PLA scaffolds consisted of thin straight fibers, which located more sparsely, forming large pores. Culture of EA.hy 926 endothelial cells on these scaffolds during 7 days and further fluorescent microscopy demonstrated that the surface of PHBV/PCL scaffolds was most favorable for efficient adhesion, proliferation, and viability of endothelial cells. The lowest proliferation rate and cell viability were detected on PLA scaffolds. Therefore, PHBV/PCL electrospun nonwoven scaffolds demonstrated the best results regarding endothelial cell proliferation and viability as compared to PCL and PLA scaffolds.

Factors influencing [F-18]2-fluoro-2-deoxy-D-glucose (F-18 FDG) uptake in melanoma cells. The role of proliferation rate, viability, glucose transporter expression and hexokinase activity

International Nuclear Information System (INIS)

Yamada, Kiyoshi; Brink, I.; Bisse, E.; Epting, T.; Engelhardt, R.

2005-01-01

Using human (SK-MEL 23, SK-MEL 24 and G361) and murine (B16) melanoma cell lines, the coregulatory potential of the uptake of the positron emission tomography (PET) tracer, [Fluorine-18]2-fluoro-2-deoxy-D-glucose (F-18 FDG) has been investigated in relationship to tumor characteristics. Comparative studies among the four melanoma cell lines demonstrated that the lowest FDG uptake in SK-MEL 24 corresponded strongly to the data for DT (population doubling time) and MTT (tetrazolium salt) cell viability as well as hexokinase (HK) activity, but was not related to the glucose transporter 1 (GLUT 1) expression level. Furthermore, the FDG uptake in each melanoma cell line measured by cell cycle kinetics was significantly positively correlated to both the proliferation index (PI=S/G 2 M phase fractions) and the cell viability, though with one exception relating to the proliferation index (PI) of the lowest FDG uptake cell line, SK-MEL 24. No positive correlation was found between the expression of GLUT 1 and FDG uptake in any individual cell line. However, the HK activities in SK-MEL 23 and 24 showed considerable positive relationships with FDG uptake. Our present study suggests that both the proliferation rate and the cell viability of melanoma cells may be key factors for FDG uptake and that HK activity, rather than GLUT 1 expression, seems to be a major factor. (author)

Nuclear proliferation and terrorism

International Nuclear Information System (INIS)

Anon.

1977-01-01

This section of the book, Part III, has two chapters (9 and 10). Chapter 9, Nuclear Power and Proliferation of Nuclear Weapons, is disucssed under these subjects: nuclear nonproliferation: origins and status; requirements for nuclear weapons manufacture; current nuclear programs and proliferation capabilities; encouraging decisions to forego weapons; arms control; safeguards; attitudes and expectations. Chapter 10, Nuclear Terrorism, discusses these areas: theft of nuclear materials; attacks on nuclear reactors; responding to nuclear terrorism; security and civil liberties

Nuclear power and nuclear-weapons proliferation

International Nuclear Information System (INIS)

Moniz, E.J.; Neff, T.L.

1978-01-01

Concern over the risk of nuclear proliferation has led to extensive reexamination of the technical, economic, and political assumptions underlying both national and international nuclear policies. An attempt is made in the present article to clarify the basic technical and political issues. The connections between various fuel cycles and their possible proliferation risks are discussed. As the resolution of the existing differing views on proliferation risks will be largely a political process, solutions to the problem are not proposed

China's position on nuclear non-proliferation

International Nuclear Information System (INIS)

Qian Jiadong.

1986-01-01

The paper discusses China's position on nuclear non-proliferation, in view of the fact that China does not subscribe to the Non-Proliferation Treaty (NPT). China refuses to accede to the NPT because it considers the treaty to be discriminatory, and reasons are given for this point of view. However its stand for nuclear disarmament and disapproval of nuclear proliferation are declared. Nuclear arms race, prevention of nuclear war, and nuclear disarmament are also considered. (UK)

Hydrogen sulfide lowers proliferation and induces protective autophagy in colon epithelial cells.

Directory of Open Access Journals (Sweden)

Ya C Wu

Full Text Available Hydrogen sulfide (H(2S is a gaseous bacterial metabolite that reaches high levels in the large intestine. In the present study, the effect of H(2S on the proliferation of normal and cancerous colon epithelial cells was investigated. An immortalized colon epithelial cell line (YAMC and a panel of colon cancer cell lines (HT-29, SW1116, HCT116 were exposed to H(2S at concentrations similar to those found in the human colon. H(2S inhibited normal and cancerous colon epithelial cell proliferation as measured by MTT assay. The anti-mitogenic effect of H(2S was accompanied by G(1-phase cell cycle arrest and the induction of the cyclin-dependent kinase inhibitor p21(Cip. Moreover, exposure to H(2S led to features characteristic of autophagy, including increased formation of LC3B(+ autophagic vacuoles and acidic vesicular organelles as determined by immunofluorescence and acridine orange staining, respectively. Abolition of autophagy by RNA interference targeting Vps34 or Atg7 enhanced the anti-proliferative effect of H(2S. Further mechanistic investigation revealed that H(2S stimulated the phosphorylation of AMP-activated protein kinase (AMPK and inhibited the phosphorylation of mammalian target of rapamycin (mTOR and S6 kinase. Inhibition of AMPK significantly reversed H(2S-induced autophagy and inhibition of cell proliferation. Collectively, we demonstrate that H(2S inhibits colon epithelial cell proliferation and induces protective autophagy via the AMPK pathway.

Analytical and functional similarity of Amgen biosimilar ABP 215 to bevacizumab.

Science.gov (United States)

Seo, Neungseon; Polozova, Alla; Zhang, Mingxuan; Yates, Zachary; Cao, Shawn; Li, Huimin; Kuhns, Scott; Maher, Gwendolyn; McBride, Helen J; Liu, Jennifer

ABP 215 is a biosimilar product to bevacizumab. Bevacizumab acts by binding to vascular endothelial growth factor A, inhibiting endothelial cell proliferation and new blood vessel formation, thereby leading to tumor vasculature normalization. The ABP 215 analytical similarity assessment was designed to assess the structural and functional similarity of ABP 215 and bevacizumab sourced from both the United States (US) and the European Union (EU). Similarity assessment was also made between the US- and EU-sourced bevacizumab to assess the similarity between the two products. The physicochemical properties and structural similarity of ABP 215 and bevacizumab were characterized using sensitive state-of-the-art analytical techniques capable of detecting small differences in product attributes. ABP 215 has the same amino acid sequence and exhibits similar post-translational modification profiles compared to bevacizumab. The functional similarity assessment employed orthogonal assays designed to interrogate all expected biological activities, including those known to affect the mechanisms of action for ABP 215 and bevacizumab. More than 20 batches of bevacizumab (US) and bevacizumab (EU), and 13 batches of ABP 215 representing unique drug substance lots were assessed for similarity. The large dataset allows meaningful comparisons and garners confidence in the overall conclusion for the analytical similarity assessment of ABP 215 to both US- and EU-sourced bevacizumab. The structural and purity attributes, and biological properties of ABP 215 are demonstrated to be highly similar to those of bevacizumab.

Influence of chitosan-chitin nanofiber composites on cytoskeleton structure and the proliferation of rat bone marrow stromal cells.

Science.gov (United States)

Kiroshka, Victoria V; Petrova, Valentina A; Chernyakov, Daniil D; Bozhkova, Yulia O; Kiroshka, Katerina V; Baklagina, Yulia G; Romanov, Dmitry P; Kremnev, Roman V; Skorik, Yury A

2017-01-01

Chitosan scaffolds have gained much attention in various tissue engineering applications, but the effect of their microstructure on cell-material spatial interactions remains unclear. Our objective was to evaluate the effect of chitosan-based matrices doping with chitin nano-whiskers (CNW) on adhesion, spreading, cytoskeleton structure, and proliferation of rat bone marrow stromal cells (BMSCs). The behavior of BMSCs during culture on chitosan-CNW films was determined by the molecular mass, hydrophobicity, porosity, crosslinking degree, protonation degree and molecular structure of the composite chitosan-CNW films. The shape, spreading area, cytoskeleton structure, and proliferation of BMSCs on chitosan matrices with a crystalline structure and high porosity were similar to that observed for BMSCs cultured on polystyrene tissue culture plates. The amorphous polymer structure and high swelling led to a decrease in the spreading area and cell proliferation. Thus, we can control the behavior of cells in culture (adhesion, spreading, and proliferation) by changing the physico-chemical properties of the chitosan-CNW films.

Monitoring in real time the effect of TLX overexpression on proliferation and migration of C6 cells.

Science.gov (United States)

Li, G L; Fang, S H; Xu, B

2017-01-01

Orphan nuclear receptor TLX has been shown to play an essential role in regulating the self-renewal and proliferation of neural stem cells (NSCs). However, TLX overexpression in NSCs induces long-term NSC expansion and further leads to glioma initiation in mouse when combined with p53 mutations. Whether overexpression of TLX plays a role in glioma stem cell (GSC) proliferation and migration still remains largely unknown. In this study, we infected C6 cells, a special glioma cell line which is mainly composed of cancer stem cells(CSCs), with lentiviruses expressing GFP(LV-GFP) or GFP-T2A-TLX(LV-TLX) and then monitored cell proliferation and migration using the real-time analyzer system (RTCA, xCELLigence, Roche). We found that the cell index (CI) observed for the TLX overexpressing C6 cells showed a lower value than that of the LV-GFP transduced cells. And the MTT results correlated highly with the RTCA proliferation assessments. Furthermore, the expression of p21 was decreased while other downstream genes PTEN and p53 were not significantly changed in TLX overexpressing C6 cells . These findings strongly indicate that TLX overexpression has the ability to decrease the proliferating and migratory properties of C6 cells by targeting p21. Further, our results suggest that TLX overexpression may also have a similar inhibitory effect on GSC proliferation and migration.

A comparison of cell proliferation in normal and neoplastic intestinal epithelia following either biogenic amine depletion or monoamine oxidase inhibition.

Science.gov (United States)

Tutton, P J; Barkla, D H

1976-08-11

Epithelial cell proliferation was studied in the jejunum and in the colon of normal rats, in the colon of dimethylhydrazine-treated rats and in dimethylhydrazine-induced adenocarcinoma of the colon using a stathmokinetic technique. Estimates of cell proliferation rates in these four tissues were then repeated in animals which had been depleted of biogenic animes by treatment with reserpine and in animals whose monoamine oxidase was inhibited by treatment with nialamide. In amine-depleted animals cell proliferation essentially ceased in all four tissues examined. Inhibition of monoamine oxidase did not significantly influence cell proliferation in nonmalignant tissues but accelerated cell division in colonic tumours.

Nuclear energy and nuclear weapons proliferation

International Nuclear Information System (INIS)

1989-01-01

A summary of the report dispatched in the middle of 1978 by the Atlantic Council of United States, organized by North American citizens, is presented. The report considers the relation between the production of nucleoelectric energy and the capacity of proliferation of nuclear weapons. The factors which affect the grade of proliferation risk represented by the use of nuclear energy in the world comparing this risk with the proliferation risks independently of nuclear energy, are examined. (M.C.K.) [pt

Nuclear proliferation and safeguards. Summary

International Nuclear Information System (INIS)

1982-03-01

This comprehensive analysis of the technological, economic, and political factors affecting the potential spread of nuclear weapons proved useful in the congressional debate which culminated in the Nuclear Non-Proliferation Act of 1978. The report was subsequently published commercially and has been a frequently cited reference in the literature on proliferation and nuclear power. Despite developments since 1977, the information in the OTA report is still useful to those wishing to obtain an indepth understanding of the issues. Included is an analysis of why a nation might want nuclear weapons development program and the various sources of nuclear material are discussed. The control of proliferation is considered as well as its relation to the nuclear industry

Israel's position on non-proliferation

International Nuclear Information System (INIS)

Marom, R.

1986-01-01

Israel maintained that the complex international system and worldwide political tension created a situation in which comprehensive plans of disarmament could not produce any positive result. The deadlock in the field of general and complete disarmament has brought Israel to the realization that one possible way to alleviate the stalemate could be progress by stages through partial measures of disarmament. Israel's position on non-proliferation indicates that the establishment of a nuclear-weapon-free-zone (NWFZ), as it relates to the Middle-East, could serve as a credible alternative to the unilateral adherence to the Non-Proliferation of Nuclear Weapon (NPT) and an effective measure of non-proliferation in the region. (Author)

Nuclear exports and non-proliferation

International Nuclear Information System (INIS)

Courteix, Simone.

1978-01-01

Increased preoccupation in present times with the risk of proliferation of nuclear weapons is reflected in the multiplication of international agreements such as the Non-proliferation Treaty and in the strengthening of consultations between industrialised countries (London Club). After analysing the IAEA safeguards system under the Non-proliferation Treaty and its shortcomings both technically and otherwise, the author considers how this situation can be remedied in the light of the London Agreements and in view of the position of the main countries concerned. The annex to the book contains the texts of many international agreements and relevant national regulations as well as nuclear policy statements. It also includes a detailed bibliograaphy. (NEA) [fr

Oesophageal epithelial cell proliferation and food consumption patterns following irradiation

International Nuclear Information System (INIS)

Burholt, D.R.

1986-01-01

The murine data presented illustrate the influence of food consumption on the proliferative rate of the oesophageal epithelium during recovery from radiation damage. Refeeding at a time before the initiation of the normal hyperplastic response results in a decreased time interval between treatment and increased rates of cell proliferation, while reduced food consumption during the normal period of hyperproliferation results in reduced proliferative activity. The finding that recovery kinetics may be altered by changing food consumption patterns should be an important consideration in the analysis of antineoplastic agent-induced proliferative perturbations, as many treatments themselves produce reduced levels of food consumption. (UK)

Targeting cyclin B1 inhibits proliferation and sensitizes breast cancer cells to taxol

International Nuclear Information System (INIS)

Androic, Ilija; Krämer, Andrea; Yan, Ruilan; Rödel, Franz; Gätje, Regine; Kaufmann, Manfred; Strebhardt, Klaus; Yuan, Juping

2008-01-01

Cyclin B1, the regulatory subunit of cyclin-dependent kinase 1 (Cdk1), is essential for the transition from G2 phase to mitosis. Cyclin B1 is very often found to be overexpressed in primary breast and cervical cancer cells as well as in cancer cell lines. Its expression is correlated with the malignancy of gynecological cancers. In order to explore cyclin B1 as a potential target for gynecological cancer therapy, we studied the effect of small interfering RNA (siRNA) on different gynecological cancer cell lines by monitoring their proliferation rate, cell cycle profile, protein expression and activity, apoptosis induction and colony formation. Tumor formation in vivo was examined using mouse xenograft models. Downregulation of cyclin B1 inhibited proliferation of several breast and cervical cancer cell lines including MCF-7, BT-474, SK-BR-3, MDA-MB-231 and HeLa. After combining cyclin B1 siRNA with taxol, we observed an increased apoptotic rate accompanied by an enhanced antiproliferative effect in breast cancer cells. Furthermore, control HeLa cells were progressively growing, whereas the tumor growth of HeLa cells pre-treated with cyclin B1 siRNA was strongly inhibited in nude mice, indicating that cyclin B1 is indispensable for tumor growth in vivo. Our data support the notion of cyclin B1 being essential for survival and proliferation of gynecological cancer cells. Concordantly, knockdown of cyclin B1 inhibits proliferation in vitro as well as in vivo. Moreover, targeting cyclin B1 sensitizes breast cancer cells to taxol, suggesting that specific cyclin B1 targeting is an attractive strategy for the combination with conventionally used agents in gynecological cancer therapy

Director`s series on proliferation

Energy Technology Data Exchange (ETDEWEB)

Bailey, K.C.; Price, M.E. [eds.

1995-11-17

This is an occasional publication of essays on the topics of nuclear, chemical, biological, and missile proliferation. The views represented are those of the author`s. Essay topics include: Nuclear Proliferation: Myth and Reality; Problems of Enforcing Compliance with Arms Control Agreements; The Unreliability of the Russian Officer Corps: Reluctant Domestic Warriors; and Russia`s Nuclear Legacy.

Quantifying rates of cell migration and cell proliferation in co-culture barrier assays reveals how skin and melanoma cells interact during melanoma spreading and invasion.

Science.gov (United States)

Haridas, Parvathi; Penington, Catherine J; McGovern, Jacqui A; McElwain, D L Sean; Simpson, Matthew J

2017-06-21

Malignant spreading involves the migration of cancer cells amongst other native cell types. For example, in vivo melanoma invasion involves individual melanoma cells migrating through native skin, which is composed of several distinct subpopulations of cells. Here, we aim to quantify how interactions between melanoma and fibroblast cells affect the collective spreading of a heterogeneous population of these cells in vitro. We perform a suite of circular barrier assays that includes: (i) monoculture assays with fibroblast cells; (ii) monoculture assays with SK-MEL-28 melanoma cells; and (iii) a series of co-culture assays initiated with three different ratios of SK-MEL-28 melanoma cells and fibroblast cells. Using immunostaining, detailed cell density histograms are constructed to illustrate how the two subpopulations of cells are spatially arranged within the spreading heterogeneous population. Calibrating the solution of a continuum partial differential equation to the experimental results from the monoculture assays allows us to estimate the cell diffusivity and the cell proliferation rate for the melanoma and the fibroblast cells, separately. Using the parameter estimates from the monoculture assays, we then make a prediction of the spatial spreading in the co-culture assays. Results show that the parameter estimates obtained from the monoculture assays lead to a reasonably accurate prediction of the spatial arrangement of the two subpopulations in the co-culture assays. Overall, the spatial pattern of spreading of the melanoma cells and the fibroblast cells is very similar in monoculture and co-culture conditions. Therefore, we find no clear evidence of any interactions other than cell-to-cell contact and crowding effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

The non-proliferation regime, vertical proliferation and the interests of the Federal Republic of Germany

International Nuclear Information System (INIS)

Fischer, W.

1988-12-01

The disarmament orientation of the NPT, which stands beside the central aim of avoiding horizontal proliferation, raises a question: Does a compatibility exist between the non-proliferation policy of the Federal Republic and its security policy, which has its basic pillar in the nuclear deterrence strategy? Critics of this deterrence policy therefore, hinting to the disarmament determination of the NPT, demand that the Federal Republic should exercise its influence for the conclusion of a 'Comprehensive Test Ban Treaty' (CTBT), the establishment of a 'Nuclear-Weapons-Free-Zones' (NWFZ) in Europe, a 'No First Use'-Treaty (NFU) and finally the abolishment of all atomic weapons ('Zero Solution'). According to them such disarmament 'remedies' can reestablish or assure the waning or damaged international consensus for horizontal non-proliferation. This is a contribution for the establishment of a stable world order and will smooth the way for a prolongation of the NPT in the year 1995. An analysis of the history and the structure of interests shows that the policy of the Federal Republic of Germany is deeply rooted in the NPT and that a prolongation of the treaty and its own membership is a substantial object of the foreign and security policy. Consequently the Federal Republic has to face the demands for an intensification of 'anti-nuclear measures' and has to examine their acceptability and their usefulness with respect to non-proliferation. The structure of the problem encloses the following aspects: The security conception of the Federal Republic with its military-strategic essence; the provisions in article VI NPT for negotiations with the object of a world free of atomic weapons; the derived disarmament 'remedies' for strengthening the consensus for horizontal non-proliferation and, finally, the real interface between horizontal and vertical proliferation. (orig./DG) [de

Position paper on nuclear proliferation issues preventing nuclear proliferation. A duty for the nuclear community

Energy Technology Data Exchange (ETDEWEB)

Goldschmidt, Pierre; Bonin, Bernard [ENS High Scientific Council, Brussels (Belgium)

2010-06-15

The production of electricity from nuclear power plants is widely seen today as having an increasing role to play in meeting global energy requirements in a sustainable manner. Conscious of the inherently sensitive nature of nuclear technology and materials the ENS-HSC (European Nuclear Society - High Scientific Council) is well aware that a severe safety, security, environmental or proliferation mishap stemming from nuclear energy anywhere in the world would undermine the potential for nuclear energy to contribute to the global energy supply and the minimization of harmful carbon emissions. While the safety of nuclear power plants has continuously improved over the last three decades, the same degree of success cannot be claimed when it comes to the achievements of the international community in stemming the risk of nuclear weapons proliferation. This unfortunate situation is due to both technical and political reasons. The European nuclear industry is committed to the exclusively peaceful use of nuclear energy and to export nuclear facilities and related materials, equipment and technology solely in accordance with relevant national export laws and regulations, Nuclear Suppliers Group guidelines and pertinent United Nations Security Council Resolutions. The ENS-HSC considers that, as a manifestation of their strong commitment to nonproliferation, it is important for the nuclear industry to pay special attention to and promote proliferation-resistant designs and to take IAEA safeguards requirements into account at the design stage. Preventing nuclear proliferation is primarily the responsibility of states but, as major stakeholders, the nuclear industry and scientific community should actively support nuclear disarmament as foreseen in the Non-Proliferation Treaty and measures necessary to strengthen the non-proliferation regime, particularly the international control of the flux of nuclear material and technology. (orig.)

Position paper on nuclear proliferation issues preventing nuclear proliferation. A duty for the nuclear community

International Nuclear Information System (INIS)

Goldschmidt, Pierre; Bonin, Bernard

2010-01-01

The production of electricity from nuclear power plants is widely seen today as having an increasing role to play in meeting global energy requirements in a sustainable manner. Conscious of the inherently sensitive nature of nuclear technology and materials the ENS-HSC (European Nuclear Society - High Scientific Council) is well aware that a severe safety, security, environmental or proliferation mishap stemming from nuclear energy anywhere in the world would undermine the potential for nuclear energy to contribute to the global energy supply and the minimization of harmful carbon emissions. While the safety of nuclear power plants has continuously improved over the last three decades, the same degree of success cannot be claimed when it comes to the achievements of the international community in stemming the risk of nuclear weapons proliferation. This unfortunate situation is due to both technical and political reasons. The European nuclear industry is committed to the exclusively peaceful use of nuclear energy and to export nuclear facilities and related materials, equipment and technology solely in accordance with relevant national export laws and regulations, Nuclear Suppliers Group guidelines and pertinent United Nations Security Council Resolutions. The ENS-HSC considers that, as a manifestation of their strong commitment to nonproliferation, it is important for the nuclear industry to pay special attention to and promote proliferation-resistant designs and to take IAEA safeguards requirements into account at the design stage. Preventing nuclear proliferation is primarily the responsibility of states but, as major stakeholders, the nuclear industry and scientific community should actively support nuclear disarmament as foreseen in the Non-Proliferation Treaty and measures necessary to strengthen the non-proliferation regime, particularly the international control of the flux of nuclear material and technology. (orig.)

Cell proliferation and apoptosis in rat mammary glands following combinational exposure to bisphenol A and genistein

International Nuclear Information System (INIS)

Wang, Jun; Jenkins, Sarah; Lamartiniere, Coral A

2014-01-01

Humans are exposed to an array of both harmful and beneficial hormonally active compounds in the environment and through diet. Two such chemicals are Bisphenol A (BPA), a plasticizer, and genistein, a component of soy. Prepubertal exposure to BPA increased mammary carcinogenesis, while genistein suppressed cancer in a chemically-induced model of rodent mammary cancer. The purpose of this research was to determine the effects of combinational exposure to genistein and BPA on cell proliferation, apoptosis, and associated proteins as markers of cancer in mammary glands of rats exposed prepubertally to these environmental chemicals. Prepubertal rats (postpartum days (PND) 2–20) were exposed through lactation via nursing dams treated orally with sesame oil (SO), BPA, genistein, or a combination of BPA and genistein (BPA + Gen). Cell proliferation, apoptosis and protein expressions were investigated for mechanistic studies in mammary glands of rats exposed to these environmental chemicals. Prepubertal exposure to genistein increased cell proliferation in mammary glands of PND21 rats, while BPA increased cell proliferation in adult (PND50) rats. Prepubertal combinational exposure to BPA + Gen increased cell proliferation and reduced apoptosis in PND21 rats, but reduced cell proliferation and increased apoptosis in PND50 rats. The altered mechanisms behind these cellular responses appear to be centered on differential protein expression of caspases, PARP, Bad, p21, Akts, PTEN, ER-β and SRCs 1–3, in the rat mammary gland. Prepubertal BPA exposure resulted in increased cell proliferation in mammary glands of PND50 rats, a process associated with increased risk of cancer development in a chemically-induced mammary cancer. On the other hand, genistein stimulated cell proliferation at PND21, a process that correlates with mammary gland maturation and chemoprevention. In contrast to single chemical exposure, combinational exposure to BPA + Gen performed most similarly to

Non-proliferation issues for the disposition of fissile materials using reactor alternatives

International Nuclear Information System (INIS)

Jaeger, C.D.; Duggan, R.A.; Tolk, K.M.

1996-01-01

The Department of Energy (DOE) is analyzing long-term storage imposition options for excess weapons-usable fissile materials. A number of the disposition alternatives are being considered which involve the use of reactors. The various reactor alternatives are all very similar and include front-end processes that could convert plutonium to a usable form for fuel fabrication, a MOX fuel fab facility, reactors to burn the MOX fuel and ultimate disposal of spent fuel in some geologic repository. They include existing, partially completed, advanced or evolutionary light water reactors and Canadian deuterium uranium (CANDU) reactors. In addition to the differences in the type of reactors, other variants on these alternatives are being evaluated to include the location and number of the reactors, the location of the mixed oxide (MOX) fabrication facility, the ownership of the facilities (private or government) and the colocation and/or separation of these facilities. All of these alternatives and their variants must be evaluated with respect to non-proliferation resistance. Both domestic and international safeguards support are being provided to DOE's Fissile Materials Disposition Program (FMDP) and includes such areas as physical protection, nuclear materials accountability and material containment and surveillance. This paper will focus on how the non-proliferation objective of reducing security risks and strengthening arms reduction will be accomplished and what some of the non-proliferation issues are for the reactor alternatives. Proliferation risk has been defined in terms of material form, physical environment, and the level of security and safeguards that is applied to the material. Metrics have been developed for each of these factors. The reactor alternatives will be evaluated with respect to these proliferation risk factors at each of the unit process locations in the alternative

Proliferation and mineralization ability of dental pulp cells derived from primary and permanent teeth

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Suttatip Kamolmatyakul

2011-04-01

Full Text Available The aims of this study were to compare the proliferation and mineralization ability of CFU-F selected dental pulp cellsderived from primary and permanent teeth. Those cells were isolated by enzyme digestion and analyzed for their colonyformingcapacity. The cell proliferation was measured by the MTT assay on day 1, day 7, and day14. Alizarin Red S stainingwas used to detect mineralized nodule formation of the cells on day 7, 14, 21, and 28. Proliferation of CFU-F selected pulpcells from primary teeth was significantly higher than that of CFU-F selected pulp cells from permanent teeth in all periods ofthe experiment. Upon cultured cells in mineralization inducing media, the mineralized nodules appeared as early as day 14 inCFU-F selected pulp cells from primary teeth and MG-63, whereas those of CFU-F selected pulp cells from permanent teethcan be found at day 21. On day 21 and day 28, the mineralized nodules of the CFU-F selected pulp cells from the primaryteeth group were more than those in the CFU-F selected pulp cells from the permanent teeth group. Mineralized noduleformation in the CFU-F selected pulp cells from the permanent teeth group appeared later and were less than those ofCFU-F selected pulp cells from primary teeth. However, mineralized nodules in CFU-F selected pulp cells from the permanentteeth group increased very fast after their appearance. Those results suggest that CFU-F selected pulp cells from primaryteeth had a higher proliferation rate and mineralization rate when compared to CFU-F selected pulp cells from permanentteeth.

Criteria for proliferation resistance of nuclear fuel cycle options

International Nuclear Information System (INIS)

Kiriyama, Eriko; Pickett, Susan; Suzuki, Tatsujiro

2000-01-01

In order to understand the concept of nuclear proliferation resistance, this paper examines the technical definitions of proliferation resistance. Although nuclear proliferation resistance is often included as one of the major goals of advanced reactor research and development, the criteria for nuclear proliferation resistance of nuclear fuel cycles is not defined clearly. The implied meaning of proliferation resistance was compared in proposals regarding the nuclear fuel cycle. Discrepancies amongst the proposals regarding the technical definition of proliferation resistance is found. While all these proposals indicate proliferation resistance, few clearly spell out exactly what criteria they are measuring themselves against. However we found there are also common feature in many proposals. They are; (1) Reduction of Pu, (2) Less separated Weapon Usable Materials, (3) Fewer steps, (4) Barrier for Weapon Usable Materials. Recognizing that there are numerous political and infrastructure measures that may also be taken to guard against proliferation risks, we have focused here on the definition of proliferation resistance in terms of technical characteristics. Another important conclusion is that in many proposals proliferation resistance is only one of the important criteria such as energy security, economical efficiency, and safety. (author)

Tumour alpha/beta ratios and dose-rate selection in brachytherapy

International Nuclear Information System (INIS)

Duchesne, G.M.

2003-01-01

Traditionally brachytherapy employed low dose rate (LDR) techniques. Recent adoption of high dose rate (HDR) applications, addressing radiation protection concerns, has sparked debate over possible reductions in therapeutic ratio. The radiobiological characteristics of two contrasting examples, prostate cancer and cervical cancer, are examined. Both in-vitro and clinical observations of prostate cancer suggest a low α/β ratio. Labelling indices are below 2.5%, translating into long potential doubling times (Tpot ) of 16 to 61 days or more. Clinical PSA doubling times are in the order of years. Analysis of clinical endpoints in prostate cancer treated with either LDR or HDR techniques indicates that its α/β ratio may lie between 1 - 4 Gy, similar to slowly proliferating late reacting tissues. As such, therapeutic gain may arise from the use of hypofractionated HDR treatments, exploiting the sensitivity to large fraction sizes, effectively escalating dose. The slow proliferative rate also gives credence to the use of LDR, although several tumour doublings may occur during the effective treatment time, and analysis of the clinical data using a low α/β ratio suggests that LDR doses are only equivalent to 70 Gy with conventional fractionation. Cervical carcinoma is a rapidly proliferating tumour with Tpot values of 3-6 days. LDR implants were delivered over relatively short treatment times, negating repopulation effects, and the 'hyperfractionation' effect of LDR was suited to the high α/β ratio. HDR, although also preventing significant repopulation, has the potential to decrease the therapeutic ratio if low α/β , late-reacting tissues are not protected. Clinical data however show improved outcomes and reduced morbidity with HDR through reduced doses to normal tissues. Choosing the optimal dose rate in brachytherapy depends on tumour behaviour and achievable accuracy. HDR offers some advantages even for high α/β ratio tumours, and may be the technique of

Proliferation zones in the axolotl brain and regeneration of the telencephalon

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Maden Malcolm

2013-01-01

located within the ventricular zone of the axolotl brain. Variable rates of proliferation were detected across brain regions. These neural progenitor cells appear to mediate telencephalic tissue regeneration through an injury-induced olfactory cue. Identification of this cue is our future goal.

Successful Immunosuppressive Therapy for Severe Infectious Mononucleosis in a Patient with Clonal Proliferation of EBV-infected CD8-positive Cells.

Science.gov (United States)

Hosoi, Hiroki; Sonoki, Takashi; Murata, Shogo; Mushino, Toshiki; Kuriyama, Kodai; Nishikawa, Akinori; Hanaoka, Nobuyoshi; Ohshima, Koichi; Imadome, Ken-Ichi; Nakakuma, Hideki

2015-01-01

A 30-year-old woman was diagnosed with severe infectious mononucleosis (IM). The Epstein-Barr virus (EBV) had infected both CD19- and CD8-positive cells, and clonal proliferation of EBV-infected cells and T-cells was detected. Although we suspected malignant lymphoma, her condition improved following immunosuppressive therapy. A similar case was recently reported; therefore, this case is the second case of IM with EBV-infected CD8-positive cells and clonal proliferation of EBV-infected cells. Our results demonstrate that the clonal proliferation of EBV-infected cells is not always an indication for chemotherapy in the primary infection phase and that monitoring the EBV viral load is useful for therapeutic decision-making.

The effects of radiofrequency fields on cell proliferation are non-thermal.

Science.gov (United States)

Velizarov, S; Raskmark, P; Kwee, S

1999-02-01

The number of reports on the effects induced by radiofrequency (RF) electromagnetic fields and microwave (MW) radiation in various cellular systems is still increasing. Until now no satisfactory mechanism has been proposed to explain the biological effects of these fields. One of the current theories is that heat generation by RF/MW is the cause, in spite of the fact that a great number of studies under isothermal conditions have reported significant cellular changes after exposure to RF/MW. Therefore, this study was undertaken to investigate which effect MW radiation from these fields in combination with a significant change of temperature could have on cell proliferation. The experiments were performed on the same cell line, and with the same exposure system as in a previous work [S. Kwee, P. Raskmark, Changes in cell proliferation due to environmental non-ionizing radiation: 2. Microwave radiation, Bioelectrochem. Bioenerg., 44 (1998), pp. 251-255]. The field was generated by signal simulation of the Global System for Mobile communications (GSM) of 960 MHz. Cell cultures, growing in microtiter plates, were exposed in a specially constructed chamber, a Transverse Electromagnetic (TEM) cell. The Specific Absorption Rate (SAR) value for each cell well was calculated for this exposure system. However, in this study the cells were exposed to the field at a higher or lower temperature than the temperature in the field-free incubator i.e., the temperature in the TEM cell was either 39 or 35 +/- 0.1 degrees C. The corresponding sham experiments were performed under exactly the same experimental conditions. The results showed that there was a significant change in cell proliferation in the exposed cells in comparison to the non-exposed (control) cells at both temperatures. On the other hand, no significant change in proliferation rate was found in the sham-exposed cells at both temperatures. This shows that biological effects due to RF/MW cannot be attributed only to a

Leukemia inhibitory factor increases the proliferation of human endometrial stromal cells and expression of genes related to pluripotency

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Mojdeh Salehnia

2017-08-01

Full Text Available Background: Concerning the low population of human endometrial mesenchymal cells within the tissue and their potential application in the clinic and tissue engineering, some researches have been focused on their in vitro expansion. Objective: The aim of this study was to evaluate the effect of leukemia inhibitory factor (LIF as a proliferative factor on the expansion and proliferation of human endometrial stromal cells. Materials and Methods: In this experimental study, the isolated and cultured human endometrial stromal cells from women at ovulatory phase aged 20-35 years, after fourth passage were divided into control and LIF-treated groups. In the experimental group, the endometrial cells were treated by 10 ng/ml LIF in culture media and the cultured cells without adding LIF considered as control group. Both groups were evaluated and compared for proliferation rate using MTT assay, for CD90 marker by flow cytometric analysis and for the expression of Oct4, Nanog, PCNA and LIFr genes using real-time RT-PCR. Results: The proliferation rate of control and LIF-treated groups were 1.17±0.17 and 1.61±0.06 respectively and there was a significant increase in endometrial stromal cell proliferation following in vitro treatment by LIF compared to control group (p=0.049. The rate of CD90 positive cells was significantly increased in LIFtreated group (98.96±0.37% compared to control group (94.26±0.08% (p=0.0498. Also, the expression ratio of all studied genes was significantly increased in the LIFtreated group compared to control group (p=0.0479. Conclusion: The present study showed that LIF has a great impact on proliferation, survival, and maintenance of pluripotency of human endometrial stromal cells and it could be applicable in cell therapies.

Random mtDNA mutations modulate proliferation capacity in mouse embryonic fibroblasts

International Nuclear Information System (INIS)

Kukat, Alexandra; Edgar, Daniel; Bratic, Ivana; Maiti, Priyanka; Trifunovic, Aleksandra

2011-01-01

Highlights: → Increased mtDNA mutations in MEFs lead to high level of spontaneous immortalization. → This process is independent of endogenous ROS production. → Aerobic glycolysis significantly contributes to spontaneous immortalization of MEFs. -- Abstract: An increase in mtDNA mutation load leads to a loss of critical cells in different tissues thereby contributing to the physiological process of organismal ageing. Additionally, the accumulation of senescent cells that display changes in metabolic function might act in an active way to further disrupt the normal tissue function. We believe that this could be the important link missing in our understanding of the molecular mechanisms of premature ageing in the mtDNA mutator mice. We tested proliferation capacity of mtDNA mutator cells in vitro. When cultured in physiological levels of oxygen (3%) their proliferation capacity is somewhat lower than wild-type cells. Surprisingly, in conditions of increased oxidative stress (20% O 2 ) mtDNA mutator mouse embryonic fibroblasts exhibit continuous proliferation due to spontaneous immortalization, whereas the same conditions promote senescence in wild-type cells. We believe that an increase in aerobic glycolysis observed in mtDNA mutator mice is a major mechanism behind this process. We propose that glycolysis promotes proliferation and allows a fast turnover of metabolites, but also leads to energy crisis due to lower ATP production rate. This could lead to compromised replication and/or repair and therefore, in rare cases, might lead to mutations in tumor suppressor genes and spontaneous immortalization.

Inosine Released from Dying or Dead Cells Stimulates Cell Proliferation via Adenosine Receptors

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Yi Zhao

2017-04-01

Full Text Available IntroductionMany antitumor therapies induce apoptotic cell death in order to cause tumor regression. Paradoxically, apoptotic cells are also known to promote wound healing, cell proliferation, and tumor cell repopulation in multicellular organisms. We aimed to characterize the nature of the regenerative signals concentrated in the micromilieu of dead and dying cells.MethodsCultures of viable melanoma B16F10 cells, mouse fibroblasts, and primary human fibroblast-like synoviocytes (FLS in the presence of dead and dying cells, their supernatants (SNs, or purified agonists and antagonists were used to evaluate the stimulation of proliferation. Viable cell quantification was performed by either flow cytometry of harvested cells or by crystal violet staining of adherent cells. High-performance liquid chromatography and liquid chromatography coupled with mass spectrometry of cell SNs were deployed to identify the nature of growth-promoting factors. Coimplantation of living cells in the presence of SNs collected from dead and dying cells and specific agonists was used to evaluate tumor growth in vivo.ResultsThe stimulation of proliferation of few surviving cells by bystander dead cells was confirmed for melanoma cells, mouse fibroblasts, and primary FLS. We found that small soluble molecules present in the protein-free fraction of SNs of dead and dying cells were responsible for the promotion of proliferation. The nucleoside inosine released by dead and dying cells acting via adenosine receptors was identified as putative inducer of proliferation of surviving tumor cells after irradiation and heat treatment.ConclusionInosine released by dead and dying cells mediates tumor cell proliferation via purinergic receptors. Therapeutic strategies surmounting this pathway may help to reduce the rate of recurrence after radio- and chemotherapy.

Oxidative stress induced pulmonary endothelial cell proliferation is ...

African Journals Online (AJOL)

Cellular hyper-proliferation, endothelial dysfunction and oxidative stress are hallmarks of the pathobiology of pulmonary hypertension. Indeed, pulmonary endothelial cells proliferation is susceptible to redox state modulation. Some studies suggest that superoxide stimulates endothelial cell proliferation while others have ...

Comparative analysis of cell proliferation ratio in plaque and erosive oral lichen planus: An immunohistochemical study

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C Pramod Redder

2014-01-01

Full Text Available Background: Proliferating cell nuclear antigen (PCNA is a nuclear protein synthesized in the late G1 and S-phase of the cell cycle. Detection of this protein represents a useful marker of the proliferation status of lesions. This study has been carried out to evaluate the cell proliferation rate in oral lichen planus (OLP and comparison between plaque and erosive lichen planus, which indicates the potential for malignant transformation. Materials and Methods: This study was comprised of 64 cases of histologically proven lichen planus, out of which 32 cases of plaque and erosive each was taken. Two sections were taken from each, one for H and E staining to verify histological diagnosis according to Eisenberg criteria, other sections were stained according to super sensitive polymer horse radish peroxidise method for identifying immunohistochemical expression of PCNA. Data were statistically analyzed by Tukey high-range statistical domain test. Statistically significant P value was considered <0.05. Results: In two types of lichen planus, erosive type (66.86% showed higher expression of PCNA followed by plaque (17.07%. Overall, P value was <0.001, which was statistically significant. It indicates that proliferation activity is more in erosive lichen planus followed by plaque type, which ultimately results in increased rate of malignant transformation. Conclusion: PCNA is a good nuclear protein marker to evaluate the proliferation status of OLP. Out of the two types of lichen planus, erosive type possesses more proliferative ratio and chances of malignant change is more in this type. It emphasizes the importance of long-term follow-up with erosive type when compared with plaque type.

Pueraria mirifica inhibits 17β-estradiol-induced cell proliferation of human endometrial mesenchymal stem cells.

Science.gov (United States)

Lin, Ta-Chin; Wang, Kai-Hung; Kao, An-Pei; Chuang, Kuo-Hsiang; Kuo, Tsung-Cheng

2017-12-01

The notion that the human endometrium may contain a population of stem cells has recently been proposed. The mesenchymal stem cells (MSCs) in the endometrium are believed to be responsible for the remarkable regenerative ability of endometrial cells. Estrogens influence the physiological and pathological processes of several hormone-dependent tissues, such as the endometrium. Pueraria mirifica (PM) is a herbal plant that contains several phytoestrogens, including isoflavones, lignans, and coumestans, and is known to exert an estrogenic effect on animal models. The present study investigated the effects of PM on the proliferation of human endometrial MSCs (hEN-MSCs). The hEN-MSCs were isolated from human endometrial tissue. The surface markers of these hEN-MSCs were identified through reverse transcription-polymerase chain reaction analysis. The proliferation potential of hEN-MSCs was measured through a cell proliferation assay. Multilineage differentiation ability was confirmed through Oil red O and von Kossa staining. This study demonstrated that 17β-estradiol-responsive MSCs with Oct-4, CD90, and CD105 gene expression can be derived from the human endometrium and that PM exerts biological effects on hEN-MSCs, specifically, enhanced cell growth rate, through the estrogen receptor. Furthermore, PM at 1500 and 2000 μg/mL significantly increased cell proliferation compared with the vehicle control, and PM concentration at 1000 μg/mL significantly inhibited the enhanced cell growth rate induced by 17β-estradiol in hEN-MSCs. This study provides new insights into the possible biological effects of PM on the proliferation of hEN-MSCs. Copyright © 2017. Published by Elsevier B.V.

CXC chemokines function as a rheostat for hepatocyte proliferation and liver regeneration.

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Gregory C Wilson

Full Text Available Our previous in vitro studies have demonstrated dose-dependent effects of CXCR2 ligands on hepatocyte cell death and proliferation. In the current study, we sought to determine if CXCR2 ligand concentration is responsible for the divergent effects of these mediators on liver regeneration after ischemia/reperfusion injury and partial hepatectomy.Murine models of partial ischemia/reperfusion injury and hepatectomy were used to study the effect of CXCR2 ligands on liver regeneration.We found that hepatic expression of the CXCR2 ligands, macrophage inflammatory protein-2 (MIP-2 and keratinocyte-derived chemokine (KC, was significantly increased after both I/R injury and partial hepatectomy. However, expression of these ligands after I/R injury was 30-100-fold greater than after hepatectomy. Interestingly, the same pattern of expression was found in ischemic versus non-ischemic liver lobes following I/R injury with expression significantly greater in the ischemic liver lobes. In both systems, lower ligand expression was associated with increased hepatocyte proliferation and liver regeneration in a CXCR2-dependent fashion. To confirm that these effects were related to ligand concentration, we administered exogenous MIP-2 and KC to mice undergoing partial hepatectomy. Mice received a "high" dose that replicated serum levels found after I/R injury and a "low" dose that was similar to that found after hepatectomy. Mice receiving the "high" dose had reduced levels of hepatocyte proliferation and regeneration whereas the "low" dose promoted hepatocyte proliferation and regeneration.Together, these data demonstrate that concentrations of CXC chemokines regulate the hepatic proliferative response and subsequent liver regeneration.

Cyclooxygenase-2 Inhibition Enhances Proliferation of NKT Cells Derived from Patients with Laryngeal Cancer.

Science.gov (United States)

Klatka, Janusz; Grywalska, Ewelina; Hymos, Anna; Guz, Małgorzata; Polberg, Krzysztof; Roliński, Jacek; Stepulak, Andrzej

2017-08-01

The aim of this study was to analyze whether inhibition of cyclooxygenase-2 by celecoxib and the subsequent enhancement in the proliferation of natural killer T (NKT) cells could play a role in dendritic cell (DC)-based laryngeal cancer (LC) immunotherapy. Peripheral blood mononuclear cells were obtained from 48 male patients diagnosed with LC and 30 control patients without cancer disease. Neoplastic cell lysate preparations were made from cancer tissues obtained after surgery and used for in vitro DCs generation. NKT cells proliferation assay was performed based on 3 H-thymidine incorporation assay. An increased proliferation of NKT cells was obtained from control patients compared to NKT cells obtained from LC patients regardless of the type of stimulation or treatment. In the patient group diagnosed with LC, COX-2 inhibition resulted in a significantly enhanced proliferation of NKT cells when stimulated with autologous DCs than NKT cells stimulated with DCs without COX-2 inhibition. These correlations were not present in the control group. Higher proliferation rate of NKT cells was also observed in non-metastatic and highly differentiated LC, which was independent of the type of stimulation or treatment. COX-2 inhibition could be regarded as immunotherapy-enhancing tool in patients with LC. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Suspect filler similarity in eyewitness lineups: a literature review and a novel methodology.

Science.gov (United States)

Fitzgerald, Ryan J; Oriet, Chris; Price, Heather L

2015-02-01

Eyewitness lineups typically contain a suspect (guilty or innocent) and fillers (known innocents). The degree to which fillers should resemble the suspect is a complex issue that has yet to be resolved. Previously, researchers have voiced concern that eyewitnesses would be unable to identify their target from a lineup containing highly similar fillers; however, our literature review suggests highly similar fillers have only rarely been shown to have this effect. To further examine the effect of highly similar fillers on lineup responses, we used morphing software to create fillers of moderately high and very high similarity to the suspect. When the culprit was in the lineup, a higher correct identification rate was observed in moderately high similarity lineups than in very high similarity lineups. When the culprit was absent, similarity did not yield a significant effect on innocent suspect misidentification rates. However, the correct rejection rate in the moderately high similarity lineup was 20% higher than in the very high similarity lineup. When choosing rates were controlled by calculating identification probabilities for only those who made a selection from the lineup, culprit identification rates as well as innocent suspect misidentification rates were significantly higher in the moderately high similarity lineup than in the very high similarity lineup. Thus, very high similarity fillers yielded costs and benefits. Although our research suggests that selecting the most similar fillers available may adversely affect correct identification rates, we recommend additional research using fillers obtained from police databases to corroborate our findings.

In vitro proliferation of adult human beta-cells.

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Sabine Rutti

Full Text Available A decrease in functional beta-cell mass is a key feature of type 2 diabetes. Glucagon-like peptide 1 (GLP-1 analogues induce proliferation of rodent beta-cells. However, the proliferative capacity of human beta-cells and its modulation by GLP-1 analogues remain to be fully investigated. We therefore sought to quantify adult human beta-cell proliferation in vitro and whether this is affected by the GLP-1 analogue liraglutide.Human islets from 7 adult cadaveric organ donors were dispersed into single cells. Beta-cells were purified by FACS. Non-sorted cells and the beta-cell enriched ("beta-cells" population were plated on extracellular matrix from rat (804G and human bladder carcinoma cells (HTB9 or bovine corneal endothelial ECM (BCEC. Cells were maintained in culture+/-liraglutide for 4 days in the presence of BrdU.Rare human beta-cell proliferation could be observed either in the purified beta-cell population (0.051±0.020%; 22 beta-cells proliferating out of 84'283 beta-cells counted or in the non-sorted cell population (0.055±0.011%; 104 proliferating beta-cells out of 232'826 beta-cells counted, independently of the matrix or the culture conditions. Liraglutide increased human beta-cell proliferation on BCEC in the non-sorted cell population (0.082±0.034% proliferating beta-cells vs. 0.017±0.008% in control, p<0.05.These results indicate that adult human beta-cell proliferation can occur in vitro but remains an extremely rare event with these donors and particular culture conditions. Liraglutide increases beta-cell proliferation only in the non-sorted cell population and only on BCEC. However, it cannot be excluded that human beta-cells may proliferate to a greater extent in situ in response to natural stimuli.

EFFECT OF dbcAMP ON PROLIFERATION AND APOPTOSIS OF PORCINE GRANULOSA CELLS in vitro

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Richard Alexa

2013-02-01

Full Text Available Cyclic nucleotide cAMP and its target protein kinase A (PKA dependent intracellular mechanisms can play an important role in regulation of ovarian cell function and in mediating gonadotropin action on these cells. The aim of the present study was to examine the effect of cAMP analogue, dibutyryl cyclic adenosine monophosphate (dbcAMP (0; 0.1; 1 and 10 µg/ml or FSH (0; 0,01; 1 IU/ml on proliferation and apoptosis of porcine granulosa cells in vitro. Indices of cell apoptosis (expression of apoptotic peptide bax and proliferation (expression of proliferation-associated peptide PCNA within ovarian granulosa cells were analysed by immunocytochemistry. It was observed that accumulation of PCNA was increased by dbcAMP and FSH at all doses added. The occurrence of bax was also stimulated by dbcAMP after exposition (at 0,1 and 1 µg/ml, but not at dose 10 µg/ml and by FSH (at all doses added. The stimulatory effect of both dbcAMP and FSH on both ovarian cell apoptosis and proliferation suggest, that these substances may promote ovarian follicular cell turnover. The similarity of dbcAMP and FSH effect may indicate that FSH can affect ovarian functions via cAMP-dependent intracellular mechanisms. The present data may provide new tools to regulate human and animal reproductive processes via cAMP-dependent mechanisms.

Potential Effect of CD271 on Human Mesenchymal Stromal Cell Proliferation and Differentiation.

Science.gov (United States)

Calabrese, Giovanna; Giuffrida, Raffaella; Lo Furno, Debora; Parrinello, Nunziatina Laura; Forte, Stefano; Gulino, Rosario; Colarossi, Cristina; Schinocca, Luciana Rita; Giuffrida, Rosario; Cardile, Venera; Memeo, Lorenzo

2015-07-09

The Low-Affinity Nerve Growth Factor Receptor (LNGFR), also known as CD271, is a member of the tumor necrosis factor receptor superfamily. The CD271 cell surface marker defines a subset of multipotential mesenchymal stromal cells and may be used to isolate and enrich cells derived from bone marrow aspirate. In this study, we compare the proliferative and differentiation potentials of CD271+ and CD271- mesenchymal stromal cells. Mesenchymal stromal cells were isolated from bone marrow aspirate and adipose tissue by plastic adherence and positive selection. The proliferation and differentiation potentials of CD271+ and CD271- mesenchymal stromal cells were assessed by inducing osteogenic, adipogenic and chondrogenic in vitro differentiation. Compared to CD271+, CD271- mesenchymal stromal cells showed a lower proliferation rate and a decreased ability to give rise to osteocytes, adipocytes and chondrocytes. Furthermore, we observed that CD271+ mesenchymal stromal cells isolated from adipose tissue displayed a higher efficiency of proliferation and trilineage differentiation compared to CD271+ mesenchymal stromal cells isolated from bone marrow samples, although the CD271 expression levels were comparable. In conclusion, these data show that both the presence of CD271 antigen and the source of mesenchymal stromal cells represent important factors in determining the ability of the cells to proliferate and differentiate.

Upregulation of miR-3607 promotes lung adenocarcinoma proliferation by suppressing APC expression.

Science.gov (United States)

Lin, Yong; Gu, Qiangye; Sun, Zongwen; Sheng, Baowei; Qi, Congcong; Liu, Bing; Fu, Tian; Liu, Cun; Zhang, Yan

2017-11-01

Lung cancer is the leading cause of worldwide cancer-related deaths, although many drugs and new therapeutic approaches have been used, the 5-years survival rate is still low for lung cancer patients. microRNAs have been shown to regulate lung cancer initiation and development, here we studied the role of miR-3607 in lung cancer cell proliferation. We found miR-3607 was upregulated in lung cancer tissues and cells, miR-3607 overexpression promoted lung cancer cell A549 proliferation determined by MTT assay, colony formation assay, anchorage-independent growth ability assay and bromodeoxyuridine incorporation assay, while the opposite phenotypes were shown when miR-3607 was knocked down. Predicted analysis suggested a Wnt signaling pathway regulator adenomatous polyposis coli (APC) was the target of miR-3607, miR-3607 could directly bind to the 3'UTR of APC, and promoted Cyclin D1 and c-Myc expression which can be suppressed by APC. Double knockdown of miR-3607 and APC copied the phenotypes of miR-3607 overexpression, suggesting miR-3607 promoted lung cancer cell A549 proliferation by targeting APC. In conclusion, our study suggested miR-3607 contributes to lung cancer cell proliferation by inhibiting APC. Copyright © 2017. Published by Elsevier Masson SAS.

Information report on Proliferation geo-strategic stakes

International Nuclear Information System (INIS)

2009-11-01

This large report, notably based on interviews of many representatives of international institutions and politicians, ambassadors and researchers of different countries, all involved or specialized in nuclear and defence issues, starts with a description of the evolution of the international and geo-strategic context from the Cold War to a period of a new nuclear proliferation, with, in between, a period of stabilisation between the USA and the USSR. It also questions the various forms of proliferation which could be ballistic, biological, chemical, and cybernetic. Then, it analyses the role which mass destruction weapons have in international relationships, making a distinction between countries possessing such weapons (USA, Russia, China, France, Great-Britain), Israel which has been a newcomer for thirty years, the new actors (India, Pakistan, Iran, North Korea) with their own and different motivations, and the possible new actors (Libya, Syria). It comments the meaning of the ballistic threat and of the anti-missile defence. The third part of this report deals with the dissemination of proliferating technologies, describing the proliferation networks and the failure of actions against state-based proliferations, questioning the reality of the associated risks (discussion about the impact of September 11 attacks, about a chemical and biological terrorist threat which is realistic as well as difficult to be implemented, and about cybernetic attacks). The fourth part comments the impact of the international community on proliferation, outlining the different efficiencies of the international agreements and institutions (Chemical Weapons Convention, IAEA, Non Proliferation Treaty, Biological Weapons Convention, The Hague Code of Conduct), commenting the opportunities associated with other texts (those about nuclear free areas, or those produced by exporter groups), and discussing the attitude of the international community with respect to proliferation, and the

Targeting cyclin B1 inhibits proliferation and sensitizes breast cancer cells to taxol

Directory of Open Access Journals (Sweden)

Strebhardt Klaus

2008-12-01

Full Text Available Abstract Background Cyclin B1, the regulatory subunit of cyclin-dependent kinase 1 (Cdk1, is essential for the transition from G2 phase to mitosis. Cyclin B1 is very often found to be overexpressed in primary breast and cervical cancer cells as well as in cancer cell lines. Its expression is correlated with the malignancy of gynecological cancers. Methods In order to explore cyclin B1 as a potential target for gynecological cancer therapy, we studied the effect of small interfering RNA (siRNA on different gynecological cancer cell lines by monitoring their proliferation rate, cell cycle profile, protein expression and activity, apoptosis induction and colony formation. Tumor formation in vivo was examined using mouse xenograft models. Results Downregulation of cyclin B1 inhibited proliferation of several breast and cervical cancer cell lines including MCF-7, BT-474, SK-BR-3, MDA-MB-231 and HeLa. After combining cyclin B1 siRNA with taxol, we observed an increased apoptotic rate accompanied by an enhanced antiproliferative effect in breast cancer cells. Furthermore, control HeLa cells were progressively growing, whereas the tumor growth of HeLa cells pre-treated with cyclin B1 siRNA was strongly inhibited in nude mice, indicating that cyclin B1 is indispensable for tumor growth in vivo. Conclusion Our data support the notion of cyclin B1 being essential for survival and proliferation of gynecological cancer cells. Concordantly, knockdown of cyclin B1 inhibits proliferation in vitro as well as in vivo. Moreover, targeting cyclin B1 sensitizes breast cancer cells to taxol, suggesting that specific cyclin B1 targeting is an attractive strategy for the combination with conventionally used agents in gynecological cancer therapy.

Which future for the nuclear counter-proliferation?; Quel avenir pour la contre-proliferation nucleaire?

Energy Technology Data Exchange (ETDEWEB)

Duval, M

2004-10-01

After a recall of the permanent data about proliferation and of the safeguards implemented by the international community, the author demonstrates that proliferation has moved towards Asia where a real 'black market' has been created. Then he analyzes the consequences of this change on the future of nuclear deterrent. Finally, he expresses his nostalgia in front of this drift and worries about the future uselessness of the means devoted to this 'pacifying' strategy. (J.S.)

An Autocrine Proliferation Repressor Regulates Dictyostelium discoideum Proliferation and Chemorepulsion Using the G Protein-Coupled Receptor GrlH

OpenAIRE

Yu Tang; Yuantai Wu; Sarah E. Herlihy; Francisco J. Brito-Aleman; Jose H. Ting; Chris Janetopoulos; Richard H. Gomer; Scott D. Emr

2018-01-01

In eukaryotic microbes, little is known about signals that inhibit the proliferation of the cells that secrete the signal, and little is known about signals (chemorepellents) that cause cells to move away from the source of the signal. Autocrine proliferation repressor protein A (AprA) is a protein secreted by the eukaryotic microbe Dictyostelium discoideum. AprA is a chemorepellent for and inhibits the proliferation of D. discoideum. We previously found that cells sense AprA using G proteins...

Poisson-event-based analysis of cell proliferation.

Science.gov (United States)

Summers, Huw D; Wills, John W; Brown, M Rowan; Rees, Paul

2015-05-01

A protocol for the assessment of cell proliferation dynamics is presented. This is based on the measurement of cell division events and their subsequent analysis using Poisson probability statistics. Detailed analysis of proliferation dynamics in heterogeneous populations requires single cell resolution within a time series analysis and so is technically demanding to implement. Here, we show that by focusing on the events during which cells undergo division rather than directly on the cells themselves a simplified image acquisition and analysis protocol can be followed, which maintains single cell resolution and reports on the key metrics of cell proliferation. The technique is demonstrated using a microscope with 1.3 μm spatial resolution to track mitotic events within A549 and BEAS-2B cell lines, over a period of up to 48 h. Automated image processing of the bright field images using standard algorithms within the ImageJ software toolkit yielded 87% accurate recording of the manually identified, temporal, and spatial positions of the mitotic event series. Analysis of the statistics of the interevent times (i.e., times between observed mitoses in a field of view) showed that cell division conformed to a nonhomogeneous Poisson process in which the rate of occurrence of mitotic events, λ exponentially increased over time and provided values of the mean inter mitotic time of 21.1 ± 1.2 hours for the A549 cells and 25.0 ± 1.1 h for the BEAS-2B cells. Comparison of the mitotic event series for the BEAS-2B cell line to that predicted by random Poisson statistics indicated that temporal synchronisation of the cell division process was occurring within 70% of the population and that this could be increased to 85% through serum starvation of the cell culture. © 2015 International Society for Advancement of Cytometry.

Nuclear experts and nuclear weapons proliferation

International Nuclear Information System (INIS)

Mueller, H.

1979-01-01

In Germany the issue of nuclear weapons proliferation has attracted scant attention. Most potential nuclear weapon states are important trade partners of the FRG and, since further proliferation of nuclear weapons could worsen conflicts involving these, it should be in the FRG's interest to limit proliferation. The security of the FRG is also dependent on the common interest of the great powers to avoid nuclear war. The contradictory positions of Usa and the USSR on nuclear weapons policy regarding themselves and non-nuclear weapon states encourages less developed countries to see nuclear weaponry as useful. The NPT and IAEA safeguards have only limited inhibiting effect. The nuclear export policy of the FRG has been dominated by short term economic advantage, neglecting the negative long term effects of decreased political stability. The FRG should formulate a policy based on self-restraint, positive stimuli and extension of controls, using its economic strength to deter proliferation. (JIW)

Effects of voluntary exercise on the viability, proliferation and BDNF levels of bone marrow stromal cells in rat pups born from morphine- dependent mothers during pregnancy.

Science.gov (United States)

Haydari, Sakineh; Safari, Manouchehr; Zarbakhsh, Sam; Bandegi, Ahmad Reza; Miladi-Gorji, Hossein

2016-11-10

This study was designed to investigate whether free access to a running wheel during pregnancy in morphine-dependent mothers would influence the viability, proliferation and BDNF levels of bone marrow stromal cells in rat pups. Pregnant rats were made dependent by chronic administration of morphine in drinking water simultaneously with free access to a running wheel. Male pups are weaned at 21days of birth and their bones marrows were aspirated from the femurs and tibias and also the bone marrow stromal cells (BMSCs) cultured. MTT assay was used to determine cell viability and proliferation rate. The level of BDNF was measured in the supernant of BMSCs culture by ELISA. The sedentary morphine-dependent mothers' pups showed a significant increase in the percentage cell viability and proliferation rate and also a significant decrease in the BDNF protein levels in BMSCs. The rat pups borne from exercising the control and morphine-dependent mothers exhibited an increase in the percentage viability, proliferation rate and BDNF levels of the BMSCs. This study showed that maternal exercise during pregnancy in morphine-dependent and non-dependent mothers, with increasing of BDNF levels increased the proliferation and viability of BMSCs in the rat pups. Also, chronic administration of morphine during pregnancy was able to increase the proliferation and viability of BMSCs in the rat pups. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Density-dependent quiescence in glioma invasion: instability in a simple reaction–diffusion model for the migration/proliferation dichotomy

KAUST Repository

Pham, Kara

2012-01-01

Gliomas are very aggressive brain tumours, in which tumour cells gain the ability to penetrate the surrounding normal tissue. The invasion mechanisms of this type of tumour remain to be elucidated. Our work is motivated by the migration/proliferation dichotomy (go-or-grow) hypothesis, i.e. the antagonistic migratory and proliferating cellular behaviours in a cell population, which may play a central role in these tumours. In this paper, we formulate a simple go-or-grow model to investigate the dynamics of a population of glioma cells for which the switch from a migratory to a proliferating phenotype (and vice versa) depends on the local cell density. The model consists of two reaction-diffusion equations describing cell migration, proliferation and a phenotypic switch. We use a combination of numerical and analytical techniques to characterize the development of spatio-temporal instabilities and travelling wave solutions generated by our model. We demonstrate that the density-dependent go-or-grow mechanism can produce complex dynamics similar to those associated with tumour heterogeneity and invasion.

Intraepidermal proliferation of Merkel cells within a seborrheic keratosis: Merkel cell carcinoma in situ or Merkel cell hyperplasia?

Science.gov (United States)

McFalls, Jeanne; Okon, Lauren; Cannon, Sarah; Lee, Jason B

2017-05-01

Intradepidermal proliferation of Merkel cells without any dermal component has been interpreted as either a hyperplastic process secondary to chronic ultraviolet radiation or a neoplastic process, namely Merkel cell carcinoma (MCC) in situ. The recent criteria that have been proffered to diagnose MCC in situ, unfortunately, are identical to those that have been applied to Merkel cell hyperplasia in the past, posing a diagnostic quandary when faced with an intraepidermal proliferation of Merkel cells. Most previously reported cases of MCC in situ have occurred within associated epithelial lesion that includes solar (actinic) keratosis and squamous-cell carcinoma in situ. Similarly, Merkel cell hyperplasia has been reported to occur in association with a variety of epithelial lesions as well as on chronically sun-damaged skin. Herein, a case of an intraepidermal proliferation of Merkel cells within a seborrheic keratosis is presented accompanied by a discussion on whether the proliferation represents another case of Merkel cell carcinoma in situ or an incidental hyperplastic process on chronically sun-damaged skin. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Brand name confusion: Subjective and objective measures of orthographic similarity.

Science.gov (United States)

Burt, Jennifer S; McFarlane, Kimberley A; Kelly, Sarah J; Humphreys, Michael S; Weatherall, Kimberlee; Burrell, Robert G

2017-09-01

Determining brand name similarity is vital in areas of trademark registration and brand confusion. Students rated the orthographic (spelling) similarity of word pairs (Experiments 1, 2, and 4) and brand name pairs (Experiment 5). Similarity ratings were consistently higher when words shared beginnings rather than endings, whereas shared pronunciation of the stressed vowel had small and less consistent effects on ratings. In Experiment 3 a behavioral task confirmed the similarity of shared beginnings in lexical processing. Specifically, in a task requiring participants to decide whether 2 words presented in the clear (a probe and a later target) were the same or different, a masked prime word preceding the target shortened response latencies if it shared its initial 3 letters with the target. The ratings of students for word and brand name pairs were strongly predicted by metrics of orthographic similarity from the visual word identification literature based on the number of shared letters and their relative positions. The results indicate a potential use for orthographic metrics in brand name registration and trademark law. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

[Knockdown of NEDD9 inhibits the proliferation, invasion and migration of esophageal carcinoma EC109 cells].

Science.gov (United States)

Zhang, Wen; Li, Shaojun; Zhao, Yunlong; Guo, Nannan; Li, Yingjie

2016-12-01

Objective To observe the expression of the neural precursor cell expressed, developmentally down-regulated 9 (NEDD9) in esophageal cancer, to investigate the impact of decreased expression of NEDD9 on invasion and migration, and to explicit the function of NEDD9 in EC109 human esophageal cancer cell line. Methods Immunohistochemical staining was used to detect the expression of NEDD9 in human esophageal cancer tissues and paracancerous normal tissues. RNA interfering (RNAi) was used to knockdown NEDD9 in EC109 cells. The interference efficiency was detected by reverse transcription PCR (RT-PCR) and Western blot analysis. Cell proliferation was determined by MTT assay and the invasion and migration abilities of EC109 cells were monitored by Transwell TM assay. The protein levels of proliferating cell nuclear antigen (PCNA), Bax and Bcl-2 were tested by Western blotting. Results The positive expression rate of NEDD9 in esophageal carcinoma tissues was significantly higher compared with that in the paracancerous tissues. After NEDD9 expression was successfully downregulated in EC109 cells by siRNA, the proliferation, invasion and migration rates in transfection group were significantly lower than those in control group; meanwhile, the expression of Bcl-2 was reduced and Bax expression was enhanced. Conclusion The protein expression level of NEDD9 is higher in esophageal carcinoma tissues than that in adjacent normal tissues. Knockdown of NEDD9 expression can restrain the proliferation, invasion and migration of EC109 cells.

Comparative analysis of cell proliferation ratio in plaque and erosive oral lichen planus: An immunohistochemical study.

Science.gov (United States)

Redder, C Pramod; Pandit, Siddharth; Desai, Dinkar; Kandagal, V Suresh; Ingaleshwar, Pramod S; Shetty, Sharan J; Vibhute, Nupura

2014-05-01

Proliferating cell nuclear antigen (PCNA) is a nuclear protein synthesized in the late G1 and S-phase of the cell cycle. Detection of this protein represents a useful marker of the proliferation status of lesions. This study has been carried out to evaluate the cell proliferation rate in oral lichen planus (OLP) and comparison between plaque and erosive lichen planus, which indicates the potential for malignant transformation. This study was comprised of 64 cases of histologically proven lichen planus, out of which 32 cases of plaque and erosive each was taken. Two sections were taken from each, one for H and E staining to verify histological diagnosis according to Eisenberg criteria, other sections were stained according to super sensitive polymer horse radish peroxidise method for identifying immunohistochemical expression of PCNA. Data were statistically analyzed by Tukey high-range statistical domain test. Statistically significant P value was considered lichen planus, erosive type (66.86%) showed higher expression of PCNA followed by plaque (17.07%). Overall, P value was lichen planus followed by plaque type, which ultimately results in increased rate of malignant transformation. PCNA is a good nuclear protein marker to evaluate the proliferation status of OLP. Out of the two types of lichen planus, erosive type possesses more proliferative ratio and chances of malignant change is more in this type. It emphasizes the importance of long-term follow-up with erosive type when compared with plaque type.

Proliferation in cycle

Energy Technology Data Exchange (ETDEWEB)

Piao Yunsong [College of Physical Sciences, Graduate School of Chinese Academy of Sciences, Beijing 100049 (China)], E-mail: yspiao@gucas.ac.cn

2009-06-15

In the contracting phase with w{approx_equal}0, the scale invariant spectrum of curvature perturbation is given by the increasing mode of metric perturbation. In this Letter, it is found that if the contracting phase with w{approx_equal}0 is included in each cycle of a cycle universe, since the metric perturbation is amplified on super horizon scale cycle by cycle, after each cycle the universe will be inevitably separated into many parts independent of one another, each of which corresponds to a new universe and evolves up to next cycle, and then is separated again. In this sense, a cyclic multiverse scenario is actually presented, in which the universe proliferates cycle by cycle. We estimate the number of new universes proliferated in each cycle, and discuss the implications of this result.

Proliferation in cycle

International Nuclear Information System (INIS)

Piao Yunsong

2009-01-01

In the contracting phase with w≅0, the scale invariant spectrum of curvature perturbation is given by the increasing mode of metric perturbation. In this Letter, it is found that if the contracting phase with w≅0 is included in each cycle of a cycle universe, since the metric perturbation is amplified on super horizon scale cycle by cycle, after each cycle the universe will be inevitably separated into many parts independent of one another, each of which corresponds to a new universe and evolves up to next cycle, and then is separated again. In this sense, a cyclic multiverse scenario is actually presented, in which the universe proliferates cycle by cycle. We estimate the number of new universes proliferated in each cycle, and discuss the implications of this result.

Utility of Social Modeling for Proliferation Assessment - Preliminary Findings

International Nuclear Information System (INIS)

Coles, Garill A.; Gastelum, Zoe N.; Brothers, Alan J.; Thompson, Sandra E.

2009-01-01

Often the methodologies for assessing proliferation risk are focused around the inherent vulnerability of nuclear energy systems and associated safeguards. For example an accepted approach involves ways to measure the intrinsic and extrinsic barriers to potential proliferation. This paper describes preliminary investigation into non-traditional use of social and cultural information to improve proliferation assessment and advance the approach to assessing nuclear material diversion. Proliferation resistance assessment, safeguard assessments and related studies typically create technical information about the vulnerability of a nuclear energy system to diversion of nuclear material. The purpose of this research project is to find ways to integrate social information with technical information by explicitly considering the role of culture, groups and/or individuals to factors that impact the possibility of proliferation. When final, this work is expected to describe and demonstrate the utility of social science modeling in proliferation and proliferation risk assessments.

RELATIVE PROLIFERATION RISKS FOR NUCLEAR FUEL LEASING ARRANGEMENT

International Nuclear Information System (INIS)

CHENG, L.Y.; YUE, M.; BARI, R.A.

2007-01-01

The present study demonstrates a probabilistic approach to quantify the proliferation risks of fuel leasing and recycling. A Markov model approach is applied to evaluate the probability of proliferation success by diversion or theft. Proliferation risk is calculated as a product of the probability of success and the corresponding consequences

Lithium doped calcium phosphate cement maintains physical mechanical properties and promotes osteoblast proliferation and differentiation.

Science.gov (United States)

Li, Li; Wang, Renchong; Li, Baichuan; Liang, Wei; Pan, Haobo; Cui, Xu; Tang, Jingli; Li, Bing

2017-07-01

Calcium phosphate cement (CPC) has been widely used in bone tissue repairing due to its physical mechanical properties and biocompatibility. Addition of trace element to CPC has shown promising evidence to improve the physical properties and biological activities of CPC. Lithium (Li) has effect on osteoblast proliferation and differentiation. In this study, we incorporated Li to CPC and examined the physical properties of Li/CPC and its effect on osteoblast proliferation and differentiation. We found that Li doped CPC maintained similar setting time, pore size distribution, compressive strength, composition, and morphology as CPC without Li. Additionally, Li doped CPC improved osteoblast proliferation and differentiation significantly compared to CPC without Li. To our knowledge, our results, for the first time, show that Li doped CPC has beneficial effect on osteoblast in cell culture while keeps the excellent physical-mechanical properties of CPC. This study will lead to potential application of Li doped CPC in bone tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 944-952, 2017. © 2016 Wiley Periodicals, Inc.

Chitosan-based hydrogel tissue scaffolds made by 3D plotting promotes osteoblast proliferation and mineralization.

Science.gov (United States)

Liu, I-Hsin; Chang, Shih-Hsin; Lin, Hsin-Yi

2015-05-13

A 3D plotting system was used to make chitosan-based tissue scaffolds with interconnected pores using pure chitosan (C) and chitosan cross-linked with pectin (CP) and genipin (CG). A freeze-dried chitosan scaffold (CF/D) was made to compare with C, to observe the effects of structural differences. The fiber size, pore size, porosity, compression strength, swelling ratio, drug release efficacy, and cumulative weight loss of the scaffolds were measured. Osteoblasts were cultured on the scaffolds and their proliferation, type I collagen production, alkaline phosphatase activity, calcium deposition, and morphology were observed. C had a lower swelling ratio, degradation, porosity and drug release efficacy and a higher compressional stiffness and cell proliferation compared to CF/D (p 3D-plotted samples, cells on CP exhibited the highest degree of mineralization after 21 d (p 3D-plotted scaffolds were stronger, less likely to degrade and better promoted osteoblast cell proliferation in vitro compared to the freeze-dried scaffolds. C, CP and CG were structurally similar, and the different crosslinking caused significant changes in their physical and biological performances.

Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis

Energy Technology Data Exchange (ETDEWEB)

Takahara, Kiyoshi [Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka (Japan); Ii, Masaaki, E-mail: masaii@art.osaka-med.ac.jp [Department of Pharmacology, Faculty of Medicine, Osaka Medical College, Osaka (Japan); Inamoto, Teruo; Komura, Kazumasa; Ibuki, Naokazu; Minami, Koichiro; Uehara, Hirofumi; Hirano, Hajime; Nomi, Hayahito; Kiyama, Satoshi [Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka (Japan); Asahi, Michio [Department of Pharmacology, Faculty of Medicine, Osaka Medical College, Osaka (Japan); Azuma, Haruhito [Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka (Japan)

2014-04-18

Highlights: • AdSC transplantation exhibits inhibitory effect on tumor progressions of PCa cells. • AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway. • High expression of the TGF-β1 gene in AdSCs. - Abstract: Mesenchymal stem cells (MSCs) have generated a great deal of interest in the field of regenerative medicine. Adipose-derived stromal cells (AdSCs) are known to exhibit extensive proliferation potential and can undergo multilineage differentiation, sharing similar characteristics to bone marrow-derived MSCs. However, as the effect of AdSCs on tumor growth has not been studied sufficiently, we assessed the degree to which AdSCs affect the proliferation of prostate cancer (PCa) cell. Human AdSCs exerted an inhibitory effect on the proliferation of androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) human PCa cells, while normal human dermal fibroblasts (NHDFs) did not, and in fact promoted PCa cell proliferation to a degree. Moreover, AdSCs induced apoptosis of LNCaP cells and PC3 cells, activating the caspase3/7 signaling pathway. cDNA microarray analysis suggested that AdSC-induced apoptosis in both LNCaP and PC3 cells was related to the TGF-β signaling pathway. Consistent with our in vitro observations, local transplantation of AdSCs delayed the growth of tumors derived from both LNCaP- and PC3-xenografts in immunodeficient mice. This is the first preclinical study to have directly demonstrated that AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway, irrespective of androgen-responsiveness. Since autologous AdSCs can be easily isolated from adipose tissue without any ethical concerns, we suggest that therapy with these cells could be a novel approach for patients with PCa.

Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis

International Nuclear Information System (INIS)

Takahara, Kiyoshi; Ii, Masaaki; Inamoto, Teruo; Komura, Kazumasa; Ibuki, Naokazu; Minami, Koichiro; Uehara, Hirofumi; Hirano, Hajime; Nomi, Hayahito; Kiyama, Satoshi; Asahi, Michio; Azuma, Haruhito

2014-01-01

Highlights: • AdSC transplantation exhibits inhibitory effect on tumor progressions of PCa cells. • AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway. • High expression of the TGF-β1 gene in AdSCs. - Abstract: Mesenchymal stem cells (MSCs) have generated a great deal of interest in the field of regenerative medicine. Adipose-derived stromal cells (AdSCs) are known to exhibit extensive proliferation potential and can undergo multilineage differentiation, sharing similar characteristics to bone marrow-derived MSCs. However, as the effect of AdSCs on tumor growth has not been studied sufficiently, we assessed the degree to which AdSCs affect the proliferation of prostate cancer (PCa) cell. Human AdSCs exerted an inhibitory effect on the proliferation of androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) human PCa cells, while normal human dermal fibroblasts (NHDFs) did not, and in fact promoted PCa cell proliferation to a degree. Moreover, AdSCs induced apoptosis of LNCaP cells and PC3 cells, activating the caspase3/7 signaling pathway. cDNA microarray analysis suggested that AdSC-induced apoptosis in both LNCaP and PC3 cells was related to the TGF-β signaling pathway. Consistent with our in vitro observations, local transplantation of AdSCs delayed the growth of tumors derived from both LNCaP- and PC3-xenografts in immunodeficient mice. This is the first preclinical study to have directly demonstrated that AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway, irrespective of androgen-responsiveness. Since autologous AdSCs can be easily isolated from adipose tissue without any ethical concerns, we suggest that therapy with these cells could be a novel approach for patients with PCa

Ablation of cdk4 and cdk6 affects proliferation of basal progenitor cells in the developing dorsal and ventral forebrain.

Science.gov (United States)

Grison, Alice; Gaiser, Carine; Bieder, Andrea; Baranek, Constanze; Atanasoski, Suzana

2018-03-23

Little is known about the molecular players driving proliferation of neural progenitor cells (NPCs) during embryonic mouse development. Here, we demonstrate that proliferation of NPCs in the developing forebrain depends on a particular combination of cell cycle regulators. We have analyzed the requirements for members of the cyclin-dependent kinase (cdk) family using cdk-deficient mice. In the absence of either cdk4 or cdk6, which are both regulators of the G1 phase of the cell cycle, we found no significant effects on the proliferation rate of cortical progenitor cells. However, concomitant loss of cdk4 and cdk6 led to a drastic decrease in the proliferation rate of NPCs, specifically the basal progenitor cells of both the dorsal and ventral forebrain at embryonic day 13.5 (E13.5). Moreover, basal progenitors in the forebrain of Cdk4;Cdk6 double mutant mice exhibited altered cell cycle characteristics. Cdk4;cdk6 deficiency led to an increase in cell cycle length and cell cycle exit of mutant basal progenitor cells in comparison to controls. In contrast, concomitant ablation of cdk2 and cdk6 had no effect on the proliferation of NCPs. Together, our data demonstrate that the expansion of the basal progenitor pool in the developing telencephalon is dependent on the presence of distinct combinations of cdk molecules. Our results provide further evidence for differences in the regulation of proliferation between apical and basal progenitors during cortical development. © 2018 Wiley Periodicals, Inc. Develop Neurobiol, 2018. © 2018 Wiley Periodicals, Inc.

An Autocrine Proliferation Repressor Regulates Dictyostelium discoideum Proliferation and Chemorepulsion Using the G Protein-Coupled Receptor GrlH

Directory of Open Access Journals (Sweden)

Yu Tang

2018-02-01

Full Text Available In eukaryotic microbes, little is known about signals that inhibit the proliferation of the cells that secrete the signal, and little is known about signals (chemorepellents that cause cells to move away from the source of the signal. Autocrine proliferation repressor protein A (AprA is a protein secreted by the eukaryotic microbe Dictyostelium discoideum. AprA is a chemorepellent for and inhibits the proliferation of D. discoideum. We previously found that cells sense AprA using G proteins, suggesting the existence of a G protein-coupled AprA receptor. To identify the AprA receptor, we screened mutants lacking putative G protein-coupled receptors. We found that, compared to the wild-type strain, cells lacking putative receptor GrlH (grlH{macron} cells show rapid proliferation, do not have large numbers of cells moving away from the edges of colonies, are insensitive to AprA-induced proliferation inhibition and chemorepulsion, and have decreased AprA binding. Expression of GrlH in grlH{macron} cells (grlH{macron}/grlHOE rescues the phenotypes described above. These data indicate that AprA signaling may be mediated by GrlH in D. discoideum.

A Sox Transcription Factor Is a Critical Regulator of Adult Stem Cell Proliferation in the Drosophila Intestine

Directory of Open Access Journals (Sweden)

Fanju W. Meng

2015-11-01

Full Text Available Adult organs and their resident stem cells are constantly facing the challenge of adapting cell proliferation to tissue demand, particularly in response to environmental stresses. Whereas most stress-signaling pathways are conserved between progenitors and differentiated cells, stem cells have the specific ability to respond by increasing their proliferative rate, using largely unknown mechanisms. Here, we show that a member of the Sox family of transcription factors in Drosophila, Sox21a, is expressed in intestinal stem cells (ISCs in the adult gut. Sox21a is essential for the proliferation of these cells during both normal epithelium turnover and repair. Its expression is induced in response to tissue damage, downstream of the Jun N-terminal kinase (JNK and extracellular signal-regulated kinase (ERK pathways, to promote ISC proliferation. Although short-lived, Sox21a mutant flies show no developmental defects, supporting the notion that this factor is a specific regulator of adult stem cell proliferation.

Trends in the proliferation of weapons of mass destruction

International Nuclear Information System (INIS)

Karp, A.

1995-01-01

Nuclear and missile proliferation are neither unique nor necessarily the most imposing proliferation challenges, but they are probably the most visible and mature aspects of the proliferation problem. In nuclear proliferation there the news are very ambivalent. Today we face somewhat between 7 and 9 counties with nuclear weapons: 5 acknowledged nuclear powers, Israel and Ukraine as well as the uncertain status of Pakistan and North Korea. The growing number of countries that have given up their nuclear programs is impressive, most spectacularly Argentina, Brazil and South Africa. Recently Kazakhstan has signed the Non-proliferation Treaty, and Belarus seems certain to follow. Thus the problem list is a short one now. The remaining issues are to be treated at the 1995 Non-proliferation Treaty Extension Conference

Effect of different presentations of resveratrol on cell proliferation and epitelial thickness of the oral mucosa of wistar rats

Directory of Open Access Journals (Sweden)

Luciano Henrique Jesus

2017-09-01

Full Text Available Introduction: Grape is one of the most important fruit crops across the world and can be consumed in different ways. There has been a growing interest in the role of antioxidants such as resveratrol, which can be found in grape skin, in oral and dental tissues. Thus, the objective of this study was to analyze the effect of different presentations of resveratrol on cell proliferation and epithelial thickness of the oral mucosa of Wistar rats. Methods: Fifty male Wistar rats were randomly divided into five groups: water/control, red wine, grape juice, 12% alcoholic solution/ethanol and aqueous solution of resveratrol. Samples of palatal and tongue mucosa were collected for a histomorphometric analysis using hematoxylin-eosin staining and the argyrophilic nucleolar organizer region (AgNOR technique for quantification of cell proliferation. Results: As to epithelial thickness, both the tongue and the palate showed a statistically significant difference between the control group and the other groups, with greater decrease in the resveratrol and the wine groups. In the suprabasal layer of both the tongue and the palate epithelium, red wine reduced the rate of cell proliferation, while ethanol increased it. In the basal layer of the tongue epithelium, there was a statistically significant difference between the control, the grape juice and the resveratrol groups and the ethanol group, with increased cell proliferation in the ethanol group. Conclusions: Wine does not interfere in the physiological renewal of the basal layer of the buccal epithelium and exerts a protective action by reducing the cell proliferation rate of the suprabasal layer. Keywords: Resveratrol; grape juice; wine; cell proliferation; epithelial thickness

Similar Pregnancy Rates Between Different Endometrial Echo Patterns in ART

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Serdar Ünlü

2008-08-01

CONCLUSION: As the morphological assessment of endometrium by sonography has a high inter observer variability and the influence of sonographic patterns of endometrium on pregnancy rates remains unclear, we conclude that evaluating endometrial patterns by sonography alone is not an optimal diagnostic procedure for determining the success of IVF outcome.

[Effects of metformin on human oral cancer KB cell proliferation and apoptosis in vitro].

Science.gov (United States)

Wang, Fang; Xu, Jincheng; Xia, Fei; Liu, Zhe; Zhao, Surong; Liu, Hao; Jiang, Zhiwen

2014-02-01

To investigate the effects of metformin on the proliferation and apoptosis of human oral cancer cell line KB in vitro. Human oral cancer cell line KB was exposed to different doses of metformin (0, 1.25, 2.5, 5, 10, and 20 mmol/L), and the changes in cell viability were detected using MTT assay. Colony formation of the cells was observed following an 8-day metformin exposure. The changes in mitochondrial membrane potential were measured by JC-1 assay, and PI staining was used to observe the cell apoptosis. Western blotting was employed to detect the changes in the protein expressions of GRP78 and activated caspase-3. Metformin exposure caused time- and dose-dependent suppression of KB cell proliferation, and exposure to 5 mmol/L metformin for 24, 48 and 72 h resulted in cell survival rates of 68.0%, 36.9%, and 14.5%, respectively. Metformin significantly inhibited KB cell colony formation. Exposure of the cells to increased concentrations of metformin gradually increased the apoptotic rate and decreased mitochondrial membrane potential. Metformin caused an initial up-regulation followed by a down-regulation of GRP78 expression in KB cells and increased the expression of activated caspase-3. Metformin can inhibit the proliferation and induce apoptosis of KB cells, the mechanism of which may involve the activation of the mitochondrial apoptotic pathway and endoplasmic reticulum stress.

The effect of oscillatory mechanical stimulation on osteoblast attachment and proliferation

International Nuclear Information System (INIS)

Aryaei, Ashkan; Jayasuriya, Ambalangodage C.

2015-01-01

The aim of this paper is to investigate the effect of the magnitude and duration of oscillatory mechanical stimulation on osteoblast attachment and proliferation as well as the time gap between seeding and applying the stimulation. Cells were exposed to three levels of speed at two different conditions. For the first group, mechanical shear stress was applied after 20 min of cell seeding. For the second group there was no time gap between cell seeding and applying mechanical stimulation. The total area subjected to shear stress was divided into three parts and for each part a comparative study was conducted at defined time points. Our results showed that both shear stress magnitude and the time gap between cell seeding and applying shear stress, are important in further cell proliferation and attachment. The effect of shear stress was not significant at lower speeds for both groups at earlier time points. However, a higher percentage of area was covered by cells at later time points under shear stress. In addition, the time gap can also improve osteoblast attachment. For the best rate of cell attachment and proliferation, the magnitude of shear stress and time gap should be optimized. The results of this paper can be utilized to improve cell attachment and proliferation in bioreactors. - Highlights: • The effect of oscillatory mechanical stimulation on osteoblast functions was studied. • Cells were exposed at three levels of speed to attach cells. • Shear stress magnitude and time gap are important for cell functions. • Cells start developing extracellular components at the early stage of seeding

Peroxisome Proliferator-Activated Receptor ß/ (PPARß/) but Not PPAR Serves as a Plasma Free Fatty Acid Sensor in Liver

NARCIS (Netherlands)

Sanderson, L.; Degerhardt, T.; Desvergne, B.; Koppen, A.; Kalkhoven, E.; Müller, M.R.; Kersten, A.H.

2009-01-01

Peroxisome proliferator-activated receptor alpha (PPAR alpha) is an important transcription factor in liver that can be activated physiologically by fasting or pharmacologically by using high-affinity synthetic agonists. Here we initially set out to elucidate the similarities in gene induction

Proliferation of Schwann cells induced by axolemmal and myelin membranes

International Nuclear Information System (INIS)

Dinneen, M.

1985-01-01

Purified Schwann Cells were cultured from neonatal rat sciatic nerve using a modification of the method of Brockes. Schwann cells and contaminating fibroblasts were unambiguously identified using fluorescent antibodies of 2'3' cyclic nucleotide 3'-phosphodiesterase and the thy 1.1 antigen respectively. The Schwann cells were quiescent unless challenged with mitogens. They proliferated rapidly in response to the soluble mitogen, cholera toxin, or to membrane fractions from rat CNS or PNS, prepared by the method of DeVries. Mitogenic activity was present in both axolemmal and myelin enriched fractions and promoted a 10-15 fold increase in the rate of 3 H-thymidine uptake. The axolemmal mitogen was sensitive to heat (80 0 C for 10 minutes), trypsin digestion (0.05% x 30 mins) or to treatment with endoglycosidase D, suggesting that it could be a glycoprotein. Fifty percent of the axolemmal mitogenic activity was solubilized in 1% octyl-glucoside. The solubilized material, however, was very unstable and further purification was not possible. The myelin associated mitogenic activity was markedly different. It was resistant to freeze thaw cycles, trypsin digestion of endoglycosidase treatment and the activity was actually enhanced by heating at 100 0 C for two hours. It is proposed that the axolemmal activity is responsible for Schwann cell proliferation during development and that the myelin associated activity promotes Schwann cell proliferation during Wallerian degeneration

Supporting non proliferation and global security efforts

International Nuclear Information System (INIS)

Pochon, E.

2013-01-01

CEA contributes as a major actor of France's action against nuclear proliferation and to the strengthening of nuclear security at national level as European and International levels, in particular through the support of the IAEA activities in nuclear non proliferation with the French Support Programme for the IAEA safeguards system and security with the contribution to the IAEA Nuclear Security Plan and cooperation projects with the European Commission. The CEA is a French government funded technological research organization, organized around 5 branches: Nuclear Energy, Technological Researches, Defence (DAM), Material Sciences and Life Sciences. Within the scope of its activities, CEA covers most of the research areas and techniques in nuclear non-proliferation and security. The CEA is also the advisor of the French Government on nuclear policy. Treaty monitoring and the development and implementation of non proliferation and global security programs is an important mission of DAM which rely on nuclear weapons manufacture and past testing experience. The programmes on non proliferation and global security carried out to fulfil DAM's mission cover the following areas: development of monitoring and detection methods and equipments, country profiles and nuclear stockpiles assessment, arms control instruments, proliferation resistance of nuclear fuel cycle, monitoring of nuclear tests, operation and maintenance of national detection capabilities and contribution to CTBT verification systems. (A.C.)

The US proliferation security initiative (PSI); L'initiative americaine de securite contre la proliferation (PSI)

Energy Technology Data Exchange (ETDEWEB)

Gregoire, B

2004-10-01

The proliferation security initiative (PSI), launched by President Bush on May 31, 2003, aims at intercepting any transfer of mass destruction weapons, of their vectors and related equipments, towards or coming from countries or organizations suspected to have a proliferation activity. This initiative, which involves coercive means to fight against proliferation, raises international lawfulness and legal questions, the answers of which are today under construction. This article analyzes the place of the European Union in the PSI, the action means (optimization of existing means, cooperation between intelligence and interception services), and the PSI stakes (lawfulness with respect to the international law, bilateral agreements, draft boarding agreement, sustain of the United Nations, widening of the partnership and of the field of action). (J.S.)

Differential effects of oestrogenic hormones on cell proliferation in the colonic crypt epithelium and in colonic carcinomata of rats.

Science.gov (United States)

Tutton, P J; Barkla, D H

1982-01-01

A number of hormones, including some steroids, have previously been shown to influence the rate of cell division in the colonic crypt epithelium and in colonic tumours. In this report the effect of oophorectomy and of treatment with ovarian hormones on cell proliferation in these tissues is compared. Colonic tumours cell proliferation was retarded following oophorectomy and this retardation was reversed by the administration of oestradiol, but not by the administration of progesterone. Oophorectomy did not retard cell proliferation in the colonic crypts. The possible significance of these findings in relation to age-dependent variations in the sex ratio for human bowel cancer is discussed.

ASSESSING THE PROLIFERATION RESISTANCE OF INNOVATIVE NUCLEAR FUEL CYCLES

International Nuclear Information System (INIS)

BARI, R.; ROGLANS, J.; DENNING, R.; MLADINEO, S.

2003-01-01

The National Nuclear Security Administration is developing methods for nonproliferation assessments to support the development and implementation of U.S. nonproliferation policy. This paper summarizes the key results of that effort. Proliferation resistance is the degree of difficulty that a nuclear material, facility, process, or activity poses to the acquisition of one or more nuclear weapons. A top-level measure of proliferation resistance for a fuel cycle system is developed here from a hierarchy of metrics. At the lowest level, intrinsic and extrinsic barriers to proliferation are defined. These barriers are recommended as a means to characterize the proliferation characteristics of a fuel cycle. Because of the complexity of nonproliferation assessments, the problem is decomposed into: metrics to be computed, barriers to proliferation, and a finite set of threats. The spectrum of potential threats of nuclear proliferation is complex and ranges from small terrorist cells to industrialized countries with advanced nuclear fuel cycles. Two general categories of methods have historically been used for nonproliferation assessments: attribute analysis and scenario analysis. In the former, attributes of the systems being evaluated (often fuel cycle systems) are identified that affect their proliferation potential. For a particular system under consideration, the attributes are weighted subjectively. In scenario analysis, hypothesized scenarios of pathways to proliferation are examined. The analyst models the process undertaken by the proliferant to overcome barriers to proliferation and estimates the likelihood of success in achieving a proliferation objective. An attribute analysis approach should be used at the conceptual design level in the selection of fuel cycles that will receive significant investment for development. In the development of a detailed facility design, a scenario approach should be undertaken to reduce the potential for design vulnerabilities

The future of non-proliferation

International Nuclear Information System (INIS)

Gere, F.

2000-01-01

This paper comprises two parts. The first part makes a status of the non-proliferation policy: problems of ratification of Start 2 and CTBT treaties, nuclear tests in India and Pakistan in May 1998 etc. The second part makes a prospective reflexion on the evolution of the position of nuclearized countries at the 2015-2030 vista: role of Asia, nuclear perception, evolution of the US perception of non-proliferation, military strategy and European unification. (J.S.)

Director`s series on proliferation

Energy Technology Data Exchange (ETDEWEB)

Bailey, K.C. [ed.

1993-09-07

Two essays are included in this booklet. Their titles are ``The Dynamics of the NPT Extension Decision`` and ``North Korea`s Nuclear Gambit.`` The first paper discusses the conference to be held in 1995 to review the Nuclear Non-Proliferation Treaty (NPT) which will decide whether the treaty shall continue in force indefinitely, or shall be extended for an additional fixed period or periods. Topics relevant to this discussion are: Arms control issues, the nuclear test ban, the limited test ban treaty, the French nuclear testing moratorium, former Soviet nuclear weapons, Iraq, North Korea, nuclear-weapon-free zones, security, controls on nuclear weapon materials, peaceful uses of nuclear energy, safeguards, politics, and organizational and procedural issues. The second paper examines short, medium, and long term issues entailed in Korea`s nuclear proliferation. Topics considered include: Korean unification, North Korean politics, the nuclear issue as leverage, and the Nuclear Non- Proliferation Treaty.

Stanniocalcin 2 promotes cell proliferation and cisplatin resistance in cervical cancer

International Nuclear Information System (INIS)

Wang, Yuxia; Gao, Ying; Cheng, Hairong; Yang, Guichun; Tan, Wenhua

2015-01-01

Cervical cancer is one of the most common carcinomas in the female reproductive system. Treatment of cervical cancer involves surgical removal and chemotherapy. Resistance to platinum-based chemotherapy drugs including cisplatin has increasingly become an important problem in the treatment of cervical cancer patients. We found in this study that stanniocalcin 2 (STC2) expression was upregulated in both cervical cancer tissues and cell lines. The levels of STC2 expression in cervical cancer cell lines were positively correlated with the rate of cell proliferation. Furthermore, in cisplatin resistant cervical cancer cells, the levels of STC2 expression were significantly elevated. Modulation of STC2 expression by siRNA or overexpression in cisplatin resistant cells resulted in altered cell survival, apoptosis, and cisplatin resistance. Finally, we found that there was significant difference in the activity of the MAPK signaling pathway between cisplatin sensitive and resistant cervical cancer cells, and that STC2 could regulate the activity of the MAPK signaling pathway. - Highlights: • STC2 was upregulated in cervical cancer and promoted cervical cancer cell proliferation. • Cisplatin resistant cells had elevated STC2 levels and enhanced proliferation. • STC2 regulated cisplatin chemosensitivity in cervical cancer cells. • STC2 regulated the activity of the MAPK signaling pathway.

[RITA combined with temozolomide inhibits the proliferation of human glioblastoma U87 cells].

Science.gov (United States)

He, Xiao-Yan; Feng, Xiao-Li; Song, Xin-Pei; Zeng, Huan-Chao; Cao, Zhong-Xu; Xiao, Wei-Wei; Zhang, Bao; Wu, Qing-Hua

2016-10-20

To observe the effect of RITA, a small molecule that targets p53, combined with temozolomide (TMZ) on proliferation, colony formation and apoptosis of human glioblastoma U87 cells and explore the underlying mechanism. Cultured U87 cells were treated with RITA (1, 5, 10, 20 µmol/L), TMZ, or RITA+TMZ (half dose) for 24, 48 or 72 h. MTS assay were used to detect the cell proliferation, and the cell proliferation rate and inhibitory rate were calculated. The effect of combined treatments was evaluated by the q value. The expressions of p53, p21 and other apoptosis-associated genes were detected by qRT-PCR and Western blotting; cell apoptosis was assayed using flow cytometry with Annexin V/PI double staining; colony formation of the cells was detected with crystal violet staining. MTS assay showed that RITA at the 4 doses more potently inhibited U87 cell viability than TMZ at 72 h (P=0.000) with inhibitory rates of 25.94%-41.38% and 3.84%-8.20%, respectively. RITA combined with TMZ caused a more significant inhibition of U87 cells (29.21%-52.11%) than RITA (PRITA+TMZ for 48 h resulted in q values exceeding 1.2 and showed an obvious synergistic effect of the drugs. Both RITA and TMZ, especially the latter, significantly increased the expressions of p53, p21, puma, and other apoptosis-associated genes to accelerate apoptosis and inhibit the growth and colony formation of U87 cells, and the effect was more obvious with a combined treatment. RITA inhibits the growth of human glioblastoma cells and enhance their sensitivity to TMZ by up-regulating p53 expression, and when combined, RITA and TMZ show a synergistic effect to cause a stronger cell inhibition.

Dedifferentiation and proliferation of mammalian cardiomyocytes.

Directory of Open Access Journals (Sweden)

Yiqiang Zhang

2010-09-01

Full Text Available It has long been thought that mammalian cardiomyocytes are terminally-differentiated and unable to proliferate. However, myocytes in more primitive animals such as zebrafish are able to dedifferentiate and proliferate to regenerate amputated cardiac muscle.Here we test the hypothesis that mature mammalian cardiomyocytes retain substantial cellular plasticity, including the ability to dedifferentiate, proliferate, and acquire progenitor cell phenotypes. Two complementary methods were used: 1 cardiomyocyte purification from rat hearts, and 2 genetic fate mapping in cardiac explants from bi-transgenic mice. Cardiomyocytes isolated from rodent hearts were purified by multiple centrifugation and Percoll gradient separation steps, and the purity verified by immunostaining and RT-PCR. Within days in culture, purified cardiomyocytes lost their characteristic electrophysiological properties and striations, flattened and began to divide, as confirmed by proliferation markers and BrdU incorporation. Many dedifferentiated cardiomyocytes went on to express the stem cell antigen c-kit, and the early cardiac transcription factors GATA4 and Nkx2.5. Underlying these changes, inhibitory cell cycle molecules were suppressed in myocyte-derived cells (MDCs, while microRNAs known to orchestrate proliferation and pluripotency increased dramatically. Some, but not all, MDCs self-organized into spheres and re-differentiated into myocytes and endothelial cells in vitro. Cell fate tracking of cardiomyocytes from 4-OH-Tamoxifen-treated double-transgenic MerCreMer/ZEG mouse hearts revealed that green fluorescent protein (GFP continues to be expressed in dedifferentiated cardiomyocytes, two-thirds of which were also c-kit(+.Contradicting the prevailing view that they are terminally-differentiated, postnatal mammalian cardiomyocytes are instead capable of substantial plasticity. Dedifferentiation of myocytes facilitates proliferation and confers a degree of stemness

Ultracentrifuge and non-proliferation

International Nuclear Information System (INIS)

Voortman, A.J.

1977-01-01

The author states that there is no meaningful difference, from the point of view of proliferation between peaceful, civil, scientific application of nuclear fission, and the use of it in nuclear weapons. The proliferation of the nuclear technology for weapons appeared and appears to be closely connected with the spread of peaceful applications of nuclear technology. In connection with this, he discusses the Ultracentrifuge plant at Almelo (Netherlands) and the supply of nuclear technology by West-Germany especially to Brazil. Further the changed American policy and the possibility of an American/Russian deal to prevent the spread of the nuclear enrichment technology is discussed

Evaluation of proliferation resistance using the INPRO methodology

International Nuclear Information System (INIS)

Yang, Myung Seung; Park, Joo Hwan; Ko, Won Il; Song, Kee Chan; Choi, Kun Mo; Kim, Jin Kyoung

2007-01-01

The IAEA launched the International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO) and developed the INPRO Methodology to provide guidelines and to assess the characteristics of a future innovative nuclear energy system in areas such as safety, economics, waste management, and proliferation resistance. The proliferation resistance area of the INPRO Methodology is reviewed here, and modifications for further improvements are proposed. The evaluation metrics including the evaluation parameters, evaluation scales and acceptance limits are developed for a practical application of the methodology to assess the proliferation resistance. The proliferation resistant characteristics of the DUPIC fuel cycle are assessed by applying the modified INPRO Methodology based on the developed evaluation metrics and acceptance criteria. The evaluation procedure and the metrics can be utilized as a reference for an evaluation of the proliferation resistance of a future innovative nuclear energy system

The p21-activated kinase (PAK family member PakD is required for chemorepulsion and proliferation inhibition by autocrine signals in Dictyostelium discoideum.

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Jonathan E Phillips

Full Text Available In Dictyostelium discoideum, the secreted proteins AprA and CfaD function as reporters of cell density and regulate cell number by inhibiting proliferation at high cell densities. AprA also functions to disperse groups of cells at high density by acting as a chemorepellent. However, the signal transduction pathways associated with AprA and CfaD are not clear, and little is known about how AprA affects the cytoskeleton to regulate cell movement. We found that the p21-activated kinase (PAK family member PakD is required for both the proliferation-inhibiting activity of AprA and CfaD and the chemorepellent activity of AprA. Similar to cells lacking AprA or CfaD, cells lacking PakD proliferate to a higher cell density than wild-type cells. Recombinant AprA and CfaD inhibit the proliferation of wild-type cells but not cells lacking PakD. Like AprA and CfaD, PakD affects proliferation but does not significantly affect growth (the accumulation of mass on a per-nucleus basis. In contrast to wild-type cells, cells lacking PakD are not repelled from a source of AprA, and colonies of cells lacking PakD expand at a slower rate than wild-type cells, indicating that PakD is required for AprA-mediated chemorepulsion. A PakD-GFP fusion protein localizes to an intracellular punctum that is not the nucleus or centrosome, and PakD-GFP is also occasionally observed at the rear cortex of moving cells. Vegetative cells lacking PakD show excessive actin-based filopodia-like structures, suggesting that PakD affects actin dynamics, consistent with previously characterized roles of PAK proteins in actin regulation. Together, our results implicate PakD in AprA/CfaD signaling and show that a PAK protein is required for proper chemorepulsive cell movement in Dictyostelium.

The p21-activated kinase (PAK) family member PakD is required for chemorepulsion and proliferation inhibition by autocrine signals in Dictyostelium discoideum.

Science.gov (United States)

Phillips, Jonathan E; Gomer, Richard H

2014-01-01

In Dictyostelium discoideum, the secreted proteins AprA and CfaD function as reporters of cell density and regulate cell number by inhibiting proliferation at high cell densities. AprA also functions to disperse groups of cells at high density by acting as a chemorepellent. However, the signal transduction pathways associated with AprA and CfaD are not clear, and little is known about how AprA affects the cytoskeleton to regulate cell movement. We found that the p21-activated kinase (PAK) family member PakD is required for both the proliferation-inhibiting activity of AprA and CfaD and the chemorepellent activity of AprA. Similar to cells lacking AprA or CfaD, cells lacking PakD proliferate to a higher cell density than wild-type cells. Recombinant AprA and CfaD inhibit the proliferation of wild-type cells but not cells lacking PakD. Like AprA and CfaD, PakD affects proliferation but does not significantly affect growth (the accumulation of mass) on a per-nucleus basis. In contrast to wild-type cells, cells lacking PakD are not repelled from a source of AprA, and colonies of cells lacking PakD expand at a slower rate than wild-type cells, indicating that PakD is required for AprA-mediated chemorepulsion. A PakD-GFP fusion protein localizes to an intracellular punctum that is not the nucleus or centrosome, and PakD-GFP is also occasionally observed at the rear cortex of moving cells. Vegetative cells lacking PakD show excessive actin-based filopodia-like structures, suggesting that PakD affects actin dynamics, consistent with previously characterized roles of PAK proteins in actin regulation. Together, our results implicate PakD in AprA/CfaD signaling and show that a PAK protein is required for proper chemorepulsive cell movement in Dictyostelium.

Six1 promotes proliferation of pancreatic cancer cells via upregulation of cyclin D1 expression.

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Zhaoming Li

Full Text Available Six1 is one of the transcription factors that act as master regulators of development and are frequently dysregulated in cancers. However, the role of Six1 in pancreatic cancer is not clear. Here we show that the relative expression of Six1 mRNA is increased in pancreatic cancer and correlated with advanced tumor stage. In vitro functional assays demonstrate that forced overexpression of Six1 significantly enhances the growth rate and proliferation ability of pancreatic cancer cells. Knockdown of endogenous Six1 decreases the proliferation of these cells dramatically. Furthermore, Six1 promotes the growth of pancreatic cancer cells in a xenograft assay. We also show that the gene encoding cyclin D1 is a direct transcriptional target of Six1 in pancreatic cancer cells. Overexpression of Six1 upregulates cyclin D1 mRNA and protein, and significantly enhances the activity of the cyclin D1 promoter in PANC-1 cells. We demonstrate that Six1 promotes cell cycle progression and proliferation by upregulation of cyclin D1. These data suggest that Six1 is overexpressed in pancreatic cancer and may contribute to the increased cell proliferation through upregulation of cyclin D1.

High similarity of phylogenetic profiles of rate-limiting enzymes with inhibitory relation in Human, Mouse, Rat, budding Yeast and E. coli.

Science.gov (United States)

Zhao, Min; Qu, Hong

2011-11-30

The phylogenetic profile is widely used to characterize functional linkage and conservation between proteins without amino acid sequence similarity. To survey the conservative regulatory properties of rate-limiting enzymes (RLEs) in metabolic inhibitory network across different species, we define the enzyme inhibiting pair as: where the first enzyme in a pair is the inhibitor provider and the second is the target of the inhibitor. Phylogenetic profiles of enzymes in the inhibiting pairs are further generated to measure the functional linkage of these enzymes during evolutionary history. We find that the RLEs generate, on average, over half of all in vivo inhibitors in each surveyed model organism. And these inhibitors inhibit on average over 85% targets in metabolic inhibitory network and cover the majority of targets of cross-pathway inhibiting relations. Furthermore, we demonstrate that the phylogenetic profiles of the enzymes in inhibiting pairs in which at least one enzyme is rate-limiting often show higher similarities than those in common inhibiting enzyme pairs. In addition, RLEs, compared to common metabolic enzymes, often tend to produce ADP instead of AMP in conservative inhibitory networks. Combined with the conservative roles of RLEs in their efficiency in sensing metabolic signals and transmitting regulatory signals to the rest of the metabolic system, the RLEs may be important molecules in balancing energy homeostasis via maintaining the ratio of ATP to ADP in living cells. Furthermore, our results indicate that similarities of phylogenetic profiles of enzymes in the inhibiting enzyme pairs are not only correlated with enzyme topological importance, but also related with roles of the enzymes in metabolic inhibitory network.

Inhibitory efficacy of bufadienolides on Na+,K+-pump activity versus cell proliferation.

Science.gov (United States)

Xu, Yinfang; Liu, Xuan; Schwarz, Silvia; Hu, Lihong; Guo, Dean; Gu, Quanbao; Schwarz, Wolfgang

2016-07-01

Bufadienolides are cytotoxic drugs that may form the basis for anticancer agents. Due to structural and functional similarity to cardiotonic glycosides, application is restricted. We, therefore, investigated correlation of their putative anticancer effects with inhibition of Na + ,K + pumps. The natural bufalin and three derivatives were tested. The anticancer effects of the drugs were checked by observing their inhibitory effects on proliferation of rat liver cancer cells using MTT assay. Inhibition of Na + ,K + -pump was determined by measuring pump-mediated current of rat α1/β1 and α2/β1 Na + ,K + pumps expressed in Xenopus oocytes. All tested bufadienolides inhibited cell proliferation and Na + ,K + pump activity. An activity coefficient A =100x IC 50 Na,K pump /IC 50 pr o liferation was used to describe drug effectivity as anticancer drug. Natural bufalin exhibited lowest effectivity on cell proliferation, and also the A value for rat α1 isoform was the lowest (0.08), the α2 isoform was much less sensitive ( A =1.00). The highest A values were obtained for the BF238 derivative with A =0.88 and 2.64 for the α1 and α2 isoforms, respectively. Therefore, we suggest that search for bufalin derivatives with high anticancer effect and low affinity for both Na + ,K + pump isoforms may be a promising strategy for development of anticancer drugs.

Potential Effect of CD271 on Human Mesenchymal Stromal Cell Proliferation and Differentiation

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Giovanna Calabrese

2015-07-01

Full Text Available The Low-Affinity Nerve Growth Factor Receptor (LNGFR, also known as CD271, is a member of the tumor necrosis factor receptor superfamily. The CD271 cell surface marker defines a subset of multipotential mesenchymal stromal cells and may be used to isolate and enrich cells derived from bone marrow aspirate. In this study, we compare the proliferative and differentiation potentials of CD271+ and CD271− mesenchymal stromal cells. Mesenchymal stromal cells were isolated from bone marrow aspirate and adipose tissue by plastic adherence and positive selection. The proliferation and differentiation potentials of CD271+ and CD271− mesenchymal stromal cells were assessed by inducing osteogenic, adipogenic and chondrogenic in vitro differentiation. Compared to CD271+, CD271− mesenchymal stromal cells showed a lower proliferation rate and a decreased ability to give rise to osteocytes, adipocytes and chondrocytes. Furthermore, we observed that CD271+ mesenchymal stromal cells isolated from adipose tissue displayed a higher efficiency of proliferation and trilineage differentiation compared to CD271+ mesenchymal stromal cells isolated from bone marrow samples, although the CD271 expression levels were comparable. In conclusion, these data show that both the presence of CD271 antigen and the source of mesenchymal stromal cells represent important factors in determining the ability of the cells to proliferate and differentiate.

Lineup member similarity effects on children's eyewitness identification

OpenAIRE

Fitzgerald, Ryan J.; Whiting, Brittany F.; Therrien, Natalie M.; Price, Heather L.

2014-01-01

To date, research investigating the similarity among lineup members has focused on adult eyewitnesses. In the present research, children made identifications from lineups containing members of lower or higher similarity to a target person. In Experiment 1, following a live interaction, children's (6–14 years) correct identification rate was reduced in higher-similarity relative to lower-similarity lineups. In Experiment 2, children (6–12 years) and adults watched a video containing a target p...

Relationships betwen mitotic delay and the dose rate of X radiation

International Nuclear Information System (INIS)

Yi, P.N.; Rha, C.K.; Evans, H.H.; Beer, J.Z.

1994-01-01

Upon exposure of cells to radiation delivered at a continuous low dose rate, cell proliferation may be sustained with the cells exhibiting a constant doubling time that is independent of the total dose. The doubling time or mitotic delay under these conditions has been shown to depend on the dose rate in HeLa, V79 and P388F cells. Reanalysis of the data for these particular cell lines shows that there is a threshold dose rate for mitotic delay, and that above the threshold there is a linear relationship between the length of mitotic delay and the logarithm of the dose rate which is referred to as the dose-rate response. We have observed the same relationships for L5178Y (LY)-R and LY-S cells exposed to low-dose-rate radiation. The threshold dose rates for LY-R, LY-S and P388F cells are similar (0.01-0.02 Gy/h) and are much lower than for V79 and HeLa cells. The slope of the dose-rate response curve is the greatest for HeLa cells, followed in order by LY-S, V79 and P388F cells, and finally by LY-R cells. The slopes for HeLa and LY-R cells differ by a factor of 35. 20 refs., 3 figs., 1 tab

Environmental enrichment, age and PPARα interact to regulate proliferation in neurogenic niches

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Margarita ePerez-Martin

2016-03-01

Full Text Available Peroxisome proliferator-activated receptor alpha (PPARα ligands have been shown to modulate recovery after brain insults such as ischemia and irradiation by enhancing neurogenesis. In the present study, we investigated the effect of the genetic deletion of PPARα receptors on the proliferative rate of neural precursor cells (NPC in the adult brain. The study was performed in aged Pparα-/- mice exposed to nutritional (treats and environmental (games enrichments for 20 days. We performed immunohistochemical analyses of cells containing the replicating cell DNA marker 5-bromo-2’-deoxyuridine (BrdU+ and the immature neuronal marker doublecortin (Dcx+ in the main neurogenic zones of the adult brain: subgranular zone of dentate gyrus (SGZ, subventricular zone of lateral ventricles (SVZ and/or hypothalamus. Results indicated a reduction in the number of BrdU+ cells in the neurogenic zones analyzed as well as Dcx+ cells in the SGZ during aging (2, 6, 18 months. Pparα deficiency alleviated the age-related reduction of NPC proliferation (BrdU+ cells in the SVZ of the 18-months-old mice. While no genotype effect on NPC proliferation was detected in the SGZ during aging, an accentuated reduction in the number of Dcx+ cells was observed in the SGZ of the 6-months-old Pparα-/- mice. Exposing the 18-months-old mice to nutritional and environmental enrichments reversed the Pparα-/--induced impairment of NPC proliferation in the neurogenic zones analyzed. The enriched environment did not modify the number of SGZ Dcx+ cells in the 18 months old Pparα-/- mice. These results identify PPARα receptors as a potential target to counteract the naturally observed decline in adult NPC proliferation associated with aging and impoverished environments.

Does donor proliferation in development aid for health affect health service delivery and population health? Cross-country regression analysis from 1995 to 2010.

Science.gov (United States)

Pallas, Sarah Wood; Ruger, Jennifer Prah

2017-05-01

Previous literature suggests that increasing numbers of development aid donors can reduce aid effectiveness but this has not been tested in the health sector, which has experienced substantial recent growth in aid volume and number of donors. Based on annual data for 1995-2010 on 139 low- and middle-income countries that received health sector aid from donors reporting to the OECD's Creditor Reporting System, the study used two-step system generalized method of moments regression models to test whether the number of health aid donors and an index of health aid donor fragmentation affect health services (measured by DTP3 immunization rate) or health outcomes (measured by infant mortality rate) for three subsectors of health aid. For total health aid and for the general and basic health aid subsector, controlling for economic and political conditions, increases in the number of donors were associated with increases in DTP3 immunization rate and reductions in infant mortality while increases in the donor fragmentation index were associated with decreases in DTP3 immunization rate and increases in infant mortality, though none of these relationships were statistically significant. For the population and reproductive health aid subsector, a one percent increase in the number of donors was associated with a 0.23 percent decrease in DTP3 immunization ( P <  0.01) while a one percent increase in donor fragmentation was associated with a 0.54 percent increase in DTP3 immunization rate ( P <  0.01); associations with infant mortality rates for this subsector were similar to those for total health aid. The results do not provide clear evidence in support of the hypothesis that donor proliferation negatively impacts development results in the health sector. Aid effectiveness policy prescriptions should distinguish responses to donor proliferation versus donor fragmentation and be adapted to specific subsectors of health aid. © The Author 2016. Published by Oxford

The Asian countries and the non-proliferation treaty prorogation

International Nuclear Information System (INIS)

Hoffmann, N.

1995-01-01

This work deals with the non-proliferation treaty prorogation of Asia. The position of the asian countries under the old non-proliferation treaty is given. It includes the 1968 non-proliferation treaty signatories, the calling in question again and the criticisms revealed by the asian countries. The positions and the open forecasts expressed on the non-proliferation treaty prorogation and the article on the elimination of the nuclear weapons are also given. (O.L.)

Adherence, proliferation and collagen turnover by human fibroblasts seeded into different types of collagen sponges

NARCIS (Netherlands)

Middelkoop, E.; de Vries, H. J.; Ruuls, L.; Everts, V.; Wildevuur, C. H.; Westerhof, W.

1995-01-01

We describe an in vitro model that we have used to evaluate dermal substitutes and to obtain data on cell proliferation, the rate of degradation of the dermal equivalent, contractibility and de novo synthesis of collagen. We tested three classes of collagenous materials: (1) reconstituted

ADHERENCE, PROLIFERATION AND COLLAGEN TURNOVER BY HUMAN FIBROBLASTS SEEDED INTO DIFFERENT TYPES OF COLLAGEN SPONGES

NARCIS (Netherlands)

MIDDELKOOP, E; DEVRIES, HJC; RUULS, L; EVERTS, [No Value; WILDEVUUR, CHR; WESTERHOF, W

We describe an in vitro model that we have used to evaluate dermal substitutes and to obtain data on cell proliferation, the rate of degradation of the dermal equivalent, contractibility and de novo synthesis of collagen. We tested three classes of collagenous materials: (1) reconstituted

Effects of composite films of silk fibroin and graphene oxide on the proliferation, cell viability and mesenchymal phenotype of periodontal ligament stem cells.

Science.gov (United States)

Rodríguez-Lozano, F J; García-Bernal, D; Aznar-Cervantes, S; Ros-Roca, M A; Algueró, M C; Atucha, N M; Lozano-García, A A; Moraleda, J M; Cenis, J L

2014-12-01

In regenerative dentistry, stem cell-based therapy often requires a scaffold to deliver cells and/or growth factors to the injured site. Graphene oxide (GO) and silk fibroin (SF) are promising biomaterials for tissue engineering as they are both non toxic and promote cell proliferation. On the other hand, periodontal ligament stem cells (PDLSCs) are mesenchymal stem cells readily accessible with a promising use in cell therapy. The purpose of this study was to investigate the effects of composite films of GO, SF and GO combined with fibroin in the mesenchymal phenotype, viability, adhesion and proliferation rate of PDLSCs. PDLSCs obtained from healthy extracted teeth were cultured on GO, SF or combination of GO and SF films up to 10 days. Adhesion level of PDSCs on the different biomaterials were evaluated after 12 h of culture, whereas proliferation rate of cells was assessed using the MTT assay. Level of apoptosis was determined using Annexin-V and 7-AAD and mesenchymal markers expression of PDLSCs were analyzed by flow cytometry. At day 7 of culture, MTT experiments showed a high rate of proliferation of PDLSCs growing on GO films compared to the other tested biomaterials, although it was slightly lower than in plastic (control). However PDLSCs growing in fibroin or GO plus fibroin films showed a discrete proliferation. Importantly, at day 10 of culture it was observed a significant increase in PDLSCs proliferation rate in GO films compared to plastic (P < 0.05), as well as in GO plus fibroin compared to fibroin alone (P < 0.001). Flow cytometry analysis showed that culture of PDLSCs in fibroin, GO or GO plus fibroin films did not significantly alter the level of expression of the mesenchymal markers CD73, CD90 or CD105 up to 168 h, being the cell viability in GO even better than obtained in plastic. Our findings suggest that the combination of human dental stem cells/fibroin/GO based-bioengineered constructs have strong potential for their therapeutic

Oral feeding with L-Glutamine and Nucleotides: impact on some GALT (gut associated lymphoid tissue parameters and cell proliferation/death rates in weaning piglets

Directory of Open Access Journals (Sweden)

V. Bontempo

2011-03-01

Full Text Available Dietary supplementation with glutamine and nucleotides may be useful during piglets weaning, when a rough passage from milk suckling to a solid feed may cause a strong reduction of the length of intestinal villi height and the depth of the crypts, and consequently of the intestinal digestive and absorptive capacities (Van Beers-Schreurs et al., 1998. Glutamine stimulates cell proliferation and activates protein kinases, suggesting that it could control the regularly alternating cellular apoptosis/proliferation sequence (Rhoads et al., 2000...

Domestic Politics and Nuclear Proliferation

Energy Technology Data Exchange (ETDEWEB)

Kim, Chul Min; Yim, Man Sung [KAIST, Daejeon (Korea, Republic of)

2016-05-15

The external security threat is known as the most important factor of nuclear weapons program, the domestic politics situation can also affect the nuclear proliferation decision of a country. For example, when a leader wants nuclear weapons as an ultimate weapon, the domestic politics situation can determine the effectiveness of the weapons program of a country. This study analyzes the current knowledge of the relationship between domestic politics and nuclear proliferation and suggests the main challenges of the quantitative models trying to calculate nuclear proliferation risk of countries. The domestic politics status is one of the most important indicators of nuclear program. However, some variables have never been used in quantitative analyses; for example, number of veto players and the public opinion on nuclear weapons; despite they are considered to be important in various qualitative studies. Future studies should focus on how should they be coded and how can they be linked with existing domestic politics variables.

Domestic Politics and Nuclear Proliferation

International Nuclear Information System (INIS)

Kim, Chul Min; Yim, Man Sung

2016-01-01

The external security threat is known as the most important factor of nuclear weapons program, the domestic politics situation can also affect the nuclear proliferation decision of a country. For example, when a leader wants nuclear weapons as an ultimate weapon, the domestic politics situation can determine the effectiveness of the weapons program of a country. This study analyzes the current knowledge of the relationship between domestic politics and nuclear proliferation and suggests the main challenges of the quantitative models trying to calculate nuclear proliferation risk of countries. The domestic politics status is one of the most important indicators of nuclear program. However, some variables have never been used in quantitative analyses; for example, number of veto players and the public opinion on nuclear weapons; despite they are considered to be important in various qualitative studies. Future studies should focus on how should they be coded and how can they be linked with existing domestic politics variables

Impact of low oxygen tension on stemness, proliferation and differentiation potential of human adipose-derived stem cells

Energy Technology Data Exchange (ETDEWEB)

Choi, Jane Ru; Pingguan-Murphy, Belinda; Wan Abas, Wan Abu Bakar [Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur (Malaysia); Noor Azmi, Mat Adenan; Omar, Siti Zawiah [Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur (Malaysia); Chua, Kien Hui [Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur (Malaysia); Wan Safwani, Wan Kamarul Zaman, E-mail: wansafwani@um.edu.my [Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur (Malaysia)

2014-05-30

Highlights: • Hypoxia maintains the stemness of adipose-derived stem cells (ASCs). • ASCs show an increased proliferation rate under low oxygen tension. • Oxygen level as low as 2% enhances the chondrogenic differentiation potential of ASCs. • HIF-1α may regulate the proliferation and differentiation activities of ASCs under hypoxia. - Abstract: Adipose-derived stem cells (ASCs) have been found adapted to a specific niche with low oxygen tension (hypoxia) in the body. As an important component of this niche, oxygen tension has been known to play a critical role in the maintenance of stem cell characteristics. However, the effect of O{sub 2} tension on their functional properties has not been well determined. In this study, we investigated the effects of O{sub 2} tension on ASCs stemness, differentiation and proliferation ability. Human ASCs were cultured under normoxia (21% O{sub 2}) and hypoxia (2% O{sub 2}). We found that hypoxia increased ASC stemness marker expression and proliferation rate without altering their morphology and surface markers. Low oxygen tension further enhances the chondrogenic differentiation ability, but reduces both adipogenic and osteogenic differentiation potential. These results might be correlated with the increased expression of HIF-1α under hypoxia. Taken together, we suggest that growing ASCs under 2% O{sub 2} tension may be important in expanding ASCs effectively while maintaining their functional properties for clinical therapy, particularly for the treatment of cartilage defects.

Canada and international safeguards. Verifying nuclear non-proliferation

International Nuclear Information System (INIS)

1990-01-01

The Non-Proliferation Treaty (NPT) came into force in 1970 and now has about 140 signatory nations. By creating legal barriers against proliferation and by promoting an international non-proliferation ethic, the NPT has promoted international peace and security. A key ingredient has been the confidence generated through verification by IAEA safeguards. By the end of 1988 IAEA safeguards agreements had been concluded with about 100 countries, including Canada. Over 500 nuclear facilities worldwide are under safeguards or contain safeguarded nuclear material. The existence of this credible and effective safeguards system makes international trade in nuclear equipment and materials possible, monitoring the transfer of nuclear technology to developing countries as well as between industrial countries. Canada is committed to non-proliferation and IAEA safeguards. Canadian non-proliferation policy is among the strictest in the world, even though opportunities have been lost to sell Canadian technology abroad as a result

Non-proliferation

International Nuclear Information System (INIS)

Deiseroth, D.; Gustafsson, S.

1993-01-01

The issue of Nuclear Non Proliferation has been moved to a leading place on the contemporary international security agenda. What about the situation of nuclear weapons and nuclear technology in Russia, Kazakhstan, Ukraine and Belorussia? Why did the IAEA-inspectors totally failed to discover any sign of Iraq's clandestine nuclear-weapon programme before the Gulf War? Do the NATO and their nuclear power states violate Art. VI of the Non-Proliferation-Treaty (NPT), because they are - despite the end of the cold war - not willing to renounce of the ''option of the first use of nuclear weapons''? Does the NPT establish a form of nuclear apartheid? What will be the situation if the NPT-Extension-Conference in 1995 will be unable to obtain a majority of the parties for any one extension proposal? Do we need a new international nuclear control agency with severe powers, a sort of nuclear Interpol? The Colloquium ''Saving NPT and abolishing Nuclear Weapons'', held in Stockholm in September 1992, organized by the Swedish and the German Sections of IALANA, tried to analyse some of the raised issues. (orig.) [de

The US proliferation security initiative (PSI)

International Nuclear Information System (INIS)

Gregoire, B.

2004-01-01

The proliferation security initiative (PSI), launched by President Bush on May 31, 2003, aims at intercepting any transfer of mass destruction weapons, of their vectors and related equipments, towards or coming from countries or organizations suspected to have a proliferation activity. This initiative, which involves coercive means to fight against proliferation, raises international lawfulness and legal questions, the answers of which are today under construction. This article analyzes the place of the European Union in the PSI, the action means (optimization of existing means, cooperation between intelligence and interception services), and the PSI stakes (lawfulness with respect to the international law, bilateral agreements, draft boarding agreement, sustain of the United Nations, widening of the partnership and of the field of action). (J.S.)

The economics of proliferation and counterproliferation

International Nuclear Information System (INIS)

Murray, B.L.; Hallenbeck, R.A.; Gill, J.M.

1993-01-01

On June 2, 1993, the fourth meeting of the seminar series on open-quotes Proliferation of Ballistic Missiles and Weapons of Mass Destruction and Implications for Regional Stabilityclose quotes was held at SAIC in McLean, Virginia. This series is sponsored by the Arms Control and Disarmament Agency and is cosponsored by the Ballistic Missile Defense Organization, the Defense Nuclear Agency, the Department of Energy, and the Office of the Secretary of Defense for International Security Policy. The June seminar, open-quotes The Economics of Proliferation and Counterproliferation,close quotes discussed how economic issues and interests affect proliferation judgments. Seminar participants also examined three economic tools for advancing counterproliferation objectives: Economic Development Assistance, Export Controls, and Economic open-quotes Burdensharingclose quotes and Conversion Assistance

Proliferation risks; Proliferatierisico's

Energy Technology Data Exchange (ETDEWEB)

Carchon, R

1998-09-01

The report gives an overview of different aspects related to safeguards of fissile materials. Existing treaties including the Non-Proliferation Treaty, and the Tlatelolco and the Rarotonga Treaties are discussed. An overview of safeguards systems for the control of fissile materials as well as the role of various authorities is given. An overall overview of proliferation risks, the physical protection of fissile materials and the trade in fissile materials is given. Finally, the status in problem countries and de facto nuclear weapon states is discussed.

Similar star formation rate and metallicity variability time-scales drive the fundamental metallicity relation

Science.gov (United States)

Torrey, Paul; Vogelsberger, Mark; Hernquist, Lars; McKinnon, Ryan; Marinacci, Federico; Simcoe, Robert A.; Springel, Volker; Pillepich, Annalisa; Naiman, Jill; Pakmor, Rüdiger; Weinberger, Rainer; Nelson, Dylan; Genel, Shy

2018-06-01

The fundamental metallicity relation (FMR) is a postulated correlation between galaxy stellar mass, star formation rate (SFR), and gas-phase metallicity. At its core, this relation posits that offsets from the mass-metallicity relation (MZR) at a fixed stellar mass are correlated with galactic SFR. In this Letter, we use hydrodynamical simulations to quantify the time-scales over which populations of galaxies oscillate about the average SFR and metallicity values at fixed stellar mass. We find that Illustris and IllustrisTNG predict that galaxy offsets from the star formation main sequence and MZR oscillate over similar time-scales, are often anticorrelated in their evolution, evolve with the halo dynamical time, and produce a pronounced FMR. Our models indicate that galaxies oscillate about equilibrium SFR and metallicity values - set by the galaxy's stellar mass - and that SFR and metallicity offsets evolve in an anticorrelated fashion. This anticorrelated variability of the metallicity and SFR offsets drives the existence of the FMR in our models. In contrast to Illustris and IllustrisTNG, we speculate that the SFR and metallicity evolution tracks may become decoupled in galaxy formation models dominated by feedback-driven globally bursty SFR histories, which could weaken the FMR residual correlation strength. This opens the possibility of discriminating between bursty and non-bursty feedback models based on the strength and persistence of the FMR - especially at high redshift.

Adrenaline promotes cell proliferation and increases chemoresistance in colon cancer HT29 cells through induction of miR-155

International Nuclear Information System (INIS)

Pu, Jun; Bai, Danna; Yang, Xia; Lu, Xiaozhao; Xu, Lijuan; Lu, Jianguo

2012-01-01

Highlights: ► Adrenaline increases colon cancer cell proliferation and its resistance to cisplatin. ► Adrenaline activates NFκB in a dose dependent manner. ► NFκB–miR-155 pathway contributes to cell proliferation and resistance to cisplatin. -- Abstract: Recently, catecholamines have been described as being involved in the regulation of cancer genesis and progression. Here, we reported that adrenaline increased the cell proliferation and decreased the cisplatin induced apoptosis in HT29 cells. Further study found that adrenaline increased miR-155 expression in an NFκB dependent manner. HT29 cells overexpressing miR-155 had a higher cell growth rate and more resistance to cisplatin induced apoptosis. In contrast, HT29 cells overexpressing miR-155 inhibitor displayed decreased cell proliferation and sensitivity to cisplatin induced cell death. In summary, our study here revealed that adrenaline–NFκB–miR-155 pathway at least partially contributes to the psychological stress induced proliferation and chemoresistance in HT29 cells, shedding light on increasing the therapeutic strategies of cancer chemotherapy.

Dynamics of cell proliferation and apoptosis reflect different life strategies in hydrothermal vent and cold seep vestimentiferan tubeworms.

Science.gov (United States)

Pflugfelder, Bettina; Cary, S Craig; Bright, Monika

2009-07-01

Deep-sea vestimentiferan tubeworms, which live in symbiosis with bacteria, exhibit different life strategies according to their habitat. At unstable and relatively short-lived hydrothermal vents, they grow extremely fast, whereas their close relatives at stable and long-persisting cold seeps grow slowly and live up to 300 years. Growth and age differences are thought to occur because of ecological and physiological adaptations. However, the underlying mechanisms of cell proliferation and death, which are closely linked to homeostasis, growth, and longevity, are unknown. Here, we show by immunohistochemical and ultrastructural cell cycle analyses that cell proliferation activities of the two species studied are higher than in any other characterized invertebrate, being only comparable with tumor and wound-healing processes. The slow growth in Lamellibrachia luymesi from cold seeps results from balanced activities of proliferation and apoptosis in the epidermis. In contrast, Riftia pachyptila from hydrothermal vents grows fast because apoptosis is down-regulated in this tissue. The symbiont-housing organ, the trophosome, exhibits a complex cell cycle and terminal differentiation pattern in both species, and growth is regulated by proliferation. These mechanisms have similarities to the up- and down-regulation of proliferation or apoptosis in various types of tumor, although they occur in healthy animals in this study, thus providing significant insights into the underlying mechanisms of growth and longevity.

Cell kinetics of irradiated experimental tumors: cell transition from the non-proliferating to the proliferating pool

International Nuclear Information System (INIS)

Potmesil, M.; Goldfeder, A.

1980-01-01

In murine mammary carcinomas, parenchymal tumor cells with dense nucleoli traverse the cell cycle and divide, thus constituting the proliferating pool. Cells with trabeculate or ring-shaped nucleoli either proceed slowly through G 1 phase or are arrested in it. The role of these non-proliferating, G 1 phase-confined cells in tumor regeneration was studied in vivo after a subcurative dose of X-irradiation in two transplantable tumor lines. Tumor-bearing mice were continuously injected with methyl[ 3 H]thymidine before and after irradiation. Finally, the labeling was discontinued, mice injected with vincristine sulfate and cells arrested in metaphase were accumulated over 10-hrs. Two clearly delineated groups of vincristine-arrested mitoses emerged in autoradiograms prepared from tumor tissue at the time of starting tumor regrowth: one group with the silver-grain counts corresponding to the background level, the other with heavily labeled mitoses. As the only source of unlabeled mitoses was unlabeled G 1 phase-confined cells persisting in the tumor, this indicated cell transition from the non-proliferating to the proliferating pool, which took place in the initial phase of the tumor regrowth. Unlabeled progenitors have apparently remained in G 1 phase for at least 5-12 days after irradiation. (author)

BMP and Ihh/PTHrP signaling interact to coordinate chondrocyte proliferation and differentiation.

Science.gov (United States)

Minina, E; Wenzel, H M; Kreschel, C; Karp, S; Gaffield, W; McMahon, A P; Vortkamp, A

2001-11-01

During endochondral ossification, two secreted signals, Indian hedgehog (Ihh) and parathyroid hormone-related protein (PTHrP), have been shown to form a negative feedback loop regulating the onset of hypertrophic differentiation of chondrocytes. Bone morphogenetic proteins (BMPs), another family of secreted factors regulating bone formation, have been implicated as potential interactors of the Ihh/PTHrP feedback loop. To analyze the relationship between the two signaling pathways, we used an organ culture system for limb explants of mouse and chick embryos. We manipulated chondrocyte differentiation by supplementing these cultures either with BMP2, PTHrP and Sonic hedgehog as activators or with Noggin and cyclopamine as inhibitors of the BMP and Ihh/PTHrP signaling systems. Overexpression of Ihh in the cartilage elements of transgenic mice results in an upregulation of PTHrP expression and a delayed onset of hypertrophic differentiation. Noggin treatment of limbs from these mice did not antagonize the effects of Ihh overexpression. Conversely, the promotion of chondrocyte maturation induced by cyclopamine, which blocks Ihh signaling, could not be rescued with BMP2. Thus BMP signaling does not act as a secondary signal of Ihh to induce PTHrP expression or to delay the onset of hypertrophic differentiation. Similar results were obtained using cultures of chick limbs. We further investigated the role of BMP signaling in regulating proliferation and hypertrophic differentiation of chondrocytes and identified three functions of BMP signaling in this process. First we found that maintaining a normal proliferation rate requires BMP and Ihh signaling acting in parallel. We further identified a role for BMP signaling in modulating the expression of IHH: Finally, the application of Noggin to mouse limb explants resulted in advanced differentiation of terminally hypertrophic cells, implicating BMP signaling in delaying the process of hypertrophic differentiation itself. This

Transient inhibition of cell proliferation does not compromise self-renewal of mouse embryonic stem cells.

Science.gov (United States)

Wang, Ruoxing; Guo, Yan-Lin

2012-10-01

Embryonic stem cells (ESCs) have unlimited capacity for self-renewal and can differentiate into various cell types when induced. They also have an unusual cell cycle control mechanism driven by constitutively active cyclin dependent kinases (Cdks). In mouse ESCs (mESCs). It is proposed that the rapid cell proliferation could be a necessary part of mechanisms that maintain mESC self-renewal and pluripotency, but this hypothesis is not in line with the finding in human ESCs (hESCs) that the length of the cell cycle is similar to differentiated cells. Therefore, whether rapid cell proliferation is essential for the maintenance of mESC state remains unclear. We provide insight into this uncertainty through chemical intervention of mESC cell cycle. We report here that inhibition of Cdks with olomoucine II can dramatically slow down cell proliferation of mESCs with concurrent down-regulation of cyclin A, B and E, and the activation of the Rb pathway. However, mESCs display can recover upon the removal of olomoucine II and are able to resume normal cell proliferation without losing self-renewal and pluripotency, as demonstrated by the expression of ESC markers, colony formation, embryoid body formation, and induced differentiation. We provide a mechanistic explanation for these observations by demonstrating that Oct4 and Nanog, two major transcription factors that play critical roles in the maintenance of ESC properties, are up-regulated via de novo protein synthesis when the cells are exposed to olomoucine II. Together, our data suggest that short-term inhibition of cell proliferation does not compromise the basic properties of mESCs. Copyright © 2012 Elsevier Inc. All rights reserved.

Proliferation resistance assessment of pyro processing

Energy Technology Data Exchange (ETDEWEB)

Kwon, E. H.; Ko, W. I.; Kim, H. D. [KAERI, Daejeon (Korea, Republic of)

2012-10-15

In 2002, world experts gathered and defined the term proliferation resistance as 'the characteristic of a nuclear energy system that impedes the diversion or undeclared production of nuclear material, or misuse of technology, by State in order to acquire nuclear weapons or other nuclear explosive devices.' The same report also defines the following terms: Intrinsic barriers (technical features) of proliferation resistance are features that result from the technical design of nuclear energy systems, including those that facilitate the implementation of extrinsic measures. Extrinsic barriers (institutional measures) of proliferation resistance are features that result from the decisions and undertakings of states related to nuclear energy system. Intrinsic barriers are further divided into material barriers.the 'intrinsic, or inherent, qualities of materials that reduce the inherent desirability or attractiveness of the material as an explosive' and technical barriers. The 'intrinsic technical lements of the fuel cycle, its facilities, processes, and equipment that serve to make it difficult to gain access to materials and/or to use or misuse facilities to obtain weapons usable materials.' Material barriers include isotopic, chemical, radiological, mass and bulk, and detectability, whereas technical barriers include facility unattractiveness, accessibility, available fissile mass, detectability of and time required for diversion, and skills, expertise, and knowledge. Assessing the proliferation resistance of pyro processing is meaningful only when compared with other processes. This paper attempts to discuss the features of pyro processing by comparing it with direct disposal and aqueous separation processes from a proliferation resistance viewpoint.

Panel on nuclear export and proliferation

International Nuclear Information System (INIS)

Kimel, W.R.

1977-01-01

Summaries of six panelists' remarks make the following points: one cannot suppress nuclear weapons by suppressing nuclear power; a proliferated world would be extremely dangerous; US supports IAEA safeguards; plutonium shouldn't be recycled in power reactors; and the problem of nonproliferation is a social and institutional problem, not a technological one. Viewographs showing the semantics of proliferation, ways to get nuclear weapons materials, etc. are included

Russia and proliferation in Northeast Asia

International Nuclear Information System (INIS)

Ignatov, A.I.

1995-01-01

For Russia, security, including non-proliferation, in Northeast Asia means in particular the maintenance of stability. Progress in arms control and non-proliferation may enhance regional stability. A common regional approach is proposed. Russia recognizes the US alliances with Japan and republic of Korea and is searching for a new cooperation framework in the region, namely further development of relations with China and reasonable rapprochement with Japan

Y-27632, a ROCK Inhibitor, Promoted Limbal Epithelial Cell Proliferation and Corneal Wound Healing.

Directory of Open Access Journals (Sweden)

Chi-Chin Sun

Full Text Available Transplantation of ex vivo cultured limbal epithelial cells is proven effective in restoring limbal stem cell deficiency. The present study aimed to investigate the promoting effect of Y-27632 on limbal epithelial cell proliferation. Limbal explants isolated from human donor eyes were expanded three weeks on culture dishes and outgrowth of epithelial cells was subsequently subcultured for in vitro experiments. In the presence of Y-27632, the ex vivo limbal outgrowth was accelerated, particularly the cells with epithelial cell-like morphology. Y-27632 dose-dependently promoted the proliferation of in vitro cultured human limbal epithelial cells as examined by phase contrast microscopy and luminescent cell-viability assay 30 hours after the treatment. The colony forming efficacy determined 7 days after the treatment was enhanced by Y-27632 also in a dose-dependent manner. The number of p63- or Ki67-positive cells was dose-dependently increased in Y-27632-treated cultures as detected by immunofluorescent staining and western blotanalysis. Cell cycle analysis by flow cytometric method revealed an increase in S-phase proliferating cells. The epithelial woundclosure rate was shown to be faster in experimental group received topical treatment withY-27632 than the sham control using a rat corneal wounding model. These resultsdemonstrate that Y-27632 can promote both the ex vivo and in vitro proliferation oflimbal epithelial cell proliferation. The in vivo enhanced epithelial wound healingfurther implies that the Y-27632 may act as a new strategy for treating limbal stem cell deficiency.

Non proliferation 1980 - INFCE and TnP

International Nuclear Information System (INIS)

Rainer, R.

1981-01-01

The TNP (non-proliferation agreement of nuclear weapons), its non proliferation policy and the peaceful use of fuel cycle are described, as well as the safeguards of IAEA. It is also mentioned the functions of INFCE (International Nuclear Fuel Cycle Evaluation). (A.B.T.) [pt

Non-proliferation issues for the disposition of fissile materials using reactor alternatives

International Nuclear Information System (INIS)

Jaeger, C.D.; Duggan, R.A.; Tolk, K.M.

1996-01-01

The Department of Energy (DOE) is analyzing long-term storage on options for excess weapons-usable fissile materials. A number of the disposition alternatives are being considered which involve the use of reactors. The various reactor alternatives are all very similar and include front-end processes that could convert plutonium to a usable form for fuel fabrication, a MOX fuel fab facility, reactors to bum the MOX fuel and ultimate disposal of spent fuel in some geologic repository. They include existing, partially completed, advanced or evolutionary light water reactors and Canadian deuterium uranium (CANDU) reactors. In addition to the differences in the type of reactors, other variants on these alternatives are being evaluated to include the location and number of the reactors, the location of the mixed oxide (MOX) fabrication facility, the ownership of the facilities (private or government) and the colocation and/or separation of these facilities. All of these alternatives and their variants must be evaluated with respect to non-proliferation resistance. Both domestic and international safeguards support are being provided to DOE's Fissile Materials Disposition Program (FMDP) and includes such areas as physical protection, nuclear materials accountability and material containment and surveillance. This paper will focus on how the non-proliferation objective of reducing security risks and strengthening arms reduction will be accomplished and what some of the nonproliferation issues are for the reactor alternatives. Proliferation risk has been defined in terms of material form, physical environment, and the level of security and safeguards that is applied to the material. Metrics have been developed for each of these factors. The reactor alternatives will be evaluated with respect to these proliferation risk factors at each of the unit process locations in the alternative

Plant root proliferation in nitrogen-rich patches confers competitive advantage

Science.gov (United States)

Robinson, D.; Hodge, A.; Griffiths, B. S.; Fitter, A. H.

1999-01-01

Plants respond strongly to environmental heterogeneity, particularly below ground, where spectacular root proliferations in nutrient-rich patches may occur. Such 'foraging' responses apparently maximize nutrient uptake and are now prominent in plant ecological theory. Proliferations in nitrogen-rich patches are difficult to explain adaptively, however. The high mobility of soil nitrate should limit the contribution of proliferation to N capture. Many experiments on isolated plants show only a weak relation between proliferation and N uptake. We show that N capture is associated strongly with proliferation during interspecific competition for finite, locally available, mixed N sources, precisely the conditions under which N becomes available to plants on generally infertile soils. This explains why N-induced root proliferation is an important resource-capture mechanism in N-limited plant communities and suggests that increasing proliferation by crop breeding or genetic manipulation will have a limited impact on N capture by well-fertilized monocultures.

Modeling and evaluating proliferation resistance of nuclear energy systems for strategy switching proliferation

International Nuclear Information System (INIS)

Yue, M.; Cheng, L.-Y.; Bari, R.A.

2013-01-01

Highlights: ► Sensitivity analysis is carried out for the model and physical input parameters. ► Interphase drag has minor effect on the dryout heat flux (DHF) in 1D configuration. ► Model calibration on pressure drop experiments fails to improve prediction of DHF. ► Calibrated classical model provides the best agreement with DHF data from 1D tests. ► Further validation of drag models requires data from 2D and 3D experiments on DHF. - Abstract: This paper reports a Markov model based approach to systematically evaluating the proliferation resistance (PR) of nuclear energy systems (NESs). The focus of the study is on the development of the Markov models for a class of complex PR scenarios, i.e., mixed covert/overt strategy switching proliferation, for NESs with two modes of material flow, batch and continuous. In particular, a set of diversion and/or breakout scenarios and covert/overt misuse scenarios are studied in detail for an Example Sodium Fast Reactor (ESFR) system. Both probabilistic and deterministic PR measures are calculated using a software tool that implements the proposed approach and can be used to quantitatively compare proliferation resistant characteristics of different scenarios for a given NES, according to the computed PR measures

Docosahexaenoic acid (DHA) effects on proliferation and steroidogenesis of bovine granulosa cells.

Science.gov (United States)

Maillard, Virginie; Desmarchais, Alice; Durcin, Maeva; Uzbekova, Svetlana; Elis, Sebastien

2018-04-26

Docosahexaenoic acid (DHA) is a n-3 polyunsaturated fatty acid (PUFA) belonging to a family of biologically active fatty acids (FA), which are known to have numerous health benefits. N-3 PUFAs affect reproduction in cattle, and notably directly affect follicular cells. In terms of reproduction in cattle, n-3 PUFA-enriched diets lead to increased follicle size or numbers. The objective of the present study was to analyze the effects of DHA (1, 10, 20 and 50 μM) on proliferation and steroidogenesis (parametric and/or non parametric (permutational) ANOVA) of bovine granulosa cells in vitro and mechanisms of action through protein expression (Kruskal-Wallis) and signaling pathways (non parametric ANOVA) and to investigate whether DHA could exert part of its action through the free fatty acid receptor 4 (FFAR4). DHA (10 and 50 μM) increased granulosa cell proliferation and DHA 10 μM led to a corresponding increase in proliferating cell nuclear antigen (PCNA) expression level. DHA also increased progesterone secretion at 1, 20 and 50 μM, and estradiol secretion at 1, 10 and 20 μM. Consistent increases in protein levels were also reported for the steroidogenic enzymes, cytochrome P450 family 11 subfamily A member 1 (CYP11A1) and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 (HSD3B1), and of the cholesterol transporter steroidogenic acute regulatory protein (StAR), which are necessary for production of progesterone or androstenedione. FFAR4 was expressed in all cellular types of bovine ovarian follicles, and in granulosa cells it was localized close to the cellular membrane. TUG-891 treatment (1 and 50 μM), a FFAR4 agonist, increased granulosa cell proliferation and MAPK14 phosphorylation in a similar way to that observed with DHA treatment. However, TUG-891 treatment (1, 10 and 50 μM) showed no effect on progesterone or estradiol secretion. These data show that DHA stimulated proliferation and steroidogenesis of bovine

Nuclear power and nuclear weapon proliferation

International Nuclear Information System (INIS)

Apold, A.

1978-01-01

The theme of Dr. Marshall's lecture was that it is, from the viewpoint of prevention of proliferation of nuclear weapons,preferable to use plutonium as a fuel in FBR reactors rather than store it in what, in effect, would be plutonium mines. The true threat of proliferation lies in uranium enrichment. The FBR reactor is misunderstood and the US policy is not against breeders as such. Safeguards against the misuse of plutonium by leaving a residue of radioactivity after reprocessing is quite feasible, despite certain practical problems and extra costs. Weapon proliferation is subject to political objectives and intentions. Definite proposals are, (a) a limited number of reprocessing centres, (b) an accelerated development of FBR reactors, (c) a new FBR fuel cycle, (d) stop storage of spent thermal reactor fuel, (e) reinforced safeguards. (JIW)

Nuclear non-proliferation

International Nuclear Information System (INIS)

Anon.

1990-01-01

This patent describes the treaty on the non-proliferation of nuclear weapons which is the corner-stone of an international non-proliferation regime which has grown to embrace the overwhelming majority of countries in the world in the period since the Treaty. The other elements of the regime include, first of all, the safeguards system of IAEA-which operates to prevent the diversion of nuclear materials to military or other prohibited activities and must be accepted by all non-nuclear-weapon parties to the Treaty and, secondly, the Antarctic Treaty, the Treaty for the Prohibition of Nuclear Weapons in Latin America (Treaty of Tlatelolco) and the south Pacific Nuclear Free zone Treaty (Treaty of Rarotonga)-which serve to extend the regime geographically. The last two Treaties require safeguards agreements with IAEA. In addition, the Treaty of Tlatelolco contains provisions establishing the agency for the Prohibition of Nuclear Weapons in Latin America and the Caribbean to ensure compliance

Species-specific differences in peroxisome proliferation, catalase, and SOD2 upregulation as well as toxicity in human, mouse, and rat hepatoma cells induced by the explosive and environmental pollutant 2,4,6-trinitrotoluene.

Science.gov (United States)

Naumenko, Ekaterina Anatolevna; Ahlemeyer, Barbara; Baumgart-Vogt, Eveline

2017-03-01

2,4,6-Trinitrotoluene (TNT) has been widely used as an explosive substance and its toxicity is still of interest as it persisted in polluted areas. TNT is metabolized in hepatocytes which are prone to its toxicity. Since analysis of the human liver or hepatocytes is restricted due to ethical reasons, we investigated the effects of TNT on cell viability, reactive oxygen species (ROS) production, peroxisome proliferation, and antioxidative enzymes in human (HepG2), mouse (Hepa 1-6), and rat (H4IIEC3) hepatoma cell lines. Under control conditions, hepatoma cells of all three species were highly comparable exhibiting identical proliferation rates and distribution of their cell cycle phases. However, we found strong differences in TNT toxicity with the lowest IC 50 values (highest cell death rate) for rat cells, whereas human and mouse cells were three to sevenfold less sensitive. Moreover, a strong decrease in cellular dehydrogenase activity (MTT assay) and increased ROS levels were noted. TNT caused peroxisome proliferation with rat hepatoma cells being most responsive followed by those from mouse and human. Under control conditions, rat cells contained fivefold higher peroxisomal catalase and mitochondrial SOD2 activities and a twofold higher capacity to reduce MTT than human and mouse cells. TNT treatment caused an increase in catalase and SOD2 mRNA and protein levels in human and mouse, but not in rat cells. Similarly, human and mouse cells upregulated SOD2 activity, whereas rat cells failed therein. We conclude that TNT induced oxidative stress, peroxisome proliferation and mitochondrial damage which are highest in rat cells rendering them most susceptible toward TNT. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 989-1006, 2017. © 2016 Wiley Periodicals, Inc.

Fisetin regulates astrocyte migration and proliferation in vitro

OpenAIRE

Wang, Nan; Yao, Fang; Li, Ke; Zhang, Lanlan; Yin, Guo; Du, Mingjun; Wu, Bingyi

2017-01-01

Fisetin (3,3?,4?,7-tetrahydroxyflavone) is a plant flavonol found in fruits and vegetables that has been reported to inhibit migration and proliferation in several types of cancer. Reactive astrogliosis involves astrocyte migration and proliferation, and contributes to the formation of glial scars in central nervous system (CNS) disorders. However, the effect of fisetin on the migration and proliferation of astrocytes remains unclear. In this study, we found that fisetin inhibited astrocyte m...

Nuclear proliferation in developing countries: A comparative study for selected countries

International Nuclear Information System (INIS)

Chun Woong.

1991-01-01

This study explores major conditions conducive to nuclear proliferation to project possible proliferation trends in the future and, hopefully, to suggest some effective strategies to address the problem of nuclear proliferation. It attempts to provide a qualitative analysis of the causes and trends of nuclear proliferation by presenting generalizations of the causes of proliferation. While a variety of factors can be considered as causes of proliferation, three primary factors appear to influence the prospects for proliferation: (1) the technical capabilities and constraints; (2) motivation: incentives and disincentives; and (3) particular domestic and international situations. It is generally hypothesized that in order for a country to go nuclear, two basic conditions - some minimum level of indigenous national capability and strong motivations - must be simultaneously satisfied. It is concluded that while technology is, of course, one element necessary for the nuclear-proliferation process, the fundamental conditions of nuclear proliferation appear to be motivational factors

Effect of gamma irradiation on proliferation and survival of Sf9 cells: radioresistance in a Lepidopteran insect cell line

International Nuclear Information System (INIS)

Seth, R.K.; Lovell, K.V.; Reynolds, S.E.

2003-01-01

Sf9 cells of Spodoptera frugiperda, when exposed to gamma-irradiation from a 60 Co source, were found markedly less sensitive to ionising radiation than mammalian cells in terms of both growth kinetics and survival. Following irradiation at 1.2 Gy S -1 there was a dose-dependent delay in Sf9 cell proliferation and plateau cell density was reduced. These effects were dependent on dose rate too. In the range 0.3 - 1.2 Gy s -1 , growth was delayed longer and reached a lower plateau with increasing dose rate. Exposure to radiation caused a decrease in adherence of cells to the substrate, and an increase in number of enlarged ('giant') cells. Analysis of colony formation after irradiation at 1.2 Gy s -1 gave a survival curve of conventional shape but with a very large D o value of 24 Gy. Extrapolation number (N) was 2.9, a value within the normal range for mammalian cells. At 0.12 Gy s -1 N had a similar value of 3.2, but D o was higher (30 Gy) than at the higher dose rate. This study indicates that the relative insensitivity of lepidoptera insects may be attributed to some extent to the intrinsic properties of their constituent cells. (author)

Non-circadian rhythm in proliferation of haematopoietic stem cells

International Nuclear Information System (INIS)

Necas, E.; Znojil, V.

1988-01-01

The proportion of haematopoietic stem cells (CFU-s) engaged in DNA synthesis was determined by means of the [ 3 H]-thymidine ([ 3 H]TdR) suicide technique during recovery of bone marrow from the damage caused by a sublethal total body irradiation. In contrast with previous reports the [ 3 H]TdR suicide rate was not permanently increased. It was observed that CFU-s passed through S phase in synchronous waves, following a dose of irradiation of 1.5 Gy. After a dose of 2.6 Gy, there was only one initial wave of increased CFU-s sensitivity to the action of [ 3 H]TdR. Following the depression occurring 26 hr after the irradiation with 2.6 Gy, the proportion of CFU-s killed by the [ 3 H]TdR was permanently increased until 5-6 days after irradiation. Thereafter large differences in the [ 3 H]TdR suicide data were observed among individual mice. Evidence was obtained that individual mice, which had been irradiated by a dose of 2.6 Gy 8-9 days before, had identical values of the CFU-s [ 3 H]TdR suicide rate in the bone marrow from different bones of the lower extremities. The recurrence of the synchronous waves in CFU-s passage through the cell cycle was recorded when the CFU-s population regenerated to only about 10% of its normal value. It is concluded that the synchronous waves in which CFU-s proliferation occurred reflected the action of the control mechanism on CFU-s proliferation. (author)

Non-circadian rhythm in proliferation of haematopoietic stem cells

Energy Technology Data Exchange (ETDEWEB)

Necas, E; Znojil, V [Charles Univ., Prague (Czechoslovakia). Faculty of Medicine

1988-03-01

The proportion of haematopoietic stem cells (CFU-s) engaged in DNA synthesis was determined by means of the (/sup 3/H)-thymidine ((/sup 3/H)TdR) suicide technique during recovery of bone marrow from the damage caused by a sublethal total body irradiation. In contrast with previous reports the (/sup 3/H)TdR suicide rate was not permanently increased. It was observed that CFU-s passed through S phase in synchronous waves, following a dose of irradiation of 1.5 Gy. After a dose of 2.6 Gy, there was only one initial wave of increased CFU-s sensitivity to the action of (/sup 3/H)TdR. Following the depression occurring 26 hr after the irradiation with 2.6 Gy, the proportion of CFU-s killed by the (/sup 3/H)TdR was permanently increased until 5-6 days after irradiation. Thereafter large differences in the (/sup 3/H)TdR suicide data were observed among individual mice. Evidence was obtained that individual mice, which had been irradiated by a dose of 2.6 Gy 8-9 days before, had identical values of the CFU-s (/sup 3/H)TdR suicide rate in the bone marrow from different bones of the lower extremities. The recurrence of the synchronous waves in CFU-s passage through the cell cycle was recorded when the CFU-s population regenerated to only about 10% of its normal value. It is concluded that the synchronous waves in which CFU-s proliferation occurred reflected the action of the control mechanism on CFU-s proliferation. (author).

The challenge of nuclear proliferation control in South Asia

International Nuclear Information System (INIS)

Mian, J.A.

1996-01-01

Prevention of nuclear weapon proliferation in South Asia is considered a a difficult challenge. The paper discusses the difficulties met in implementing the nuclear non-proliferation policy due to numerous disputes concerning China, North and South Korea, India and Pakistan, and the countries of former Soviet Union. Matters preventing proliferation are mentioned as well as obstacles to non-proliferation proposing that decisions whether voluntary or, eventually, compulsory would have to be consistently enforced by the Security Council, if states are to rely upon those methods for their security

Colon Cancer Chemoprevention by Sage Tea Drinking: Decreased DNA Damage and Cell Proliferation.

Science.gov (United States)

Pedro, Dalila F N; Ramos, Alice A; Lima, Cristovao F; Baltazar, Fatima; Pereira-Wilson, Cristina

2016-02-01

Salvia officinalis and some of its isolated compounds have been found to be preventive of DNA damage and increased proliferation in vitro in colon cells. In the present study, we used the azoxymethane model to test effects of S. officinalis on colon cancer prevention in vivo. The results showed that sage treatment reduced the number of ACF formed only if administered before azoxymethane injection, demonstrating that sage tea drinking has a chemopreventive effect on colorectal cancer. A decrease in the proliferation marker Ki67 and in H2 O2 -induced and azoxymethane-induced DNA damage to colonocytes and lymphocytes were found with sage treatment. This confirms in vivo the chemopreventive effects of S. officinalis. Taken together, our results show that sage treatment prevented initiation phases of colon carcinogenesis, an effect due, at least in part, to DNA protection, and reduced proliferation rates of colon epithelial cell that prevent mutations and their fixation through cell replication. These chemopreventive effects of S. officinalis on colon cancer add to the many health benefits attributed to sage and encourage its consumption. Copyright © 2015 John Wiley & Sons, Ltd.

Nuclear power and the proliferation issue

International Nuclear Information System (INIS)

Marshall, W.

1978-02-01

The purpose of the lecture is to discuss nuclear proliferation, analyse which problems are real and which are a misapprehension, and to suggest a way forward which retains the benefits of nuclear power while providing a more certain protection against undesirable proliferation. After an introductory section the lecture continues under the following headings: plutonium production and accessibility; the use of plutonium; fast reactor fuel; the interim period; conclusions. (U.K.)

Increased classical endoplasmic reticulum stress is sufficient to reduce chondrocyte proliferation rate in the growth plate and decrease bone growth.

Directory of Open Access Journals (Sweden)

Louise H W Kung

Full Text Available Mutations in genes encoding cartilage oligomeric matrix protein and matrilin-3 cause a spectrum of chondrodysplasias called multiple epiphyseal dysplasia (MED and pseudoachondroplasia (PSACH. The majority of these diseases feature classical endoplasmic reticulum (ER stress and activation of the unfolded protein response (UPR as a result of misfolding of the mutant protein. However, the importance and the pathological contribution of ER stress in the disease pathogenesis are unknown. The aim of this study was to investigate the generic role of ER stress and the UPR in the pathogenesis of these diseases. A transgenic mouse line (ColIITgcog was generated using the collagen II promoter to drive expression of an ER stress-inducing protein (Tgcog in chondrocytes. The skeletal and histological phenotypes of these ColIITgcog mice were characterised. The expression and intracellular retention of Tgcog induced ER stress and activated the UPR as characterised by increased BiP expression, phosphorylation of eIF2α and spliced Xbp1. ColIITgcog mice exhibited decreased long bone growth and decreased chondrocyte proliferation rate. However, there was no disruption of chondrocyte morphology or growth plate architecture and perturbations in apoptosis were not apparent. Our data demonstrate that the targeted induction of ER stress in chondrocytes was sufficient to reduce the rate of bone growth, a key clinical feature associated with MED and PSACH, in the absence of any growth plate dysplasia. This study establishes that classical ER stress is a pathogenic factor that contributes to the disease mechanism of MED and PSACH. However, not all the pathological features of MED and PSACH were recapitulated, suggesting that a combination of intra- and extra-cellular factors are likely to be responsible for the disease pathology as a whole.

Andrographolide suppresses preadipocytes proliferation through glutathione antioxidant systems abrogation.

Science.gov (United States)

Chen, Wei; Su, Hongming; Feng, Lina; Zheng, Xiaodong

2016-07-01

Oxidative stress is considered to play a profound role in lipid storage and whole-body energy homeostasis. Inhibition of preadipocytes proliferation by natural products is one of the strategies to prevent obesity. Andrographolide, a small molecule, has been reported to possess versatile bioactivities. However, molecular mechanism underlying the potential effect of andrographolide on preadipocytes proliferation remains obscure. In the present study, 3T3-L1 preadipocytes were employed to determine whether andrographolide could affect the proliferation of preadipocytes. Our results demonstrated andrographolide suppressed 3T3-L1 preadipocytes proliferation. The casual relationship analysis indicated that andrographolide (10 and 20μg/ml) appeared to exert the proliferation inhibitory effect through suppression of glutathione peroxidase 1 (GPX1) activity and depleting GSH by promoting its efflux in 3T3-L1 preadipocytes, which subsequently resulted in 2.06-2.41 fold increase in ROS accumulation. Excessive ROS eruption could account for oxidative damage to mitochondrial membranes as well as ultimately inhibition of cell proliferation. Taken together, our study reveals that suppression of GPX1 and GSH depletion by andrographolide seems to play a critical role in the inhibition of 3T3-L1 preadipocytes proliferation, which might have implication for obesity prevention and treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Emerging nuclear energy systems and nuclear weapon proliferation

International Nuclear Information System (INIS)

Gsponer, A.; Sahin, S.; Jasani, B.

1983-01-01

Generally when considering problems of proliferation of nuclear weapons, discussions are focused on horizontal proliferation. However, the emerging nuclear energy systems currently have an impact mainly on vertical proliferation. The paper indicates that technologies connected with emerging nuclear energy systems, such as fusion reactors and accelerators, enhance the knowledge of thermonuclear weapon physics and will enable production of military useful nuclear materials (including some rare elements). At present such technologies are enhancing the arsenal of the nuclear weapon states. But one should not forget the future implications for horizontal proliferation of nuclear weapons as some of the techniques will in the near future be within the technological and economic capabilities of non-nuclear weapon states. Some of these systems are not under any international control. (orig.) [de

Effects of prefeeding a prebiotic on diarrhea and colonic cell proliferation in piglets fed lactulose.

Science.gov (United States)

Kien, C Lawrence; Chang, J C; Cooper, James R; Frankel, Wendy L

2004-01-01

Severe lactulose malabsorption causes osmotic diarrhea and decreased cecal cell proliferation. We tested the hypothesis that prefeeding with inulin, a prebiotic, would attenuate these effects. Piglets aged 10 days were randomized to 3 feeding groups (n = 6 each group): Control (CON), fed sow-milk replacement formula (SMR; lactose, 60 g/L) for 14 days; a lactulose-challenged group (LAC) that was fed SMR for 7 days and then a formula containing lactose (30 g/L) and lactulose (60 g/L) for 7 days; and a group prefed SMR containing inulin (3 g/L) for 7 days and then fed the lactulose-supplemented formula (INULIN). Groups CON and INULIN were pair-fed to LAC. Then, cecal tissue was collected for histology, determination of crypt cell proliferation index, apoptosis, and Western blot determination of expression of Bax, a pro-apoptotic protein. The fraction of days when diarrhea was present (mean +/- SD) was greater for LAC (0.87 +/- 0.14; p = .004) than CON (0.28 +/- 0.22; INULIN: 0.52 +/- 0.44; p = .058 vs LAC). Cell proliferation index for the total crypt was less for LAC (0.12 +/- 0.04; p = .016) compared with CON (0.20 +/- 0.04; INULIN: 0.15 +/- 0.04; p = .06 vs LAC). BAX protein expression and apoptosis were similar in the 3 groups. We observed trends consistent with the hypothesis that prefeeding inulin attenuates diarrhea and the reduction in cell proliferation caused by lactulose.

Accelerated in vivo proliferation of memory phenotype CD4+ T-cells in human HIV-1 infection irrespective of viral chemokine co-receptor tropism.

Directory of Open Access Journals (Sweden)

Yan Zhang

Full Text Available CD4(+ T-cell loss is the hallmark of HIV-1 infection. CD4 counts fall more rapidly in advanced disease when CCR5-tropic viral strains tend to be replaced by X4-tropic viruses. We hypothesized: (i that the early dominance of CCR5-tropic viruses results from faster turnover rates of CCR5(+ cells, and (ii that X4-tropic strains exert greater pathogenicity by preferentially increasing turnover rates within the CXCR4(+ compartment. To test these hypotheses we measured in vivo turnover rates of CD4(+ T-cell subpopulations sorted by chemokine receptor expression, using in vivo deuterium-glucose labeling. Deuterium enrichment was modeled to derive in vivo proliferation (p and disappearance (d* rates which were related to viral tropism data. 13 healthy controls and 13 treatment-naive HIV-1-infected subjects (CD4 143-569 cells/ul participated. CCR5-expression defined a CD4(+ subpopulation of predominantly CD45R0(+ memory cells with accelerated in vivo proliferation (p = 2.50 vs 1.60%/d, CCR5(+ vs CCR5(-; healthy controls; P<0.01. Conversely, CXCR4 expression defined CD4(+ T-cells (predominantly CD45RA(+ naive cells with low turnover rates. The dominant effect of HIV infection was accelerated turnover of CCR5(+CD45R0(+CD4(+ memory T-cells (p = 5.16 vs 2.50%/d, HIV vs controls; P<0.05, naïve cells being relatively unaffected. Similar patterns were observed whether the dominant circulating HIV-1 strain was R5-tropic (n = 9 or X4-tropic (n = 4. Although numbers were small, X4-tropic viruses did not appear to specifically drive turnover of CXCR4-expressing cells (p = 0.54 vs 0.72 vs 0.44%/d in control, R5-tropic, and X4-tropic groups respectively. Our data are most consistent with models in which CD4(+ T-cell loss is primarily driven by non-specific immune activation.

H2A/K pseudogene mutation may promote cell proliferation

Energy Technology Data Exchange (ETDEWEB)

Guo, Jisheng; Jing, Ruirui; Lv, Xin; Wang, Xiaoyue; Li, Junqiang; Li, Lin; Li, Cuiling; Wang, Daoguang; Bi, Baibing; Chen, Xinjun [Cancer Research Center, Shandong University School of Medicine, Jinan 250012 (China); Yang, Jing-Hua, E-mail: sdu_crc_group1@126.com [Cancer Research Center, Shandong University School of Medicine, Jinan 250012 (China); Department of Surgery, VA Boston Healthcare System, Boston University School of Medicine, Boston 510660, MA (United States)

2016-05-15

Highlights: • The mutant H2A/K pseudogene is active. • The mutant H2A/K pseudogene can promote cell proliferation. - Abstract: Little attention has been paid to the histone H2A/K pseudogene. Results from our laboratory showed that 7 of 10 kidney cancer patients carried a mutant H2A/K pseudogene; therefore, we were interested in determining the relationship between mutant H2A/K and cell proliferation. We used shotgun and label-free proteomics methods to study whether mutant H2A/K lncRNAs affected cell proliferation. Quantitative proteomic analysis indicated that the expression of mutant H2A/K lncRNAs resulted in the upregulation of many oncogenes, which promoted cell proliferation. Further interaction analyses revealed that a proliferating cell nuclear antigen (PCNA)-protein interaction network, with PCNA in the center, contributes to cell proliferation in cells expressing the mutant H2A/K lncRNAs. Western blotting confirmed the critical upregulation of PCNA by mutant H2A/K lncRNA expression. Finally, the promotion of cell proliferation by mutant H2A/K lncRNAs (C290T, C228A and A45G) was confirmed using cell proliferation assays. Although we did not determine the exact mechanism by which the oncogenes were upregulated by the mutant H2A/K lncRNAs, we confirmed that the mutant H2A/K lncRNAs promoted cell proliferation by upregulating PCNA and other oncogenes. The hypothesis that cell proliferation is promoted by the mutant H2A/K lncRNAs was supported by the protein expression and cell proliferation assay results. Therefore, mutant H2A/K lncRNAs may be a new factor in renal carcinogenesis.

Synemin promotes AKT-dependent glioblastoma cell proliferation by antagonizing PP2A.

Science.gov (United States)

Pitre, Aaron; Davis, Nathan; Paul, Madhumita; Orr, A Wayne; Skalli, Omar

2012-04-01

The intermediate filament protein synemin is present in astrocyte progenitors and glioblastoma cells but not in mature astrocytes. Here we demonstrate a role for synemin in enhancing glioblastoma cell proliferation and clonogenic survival, as synemin RNA interference decreased both behaviors by inducing G1 arrest along with Rb hypophosphorylation and increased protein levels of the G1/S inhibitors p21(Cip1) and p27(Kip1). Akt involvement was demonstrated by decreased phosphorylation of its substrate, p21(Cip1), and reduced Akt catalytic activity and phosphorylation at essential activation sites. Synemin silencing, however, did not affect the activities of PDPK1 and mTOR complex 2, which directly phosphorylate Akt activation sites, but instead enhanced the activity of the major regulator of Akt dephosphorylation, protein phosphatase type 2A (PP2A). This was accompanied by changes in PP2A subcellular distribution resulting in increased physical interactions between PP2A and Akt, as shown by proximity ligation assays (PLAs). PLAs and immunoprecipitation experiments further revealed that synemin and PP2A form a protein complex. In addition, treatment of synemin-silenced cells with the PP2A inhibitor cantharidic acid resulted in proliferation and pAkt and pRb levels similar to those of controls. Collectively these results indicate that synemin positively regulates glioblastoma cell proliferation by helping sequester PP2A away from Akt, thereby favoring Akt activation.

International nuclear proliferation: multilateral diplomacy and regional aspects

Energy Technology Data Exchange (ETDEWEB)

Kapur, A.

1979-01-01

Confidential interviews with about 200 officials at 18 nuclear research sites around the world form the background for this discussion of the proliferation issues as they affect the Nuclear Non-Proliferation Treaty (NPT). Critics of the NPT cite its narrow focus on horizontal proliferation and its failures in the areas of vertical proliferation, nuclear technology transfers, heavy-water-reactor systems, and safeguards. The international negotiations necessary to resolve these issues and the difficulty of reaching a global consensus indicate a need to restructure the U.S. decision process before diplomacy can progress. The book discusses the history and nature of proliferation and its relationship to multinational diplomacy; the problems of permanent and workable safeguards; and regional political ramifications in the creeping dependencies of South Asia, apartheid in South Africa, militarization in Japan, and the nuclearization of Brazil and Argentina. The analysis concludes that central issues were not settled by the NPT and that U.S. failures to speak without consulting allies may mean that a bilateral rather than multinational approach should be tried. 105 references, 5 figures, 12 tables. (DCK)

Canada's nuclear non-proliferation policy

International Nuclear Information System (INIS)

1985-01-01

Canada's non-proliferation and safeguards policy has two objectives: 1) to promote the emergence of a more effective and comprehensive international non-proliferation regime; and 2) to assure the Canadian people and the international community that Canadian nuclear exports will not be used for any nuclear explosive purpose. By emphasizing the key role of the NPT, by promoting reliance upon and improvements in the IAEA safeguards system, by treating nuclear weapon and non-nuclear weapon states alike regarding Canadian nuclear exports, by working for new approaches covering the sensitive phases (e.g. reprocessing) of the nuclear fuel cycle, Canada's policy promotes attainment of the first objective. The latter objective is served through the network of bilateral nuclear agreements that Canada has put into place with its nuclear partners. Those agreements provide assurance that Canada's nuclear exports are used solely for legitimate, peaceful, nuclear energy production purposes. At the same time, Canada, having formulated its non-proliferation and safeguards policy during the period 1945 to 1980, has recognized that it has gone as far as it can on its own in this field and that from this point on any further changes should be made on the basis of international agreement. The Canadian objective in post-INFCE forums such as the Committee on Assurances of Supply is to exert Canada's best efforts to persuade the international community to devise a more effective and comprehensive international non-proliferation regime into which Canada and other suppliers might subsume their national requirements

Nuclear Proliferation Technology Trends Analysis

Energy Technology Data Exchange (ETDEWEB)

Zentner, Michael D.; Coles, Garill A.; Talbert, Robert J.

2005-10-04

A process is underway to develop mature, integrated methodologies to address nonproliferation issues. A variety of methodologies (both qualitative and quantitative) are being considered. All have one thing in common, a need for a consistent set of proliferation related data that can be used as a basis for application. One approach to providing a basis for predicting and evaluating future proliferation events is to understand past proliferation events, that is, the different paths that have actually been taken to acquire or attempt to acquire special nuclear material. In order to provide this information, this report describing previous material acquisition activities (obtained from open source material) has been prepared. This report describes how, based on an evaluation of historical trends in nuclear technology development, conclusions can be reached concerning: (1) The length of time it takes to acquire a technology; (2) The length of time it takes for production of special nuclear material to begin; and (3) The type of approaches taken for acquiring the technology. In addition to examining time constants, the report is intended to provide information that could be used to support the use of the different non-proliferation analysis methodologies. Accordingly, each section includes: (1) Technology description; (2) Technology origin; (3) Basic theory; (4) Important components/materials; (5) Technology development; (6) Technological difficulties involved in use; (7) Changes/improvements in technology; (8) Countries that have used/attempted to use the technology; (9) Technology Information; (10) Acquisition approaches; (11) Time constants for technology development; and (12) Required Concurrent Technologies.

Comparative analysis of proliferation resistance assessment methodologies

International Nuclear Information System (INIS)

Takaki, Naoyuki; Kikuchi, Masahiro; Inoue, Naoko; Osabe, Takeshi

2005-01-01

Comparative analysis of the methodologies was performed based on the discussions in the international workshop on 'Assessment Methodology of Proliferation Resistance for Future Nuclear Energy Systems' held in Tokyo, on March 2005. Through the workshop and succeeding considerations, it is clarified that the proliferation resistance assessment methodologies are affected by the broader nuclear options being pursued and also by the political situations of the state. Even the definition of proliferation resistance, despite the commonality of fundamental issues, derives from perceived threat and implementation circumstances inherent to the larger programs. Deep recognitions of the 'difference' among communities would help us to make further essential and progressed discussion with harmonization. (author)

Limiting Future Proliferation and Security Risks

International Nuclear Information System (INIS)

Bari, R.

2011-01-01

A major new technical tool for evaluation of proliferation and security risks has emerged over the past decade as part the activities of the Generation IV International Forum. The tool has been developed by a consensus group from participating countries and organizations and is termed the Proliferation Resistance and Physical Protection (PR and PP) Evaluation Methodology. The methodology defines a set of challenges, analyzes system response to these challenges, and assesses outcomes. The challenges are the threats posed by potential actors (proliferant states or sub-national adversaries). It is of paramount importance in an evaluation to establish the objectives, capabilities, resources, and strategies of the adversary as well as the design and protection contexts. Technical and institutional characteristics are both used to evaluate the response of the system and to determine its resistance against proliferation threats and robustness against sabotage and terrorism threats. The outcomes of the system response are expressed in terms of a set of measures, which thereby define the PR and PP characteristics of the system. This paper summarizes results of applications of the methodology to nuclear energy systems including reprocessing facilities and large and small modular reactors. The use of the methodology in the design phase a facility will be discussed as it applies to future safeguards concepts.

Nuclear Society and non-proliferation problems

International Nuclear Information System (INIS)

Gagarinskij, A.Ya.; Kushnarev, S.V.; Ponomarev-Stepnoj, N.N.; Sukhoruchkin, V.K.; Khromov, V.V.; Shmelev, V.M.

1997-01-01

In the USSR Nuclear Society in 1991 the special working group on the problems of nuclear weapons non-proliferation and nuclear materials control, uniting the experts of different types (nuclear physicists, lawyers, teachers), was created. This group became the mechanism of the practical Nuclear Society activity realization in this sphere. Three milestones of the innovative activity can be specified. First Milestone. In January 1992 the Central Nuclear Society Board (of the International Public Nuclear Society Association) published a special appeal to the First Leaders of all countries - former USSR republics. This address paid a special attention to the unity of the USSR power-industrial complex, and numerous problems arisen while separating this complex, including nuclear weapons non-proliferation problems, were indicated as well. Second Milestone. In 1992 and 1993 the Nuclear Society experts issued two selection 'Nuclear Non-proliferation and Control Problems' including reviewing basic papers. In addition, materials on non-proliferation and control are published regularly in the organs. Third Milestone.In 1993 - 1997 some special scientific and technical events (conferences, workshops, meetings) allowing to analyze the joint international projects and contracts outcomes, and establish new contacts between the specialists of NIS, Baltic states and others, have been hold

Mullerian papilloma-like proliferation arising in cystic pelvic endosalpingiosis.

Science.gov (United States)

McCluggage, W Glenn; O'Rourke, Declan; McElhenney, Clodagh; Crooks, Michael

2002-09-01

This report describes an unusual epithelial proliferation occurring in pelvic cystic endosalpingiosis. A cyst mass lined by a layer of ciliated epithelial cells involved the posterior surface of the cervix and vagina. The epithelial proliferation within the wall resembled a mullerian papilloma with fibrous and fibrovascular cores lined by bland cuboidal epithelial cells. Other areas had a microglandular growth pattern resembling cervical microglandular hyperplasia, and focally there was a solid growth pattern. Foci of typical endosalpingiosis involved the surface of both ovaries and pelvic soft tissues. The cystic lesion recurred after partial cystectomy and drainage and was followed up radiologically and with periodic fine-needle aspiration. Part of the wall of the cyst removed 11 years after the original surgery showed an identical epithelial proliferation. MIB1 staining showed a proliferation index of less than 5%, contrasting with the higher proliferation index of a typical serous borderline tumor. The differential diagnosis is discussed. As far as we are aware, this is the first report of such a benign epithelial proliferation involving cystic endosalpingiosis. Copyright 2002, Elsevier Science (USA). All rights reserved.

Transient inhibition of cell proliferation does not compromise self-renewal of mouse embryonic stem cells

Energy Technology Data Exchange (ETDEWEB)

Wang, Ruoxing [Department of Biological Sciences, The University of Southern Mississippi, 118 College Drive 5018, Hattiesburg, MS 39406 (United States); Guo, Yan-Lin, E-mail: yanlin.guo@usm.edu [Department of Biological Sciences, The University of Southern Mississippi, 118 College Drive 5018, Hattiesburg, MS 39406 (United States)

2012-10-01

Embryonic stem cells (ESCs) have unlimited capacity for self-renewal and can differentiate into various cell types when induced. They also have an unusual cell cycle control mechanism driven by constitutively active cyclin dependent kinases (Cdks). In mouse ESCs (mESCs). It is proposed that the rapid cell proliferation could be a necessary part of mechanisms that maintain mESC self-renewal and pluripotency, but this hypothesis is not in line with the finding in human ESCs (hESCs) that the length of the cell cycle is similar to differentiated cells. Therefore, whether rapid cell proliferation is essential for the maintenance of mESC state remains unclear. We provide insight into this uncertainty through chemical intervention of mESC cell cycle. We report here that inhibition of Cdks with olomoucine II can dramatically slow down cell proliferation of mESCs with concurrent down-regulation of cyclin A, B and E, and the activation of the Rb pathway. However, mESCs display can recover upon the removal of olomoucine II and are able to resume normal cell proliferation without losing self-renewal and pluripotency, as demonstrated by the expression of ESC markers, colony formation, embryoid body formation, and induced differentiation. We provide a mechanistic explanation for these observations by demonstrating that Oct4 and Nanog, two major transcription factors that play critical roles in the maintenance of ESC properties, are up-regulated via de novo protein synthesis when the cells are exposed to olomoucine II. Together, our data suggest that short-term inhibition of cell proliferation does not compromise the basic properties of mESCs. -- Highlights: Black-Right-Pointing-Pointer Inhibition of Cdks slows down mESCs proliferation. Black-Right-Pointing-Pointer mESCs display remarkable recovery capacity from short-term cell cycle interruption. Black-Right-Pointing-Pointer Short-term cell cycle interruption does not compromise mESC self-renewal. Black

Transient inhibition of cell proliferation does not compromise self-renewal of mouse embryonic stem cells

International Nuclear Information System (INIS)

Wang, Ruoxing; Guo, Yan-Lin

2012-01-01

Embryonic stem cells (ESCs) have unlimited capacity for self-renewal and can differentiate into various cell types when induced. They also have an unusual cell cycle control mechanism driven by constitutively active cyclin dependent kinases (Cdks). In mouse ESCs (mESCs). It is proposed that the rapid cell proliferation could be a necessary part of mechanisms that maintain mESC self-renewal and pluripotency, but this hypothesis is not in line with the finding in human ESCs (hESCs) that the length of the cell cycle is similar to differentiated cells. Therefore, whether rapid cell proliferation is essential for the maintenance of mESC state remains unclear. We provide insight into this uncertainty through chemical intervention of mESC cell cycle. We report here that inhibition of Cdks with olomoucine II can dramatically slow down cell proliferation of mESCs with concurrent down-regulation of cyclin A, B and E, and the activation of the Rb pathway. However, mESCs display can recover upon the removal of olomoucine II and are able to resume normal cell proliferation without losing self-renewal and pluripotency, as demonstrated by the expression of ESC markers, colony formation, embryoid body formation, and induced differentiation. We provide a mechanistic explanation for these observations by demonstrating that Oct4 and Nanog, two major transcription factors that play critical roles in the maintenance of ESC properties, are up-regulated via de novo protein synthesis when the cells are exposed to olomoucine II. Together, our data suggest that short-term inhibition of cell proliferation does not compromise the basic properties of mESCs. -- Highlights: ► Inhibition of Cdks slows down mESCs proliferation. ► mESCs display remarkable recovery capacity from short-term cell cycle interruption. ► Short-term cell cycle interruption does not compromise mESC self-renewal. ► Oct4 and Nanog are up-regulated via de novo synthesis by cell cycle interruption.

Nuclear dilemma: power, proliferation, and development

International Nuclear Information System (INIS)

Miller, M.

1979-01-01

Debate over President Carter's nuclear energy policy centers on how to develop nuclear power for civilian use and prevent the proliferation of nuclear materials for weapons. Both supporters and opponents of nuclear energy have been critical of Carter's policies because each side fails to see the linkage between the two concerns as codified in the 1978 Non-Proliferation Act. The author uses a dialogue format to illustrate the arguments for resisting proliferation and recognizing nuclear energy as an appropriate technology. The consequences of a nuclear moratorium are explored along with implications for foreign policy. U.S. leadership in developing energy technologies that can meet a broad range of appropriate applications, combined with leadership in building appropriate political frameworks, is needed if nuclear energy is to make a positive contribution toward world peace and acceptable living standards. 8 references

Safeguards and non-proliferation: current challenges and the implications for Australia

International Nuclear Information System (INIS)

Leask, A.; Carlson, J.

2006-01-01

Full text: The expansion of nuclear programs raises the issue of how to ensure this does not increase the risk of nuclear weapons proliferation. The non-proliferation regime - based on the NPT and its verification mechanism, the IAEA safeguards system - has been developed to provide assurance that nuclear programs are exclusively peaceful. Although to date the non-proliferation regime has been remarkably successful, in recent years it has come under serious challenge. Nuclear proliferation is emerging as one of the major issues facing the international community. Addressing technical and institutional aspects of the non-proliferation regime - especially safeguards, but also complementary measures such as export controls, proliferation-resistant technology, and an international framework on sensitive technology - is important. But proliferation is a political problem, and ultimately the success of the non-proliferation regime depends on political resolve to uphold compliance, using incentives and if necessary sanctions. These issues are vitally important to Australia's future. Being a major uranium supplier has strengthened Australia's influence in non-proliferation and safeguards developments

Wnt5b-associated exosomes promote cancer cell migration and proliferation.

Science.gov (United States)

Harada, Takeshi; Yamamoto, Hideki; Kishida, Shosei; Kishida, Michiko; Awada, Chihiro; Takao, Toshifumi; Kikuchi, Akira

2017-01-01

Wnt5b is a member of the same family of proteins as Wnt5a, the overexpression of which is associated with cancer aggressiveness. Wnt5b is also suggested to be involved in cancer progression, however, details remain unclarified. We analyzed the biochemical properties of purified Wnt5b and the mode of secretion of Wnt5b by cancer cells. Wnt5b was glycosylated at three asparagine residues and lipidated at one serine residue, and these post-translational modifications of Wnt5b were essential for secretion. Purified Wnt5b showed Dvl2 phosphorylation and Rac activation abilities to a similar extent as Wnt5a. In cultured-cell conditioned medium, Wnt5b was detected in supernatant or precipitation fractions that were separated by centrifugation at 100 000 g. In PANC-1 pancreatic cancer cells, 55% of secreted endogenous Wnt5b was associated with exosomes. Exosomes from wild-type PANC-1 cells, but not those from Wnt5b-knockout PANC-1 cells, activated Wnt5b signaling in CHO cells and stimulated migration and proliferation of A549 lung adenocarcinoma cells, suggesting that endogenous, Wnt5b-associated exosomes are active. The exosomes were taken up by CHO cells and immunoelectron microscopy revealed that Wnt5b is indeed associated with exosomes. In Caco-2 colon cancer cells, most Wnt5b was recovered in precipitation fractions when Wnt5b was ectopically expressed (Caco-2/Wnt5b cells). Knockdown of TSG101, an exosome marker, decreased the secretion of Wnt5b-associated exosomes from Caco-2/Wnt5b cells and inhibited Wnt5b-dependent cell proliferation. Exosomes secreted from Caco-2/Wnt5b cells stimulated migration and proliferation of A549 cells. These results suggest that Wnt5b-associated exosomes promote cancer cell migration and proliferation in a paracrine manner. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Inhibition of human lung cancer cell proliferation and survival by wine

Science.gov (United States)

2014-01-01

Background Compounds of plant origin and food components have attracted scientific attention for use as agents for cancer prevention and treatment. Wine contains polyphenols that were shown to have anti-cancer and other health benefits. The survival pathways of Akt and extracellular signal-regulated kinase (Erk), and the tumor suppressor p53 are key modulators of cancer cell growth and survival. In this study, we examined the effects of wine on proliferation and survival of human Non-small cell lung cancer (NSCLC) cells and its effects on signaling events. Methods Human NSCLC adenocarcinoma A549 and H1299 cells were used. Cell proliferation was assessed by thymidine incorporation. Clonogenic assays were used to assess cell survival. Immunoblotting was used to examine total and phosphorylated levels of Akt, Erk and p53. Results In A549 cells red wine inhibited cell proliferation and reduced clonogenic survival at doses as low as 0.02%. Red wine significantly reduced basal and EGF-stimulated Akt and Erk phosphorylation while it increased the levels of total and phosphorylated p53 (Ser15). Control experiments indicated that the anti-proliferative effects of wine were not mediated by the associated contents of ethanol or the polyphenol resveratrol and were independent of glucose transport into cancer cells. White wine also inhibited clonogenic survival, albeit at a higher doses (0.5-2%), and reduced Akt phosphorylation. The effects of both red and white wine on Akt phosphorylation were also verified in H1299 cells. Conclusions Red wine inhibits proliferation of lung cancer cells and blocks clonogenic survival at low concentrations. This is associated with inhibition of basal and EGF-stimulated Akt and Erk signals and enhancement of total and phosphorylated levels of p53. White wine mediates similar effects albeit at higher concentrations. Our data suggest that wine may have considerable anti-tumour and chemoprevention properties in lung cancer and deserves further

Effects of celecoxib on proliferation and tenocytic differentiation of tendon-derived stem cells

Energy Technology Data Exchange (ETDEWEB)

Zhang, Kairui; Zhang, Sheng [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Li, Qianqian [Cancer Research Institute, Southern Medical University, Guangzhou 510515 (China); Yang, Jun [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Department of Orthopaedics, 421 Hospital of PLA, Guangzhou 510318 (China); Dong, Weiqiang [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Department of Orthopaedics, The First Affiliated Hospital to Guangzhou Medical University, Guangzhou 510120 (China); Wang, Shengnan; Cheng, Yirong; Al-Qwbani, Mohammed [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Wang, Qiang, E-mail: 1780468505@qq.com [Department of Orthopaedics, Subei People’s Hospital of Jiangsu Province (Clinical Medical College of Yangzhou University), Yangzhou, Jiangsu Province 225001 (China); Yu, Bin, E-mail: carryzhang1985@live.com [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China)

2014-07-18

Highlights: • Celecoxib has no effects on TDSCs cell proliferation in various concentrations. • Celecoxib reduced mRNAs levels of tendon associated transcription factor. • Celecoxib reduced mRNAs levels of main tendon associated collagen. • Celecoxib reduced mRNAs levels of tendon associated molecules. - Abstract: NSAIDs are often ingested to reduce the pain and improve regeneration of tendon after tendon injury. Although the effects of NSAIDs in tendon healing have been reported, the data and conclusions are not consistent. Recently, tendon-derived stem cells (TDSCs) have been isolated from tendon tissues and has been suggested involved in tendon repair. Our study aims to determine the effects of COX-2 inhibitor (celecoxib) on the proliferation and tenocytic differentiation of TDSCs. TDSCs were isolated from mice Achilles tendon and exposed to celecoxib. Cell proliferation rate was investigated at various concentrations (0.1, 1, 10 and 100 μg/ml) of celecoxib by using hemocytometer. The mRNA expression of tendon associated transcription factors, tendon associated collagens and tendon associated molecules were determined by reverse transcription-polymerase chain reaction. The protein expression of Collagen I, Collagen III, Scleraxis and Tenomodulin were determined by Western blotting. The results showed that celecoxib has no effects on TDSCs cell proliferation in various concentrations (p > 0.05). The levels of most tendon associated transcription factors, tendon associated collagens and tendon associated molecules genes expression were significantly decreased in celecoxib (10 μg/ml) treated group (p < 0.05). Collagen I, Collagen III, Scleraxis and Tenomodulin protein expression were also significantly decreased in celecoxib (10 μg/ml) treated group (p < 0.05). In conclusion, celecoxib inhibits tenocytic differentiation of tendon-derived stem cells but has no effects on cell proliferation.

Effects of celecoxib on proliferation and tenocytic differentiation of tendon-derived stem cells

International Nuclear Information System (INIS)

Zhang, Kairui; Zhang, Sheng; Li, Qianqian; Yang, Jun; Dong, Weiqiang; Wang, Shengnan; Cheng, Yirong; Al-Qwbani, Mohammed; Wang, Qiang; Yu, Bin

2014-01-01

Highlights: • Celecoxib has no effects on TDSCs cell proliferation in various concentrations. • Celecoxib reduced mRNAs levels of tendon associated transcription factor. • Celecoxib reduced mRNAs levels of main tendon associated collagen. • Celecoxib reduced mRNAs levels of tendon associated molecules. - Abstract: NSAIDs are often ingested to reduce the pain and improve regeneration of tendon after tendon injury. Although the effects of NSAIDs in tendon healing have been reported, the data and conclusions are not consistent. Recently, tendon-derived stem cells (TDSCs) have been isolated from tendon tissues and has been suggested involved in tendon repair. Our study aims to determine the effects of COX-2 inhibitor (celecoxib) on the proliferation and tenocytic differentiation of TDSCs. TDSCs were isolated from mice Achilles tendon and exposed to celecoxib. Cell proliferation rate was investigated at various concentrations (0.1, 1, 10 and 100 μg/ml) of celecoxib by using hemocytometer. The mRNA expression of tendon associated transcription factors, tendon associated collagens and tendon associated molecules were determined by reverse transcription-polymerase chain reaction. The protein expression of Collagen I, Collagen III, Scleraxis and Tenomodulin were determined by Western blotting. The results showed that celecoxib has no effects on TDSCs cell proliferation in various concentrations (p > 0.05). The levels of most tendon associated transcription factors, tendon associated collagens and tendon associated molecules genes expression were significantly decreased in celecoxib (10 μg/ml) treated group (p < 0.05). Collagen I, Collagen III, Scleraxis and Tenomodulin protein expression were also significantly decreased in celecoxib (10 μg/ml) treated group (p < 0.05). In conclusion, celecoxib inhibits tenocytic differentiation of tendon-derived stem cells but has no effects on cell proliferation

Director`s series on proliferation

Energy Technology Data Exchange (ETDEWEB)

Bailey, K.C.; Price, M.E. [eds.

1994-12-27

The Director`s Series on Proliferation is an occasional publication of essays on the topics of nuclear, chemical, biological, and missile proliferation. The seven papers presented in this issue cover the following topics: Should the Treaty on the Nonproliferation of Nuclear Weapons (NPT) be amended?; NPT extension - Legal and procedural issues; An Indonesian view of NPT review conference issues; The treaty of Tlatelolco and the NPT - Tools for peace and development; Perspectives on cut-off, weapons dismantlement, and security assurances; Belarus and NPT challenges; A perspective on the chemical weapons convention - Lessons learned from the preparatory commission.

Microfluidic system for monitoring of cardiac (H9C2) cell proliferation

Science.gov (United States)

Kobuszewska, A.; Cwik, P.; Jastrzebska, E.; Brzozka, Z.; Chudy, M.; Renaud, P.; Dybko, A.

2017-05-01

The paper presents the application of electrical impedance spectroscopy (EIS) analysis for investigation of cardiac cell (H9C2 - rat cardiomyoblast) proliferation after verapamil hydrochloride exposure. For this purpose, two different PDMS/glass microsystems with circular microchamber and longitudinal microchannel integrated with Pt/Al electrodes were used. The microchambers were fabricated in PDMS using photolithography and replica moulding techniques. Pt/Al electrodes were fabricated on a 4-inch glass substrate using Physical Vapor Deposition (PVD). Solution of verapamil hydrochloride was continuously introduced into the microsystems with H9C2 cell culture (a flow rate of 1 μl/min) for 72 h. The impedance spectra were recorded from 100 Hz to 1 MHz. We confirmed that impedance spectroscopy can be used for non-invasive, label-free and real-time analysis of cardiac cells proliferation based on cells dielectric properties and biological structure.

Energy efficiency and proliferation assessment factors

International Nuclear Information System (INIS)

1979-02-01

The objective of INFCE is to evaluate the nuclear fuel cycles from the point of view of their ability to satisfy the worldwide nuclear energy needs, while minimizing the proliferation risks. Accordingly, the different working groups have to take into consideration as well the energy-efficiency and the proliferation-resistance of these nuclear fuel cycles. The present working paper is aimed at suggesting the main assessment factors which should be taken into consideration

An Introduction to The Interdisciplinary Concept of Risk-Informed Proliferation Resistance

International Nuclear Information System (INIS)

Gouveia, Fernando

2010-01-01

The nonproliferation community is rich in diverse attempts aimed at predicting and preventing attempts at nuclear proliferation. Such efforts, however, are rarely incorporated into a holistic approach well-suited to solving both existing and emerging proliferation dilemmas. This division is particularly apparent with respect to the partition that separates the socio-political and technical approaches to solving such problems, approaches which are very often developed and utilized in isolation. Complicating matters further, are the diverse positions taken by various entities as they relate to the secure implementation of nuclear energy world-wide. Such positions range from the obdurate belief in the supposed inherent proliferation resistance of traditional spent fuel, to those regarding all nuclear energy systems as inherently proliferation prone, given their core reliance on the sensitive technologies of enrichment and reprocessing. Accordingly, moderates have argued for a risk-informed approach to combat nuclear proliferation, combining institutional factors, such as IAEA safeguards, with innovative reactor and fuel designs to bring about an acceptable notion of proliferation resistance. To this end, methodologies have been developed, which seek to assess and score attained proliferation resistance. Most notably, these include, the Proliferation Resistance and Physical Protection (PR and PP) methodology prepared by the GEN-IV International Forum and the IAEA's International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO). Such approaches have greatly advanced the concept of proliferation resistance; however, they remain limited by their exclusive concentration on the technological determinants of proliferation and non-consideration of other, equally important, socio-political determinants. This limitation is significant as numerous incidents have illustrated the ability of atypical states to find alternate paths to proliferation, for example

Proliferation of massive destruction weapons: fantasy or reality?

International Nuclear Information System (INIS)

Duval, M.

2001-01-01

This article evaluates the threat of massive destruction weapons (nuclear, chemical, biological) for Europe and recalls the existing safeguards against the different forms of nuclear proliferation: legal (non-proliferation treaty (NPT), comprehensive nuclear test ban treaty (CTBT), fissile material cut off treaty (FMCT) etc..), technical (fabrication of fissile materials, delays). However, all these safeguards can be overcome as proven by the activities of some countries. The situation of proliferation for the other type of massive destruction weapons is presented too. (J.S.)

Pooled human platelet lysate versus fetal bovine serum-investigating the proliferation rate, chromosome stability and angiogenic potential of human adipose tissue-derived stem cells intended for clinical use.

Science.gov (United States)

Trojahn Kølle, Stig-Frederik; Oliveri, Roberto S; Glovinski, Peter V; Kirchhoff, Maria; Mathiasen, Anders Bruun; Elberg, Jens Jørgen; Andersen, Peter Stemann; Drzewiecki, Krzysztof Tadeusz; Fischer-Nielsen, Anne

2013-09-01

Because of an increasing focus on the use of adipose-derived stem cells (ASCs) in clinical trials, the culture conditions for these cells are being optimized. We compared the proliferation rates and chromosomal stability of ASCs that had been cultured in Dulbecco's modified Eagle's Medium (DMEM) supplemented with either pooled human platelet lysate (pHPL) or clinical-grade fetal bovine serum (FBS) (DMEM(pHPL) versus DMEM(FBS)). ASCs from four healthy donors were cultured in either DMEM(pHPL) or DMEM(FBS), and the population doubling time (PDT) was calculated. ASCs from two of the donors were expanded in DMEM(pHPL) or DMEM(FBS) and cultured for the final week before harvesting with or without the addition of vascular endothelial growth factor. We assessed the chromosomal stability (through the use of array comparative genomic hybridization), the expression of ASC and endothelial surface markers and the differentiation and angiogenic potential of these cells. The ASCs that were cultured in pHPL exhibited a significantly shorter PDT of 29.6 h (95% confidence interval, 22.3-41.9 h) compared with those cultured in FBS, for which the PDT was 123.9 h (95% confidence interval, 95.6-176.2 h). Comparative genomic hybridization analyses revealed no chromosomal aberrations. Cell differentiation, capillary structure formation and cell-surface marker expression were generally unaffected by the type of medium supplement that was used or by the addition of vascular endothelial growth factor. We observed that the use of pHPL as a growth supplement for ASCs facilitated a significantly higher proliferation rate compared with FBS without compromising genomic stability or differentiation capacity. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Phonological Similarity in American Sign Language.

Science.gov (United States)

Hildebrandt, Ursula; Corina, David

2002-01-01

Investigates deaf and hearing subjects' ratings of American Sign Language (ASL) signs to assess whether linguistic experience shapes judgments of sign similarity. Findings are consistent with linguistic theories that posit movement and location as core structural elements of syllable structure in ASL. (Author/VWL)

Passive leg movement enhances interstitial VEGF protein, endothelial cell proliferation, and eNOS mRNA content in human skeletal muscle

DEFF Research Database (Denmark)

Hellsten, Ylva; Rufener, Nora; Nielsen, Jens J

2008-01-01

.05) in blood flow without a significant enhancement in oxygen uptake. Muscle interstitial fluid was sampled with microdialysis technique and analyzed for vascular endothelial growth factor (VEGF) protein and for the effect on endothelial cell proliferation. Biopsies obtained from the musculus vastus lateralis...... to cultured endothelial cells revealed that dialysate obtained during leg movement induced a 3.2-fold higher proliferation rate (P level fourfold above resting levels. VEGF mRNA and MMP-2 mRNA levels were...

The year 2000 examination conference of the non-proliferation treaty and the future of the nuclear non-proliferation regime

International Nuclear Information System (INIS)

Grand, C.

2001-01-01

The nuclear weapons non-proliferation treaty (NPT), signed on July 1, 1968 and enforced on March 5, 1970, has been progressively considered as the headstone of the international non-proliferation and disarmament regime. The sixth NPT examination conference took place at New York (USA) in the year 2000, 5 years after the previous conference but also after the first nuclear weapon tests of India and Pakistan. This article recalls up the main non-proliferation events that took place between the 1995 and 2000 conferences and presents the progresses and results of the New York conference. Finally, it wonders about the ambiguities in the conclusions of this last conference. (J.S.)

Bizarre parosteal osteochondromatous proliferation of the proximal humerus: case report

Energy Technology Data Exchange (ETDEWEB)

Bush, J.B.; Meyer, Mark S. [Ochsner Clinic Foundation, Department of Orthopedics, New Orleans, LA (United States); Reith, John D. [University of Florida College of Medicine, Departments of Pathology, Immunology and Laboratory Medicine and Orthopaedics and Rehabilitation, Gainesville, Florida (United States)

2007-06-15

Bizarre parosteal osteochondromatous proliferation (BPOP), or Nora's lesion, is a rare lesion of bone occurring predominantly in the long bones of the hands and feet. It exists as a puzzling clinical entity of uncertain origins and high recurrence rates after surgical resection. To our knowledge, this clinical entity has not been reported in the proximal aspect of the humerus. An interesting report of a lesion occurring in the proximal humerus, which initially was misinterpreted as a parosteal osteosarcoma, is discussed outlining the clinical, radiographic and pathologic features of the BPOP lesion. (orig.)

Bizarre parosteal osteochondromatous proliferation of the proximal humerus: case report

International Nuclear Information System (INIS)

Bush, J.B.; Meyer, Mark S.; Reith, John D.

2007-01-01

Bizarre parosteal osteochondromatous proliferation (BPOP), or Nora's lesion, is a rare lesion of bone occurring predominantly in the long bones of the hands and feet. It exists as a puzzling clinical entity of uncertain origins and high recurrence rates after surgical resection. To our knowledge, this clinical entity has not been reported in the proximal aspect of the humerus. An interesting report of a lesion occurring in the proximal humerus, which initially was misinterpreted as a parosteal osteosarcoma, is discussed outlining the clinical, radiographic and pathologic features of the BPOP lesion. (orig.)

Nuclear power the challenges of non-proliferation

International Nuclear Information System (INIS)

Anon.

2010-01-01

The revival of the civil nuclear power industry rekindles the debate on proliferation, in other words, on the increase in the number of States likely to achieve nuclear weapon capability. The history of the past thirty years shows that none of the known attempts at proliferation has occurred within the scope of civil nuclear program development. No country that has decided to 'proliferate' has done so by diverting materials or installations governed by the commitment to peaceful utilization and under IAEA control. The only borderline case is India, which did not sign the NPT, and which in 1974 cleverly played on the clauses imposed on it by Canada without violating them in the strictest sense of the word. The exporters of civil nuclear technologies subsequently got organized to control the export of sensitive materials by creating the Club of London, since renamed the Nuclear Suppliers Group. Another crisis occurred in 1991 following the first Gulf war, with the discovery of an extensive covert nuclear program in Iraq (an NPT signatory country); this caused a shock similar to that of 1974 and resulted in the strengthening of the IAEA's powers and inspection resources. India subsequently carried out several nuclear tests in 1998, at least one of which was a thermonuclear device. Pakistan, India's rival since the 1948 partition, crossed the 'nuclear threshold' in 1999. Proliferation also made headlines in 2003. First of all with Libya which, having decided to sign the NPT, revealed the existence of what is called the 'Nuke AQ Khan Bazaar'. In the presumed ignorance of his government, Dr. Abdul Qadeer Khan had stolen an uranium enrichment technology, becoming the 'father' of the Pakistani bomb, and had organized the traffic of military nuclear technologies, namely with Libya, North Korea and Iran. Again in 2003, North Korea announced its withdrawal from the NPT. This retreat raises the question of what will become of the possible transfers of nuclear technologies that

Mobile phone radiation alters proliferation of hepatocarcinoma cells.

Science.gov (United States)

Ozgur, Elcin; Guler, Goknur; Kismali, Gorkem; Seyhan, Nesrin

2014-11-01

This study investigated the effects of intermittent exposure (15 min on, 15 min off for 1, 2, 3, or 4 h, at a specific absorption rate of 2 W/kg) to enhanced data rates for global system for mobile communication evolution-modulated radiofrequency radiation (RFR) at 900- and 1,800-MHz frequencies on the viability of the Hepatocarcinoma cells (Hep G2). Hep G2 cell proliferation was measured by a colorimetric assay based on the cleavage of the tetrazolium salt WST-1 by mitochondrial dehydrogenases in viable cells. Cell injury was evaluated by analyzing the levels of lactate dehydrogenase (LDH) and glucose released from lysed cells into the culture medium. Morphological observation of the nuclei was carried out by 4',6-diamidino-2-phenylindole (DAPI) staining using fluorescence microscopy. In addition, TUNEL assay was performed to confirm apoptotic cell death. It was observed that cell viability, correlated with the LDH and glucose levels, changed according to the frequency and duration of RFR exposure. Four-hour exposure produced more pronounced effects than the other exposure durations. 1,800-MHz RFR had a larger impact on cell viability and Hep G2 injury than the RFR at 900 MHz. Morphological observations also supported the biochemical results indicating that most of the cells showed irregular nuclei pattern determined by using the DAPI staining, as well as TUNEL assay which shows DNA damage especially in the cells after 4 h of exposure to 1,800-MHz RFR. Our results indicate that the applications of 900- and 1,800-MHz (2 W/kg) RFR cause to decrease in the proliferation of the Hep G2 cells after 4 h of exposure. Further studies will be conducted on other frequency bands of RFR and longer duration of exposure.

Contrasting ecosystem-effects of morphologically similar copepods.

Directory of Open Access Journals (Sweden)

Blake Matthews

Full Text Available Organisms alter the biotic and abiotic conditions of ecosystems. They can modulate the availability of resources to other species (ecosystem engineering and shape selection pressures on other organisms (niche construction. Very little is known about how the engineering effects of organisms vary among and within species, and, as a result, the ecosystem consequences of species diversification and phenotypic evolution are poorly understood. Here, using a common gardening experiment, we test whether morphologically similar species and populations of Diaptomidae copepods (Leptodiaptomus ashlandi, Hesperodiaptomus franciscanus, Skistodiaptomus oregonensis have similar or different effects on the structure and function of freshwater ecosystems. We found that copepod species had contrasting effects on algal biomass, ammonium concentrations, and sedimentation rates, and that copepod populations had contrasting effects on prokaryote abundance, sedimentation rates, and gross primary productivity. The average size of ecosystem-effect contrasts between species was similar to those between populations, and was comparable to those between fish species and populations measured in previous common gardening experiments. Our results suggest that subtle morphological variation among and within species can cause multifarious and divergent ecosystem-effects. We conclude that using morphological trait variation to assess the functional similarity of organisms may underestimate the importance of species and population diversity for ecosystem functioning.

Why heavy and light quarks radiate energy with similar rates

International Nuclear Information System (INIS)

Kopeliovich, B. Z.; Potashnikova, I. K.; Schmidt, Ivan

2010-01-01

The dead-cone effect has been predicted to reduce the magnitude of energy loss and jet quenching for heavy flavors produced with large p T in heavy-ion collisions. On the contrary, data from the Relativistic Heavy Ion Collider demonstrate a strong suppression of high-p T electrons from charm and bottom decays. We show that vacuum radiation of a highly virtual quark produced at high p T with a stripped-off color field develops a much wider dead cone, which screens the one related to the quark mass. Lacking the field, gluons cannot be radiated within this cone until the color field is regenerated and the quark virtuality cools down to the scale of the order of the quark mass. However, this takes longer than is essential for the observed jet quenching, leading to similar nuclear effects for the light and charm quark jets. Open beauty is expected to radiate much less within the p T range studied so far in heavy-ion collisions.

Adrenaline promotes cell proliferation and increases chemoresistance in colon cancer HT29 cells through induction of miR-155

Energy Technology Data Exchange (ETDEWEB)

Pu, Jun [Department of General Surgery, Tangdu Hospital of the Fourth Military Medical University, Xi' an 710038 (China); Bai, Danna [Department of Cardiology, 323 Hospital of PLA, Xi' an 710054 (China); Yang, Xia [Department of Teaching and Medical Administration, Tangdu Hospital of the Fourth Military Medical University, Xi' an 710038 (China); Lu, Xiaozhao [Department of Nephrology, The 323 Hospital of PLA, Xi' an 710054 (China); Xu, Lijuan, E-mail: 13609296272@163.com [Department of Nephrology, The 323 Hospital of PLA, Xi' an 710054 (China); Lu, Jianguo, E-mail: lujianguo029@yahoo.com.cn [Department of General Surgery, Tangdu Hospital of the Fourth Military Medical University, Xi' an 710038 (China)

2012-11-16

Highlights: Black-Right-Pointing-Pointer Adrenaline increases colon cancer cell proliferation and its resistance to cisplatin. Black-Right-Pointing-Pointer Adrenaline activates NF{kappa}B in a dose dependent manner. Black-Right-Pointing-Pointer NF{kappa}B-miR-155 pathway contributes to cell proliferation and resistance to cisplatin. -- Abstract: Recently, catecholamines have been described as being involved in the regulation of cancer genesis and progression. Here, we reported that adrenaline increased the cell proliferation and decreased the cisplatin induced apoptosis in HT29 cells. Further study found that adrenaline increased miR-155 expression in an NF{kappa}B dependent manner. HT29 cells overexpressing miR-155 had a higher cell growth rate and more resistance to cisplatin induced apoptosis. In contrast, HT29 cells overexpressing miR-155 inhibitor displayed decreased cell proliferation and sensitivity to cisplatin induced cell death. In summary, our study here revealed that adrenaline-NF{kappa}B-miR-155 pathway at least partially contributes to the psychological stress induced proliferation and chemoresistance in HT29 cells, shedding light on increasing the therapeutic strategies of cancer chemotherapy.

Early diagnosis and successful treatment of paraneoplastic melanocytic proliferation.

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Jansen, Joyce C G; Van Calster, Joachim; Pulido, Jose S; Miles, Sarah L; Vile, Richard G; Van Bergen, Tine; Cassiman, Catherine; Spielberg, Leigh H; Leys, Anita M

2015-07-01

Paraneoplastic melanocytic proliferation (bilateral diffuse uveal melanocytic proliferation, BDUMP) is a rare but devastating disease that causes progressive visual loss in patients who usually have an occult malignancy. Visual loss occurs as a result of paraneoplastic changes in the uveal tissue. In a masked fashion, the serum of two patients with BDUMP was evaluated for the presence of cultured melanocyte elongation and proliferation (CMEP) factor using cultured human melanocytes. We evaluated the efficacy of plasmapheresis as a treatment modality early in the disease in conjunction with radiation and chemotherapy. The serum of the first case patient was investigated after plasmapheresis and did not demonstrate proliferation of cultured human melanocytes. The serum of the second case was evaluated prior to treatment with plasmapheresis and did induce this proliferation. These findings are in accordance with the diminution of CMEP factor after plasmapheresis. Treatment with plasmapheresis managed to stabilise the ocular disease progression in both patients. In the past, visual loss due to paraneoplastic melanocytic proliferation was considered progressive and irreversible. We treated two patients successfully with plasmapheresis and demonstrated a relation between CMEP factor in the serum of these patients and proliferation of cultured melanocytes. 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.

Lactoferricin treatment decreases the rate of cell proliferation of a human colon cancer cell line.

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Freiburghaus, C; Janicke, B; Lindmark-Månsson, H; Oredsson, S M; Paulsson, M A

2009-06-01

Food components modify the risk of cancer at a large number of sites but the mechanism of action is unknown. In the present investigation, we studied the effect of the peptide lactoferricin derived from bovine milk lactoferrin on human colon cancer CaCo-2 cells. The cells were either untreated or treated with 2.0, 0.2, or 0.02 microM lactoferricin. Cell cycle kinetics were investigated with a bromodeoxyuridine DNA flow cytometric method. The results show that lactoferricin treatment slightly but significantly prolonged the S phase of the cell cycle. Lactoferricin treatment lowered the level of cyclin E1, a protein involved in the regulation of genes required for G(1)/S transition and consequently for efficient S phase progression. The slight prolongation of the S phase resulted in a reduction of cell proliferation, which became more apparent after a long treatment time.

The threonine protease activity of testes-specific protease 50 (TSP50 is essential for its function in cell proliferation.

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Yu-Yin Li

Full Text Available BACKGROUND: Testes-specific protease 50 (TSP50, a newly discovered threonine enzyme, has similar amino acid sequences and enzymatic structures to those of many serine proteases. It may be an oncogene. TSP50 is up-regulated in breast cancer epithelial cells, and ectopic expression of TSP50 in TSP50-deficient Chinese hamster ovary (CHO cells has been found to promote cell proliferation. However, the mechanisms by which TSP50 exerts its growth-promoting effects are not yet fully understood. METHODOLOGY/PRINCIPAL FINDINGS: To delineate whether the threonine protease activity of TSP50 is essential to its function in cell proliferation, we constructed and characterized a mutant TSP50, called TSP50 T310A, which was identified as a protease-dead mutant of TSP50. By a series of proliferation analyses, colony formation assays and apoptosis analyses, we showed that T310A mutation significantly depresses TSP50-induced cell proliferation in vitro. Next, the CHO stable cell line expressing either wild-type or T310A mutant TSP50 was injected subcutaneously into nude mice. We found that the T310A mutation could abolish the tumorigenicity of TSP50 in vivo. A mechanism investigation revealed that the T310A mutation prevented interaction between TSP50 and the NF-κBIκBα complex, which is necessary for TSP50 to perform its function in cell proliferation. CONCLUSION: Our data highlight the importance of threonine 310, the most critical protease catalytic site in TSP50, to TSP50-induced cell proliferation and tumor formation.

Hyaluronan in aged collagen matrix increases prostate epithelial cell proliferation

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Damodarasamy, Mamatha; Vernon, Robert B.; Chan, Christina K.; Plymate, Stephen R.; Wight, Thomas N.

2015-01-01

The extracellular matrix (ECM) of the prostate, which is comprised primarily of collagen, becomes increasingly disorganized with age, a property that may influence the development of hyperplasia and cancer. Collageous ECM extracted from the tails of aged mice exhibits many characteristics of collagen in aged tissues, including the prostate. When polymerized into a 3-dimensional (3D) gel, these collagen extracts can serve as models for the study of specific cell-ECM interactions. In the present study, we examined the behaviors of human prostatic epithelial cell lines representing normal prostate epithelial cells (PEC), benign prostatic hyperplasia (BPH-1), and adenocarcinoma (LNCaP) cultured in contact with 3D gels made from collagen extracts of young and aged mice. We found that proliferation of PEC, BPH-1, and LNCaP cells were all increased by culture on aged collagen gels relative to young collagen gels. In examining age-associated differences in the composition of the collagen extracts, we found that aged and young collagen had a similar amount of several collagen-associated ECM components, but aged collagen had a much greater content of the glycosaminoglycan hyaluronan (HA) than young collagen. The addition of HA (of similar size and concentration to that found in aged collagen extracts) to cells placed in young collagen elicited significantly increased proliferation in BPH-1 cells, but not in PEC or LNCaP cells, relative to controls not exposed to HA. Of note, histochemical analyses of human prostatic tissues showed significantly higher expression of HA in BPH and prostate cancer stroma relative to stroma of normal prostate. Collectively, these results suggest that changes in ECM involving increased levels of HA contribute to the growth of prostatic epithelium with aging. PMID:25124870