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Sample records for conditionally immortalized gdnf-producing

  1. Isolation and characterization of conditionally immortalized mouse glomerular endothelial cell lines.

    Science.gov (United States)

    Rops, Angelique L; van der Vlag, Johan; Jacobs, Cor W; Dijkman, Henry B; Lensen, Joost F; Wijnhoven, Tessa J; van den Heuvel, Lambert P; van Kuppevelt, Toin H; Berden, Jo H

    2004-12-01

    The culture and establishment of glomerular cell lines has proven to be an important tool for the understanding of glomerular cell functions in glomerular physiology and pathology. Especially, the recent establishment of a conditionally immortalized visceral epithelial cell line has greatly boosted the research on podocyte biology. Glomeruli were isolated from H-2Kb-tsA58 transgenic mice that contain a gene encoding a temperature-sensitive variant of the SV40 large tumor antigen, facilitating proliferative growth at 33 degrees C and differentiation at 37 degrees C. Glomerular endothelial cells were isolated from glomerular outgrowth by magnetic beads loaded with CD31, CD105, GSL I-B4, and ULEX. Clonal cell lines were characterized by immunofluorescence staining with antibodies/lectins specific for markers of endothelial cells, podocytes, and mesangial cells. Putative glomerular endothelial cell lines were analyzed for (1) cytokine-induced expression of adhesion molecules; (2) tube formation on Matrigel coating; and (3) the presence of fenestrae. As judged by immunostaining for Wilms tumor-1, smooth muscle actin (SMA), podocalyxin, and von Willebrand factor (vWF), we obtained putative endothelial, podocyte and mesangial cell lines. The mouse glomerular endothelial cell clone #1 (mGEnC-1) was positive for vWF, podocalyxin, CD31, CD105, VE-cadherin, GSL I-B4, and ULEX, internalized acetylated-low-density lipoprotein (LDL), and showed increased expression of adhesion molecules after activation with proinflammatory cytokines. Furthermore, mGEnC-1 formed tubes and contained nondiaphragmed fenestrae. The mGEnC-1 represents a conditionally immortalized cell line with various characteristics of differentiated glomerular endothelial cells when cultured at 37 degrees C. Most important, mGEnC-1 contains nondiaphragmed fenestrae, which is a unique feature of glomerular endothelial cells.

  2. Immortal ethics.

    Science.gov (United States)

    Harris, John

    2004-06-01

    This article draws on ideas published in my "Intimations of Immortality" essay in Science (Vol. 288, No. 5463, p. 59, April 7, 2000) and my "Intimations of Immortality-The Ethics and Justice of Life Extending Therapies" in editor Michael Freeman's Current Legal Problems (Oxford University Press 2002: 65-97). This article outlines the ethical issues involved in life-extending therapies. The arguments against life extension are examined and found wanting. The consequences of life extension are explored and found challenging but not sufficiently daunting to warrant regulation or control. In short, there is no doubt that immortality would be a mixed blessing, but we should be slow to reject cures for terrible diseases that may be an inextricable part of life-extending procedures even if the price we have to pay for those cures is increasing life expectancy and even creating immortals. Better surely to accompany the scientific race to achieve immortality with commensurate work in ethics and social policy to ensure that we know how to cope with the transition to parallel populations of mortals and immortals as envisaged in mythology.

  3. Conditionally immortalized human pancreatic stellate cell lines demonstrate enhanced proliferation and migration in response to IGF-I

    Energy Technology Data Exchange (ETDEWEB)

    Rosendahl, Ann H., E-mail: ann.rosendahl@med.lu.se [Lund University, Department of Clinical Sciences Lund, Division of Surgery, Lund (Sweden); Lund University and Skåne University Hospital, Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund (Sweden); Gundewar, Chinmay; Said Hilmersson, Katarzyna [Lund University, Department of Clinical Sciences Lund, Division of Surgery, Lund (Sweden); Ni, Lan; Saleem, Moin A. [University of Bristol, School of Clinical Sciences, Children' s Renal Unit and Academic Renal Unit, Bristol (United Kingdom); Andersson, Roland [Lund University, Department of Clinical Sciences Lund, Division of Surgery, Lund (Sweden)

    2015-01-15

    Pancreatic stellate cells (PSCs) play a key role in the dense desmoplastic stroma associated with pancreatic ductal adenocarcinoma. Studies on human PSCs have been minimal due to difficulty in maintaining primary PSC in culture. We have generated the first conditionally immortalized human non-tumor (NPSC) and tumor-derived (TPSC) pancreatic stellate cells via transformation with the temperature-sensitive SV40 large T antigen and human telomerase (hTERT). These cells proliferate at 33°C. After transfer to 37°C, the SV40LT is switched off and the cells regain their primary PSC phenotype and growth characteristics. NPSC contained cytoplasmic vitamin A-storing lipid droplets, while both NPSC and TPSC expressed the characteristic markers αSMA, vimentin, desmin and GFAP. Proteome array analysis revealed that of the 55 evaluated proteins, 27 (49%) were upregulated ≥3-fold in TPSC compared to NPSC, including uPA, pentraxin-3, endoglin and endothelin-1. Two insulin-like growth factor binding proteins (IGFBPs) were inversely expressed. Although discordant IGFBP-2 and IGFBP-3 levels, IGF-I was found to stimulate proliferation of both NPSC and TPSC. Both basal and IGF-I stimulated motility was significantly enhanced in TPSC compared to NPSC. In conclusion, these cells provide a unique resource that will facilitate further study of the active stroma compartment associated with pancreatic cancer. - Highlights: • Generation of human conditionally immortalized human pancreatic stellate cell lines. • Temperature-sensitive SV40LT allows switch to primary PSC phenotype characteristics. • Proteome profiling revealed distinct expression patterns between TPSC and NPSC. • Enhanced IGF-I-stimulated proliferation and motility by TPSC compared to NPSC.

  4. Choline transport via choline transporter-like protein 1 in conditionally immortalized rat syncytiotrophoblast cell lines TR-TBT.

    Science.gov (United States)

    Lee, N-Y; Choi, H-M; Kang, Y-S

    2009-04-01

    Choline is an essential nutrient for phospholipids and acetylcholine biosynthesis in normal development of fetus. In the present study, we investigated the functional characteristics of choline transport system and inhibitory effect of cationic drugs on choline transport in rat conditionally immortalized syncytiotrophoblast cell line (TR-TBT). Choline transport was weakly Na(+) dependent and significantly influenced by extracellular pH and by membrane depolarization. The transport process of choline is saturable with Michaelis-Menten constants (K(m)) of 68microM and 130microM in TR-TBT 18d-1 and TR-TBT 18d-2 respectively. Choline uptake in the cells was inhibited by unlabeled choline and hemicholinium-3 as well as various organic cations including guanidine, amiloride and acetylcholine. However, the prototypical organic cation tetraethylammonium and cimetidine showed very little inhibitory effect of choline uptake in TR-TBT cells. RT-PCR revealed that choline transporter-like protein 1 (CTL1) and organic cation transporter 2 (OCT2) are expressed in TR-TBT cells. The transport properties of choline in TR-TBT cells were similar or identical to that of CTL1 but not OCT2. CTL1 was also detected in human placenta. In addition, several cationic drugs such as diphenhydramine and verapamil competitively inhibited choline uptake in TR-TBT 18d-1 with K(i) of 115microM and 55microM, respectively. Our results suggest that choline transport system, which has intermediate affinity and weakly Na(+) dependent, in TR-TBT seems to occur through a CTL1 and this system may have relevance with the uptake of pharmacologically important organic cation drugs.

  5. Immortalization of human myogenic progenitor cell clone retaining multipotentiality

    International Nuclear Information System (INIS)

    Hashimoto, Naohiro; Kiyono, Tohru; Wada, Michiko R.; Shimizu, Shirabe; Yasumoto, Shigeru; Inagawa, Masayo

    2006-01-01

    Human myogenic cells have limited ability to proliferate in culture. Although forced expression of telomerase can immortalize some cell types, telomerase alone delays senescence of human primary cultured myogenic cells, but fails to immortalize them. In contrast, constitutive expression of both telomerase and the E7 gene from human papillomavirus type 16 immortalizes primary human myogenic cells. We have established an immortalized primary human myogenic cell line preserving multipotentiality by ectopic expression of telomerase and E7. The immortalized human myogenic cells exhibit the phenotypic characteristics of their primary parent, including an ability to undergo myogenic, osteogenic, and adipogenic terminal differentiation under appropriate culture conditions. The immortalized cells will be useful for both basic and applied studies aimed at human muscle disorders. Furthermore, immortalization by transduction of telomerase and E7 represents a useful method by which to expand human myogenic cells in vitro without compromising their ability to differentiate

  6. Genetic dissection of the maize kernel development process via conditional QTL mapping for three developing kernel-related traits in an immortalized F2 population.

    Science.gov (United States)

    Zhang, Zhanhui; Wu, Xiangyuan; Shi, Chaonan; Wang, Rongna; Li, Shengfei; Wang, Zhaohui; Liu, Zonghua; Xue, Yadong; Tang, Guiliang; Tang, Jihua

    2016-02-01

    Kernel development is an important dynamic trait that determines the final grain yield in maize. To dissect the genetic basis of maize kernel development process, a conditional quantitative trait locus (QTL) analysis was conducted using an immortalized F2 (IF2) population comprising 243 single crosses at two locations over 2 years. Volume (KV) and density (KD) of dried developing kernels, together with kernel weight (KW) at different developmental stages, were used to describe dynamic changes during kernel development. Phenotypic analysis revealed that final KW and KD were determined at DAP22 and KV at DAP29. Unconditional QTL mapping for KW, KV and KD uncovered 97 QTLs at different kernel development stages, of which qKW6b, qKW7a, qKW7b, qKW10b, qKW10c, qKV10a, qKV10b and qKV7 were identified under multiple kernel developmental stages and environments. Among the 26 QTLs detected by conditional QTL mapping, conqKW7a, conqKV7a, conqKV10a, conqKD2, conqKD7 and conqKD8a were conserved between the two mapping methodologies. Furthermore, most of these QTLs were consistent with QTLs and genes for kernel development/grain filling reported in previous studies. These QTLs probably contain major genes associated with the kernel development process, and can be used to improve grain yield and quality through marker-assisted selection.

  7. Effects of simvastatin on CAT-1-mediated arginine transport and NO level under high glucose conditions in conditionally immortalized rat inner blood-retinal barrier cell lines (TR-iBRB).

    Science.gov (United States)

    Tun, Temdara; Kang, Young-Sook

    2017-05-01

    Hyperglycemia causes the breakdown of the blood-retinal barrier by impairing endothelial nitric oxide synthase (eNOS) function. Statins have many pleiotropic effects such as improving endothelial barrier permeability and increasing eNOS mRNA stability. The objective of this study was to determine effect of simvastatin on l-arginine transport and NO production under high-glucose conditions in conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB). Changes in l-arginine transport uptake and, expression levels of cationic amino acid transporter 1 (CAT-1) and eNOS mRNA were investigated after pre-treatment with simvastatin and NOS inhibitors (l-NMMA and l-NAME) under high-glucose conditions using TR-iBRB, an in vitro model of iBRB. The NO level released from TR-iBRB cells was examined using Griess reagents. Under high glucose conditions, [ 3 H]l-arginine uptake was decreased in TR-iBRB cells. Simvastatin pretreatment elevated [ 3 H]l-arginine uptake, the expression levels of CAT-1 and eNOS mRNA, and NO production under high-glucose conditions. Moreover, the co-treatment with simvastatin and NOS inhibitors reduced [ 3 H]l-arginine uptake compared to pretreatment with simvastatin alone. Our results suggest that, in the presence of high-glucose levels, increased l-arginine uptake due to simvastatin treatment was associated with increased CAT-1 and eNOS mRNA levels, leading to higher NO production in TR-iBRB cells. Thus, simvastatin might be a good modulator for diabetic retinopathy therapy by increasing of the l-arginine uptake and improving endothelial function in retinal capillary endothelial cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Establishment and culture optimization of a new type of pituitary immortalized cell line

    Energy Technology Data Exchange (ETDEWEB)

    Kokubu, Yuko [Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki 305-8562 (Japan); Asashima, Makoto [Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki 305-8562 (Japan); Life Science Center of TARA, The University of Tsukuba, Ibaraki-ken 305-8577 (Japan); Kurisaki, Akira, E-mail: akikuri@hotmail.com [Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki 305-8562 (Japan); Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8562 (Japan)

    2015-08-07

    The pituitary gland is a center of the endocrine system that controls homeostasis in an organism by secreting various hormones. The glandular anterior pituitary consists of five different cell types, each expressing specific hormones. However, their regulation and the appropriate conditions for their in vitro culture are not well defined. Here, we report the immortalization of mouse pituitary cells by introducing TERT, E6, and E7 transgenes. The immortalized cell lines mainly expressed a thyrotroph-specific thyroid stimulating hormone beta (Tshb). After optimization of the culture conditions, these immortalized cells proliferated and maintained morphological characteristics similar to those of primary pituitary cells under sphere culture conditions in DMEM/F12 medium supplemented with N2, B27, basic FGF, and EGF. These cell lines responded to PKA or PKC pathway activators and induced the expression of Tshb mRNA. Moreover, transplantation of the immortalized cell line into subcutaneous regions and kidney capsules of mice further increased Tshb expression. These results suggest that immortalization of pituitary cells with TERT, E6, and E7 transgenes is a useful method for generating proliferating cells for the in vitro analysis of pituitary regulatory mechanisms. - Highlights: • Mouse pituitary cell lines were immortalized by introducing TERT, E6, and E7. • The immortalized cell lines mainly expressed thyroid stimulating hormone beta. • The cell lines responded to PKA or PKC pathway activators, and induced Tshb.

  9. Periodicity and Immortality in Reversible Computing

    OpenAIRE

    Kari , Jarkko; Ollinger , Nicolas

    2008-01-01

    Additional material available on the web at http://www.lif.univ-mrs.fr/~nollinge/rec/gnirut/; We investigate the decidability of the periodicity and the immortality problems in three models of reversible computation: reversible counter machines, reversible Turing machines and reversible one-dimensional cellular automata. Immortality and periodicity are properties that describe the behavior of the model starting from arbitrary initial configurations: immortality is the property of having at le...

  10. Myelination competent conditionally immortalized mouse Schwann cells

    NARCIS (Netherlands)

    Saavedra, José T.; Wolterman, Ruud A.; Baas, Frank; ten Asbroek, Anneloor L. M. A.

    2008-01-01

    Numerous mouse myelin mutants are available to analyze the biology of the peripheral nervous system related to health and disease in vivo. However, robust in vitro biochemical characterizations of players in peripheral nerve processes are still not possible due to the limited growth capacities of

  11. Universal mortality law and immortality

    Science.gov (United States)

    Azbel', Mark Ya.

    2004-10-01

    Well-protected human and laboratory animal populations with abundant resources are evolutionarily unprecedented. Physical approach, which takes advantage of their extensively quantified mortality, establishes that its dominant fraction yields the exact law, which is universal for all animals from yeast to humans. Singularities of the law demonstrate new kinds of stepwise adaptation. The law proves that universal mortality is an evolutionary by-product, which at any given age is reversible, independent of previous life history, and disposable. Life expectancy may be extended, arguably to immortality, by minor biological amendments in the animals. Indeed, in nematodes with a small number of perturbed genes and tissues it increased 6-fold (to 430 years in human terms), with no apparent loss in health and vitality. The law relates universal mortality to specific processes in cells and their genetic regulation.

  12. Immortalization of Werner syndrome and progeria fibroblasts

    International Nuclear Information System (INIS)

    Saito, H.; Moses, R.E.

    1991-01-01

    Human fibroblast cells from two different progeroid syndromes, Werner syndrome (WS) and progeria, were established as immortalized cell lines by transfection with plasmid DNA containing the SV40 early region. The lineage of each immortalized cell line was confirmed by VNTR analysis. Each of the immortalized cell lines maintained its original phenotype of slow growth. DNA repair ability of these cells was also studied by measuring sensitivity to killing by uv or the DNA-damaging drugs methyl methansulfonate, bleomycin, and cis-dichlorodiamine platinum. The results showed that both WS and progeria cells have normal sensitivity to these agents

  13. Change alone is eternal, perpetual, immortal : pharmacological immortality in science fiction

    OpenAIRE

    Grech, Victor E.; Vassallo, Clare; Callus, Ivan

    2012-01-01

    Immortality is a common feature in science-fiction (SF). This paper lists the ways in which the pharmacological induction of immortality has been depicted in SF, and the resultant outcomes. Immortality or extreme longevity are often melded with infertility in order to eliminate the overpopulation issues that would inevitably arise. This is only one way in which theoretical utopias which afford life extension become dystopias, cautionary tales that admonish against hubris. In this fashion, SF ...

  14. Establishment of a Conditionally Immortalized Wilms Tumor Cell Line with a Homozygous WT1 Deletion within a Heterozygous 11p13 Deletion and UPD Limited to 11p15.

    Directory of Open Access Journals (Sweden)

    Artur Brandt

    Full Text Available We describe a stromal predominant Wilms tumor with focal anaplasia and a complex, tumor specific chromosome 11 aberration: a homozygous deletion of the entire WT1 gene within a heterozygous 11p13 deletion and an additional region of uniparental disomy (UPD limited to 11p15.5-p15.2 including the IGF2 gene. The tumor carried a heterozygous p.T41A mutation in CTNNB1. Cells established from the tumor carried the same chromosome 11 aberration, but a different, homozygous p.S45Δ CTNNB1 mutation. Uniparental disomy (UPD 3p21.3pter lead to the homozygous CTNNB1 mutation. The tumor cell line was immortalized using the catalytic subunit of human telomerase (hTERT in conjunction with a novel thermolabile mutant (U19dl89-97tsA58 of SV40 large T antigen (LT. This cell line is cytogenetically stable and can be grown indefinitely representing a valuable tool to study the effect of a complete lack of WT1 in tumor cells. The origin/fate of Wilms tumors with WT1 mutations is currently poorly defined. Here we studied the expression of several genes expressed in early kidney development, e.g. FOXD1, PAX3, SIX1, OSR1, OSR2 and MEIS1 and show that these are expressed at similar levels in the parental and the immortalized Wilms10 cells. In addition the limited potential for muscle/ osteogenic/ adipogenic differentiation similar to all other WT1 mutant cell lines is also observed in the Wilms10 tumor cell line and this is retained in the immortalized cells. In summary these Wilms10 cells are a valuable model system for functional studies of WT1 mutant cells.

  15. Establishment of a Conditionally Immortalized Wilms Tumor Cell Line with a Homozygous WT1 Deletion within a Heterozygous 11p13 Deletion and UPD Limited to 11p15

    Science.gov (United States)

    Brandt, Artur; Löhers, Katharina; Beier, Manfred; Leube, Barbara; de Torres, Carmen; Mora, Jaume; Arora, Parineeta; Jat, Parmjit S.; Royer-Pokora, Brigitte

    2016-01-01

    We describe a stromal predominant Wilms tumor with focal anaplasia and a complex, tumor specific chromosome 11 aberration: a homozygous deletion of the entire WT1 gene within a heterozygous 11p13 deletion and an additional region of uniparental disomy (UPD) limited to 11p15.5-p15.2 including the IGF2 gene. The tumor carried a heterozygous p.T41A mutation in CTNNB1. Cells established from the tumor carried the same chromosome 11 aberration, but a different, homozygous p.S45Δ CTNNB1 mutation. Uniparental disomy (UPD) 3p21.3pter lead to the homozygous CTNNB1 mutation. The tumor cell line was immortalized using the catalytic subunit of human telomerase (hTERT) in conjunction with a novel thermolabile mutant (U19dl89-97tsA58) of SV40 large T antigen (LT). This cell line is cytogenetically stable and can be grown indefinitely representing a valuable tool to study the effect of a complete lack of WT1 in tumor cells. The origin/fate of Wilms tumors with WT1 mutations is currently poorly defined. Here we studied the expression of several genes expressed in early kidney development, e.g. FOXD1, PAX3, SIX1, OSR1, OSR2 and MEIS1 and show that these are expressed at similar levels in the parental and the immortalized Wilms10 cells. In addition the limited potential for muscle/ osteogenic/ adipogenic differentiation similar to all other WT1 mutant cell lines is also observed in the Wilms10 tumor cell line and this is retained in the immortalized cells. In summary these Wilms10 cells are a valuable model system for functional studies of WT1 mutant cells. PMID:27213811

  16. The immortality of humoral immunity.

    Science.gov (United States)

    Elgueta, Raul; de Vries, Victor C; Noelle, Randolph J

    2010-07-01

    Decades of high-titered antibody are sustained due to the persistence of memory B cells and long-lived plasma cells (PCs). The differentiation of each of these subsets is antigen- and T-cell driven and is dependent on signals acquired and integrated during the germinal center response. Inherent in the primary immune response must be the delivery of signals to B cells to create these populations, which have virtual immortality. Differences in biology and chemotactic behavior disperse memory B cells and long-lived PCs to a spectrum of anatomic sites. Each subset must rely on survival factors that can support their longevity. This review focuses on the generation of each of these subsets, their survival, and renewal, which must occur to sustain serological memory. In this context, we discuss the role of antigen, bystander inflammation, and cellular niches. The contribution of BAFF (B-cell activating factor belonging to the tumor necrosis factor family) and APRIL (a proliferation-inducing ligand) to the persistence of memory B cells and PCs are also detailed. Insights that have been provided over the past few years in the regulation of long-lived B-cell responses will have profound impact on vaccine development, the treatment of pre-sensitized patients for organ transplantation, and therapeutic interventions in both antibody- and T-cell-mediated autoimmunity.

  17. Universe, human immortality and future human evaluation

    CERN Document Server

    Bolonkin, Alexander

    2011-01-01

    This book debates the universe, the development of new technologies in the 21st century and the future of the human race. Dr Bolonkin shows that a human soul is only the information in a person's head. He offers a new unique method for re-writing the main brain information in chips without any damage to the human brain. This is the scientific prediction of the non-biological (electronic) civilization and immortality of the human being. Such a prognosis is predicated upon a new law, discovered by the author, for the development of complex systems. According to this law, every self-copying system tends to be more complex than the previous system, provided that all external conditions remain the same. The consequences are disastrous: humanity will be replaced by a new civilization created by intellectual robots (which Dr Bolonkin refers to as "E-humans" and "E-beings"). These creatures, whose intellectual and mechanical abilities will far exceed those of man, will require neither food nor oxygen to sustain their...

  18. Immortality in view of Maimonides and Spinoza

    Directory of Open Access Journals (Sweden)

    Morteza Shajari

    2014-12-01

    Full Text Available Desire for immortality can be seen as the essential natural impulse. Therefore, different religions and thinkers have attempted to see the issue from different viewpoints. The great Jewish philosopher. Maimonides, due to deep fixation to Judaism, has tried to express their issues to be consistent with the Bible and his own community believes. He, in his discussion of resurrection, believed to three basic steps: The Messiah, the resurrection, and the world hereafter. His standpoint of eternity is dedicated to the hereafter. And we can be immortalized only by acting and teachings in accordance with the Bible and righteousness. Like Maimonides, Spinoza – the other Jewish philosopher - considered the immortality as Ultimate bliss through which the “immutable and eternal love of God" can be achieved. In his opinion, a person reaches this stage, when the lusts and emotions can reasonably be overcome, and also, when the power and anger and contempt and disregard others will respond with love and dignity. Thus, a man can be reached its proper perfection and immortality is reached. The difference between these two philosophers is that Maimonides believes through "actual intellect" -that is Emanation of the active intellect- can be immortalized but, for Spinoza, eternity can be reached through the adequate Ideas.

  19. Network signatures of cellular immortalization in human lymphoblastoid cell lines

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    Shim, Sung-Mi; Jung, So-Young; Nam, Hye-Young; Kim, Hye-Ryun; Lee, Mee-Hee; Kim, Jun-Woo; Han, Bok-Ghee [National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Osong 363-951 (Korea, Republic of); Jeon, Jae-Pil, E-mail: jaepiljeon@hanmail.net [Division of Brain Diseases, Center for Biomedical Science, Korea National Institute of Health, Osong 363-951 (Korea, Republic of)

    2013-11-15

    Highlights: •We identified network signatures of LCL immortalization from transcriptomic profiles. •More than 41% of DEGs are possibly regulated by miRNAs in LCLs. •MicroRNA target genes in LCLs are involved in apoptosis and immune-related functions. •This approach is useful to find functional miRNA targets in specific cell conditions. -- Abstract: Human lymphoblastoid cell line (LCL) has been used as an in vitro cell model in genetic and pharmacogenomic studies, as well as a good model for studying gene expression regulatory machinery using integrated genomic analyses. In this study, we aimed to identify biological networks of LCL immortalization from transcriptomic profiles of microRNAs and their target genes in LCLs. We first selected differentially expressed genes (DEGs) and microRNAs (DEmiRs) between early passage LCLs (eLCLs) and terminally differentiated late passage LCLs (tLCLs). The in silico and correlation analysis of these DEGs and DEmiRs revealed that 1098 DEG–DEmiR pairs were found to be positively (n = 591 pairs) or negatively (n = 507 pairs) correlated with each other. More than 41% of DEGs are possibly regulated by miRNAs in LCL immortalizations. The target DEGs of DEmiRs were enriched for cellular functions associated with apoptosis, immune response, cell death, JAK–STAT cascade and lymphocyte activation while non-miRNA target DEGs were over-represented for basic cell metabolisms. The target DEGs correlated negatively with miR-548a-3p and miR-219-5p were significantly associated with protein kinase cascade, and the lymphocyte proliferation and apoptosis, respectively. In addition, the miR-106a and miR-424 clusters located in the X chromosome were enriched in DEmiR–mRNA pairs for LCL immortalization. In this study, the integrated transcriptomic analysis of LCLs could identify functional networks of biologically active microRNAs and their target genes involved in LCL immortalization.

  20. Characterization of neurons from immortalized dental pulp stem cells for the study of neurogenetic disorders

    Directory of Open Access Journals (Sweden)

    Nora Urraca

    2015-11-01

    Full Text Available A major challenge to the study and treatment of neurogenetic syndromes is accessing live neurons for study from affected individuals. Although several sources of stem cells are currently available, acquiring these involve invasive procedures, may be difficult or expensive to generate and are limited in number. Dental pulp stem cells (DPSCs are multipotent stem cells that reside deep the pulp of shed teeth. To investigate the characteristics of DPSCs that make them a valuable resource for translational research, we performed a set of viability, senescence, immortalization and gene expression studies on control DPSC and derived neurons. We investigated the basic transport conditions and maximum passage number for primary DPSCs. We immortalized control DPSCs using human telomerase reverse transcriptase (hTERT and evaluated neuronal differentiation potential and global gene expression changes by RNA-seq. We show that neurons from immortalized DPSCs share morphological and electrophysiological properties with non-immortalized DPSCs. We also show that differentiation of DPSCs into neurons significantly alters gene expression for 1305 transcripts. Here we show that these changes in gene expression are concurrent with changes in protein levels of the transcriptional repressor REST/NRSF, which is known to be involved in neuronal differentiation. Immortalization significantly altered the expression of 183 genes after neuronal differentiation, 94 of which also changed during differentiation. Our studies indicate that viable DPSCs can be obtained from teeth stored for ≥72 h, these can then be immortalized and still produce functional neurons for in vitro studies, but that constitutive hTERT immortalization is not be the best approach for long term use of patient derived DPSCs for the study of disease.

  1. Characterization of neurons from immortalized dental pulp stem cells for the study of neurogenetic disorders.

    Science.gov (United States)

    Urraca, Nora; Memon, Rawaha; El-Iyachi, Ikbale; Goorha, Sarita; Valdez, Colleen; Tran, Quynh T; Scroggs, Reese; Miranda-Carboni, Gustavo A; Donaldson, Martin; Bridges, Dave; Reiter, Lawrence T

    2015-11-01

    A major challenge to the study and treatment of neurogenetic syndromes is accessing live neurons for study from affected individuals. Although several sources of stem cells are currently available, acquiring these involve invasive procedures, may be difficult or expensive to generate and are limited in number. Dental pulp stem cells (DPSCs) are multipotent stem cells that reside deep the pulp of shed teeth. To investigate the characteristics of DPSCs that make them a valuable resource for translational research, we performed a set of viability, senescence, immortalization and gene expression studies on control DPSC and derived neurons. We investigated the basic transport conditions and maximum passage number for primary DPSCs. We immortalized control DPSCs using human telomerase reverse transcriptase (hTERT) and evaluated neuronal differentiation potential and global gene expression changes by RNA-seq. We show that neurons from immortalized DPSCs share morphological and electrophysiological properties with non-immortalized DPSCs. We also show that differentiation of DPSCs into neurons significantly alters gene expression for 1305 transcripts. Here we show that these changes in gene expression are concurrent with changes in protein levels of the transcriptional repressor REST/NRSF, which is known to be involved in neuronal differentiation. Immortalization significantly altered the expression of 183 genes after neuronal differentiation, 94 of which also changed during differentiation. Our studies indicate that viable DPSCs can be obtained from teeth stored for ≥72 h, these can then be immortalized and still produce functional neurons for in vitro studies, but that constitutive hTERT immortalization is not be the best approach for long term use of patient derived DPSCs for the study of disease. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  2. [The concept of cellular immortality, a myth or a reality. Example of "immortalized" articular chondrocytes].

    Science.gov (United States)

    Adolphe, M; Thenet, S

    1990-01-01

    The concept of cellular immortality, which arose from the historical studies of A. Carrel, is getting a new start with the progress of virology. However, the definition of cell immortalization is still ambiguous. Although scientists agree that cells regarded as immortal have acquired an infinite growth capacity, the relationship of this change with the first stages of transformation is difficult to clearly define. Immortalized cell lines have already been obtained from numerous cell types by using viral infection or transfection with viral and cellular genes. Immortalization of cells is interesting for three main reasons: it permits study of the steps in progression to transformation, allows establishment of cell lines for producing biological products, and permits various cell types to maintain a part of their differentiated functions. For example, hypothalamic neurosecretory cells, macrophages, astrocytes and intestinal epithelial cells have been immortalized and these lines can be used for understanding the balance between division and differentiation, and also for pharmacotoxicological studies. In our laboratory, we immortalized rabbit articular chondrocytes by transfection with SV40 large T and little t encoding genes. At the 9th subculture, when the control culture was senescent, clones of polygonal cells appeared in the transfected cell cultures. Three clones have been selected and have been maintained in culture for two years. Growth curves of normal and SV40-transfected chondrocytes were compared and displayed similar doubling times (approximately 20 hours). The exponential phase of growth was longer for immortalized cells resulting in a 2-fold higher saturation density. These cells appear to be not fully transformed and maintain some properties of differentiated chondrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. The (not so immortal strand hypothesis

    Directory of Open Access Journals (Sweden)

    Cristian Tomasetti

    2015-03-01

    Significance: Utilizing an approach that is fundamentally different from previous efforts to confirm or refute the immortal strand hypothesis, we provide evidence against non-random segregation of DNA during stem cell replication. Our results strongly suggest that parental DNA is passed randomly to stem cell daughters and provides new insight into the mechanism of DNA replication in stem cells.

  4. Comparative study of four immortalized human brain capillary endothelial cell lines, hCMEC/D3, hBMEC, TY10, and BB19, and optimization of culture conditions, for an in vitro blood-brain barrier model for drug permeability studies.

    Science.gov (United States)

    Eigenmann, Daniela E; Xue, Gongda; Kim, Kwang S; Moses, Ashlee V; Hamburger, Matthias; Oufir, Mouhssin

    2013-11-22

    Reliable human in vitro blood-brain barrier (BBB) models suitable for high-throughput screening are urgently needed in early drug discovery and development for assessing the ability of promising bioactive compounds to overcome the BBB. To establish an improved human in vitro BBB model, we compared four currently available and well characterized immortalized human brain capillary endothelial cell lines, hCMEC/D3, hBMEC, TY10, and BB19, with respect to barrier tightness and paracellular permeability. Co-culture systems using immortalized human astrocytes (SVG-A cell line) and immortalized human pericytes (HBPCT cell line) were designed with the aim of positively influencing barrier tightness. Tight junction (TJ) formation was assessed by transendothelial electrical resistance (TEER) measurements using a conventional epithelial voltohmmeter (EVOM) and an automated CellZscope system which records TEER and cell layer capacitance (CCL) in real-time.Paracellular permeability was assessed using two fluorescent marker compounds with low BBB penetration (sodium fluorescein (Na-F) and lucifer yellow (LY)). Conditions were optimized for each endothelial cell line by screening a series of 24-well tissue culture inserts from different providers. For hBMEC cells, further optimization was carried out by varying coating material, coating procedure, cell seeding density, and growth media composition. Biochemical characterization of cell type-specific transmembrane adherens junction protein VE-cadherin and of TJ proteins ZO-1 and claudin-5 were carried out for each endothelial cell line. In addition, immunostaining for ZO-1 in hBMEC cell line was performed. The four cell lines all expressed the endothelial cell type-specific adherens junction protein VE-cadherin. The TJ protein ZO-1 was expressed in hCMEC/D3 and in hBMEC cells. ZO-1 expression could be confirmed in hBMEC cells by immunocytochemical staining. Claudin-5 expression was detected in hCMEC/D3, TY10, and at a very low level

  5. Immortality in view of Maimonides and Spinoza

    OpenAIRE

    Morteza Shajari; Yousef Nozohur; Abbas Fanni Asl

    2014-01-01

    Desire for immortality can be seen as the essential natural impulse. Therefore, different religions and thinkers have attempted to see the issue from different viewpoints. The great Jewish philosopher. Maimonides, due to deep fixation to Judaism, has tried to express their issues to be consistent with the Bible and his own community believes. He, in his discussion of resurrection, believed to three basic steps: The Messiah, the resurrection, and the world hereafter. His standpoint of eternity...

  6. The (not so) immortal strand hypothesis.

    Science.gov (United States)

    Tomasetti, Cristian; Bozic, Ivana

    2015-03-01

    Non-random segregation of DNA strands during stem cell replication has been proposed as a mechanism to minimize accumulated genetic errors in stem cells of rapidly dividing tissues. According to this hypothesis, an "immortal" DNA strand is passed to the stem cell daughter and not the more differentiated cell, keeping the stem cell lineage replication error-free. After it was introduced, experimental evidence both in favor and against the hypothesis has been presented. Using a novel methodology that utilizes cancer sequencing data we are able to estimate the rate of accumulation of mutations in healthy stem cells of the colon, blood and head and neck tissues. We find that in these tissues mutations in stem cells accumulate at rates strikingly similar to those expected without the protection from the immortal strand mechanism. Utilizing an approach that is fundamentally different from previous efforts to confirm or refute the immortal strand hypothesis, we provide evidence against non-random segregation of DNA during stem cell replication. Our results strongly suggest that parental DNA is passed randomly to stem cell daughters and provides new insight into the mechanism of DNA replication in stem cells. Copyright © 2015. Published by Elsevier B.V.

  7. Immortality versus resurrection in the Christian tradition.

    Science.gov (United States)

    Murphy, Nancey

    2011-10-01

    For those in contemporary society who believe in an afterlife, there are a number of views available. The most common may be based on belief in an immortal soul. However, the early Christian account was, instead, bodily resurrection. As Christianity moved throughout the Mediterranean world, apologists and theologians adapted their teaching on human nature and the afterlife to Greek and Roman philosophies. By the time of Augustine (d. 430), the doctrines of body-soul dualism and immortality of the soul were firmly entrenched in Christian teaching. The incorporation of the concept of an immortal soul into Christian accounts of life after death produced a hybrid account. The body dies, the soul (at least of those who were to be saved) travels to heaven. At the end of history, there would be a general resurrection, and the souls would be reunited with their bodies, although the bodies would be in a transformed, indestructible state. This hybrid account of life after death went largely uncontested until the twentieth century. In this essay, I describe this history and argue for a return to the early Christian view of humans as a unity, not a duality, and for belief in resurrection of the body as the appropriate expectation for eternal life. This would not only be truer to Christian sources, but, valuable, I believe, in focusing Christian attention on the need to care for the environment. © 2011 New York Academy of Sciences.

  8. Successful immortalization of mesenchymal progenitor cells derived from human placenta and the differentiation abilities of immortalized cells

    International Nuclear Information System (INIS)

    Zhang Xiaohong; Soda, Yasushi; Takahashi, Kenji; Bai, Yuansong; Mitsuru, Ayako; Igura, Koichi; Satoh, Hitoshi; Yamaguchi, Satoru; Tani, Kenzaburo; Tojo, Arinobu; Takahashi, Tsuneo A.

    2006-01-01

    We reported previously that mesenchymal progenitor cells derived from chorionic villi of the human placenta could differentiate into osteoblasts, adipocytes, and chondrocytes under proper induction conditions and that these cells should be useful for allogeneic regenerative medicine, including cartilage tissue engineering. However, similar to human mesenchymal stem cells (hMSCs), though these placental cells can be isolated easily, they are difficult to study in detail because of their limited life span in vitro. To overcome this problem, we attempted to prolong the life span of human placenta-derived mesenchymal cells (hPDMCs) by modifying hTERT and Bmi-1, and investigated whether these modified hPDMCs retained their differentiation capability and multipotency. Our results indicated that the combination of hTERT and Bmi-1 was highly efficient in prolonging the life span of hPDMCs with differentiation capability to osteogenic, adipogenic, and chondrogenic cells in vitro. Clonal cell lines with directional differentiation ability were established from the immortalized parental hPDMC/hTERT + Bmi-1. Interestingly, hPDMC/Bmi-1 showed extended proliferation after long-term growth arrest and telomerase was activated in the immortal hPDMC/Bmi-1 cells. However, the differentiation potential was lost in these cells. This study reports a method to extend the life span of hPDMCs with hTERT and Bmi-1 that should become a useful tool for the study of mesenchymal stem cells

  9. TRANSPLANTATION AND POTENTIAL IMMORTALITY OF MAMMALIAN TISSUES.

    Science.gov (United States)

    Loeb, L

    1926-06-20

    1. Serial transplantation of tumors made it possible in 1901 and following years to draw the conclusion that various mammalian tissues have potential immortality. Serial transplantations of normal tissues did not succeed at first, because the homoioreaction on the part of the lymphocytes and connective tissue of the host injures the transplant. 2. In continuation of these experiments we found that cartilage of the rat can be transplanted serially to other rats at least for a period of 3 years. At the end of that time great parts of the transplanted cartilage and perichondrium are alive. 3. Not only the cartilage of young rats can be homoiotransplanted, but also the cartilage of very old rats which are nearing the end of life. By using such animals we have been able to obtain cartilage and perichondrium approaching an age of 6 years which is almost double the average age of a rat. 4. We found that cartilage can be homoiotransplanted more readily than other tissues for the following reasons: (a) While in principle the homoioreaction towards cartilage is the same as against other tissues, cartilage elicits this reaction with less intensity; (b) cartilage is better able to resist the invasion of lymphocytes and connective tissue than the majority of other tissues; (c) a gradual adaptation between transplant and host seems to take place in the case of cartilage transplantation, as a result of which the lymphocytic reaction on the part of the host tissue decreases progressively the longer the cartilage is kept in the strange host. 5. At time of examination we not only found living transplanted cartilage tissue, but also perichondrial tissue, which in response to a stimulus apparently originating in the necrotic central cartilage, had been proliferating and replacing it. These results suggest that it may perhaps be possible under favorable conditions to keep cartilage alive indefinitely through serial transplantations. 6. At the same time these experiments permit the

  10. A human beta cell line with drug inducible excision of immortalizing transgenes

    Science.gov (United States)

    Benazra, Marion; Lecomte, Marie-José; Colace, Claire; Müller, Andreas; Machado, Cécile; Pechberty, Severine; Bricout-Neveu, Emilie; Grenier-Godard, Maud; Solimena, Michele; Scharfmann, Raphaël; Czernichow, Paul; Ravassard, Philippe

    2015-01-01

    Objectives Access to immortalized human pancreatic beta cell lines that are phenotypically close to genuine adult beta cells, represent a major tool to better understand human beta cell physiology and develop new therapeutics for Diabetes. Here we derived a new conditionally immortalized human beta cell line, EndoC-βH3 in which immortalizing transgene can be efficiently removed by simple addition of tamoxifen. Methods We used lentiviral mediated gene transfer to stably integrate a tamoxifen inducible form of CRE (CRE-ERT2) into the recently developed conditionally immortalized EndoC βH2 line. The resulting EndoC-βH3 line was characterized before and after tamoxifen treatment for cell proliferation, insulin content and insulin secretion. Results We showed that EndoC-βH3 expressing CRE-ERT2 can be massively amplified in culture. We established an optimized tamoxifen treatment to efficiently excise the immortalizing transgenes resulting in proliferation arrest. In addition, insulin expression raised by 12 fold and insulin content increased by 23 fold reaching 2 μg of insulin per million cells. Such massive increase was accompanied by enhanced insulin secretion upon glucose stimulation. We further observed that tamoxifen treated cells maintained a stable function for 5 weeks in culture. Conclusions EndoC βH3 cell line represents a powerful tool that allows, using a simple and efficient procedure, the massive production of functional non-proliferative human beta cells. Such cells are close to genuine human beta cells and maintain a stable phenotype for 5 weeks in culture. PMID:26909308

  11. 'Immortal' energy systems and intergenerational justice

    International Nuclear Information System (INIS)

    Weinberg, A.M.

    1985-01-01

    Some critics of our technological society have asserted that we are leaving a legacy of problems for our descendants - in the shape, for example, of CO 2 pollution of the atmosphere and radioactive waste. The author argues that if some of our power generation systems turn out to be near 'immortal', with lives much longer than their book lives, on the contrary, great benefits may be bequeathed to our successors - in fully amortized plant with very low running costs. There are examples in history of similar benefits conferred by dams built hundreds of years ago but which still serve useful purposes today. (author)

  12. Analysis of proviral integration in human mammary epithelial cell lines immortalized by retroviral infection with a temperature-sensitive SV40 T-antigen construct.

    Science.gov (United States)

    Stamps, A C; Davies, S C; Burman, J; O'Hare, M J

    1994-06-15

    A panel of eight conditionally immortal lines derived by infection of human breast epithelial cells with an amphotropic retrovirus transducing a ts mutant of SV40 large T-antigen was analyzed with respect to individual retroviral integration patterns. Each line contained multiple integration sites which were clonal and stable over extended passage. Similar integration patterns were observed between individual lines arising separately from the same stock of pre-immortal cells, suggesting a common progenitor. Retroviral integration analysis of pre-immortal cells at different stages of pre-crisis growth showed changes indicative of a progressive transition from polyclonality to clonality as the cells approached crisis. Each of the immortal lines contained a sub-set of the integration sites of their pre-immortal progenitors, with individual combinations and copy numbers of sites. Since all the cell lines appeared to originate from single foci in separate flasks, it is likely that each set arose from a common clone of pre-immortal cells as the result of separate genetic events. There was no evidence from this analysis to suggest that specific integration sites played any part either in the selection of pre-crisis clones or in the subsequent establishment of immortal lines.

  13. Telomere elongation in immortal human cells without detectable telomerase activity.

    Science.gov (United States)

    Bryan, T M; Englezou, A; Gupta, J; Bacchetti, S; Reddel, R R

    1995-09-01

    Immortalization of human cells is often associated with reactivation of telomerase, a ribonucleoprotein enzyme that adds TTAGGG repeats onto telomeres and compensates for their shortening. We examined whether telomerase activation is necessary for immortalization. All normal human fibroblasts tested were negative for telomerase activity. Thirteen out of 13 DNA tumor virus-transformed cell cultures were also negative in the pre-crisis (i.e. non-immortalized) stage. Of 35 immortalized cell lines, 20 had telomerase activity as expected, but 15 had no detectable telomerase. The 15 telomerase-negative immortalized cell lines all had very long and heterogeneous telomeres of up to 50 kb. Hybrids between telomerase-negative and telomerase-positive cells senesced. Two senescent hybrids demonstrated telomerase activity, indicating that activation of telomerase is not sufficient for immortalization. Some hybrid clones subsequently recommenced proliferation and became immortalized either with or without telomerase activity. Those without telomerase activity also had very long and heterogeneous telomeres. Taken together, these data suggest that the presence of lengthened or stabilized telomeres is necessary for immortalization, and that this may be achieved either by the reactivation of telomerase or by a novel and as yet unidentified mechanism.

  14. Clonal nature of spontaneously immortalized 3T3 cells.

    Science.gov (United States)

    Rittling, S R

    1996-11-25

    Mouse embryo fibroblasts (MEFs), when plated at appropriate densities, proliferate vigorously for several passages, and then the growth rate of the culture slows considerably. If the cells are plated at a high enough density and continuously passed, the cultures will eventually overcome this "crisis" period and resume rapid growth. Here, we have addressed the question of what the changes are that cells undergo in overcoming the growth restraints of crisis. Primary MEF cells were infected with a retrovirus which confers G418 resistance and selected in G418. The resultant pre-crisis population comprised cells which each contained a retrovirus integrated at a unique genomic location. These cells were then passed according to the 3T3 protocol until immortal, rapidly growing cells emerged. The integration pattern of the retrovirus in the immortal population was examined. In two independent experiments, the immortal population of cells grown in the presence of G418 comprised two independent clones of cells, with additional clones undetectable at the level of detection of the assays used. The integration pattern was also examined in parallel infected cultures grown in the absence of selection. In one experiment the unselected immortal population contained the same labeled clone that appeared in the sister infected culture, indicating that an immortal precursor was present in the precrisis population. These results are consistent with the idea that a mutation is responsible for the immortal phenotype.

  15. Immortality in the Christian Physicalistic Theology: A Critical Survey

    Directory of Open Access Journals (Sweden)

    Hasan Ahmadizade

    2017-07-01

    Full Text Available Physicalistic Theology is a term that has no exact definition in theologian views. In the 20th century some of Christian thinkers on theology, like Nancy Murphy and Peter van Inwagen, by accepting a Physicalistic approach on human being, tried to analyze the Christian beliefs about human identity and his immortality. This approach today is called Physicalistic Theology. According to this approach, human is not but this physical body itself and so we can simply analyze the immortality problem. In this article we try to by an analytic and descriptive method, analyze the immortality of human according to the view of Physicalistic Theology. We will analyze the most important reasoning of Physicalistic Theology that is: no-interaction between the material and the immaterial, interaction between the person and the body, and the physicalism in Christian beliefs. One of the conclusions of this article is that according to Physicalistic view, the person that at some time has not been in the world, must exists any time to destroyed forever because the Christians believe to things that cannot justify rationally. The problem of immortality is one of these matters. Physicalistic Theology try to prove the immortality based on the miracles and the absolute power of God.

  16. Comparative study of four immortalized human brain capillary endothelial cell lines, hCMEC/D3, hBMEC, TY10, and BB19, and optimization of culture conditions, for an in vitro blood–brain barrier model for drug permeability studies

    OpenAIRE

    Eigenmann, Daniela E; Xue, Gongda; Kim, Kwang S; Moses, Ashlee V; Hamburger, Matthias; Oufir, Mouhssin

    2013-01-01

    Background: Reliable human in vitro blood brain barrier (BBB) models suitable for high throughput screening are urgently needed in early drug discovery and development for assessing the ability of promising bioactive compounds to overcome the BBB. To establish an improved human in vitro BBB model we compared four currently available and well characterized immortalized human brain capillary endothelial cell lines hCMEC/D3 hBMEC TY10 and BB19 with respect to barrier tightness and paracellular p...

  17. Aging in bacteria, immortality or not-a critical review.

    Science.gov (United States)

    Gómez, José M G

    2010-12-01

    Bacteria were traditionally thought to have a symmetrical binary fission without a clear distinction between soma and germ-line, being thus considered as immortal biological entities. Yet it has been recently described that bacteria also undergo replicative aging (RA). That is, they exhibit finite replicative abilities under good conditions to growth. The apparently initial indistinguishability of sibling cells after cytokinesis is broken. After division, the daughter cell that inherits the "old" pole present in the "mother cell" progressively exhibits a decline in its proliferative capacity with increasing cell pole age. This is a clear hallmark and phenotypic manifestation of a bona fide RA phenomenon in toto. While the exact molecular mechanism(s) underlying to this lost of replicative potential are not yet fully understood, the "old pole cell" is considered as an aging parent that in a repeatedly manner is able to produce rejuvenated offspring which inherit a resetting of the biological clock. On the order hand, bacteria exhibit in addition to this "mandatory" RA the dubbed conditional senescence (CS). CS is defined as a decline in cellular viability observed in arrested-growing bacteria populations, a phenomenon apparently not related to RA under growing active conditions. To understand bacterial aging, it is necessary to put it within the sociality-multicellularity framework. This is a new conceptual paradigm that expresses the natural reality of the bacterial world. From this more ecological perspective these bacterial aging phenomena probably should represent an insurance/bethedging anticipative survival strategy. This is underpinned in a self-generation of an appropriate level of populational phenotypic diversity. That is, bacterial aging could be considered a communitarian adaptive response to cope with different environmental stresses and threats. I have highlighted the necessity to construct an integrative conceptual framework to achieve a unified view

  18. Generation and Characterization of an Immortalized Human Esophageal Myofibroblast Line.

    Directory of Open Access Journals (Sweden)

    Chao Niu

    Full Text Available Stromal cells with a myofibroblast phenotype present in the normal human esophagus are increased in individuals with gastro-esophageal reflux disease (GERD. We have previously demonstrated that myofibroblasts stimulated with acid and TLR4 agonists increase IL-6 and IL-8 secretion using primary cultures of myofibroblasts established from normal human esophagus. While primary cultures have the advantage of reflecting the in vivo environment, a short life span and unavoidable heterogeneity limits the usefulness of this model in larger scale in vitro cellular signaling studies. The major aim of this paper therefore was to generate a human esophageal myofibroblast line with an extended lifespan. In the work presented here we have generated and characterized an immortalized human esophageal myofibroblast line by transfection with a commercially available GFP-hTERT lentivirus. Immortalized human esophageal myofibroblasts demonstrate phenotypic, genotypic and functional similarity to primary cultures of esophageal myofibroblasts we have previously described. We found that immortalized esophageal myofibroblasts retain myofibroblast spindle-shaped morphology at low and high confluence beyond passage 80, and express α-SMA, vimentin, and CD90 myofibroblast markers. Immortalized human esophageal myofibroblasts also express the putative acid receptor TRPV1 and TLR4 and retain the functional capacity to respond to stimuli encountered in GERD with secretion of IL-6. Finally, immortalized human esophageal myofibroblasts also support the stratified growth of squamous esophageal epithelial cells in 3D organotypic cultures. This newly characterized immortalized human esophageal myofibroblast cell line can be used in future cellular signaling and co-culture studies.

  19. Genes involved in immortalization of human mammary cells

    Energy Technology Data Exchange (ETDEWEB)

    Stampfer, Martha R.; Yaswen, Paul

    2001-09-27

    Breast cancer progression is characterized by inappropriate cell growth. Normal cells cease growth after a limited number of cell divisions--a process called cellular senescence-while tumor cells may acquire the ability to proliferate indefinitely (immortality). Inappropriate expression of specific oncogenes in a key cellular signaling pathway (Ras, Raf) can promote tumorigenicity in immortal cells, while causing finite lifespan cells to undergo a rapid senescence-like arrest. We have studied when in the course of transformation of cultured human mammary epithelial cells (HMEC), the response to overexpressed oncogenic Raf changes from being tumor-suppressive to tumor enhancing, and what are the molecular underpinnings of this response. Our data indicate: (1) HMEC acquire the ability to maintain growth in the presence of oncogenic Raf not simply as a consequence of overcoming senescence, but as a result of a newly discovered step in the process of immortal transformation uncovered by our lab, termed conversion. Immortal cells that have not undergone conversion (e.g., cells immortalized by exogenous introduction of the immortalizing enzyme, telomerase) remain growth inhibited. (2) Finite lifespan HMEC growth arrest in response to oncogenic Raf using mediators of growth inhibition that are very different from those used in response to oncogenic Raf by rodent cells and certain other human cell types, including the connective tissue cells from the same breast tissue. While many diverse cell types appear to have in common a tumor-suppressive response to this oncogenic signal, they also have developed multiple mechanisms to elicit this response. Understanding how cancer cells acquire the crucial capacity to be immortal and to abrogate normal tumor-suppressive mechanisms may serve both to increase our understanding of breast cancer progression, and to provide new targets for therapeutic intervention. Our results indicate that normal HMEC have novel means of enforcing a Raf

  20. [Immortal time bias in pharmacoepidemiological studies: definition, solutions and examples].

    Science.gov (United States)

    Faillie, Jean-Luc; Suissa, Samy

    2015-01-01

    Among the observational studies of drug effects in chronic diseases, many of them have found effects that were exaggerated or wrong. Among bias responsible for these errors, the immortal time bias, concerning the definition of exposure and exposure periods, is relevantly important as it usually tends to wrongly attribute a significant benefit to the study drug (or exaggerate a real benefit). In this article, we define the mechanism of immortal time bias, we present possible solutions and illustrate its consequences through examples of pharmacoepidemiological studies of drug effects. © 2014 Société Française de Pharmacologie et de Thérapeutique.

  1. Locus of Control and Level of Conflict as Correlates of Immortality Orientation.

    Science.gov (United States)

    O'Dowd, William

    1985-01-01

    Assessed the orientation of 14 male professors toward immortality as a psychological motive. Results showed a generally low conscious concern with immortality issues; however, respondents who have accepted some sort of immortality show a more internal locus of control and better adjustment. (JAC)

  2. On Persons and Immortality Symposium on Pedro Tabensky ...

    African Journals Online (AJOL)

    ... disadvantages associated with the immortal life, these are contingent rather than essential to the notion of being a person. In fact, we have very little idea of the boundaries of that concept. The paper concludes by looking at the consequences of Tabensky\\'s approach for issues surrounding moral vision and improvement, ...

  3. Exploring the motifs of death and immortality | Maina | Journal of ...

    African Journals Online (AJOL)

    felt threatened by the eventuality of death, inculcating in them a fear so great that all possible strategies are engaged in the search for an avenue that would prepare them for this eventuality. A careful exploration of human activities surrounding the issues of death and immortality reveals an obsession with the expression of ...

  4. The Golden Bough: Literature and the Idea of Immortality.

    Science.gov (United States)

    Klotz, Kenneth

    1979-01-01

    All works of literature reflect man's obsession with death and his creative attempts to evade or postpone it. Art cannot solve the problem, but within the limits of human capabilities, we come to art, whether as artists or audience, for our own small share in the "intimations of immortality." (Author/SJL)

  5. Staphylococcal superantigens stimulate immortalized human adipocytes to produce chemokines.

    Directory of Open Access Journals (Sweden)

    Bao G Vu

    Full Text Available BACKGROUND: Human adipocytes may have significant functions in wound healing and the development of diabetes through production of pro-inflammatory cytokines after stimulation by gram-negative bacterial endotoxin. Diabetic foot ulcers are most often associated with staphylococcal infections. Adipocyte responses in the area of the wound may play a role in persistence and pathology. We studied the effect of staphylococcal superantigens (SAgs on immortalized human adipocytes, alone and in the presence of bacterial endotoxin or staphylococcal α-toxin. METHODOLOGY/PRINCIPAL FINDINGS: Primary non-diabetic and diabetic human preadipocytes were immortalized by the reverse transcriptase component of telomerase (TERT and the E6/E7 genes of human papillomavirus. The immortal cells were demonstrated to have properties of non-immortalized pre-adipocytes and could be differentiated into mature and functional adipocytes. Differentiated adipocytes exposed to staphylococcal SAgs produced robust levels of cytokines IL-6 and IL-8, but there were no significant differences in levels between the non-diabetic and diabetic cells. Cytokine production was increased by co-incubation of adipocytes with SAgs and endotoxin together. In contrast, α-toxin alone was cytotoxic at high concentrations, but, at sub-cytotoxic doses, did not stimulate production of IL-6 and IL-8. CONCLUSIONS/SIGNIFICANCE: Endotoxin has been proposed to contribute to diabetes through enhanced insulin resistance after chronic exposure and stimulation of adipocytes to produce cytokines. Our data indicate staphylococcal SAgs TSST-1 and SEB alone and in combination with bacterial endotoxin also stimulate adipocytes to produce cytokines and thus may contribute to the inflammatory response found in chronic diabetic ulcers and in the systemic inflammation that is associated with the development and persistence of diabetes. The immortal human pre-adipocytes reported here will be useful for studies to

  6. Life Beyond the Physical Body: The Possibilities of Digital Immortality

    OpenAIRE

    Galvão, Vinícius F.; Maciél, Cristiano; Garcia, Ana Cristina B.; Viterbo, José

    2017-01-01

    We are on the verge of a major shift in the way we perceive digital life, what may cause a significant impact to the real world. Gradually, through increasing knowledge in the areas of artificial intelligence, big data and machine learning, computers have been emulating deceased human beings and, symbolically, with the aid of technology, have been managing to conquer death. This article seeks to understand and problematize the ways in which digital immortality has manifested itself, particula...

  7. Variation in the loss of O6-methylguanine-DNA methyltransferase during immortalization of human fibroblasts.

    Science.gov (United States)

    Green, M H; Karran, P; Lowe, J E; Priestley, A; Arlett, C F; Mayne, L

    1990-01-01

    We have examined O6-methylguanine-DNA methyltransferase (MT) activity in four human fibroblast cell lines during immortalization. Transfection of primary fibroblasts with the plasmid pSV3gpt or pSV3neo, which encode the SV40 large T antigen, confers a transformed phenotype but not immediate immortality. After a period of growth (pre-crisis) the cells enter a quiescent phase (crisis) from which an immortal clone of cells eventually grows out. From measurements of MT activity in extracts of cells taken at different defined stages of the immortalization process, we conclude that the establishment of a Mex- (MT-deficient) cell population is not specifically associated with cellular transformation or with any particular stage of immortalization. It appears that in different cell populations the change from Mex+ to Mex- may occur at different times during the immortalization process and that the change may be very abrupt.

  8. Effects of hTERT immortalization on osteogenic and adipogenic differentiation of dental pulp stem cells

    Directory of Open Access Journals (Sweden)

    El-Ayachi Ikbale

    2016-03-01

    Full Text Available These data relate to the differentiation of human dental pulp stem cells (DPSC and DPSC immortalized by constitutively expressing human telomerase reverse transcriptase (hTERT through both osteogenic and adipogenic lineages (i.e. to make bone producing and fat producing cells from these dental pulp stem cells. The data augment another study to characterize immortalized DPSC for the study of neurogenetic “Characterization of neurons from immortalized dental pulp stem cells for the study of neurogenetic disorders” [1]. Two copies of one typical control cell line (technical replicates were used in this study. The data represent the differentiation of primary DPSC into osteoblast cells approximately 60% more effectively than hTERT immortalized DPSC. Conversely, both primary and immortalized DPSC are poorly differentiated into adipocytes. The mRNA expression levels for both early and late adipogenic and osteogenic gene markers are shown. Keywords: Stem cells, Osteogenic, Adipogenic, Immortalized, hTERT, DPSC

  9. Aging and immortality in unicellular species.

    Science.gov (United States)

    Florea, Michael

    2017-10-01

    It has been historically thought that in conditions that permit growth, most unicellular species do not to age. This was particularly thought to be the case for symmetrically dividing species, as such species lack a clear distinction between the soma and the germline. Despite this, studies of the symmetrically dividing species Escherichia coli and Schizosaccharomyces pombe have recently started to challenge this notion. They indicate that E. coli and S. pombe do age, but only when subjected to environmental stress. If true, this suggests that aging may be widespread among microbial species in general, and that studying aging in microbes may inform other long-standing questions in aging. This review examines the recent evidence for and against replicative aging in symmetrically dividing unicellular organisms, the mechanisms that underlie aging, why aging evolved in these species, and how microbial aging fits into the context of other questions in aging. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Efficient immortalization of primary human cells by p16INK4a-specific short hairpin RNA or Bmi-1, combined with introduction of hTERT.

    Science.gov (United States)

    Haga, Kei; Ohno, Shin-ichi; Yugawa, Takashi; Narisawa-Saito, Mako; Fujita, Masatoshi; Sakamoto, Michiie; Galloway, Denise A; Kiyono, Tohru

    2007-02-01

    Activation of telomerase is sufficient for immortalization of some types of human cells but additional factors may also be essential. It has been proposed that stress imposed by inadequate culture conditions induces senescence due to accumulation of p16(INK4a). Here, we present evidence that many human cell types undergo senescence by activation of the p16(INK4a)/Rb pathway, and that introduction of Bmi-1 can inhibit p16(INK4a) expression and extend the life span of human epithelial cells derived from skin, mammary gland and lung. Introduction of p16(INK4a)-specific short hairpin RNA, as well as Bmi-1, suppressed p16(INK4a) expression in human mammary epithelial cells without promoter methylation, and extended their life span. Subsequent introduction of hTERT, the telomerase catalytic subunit, into cells with low p16(INK4a) levels resulted in efficient immortalization of three cell types without crisis or growth arrest. The majority of the human mammary epithelial cells thus immortalized showed almost normal ploidy as judged by G-banding and spectral karyotyping analysis. Our data suggest that inhibition of p16(INK4a) and introduction of hTERT can immortalize many human cell types with little chromosomal instability.

  11. Immortalization of normal human fibroblasts by treatment with 4-nitroquinoline 1-oxide.

    Science.gov (United States)

    Bai, L; Mihara, K; Kondo, Y; Honma, M; Namba, M

    1993-02-01

    Normal human fibroblasts (the OUMS-24 strain), derived from a 6-week-old human embryo, were transformed (into the OUMS-24F line) and immortalized by repeated treatments (59 times) with 4-nitroquinoline 1-oxide (4NQO). Treatment began during primary culture and ended at the 51st population doubling level (PDL). At the 57th PDL (146 days after the last treatment), morphologically altered, epithelial-type cells appeared, began to grow and became immortal (now past the 100th PDL). However, the control fibroblasts, which were not treated with 4NQO, senesced at the 62nd PDL. The finding that extensive, repeated treatments with 4NQO are required for the immortalization of normal human cells, indicates that multiple mutational events are involved in the immortalization of human cells in general. In other words, immortalization itself seems to be a multi-step process. Karyotypic analysis showed that many cells were hypodiploid before immortalization, but that afterwards chromosomes were distributed broadly in the diploid to tetraploid regions. The immortalized cells showed amplification and enhanced expression of c-myc. Two-dimensional electrophoretic analysis showed that the number of disappearing cellular proteins was greater than the number of the newly appearing ones after the cells became immortalized. Since the immortalized cells showed neither anchorage-independent growth nor tumorigenicity, they are useful for studying factors that can contribute to multi-step carcinogenesis in human cells. In addition, genetically matched normal (OUMS-24) and immortalized (OUMS-24F) cells will be useful for analyzing the genes related to cellular mortality and immortalization.

  12. Mortal Ancestors, Immortal Images: Zhang Dai’s Biographical Portraits

    OpenAIRE

    Duncan M. Campbell

    2012-01-01

    Towards the end of his long life, the prolific late-Ming historian and essayist Zhang Dai 張岱 (1597-?1684) completed a book that he had been working on for many years. Entitled Portraits of the Eminent and Worthy Immortals of Zhejiang During the Ming Dynasty (You Ming yuyue san bu xiu tuzan 有明於越三不朽名賢圖贊) the book included the short biographies (with poetic panegyrics) and portraits of 109 men and women of Zhang Dai’s hometown of Shaoxing, one of the epicentres of China’s élite cultural life. Th...

  13. The use of hTERT-immortalized cells in tissue engineering

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Abdallah, Basem; Yu, Zentao

    2004-01-01

    The use of human telomerase reverse transcriptase (hTERT)-immortalized cells in tissue engineering protocols is a potentially important application of telomere biology. Several human cell types have been created that overexpress the hTERT gene with enhanced telomerase activity, extended life span...... and maintained or even improved functional activities. Furthermore, some studies have employed the telomerized cells in tissue engineering protocols with very good results. However, high telomerase activity allows extensive cell proliferation that may be associated with genomic instability and risk for cell...... transformation. Thus, safety issues should be studied carefully before using the telomerized tissues in the clinic. Alternatively, the development of conditional or intermittent telomerase activation protocols is needed....

  14. Comparison of the biological features between human fetal hepatocyte and immortalized L-02 hepatocyte in vitro

    International Nuclear Information System (INIS)

    Kong Weiwei; Teng Gaojun

    2004-01-01

    Objective: To evaluate the feasibilities of the potential donors in liver cell transplantation using the human fetal hepatocytes and immortalized L-02 hepatocytes by comparing their biological features. Methods: Human fetal hepatocytes were isolated from aborted fetal livers (gestational ages from 14 w to 24 w) by an improved two-stage perfusion method and cultured in a conditioned medium without any growth factors. α-fetal protein (AFP) and albumin (ALB) were detected by radioimmunoassay (RIA) and cytokeratin-19 (CK-19 ) was identified by cellular immunochemistry study. Immortalized L-02 hepatocytes were cultured in the same condition and the characteristic proteins were detected by the same methods. Results: The viability of human fetal hepatocytes was approximately 95% using the perfusion method, and the maximum survival time of the cultured hepatocytes was 3 weeks. The expression of AFP, ALB, and CK19 was detected at the same time, especially during Day 3 to Day 7 in the culture. By comparison, the proliferation ability of L-02 hepatocyte was greater, although with a lower level of ALB secretion. The expression of AFP and CK19 was not detected. Furthermore, during the long culture, L-02 hepatocytes may undergo a morphologic change and fail to express ALB. Conclusion: Human fetal hepatocyte may be a practical donor for hepatocyte transplantation with its high-level protein expression and potential bi-differentiation ability. In view of the absent expression of ALB and the morphologic change in culture, although with better proliferation, L-02 hepatocyte seems not useful for hepatocyte transplantation

  15. Immortalized human hepatocytes as a tool for the study of hepatocytic (de-)differentiation

    NARCIS (Netherlands)

    Schippers, IJ; Moshage, H; Roelofsen, H; Muller, M; Heymans, HSA; Ruiters, M; Kuipers, F

    Primary human hepatocytes were immortalized by stable transfection with a recombinant plasmid containing the early region of simian virus (SV) 40. The cells were cultured in serum-free, hormonally defined medium during the immortalization procedure. Foci of dividing cells were seen after 3 months.

  16. Immortalization protocols used in cell culture models of human breast morphogenesis

    DEFF Research Database (Denmark)

    Gudjonsson, T; Villadsen, R; Rønnov-Jessen, L

    2004-01-01

    of the tissue of origin. In recent years, we have sought to establish immortalized primary breast cells, which retain crucial characteristics of their original in situ tissue pattern. This review discusses various approaches to immortalization of breast-derived epithelial and stromal cells and the application...

  17. Immortalization of canine adipose-derived mesenchymal stem cells and their seminiferous tubule transplantation.

    Science.gov (United States)

    Fang, Jia; Wei, Yudong; Teng, Xin; Zhao, Shanting; Hua, Jinlian

    2018-04-01

    Adipose-derived mesenchymal stem cells (ADSCs) are proven to provide good effects in numerous tissue engineering application and other cell-based therapies. However, the difficulty in the proliferation of ADSCs, known as the "Hayflick limit" in vitro, limits their clinical application. Here, we immortalized canine ADSCs (cADSCs) with SV40 gene and transplanted them into busulfan-induced seminiferous tubules of infertile mice. The proliferation of these immortalized cells was improved significantly. Then, cellular differentiation assays showed that the immortalized cADSCs could differentiate into three-germ-layer cells, osteogenesis, chondrogenesis, adipogenesis phenotypes, and primordial germ cell-like cells (PGCLCs). In addition, the immortalized cADSCs can proliferate in the busulfan-induced seminiferous tubules of infertile mice. These findings confirmed that the immortalized cADSCs maintain the criteria of cADSCs. © 2017 Wiley Periodicals, Inc.

  18. DNA asymmetry in stem cells - immortal or mortal?

    Science.gov (United States)

    Yadlapalli, Swathi; Yamashita, Yukiko M

    2013-09-15

    The immortal strand hypothesis proposes that stem cells retain a template copy of genomic DNA (i.e. an 'immortal strand') to avoid replication-induced mutations. An alternative hypothesis suggests that certain cells segregate sister chromatids non-randomly to transmit distinct epigenetic information. However, this area of research has been highly controversial, with conflicting data even from the same cell types. Moreover, historically, the same term of 'non-random sister chromatid segregation' or 'biased sister chromatid segregation' has been used to indicate distinct biological processes, generating a confusion in the biological significance and potential mechanism of each phenomenon. Here, we discuss the models of non-random sister chromatid segregation, and we explore the strengths and limitations of the various techniques and experimental model systems used to study this question. We also describe our recent study on Drosophila male germline stem cells, where sister chromatids of X and Y chromosomes are segregated non-randomly during cell division. We aim to integrate the existing evidence to speculate on the underlying mechanisms and biological relevance of this long-standing observation on non-random sister chromatid segregation.

  19. Mortal Ancestors, Immortal Images: Zhang Dai’s Biographical Portraits

    Directory of Open Access Journals (Sweden)

    Duncan M. Campbell

    2012-11-01

    Full Text Available Towards the end of his long life, the prolific late-Ming historian and essayist Zhang Dai 張岱 (1597-?1684 completed a book that he had been working on for many years. Entitled Portraits of the Eminent and Worthy Immortals of Zhejiang During the Ming Dynasty (You Ming yuyue san bu xiu tuzan 有明於越三不朽名賢圖贊 the book included the short biographies (with poetic panegyrics and portraits of 109 men and women of Zhang Dai’s hometown of Shaoxing, one of the epicentres of China’s élite cultural life. The book was organised according to the “Three Immortalities of Life”: moral force, meritorious service, and wise words. Zhang also included a number of his own friends and family members in this collection. This paper discusses aspects the relationship between text and image in this late-imperial Chinese work, both in the context of Zhang Dai’s practice as a biographer who had a strong visual sense and in regard to his particular historical plight as someone who had survived the collapse of one dynasty and who had lived on under its successor regime.

  20. Towards Maturity in 1 Peter: Freedom, Holiness, Immortality

    Directory of Open Access Journals (Sweden)

    Paul B. Decock

    2016-11-01

    Full Text Available Growth towards maturity is dependent on the presence of freedom, holiness and immortality. These are presented as divine qualities that are utterly lacking in human beings. However, while human beings are ignorant and weak, sinful and mortal the addressees of 1 Peter1 are reminded that they have also been begotten anew by the imperishable seed of God’s Word, the Good News of Jesus Christ in order to share immortal life. This article looks first at human beings who as God’s creatures are ‘flesh’, but are also enabled to acknowledge their ‘fleshly’ state, to appreciate (‘desire’ and ‘taste’ (2:2–3 the Gospel and to submit to God. The second part considers the saving role of Christ as the powerful yet rejected ‘stone’ placed and offered by God as the model and means to transcend the ‘flesh’ in the flesh (4:1–2. A final part focuses on the new birth and the growth process in which the fleshly desires and ways of living give way to a manner of life, which is a witness to God’s saving power.

  1. Amplification and overexpression of aurora kinase A (AURKA) in immortalized human ovarian epithelial (HOSE) cells.

    Science.gov (United States)

    Chung, C M; Man, C; Jin, Y; Jin, C; Guan, X Y; Wang, Q; Wan, T S K; Cheung, A L M; Tsao, S W

    2005-07-01

    Immortalization is an early and essential step of human carcinogenesis. Amplification of chromosome 20q has been shown to be a common event in immortalized cells and cancers. We have previously reported that gain and amplification of chromosome 20q is a non-random and common event in immortalized human ovarian surface epithelial (HOSE) cells. The chromosome 20q harbors genes including TGIF2 (20q11.2-q12), AIB1 (20q12), PTPN1 (20q13.1), ZNF217 (20q13.2), and AURKA (20q13.2-q13.3), which were previously reported to be amplified and overexpressed in ovarian cancers. Some of these genes may be involved in immortalization of HOSE cells and represent crucial premalignant changes in ovarian surface epithelium. Investigation of the involvement of these genes was examined in four pairs of pre-crisis (preimmortalized) and post-crisis (immortalized) HOSE cells. Overexpression of AURKA (Aurora kinase A), also known as BTAK and STK15, by both real time-quantitative polymerase chain reaction (RT-QPCR) and Western blotting was detected in all the four immortalized HOSE cells examined while overexpression of AIB1 and ZNF217 was observed in two of four immortalized HOSE cells examined. Overexpression of TGIF2 and PTPN1 was not significant in our immortalized HOSE cell systems. The degree of overexpression of AURKA was shown to be closely associated with the amplification of chromosome 20q in immortalized HOSE cells. Fluorescence in situ hybridization (FISH) with labeled P1 artificial clone (PAC) confirmed the amplification of the chromosomal region (20q13.2-13.3) where AURKA resides. DNA amplification of AURKA was also confirmed using semi-quantitative PCR. Our study showed that amplification and overexpression of AURKA is a common and significant event during immortalization of HOSE cells and may represent an important premalignant change in ovarian carcinogenesis. Copyright (c) 2005 Wiley-Liss, Inc.

  2. Generation of human cortical neurons from a new immortal fetal neural stem cell line

    International Nuclear Information System (INIS)

    Cacci, E.; Villa, A.; Parmar, M.; Cavallaro, M.; Mandahl, N.; Lindvall, O.; Martinez-Serrano, A.; Kokaia, Z.

    2007-01-01

    Isolation and expansion of neural stem cells (NSCs) of human origin are crucial for successful development of cell therapy approaches in neurodegenerative diseases. Different epigenetic and genetic immortalization strategies have been established for long-term maintenance and expansion of these cells in vitro. Here we report the generation of a new, clonal NSC (hc-NSC) line, derived from human fetal cortical tissue, based on v-myc immortalization. Using immunocytochemistry, we show that these cells retain the characteristics of NSCs after more than 50 passages. Under proliferation conditions, when supplemented with epidermal and basic fibroblast growth factors, the hc-NSCs expressed neural stem/progenitor cell markers like nestin, vimentin and Sox2. When growth factors were withdrawn, proliferation and expression of v-myc and telomerase were dramatically reduced, and the hc-NSCs differentiated into glia and neurons (mostly glutamatergic and GABAergic, as well as tyrosine hydroxylase-positive, presumably dopaminergic neurons). RT-PCR analysis showed that the hc-NSCs retained expression of Pax6, Emx2 and Neurogenin2, which are genes associated with regionalization and cell commitment in cortical precursors during brain development. Our data indicate that this hc-NSC line could be useful for exploring the potential of human NSCs to replace dead or damaged cortical cells in animal models of acute and chronic neurodegenerative diseases. Taking advantage of its clonality and homogeneity, this cell line will also be a valuable experimental tool to study the regulatory role of intrinsic and extrinsic factors in human NSC biology

  3. Cytogenetic characterization and H-ras associated transformation of immortalized human mammary epithelial cells

    Directory of Open Access Journals (Sweden)

    Larivee Siobhan

    2006-05-01

    Full Text Available Abstract Introduction Immortalization is a key step in malignant transformation, but immortalization alone is insufficient for transformation. Human mammary epithelial cell (HMEC transformation is a complex process that requires additional genetic changes beyond immortalization and can be accomplished in vitro by accumulation of genetic changes and expression of H-ras. Methods HMEC were immortalized by serial passaging and transduction with the catalytic subunit of the human telomerase gene (hTERT. The immortalized cells were passaged in vitro and studied by a combination of G- banding and Spectral Karyotyping (SKY. H-ras transduced, hTERT immortalized cells were cloned in soft agar and injected into nude mice. Extensive analysis was performed on the tumors that developed in nude mice, including immunohistochemistry and western blotting. Results Immortal HMEC alone were not tumorigenic in γ-irradiated nude mice and could not grow in soft agar. Late passage hTERT immortalized HMEC from a donor transduced with a retroviral vector containing the mutant, autoactive, human H-ras61L gene acquired anchorage independent growth properties and the capacity for tumorigenic growth in vivo. The tumors that developed in the nude mice were poorly differentiated epithelial carcinomas that continued to overexpress ras. These cells were resistant to doxorubicin mediated G1/S phase arrest but were sensitive to treatment with a farnesyltransferase inhibitor. Conclusion Some of the cytogenetic changes are similar to what is observed in premalignant and malignant breast lesions. Despite these changes, late passage immortal HMEC are not tumorigenic and could only be transformed with overexpression of a mutant H-ras oncogene.

  4. Higher 5-hydroxymethylcytosine identifies immortal DNA strand chromosomes in asymmetrically self-renewing distributed stem cells.

    Science.gov (United States)

    Huh, Yang Hoon; Cohen, Justin; Sherley, James L

    2013-10-15

    Immortal strands are the targeted chromosomal DNA strands of nonrandom sister chromatid segregation, a mitotic chromosome segregation pattern unique to asymmetrically self-renewing distributed stem cells (DSCs). By nonrandom segregation, immortal DNA strands become the oldest DNA strands in asymmetrically self-renewing DSCs. Nonrandom segregation of immortal DNA strands may limit DSC mutagenesis, preserve DSC fate, and contribute to DSC aging. The mechanisms responsible for specification and maintenance of immortal DNA strands are unknown. To discover clues to these mechanisms, we investigated the 5-methylcytosine and 5-hydroxymethylcytosine (5hmC) content on chromosomes in mouse hair follicle DSCs during nonrandom segregation. Although 5-methylcytosine content did not differ significantly, the relative content of 5hmC was significantly higher in chromosomes containing immortal DNA strands than in opposed mitotic chromosomes containing younger mortal DNA strands. The difference in relative 5hmC content was caused by the loss of 5hmC from mortal chromosomes. These findings implicate higher 5hmC as a specific molecular determinant of immortal DNA strand chromosomes. Because 5hmC is an intermediate during DNA demethylation, we propose a ten-eleven translocase enzyme mechanism for both the specification and maintenance of nonrandomly segregated immortal DNA strands. The proposed mechanism reveals a means by which DSCs "know" the generational age of immortal DNA strands. The mechanism is supported by molecular expression data and accounts for the selection of newly replicated DNA strands when nonrandom segregation is initiated. These mechanistic insights also provide a possible basis for another characteristic property of immortal DNA strands, their guanine ribonucleotide dependency.

  5. Peroxisomal abnormalities in the immortalized human hepatocyte (IHH) cell line.

    Science.gov (United States)

    Klouwer, Femke C C; Koster, Janet; Ferdinandusse, Sacha; Waterham, Hans R

    2017-04-01

    The immortalized human hepatocyte (IHH) cell line is increasingly used for studies related to liver metabolism, including hepatic glucose, lipid, lipoprotein and triglyceride metabolism, and the effect of therapeutic interventions. To determine whether the IHH cell line is a good model to investigate hepatic peroxisomal metabolism, we measured several peroxisomal parameters in IHH cells and, for comparison, HepG2 cells and primary skin fibroblasts. This revealed a marked plasmalogen deficiency and a deficient fatty acid α-oxidation in the IHH cells, due to a defect of PEX7, a cytosolic receptor protein required for peroxisomal import of a subset of peroxisomal proteins. These abnormalities have consequences for the lipid homeostasis of these cells and thus should be taken into account for the interpretation of data previously generated by using this cell line and when considering using this cell line for future research.

  6. Preventive treatment of calcium oxalate crystal deposition with immortal flowers.

    Science.gov (United States)

    Orhan, Nilüfer; Onaran, Metin; Şen, İlker; Işık Gönül, İpek; Aslan, Mustafa

    2015-04-02

    A number of medicinal plants are used for their diuretic, urolithiatic and anti-inflammatory effects on urinary system problems in Turkey and the most common traditional remedy for kidney stones is the tea of immortal flowers. The aim of this study is to evaluate the preventive effect of infusions prepared from capitulums of Helichrysum graveolens (M.Bieb.) Sweet (HG) and Helichrysum stoechas ssp. barellieri (Ten.) Nyman (HS) on formation of kidney stones. Sodium oxalate (Ox-70mg/kg intraperitoneally) was used to induce kidney stones on Wistar albino rats. At the same time, two different doses of the plant extracts (HG: 62.5 and 125mg/kg; HS: 78 and 156mg/kg) were dissolved in the drinking water and administered to animals for 5 days. Potassium citrate was used as positive control in the experiments. During the experiment, water intake, urine volume and body weights of the animals were recorded. At the end of the experiments, liver, kidney and body weights of the animals were determined; biochemical analysis were conducted on urine, blood and plasma samples. Histopathological changes in kidney tissues were examined and statistical analysis were evaluated. HS extract showed the highest preventive effect at 156mg/kg dose (stone formation score: 1.16), whereas a number of kidney stones were maximum in sodium oxalate group (stone formation score: 2.66). Helichrysum extracts decreased urine oxalate and uric acid levels and increased citrate levels significantly. In addition, Helichrysum extracts regulated the negative changes in biochemical and hematological parameters occurred after Ox injection. We conclude that Helichrysum extracts could reduce the formation and growth of kidney stones in Ox-induced urolithiasis and can be beneficial for patients with recurrent stones. In addition, this is the first study on the preventive effect of immortal flowers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Genome-wide transcriptional reorganization associated with senescence-to-immortality switch during human hepatocellular carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Gokhan Yildiz

    Full Text Available Senescence is a permanent proliferation arrest in response to cell stress such as DNA damage. It contributes strongly to tissue aging and serves as a major barrier against tumor development. Most tumor cells are believed to bypass the senescence barrier (become "immortal" by inactivating growth control genes such as TP53 and CDKN2A. They also reactivate telomerase reverse transcriptase. Senescence-to-immortality transition is accompanied by major phenotypic and biochemical changes mediated by genome-wide transcriptional modifications. This appears to happen during hepatocellular carcinoma (HCC development in patients with liver cirrhosis, however, the accompanying transcriptional changes are virtually unknown. We investigated genome-wide transcriptional changes related to the senescence-to-immortality switch during hepatocellular carcinogenesis. Initially, we performed transcriptome analysis of senescent and immortal clones of Huh7 HCC cell line, and identified genes with significant differential expression to establish a senescence-related gene list. Through the analysis of senescence-related gene expression in different liver tissues we showed that cirrhosis and HCC display expression patterns compatible with senescent and immortal phenotypes, respectively; dysplasia being a transitional state. Gene set enrichment analysis revealed that cirrhosis/senescence-associated genes were preferentially expressed in non-tumor tissues, less malignant tumors, and differentiated or senescent cells. In contrast, HCC/immortality genes were up-regulated in tumor tissues, or more malignant tumors and progenitor cells. In HCC tumors and immortal cells genes involved in DNA repair, cell cycle, telomere extension and branched chain amino acid metabolism were up-regulated, whereas genes involved in cell signaling, as well as in drug, lipid, retinoid and glycolytic metabolism were down-regulated. Based on these distinctive gene expression features we developed a 15

  8. Ibn Qayyim Al-Jawziyyah and Allameh Tabataba’i on Immortality in Hell

    OpenAIRE

    Janan Izadi; Majid Sadeqi Hasan Abadi; Fatemeh Yusefi kazaj

    2016-01-01

    The Immortality of the people of hell and their eternal torment is one of the most important and complex debates, preoccupying religious scholars of different religions and sects. Each of them has taken a different way based on their intellectual principles of belief to solve this problem and the questions thereof, including how the immortality of the inhabitants of hell hellions and their eternal torment is consistent with the mercy and justice of God. How is it reasonable to endure infinite...

  9. Expectations of immortality: dam safety management into the next millennium

    International Nuclear Information System (INIS)

    Palmer, M.D.

    1999-01-01

    Topics concerning the problems associated with older and aging dams are considered including: what can be done to extent the lifetime of an old dam, the decision to decommission a dam based on a value judgment that the risk of maintaining the dam is too great for society's acceptance, the possibility of change in the level of risk tolerance with time in a technological environment, traditional surveillance methods used by dam owners in the Y2K situation, and the unreality of dam immortality. Trends and means for preserving older dams for their owner's purposes are outlined, as well as their lifetime compared to that of the downstream systems they serve. Despite the fact that we live in a throwaway society, dam owners cannot just leave their dam asset when they are through with using it. Someone has to maintain the dam, or ensure that it is safely decommissioned when the owner is finished with it. On a worldwide scale the available pool of experienced dam engineers is shrinking. This problem needs to be addressed by a shift towards operating and dam safety management skills based on a firm awareness of dam design principles. A shift in society's expectations has occurred such that dam designers and owners must now recognize the impact a dam can have both on its natural and social environments. Because of the increasing emphasis on paying attention to the impacts of people's activities on the planet, engineers more than anyone else must have a significant influence in that direction. 9 refs

  10. Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds

    Science.gov (United States)

    Arandel, Ludovic; Polay Espinoza, Micaela; Matloka, Magdalena; Bazinet, Audrey; De Dea Diniz, Damily; Naouar, Naïra; Rau, Frédérique; Jollet, Arnaud; Edom-Vovard, Frédérique; Mamchaoui, Kamel; Tarnopolsky, Mark; Puymirat, Jack; Battail, Christophe; Boland, Anne; Deleuze, Jean-Francois; Mouly, Vincent; Klein, Arnaud F.

    2017-01-01

    ABSTRACT Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA-dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here, we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA aggregates of expanded repeats, a hallmark of myotonic dystrophy. Selected clones of DM1 and DM2 immortalized myoblasts behave as parental primary myoblasts with a reduced fusion capacity of immortalized DM1 myoblasts when compared with control and DM2 cells. Alternative splicing defects were observed in differentiated DM1 muscle cell lines, but not in DM2 lines. Splicing alterations did not result from differentiation delay because similar changes were found in immortalized DM1 transdifferentiated fibroblasts in which myogenic differentiation has been forced by overexpression of MYOD1. As a proof-of-concept, we show that antisense approaches alleviate disease-associated defects, and an RNA-seq analysis confirmed that the vast majority of mis-spliced events in immortalized DM1 muscle cells were affected by antisense treatment, with half of them significantly rescued in treated DM1 cells. Immortalized DM1 muscle cell lines displaying characteristic disease-associated molecular features such as nuclear RNA aggregates and splicing defects can be used as robust readouts for the screening of therapeutic compounds. Therefore, immortalized DM1 and DM2 muscle cell lines represent new models and tools to investigate molecular pathophysiological mechanisms and evaluate the in vitro effects of compounds on RNA toxicity associated with myotonic dystrophy mutations. PMID:28188264

  11. Possible involvement of loss of imprinting in immortalization of human fibroblasts.

    Science.gov (United States)

    Okamura, Kotaro; Ohno, Maki; Tsutsui, Takeki

    2011-04-01

    Disruption of the normal pattern of parental origin-specific gene expression is referred to as loss of imprinting (LOI), which is common in various cancers. To investigate a possible role of LOI in the early stage of human cell transformation, we studied LOI in 18 human fibroblast cell lines immortalized spontaneously, by viral oncogenes, by chemical or physical carcinogens, or by infection with a retrovirus vector encoding the human telomerase catalytic subunit, hTERT cDNA. LOI was observed in all the 18 immortal cell lines. The gene most commonly exhibiting LOI was NDN which displayed LOI in 15 of the 18 cell lines (83%). The other genes exhibiting LOI at high frequencies were PEG3 (50%), MAGE-L2 (61%) and ZNF 127 (50%). Expression of NDN that was lost in the immortal cell lines was restored by treatment with 5-aza-2'-deoxycytidine. The ratio of histone H3 lysine 9 methylation to histone H3 lysine 4 methylation of the chromatin containing the NDN promoter in the immortal WI-38VA13 cells was greater than that in the parental cells, suggesting chromatin structure-mediated regulation of NDN expression. We previously demonstrated that inactivation of the p16INK4a/pRb pathway is necessary for immortalization of human cells. Human fibroblasts in the pre-crisis phase and cells with an extended lifespan that eventually senesce, both of which have the normal p16INK4a/pRb pathway, did not show LOI at any imprinted gene examined. Although it is not clear if LOI plays a causal role in immortalization of human cells or is merely coincidental, these findings indicate a possible involvement of LOI in immortalization of human cells or a common mechanism involved in both processes.

  12. Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds

    Directory of Open Access Journals (Sweden)

    Ludovic Arandel

    2017-04-01

    Full Text Available Myotonic dystrophy type 1 (DM1 and type 2 (DM2 are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA-dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here, we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA aggregates of expanded repeats, a hallmark of myotonic dystrophy. Selected clones of DM1 and DM2 immortalized myoblasts behave as parental primary myoblasts with a reduced fusion capacity of immortalized DM1 myoblasts when compared with control and DM2 cells. Alternative splicing defects were observed in differentiated DM1 muscle cell lines, but not in DM2 lines. Splicing alterations did not result from differentiation delay because similar changes were found in immortalized DM1 transdifferentiated fibroblasts in which myogenic differentiation has been forced by overexpression of MYOD1. As a proof-of-concept, we show that antisense approaches alleviate disease-associated defects, and an RNA-seq analysis confirmed that the vast majority of mis-spliced events in immortalized DM1 muscle cells were affected by antisense treatment, with half of them significantly rescued in treated DM1 cells. Immortalized DM1 muscle cell lines displaying characteristic disease-associated molecular features such as nuclear RNA aggregates and splicing defects can be used as robust readouts for the screening of therapeutic compounds. Therefore, immortalized DM1 and DM2 muscle cell lines represent new models and tools to investigate molecular pathophysiological mechanisms and evaluate the in vitro effects of compounds on RNA toxicity associated with myotonic dystrophy mutations.

  13. Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds.

    Science.gov (United States)

    Arandel, Ludovic; Polay Espinoza, Micaela; Matloka, Magdalena; Bazinet, Audrey; De Dea Diniz, Damily; Naouar, Naïra; Rau, Frédérique; Jollet, Arnaud; Edom-Vovard, Frédérique; Mamchaoui, Kamel; Tarnopolsky, Mark; Puymirat, Jack; Battail, Christophe; Boland, Anne; Deleuze, Jean-Francois; Mouly, Vincent; Klein, Arnaud F; Furling, Denis

    2017-04-01

    Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA-dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here, we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA aggregates of expanded repeats, a hallmark of myotonic dystrophy. Selected clones of DM1 and DM2 immortalized myoblasts behave as parental primary myoblasts with a reduced fusion capacity of immortalized DM1 myoblasts when compared with control and DM2 cells. Alternative splicing defects were observed in differentiated DM1 muscle cell lines, but not in DM2 lines. Splicing alterations did not result from differentiation delay because similar changes were found in immortalized DM1 transdifferentiated fibroblasts in which myogenic differentiation has been forced by overexpression of MYOD1. As a proof-of-concept, we show that antisense approaches alleviate disease-associated defects, and an RNA-seq analysis confirmed that the vast majority of mis-spliced events in immortalized DM1 muscle cells were affected by antisense treatment, with half of them significantly rescued in treated DM1 cells. Immortalized DM1 muscle cell lines displaying characteristic disease-associated molecular features such as nuclear RNA aggregates and splicing defects can be used as robust readouts for the screening of therapeutic compounds. Therefore, immortalized DM1 and DM2 muscle cell lines represent new models and tools to investigate molecular pathophysiological mechanisms and evaluate the in vitro effects of compounds on RNA toxicity associated with myotonic dystrophy mutations. © 2017. Published by The Company of Biologists Ltd.

  14. Immortalized Muscle Cell Model to Test the Exon Skipping Efficacy for Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Quynh Nguyen

    2017-10-01

    Full Text Available Duchenne muscular dystrophy (DMD is a lethal genetic disorder that most commonly results from mutations disrupting the reading frame of the dystrophin (DMD gene. Among the therapeutic approaches employed, exon skipping using antisense oligonucleotides (AOs is one of the most promising strategies. This strategy aims to restore the reading frame, thus producing a truncated, yet functioning dystrophin protein. In 2016, the Food and Drug Administration (FDA conditionally approved the first AO-based drug, eteplirsen (Exondys 51, developed for DMD exon 51 skipping. An accurate and reproducible method to quantify exon skipping efficacy is essential for evaluating the therapeutic potential of different AOs sequences. However, previous in vitro screening studies have been hampered by the limited proliferative capacity and insufficient amounts of dystrophin expressed by primary muscle cell lines that have been the main system used to evaluate AOs sequences. In this paper, we illustrate the challenges associated with primary muscle cell lines and describe a novel approach that utilizes immortalized cell lines to quantitatively evaluate the exon skipping efficacy in in vitro studies.

  15. On the acoustic wave sensor response to immortalized hypothalamic neurons at the device-liquid interface

    Directory of Open Access Journals (Sweden)

    Shilin Cheung

    2016-12-01

    Full Text Available The response of a thickness shear mode biosensor to immortalized murine hypothalamic neurons (mHypoE-38 and -46 cells under a variety of conditions and stimuli is discussed. Cellular studies which lead to the production of detectable neuronal responses include neuronal deposition, adhesion and proliferation, alteration in the extent of specific cell-surface interactions, actin filament and microtubule cytoskeletal disruptions, effects of cell depolarization, inhibition of the Na+-K+ pump via ouabain, effects of neuronal synchronization and the effects ligand-receptor interaction (glucagon. In the presence of cells, fs shifts are largely influenced by the damping of the TSM resonator. The formation of cell-surface interactions and hence the increase in coupling and acoustic energy dissipation can be modeled as an additional resistor in the BVD model. Further sensor and cellular changes can be obtained by negating the effects of damping from fs via the use of Rm and θmax. Keywords: Acoustic wave sensor, Hypothalamic neurons, Neuron cell-surface interaction

  16. Loss of Dnmt3a Immortalizes Hematopoietic Stem Cells In Vivo

    Directory of Open Access Journals (Sweden)

    Mira Jeong

    2018-04-01

    Full Text Available Summary: Somatic mutations in DNMT3A are recurrent events across a range of blood cancers. Dnmt3a loss of function in hematopoietic stem cells (HSCs skews divisions toward self-renewal at the expense of differentiation. Moreover, DNMT3A mutations can be detected in the blood of aging individuals, indicating that mutant cells outcompete normal HSCs over time. It is important to understand how these mutations provide a competitive advantage to HSCs. Here we show that Dnmt3a-null HSCs can regenerate over at least 12 transplant generations in mice, far exceeding the lifespan of normal HSCs. Molecular characterization reveals that this in vivo immortalization is associated with gradual and focal losses of DNA methylation at key regulatory regions associated with self-renewal genes, producing a highly stereotypical HSC phenotype in which epigenetic features are further buttressed. These findings lend insight into the preponderance of DNMT3A mutations in clonal hematopoiesis and the persistence of mutant clones after chemotherapy. : Jeong et al. show that a single genetic manipulation, conditional inactivation of the DNA methyltransferase enzyme Dnmt3a, removes all inherent hematopoietic stem cell (HSC self-renewal limits and replicative lifespan. Deletion of Dnmt3a allows HSCs to be propagated indefinitely in vivo. Keywords: DNMT3A, DNA methylation, HSC, self-renewal, leukemia

  17. Thallium stimulates ethanol production in immortalized hippocampal neurons.

    Directory of Open Access Journals (Sweden)

    Laura Colombaioni

    Full Text Available Lactate and ethanol (EtOH were determined in cell culture medium (CCM of immortalized hippocampal neurons (HN9.10e cell line before and after incubation with Thallium (Tl. This cell line is a reliable, in vitro model of one of the most vulnerable regions of central nervous system. Cells were incubated for 48 h with three different single Tl doses: 1, 10, 100 μg/L (corresponding to 4.9, 49 and 490 nM, respectively. After 48 h, neurons were "reperfused" with fresh CCM every 24/48 h until 7 days after the treatment and the removed CCM was collected and analysed. Confocal microscopy was employed to observe morphological changes. EtOH was determined by head space-solid phase microextraction -gas chromatography -mass spectrometry (HS-SPME-GCMS, lactate by RP-HPLC with UV detection. Tl exposure had significant effects on neuronal growth rate and morphology. The damage degree was dose-dependent. In not exposed cells, EtOH concentration was 0.18 ± 0.013 mM, which represents about 5% of lactate concentration (3.4 ± 0.10 mM. After Tl exposure lactate and EtOH increased. In CCM of 100 and 10 μg/L Tl-treated cells, lactate increased 24 h after reperfusion up to 2 and 3.3 times the control value, respectively. In CCM of 10 and 100 μg/L Tl-treated cells 24 h after reperfusion, EtOH increased up to 0.3 and 0.58 mmol/L. respectively. These results are consistent with significant alterations in energy metabolism, despite the low doses of Tl employed and the relatively short incubation time.

  18. Thallium stimulates ethanol production in immortalized hippocampal neurons.

    Science.gov (United States)

    Colombaioni, Laura; Onor, Massimo; Benedetti, Edoardo; Bramanti, Emilia

    2017-01-01

    Lactate and ethanol (EtOH) were determined in cell culture medium (CCM) of immortalized hippocampal neurons (HN9.10e cell line) before and after incubation with Thallium (Tl). This cell line is a reliable, in vitro model of one of the most vulnerable regions of central nervous system. Cells were incubated for 48 h with three different single Tl doses: 1, 10, 100 μg/L (corresponding to 4.9, 49 and 490 nM, respectively). After 48 h, neurons were "reperfused" with fresh CCM every 24/48 h until 7 days after the treatment and the removed CCM was collected and analysed. Confocal microscopy was employed to observe morphological changes. EtOH was determined by head space-solid phase microextraction -gas chromatography -mass spectrometry (HS-SPME-GCMS), lactate by RP-HPLC with UV detection. Tl exposure had significant effects on neuronal growth rate and morphology. The damage degree was dose-dependent. In not exposed cells, EtOH concentration was 0.18 ± 0.013 mM, which represents about 5% of lactate concentration (3.4 ± 0.10 mM). After Tl exposure lactate and EtOH increased. In CCM of 100 and 10 μg/L Tl-treated cells, lactate increased 24 h after reperfusion up to 2 and 3.3 times the control value, respectively. In CCM of 10 and 100 μg/L Tl-treated cells 24 h after reperfusion, EtOH increased up to 0.3 and 0.58 mmol/L. respectively. These results are consistent with significant alterations in energy metabolism, despite the low doses of Tl employed and the relatively short incubation time.

  19. Expectations of immortality: dam safety management into the next millennium

    Energy Technology Data Exchange (ETDEWEB)

    Palmer, M.D. [Tonkin and Taylor International Ltd., Auckland, (New Zealand)

    1999-07-01

    Topics concerning the problems associated with older and aging dams are considered including: what can be done to extent the lifetime of an old dam, the decision to decommission a dam based on a value judgment that the risk of maintaining the dam is too great for society's acceptance, the possibility of change in the level of risk tolerance with time in a technological environment, traditional surveillance methods used by dam owners in the Y2K situation, and the unreality of dam immortality. Trends and means for preserving older dams for their owner's purposes are outlined, as well as their lifetime compared to that of the downstream systems they serve. Despite the fact that we live in a throwaway society, dam owners cannot just leave their dam asset when they are through with using it. Someone has to maintain the dam, or ensure that it is safely decommissioned when the owner is finished with it. On a worldwide scale the available pool of experienced dam engineers is shrinking. This problem needs to be addressed by a shift towards operating and dam safety management skills based on a firm awareness of dam design principles. A shift in society's expectations has occurred such that dam designers and owners must now recognize the impact a dam can have both on its natural and social environments. Because of the increasing emphasis on paying attention to the impacts of people's activities on the planet, engineers more than anyone else must have a significant influence in that direction. 9 refs.

  20. Establishment of immortalized human erythroid progenitor cell lines able to produce enucleated red blood cells.

    Directory of Open Access Journals (Sweden)

    Ryo Kurita

    Full Text Available Transfusion of red blood cells (RBCs is a standard and indispensable therapy in current clinical practice. In vitro production of RBCs offers a potential means to overcome a shortage of transfusable RBCs in some clinical situations and also to provide a source of cells free from possible infection or contamination by microorganisms. Thus, in vitro production of RBCs may become a standard procedure in the future. We previously reported the successful establishment of immortalized mouse erythroid progenitor cell lines that were able to produce mature RBCs very efficiently. Here, we have developed a reliable protocol for establishing immortalized human erythroid progenitor cell lines that are able to produce enucleated RBCs. These immortalized cell lines produce functional hemoglobin and express erythroid-specific markers, and these markers are upregulated following induction of differentiation in vitro. Most importantly, these immortalized cell lines all produce enucleated RBCs after induction of differentiation in vitro, although the efficiency of producing enucleated RBCs remains to be improved further. To the best of our knowledge, this is the first demonstration of the feasibility of using immortalized human erythroid progenitor cell lines as an ex vivo source for production of enucleated RBCs.

  1. Immortalization of Human Fetal Hepatocyte by Ectopic Expression of Human Telomerase Reverse Transcriptase, Human Papilloma Virus (E7) and Simian Virus 40 Large T (SV40 T) Antigen Towards Bioartificial Liver Support.

    Science.gov (United States)

    Giri, Shibashish; Bader, Augustinus

    2014-09-01

    conditional human fetal hepatocytes cell line with mesenchymal characteristics. Thus immortalization of human fetal hepatocytes cell line by telomerase biology offers a great challenge to examine basic biological mechanisms which are directly related to human and best cell source having unlimited population doubling for bioartificial support without any risk of replicative senescence and pathogenic risks.

  2. Isolation, Characterization, and Establishment of Spontaneously Immortalized Cell Line HRPE-2S With Stem Cell Properties.

    Science.gov (United States)

    Shams Najafabadi, Hoda; Soheili, Zahra-Soheila; Samiei, Shahram; Ahmadieh, Hamid; Ranaei Pirmardan, Ehsan; Masoumi, Maryam

    2017-10-01

    The retinal pigment epithelium is a monolayer of highly specialized pigmented cells located between the neural retina and the Bruch's membrane of the choroid. RPE cells play a crucial role in the maintenance and function of the underlying photoreceptors. This study introduces a spontaneously arising human retinal pigment epithelial cell line, HRPE-2S, which was isolated from primary RPE cell culture of 2 days old male donor. We characterized morphology and functional properties of the new cell line. The immortalized cell line was maintained in culture for more than 70 passages and 240 divisions. The average doubling time of the cells was approximately 22 h and got freezed at 26th passage. The cell line expressed RPE-specific markers RPE65 and cell junction protein ZO1 as an epithelial cell marker. It also expressed CHX10, PAX6, Nestin, SOX2 as stem and retinal progenitor cell markers. Ki67 as a marker of cell proliferation was expressed in all HRPE-2S cells. It represented typical epithelial cobblestone morphology and did not phenotypically change through several passages. Stem cell-like aggregations (neurospheres) were observed in SEM microscopy. The cells represented high mitotic index. They could be viable under hypoxic conditions and serum deprivation. According to functional studies, the cell line exhibited stem cell-like behaviors with particular emphasis on its self-renewal capacity. LDH isoenzymes expression pattern confirmed the same cellular source for both of the HRPE-2S cells and primary RPE cells. Characteristics of HRPE-2S cells promise it as an in vitro model for RPE stem cell-based researches. J. Cell. Physiol. 232: 2626-2640, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. X-ray induction of immortalization in primary rat embryo cells associated with and without tumorigenicity

    International Nuclear Information System (INIS)

    Sierra, E.; Oberley, L.W.; Guernsey, D.L.

    1985-01-01

    Cultures of primary rat embryo fibroblasts were irradiated with X-rays (3 Gy). After 14 days the majority of colonies in both irradiated and control plates had senesced. Surviving clones were ring isolated from irradiated and control plates and grown in culture. A phase of rapid proliferation after isolation was observed, followed by a decline (crisis) leading to senescence. Several clones from the irradiated plates were able to recover from this crisis and gave rise to continuous cell lines, while all colonies from control plates senesced. Three types of cells have been identified among the irradiated survivors: (1) immortal fully transformed, capable of growth in soft agar (Aga/sup +/) and tumor formation, (2) immortal normal, not able to grow in soft agar (Aga/sup -/) and nontumorigenic, and (3) immortal Aga/sup -/ cells which progressed to malignancy (Aga/sup +/, tumorigenicity) after further sub-culture. These data support the suggestion that X-rays can induce immortalization of mammalian cells in the absence of tumorigenicity, in addition to (and separate from) the fully tumorigenetic state

  4. Immortality of Prejudice in Striving Ubuntu: Case Studies of Community Managed Schools in Nepal

    Science.gov (United States)

    Rajbhandari, Mani Man Singh; Rajbhandari, Smriti

    2016-01-01

    The immortality of prejudice after the school management transfer has not been judged. This makes communities to take responsibility for schools further by compelling the government to mandate amendments of Community Managed Schools (CMS) Directives. The purpose was to explore the CMS enduring Ubuntu against immorality of prejudice, through…

  5. Immortalized sheep microglial cells are permissive to a diverse range of ruminant viruses.

    Science.gov (United States)

    Stanton, James B; Swanson, Beryl; Orozco, Edith; Muñoz-Gutiérrez, Juan F; Evermann, James F; Ridpath, Julia F

    2017-12-01

    Ruminants, including sheep and goats (small ruminants), are key agricultural animals in many parts of the world. Infectious diseases, including many viral diseases, are significant problems to efficient production of ruminants. Unfortunately, reagents tailored to viruses of ruminants, and especially small ruminants, are lacking compared to other animals more typically used for biomedical research. The purpose of this study was to determine the permissibility of a stably immortalized, sheep microglial cell line to viruses that are reported to infect ruminants: bovine viral diarrhea virus (BVDV), bovine herpesvirus 1 (BoHV-1), small ruminant lentiviruses (SRLV), and bovine respiratory syncytial virus (BRSV). Sublines A and H of previously isolated, immortalized, and characterized (CD14-positive) ovine microglial cells were used. Bovine turbinate cells and goat synovial membrane cells were used for comparison. Cytopathic changes were used to confirm infection of individual wells, which were then counted and used to calculate the 50% tissue culture infectious dose. Uninoculated cells served as negative controls and confirmed that the cells were not previously infected with these viruses using polymerase chain reaction (PCR). Inoculation of the two microglial cell sublines with laboratory and field isolates of BVDV, BoHV-1, and BRSV resulted in viral infection in a manner similar to bovine turbinate cells. Immortalized microglia cells are also permissive to SRLV, similar to goat synovial membrane cells. These immortalized sheep microglial cells provide a new tool for the study of ruminant viruses in ruminant microglial cell line.

  6. Human papilloma virus DNAs immortalize normal human mammary epithelial cells and reduce their growth factor requirements

    International Nuclear Information System (INIS)

    Band, V.; Zajchowski, D.; Kulesa, V.; Sager, R.

    1990-01-01

    Human papilloma virus (HPV) types 16 and 18 are most commonly associated with cervical carcinoma in patients and induce immortalization of human keratinocytes in culture. HPV has not been associated with breast cancer. This report describes the immortalization of normal human mammary epithelial cells (76N) by plasmid pHPV18 or pHPV16, each containing the linearized viral genome. Transfectants were grown continuously for more than 60 passages, whereas 76N cells senesce after 18-20 passages. The transfectants also differ from 76N cells in cloning in a completely defined medium called D2 and growing a minimally supplemented defined medium (D3) containing epidermal growth factor. All transfectant tested contain integrated HPV DNA, express HPV RNA, and produce HPV E7 protein. HPV transfectants do not form tumors in a nude mouse assay. It is concluded that products of the HPV genome induce immortalization of human breast epithelial cells and reduce their growth factor requirements. This result raises the possibility that HPV might be involved in breast cancer. Furthermore, other tissue-specific primary epithelial cells that are presently difficult to grown and investigate may also be immortalized by HPV

  7. Establishment of an immortalized mouse dermal papilla cell strain with optimized culture strategy

    Directory of Open Access Journals (Sweden)

    Haiying Guo

    2018-01-01

    Full Text Available Dermal papilla (DP plays important roles in hair follicle regeneration. Long-term culture of mouse DP cells can provide enough cells for research and application of DP cells. We optimized the culture strategy for DP cells from three dimensions: stepwise dissection, collagen I coating, and optimized culture medium. Based on the optimized culture strategy, we immortalized primary DP cells with SV40 large T antigen, and established several immortalized DP cell strains. By comparing molecular expression and morphologic characteristics with primary DP cells, we found one cell strain named iDP6 was similar with primary DP cells. Further identifications illustrate that iDP6 expresses FGF7 and α-SMA, and has activity of alkaline phosphatase. During the process of characterization of immortalized DP cell strains, we also found that cells in DP were heterogeneous. We successfully optimized culture strategy for DP cells, and established an immortalized DP cell strain suitable for research and application of DP cells.

  8. Husserl, the Monad and Immortality | MacDonald | Indo-Pacific ...

    African Journals Online (AJOL)

    In an Appendix to his Analyses Concerning Passive and Active Synthesis dating from the early 1920s, Husserl makes the startling assertion that, unlike the mundane ego, the transcendental ego is immortal. The present paper argues that this claim is an ineluctable consequence of Husserl's relentless pursuit of the ever ...

  9. Characterization of lipid metabolism in insulin-sensitive adipocytes differentiated from immortalized human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Prawitt, Janne; Niemeier, Andreas; Kassem, Moustapha

    2008-01-01

    There is a great demand for cell models to study human adipocyte function. Here we describe the adipogenic differentiation of a telomerase-immortalized human mesenchymal stem cell line (hMSC-Tert) that maintains numerous features of terminally differentiated adipocytes even after prolonged...

  10. Functional analysis of a novel human serotonin transporter gene promoter in immortalized raphe cells

    DEFF Research Database (Denmark)

    Mortensen, O V; Thomassen, M; Larsen, M B

    1999-01-01

    were found to possess the additional 379 bp fragment. The integrity of the promoter was furthermore confirmed by genomic Southern blotting. The promoter activity was analyzed by reporter gene assays in neuronal and non-neuronal serotonergic cell lines. In immortalized serotonergic raphe neurons, RN46A...

  11. Recovery of important physiological functions in 3D culture of immortal hepatocytes

    DEFF Research Database (Denmark)

    Wrzesinski, Krzysztof; Fey, S. J.

    2011-01-01

    to grow human liver cells in ‘3 dimensional’ cultures so that they behave very similar to the liver in our bodies. By growing the immortal hepatocytes in specially designed bioreactors they form small pieces of ‘pseudotissue’ which exhibit several of the functions seen in the adult liver. We have grown...

  12. QTL Analysis of Kernel-Related Traits in Maize Using an Immortalized F2 Population

    Science.gov (United States)

    Hu, Yanmin; Li, Weihua; Fu, Zhiyuan; Ding, Dong; Li, Haochuan; Qiao, Mengmeng; Tang, Jihua

    2014-01-01

    Kernel size and weight are important determinants of grain yield in maize. In this study, multivariate conditional and unconditional quantitative trait loci (QTL), and digenic epistatic analyses were utilized in order to elucidate the genetic basis for these kernel-related traits. Five kernel-related traits, including kernel weight (KW), volume (KV), length (KL), thickness (KT), and width (KWI), were collected from an immortalized F2 (IF2) maize population comprising of 243 crosses performed at two separate locations over a span of two years. A total of 54 unconditional main QTL for these five kernel-related traits were identified, many of which were clustered in chromosomal bins 6.04–6.06, 7.02–7.03, and 10.06–10.07. In addition, qKL3, qKWI6, qKV10a, qKV10b, qKW10a, and qKW7a were detected across multiple environments. Sixteen main QTL were identified for KW conditioned on the other four kernel traits (KL, KWI, KT, and KV). Thirteen main QTL were identified for KV conditioned on three kernel-shape traits. Conditional mapping analysis revealed that KWI and KV had the strongest influence on KW at the individual QTL level, followed by KT, and then KL; KV was mostly strongly influenced by KT, followed by KWI, and was least impacted by KL. Digenic epistatic analysis identified 18 digenic interactions involving 34 loci over the entire genome. However, only a small proportion of them were identical to the main QTL we detected. Additionally, conditional digenic epistatic analysis revealed that the digenic epistasis for KW and KV were entirely determined by their constituent traits. The main QTL identified in this study for determining kernel-related traits with high broad-sense heritability may play important roles during kernel development. Furthermore, digenic interactions were shown to exert relatively large effects on KL (the highest AA and DD effects were 4.6% and 6.7%, respectively) and KT (the highest AA effects were 4.3%). PMID:24586932

  13. The People Paradox: Self-Esteem Striving, Immortality Ideologies, and Human Response to Climate Change

    Directory of Open Access Journals (Sweden)

    Janis L. Dickinson

    2009-06-01

    Full Text Available In 1973, Ernest Becker, a cultural anthropologist cross-trained in philosophy, sociology, and psychiatry, invoked consciousness of self and the inevitability of death as the primary sources of human anxiety and repression. He proposed that the psychological basis of cooperation, competition, and emotional and mental health is a tendency to hold tightly to anxiety-buffering cultural world views or "immortality projects" that serve as the basis for self-esteem and meaning. Although he focused mainly on social and political outcomes like war, torture, and genocide, he was increasingly aware that materialism, denial of nature, and immortality-striving efforts to control, rather than sanctify, the natural world were problems whose severity was increasing. In this paper I review Becker's ideas and suggest ways in which they illuminate human response to global climate change. Because immortality projects range from belief in technology and materialism to reverence for nature or belief in a celestial god, they act both as barriers to and facilitators of sustainable practices. I propose that Becker's cross-disciplinary "science of man," and the predictions it generates for proximate-level determinants of social behavior, add significantly to our understanding of and potential for managing the people paradox, i.e., that the very things that bring us symbolic immortality often conflict with our prospects for survival. Analysis of immortality projects as one of the proximate barriers to addressing climate change is both cautionary and hopeful, providing insights that should be included in the cross-disciplinary quest to uncover new pathways toward rational, social change.

  14. Human conditionally immortalized neural stem cells improve locomotor function after spinal cord injury in the rat

    Czech Academy of Sciences Publication Activity Database

    Amemori, Takashi; Romanyuk, Nataliya; Jendelová, Pavla; Herynek, V.; Turnovcová, Karolína; Procházka, Pavel; Kapcalová, Miroslava; Cocks, G.; Price, J.; Syková, Eva

    2013-01-01

    Roč. 4, č. 3 (2013), s. 68 ISSN 1757-6512 R&D Projects: GA ČR(CZ) GAP304/12/1370; GA ČR GA13-00939S; GA MŠk LH12024; GA ČR(CZ) GBP304/12/G069 Grant - others:GA MZd(CZ) 00023001IKEM Institutional support: RVO:68378041 Keywords : human fetal neural stem cells * spinal cord injury * motor neuron differentiation Subject RIV: FH - Neurology Impact factor: 4.634, year: 2013

  15. Immortalization of human foreskin keratinocytes by various human papillomavirus DNAs corresponds to their association with cervical carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Woodworth, C.D.; Doniger, J.; DiPaolo, J.A.

    1989-01-01

    Normal human foreskin keratinocytes cotransfected with the neomycin resistance gene and recombinant human papillomavirus (HPV) DNAs (types 16, 18, 31, and 33) that have a high or moderate association with cervical malignancy acquired immortality and contained integrated and transcriptionally active viral genomes. Only transcripts from the intact E6 and E7 genes were detected in at least one cell line, suggesting that one or both of these genes are responsible for immortalization. Recombinant HPV DNAs with low or no oncogenic potential for cervical cancer (HPV1a, -5, -6b, and -11) induced small G418-resistant colonies that senesced as did the nontransfected cells. These colonies contained only episomal virus DNA; therefore, integration of HPV sequences is important for immortalization of keratinocytes. This study suggests that the virus-encoded immortalization function contributes to the pathogenesis of cervical carcinoma.

  16. Milk as a symbol of immortality in the “Orphic” gold tablets from Thurii and Pelinna

    Directory of Open Access Journals (Sweden)

    Stian Sundell Torjussen

    2014-11-01

    Full Text Available This article offers an interpretation of the enigmatic “kid-in-milk” formula which appears in four of the “Orphic” gold tablets from Thurii and Pelinna. These tiny tablets accompanied the dead in their graves and contained texts of various lengths which were believed to help the deceased on his or her journey to the otherworld. Many see the tablets as Orphic texts, but this question has been highly debated during the last century. The four tablets in question, from two sites in southern Italy and Greece, tell how the deceased has suffered in life, but that he or she has attained immortality through initiation. The immortalization was referred to and summed up in the “kid-in-milk” formula, where, it is argued, milk was a direct reference to immortality. Thus milk in this eschatological context is a symbol of immortality which served as a focal point for both the text and the initates.

  17. Ibn Qayyim Al-Jawziyyah and Allameh Tabataba’i on Immortality in Hell

    Directory of Open Access Journals (Sweden)

    Janan Izadi

    2016-09-01

    Full Text Available The Immortality of the people of hell and their eternal torment is one of the most important and complex debates, preoccupying religious scholars of different religions and sects. Each of them has taken a different way based on their intellectual principles of belief to solve this problem and the questions thereof, including how the immortality of the inhabitants of hell hellions and their eternal torment is consistent with the mercy and justice of God. How is it reasonable to endure infinite torment for limited and finite sins? Does a Merciful God, born a sinful slave forever in the fire of the hereafter? Or  is this not the case and He punishes the sinful people for a limited period of time, whether it is short or long, and then releases them from  torture and provides them with  comfort. There is a difference of opinions on these problems in the works of Ibn Qayyim Al- Jawziyyah Al-Ash͑ari and Allameh Tabataba’i, the Shiite philosopher and commentator.Ibn Qayyim addresses widely and systematically the issue of the immortality of the inhabitants of hell. In fact, he interprets immortality (khulūd as a long time, so that the long fire and scourge annihilate the evil from the souls that evil has mixed in their being.  In his viewpoint God has created human monotheist. If the monotheistic nature of the person is changed by vices, these vices and the corrupted nature can be changed by torment and fire. He quotes in his works the ideas of the believers in immortality in torment and criticizes and rebuts them. Stating so many arguments, Ibn Qayyim Al-Jawziyya tries to deny the immortality and eternality in torment. Interpreting the verses of The Holy Quran on immortality of the inhabitants of hell in torment, Allameh Tabataba’i strongly asserts the immortality principle. He relates the happiness and misery, and good and evil among human beings to the development and appearance of the carnal states and habits they gained in the earthly

  18. Regulation of Telomere Homeostasis during Epstein-Barr virus Infection and Immortalization.

    Science.gov (United States)

    Kamranvar, Siamak A; Masucci, Maria G

    2017-08-09

    The acquisition of unlimited proliferative potential is dependent on the activation of mechanisms for telomere maintenance, which counteracts telomere shortening and the consequent triggering of the DNA damage response, cell cycle arrest, and apoptosis. The capacity of Epstein Barr virus (EBV) to infect B-lymphocytes in vitro and transform the infected cells into autonomously proliferating immortal cell lines underlies the association of this human gamma-herpesvirus with a broad variety of lymphoid and epithelial cell malignancies. Current evidence suggests that both telomerase-dependent and -independent pathways of telomere elongation are activated in the infected cells during the early and late phases of virus-induced immortalization. Here we review the interaction of EBV with different components of the telomere maintenance machinery and the mechanisms by which the virus regulates telomere homeostasis in proliferating cells. We also discuss how these viral strategies may contribute to malignant transformation.

  19. A supporting role of Chinese National Immortalized Cell Bank in life science research.

    Science.gov (United States)

    Xu, Chong-feng; Duan, Zi-yuan

    2017-01-20

    A biorepository of human samples is essential to support the research of life science. Lymphoblastoid B cell line (LCL), which is easy to be prepared and can reproduce indefinitely, is a convenient form of sample preservation. LCLs are established from human B cells transformed by Epstein-Barr virus (EBV). Chinese National Immortalized Cell Bank has preserved human LCLs from different ethnic groups in China. As there are many studies on the nature of LCLs and public available resources with genome-wide data for LCLs, they have been widely applied in genetics, immunology, pharmacogenetics/genomics, regenerative medicine, cancer pathogenesis and immunotherapy, screening and generation of fully human neutralizing monoclonal antibodies and study on EBV pathogenesis. Here, we review the characteristics of LCLs and their contributions to scientific research, and introduce preserved samples in Chinese National Immortalized Cell Bank to the scientific community. We hope this bank can support more areas in the scientific research.

  20. Random integration of SV40 in SV40-transformed, immortalized human fibroblasts.

    Science.gov (United States)

    Hara, H; Kaji, H

    1987-02-01

    We have studied the relationship between immortalization of SV40-transformed human embryonic fibroblasts and their SV40 integration sites. From several independently transformed cell pools, we have isolated clones which do not harbor unintegrated SV40 DNA. We have analysed whole-cell DNA from these clones, using the Southern blot method. Our results suggest that no specific integration sites in the cellular genome exist which are a prerequisite for the immortalization process. Although some integration sites were found to be predominant in pre-crisis clones, they could not be detected in the post-crisis clones. This suggests that none of these predominating sites is selected for during the crisis period.

  1. Original article Values and sense of symbolic immortality among non-religious adolescents in Poland

    OpenAIRE

    Michał Jaśkiewicz

    2014-01-01

    Background The aim of the study was to determine the values (Schwartz’s ten basic values) and sense of symbolic immortality among non-religious adolescents. Participants and procedure Participants were recruited from secondary schools in Gdansk and Gdynia. Results The results showed that non-religious adolescents achieved higher results in the natural mode, and lower in biological-creative and religious modes. They also scored higher on universalism and self...

  2. Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds

    OpenAIRE

    Arandel, Ludovic; Polay Espinoza, Micaela; Matloka, Magdalena; Bazinet, Audrey; De Dea Diniz, Damily; Naouar, Na?ra; Rau, Fr?d?rique; Jollet, Arnaud; Edom-Vovard, Fr?d?rique; Mamchaoui, Kamel; Tarnopolsky, Mark; Puymirat, Jack; Battail, Christophe; Boland, Anne; Deleuze, Jean-Francois

    2017-01-01

    International audience; Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA-dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here, we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA aggregates of expanded rep...

  3. A Grand Challenge: Immortal Information and Through-Life Knowledge Management (KIM

    Directory of Open Access Journals (Sweden)

    Alexander Ball

    2006-11-01

    Full Text Available ‘Immortal information and through-life knowledge management: strategies and tools for the emerging product-service business paradigm’, is a Grand Challenge project involving eleven different UK universities and incorporating substantial industry collaboration. It is investigating a range of issues associated with the move towards a product-service paradigm in the engineering sector, in particular the long-term curation of digital data, learning from production and use, and appropriate governance and management techniques.

  4. Methodological challenges to control for immortal time bias in addressing drug effects in type 2 diabetes

    OpenAIRE

    Yang, Xi-Lin; Huo, Xiao-Xu; Chan, Juliana CN

    2015-01-01

    There are multiple biases in using observational studies to examine treatment effects such as those from prevalent drug users, immortal time and drug indications. We used renin angiotensin system (RAS) inhibitors and statins as reference drugs with proven efficacies in randomized clinical trials (RCTs) and examined their effectiveness in the prospective Hong Kong Diabetes Registry using adjustment methods proposed in the literature. Using time-dependent exposures to drug treatments yielded gr...

  5. Evolutionary dynamics of adult stem cells: comparison of random and immortal-strand segregation mechanisms.

    Science.gov (United States)

    Tannenbaum, Emmanuel; Sherley, James L; Shakhnovich, Eugene I

    2005-04-01

    This paper develops a point-mutation model describing the evolutionary dynamics of a population of adult stem cells. Such a model may prove useful for quantitative studies of tissue aging and the emergence of cancer. We consider two modes of chromosome segregation: (1) random segregation, where the daughter chromosomes of a given parent chromosome segregate randomly into the stem cell and its differentiating sister cell and (2) "immortal DNA strand" co-segregation, for which the stem cell retains the daughter chromosomes with the oldest parent strands. Immortal strand co-segregation is a mechanism, originally proposed by [Cairns Nature (London) 255, 197 (1975)], by which stem cells preserve the integrity of their genomes. For random segregation, we develop an ordered strand pair formulation of the dynamics, analogous to the ordered strand pair formalism developed for quasispecies dynamics involving semiconservative replication with imperfect lesion repair (in this context, lesion repair is taken to mean repair of postreplication base-pair mismatches). Interestingly, a similar formulation is possible with immortal strand co-segregation, despite the fact that this segregation mechanism is age dependent. From our model we are able to mathematically show that, when lesion repair is imperfect, then immortal strand co-segregation leads to better preservation of the stem cell lineage than random chromosome segregation. Furthermore, our model allows us to estimate the optimal lesion repair efficiency for preserving an adult stem cell population for a given period of time. For human stem cells, we obtain that mispaired bases still present after replication and cell division should be left untouched, to avoid potentially fixing a mutation in both DNA strands.

  6. Evolutionary dynamics of adult stem cells: Comparison of random and immortal strand segregation mechanisms

    OpenAIRE

    Tannenbaum, Emmanuel; Sherley, James L.; Shakhnovich, Eugene I.

    2004-01-01

    This paper develops a point-mutation model describing the evolutionary dynamics of a population of adult stem cells. Such a model may prove useful for quantitative studies of tissue aging and the emergence of cancer. We consider two modes of chromosome segregation: (1) Random segregation, where the daughter chromosomes of a given parent chromosome segregate randomly into the stem cell and its differentiating sister cell. (2) ``Immortal DNA strand'' co-segregation, for which the stem cell reta...

  7. Derivation and Osmotolerance Characterization of Three Immortalized Tilapia (Oreochromis mossambicus) Cell Lines

    Science.gov (United States)

    Gardell, Alison M.; Qin, Qin; Rice, Robert H.; Li, Johnathan; Kültz, Dietmar

    2014-01-01

    Fish cell cultures are becoming more widely used models for investigating molecular mechanisms of physiological response to environmental challenge. In this study, we derived two immortalized Mozambique tilapia (Oreochromis mossambicus) cell lines from brain (OmB) and lip epithelium (OmL), and compared them to a previously immortalized bulbus arteriosus (TmB) cell line. The OmB and OmL cell lines were generated without or with Rho-associated kinase (ROCK) inhibitor/3T3 feeder layer supplementation. Although both approaches were successful, ROCK inhibitor/feeder layer supplementation was found to offer the advantages of selecting for epithelial-like cell type and decreasing time to immortalization. After immortalization (≥ passage 5), we characterized the proteomes of the newly derived cell lines (OmB and OmL) using LCMS and identified several unique cell markers for each line. Subsequently, osmotolerance for each of the three cell lines following acute exposure to elevated sodium chloride was evaluated. The acute maximum osmotolerance of these tilapia cell lines (>700 mOsm/kg) was markedly higher than that of any other known vertebrate cell line, but was significantly higher in the epithelial-like OmL cell line. To validate the physiological relevance of these tilapia cell lines, we quantified the effects of acute hyperosmotic challenge (450 mOsm/kg and 700 mOsm/kg) on the transcriptional regulation of two enzymes involved in biosynthesis of the compatible organic osmolyte, myo-inositol. Both enzymes were found to be robustly upregulated in all three tilapia cell lines. Therefore, the newly established tilapia cells lines represent valuable tools for studying molecular mechanisms involved in the osmotic stress response of euryhaline fish. PMID:24797371

  8. Rearrangement of Upstream Sequences of the hTERT Gene During Cellular Immortalization

    Science.gov (United States)

    Zhao, Yuanjun; Wang, Shuwen; Popova, Evgenya Y.; Grigoryev, Sergei A.; Zhu, Jiyue

    2010-01-01

    Telomerase expression, resulting from transcriptional activation of the hTERT gene, allows cells to acquire indefinite proliferative potential during cellular immortalization and tumorigenesis. However, mechanisms of hTERT gene activation in many immortal cell lines and cancer cells are poorly understood. Here, we report our studies on hTERT activation using genetically related pairs of telomerase-negative (Tel−) and -positive (Tel+) fibroblast lines. First, whereas transiently transfected plasmid reporters did not recapitulate the endogenous hTERT promoter, the promoter in chromosomally integrated bacterial artificial chromosome (BAC) reporters was activated in a subset of Tel+ cells, indicating that activation of the hTERT promoter required native chromatin context and/or distal regulatory elements. Second, the hTERT gene, located near the telomere of chromosome 5p, was translocated in all three Tel+ cell lines but not in their parental pre-crisis cells and Tel− immortal siblings. The breakage points were mapped to regions upstream of the hTERT promoter, indicating that the hTERT gene was the target of these chromosomal rearrangements. In two Tel+ cell lines, translocation of the endogenous hTERT gene appeared to be the major mechanism of its activation as the activity of hTERT promoter in many chromosomally integrated BAC reporters, with intact upstream and downstream neighboring loci, remained relatively low. Therefore, our results suggest that rearrangement of upstream sequences is an important new mechanism of hTERT promoter activation during cellular immortalization. The chromosomal rearrangements likely occurred during cellular crisis and facilitated by telomere dysfunction. Such translocations allowed the hTERT promoter to escape from the native condensed chromatin environment. PMID:19672873

  9. The People Paradox: Self-Esteem Striving, Immortality Ideologies, and Human Response to Climate Change

    OpenAIRE

    Janis L. Dickinson

    2009-01-01

    In 1973, Ernest Becker, a cultural anthropologist cross-trained in philosophy, sociology, and psychiatry, invoked consciousness of self and the inevitability of death as the primary sources of human anxiety and repression. He proposed that the psychological basis of cooperation, competition, and emotional and mental health is a tendency to hold tightly to anxiety-buffering cultural world views or "immortality projects" that serve as the basis for self-esteem and meaning. Although he focused m...

  10. Immortalization of chicken preadipocytes by retroviral transduction of chicken TERT and TR

    Science.gov (United States)

    Wang, Wei; Zhang, Tianmu; Wu, Chunyan; Wang, Shanshan; Wang, Yuxiang; Wang, Ning

    2017-01-01

    The chicken is an important agricultural animal and model for developmental biology, immunology and virology. Excess fat accumulation continues to be a serious problem for the chicken industry. However, chicken adipogenesis and obesity have not been well investigated, because no chicken preadipocyte cell lines have been generated thus far. Here, we successfully generated two immortalized chicken preadipocyte cell lines through transduction of either chicken telomerase reverse transcriptase (chTERT) alone or in combination with chicken telomerase RNA (chTR). Both of these cell lines have survived >100 population doublings in vitro, display high telomerase activity and have no sign of replicative senescence. Similar to primary chicken preadipocytes, these two cell lines display a fibroblast-like morphology, retain the capacity to differentiate into adipocytes, and do not display any signs of malignant transformation. Isoenzyme analysis and PCR-based analysis confirmed that these two cell lines are of chicken origin and are free from inter-species contamination. To our knowledge, this is the first report demonstrating the generation of immortal chicken cells by introduction of chTERT and chTR. Our established chicken preadipocyte cell lines show great promise as an in vitro model for the investigation of chicken adipogenesis, lipid metabolism, and obesity and its related diseases, and our results also provide clues for immortalizing other avian cell types. PMID:28486516

  11. Immortalization of chicken preadipocytes by retroviral transduction of chicken TERT and TR.

    Directory of Open Access Journals (Sweden)

    Wei Wang

    Full Text Available The chicken is an important agricultural animal and model for developmental biology, immunology and virology. Excess fat accumulation continues to be a serious problem for the chicken industry. However, chicken adipogenesis and obesity have not been well investigated, because no chicken preadipocyte cell lines have been generated thus far. Here, we successfully generated two immortalized chicken preadipocyte cell lines through transduction of either chicken telomerase reverse transcriptase (chTERT alone or in combination with chicken telomerase RNA (chTR. Both of these cell lines have survived >100 population doublings in vitro, display high telomerase activity and have no sign of replicative senescence. Similar to primary chicken preadipocytes, these two cell lines display a fibroblast-like morphology, retain the capacity to differentiate into adipocytes, and do not display any signs of malignant transformation. Isoenzyme analysis and PCR-based analysis confirmed that these two cell lines are of chicken origin and are free from inter-species contamination. To our knowledge, this is the first report demonstrating the generation of immortal chicken cells by introduction of chTERT and chTR. Our established chicken preadipocyte cell lines show great promise as an in vitro model for the investigation of chicken adipogenesis, lipid metabolism, and obesity and its related diseases, and our results also provide clues for immortalizing other avian cell types.

  12. Hopelessly mortal: The role of mortality salience, immortality and trait self-esteem in personal hope.

    Science.gov (United States)

    Wisman, Arnaud; Heflick, Nathan A

    2016-08-01

    Do people lose hope when thinking about death? Based on Terror Management Theory, we predicted that thoughts of death (i.e., mortality salience) would reduce personal hope for people low, but not high, in self-esteem, and that this reduction in hope would be ameliorated by promises of immortality. In Studies 1 and 2, mortality salience reduced personal hope for people low in self-esteem, but not for people high in self-esteem. In Study 3, mortality salience reduced hope for people low in self-esteem when they read an argument that there is no afterlife, but not when they read "evidence" supporting life after death. In Study 4, this effect was replicated with an essay affirming scientific medical advances that promise immortality. Together, these findings uniquely demonstrate that thoughts of mortality interact with trait self-esteem to cause changes in personal hope, and that literal immortality beliefs can aid psychological adjustment when thinking about death. Implications for understanding personal hope, trait self-esteem, afterlife beliefs and terror management are discussed.

  13. Telomere dynamics, end-to-end fusions and telomerase activation during the human fibroblast immortalization process.

    Science.gov (United States)

    Ducray, C; Pommier, J P; Martins, L; Boussin, F D; Sabatier, L

    1999-07-22

    Loss of telomeric repeats during cell proliferation could play a role in senescence. It has been generally assumed that activation of telomerase prevents further telomere shortening and is essential for cell immortalization. In this study, we performed a detailed cytogenetic and molecular characterization of four SV40 transformed human fibroblastic cell lines by regularly monitoring the size distribution of terminal restriction fragments, telomerase activity and the associated chromosomal instability throughout immortalization. The mean TRF lengths progressively decreased in pre-crisis cells during the lifespan of the cultures. At crisis, telomeres reached a critical size, different among the cell lines, contributing to the peak of dicentric chromosomes, which resulted mostly from telomeric associations. We observed a direct correlation between short telomere length at crisis and chromosomal instability. In two immortal cell lines, although telomerase was detected, mean telomere length still continued to decrease whereas the number of dicentric chromosomes associated was stabilized. Thus telomerase could protect specifically telomeres which have reached a critical size against end-to-end dicentrics, while long telomeres continue to decrease, although at a slower rate as before crisis. This suggests a balance between elongation by telomerase and telomere shortening, towards a stabilized 'optimal' length.

  14. Immortalization of normal human embryonic fibroblasts by introduction of either the human papillomavirus type 16 E6 or E7 gene alone.

    Science.gov (United States)

    Yamamoto, Akito; Kumakura, Shin-ichi; Uchida, Minoru; Barrett, J Carl; Tsutsui, Takeki

    2003-09-01

    The ability of the human papillomavirus type 16 (HPV-16) E6 or E7 gene to induce immortalization of normal human embryonic fibroblast WHE-7 cells was examined. WHE-7 cells at 9 population doublings (PD) were infected with retrovirus vectors encoding either HPV-16 E6 or E7 alone or both E6 and E7 (E6/E7). One of 4 isolated clones carrying E6 alone became immortal and is currently at >445 PD. Four of 4 isolated clones carrying E7 alone escaped from crisis and are currently at >330 PD. Three of 5 isolated clones carrying E6/E7 were also immortalized and are currently at >268 PD. The immortal clone carrying E6 only and 2 of the 3 immortal clones carrying E6/E7 expressed a high level of E6 protein, and all the immortal clones carrying E7 alone and the other immortal clone carrying E6/E7 expressed a high level of E7 protein when compared to their mortal or precrisis clones. The immortal clones expressing a high level of E6 or E7 protein were positive for telomerase activity or an alternative mechanism of telomere maintenance, respectively, known as ALT (alternative lengthening of telomeres). All the mortal or precrisis clones were negative for both phenotypes. All the immortal clones exhibited abrogation of G1 arrest after DNA damage by X-ray irradiation. The expression of INK4a protein (p16(INK4a)) was undetectable in the E6-infected mortal and immortal clones, whereas Rb protein (pRb) was hyperphosphorylated only in the immortal clone. The p16(INK4a) protein was overexpressed in all the E7-infected immortal clones and their clones in the pre-crisis period as well as all the E6/E7-infected mortal and immortal clones, but the pRb expression was downregulated in all of these clones. These results demonstrate for the first time to our knowledge that HPV-16 E6 or E7 alone can induce immortalization of normal human embryonic fibroblasts. Inactivation of p16(INK4a)/pRb pathways in combination with activation of a telomere maintenance mechanism is suggested to be necessary for

  15. hTERT gene immortalized human adipose-derived stem cells and its multiple differentiations: a preliminary investigation.

    Science.gov (United States)

    Wang, L; Song, K; Qu, X; Wang, H; Zhu, H; Xu, X; Zhang, M; Tang, Y; Yang, X

    2013-03-01

    Human adipose-derived adult stem cells (hADSCs) can express human telomerase reverse transcriptase phenotypes under an appropriate culture condition. Because adipose tissue is abundant and easily accessible, hADSCs offer a promising source of stem cells for tissue engineering application and other cell-based therapies. However, the shortage of cells number and the difficulty to proliferate, known as the "Hayflick limit" in vitro, limit their further clinical application. Here, hADSCs were transfected with human telomerase reverse transcriptase (hTERT) gene by the lentiviral vector to prolong the lifespan of stem cells and even immortalize them. Following to this, the cellular properties and functionalities of the transfected cell lines were assayed. The results demonstrated that hADSCs had been successfully transfected with hTERT gene (hTERT-ADSCs). Then, hTERT-ADSCs were initially selected by G418 and subsequently expanded over 20 passages in vitro. Moreover, the qualitative and quantitative differentiation criteria for 20 passages of hTERT-ADSCs also demonstrated that hTERT-ADSCs could differentiate into osteogenesis, chondrogenesis, and adipogenesis phenotypes in lineage-specific differentiation media. These findings confirmed that this transfection could prolong the lifespan of hADSCs.

  16. Immortalization of human neural stem cells with the c-myc mutant T58A.

    Directory of Open Access Journals (Sweden)

    Lidia De Filippis

    Full Text Available Human neural stem cells (hNSC represent an essential source of renewable brain cells for both experimental studies and cell replacement therapies. Their relatively slow rate of proliferation and physiological senescence in culture make their use cumbersome under some experimental and pre-clinical settings. The immortalization of hNSC with the v-myc gene (v-IhNSC has been shown to generate stem cells endowed with enhanced proliferative capacity, which greatly facilitates the study of hNSCs, both in vitro and in vivo. Despite the excellent safety properties displayed by v-IhNSCs--which do not transform in vitro and are not tumorigenic in vivo--the v-myc gene contains several mutations and recombination elements, whose role(s and effects remains to be elucidated, yielding unresolved safety concerns. To address this issue, we used a c-myc T58A retroviral vector to establish an immortal cell line (T-IhNSC from the same hNSCs used to generate the original v-IhNSCs and compared their characteristics with the latter, with hNSC and with hNSC immortalized using c-myc wt (c-IhNSC. T-IhNSCs displayed an enhanced self-renewal ability, with their proliferative capacity and clonogenic potential being remarkably comparable to those of v-IhNSC and higher than wild type hNSCs and c-IhNSCs. Upon growth factors removal, T-IhNSC promptly gave rise to well-differentiated neurons, astrocytes and most importantly, to a heretofore undocumented high percentage of human oligodendrocytes (up to 23%. Persistent growth-factor dependence, steady functional properties, lack of ability to generate colonies in soft-agar colony-forming assay and to establish tumors upon orthotopic transplantation, point to the fact that immortalization by c-myc T58A does not bring about tumorigenicity in hNSCs. Hence, this work describes a novel and continuous cell line of immortalized human multipotent neural stem cells, in which the immortalizing agent is represented by a single gene which, in

  17. Discordance between bovine leukemia virus tax immortalization in vitro and oncogenicity in vivo.

    Science.gov (United States)

    Twizere, J C; Kerkhofs, P; Burny, A; Portetelle, D; Kettmann, R; Willems, L

    2000-11-01

    Bovine leukemia virus (BLV) Tax protein, a transcriptional activator of viral expression, is essential for viral replication in vivo. Tax is believed to be involved in leukemogenesis because of its second function, immortalization of primary cells in vitro. These activities of Tax can be dissociated on the basis of point mutations within specific regions of the protein. For example, mutation of the phosphorylation sites at serines 106 and 293 abrogates immortalization potential in vitro but maintains transcriptional activity. This type of mutant is thus particularly useful for unraveling the role of Tax immortalization activity during leukemogenesis independently of viral replication. In this report, we describe the biological properties of BLV recombinant proviruses mutated in the Tax phosphorylation sites (BLVTax106+293). Titration of the proviral loads by semiquantitative PCR revealed that the BLV mutants propagated at wild-type levels in vivo. Furthermore, two animals (sheep 480 and 296) infected with BLVTax106+293 developed leukemia or lymphosarcoma after 16 and 36 months, respectively. These periods of time are within the normal range of latencies preceding the onset of pathogenesis induced by wild-type viruses. The phenotype of the mutant-infected cells was characteristic of a B lymphocyte (immunoglobulin M positive) expressing CD11b and CD5 (except at the final stage for the latter marker), a pattern that is typical of wild-type virus-infected target cells. Interestingly, the transformed B lymphocytes from sheep 480 also coexpressed the CD8 marker, a phenotype rarely observed in tumor biopsies from chronic lymphocytic leukemia patients. Finally, direct sequencing of the tax gene demonstrated that the leukemic cells did not harbor revertant proviruses. We conclude that viruses expressing a Tax mutant unable to transform primary cells in culture are still pathogenic in the sheep animal model. Our data thus provide a clear example of the discordant conclusions

  18. Selenium-regulated hierarchy of human selenoproteome in cancerous and immortalized cells lines.

    Science.gov (United States)

    Touat-Hamici, Zahia; Bulteau, Anne-Laure; Bianga, Juliusz; Jean-Jacques, Hélène; Szpunar, Joanna; Lobinski, Ryszard; Chavatte, Laurent

    2018-04-13

    Selenoproteins (25 genes in human) co-translationally incorporate selenocysteine using a UGA codon, normally used as a stop signal. The human selenoproteome is primarily regulated by selenium bioavailability with a tissue-specific hierarchy. We investigated the hierarchy of selenoprotein expression in response to selenium concentration variation in four cell lines originating from kidney (HEK293, immortalized), prostate (LNCaP, cancer), skin (HaCaT, immortalized) and liver (HepG2, cancer), using complementary analytical methods. We performed (i) enzymatic activity, (ii) RT-qPCR, (iii) immuno-detection, (iv) selenium-specific mass spectrometric detection after non-radioactive 76 Se labeling of selenoproteins, and (v) luciferase-based reporter constructs in various cell extracts. We characterized cell-line specific alterations of the selenoproteome in response to selenium variation that, in most of the cases, resulted from a translational control of gene expression. We established that UGA-selenocysteine recoding efficiency, which depends on the nature of the SECIS element, dictates the response to selenium variation. We characterized that selenoprotein hierarchy is cell-line specific with conserved features. This analysis should be done prior to any experiments in a novel cell line. We reported a strategy based on complementary methods to evaluate selenoproteome regulation in human cells in culture. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Plato, Symposium 212a6–7 : The Most Immortal of Men, with an Appendix on Phrases of the Type εἴπερ (τις) ἄλλος

    NARCIS (Netherlands)

    Boter, G.J.

    2017-01-01

    This article presents two hitherto neglected arguments in favour of the thesis that the philosopher’s immortality described by Diotima in Plato’s Symposium refers exclusively to immortality by means of posterity and not to some sort of personal immortality after death. Both arguments are contained

  20. Attempting immortality

    International Nuclear Information System (INIS)

    Krull, W.

    1995-01-01

    The world's population of research reactors is growing old. Many have been adapted to serve new purposes over their lives, from testing materials for nuclear power programmes and supporting neutron physics experiments, to colouring gemstones, doping silicon and generating medical isotopes. In the first article of this survey of research reactor issues, Wilfried Krull from GKSS in Germany describes the effects on a reactor of supporting these changes in application as ''design ageing'' . Managing this and other symptoms of ageing to extend plant life is a key task for operators, and Krull discusses the efforts being made internationally to handle them. Eventually, terminal decline of one vital component can determine when a reactor has to be shutdown for refurbishment. For BR2 in Belgium, it was the beryllium matrix. Edgar Koonen from SCK-CEN explains work being done to replace it and extend reactor life for around 15 years. The Triga at the University of Austria's Atomic Institute has already been running for over 30 years and Helmuth Bock, of the Institute, credits its good health to thorough routine maintenance procedures and custom-made tools for the work. The HANARO reactor in Korea achieved first criticality in February this year - one of the few new research reactors to have started up in recent years. Seong-yun Kim of KAERI describes its design and uses, including medical isotope production. About 80% of medical Mo-99 comes from the 38-year-old NRU in Canada. Russell Ball from B and W Nuclear Environmental Services describes a conceptual reactor for dedicated Mo-99 production in the last article of the survey. (UK)

  1. Attempting immortality

    Energy Technology Data Exchange (ETDEWEB)

    Krull, W. [GKSS-Forschungszentrum Geesthacht GmbH (Germany)

    1995-12-01

    The world`s population of research reactors is growing old. Many have been adapted to serve new purposes over their lives, from testing materials for nuclear power programmes and supporting neutron physics experiments, to colouring gemstones, doping silicon and generating medical isotopes. In the first article of this survey of research reactor issues, Wilfried Krull from GKSS in Germany describes the effects on a reactor of supporting these changes in application as ``design ageing`` . Managing this and other symptoms of ageing to extend plant life is a key task for operators, and Krull discusses the efforts being made internationally to handle them. Eventually, terminal decline of one vital component can determine when a reactor has to be shutdown for refurbishment. For BR2 in Belgium, it was the beryllium matrix. Edgar Koonen from SCK-CEN explains work being done to replace it and extend reactor life for around 15 years. The Triga at the University of Austria`s Atomic Institute has already been running for over 30 years and Helmuth Bock, of the Institute, credits its good health to thorough routine maintenance procedures and custom-made tools for the work. The HANARO reactor in Korea achieved first criticality in February this year - one of the few new research reactors to have started up in recent years. Seong-yun Kim of KAERI describes its design and uses, including medical isotope production. About 80% of medical Mo-99 comes from the 38-year-old NRU in Canada. Russell Ball from B and W Nuclear Environmental Services describes a conceptual reactor for dedicated Mo-99 production in the last article of the survey. (UK).

  2. The E7 protein of the cottontail rabbit papillomavirus immortalizes normal rabbit keratinocytes and reduces pRb levels, while E6 cooperates in immortalization but neither degrades p53 nor binds E6AP

    International Nuclear Information System (INIS)

    Ganzenmueller, Tina; Matthaei, Markus; Muench, Peter; Scheible, Michael; Iftner, Angelika; Hiller, Thomas; Leiprecht, Natalie; Probst, Sonja; Stubenrauch, Frank; Iftner, Thomas

    2008-01-01

    Human papillomaviruses (HPVs) cause cervical cancer and are associated with the development of non-melanoma skin cancer. A suitable animal model for papillomavirus-associated skin carcinogenesis is the infection of domestic rabbits with the cottontail rabbit papillomavirus (CRPV). As the immortalizing activity of CRPV genes in the natural target cells remains unknown, we investigated the properties of CRPV E6 and E7 in rabbit keratinocytes (RK) and their influence on the cell cycle. Interestingly, CRPV E7 immortalized RK after a cellular crisis but showed no such activity in human keratinocytes. Co-expressed CRPV E6 prevented cellular crisis. The HPV16 or CRPV E7 protein reduced rabbit pRb levels thereby causing rabbit p19 ARF induction and accumulation of p53 without affecting cellular proliferation. Both CRPV E6 proteins failed to degrade rabbit p53 in vitro or to bind E6AP; however, p53 was still inducible by mitomycin C. In summary, CRPV E7 immortalizes rabbit keratinocytes in a species-specific manner and E6 contributes to immortalization without directly affecting p53

  3. Phenotypic characterization of telomerase-immortalized primary non-malignant and malignant tumor-derived human prostate epithelial cell lines

    International Nuclear Information System (INIS)

    Gu Yongpeng; Li Hongzhen; Miki, Jun; Kim, Kee-Hong; Furusato, Bungo; Sesterhenn, Isabell A.; Chu, Wei-Sing; McLeod, David G.; Srivastava, Shiv; Ewing, Charles M.; Isaacs, William B.; Rhim, Johng S.

    2006-01-01

    In vitro human prostate cell culture models are critical for clarifying the mechanism of prostate cancer progression and for testing preventive and therapeutic agents. Cell lines ideal for the study of human primary prostate tumors would be those derived from spontaneously immortalized tumor cells; unfortunately, explanted primary prostate cells survive only short-term in culture, and rarely immortalize spontaneously. Therefore, we recently have generated five immortal human prostate epithelial cell cultures derived from both the benign and malignant tissues of prostate cancer patients with telomerase, a gene that prevents cellular senescence. Examination of these cell lines for their morphologies and proliferative capacities, their abilities to grow in low serum, to respond to androgen stimulation, to grow above the agar layer, to form tumors in SCID mice, suggests that they may serve as valid, useful tools for the elucidation of early events in prostate tumorigenesis. Furthermore, the chromosome alterations observed in these immortalized cell lines expressing aspects of the malignant phenotypes imply that these cell lines accurately recapitulate the genetic composition of primary tumors. These novel in vitro models may offer unique models for the study of prostate carcinogenesis and also provide the means for testing both chemopreventive and chemotherapeutic agents

  4. Stepwise DNA Methylation Changes Are Linked to Escape from Defined Proliferation Barriers and Mammary Epithelial Cell Immortalization

    Energy Technology Data Exchange (ETDEWEB)

    Novak, Petr; Jensen, Taylor J.; Garbe, James C.; Stampfer, Martha R.; Futscher, Bernard W.

    2009-04-20

    The timing and progression of DNA methylation changes during carcinogenesis are not completely understood. To develop a timeline of aberrant DNA methylation events during malignant transformation, we analyzed genome-wide DNA methylation patterns in an isogenic human mammary epithelial cell (HMEC) culture model of transformation. To acquire immortality and malignancy, the cultured finite lifespan HMEC must overcome two distinct proliferation barriers. The first barrier, stasis, is mediated by the retinoblastoma protein and can be overcome by loss of p16(INK4A) expression. HMEC that escape stasis and continue to proliferate become genomically unstable before encountering a second more stringent proliferation barrier, telomere dysfunction due to telomere attrition. Rare cells that acquire telomerase expression may escape this barrier, become immortal, and develop further malignant properties. Our analysis of HMEC transitioning from finite lifespan to malignantly transformed showed that aberrant DNA methylation changes occur in a stepwise fashion early in the transformation process. The first aberrant DNA methylation step coincides with overcoming stasis, and results in few to hundreds of changes, depending on how stasis was overcome. A second step coincides with immortalization and results in hundreds of additional DNA methylation changes regardless of the immortalization pathway. A majority of these DNA methylation changes are also found in malignant breast cancer cells. These results show that large-scale epigenetic remodeling occurs in the earliest steps of mammary carcinogenesis, temporally links DNA methylation changes and overcoming cellular proliferation barriers, and provides a bank of potential epigenetic biomarkers that mayprove useful in breast cancer risk assessment.

  5. Artichoke compound cynarin differentially affects the survival, growth and stress response of normal, immortalized and cancerous human cells

    DEFF Research Database (Denmark)

    Gezer, Ceren; Yücecan, Sevinç; Rattan, Suresh Inder Singh

    2015-01-01

    of CYN on the proliferative potential, survival, morphology, and stress response (SR) markers haemoxygenase-1 (HO-1) and heat shock protein-70 (HSP70) in normal human skin fibroblasts (FSF-1), telomerase-immortalized mesenchymal stem cells (hTERT-MSC) and cervical cancer cells, HeLa. Effects of CYN...

  6. MicroRNA-4739 regulates osteogenic and adipocytic differentiation of immortalized human bone marrow stromal cells via targeting LRP3

    DEFF Research Database (Denmark)

    Elsafadi, Mona; Manikandan, Muthurangan; Alajez, Nehad M

    2017-01-01

    3 (LRP3) in regulating the osteogenic and adipogenic differentiation of immortalized hBMSCs. Gene expression profiling revealed significantly higher LRP3 levels in the highly osteogenic hBMSC clone imCL1 than in the less osteogenic clone imCL2, as well as a significant upregulation of LRP3 during...

  7. Colonic stem cell data are consistent with the immortal model of stem cell division under non-random strand segregation.

    Science.gov (United States)

    Walters, K

    2009-06-01

    Colonic stem cells are thought to reside towards the base of crypts of the colon, but their numbers and proliferation mechanisms are not well characterized. A defining property of stem cells is that they are able to divide asymmetrically, but it is not known whether they always divide asymmetrically (immortal model) or whether there are occasional symmetrical divisions (stochastic model). By measuring diversity of methylation patterns in colon crypt samples, a recent study found evidence in favour of the stochastic model, assuming random segregation of stem cell DNA strands during cell division. Here, the effect of preferential segregation of the template strand is considered to be consistent with the 'immortal strand hypothesis', and explore the effect on conclusions of previously published results. For a sample of crypts, it is shown how, under the immortal model, to calculate mean and variance of the number of unique methylation patterns allowing for non-random strand segregation and compare them with those observed. The calculated mean and variance are consistent with an immortal model that incorporates non-random strand segregation for a range of stem cell numbers and levels of preferential strand segregation. Allowing for preferential strand segregation considerably alters previously published conclusions relating to stem cell numbers and turnover mechanisms. Evidence in favour of the stochastic model may not be as strong as previously thought.

  8. Transcriptome profile and cytogenetic analysis of immortalized neuronally restricted progenitor cells derived from the porcine olfactory bulb

    Science.gov (United States)

    Recently, we established and phenotypically characterized an immortalized porcine olfactory bulb neuroblast cell line, OBGF400 (Uebing-Czipura et al., 2008). To facilitate the future application of these cells in studies of neurological dysfunction and neuronal replacement therapies, a comprehensive...

  9. Multistep carcinogenesis of normal human fibroblasts. Human fibroblasts immortalized by repeated treatment with Co-60 gamma rays were transformed into tumorigenic cells with Ha-ras oncogenes.

    Science.gov (United States)

    Namba, M; Nishitani, K; Fukushima, F; Kimoto, T

    1988-01-01

    Two normal mortal human fibroblast cell strains were transformed into immortal cell lines, SUSM-1 and KMST-6, by treatment with 4-nitroquinoline 1-oxide (4NQO) and Co-60 gamma rays, respectively. These immortalized cell lines showed morphological changes of cells and remarkable chromosome aberrations, but neither of them grew in soft agar or formed tumors in nude mice. The immortal cell line, KMST-6, was then converted into neoplastic cells by treatment with Harvey murine sarcoma virus (Ha-MSV) or the c-Ha-ras oncogene derived from a human lung carcinoma. These neoplastically transformed cells acquired anchorage-independent growth potential and developed tumors when transplanted into nude mice. All the tumors grew progressively without regression until the animals died of tumors. In addition, the tumors were transplantable into other nude mice. Normal human fibroblasts, on the other hand, were not transformed into either immortal or tumorigenic cells by treatment with Ha-MSV or c-Ha-ras alone. Our present data indicate that (1) the chemical carcinogen, 4NQO, or gamma rays worked as an initiator of carcinogenesis in normal human cells, giving rise to immortality, and (2) the ras gene played a role in the progression of the immortally transformed cells to more malignant cells showing anchorage-independent growth and tumorigenicity. In other words, the immortalization process of human cells seems to be a pivotal or rate-limiting step in the carcinogenesis of human cells.

  10. Establishment, characterization and immortalization of a fibroblast cell line from the Chinese red belly toad Bombina maxima skin.

    Science.gov (United States)

    Xiang, Yang; Gao, Qian; Su, Weiting; Zeng, Lin; Wang, Jinhuan; Hu, Yi; Nie, Wenhui; Ma, Xutong; Zhang, Yong; Lee, Wenhui; Zhang, Yun

    2012-01-01

    The skin of the amphibian Bombina maxima is rich in biologically active proteins and peptides, most of which have mammalian analogues. The physiological functions of most of the mammalian analogues are still unknown. Thus, Bombina maxima skin may be a promising model to reveal the physiological role of these proteins and peptides because of their large capacity for secretion. To investigate the physiological role of these proteins and peptides in vitro, a fibroblast cell line was successfully established from Bombina maxima tadpole skin. The cell line grew to form a monolayer with cells of a uniform shape and abundant rough endoplasmic reticulum, which are typical characteristics of fibroblasts. Further identification at a molecular level revealed that they strongly expressed the fibroblast marker protein vimentin. The chromosome number of these cells is 2n = 28, and most of them were diploid. Growth property analysis showed that they grew well for 14 passages. However, cells showed decreased proliferative ability after passage 15. Thus, we tried to immortalize the cells through the overexpression of SV40 T antigen. After selecting by G418, cells stably expressed SV40 large T antigen and showed enhanced proliferative ability and increased telomerase activity. Signal transduction analysis revealed functional p42 mitogen-activated protein (MAP) kinase in immortalized Bombina maxima dermal fibroblasts. Primary fibroblast cells and the immortalized fibroblast cells from Bombina maxima cultured in the present study can be used to investigate the physiological role of Bombina maxima skin-secreted proteins and peptides. In addition, the methods for primary cell culturing and cell immortalization will be useful for culturing and immortalizing cells from other types of amphibians.

  11. Immortal DNA strand cosegregation requires p53/IMPDH-dependent asymmetric self-renewal associated with adult stem cells.

    Science.gov (United States)

    Rambhatla, Lakshmi; Ram-Mohan, Sumati; Cheng, Jennifer J; Sherley, James L

    2005-04-15

    Because they are long-lived and cycle continuously, adult stem cells (ASCs) are predicted as the most common precursor for cancers in adult mammalian tissues. Two unique attributes have been proposed to restrict the carcinogenic potential of ASCs. These are asymmetric self-renewal that limits their number and immortal DNA strand cosegregation that limits their accumulation of mutations due to DNA replication errors. Until recently, the molecular basis and regulation of these important ASC-specific functions were unknown. We developed engineered cultured cells that exhibit asymmetric self-renewal and immortal DNA strand cosegregation. These model cells were used to show that both ASC-specific functions are regulated by the p53 cancer gene. Previously, we proposed that IMP dehydrogenase (IMPDH) was an essential factor for p53-dependent asymmetric self-renewal. We now confirm this proposal and provide quantitative evidence that asymmetric self-renewal is acutely sensitive to even modest changes in IMPDH expression. These analyses reveal that immortal DNA strand cosegregation is also regulated by IMPDH and confirm the original implicit precept that immortal DNA strand cosegregation is specific to cells undergoing asymmetric self-renewal (i.e., ASCs). With IMPDH being the rate-determining enzyme for guanine ribonucleotide (rGNP) biosynthesis, its requirement implicates rGNPs as important regulators of ASC asymmetric self-renewal and immortal DNA strand cosegregation. An in silico analysis of global gene expression data from human cancer cell lines underscored the importance of p53-IMPDH-rGNP regulation for normal tissue cell kinetics, providing further support for the concept that ASCs are key targets for adult tissue carcinogenesis.

  12. Original article Values and sense of symbolic immortality among non-religious adolescents in Poland

    Directory of Open Access Journals (Sweden)

    Michał Jaśkiewicz

    2014-10-01

    Full Text Available Background The aim of the study was to determine the values (Schwartz’s ten basic values and sense of symbolic immortality among non-religious adolescents. Participants and procedure Participants were recruited from secondary schools in Gdansk and Gdynia. Results The results showed that non-religious adolescents achieved higher results in the natural mode, and lower in biological-creative and religious modes. They also scored higher on universalism and self-direction subscales of Schwartz’s ten basic values. The results are discussed in the light of humanistic personal ideology and terror management theory. Conclusions The cultural worldview that protects non-religious adolescents against death anxiety seems to be more rooted in humanistic and individualistic values.

  13. Immortalization and characterization of mouse floxed Bmp2/4 osteoblasts

    International Nuclear Information System (INIS)

    Wu, Li-An; Yuan, Guohua; Yang, Guobin; Ortiz-Gonzalez, Iris; Yang, Wuchen; Cui, Yong; MacDougall, Mary; Donly, Kevin J.; Harris, Stephen; Chen, Shuo

    2009-01-01

    Generation of a floxed Bmp2/4 osteoblast cell line is a valuable tool for studying the modulatory effects of Bmp2 and Bmp4 on osteoblast differentiation as well as relevant molecular events. In this study, primary floxed Bmp2/4 mouse osteoblasts were cultured and transfected with simian virus 40 large T-antigen. Transfection was verified by polymerase chain reaction (PCR) and immunohistochemistry. To examine the characteristics of the transfected cells, morphology, proliferation and mineralization were analyzed, expression of cell-specific genes including Runx2, ATF4, Dlx3, Osx, dentin matrix protein 1, bone sialoprotein, osteopontin, osteocalcin, osteonectin and collagen type I was detected. These results show that transfected floxed Bmp2/4 osteoblasts bypassed senescence with a higher proliferation rate, but retain the genotypic and phenotypic characteristics similar to the primary cells. Thus, we for the first time demonstrate the establishment of an immortalized mouse floxed Bmp2/4 osteoblast cell line.

  14. 3D cultured immortalized human hepatocytes useful to develop drugs for blood-borne HCV

    International Nuclear Information System (INIS)

    Aly, Hussein Hassan; Shimotohno, Kunitada; Hijikata, Makoto

    2009-01-01

    Due to the high polymorphism of natural hepatitis C virus (HCV) variants, existing recombinant HCV replication models have failed to be effective in developing effective anti-HCV agents. In the current study, we describe an in vitro system that supports the infection and replication of natural HCV from patient blood using an immortalized primary human hepatocyte cell line cultured in a three-dimensional (3D) culture system. Comparison of the gene expression profile of cells cultured in the 3D system to those cultured in the existing 2D system demonstrated an up-regulation of several genes activated by peroxisome proliferator-activated receptor alpha (PPARα) signaling. Furthermore, using PPARα agonists and antagonists, we also analyzed the effect of PPARα signaling on the modulation of HCV replication using this system. The 3D in vitro system described in this study provides significant insight into the search for novel anti-HCV strategies that are specific to various strains of HCV.

  15. The roles of telomeres and telomerase in cellular immortalization and the development of cancer.

    Science.gov (United States)

    Klingelhutz, A J

    1999-01-01

    Normal human cells have a limited lifespan in culture called the Hayflick limit. Recent studies have indicated that telomere shortening is one of the important meters utilized by cells to determine the Hayflick limit, and that activation of a mechanism to maintain telomere length is essential for cells to become immortal. It is generally believed that cells must have a means to maintain telomeres in order to progress to malignancy. Most cancers do this by activating an enzyme called telomerase which adds telomeric repeats to the telomere ends. Recently, expression of this enzyme has been shown to extend the lifespan of cells. This review discusses the research that led to the discovery of telomerase, the characteristics of telomerase complex, and how recent and future advances in the telomerase field may lead to better diagnostic and treatment protocols for many different cancer types.

  16. Immortalization and characterization of mouse floxed Bmp2/4 osteoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Li-An [Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, TX (United States); Department of Pediatric Dentistry, School of Stomatology, The Fourth Military Medical University, Xi-an (China); Yuan, Guohua; Yang, Guobin [Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, TX (United States); Key Laboratory of Oral Biomedical Engineering Ministry of Education, Wuhan (China); Ortiz-Gonzalez, Iris [Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, TX (United States); Yang, Wuchen; Cui, Yong [Department of Periodontics, Dental School, The University of Texas Health Science Center at San Antonio, TX (United States); MacDougall, Mary [Department of Oral/Maxillofacial Surgery, University of Alabama, Birmingham, AL (United States); Donly, Kevin J. [Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, TX (United States); Harris, Stephen [Department of Periodontics, Dental School, The University of Texas Health Science Center at San Antonio, TX (United States); Chen, Shuo, E-mail: chens0@uthscsa.edu [Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, TX (United States)

    2009-08-14

    Generation of a floxed Bmp2/4 osteoblast cell line is a valuable tool for studying the modulatory effects of Bmp2 and Bmp4 on osteoblast differentiation as well as relevant molecular events. In this study, primary floxed Bmp2/4 mouse osteoblasts were cultured and transfected with simian virus 40 large T-antigen. Transfection was verified by polymerase chain reaction (PCR) and immunohistochemistry. To examine the characteristics of the transfected cells, morphology, proliferation and mineralization were analyzed, expression of cell-specific genes including Runx2, ATF4, Dlx3, Osx, dentin matrix protein 1, bone sialoprotein, osteopontin, osteocalcin, osteonectin and collagen type I was detected. These results show that transfected floxed Bmp2/4 osteoblasts bypassed senescence with a higher proliferation rate, but retain the genotypic and phenotypic characteristics similar to the primary cells. Thus, we for the first time demonstrate the establishment of an immortalized mouse floxed Bmp2/4 osteoblast cell line.

  17. Long-term culture and differentiation of porcine red bone marrow hematopoietic cells co-cultured with immortalized mesenchymal cells.

    Science.gov (United States)

    Garba, Abubakar; Acar, Delphine D; Roukaerts, Inge D M; Desmarets, Lowiese M B; Devriendt, Bert; Nauwynck, Hans J

    2017-09-01

    Mesenchymal cells are multipotent stromal cells with self-renewal, differentiation and immunomodulatory capabilities. We aimed to develop a co-culture model for differentiating hematopoietic cells on top of immortalized mesenchymal cells for studying interactions between hematopoietic and mesenchymal cells, useful for adequately exploring the therapeutic potential of mesenchymal cells. In this study, we investigated the survival, proliferation and differentiation of porcine red bone marrow hematopoietic cells co-cultured with immortalized porcine bone marrow mesenchymal cells for a period of five weeks. Directly after collection, primary porcine bone marrow mesenchymal cells adhered firmly to the bottom of the culture plates and showed a fibroblast-like appearance, one week after isolation. Upon immortalization, porcine bone marrow mesenchymal cells were continuously proliferating. They were positive for simian virus 40 (SV40) large T antigen and the mesenchymal cell markers CD44 and CD55. Isolated red bone marrow cells were added to these immortalized mesenchymal cells. Five weeks post-seeding, 92±6% of the red bone marrow hematopoietic cells were still alive and their number increased 3-fold during five weekly subpassages on top of the immortalized mesenchymal cells. The red bone marrow hematopoietic cells were originally small and round; later, the cells increased in size. Some of them became elongated, while others remained round. Tiny dendrites appeared attaching hematopoietic cells to the underlying immortalized mesenchymal cells. Furthermore, weekly differential-quick staining of the cells indicated the presence of monoblasts, monocytes, macrophages and lymphocytes in the co-cultures. At three weeks of co-culture, flow cytometry analysis showed an increased surface expression of CD172a, CD14, CD163, CD169, CD4 and CD8 up to 37±0.8%, 40±8%, 41±4%, 23±3% and 19±5% of the hematopoietic cells, respectively. In conclusion, continuous mesenchymal cell

  18. Inefficiency in macromolecular transport of SCS-based microcapsules affects viability of primary human mesenchymal stem cells but not of immortalized cells

    DEFF Research Database (Denmark)

    Sanz-Nogués, Clara; Horan, Jason; Thompson, Kerry

    2015-01-01

    mesenchymal stem cells (hMSCs). Human MSCs are of interest in regenerative medicine applications due to pro-angiogenic, anti-inflammatory and immunomodulatory properties, which result from paracrine effects of this cell type. In the present work we have encapsulated primary hMSCs and hMSC-TERT immortalized...... nutrients and had a more detrimental effect on the viability of primary cell cultures compared to cell lines and immortalized cells. This article is protected by copyright. All rights reserved....

  19. Rat embryo cells immortalized with transfected oncogenes are transformed by gamma irradiation.

    Science.gov (United States)

    Endlich, B; Salavati, R; Sullivan, T; Ling, C C

    1992-12-01

    Cesium-137 gamma rays were used to transform rat embryo cells (REC) which were first transfected with activated c-myc or c-Ha-ras oncogenes to produce immortal cell lines (REC:myc and REC:ras). When exposed to 6 Gy of 137Cs gamma rays, some cells became morphologically transformed with focus formation frequencies of approximately 3 x 10(-4) for REC:myc and approximately 1 x 10(-4) for REC:ras, respectively. Cells isolated from foci of gamma-ray-transformed REC:myc (REC:myc:gamma) formed anchorage-independent colonies and were tumorigenic in nude mice, but foci from gamma-ray-transformed REC:ras (REC:ras:gamma) did not exhibit either of these criteria of transformation. Similar to the results with gamma irradiation, we observed a sequence-dependent phenomenon when myc and ras were transfected into REC, one at a time. REC immortalized by ras transfection were not converted to a tumorigenic phenotype by secondary transfection with myc, but REC transfected with myc were very susceptible to transformation by subsequent ras transfection. This suggests that myc-immortalized cells are more permissive to transformation via secondary treatments. In sequentially transfected REC, myc expression was high whether it was transfected first or second, whereas ras expression was highest when the ras gene was transfected secondarily into myc-containing REC. Molecular analysis of REC:ras:gamma transformants showed no alterations in structure of the transfected ras or of the endogenous ras, myc, p53, or fos genes. The expression of ras and p53 was increased in some isolates of REC:ras:gamma, but myc and fos expression were not affected. Similarly, REC:myc:gamma transformants did not demonstrate rearrangement or amplification of the transfected or the endogenous myc genes, or of the potentially cooperating Ha-, Ki-, or N-ras genes. Northern hybridization analysis revealed increased expression of N-ras in two isolates, REC:myc:gamma 33 and gamma 41, but no alterations in the expression

  20. Regulation of hTERT Expression and Function in Newly Immortalized p53(+) Human Mammary Epithelial Cell Lines

    Science.gov (United States)

    2007-06-01

    human mammary epithelial cell types by human papilloma virus 16 e6 or e7. Proc Nat Acad Sci USA 1995; 92:3687-91. 54. Shay JW, Pereira-Smith OM, Wright...Liu X-L, Chu Q, Gao Q, Band V. Immortalization of distinct human mammary epithelial cell types by human papilloma virus 16 e6 or e7. Proc Nat Acad

  1. Establishment and characterization of a spontaneously immortalized trophoblast cell line (HPT-8) and its hepatitis B virus-expressing clone.

    Science.gov (United States)

    Zhang, Lei; Zhang, Weilu; Shao, Chen; Zhang, Jingxia; Men, Ke; Shao, Zhongjun; Yan, Yongping; Xu, Dezhong

    2011-08-01

    Most trophoblast cell lines currently available to study vertical transmission of hepatitis B virus (HBV) are immortalized by viral transformation. Our goal was to establish and characterize a spontaneously immortalized human first-trimester trophoblast cell line and its HBV-expressing clone. Chorionic villi of Asian human first-trimester placentae were digested with trypsin and collagenase I to obtain the primary trophoblast cell culture. A spontaneously immortalized trophoblast cell line (HPT-8) was analyzed by scanning and transmission electron microscopy, cell cycle analysis, immunohistochemistry and immunofluorescence. HPT-8 cells were stably transfected with the adr subtype of HBV (HPT-8-HBV) and characterized by PCR and enzyme-linked immunosorbent assay. We obtained a clonal derivative of a spontaneously immortalized primary cell clone (HPT-8). HPT-8 cells were epithelioid and polygonal, and formed multinucleate, giant cells. They exhibited microvilli, distinct desmosomes between adjacent cells, abundant endoplasm, lipid inclusions and glycogen granules, which are all characteristic of cytotrophoblasts. HPT-8 cells expressed cytokeratin 7, cytokeratin 18, vimentin, cluster of differentiation antigen 9, epidermal growth factor receptor, stromal cell-derived factor 1 and placental alkaline phosphatase. They secreted prolactin, estradiol, progesterone and hCG, and were positive for HLA-G, a marker of extravillous trophoblasts. HPT-8-HBV cells were positive for HBV relaxed-circular, covalently closed circular DNA and pre-S sequence. HPT-8-HBV cells also produced and secreted HBV surface antigen and HBV e antigen. We established a trophoblast cell line, HPT-8 and its HBV-expressing clone which could be valuable in exploring the mechanism of HBV viral integration in human trophoblasts during intrauterine infection.

  2. Establishment of immortalized B lymphoblastoid cell lines of old residents in high background radiation area in Guangdong, China

    International Nuclear Information System (INIS)

    Lu Xue; Feng Jiangbing; Chen Deqing; Liu Qingjie; Cha Yongru; Zou Jianming

    2008-01-01

    Objective: To establish the immortalized cell lines of peripheral blood lymphocytes for old male residents in high background radiation area (HBRA) in Guangdong, China, in order to preserve the specific genomic resources of residents in HBRA for the further genetic and molecular biological study on HBRA. Methods: The peripheral blood samples of 20 old male residents in HBRA were collected after informed consent. The immortalized B lymphoblastoid cell lines, 2 fox each resident, were established with Epstein-Barr virus. After being frozen and recovered, the cell viability, the contamination of bacterium and mycoplasma were analyzed. The stabilization of cell lines was decided by comparing the karyotypes of the peripheral blood lymphocytes and the cell lines. Results: 40 cell lines for 20 residents in HBRA were successfully established.. The recovery rate of cell lines after being frozen was 100% . All the cell viablity after recovery was higher than 90%, and no contamination of bacteria and mycoplasma occurred. The karyotypes of the 20th generation cell lines were not change. Conclusion: The immortalized cell lines established in this study could provide biological resources for further study on genetics and molecular biology in HBRA. (authors)

  3. Isolation and Characterization of Exosome from Human Embryonic Stem Cell-Derived C-Myc-Immortalized Mesenchymal Stem Cells.

    Science.gov (United States)

    Lai, Ruenn Chai; Yeo, Ronne Wee Yeh; Padmanabhan, Jayanthi; Choo, Andre; de Kleijn, Dominique P V; Lim, Sai Kiang

    2016-01-01

    Mesenchymal stem cells (MSC) are currently the cell type of choice in many cell therapy trials. The number of therapeutic applications for MSCs registered as product IND submissions with the FDA and initiation of registered clinical trials has increased substantially in recent years, in particular between 2006 and 2012. However, defined mechanisms of action underpinning the therapeutic efficacy of MSCs are lacking, but they are increasingly attributed to MSC trophic secretion rather than their differentiation potential. A promising secreted therapeutic candidate is an extracellular vesicle (EV) known as the exosome. The use of exosomes instead of cells as a therapeutic agent provides several advantages. A critical advantage is the prospect of a conventional pharmaceutical manufacturing process that is highly scalable and amenable to the stringent manufacturing process. For example, MSCs used as producers of therapeutics, and not as therapeutics per se, could be immortalized to generate infinitely expansible clonal lines to enhance the reproducible production of therapeutic exosomes. In this chapter, we will describe the immortalization of MSCs, and the production, isolation, and characterization of exosomes from immortalized MSC.

  4. Immortalization of MEF is characterized by the deregulation of specific miRNAs with potential tumor suppressor activity.

    Science.gov (United States)

    Rizzo, Milena; Evangelista, Monica; Simili, Marcella; Mariani, Laura; Pitto, Letizia; Rainaldi, Giuseppe

    2011-07-01

    The life span (Hayflick limit) of primary mouse embryo fibroblasts (MEF) in culture is variable but it is still unclear if the escape of the Hayflick limit is also variable. To address this point MEF were expanded every fifteen days (6T15) instead of every three days (6T3) until they became immortal. With this protocol MEF lifespan was extended and immortalization accordingly delayed. By testing a panel of genes (p19ARF, p16, p21) and miRNAs (miR-20a, miR-21, miR-28, miR-290) related to primary MEF senescence, a switch of p21 from up to down regulation, the down regulation of specific miRNAs as well as a massive shift from diploidy to hyperdiploidy were observed in coincidence with the resumption of cell proliferation. Collectively, these data indicate that the inactivation of genes and miRNAs, important in controlling cell proliferation, might be determinant for the escape from the Hayflick limit. In support of this hypothesis was the finding that some of the down regulated miRNAs transfected in immortalized MEF inhibited cell proliferation thus displaying a tumor suppressor-like activity.

  5. Generation and characterization of the first immortalized alpaca cell line suitable for diagnostic and immunization studies.

    Directory of Open Access Journals (Sweden)

    Valentina Franceschi

    Full Text Available Raising of alpacas as exotic livestock for wool and meat production and as companion animals is growing in importance in the United States, Europe and Australia. Furthermore the alpaca, as well as the rest of the camelids, possesses the peculiarity of producing single-chain antibodies from which nanobodies can be generated. Nanobodies, due to their structural simplicity and reduced size, are very versatile in terms of manipulation and bio-therapeutic exploitation. In fact the biotech companies involved in nanobody production and application continue to grow in number and size. Hence, the development of reagents and tools to assist in the further growth of this new scientific and entrepreneurial reality is becoming a necessity. These are needed mainly to address alpaca disease diagnosis and prophylaxis, and to develop alpaca immunization strategies for nanobody generation. For instance an immortalized alpaca cell line would be extremely valuable. In the present work the first stabilized alpaca cell line from alpaca skin stromal cells (ASSCs was generated and characterized. This cell line was shown to be suitable for replication of viruses bovine herpesvirus-1, bovine viral diarrhea virus and caprine herpesvirus-1 and the endocellular parasite Neospora caninum. Moreover ASSCs were easy to transfect and transduce by several methods. These two latter characteristics are extremely useful when recombinant antigens need to be produced in a host homologous system. This work could be considered as a starting point for the expansion of the biotechnologies linked to alpaca farming and industry.

  6. Telomerase reverse transcriptase mediated immortalization of human bone marrow stromal cells

    Directory of Open Access Journals (Sweden)

    Yong Teng

    2014-02-01

    Full Text Available Primary human bone marrow stromal cells (hMSCs were transfected with human telomerase reverse transcriptase (hTERT gene with lipofection method. The hTERT transfected hMSCs of passage 100 underwent chondrogenesis induction with dexamethasone, transforming the growth factor β and vitamin C, osteogenesis induction with dexamethasone, β glycerophosphoric acid and vitamin C, and cardiomyocyte induction with 5-azacytidine. After 7, 14, 21 and 28 days of induction, immunocytochemistry was performed to detect the expressions of type I and II collagen and osteocalcin, and alizarin red staining was performed to detect the bone nodule formation in osteogenesis induction. Immunocytochemistry was carried out to detect the striated muscle actin expression in cardiomyocytes. The hMSCs undergoing successful transfection were positive for the hTERT. The hTERT transfected cells were grown in vitro successfully and passaged for 136 generations. Results showed that these cells could be induced to differentiate into chondrocytes, bone and myocardial cells. Introduction of exogenous hTERT into hMSCs could achieve immortalized hMSCs with the potential of multi-directional differentiation. Thus, these cells could be applied as seed cells in tissue engineering.

  7. Characterization of cloned cells from an immortalized fetal pulmonary type II cell line

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, R.F.; Waide, J.J.; Lechner, J.F.

    1995-12-01

    A cultured cell line that maintained expression of pulmonary type II cell markers of differentiation would be advantageous to generate a large number of homogenous cells in which to study the biochemical functions of type II cells. Type II epithelial cells are the source of pulmonary surfactant and a cell of origin for pulmonary adenomas. Last year our laboratory reported the induction of expression of two phenotypic markers of pulmonary type II cells (alkaline phosphatase activity and surfactant lipid synthesis) in cultured fetal rat lung epithelial (FRLE) cells, a spontaneously immortalized cell line of fetal rat lung type II cell origin. Subsequently, the induction of the ability to synthesize surfactant lipid became difficult to repeat. We hypothesized that the cell line was heterogenuous and some cells were more like type II cells than others. The purpose of this study was to test this hypothesis and to obtain a cultured cell line with type II cell phenotypic markers by cloning several FRLE cells and characterizing them for phenotypic markers of type II cells (alkaline phosphatase activity and presence of surfactant lipids). Thirty cloned cell lines were analyzed for induced alkaline phosphatase activity (on x-axis) and for percent of phospholipids that were disaturated (i.e., surfactant).

  8. Methamphetamine induces apoptosis in immortalized neural cells: protection by the proto-oncogene, bcl-2.

    Science.gov (United States)

    Cadet, J L; Ordonez, S V; Ordonez, J V

    1997-02-01

    Methamphetamine (METH) is an amphetamine analog that produces degeneration of the dopaminergic system in mammals. The neurotoxic effects of the drug are thought to be mediated by oxygen-based free radicals. In the present report, we have used immortalized neural cells obtained from rat mesencephalon in order to further assess the role of oxidative stress in METH-induced neurotoxicity. We thus tested if the anti-death proto-oncogene, bcl-2 could protect against METH-induced cytotoxicity. METH caused dose-dependent loss of cellular viability in control cells while bcl-2-expressing cells were protected against these deleterious effects. Using flow cytometry, immunofluorescent staining, and DNA electrophoresis, we also show that METH exposure can cause DNA strand breaks, chromatin condensation, nuclear fragmentation, and DNA laddering. All these changes were prevented by bcl-2 expression. These observations provide further support for the involvement of oxidative stress in the toxic effects of amphetamine analogs. They also document that METH-induced cytotoxicity is secondary to apoptosis. These findings may be of relevance to the cause(s) of Parkinson's disease which involves degeneration of the nigrostriatal dopaminergic pathway.

  9. Postirradiation expression of lethal mutations in an immortalized human keratinocyte cell line

    International Nuclear Information System (INIS)

    O'Reilly, S.; Mothersill, C.; Seymour, C.B.

    1994-01-01

    The quantification of the extent of delayed cell death and the rate and pattern of its occurrence in relation to the cell division cycle is important in radiotherapy and also in radiation transformation studies related to protection and dose limits. Here the numbers of lethal mutations occurring over 45 population doublings (clonal expansion to about 10 13 cells per cell originally surviving irradiation) was measured in an HPV 16 immortalized human keratinocyte cell lines used for transformation studies. The results showed that when postirradiation (dose range 1-6 Gy) growth curves were constructed, the difference in slopes could be accounted for entirely by correcting for the non-clonogenic fraction in the cell count, excluding a longer cell generation time as an explanation. When the cell loss was examined over the entire growth period of 6 weeks (about 45 doublings of the cell population), it was found to be dose dependent for the first two passages, but then to become more independent of dose. The results allow a time/cell generation dependent factor to be derived for the cell line and used in survival curve equations where effects of radiation are being measured at times distant from the original exposure. (author)

  10. Effect of surface charge of immortalized mouse cerebral endothelial cell monolayer on transport of charged solutes.

    Science.gov (United States)

    Yuan, Wei; Li, Guanglei; Gil, Eun Seok; Lowe, Tao Lu; Fu, Bingmei M

    2010-04-01

    Charge carried by the surface glycocalyx layer (SGL) of the cerebral endothelium has been shown to significantly modulate the permeability of the blood-brain barrier (BBB) to charged solutes in vivo. The cultured monolayer of bEnd3, an immortalized mouse cerebral endothelial cell line, is becoming a popular in vitro BBB model due to its easy growth and maintenance of many BBB characteristics over repeated passages. To test whether the SGL of bEnd3 monolayer carries similar charge as that in the intact BBB and quantify this charge, which can be characterized by the SGL thickness (L(f)) and charge density (C(mf)), we measured the solute permeability of bEnd3 monolayer to neutral solutes and to solutes with similar size but opposite charges: negatively charged alpha-lactalbumin (-11) and positively charged ribonuclease (+3). Combining the measured permeability data with a transport model across the cell monolayer, we predicted the L(f) and the C(mf) of bEnd3 monolayer, which is approximately 160 nm and approximately 25 mEq/L, respectively. We also investigated whether orosomucoid, a plasma glycoprotein modulating the charge of the intact BBB, alters the charge of bEnd3 monolayer. We found that 1 mg/mL orosomucoid would increase SGL charge density of bEnd3 monolayer to approximately 2-fold of its control value.

  11. Validation of an immortalized human (hBMEC) in vitro blood-brain barrier model.

    Science.gov (United States)

    Eigenmann, Daniela Elisabeth; Jähne, Evelyn Andrea; Smieško, Martin; Hamburger, Matthias; Oufir, Mouhssin

    2016-03-01

    We recently established and optimized an immortalized human in vitro blood-brain barrier (BBB) model based on the hBMEC cell line. In the present work, we validated this mono-culture 24-well model with a representative series of drug substances which are known to cross or not to cross the BBB. For each individual compound, a quantitative UHPLC-MS/MS method in Ringer HEPES buffer was developed and validated according to current regulatory guidelines, with respect to selectivity, precision, and reliability. Various biological and analytical challenges were met during method validation, highlighting the importance of careful method development. The positive controls antipyrine, caffeine, diazepam, and propranolol showed mean endothelial permeability coefficients (P e) in the range of 17-70 × 10(-6) cm/s, indicating moderate to high BBB permeability when compared to the barrier integrity marker sodium fluorescein (mean P e 3-5 × 10(-6) cm/s). The negative controls atenolol, cimetidine, and vinblastine showed mean P e values < 10 × 10(-6) cm/s, suggesting low permeability. In silico calculations were in agreement with in vitro data. With the exception of quinidine (P-glycoprotein inhibitor and substrate), BBB permeability of all control compounds was correctly predicted by this new, easy, and fast to set up human in vitro BBB model. Addition of retinoic acid and puromycin did not increase transendothelial electrical resistance (TEER) values of the BBB model.

  12. Transmutations: Rejuvenation, Longevity, and Immortality Practices in South and Inner Asia

    Directory of Open Access Journals (Sweden)

    Dagmar Wujastyk

    2017-12-01

    Full Text Available Wild and diverse outcomes are associated with transmutational practices: the prolongation of life, the recovery of youth, the cure of diseases, invincibility, immortality, enlightenment, liberation from the cycle of rebirths, and unending bliss. This range of outcomes is linked to specific practices taught in separate traditions and lineages in medical, alchemical, yogic and tantric milieus across South and Inner Asia. These practices can be individual or collective, esoteric or secular, and occur in different places from hospital to village to monastery; they involve transmutations of substances as well as transmutations of the body. Every expression by a particular lineage has a distinguishing articulation. Yet there are also very clear commonalities and interconnections between the traditions’ aims, methods and expected results. In this special issue of HSSA, we examine transmutational practices and their underlying concepts in this wider context of South and Inner Asian culture. How do these practices and ideas connect and cross-fertilise? And conversely, how are they delineated and distinct?

  13. Selling space colonization and immortality: A psychosocial, anthropological critique of the rush to colonize Mars

    Science.gov (United States)

    Slobodian, Rayna Elizabeth

    2015-08-01

    Extensive media coverage regarding the proposal to send four people to Mars by 2025 has exploded recently. Private enterprise has taken the reins to venture into space, which has typically only been reserved for government agencies. I argue, that with this new direction comes less regulation, raising questions regarding the ethics of sending people into outer space to colonize Mars within a decade. Marketers selling colonization to the public include perspectives such as biological drives, species survival, inclusiveness and utopian ideals. I challenge these narratives by suggesting that much of our desire to colonize space within the next decade is motivated by ego, money and romanticism. More specifically, I will examine the roles that fear and stories of immortality play within selling space and how those stories are marketed. I am passionate about space and hope that one day humanity will colonize other worlds, but the rush to settle is dangerous and careless. I assert that humanity should first gain more experience and knowledge before colonizing outer space, using this research to mitigate the risk to astronauts and proceed with careful consideration for the lives of potential astronauts.

  14. A lysosomal switch triggers proteostasis renewal in the immortal C. elegans germ lineage.

    Science.gov (United States)

    Bohnert, K Adam; Kenyon, Cynthia

    2017-11-30

    Although individuals age and die with time, an animal species can continue indefinitely, because of its immortal germ-cell lineage. How the germline avoids transmitting damage from one generation to the next remains a fundamental question in biology. Here we identify a lysosomal switch that enhances germline proteostasis before fertilization. We find that Caenorhabditis elegans oocytes whose maturation is arrested by the absence of sperm exhibit hallmarks of proteostasis collapse, including protein aggregation. Remarkably, sperm-secreted hormones re-establish oocyte proteostasis once fertilization becomes imminent. Key to this restoration is activation of the vacuolar H + -ATPase (V-ATPase), a proton pump that acidifies lysosomes. Sperm stimulate V-ATPase activity in oocytes by signalling the degradation of GLD-1, a translational repressor that blocks V-ATPase synthesis. Activated lysosomes, in turn, promote a metabolic shift that mobilizes protein aggregates for degradation, and reset proteostasis by enveloping and clearing the aggregates. Lysosome acidification also occurs during Xenopus oocyte maturation; thus, a lysosomal switch that enhances oocyte proteostasis in anticipation of fertilization may be conserved in other species.

  15. GSK3 Inhibitor-BIO Regulates Proliferation of Immortalized Pancreatic Mesenchymal Stem Cells (iPMSCs)

    Science.gov (United States)

    Cao, Hui; Chu, Yuankui; Lv, Xiao; Qiu, Pubin; Liu, Chao; Zhang, Huiru; Li, Dan; Peng, Sha; Dou, Zhongying; Hua, Jinlian

    2012-01-01

    Background The small molecule 6-bromoindirubin-30-oxime (BIO), a glycogen synthase kinase 3 (GSK3) inhibitor, is a pharmacological agent known to maintain self-renewal in human and mouse embryonic stem cells (ESCs). However, the precise role of GSK3 in immortalized pancreatic mesenchymal stem cells (iPMSCs) growth and survival is not completely understood at present. Results To determine whether this molecule is involved in controlling the proliferation of iPMSCs, we examined the effect of BIO on iPMSCs. We found that the inactivation of GSK3 by BIO can robustly stimulate iPMSCs proliferation and mass formation as shown by QRT-PCR, western blotting, 5-Bromo-2-deoxyuridine (BrdU) immunostaining assay and tunel assay. However, we did not find the related roles of BIO on β cell differentiation by immunostaining, QRT-PCR assay, glucose-stimulated insulin release and C-peptide content analysis. Conclusions These results suggest that BIO plays a key role in the regulation of cell mass proliferation and maintenance of the undifferentiated state of iPMSCs. PMID:22384031

  16. An elasto-visco-plastic model for immortal foams or emulsions.

    Science.gov (United States)

    Bénito, S; Bruneau, C-H; Colin, T; Gay, C; Molino, F

    2008-03-01

    A variety of complex fluids consists in soft, round objects (foams, emulsions, assemblies of copolymer micelles or of multilamellar vesicles--also known as onions). Their dense packing induces a slight deviation from their preferred circular or spherical shape. As a frustrated assembly of interacting bodies, such a material evolves from one conformation to another through a succession of discrete, topological events driven by finite external forces. As a result, the material exhibits a finite yield threshold. The individual objects usually evolve spontaneously (colloidal diffusion, object coalescence, molecular diffusion), and the material properties under low or vanishing stress may alter with time, a phenomenon known as aging. We neglect such effects to address the simpler behaviour of (uncommon) immortal fluids: we construct a minimal, fully tensorial, rheological model, equivalent to the (scalar) Bingham model. Importantly, the model consistently describes the ability of such soft materials to deform substantially in the elastic regime (be it compressible or not) before they undergo (incompressible) plastic creep--or viscous flow under even higher stresses.

  17. Mapping of imprinted quantitative trait loci using immortalized F2 populations.

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    Yongxian Wen

    Full Text Available Mapping of imprinted quantitative trait loci (iQTLs is helpful for understanding the effects of genomic imprinting on complex traits in animals and plants. At present, the experimental designs and corresponding statistical methods having been proposed for iQTL mapping are all based on temporary populations including F2 and BC1, which can be used only once and suffer some other shortcomings respectively. In this paper, we propose a framework for iQTL mapping, including methods of interval mapping (IM and composite interval mapping (CIM based on conventional low-density genetic maps and point mapping (PM and composite point mapping (CPM based on ultrahigh-density genetic maps, using an immortalized F2 (imF2 population generated by random crosses between recombinant inbred lines or doubled haploid lines. We demonstrate by simulations that imF2 populations are very desirable and the proposed statistical methods (especially CIM and CPM are very powerful for iQTL mapping, with which the imprinting effects as well as the additive and dominance effects of iQTLs can be unbiasedly estimated.

  18. Characterization of lipid metabolism in insulin-sensitive adipocytes differentiated from immortalized human mesenchymal stem cells

    International Nuclear Information System (INIS)

    Prawitt, Janne; Niemeier, Andreas; Kassem, Moustapha; Beisiegel, Ulrike; Heeren, Joerg

    2008-01-01

    There is a great demand for cell models to study human adipocyte function. Here we describe the adipogenic differentiation of a telomerase-immortalized human mesenchymal stem cell line (hMSC-Tert) that maintains numerous features of terminally differentiated adipocytes even after prolonged withdrawal of the peroxisome proliferator activated receptor γ (PPARγ) agonist rosiglitazone. Differentiated hMSC-Tert developed the characteristic monolocular phenotype of mature adipocytes. The expression of adipocyte specific markers was highly increased during differentiation. Most importantly, the presence of the PPARγ agonist rosiglitazone was not required for the stable expression of lipoprotein lipase, adipocyte fatty acid binding protein and perilipin on mRNA and protein levels. Adiponectin expression was post-transcriptionally down-regulated in the absence of rosiglitazone. Insulin sensitivity as measured by insulin-induced phosphorylation of Akt and S6 ribosomal protein was also independent of rosiglitazone. In addition to commonly used adipogenic markers, we investigated further PPARγ-stimulated proteins with a role in lipid metabolism. We observed an increase of lipoprotein receptor (VLDLR, LRP1) and apolipoprotein E expression during differentiation. Despite this increased expression, the receptor-mediated endocytosis of lipoproteins was decreased in differentiated adipocytes, suggesting that these proteins may have an additional function in adipose tissue beyond lipoprotein uptake

  19. Transformation of SV40-immortalized human uroepithelial cells by 3-methylcholanthrene increases IFN- and Large T Antigen-induced transcripts

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    Easton Marilyn J

    2010-02-01

    Full Text Available Abstract Background Simian Virus 40 (SV40 immortalization followed by treatment of cells with 3-methylcholanthrene (3-MC has been used to elicit tumors in athymic mice. 3-MC carcinogenesis has been thoroughly studied, however gene-level interactions between 3-MC and SV40 that could have produced the observed tumors have not been explored. The commercially-available human uroepithelial cell lines were either SV40-immortalized (HUC or SV40-immortalized and then 3-MC-transformed (HUC-TC. Results To characterize the SV40 - 3MC interaction, we compared human gene expression in these cell lines using a human cancer array and confirmed selected changes by RT-PCR. Many viral Large T Antigen (Tag expression-related changes occurred in HUC-TC, and it is concluded that SV40 and 3-MC may act synergistically to transform cells. Changes noted in IFP 9-27, 2'-5' OAS, IF 56, MxA and MxAB were typical of those that occur in response to viral exposure and are part of the innate immune response. Because interferon is crucial to innate immune host defenses and many gene changes were interferon-related, we explored cellular growth responses to exogenous IFN-γ and found that treatment impeded growth in tumor, but not immortalized HUC on days 4 - 7. Cellular metabolism however, was inhibited in both cell types. We conclude that IFN-γ metabolic responses were functional in both cell lines, but IFN-γ anti-proliferative responses functioned only in tumor cells. Conclusions Synergism of SV40 with 3-MC or other environmental carcinogens may be of concern as SV40 is now endemic in 2-5.9% of the U.S. population. In addition, SV40-immortalization is a generally-accepted method used in many research materials, but the possibility of off-target effects in studies carried out using these cells has not been considered. We hope that our work will stimulate further study of this important phenomenon.

  20. Human papillomavirus type 59 immortalized keratinocytes express late viral proteins and infectious virus after calcium stimulation

    International Nuclear Information System (INIS)

    Lehr, Elizabeth E.; Qadadri, Brahim; Brown, Calla R.; Brown, Darron R.

    2003-01-01

    Human papillomavirus type 59 (HPV 59) is an oncogenic type related to HPV 18. HPV 59 was recently propagated in the athymic mouse xenograft system. A continuous keratinocyte cell line infected with HPV 59 was created from a foreskin xenograft grown in an athymic mouse. Cells were cultured beyond passage 50. The cells were highly pleomorphic, containing numerous abnormally shaped nuclei and mitotic figures. HPV 59 sequences were detected in the cells by DNA in situ hybridization in a diffuse nuclear distribution. Southern blots were consistent with an episomal state of HPV 59 DNA at approximately 50 copies per cell. Analysis of the cells using a PCR/reverse blot strip assay, which amplifies a portion of the L1 open reading frame, was strongly positive. Differentiation of cells in monolayers was induced by growth in F medium containing 2 mM calcium chloride for 10 days. Cells were harvested as a single tissue-like sheet, and histologic analysis revealed a four-to-six cell-thick layer. Transcripts encoding involucrin, a cornified envelope protein, and the E1-circumflexE4 and E1-circumflexE4-circumflexL1 viral transcripts were detected after several days of growth in F medium containing 2 mM calcium chloride. The E1-circumflexE4 and L1 proteins were detected by immunohistochemical analysis, and virus particles were seen in electron micrographs in a subset of differentiated cells. An extract of differentiated cells was prepared by vigorous sonication and was used to infect foreskin fragments. These fragments were implanted into athymic mice. HPV 59 was detected in the foreskin xenografts removed 4 months later by DNA in situ hybridization and PCR/reverse blot assay. Thus, the complete viral growth cycle, including production on infectious virus, was demonstrated in the HPV 59 immortalized cells grown in a simple culture system

  1. Isolation and characterization of a spontaneously immortalized bovine retinal pigmented epithelial cell line

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    Griffiths T Daniel

    2009-05-01

    Full Text Available Abstract Background The Retinal Pigmented Epithelium (RPE is juxtaposed with the photoreceptor outer segments of the eye. The proximity of the photoreceptor cells is a prerequisite for their survival, as they depend on the RPE to remove the outer segments and are also influenced by RPE cell paracrine factors. RPE cell death can cause a progressive loss of photoreceptor function, which can diminish vision and, over time, blindness ensues. Degeneration of the retina has been shown to induce a variety of retinopathies, such as Stargardt's disease, Cone-Rod Dystrophy (CRD, Retinitis Pigmentosa (RP, Fundus Flavimaculatus (FFM, Best's disease and Age-related Macular Degeneration (AMD. We have cultured primary bovine RPE cells to gain a further understanding of the mechanisms of RPE cell death. One of the cultures, named tRPE, surpassed senescence and was further characterized to determine its viability as a model for retinal diseases. Results The tRPE cell line has been passaged up to 150 population doublings and was shown to be morphologically similar to primary cells. They have been characterized to be of RPE origin by reverse transcriptase PCR and immunocytochemistry using the RPE-specific genes RPE65 and CRALBP and RPE-specific proteins RPE65 and Bestrophin. The tRPE cells are also immunoreactive to vimentin, cytokeratin and zonula occludens-1 antibodies. Chromosome analysis indicates a normal diploid number. The tRPE cells do not grow in suspension or in soft agar. After 3H thymidine incorporation, the cells do not appear to divide appreciably after confluency. Conclusion The tRPE cells are immortal, but still exhibit contact inhibition, serum dependence, monolayer growth and secrete an extra-cellular matrix. They retain the in-vivo morphology, gene expression and cell polarity. Additionally, the cells endocytose exogenous melanin, A2E and purified lipofuscin granules. This cell line may be a useful in-vitro research model for retinal

  2. Determination of Drug Toxicity Using 3D Spheroids Constructed From an Immortal Human Hepatocyte Cell Line

    Science.gov (United States)

    Fey, Stephen J.; Wrzesinski, Krzysztof

    2012-01-01

    Numerous publications have documented that the immortal cells grown in three-dimensional (3D) cultures possess physiological behavior, which is more reminiscent of their parental organ than when the same cells are cultivated using classical two-dimensional (2D) culture techniques. The goal of this study was to investigate whether this observation could be extended to the determination of LD50 values and whether 3D data could be correlated to in vivo observations. We developed a noninvasive means to estimate the amount of protein present in a 3D spheroid from it is planar area (± 21%) so that a precise dose can be provided in a manner similar to in vivo studies. This avoided correction of the actual dose given based on a protein determination after treatment (when some cells may have lysed). Conversion of published in vitro LC50 data (mM) for six common drugs (acetaminophen, amiodarone, diclofenac, metformin, phenformin, and valproic acid) to LD50 data (mg compound/mg cellular protein) showed that the variation in LD50 values was generally less than that suggested by the original LC50 data. Toxicological analysis of these six compounds in 3D spheroid culture (either published or presented here) demonstrated similar LD50 values. Although in vitro 2D HepG2 data showed a poor correlation, the primary hepatocyte and 3D spheroid data resulted in a much higher degree of correlation with in vivo lethal blood plasma levels. These results corroborate that 3D hepatocyte cultures are significantly different from 2D cultures and are more representative of the liver in vivo. PMID:22454432

  3. Arsenic compromises conducting airway epithelial barrier properties in primary mouse and immortalized human cell cultures.

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    Cara L Sherwood

    Full Text Available Arsenic is a lung toxicant that can lead to respiratory illness through inhalation and ingestion, although the most common exposure is through contaminated drinking water. Lung effects reported from arsenic exposure include lung cancer and obstructive lung disease, as well as reductions in lung function and immune response. As part of their role in innate immune function, airway epithelial cells provide a barrier that protects underlying tissue from inhaled particulates, pathogens, and toxicants frequently found in inspired air. We evaluated the effects of a five-day exposure to environmentally relevant levels of arsenic {<4μM [~300 μg/L (ppb] as NaAsO2} on airway epithelial barrier function and structure. In a primary mouse tracheal epithelial (MTE cell model we found that both micromolar (3.9 μM and submicromolar (0.8 μM arsenic concentrations reduced transepithelial resistance, a measure of barrier function. Immunofluorescent staining of arsenic-treated MTE cells showed altered patterns of localization of the transmembrane tight junction proteins claudin (Cl Cl-1, Cl-4, Cl-7 and occludin at cell-cell contacts when compared with untreated controls. To better quantify arsenic-induced changes in tight junction transmembrane proteins we conducted arsenic exposure experiments with an immortalized human bronchial epithelial cell line (16HBE14o-. We found that arsenic exposure significantly increased the protein expression of Cl-4 and occludin as well as the mRNA levels of Cl-4 and Cl-7 in these cells. Additionally, arsenic exposure resulted in altered phosphorylation of occludin. In summary, exposure to environmentally relevant levels of arsenic can alter both the function and structure of airway epithelial barrier constituents. These changes likely contribute to the observed arsenic-induced loss in basic innate immune defense and increased infection in the airway.

  4. [SOUND CONTACTS] Transcendence and immortality in Busoni’s "Doktor Faust"

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    Antonella DiGiulio

    2015-04-01

    Full Text Available The categorization of the many musical and literary works inspired by the Faust legend is based on their two possible conclusions: Faust ends up in hell or is redeemed and attaints heaven. Busoni’s work is often categorized in terms of the redemptive form. I will analyze a third possibility: during the last part of the nineteenth century, philosophers conceptualized that man’s feelings of unhappiness came from his confinement into an eternal recurrence and that life doesn’t end with the death. Scholars tend to ignore the links between Doktor Faust and these philosophical thoughts because of Busoni’s explicit denial of such intentions. And yet Busoni wrote that an opera is the highest form of artistic expression, where music gives words to the unspoken. Therefore I will argue that Busoni characterizes Doktor Faust as a hybridization of the new philosophical theories with literature and music. Busoni’s depiction of the main character in this opera may not be intentional, but the composer summed up all the qualities of Nietzsche’s Übermensch, D’Annunzio’s Superuomo, and Pascoli’s fanciullino in Faust. Faust discovers his own transcendent power, which is independent from the material universe and yet belongs to nature’s laws that are beyond God and the evil. Doktor Faust’s attainment of immortality does not pray for divine redemption and wins out over everything: in this opera, Faust is neither redeemed nor damned. Faust becomes aware that death is nothing but the means that lead to rebirth: “ich, Faust, ein ewiger Wille”.

  5. Accumulation and altered localization of telomere-associated protein TRF2 in immortally transformed and tumor-derived human breast cells

    Energy Technology Data Exchange (ETDEWEB)

    Nijjar, Tarlochan; Bassett, Ekaterina; Garbe, James; Takenaka, Yasuhiro; Stampfer, Martha R.; Gilley, David; Yaswen, Paul

    2004-12-23

    We have used cultured human mammary epithelial cells (HMEC) and breast tumor-derived lines to gain information on defects that occur during breast cancer progression. HMEC immortalized by a variety of agents (the chemical carcinogen benzo(a)pyrene, oncogenes c-myc and ZNF217, and/or dominant negative p53 genetic suppressor element GSE22) displayed marked up regulation (10-15 fold) of the telomere binding protein, TRF2. Up-regulation of TRF2 protein was apparently due to differences in post-transcriptional regulation, as mRNA levels remained comparable in finite life span and immortal HMEC. TRF2 protein was not up-regulated by the oncogenic agents alone in the absence of immortalization, nor by expression of exogenously introduced hTERT genes. We found TRF2 levels to be at least 2-fold higher than in control cells in 11/15 breast tumor cell lines, suggesting that elevated TRF2 levels are a frequent occurrence during the transformation of breast tumor cells in vivo. The dispersed distribution of TRF2 throughout the nuclei in some immortalized and tumor-derived cells indicated that not all the TRF2 was associated with telomeres in these cells. The process responsible for accumulation of TRF2 in immortalized HMEC and breast tumor-derived cell lines may promote tumorigenesis by contributing to the cells ability to maintain an indefinite life span.

  6. Production and Functional Characterization of Murine Osteoclasts Differentiated from ER-Hoxb8-Immortalized Myeloid Progenitor Cells.

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    Frank Zach

    Full Text Available In vitro differentiation into functional osteoclasts is routinely achieved by incubation of embryonic stem cells, induced pluripotent stem cells, or primary as well as cryopreserved spleen and bone marrow-derived cells with soluble receptor activator of nuclear factor kappa-B ligand and macrophage colony-stimulating factor. Additionally, osteoclasts can be derived from co-cultures with osteoblasts or by direct administration of soluble receptor activator of nuclear factor kappa-B ligand to RAW 264.7 macrophage lineage cells. However, despite their benefits for osteoclast-associated research, these different methods have several drawbacks with respect to differentiation yields, time and animal consumption, storage life of progenitor cells or the limited potential for genetic manipulation of osteoclast precursors. In the present study, we therefore established a novel protocol for the differentiation of osteoclasts from murine ER-Hoxb8-immortalized myeloid stem cells. We isolated and immortalized bone marrow cells from wild type and genetically manipulated mouse lines, optimized protocols for osteoclast differentiation and compared these cells to osteoclasts derived from conventional sources. In vitro generated ER-Hoxb8 osteoclasts displayed typical osteoclast characteristics such as multi-nucleation, tartrate-resistant acid phosphatase staining of supernatants and cells, F-actin ring formation and bone resorption activity. Furthermore, the osteoclast differentiation time course was traced on a gene expression level. Increased expression of osteoclast-specific genes and decreased expression of stem cell marker genes during differentiation of osteoclasts from ER-Hoxb8-immortalized myeloid progenitor cells were detected by gene array and confirmed by semi-quantitative and quantitative RT-PCR approaches. In summary, we established a novel method for the quantitative production of murine bona fide osteoclasts from ER-Hoxb8 stem cells generated from

  7. Expression profile of senescence-associated beta-galactosidase and activation of telomerase in human ovarian surface epithelial cells undergoing immortalization.

    Science.gov (United States)

    Litaker, J R; Pan, J; Cheung, Y; Zhang, D K; Liu, Y; Wong, S C; Wan, T S; Tsao, S W

    1998-11-01

    Senescence is a specific physiological stage of cells characterized by long population doubling time. It accounts for the inability of normal somatic cells to undergo indefinite cell division. As the number of population doublings increase, cell cycle regulatory mechanisms come into play and signal cells to exit the cell cycle and become senescent. Senescence has been implicated in the aging process and may function as a tumor suppressor mechanism in human cells. The ability to measure the degree of cellular senescence is important in understanding the biological processes regulating cell aging and immortalization. Senescent cells exhibit an enzyme termed senescence-associated histochemical staining. Cells immortalized by viral oncogenes often enter a stage of crisis at the early phase of immortalization. The cells at crisis have a long population doubling time. Cells at the crisis stage resemble senescent cells and the expression of SA- beta-Gal may be used to monitor the process of immortalization. In this study the expression profile of SA-beta-Gal was examined in human ovarian surface epithelial cells (HOSE 6-3) undergoing immortalization by the human papilloma viral oncogene E6 and E7 (HPV E6 and E7). Our results showed a low percentage (12.0%) of HOSE 6-3 cells expressing SA-beta-Gal activity at the pre-crisis stage. The percentage of HOSE 6-3 cells expressing SA-beta-Gal activity was highest (39.2%) at the crisis stage. When HOSE 6-3 cells achieved immortalized status there was a sharp decrease in cells (1. 3%) expressing SA-beta-Gal activity. In addition, an inverse relationship between the expression of SA-beta-Gal activity and telomerase activity was noted in cells undergoing immortalization. The results confirm that the SA-beta-Gal enzyme is a good marker for monitoring the population of cells undergoing senescence at different stages of immortalization and that telomerase activation is a characteristic feature of post-crisis cells.

  8. Krása a nesmrteľnosť. O plodení u Platóna a Shakespeara (Beauty and Immortality. On Procreation in Plato and Shakespeare

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    Anton Vydra

    2007-03-01

    Full Text Available There are two moments referred in this essay: (1 A human being, which desires for immortality, desires for to be alive in his child or in an artwork. (2 Full human being’s desire is related for beauty. Is a beauty the same thing as immortality? How looks the relation between them? Shakespeare’s Sonnets begin with the challenge to his friend to procreate the offspring, because this is a way for immortality of the friend’s beauty. And if it is not a child, than verse refused him before the death or the Lethe. Similarly, Plato’s Socrates says in Symposium about his meeting with Diotima of Mantineia. She told him the oration on real Beauty without accidents. To see real Beauty means to be immortal, likewise the gods. Thus, could be a human being immortal?

  9. Reversible immortalization of Nestin-positive precursor cells from pancreas and differentiation into insulin-secreting cells

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Pei; Li, Li; Qi, Hui [The Clinical Medical Research Center, The Second Clinical Medical College (Shenzhen People' s Hospital), Jinan University, 518020 Shenzhen (China); Zhou, Han-xin [Department of General Surgery, First Hospital (Shenzhen Second People' s Hospital) of Shenzhen University, 518020 Shenzhen (China); Deng, Chun-yan [The Clinical Medical Research Center, The Second Clinical Medical College (Shenzhen People' s Hospital), Jinan University, 518020 Shenzhen (China); Li, Fu-rong, E-mail: frli62@yahoo.com [The Clinical Medical Research Center, The Second Clinical Medical College (Shenzhen People' s Hospital), Jinan University, 518020 Shenzhen (China); Shenzhen Institution of Gerontology, 518020 Shenzhen (China)

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer The NPPCs from mouse pancreas were isolated. Black-Right-Pointing-Pointer Tet-on system for SV40 large in NPPCs was used to get RINPPCs. Black-Right-Pointing-Pointer The RINPPCs can undergo at least 80 population doublings without senescence. Black-Right-Pointing-Pointer The RINPPCs can be induced to differentiate into insulin-producing cells. Black-Right-Pointing-Pointer The combination of GLP-1 and sodium butyrate promoted the differentiation process. -- Abstract: Pancreatic stem cells or progenitor cells posses the ability of directed differentiation into pancreatic {beta} cells. However, these cells usually have limited proliferative capacity and finite lifespan in vitro. In the present study, Nestin-positive progenitor cells (NPPCs) from mouse pancreas that expressed the pancreatic stem cells or progenitor cell marker Nestin were isolated to obtain a sufficient number of differentiated pancreatic {beta} cells. Tet-on system for SV40 large T-antigen expression in NPPCs was used to achieve reversible immortalization. The reversible immortal Nestin-positive progenitor cells (RINPPCs) can undergo at least 80 population doublings without senescence in vitro while maintaining their biological and genetic characteristics. RINPPCs can be efficiently induced to differentiate into insulin-producing cells that contain a combination of glucagon-like peptide-1 (GLP-1) and sodium butyrate. The results of the present study can be used to explore transplantation therapy of type I diabetes mellitus.

  10. Genetic effect of low dose rate radiation on human cells immortalized with the hTERT gene

    International Nuclear Information System (INIS)

    Nakamura, Hideaki; Fukami, Hiroko; Hayashi, Yuko; Kiyono, Tohru; Ishizaki, Kanji; Tachibana, Akira; Nakatsugawa, Shigekazu; Hamaguchi, Michinari

    2003-01-01

    We established immortal human cells by introducing the hTERT gene into skin fibroblast cells obtained from normal (SuSa) and ataxia telangiectasia (AT: AT1OS) individuals of Japanese origin. These immortalized cells showed the same characteristics as the original cells except expanded life span. We irradiated SuSa/T-n and AT1OS/T-n cells with low-dose-rate (LDR; 0.3 mGy/min) irradiation at confluent state in low-serum medium. Then, survival rate and micronucleus frequency of each cell line were analyzed. In SuSa/T-n cells, frequency of HPRT mutation induction was also determined by 6TG selection. In SuSa/T-n cells, survival rate and micronucleus frequency showed higher resistance after irradiation with LDR than high-dose-rate (HDR; 2 Gy/min) irradiation. In contrast, no significant difference was observed in survival and micronucleus induction in AT1OS/T-n cells between HDR and LDR irradiation, suggesting that AT1OS/T-n cells may have some defect in DNA repair activity. In SuSa/T-n cells, the frequency of HPRT mutation after LDR irradiation decreased to approximately one eighth that after HDR irradiation. (author)

  11. Maintenance of vascular endothelial cell-specific properties after immortalization with an amphotrophic replication-deficient retrovirus containing human papilloma virus 16 E6/E7 DNA

    NARCIS (Netherlands)

    Fontijn, R.; Hop, C.; Brinkman, H. J.; Slater, R.; Westerveld, A.; van Mourik, J. A.; Pannekoek, H.

    1995-01-01

    Primary human vascular endothelial cells were immortalized by the integration of a single DNA copy of an amphotrophic, replication-deficient retrovirus containing the E6/E7 genes of human papilloma virus. To date, the resulting cell lines, designated EC-RF7 and EC-RF24, have been cultured for more

  12. Immortalization of T-Cells Is Accompanied by Gradual Changes in CpG Methylation Resulting in a Profile Resembling a Subset of T-Cell Leukemias

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    Sofie Degerman

    2014-07-01

    Full Text Available We have previously described gene expression changes during spontaneous immortalization of T-cells, thereby identifying cellular processes important for cell growth crisis escape and unlimited proliferation. Here, we analyze the same model to investigate the role of genome-wide methylation in the immortalization process at different time points pre-crisis and post-crisis using high-resolution arrays. We show that over time in culture there is an overall accumulation of methylation alterations, with preferential increased methylation close to transcription start sites (TSSs, islands, and shore regions. Methylation and gene expression alterations did not correlate for the majority of genes, but for the fraction that correlated, gain of methylation close to TSS was associated with decreased gene expression. Interestingly, the pattern of CpG site methylation observed in immortal T-cell cultures was similar to clinical T-cell acute lymphoblastic leukemia (T-ALL samples classified as CpG island methylator phenotype positive. These sites were highly overrepresented by polycomb target genes and involved in developmental, cell adhesion, and cell signaling processes. The presence of non-random methylation events in in vitro immortalized T-cell cultures and diagnostic T-ALL samples indicates altered methylation of CpG sites with a possible role in malignant hematopoiesis.

  13. Lack of the p42 form of C/EBPα leads to spontaneous immortalization and lineage infidelity of committed myeloid progenitors

    DEFF Research Database (Denmark)

    Schuster, Mikkel B; Frank, Anne-Katrine; Bagger, Frederik O

    2013-01-01

    transforming events. In this study, we use premalignant cells from a Cebpa mutant AML model, in which the LIC population resembles granulocyte-macrophage progenitors (GMPs), to show that premalignant GMPs undergo spontaneous immortalization with a high clonal frequency when cultured in vitro, suggesting...

  14. Perspectives on Immortality and Eternal Life in the Book of Wisdom and the Gospel of John: A Conceptual Analysis Based on Metaphorical Structuring

    NARCIS (Netherlands)

    Valentin, R.I.

    2016-01-01

    The similarities between the Fourth Gospel and wisdom literature have been addressed by many scholars. This study is also intended to continue along this line by looking at the particular link between the Wisdom of Solomon and the Gospel of John with a specific focus on the concepts of immortality

  15. Immortalization of T-cells is accompanied by gradual changes in CpG methylation resulting in a profile resembling a subset of T-cell leukemias.

    Science.gov (United States)

    Degerman, Sofie; Landfors, Mattias; Siwicki, Jan Konrad; Revie, John; Borssén, Magnus; Evelönn, Emma; Forestier, Erik; Chrzanowska, Krystyna H; Rydén, Patrik; Keith, W Nicol; Roos, Göran

    2014-07-01

    We have previously described gene expression changes during spontaneous immortalization of T-cells, thereby identifying cellular processes important for cell growth crisis escape and unlimited proliferation. Here, we analyze the same model to investigate the role of genome-wide methylation in the immortalization process at different time points pre-crisis and post-crisis using high-resolution arrays. We show that over time in culture there is an overall accumulation of methylation alterations, with preferential increased methylation close to transcription start sites (TSSs), islands, and shore regions. Methylation and gene expression alterations did not correlate for the majority of genes, but for the fraction that correlated, gain of methylation close to TSS was associated with decreased gene expression. Interestingly, the pattern of CpG site methylation observed in immortal T-cell cultures was similar to clinical T-cell acute lymphoblastic leukemia (T-ALL) samples classified as CpG island methylator phenotype positive. These sites were highly overrepresented by polycomb target genes and involved in developmental, cell adhesion, and cell signaling processes. The presence of non-random methylation events in in vitro immortalized T-cell cultures and diagnostic T-ALL samples indicates altered methylation of CpG sites with a possible role in malignant hematopoiesis. Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.

  16. Dicationic and zwitterionic catalysts for the amine-initiated, immortal ring-opening polymerisation of rac-lactide: facile synthesis of amine-terminated, highly heterotactic PLA

    NARCIS (Netherlands)

    Clark, L.; Cushion, M.G.; Dyer, H.E.; Schwarz, A.D.; Duchateau, R.; Mountford, P.

    2010-01-01

    Dicationic, zwitterionic and conventional yttrium compounds act as catalysts for the primary or secondary amine-initiated immortal ROP of rac-lactide; amine-terminated, highly heterotactic poly(rac-lactides) with narrow polydispersities and well-controlled molecular weights are prepared in this

  17. Can widely used cell type markers predict the suitability of immortalized or primary mammary epithelial cell models?

    Directory of Open Access Journals (Sweden)

    Edgar Corneille Ontsouka

    Full Text Available BACKGROUND: Mammary cell cultures are convenient tools for in vitro studies of mammary gland biology. However, the heterogeneity of mammary cell types, e.g., glandular milk secretory epithelial or myoepithelial cells, often complicates the interpretation of cell-based data. The present study was undertaken to determine the relevance of bovine primary mammary epithelial cells isolated from American Holstein (bMEC US or Swiss Holstein-Friesian (bMEC CH cows, and of primary bovine mammary alveolar epithelial cells stably transfected with simian virus-40 (SV-40 large T-antigen (MAC-T for in vitro analyses. This was evaluated by testing their expression pattern of cytokeratin (CK 7, 18, 19, vimentin, and α-smooth muscle actin (α-SMA. RESULTS: The expression of the listed markers was assessed using real-time quantitative PCR, flow cytometry and immunofluorescence microscopy. Characteristic markers of the mesenchymal (vimentin, myoepithelial (α-SMA and glandular secretory cells (CKs showed differential expression among the studied cell cultures, partly depending on the analytical method used. The relative mRNA expression of vimentin, CK7 and CK19, respectively, was lower (P < 0.05 in immortalized than in primary mammary cell cultures. The stain index (based on flow cytometry of CK7 and CK19 protein was lower (P < 0.05 in MAC-T than in bMECs, while the expression of α-SMA and CK18 showed an inverse pattern. Immunofluorescence microscopy analysis mostly confirmed the mRNA data, while partly disagreed with flow cytometry data (e.g., vimentin level in MAC-T. The differential expression of CK7 and CK19 allowed discriminating between immortal and primary mammary cultures. CONCLUSIONS: The expression of the selected widely used cell type markers in primary and immortalized MEC cells did not allow a clear preference between these two cell models for in vitro analyses studying aspects of milk composition. All tested cell models exhibited to a variable

  18. Cytogenetic and molecular genetic characterization of immortalized human ovarian surface epithelial cell lines: consistent loss of chromosome 13 and amplification of chromosome 20.

    Science.gov (United States)

    Jin, Yuesheng; Zhang, Hao; Tsao, Sai Wah; Jin, Charlotte; Lv, Mei; Strömbeck, Bodil; Wiegant, Joop; Wan, Thomas Shek Kong; Yuen, Po Wing; Kwong, Yok-Lam

    2004-01-01

    This study aimed at identifying the genetic events involved in immortalization of ovarian epithelial cells, which might be important steps in ovarian carcinogenesis. The genetic profiles of five human ovarian surface epithelial (HOSE) cell lines immortalized by retroviral transfection of the human papillomavirus (HPV) E6/E7 genes were thoroughly characterized by chromosome banding and fluorescence in situ hybridization (FISH), at various passages pre- and post-crisis. In pre-crisis, most cells had simple, non-clonal karyotypic changes. Telomere association was the commonest aberration, suggesting that tolermase dysfunction might be an important genetic event leading to cellular crisis. After immortalization post-crisis, however, the karyotypic patterns were non-random. Loss of genetic materials was a characteristic feature. The commonest numerical aberrations were -13, -14, -16, -17, -18, and +5. Among them, loss of chromosome 13 was common change observed in all lines. The only recurrent structural aberration was homogeneously staining regions (hsr) observed in three lines. FISH and combined binary ratio labeling (COBRA)-FISH showed in two cases that the hsrs were derived from chromosome 20. Clonal evolution was observed in four of the lines. In one line, hsr was the only change shared by all subclones, suggesting that it might be a primary event in cell immortalization. The results of the present study suggested that loss of chromosome 13 and the amplification of chromosome 20 might be early genetic events involved in ovarian cell immortalization, and might be useful targets for the study of genomic aberrations in ovarian carcinogenesis.

  19. Inactivation of p16INK4a, with retention of pRB and p53/p21cip1 function, in human MRC5 fibroblasts that overcome a telomere-independent crisis during immortalization.

    Science.gov (United States)

    Taylor, Lisa M; James, Alexander; Schuller, Christine E; Brce, Jesena; Lock, Richard B; Mackenzie, Karen L

    2004-10-15

    Recent investigations, including our own, have shown that specific strains of fibroblasts expressing telomerase reverse transcriptase (hTERT) have an extended lifespan, but are not immortal. We previously demonstrated that hTERT-transduced MRC5 fetal lung fibroblasts (MRC5hTERTs) bypassed senescence but eventually succumbed to a second mortality barrier (crisis). In the present study, 67 MRC5hTERT clones were established by limiting dilution of a mass culture. Whereas 39/67 clones had an extended lifespan, all 39 extended lifespan clones underwent crisis. 11 of 39 clones escaped crisis and were immortalized. There was no apparent relationship between the fate of clones at crisis and the level of telomerase activity. Telomeres were hyperextended in the majority of the clones analyzed. There was no difference in telomere length of pre-crisis compared with post-crisis and immortal clones, indicating that hyperextended telomeres were conducive for immortalization and confirming that crisis was independent of telomere length. Immortalization of MRC5hTERT cells was associated with repression of the cyclin-dependent kinase inhibitor p16INK4a and up-regulation of pRB. However, the regulation of pRB phosphorylation and the response of the p53/p21cip1/waf1 pathway were normal in immortal cells subject to genotoxic stress. Overexpression of oncogenic ras failed to de-repress p16INK4a in immortal cells. Furthermore, expression of ras enforced senescent-like growth arrest in p16INK4a-positive, but not p16INK4a-negative MRC5hTERT cells. Immortal cells expressing ras formed small, infrequent colonies in soft agarose, but were non-tumorigenic. Overall, these results implicate the inactivation of p16INK4a as a critical event for overcoming telomere-independent crisis, immortalizing MRC5 fibroblasts and overcoming ras-induced premature senescence.

  20. A telomerase immortalized human proximal tubule cell line with a truncation mutation (Q4004X in polycystin-1.

    Directory of Open Access Journals (Sweden)

    Brittney-Shea Herbert

    Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is associated with a variety of cellular phenotypes in renal epithelial cells. Cystic epithelia are secretory as opposed to absorptive, have higher proliferation rates in cell culture and have some characteristics of epithelial to mesenchymal transitions. In this communication we describe a telomerase immortalized cell line that expresses proximal tubule markers and is derived from renal cysts of an ADPKD kidney. These cells have a single detectable truncating mutation (Q4004X in polycystin-1. These cells make normal appearing but shorter cilia and fail to assemble polycystin-1 in the cilia, and less uncleaved polycystin-1 in membrane fractions. This cell line has been maintained in continuous passage for over 35 passages without going into senescence. Nephron segment specific markers suggest a proximal tubule origin for these cells and the cell line will be useful to study mechanistic details of cyst formation in proximal tubule cells.

  1. Man should not let death attain the dominion of his thoughts: An Essay on Subjectivity, Self-Preservation and Immortality

    Directory of Open Access Journals (Sweden)

    Kasper Lysemose

    2010-12-01

    Full Text Available Mortality seems to have no place in the theories on subjectivity in Kant and Husserl. It is suggested that this entente cordiale is an expression of the shared principle at the heart of their philosophy, i.e. the principle of selfpreservation. Self-preservation is a principle that in a certain sense excludes mortality. It is argued that the primary sense of this exclusion is not theoretical but practical. Kant and Husserl are both endorsing the imperative that man should not let death attain the dominion of his thoughts (cf. Mann 1976, 600. The positive correlate to this is to be found in the demand that man should think of himself as if he was immortal. With special regard to Husserl the predicament that accompanies his relentless attempt to fulfill this demand is described as a sluice through which anthropology threatens to flow into the phenomenological enterprise.

  2. Myth about immortality in the contemporary pop culture: A case study about Toše Proeski

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    Stevanović Lada

    2013-01-01

    Full Text Available This paper explores the intersection of death and ideology in the sphere of popular culture, as exemplified by the afterlife destiny of Toše Proeski, a Macedonian pop singer whose huge popularity continued even after his death. His sudden, untimely death in his twenties had exploded as huge news, preoccupying all sorts of media. What I am interested in this paper is what has happened afterwards. In which way his popularity and his afterlife continue? Can we identify some kind of pop hero cult here, and is it possible to recognize common elements, or even a pattern according to which (newborn stars develop an afterlife destiny? Can we use this opportunity to discuss immortality myths? Do pop stars get monuments or are these reserved just for national heroes?

  3. Sensitive Tumorigenic Potential Evaluation of Adult Human Multipotent Neural Cells Immortalized by hTERT Gene Transduction.

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    Kee Hang Lee

    Full Text Available Stem cells and therapeutic genes are emerging as a new therapeutic approach to treat various neurodegenerative diseases with few effective treatment options. However, potential formation of tumors by stem cells has hampered their clinical application. Moreover, adequate preclinical platforms to precisely test tumorigenic potential of stem cells are controversial. In this study, we compared the sensitivity of various animal models for in vivo stem cell tumorigenicity testing to identify the most sensitive platform. Then, tumorigenic potential of adult human multipotent neural cells (ahMNCs immortalized by the human telomerase reverse transcriptase (hTERT gene was examined as a stem cell model with therapeutic genes. When human glioblastoma (GBM cells were injected into adult (4-6-week-old Balb/c-nu, adult NOD/SCID, adult NOG, or neonate (1-2-week-old NOG mice, the neonate NOG mice showed significantly faster tumorigenesis than that of the other groups regardless of intracranial or subcutaneous injection route. Two kinds of ahMNCs (682TL and 779TL were primary cultured from surgical samples of patients with temporal lobe epilepsy. Although the ahMNCs were immortalized by lentiviral hTERT gene delivery (hTERT-682TL and hTERT-779TL, they did not form any detectable masses, even in the most sensitive neonate NOG mouse platform. Moreover, the hTERT-ahMNCs had no gross chromosomal abnormalities on a karyotype analysis. Taken together, our data suggest that neonate NOG mice could be a sensitive animal platform to test tumorigenic potential of stem cell therapeutics and that ahMNCs could be a genetically stable stem cell source with little tumorigenic activity to develop regenerative treatments for neurodegenerative diseases.

  4. Krása a nesmrteľnosť. O plodení u Platóna a Shakespeara (Beauty and Immortality. On Procreation in Plato and Shakespeare)

    OpenAIRE

    Anton Vydra

    2007-01-01

    There are two moments referred in this essay: (1) A human being, which desires for immortality, desires for to be alive in his child or in an artwork. (2) Full human being’s desire is related for beauty. Is a beauty the same thing as immortality? How looks the relation between them? Shakespeare’s Sonnets begin with the challenge to his friend to procreate the offspring, because this is a way for immortality of the friend’s beauty. And if it is not a child, than verse refused him before the de...

  5. Establishment of a luciferase assay-based screening system: Fumitremorgin C selectively inhibits cellular proliferation of immortalized astrocytes expressing an active form of AKT

    International Nuclear Information System (INIS)

    Wang Lei; Sasai, Ken; Akagi, Tsuyoshi; Tanaka, Shinya

    2008-01-01

    The AKT pathway is frequently activated in glioblastoma, and as such, inhibitors of this pathway could prove very useful as anti-glioblastoma therapies. Here we established immortalized astrocytes expressing Renilla luciferase as well as those expressing both an active form of AKT and firefly luciferase. Since both luciferase activities represent the numbers of corresponding cell lines, novel inhibitors of the AKT pathway can be identified by treating co-cultures containing the two types of luciferase-expressing cells with individual compounds. Indeed, such a screening system succeeded in identifying fumitremorgin C as an efficient inhibitor of the AKT pathway, which was further confirmed by the ability of fumitremorgin C to selectively inhibit the growth of immortalized astrocytes expressing an active form of AKT. The present study proposes a broadly applicable approach for identifying therapeutic agents that target the pathways and/or molecules responsible for cancer development

  6. “Spare me the endurance of endless time”:the influence of Christian and Buddhist ethics on the view of immortality in the TV series Doctor Who

    OpenAIRE

    Vuolteenaho, L. (Leena)

    2013-01-01

    Abstract This thesis examines the influence of Christian and Buddhist ethics on British science-fiction TV series Doctor Who, by looking at how the series’ depiction of immortality as an ethical issue reflects the views of Christianity and Buddhism. The study was conducted as qualitative, using as primary data a selection of episodes from which observations were made, with reference to theoretical background based on litera...

  7. Large-scale analysis of protein expression changes in human keratinocytes immortalized by human papilloma virus type 16 E6 and E7 oncogenes

    Directory of Open Access Journals (Sweden)

    Arnouk Hilal

    2009-08-01

    Full Text Available Abstract Background Infection with high-risk type human papilloma viruses (HPVs is associated with cervical carcinomas and with a subset of head and neck squamous cell carcinomas. Viral E6 and E7 oncogenes cooperate to achieve cell immortalization by a mechanism that is not yet fully understood. Here, human keratinocytes were immortalized by long-term expression of HPV type 16 E6 or E7 oncoproteins, or both. Proteomic profiling was used to compare expression levels for 741 discrete protein features. Results Six replicate measurements were performed for each group using two-dimensional difference gel electrophoresis (2D-DIGE. The median within-group coefficient of variation was 19–21%. Significance of between-group differences was tested based on Significance Analysis of Microarray and fold change. Expression of 170 (23% of the protein features changed significantly in immortalized cells compared to primary keratinocytes. Most of these changes were qualitatively similar in cells immortalized by E6, E7, or E6/7 expression, indicating convergence on a common phenotype, but fifteen proteins (~2% were outliers in this regulatory pattern. Ten demonstrated opposite regulation in E6- and E7-expressing cells, including the cell cycle regulator p16INK4a; the carbohydrate binding protein Galectin-7; two differentially migrating forms of the intermediate filament protein Cytokeratin-7; HSPA1A (Hsp70-1; and five unidentified proteins. Five others had a pattern of expression that suggested cooperativity between the co-expressed oncoproteins. Two of these were identified as forms of the small heat shock protein HSPB1 (Hsp27. Conclusion This large-scale analysis provides a framework for understanding the cooperation between E6 and E7 oncoproteins in HPV-driven carcinogenesis.

  8. An In Vitro System Comprising Immortalized Hypothalamic Neuronal Cells (GT1?7 Cells) for Evaluation of the Neuroendocrine Effects of Essential Oils

    OpenAIRE

    Mizuno, Dai; Konoha-Mizuno, Keiko; Mori, Miwako; Yamazaki, Kentaro; Haneda, Toshihiro; Koyama, Hironari; Kawahara, Masahiro

    2015-01-01

    Aromatherapy and plant-based essential oils are widely used as complementary and alternative therapies for symptoms including anxiety. Furthermore, it was reportedly effective for the care of several diseases such as Alzheimer’s disease and depressive illness. To investigate the pharmacological effects of essential oils, we developed an in vitro assay system using immortalized hypothalamic neuronal cells (GT1–7 cells). In this study, we evaluated the effects of essential oils on neuronal deat...

  9. A gene expression signature classifying telomerase and ALT immortalization reveals an hTERT regulatory network and suggests a mesenchymal stem cell origin for ALT

    DEFF Research Database (Denmark)

    Lafferty-Whyte, K; Cairney, C J; Will, M B

    2009-01-01

    Telomere length is maintained by two known mechanisms, the activation of telomerase or alternative lengthening of telomeres (ALT). The molecular mechanisms regulating the ALT phenotype are poorly understood and it is unknown how the decision of which pathway to activate is made at the cellular le......TERT in different tumour types and normal tissues. We also show evidence to suggest a novel mesenchymal stem cell origin for ALT immortalization in cell lines and mesenchymal tissues....

  10. Characterization of a novel telomerase-immortalized human endometrial stromal cell line, St-T1b

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    Brosens Jan J

    2009-07-01

    Full Text Available Abstract Background Coordinated differentiation of the endometrial compartments in the second half of the menstrual cycle is a prerequisite for the establishment of pregnancy. Endometrial stromal cells (ESC decidualize under the influence of ovarian progesterone to accommodate implantation of the blastocyst and support establishment of the placenta. Studies into the mechanisms of decidualization are often hampered by the lack of primary ESC. Here we describe a novel immortalized human ESC line. Methods Primary ESC were immortalized by the transduction of telomerase. The resultant cell line, termed St-T1b, was characterized for its morphological and biochemical properties by immunocytochemistry, RT-PCR and immunoblotting. Its progestational response was tested using progesterone and medroxyprogesterone acetate with and without 8-Br-cAMP, an established inducer of decidualization in vitro. Results St-T1b were positive for the fibroblast markers vimentin and CD90 and negative for the epithelial marker cytokeratin-7. They acquired a decidual phenotype indistinguishable from primary ESC in response to cAMP stimulation. The decidual response was characterized by transcriptional activation of marker genes, such as PRL, IGFBP1, and FOXO1, and enhanced protein levels of the tumor suppressor p53 and the metastasis suppressor KAI1 (CD82. Progestins alone had no effect on St-T1b cells, but medroxyprogesterone acetate greatly enhanced the cAMP-stimulated expression of IGFBP-1 after 3 and 7 days. Progesterone, albeit more weakly, also augmented the cAMP-induced IGFBP-1 production but only after 7 days of treatment. The cell line remained stable in continuous culture for more than 150 passages. Conclusion St-T1b express the appropriate phenotypic ESC markers and their decidual response closely mimics that of primary cultures. Decidualization is efficiently induced by cAMP analog and enhanced by medroxyprogesterone acetate, and, to a lesser extent, by natural

  11. The combined effects of irradiation and herpes simplex virus type 1 infection on an immortal gingival cell line

    Science.gov (United States)

    2014-01-01

    Background Oral mucosa is frequently exposed to Herpes simplex virus type 1 (HSV-1) infection and irradiation due to dental radiography. During radiotherapy for oral cancer, the surrounding clinically normal tissues are also irradiated. This prompted us to study the effects of HSV-1 infection and irradiation on viability and apoptosis of oral epithelial cells. Methods Immortal gingival keratinocyte (HMK) cells were infected with HSV-1 at a low multiplicity of infection (MOI) and irradiated with 2 Gy 24 hours post infection. The cells were then harvested at 24, 72 and 144 hours post irradiation for viability assays and qRT-PCR analyses for the apoptosis-related genes caspases 3, 8, and 9, bcl-2, NFκB1, and viral gene VP16. Mann–Whitney U-test was used for statistical calculations. Results Irradiation improved the cell viability at 144 hours post irradiation (P = 0.05), which was further improved by HSV-1 infection at MOI of 0.00001 (P = 0.05). Simultaneously, the combined effects of infection at MOI of 0.0001 and irradiation resulted in upregulation in NFκB1 (P = 0.05). The combined effects of irradiation and HSV infection also significantly downregulated the expression of caspases 3, 8, and 9 at 144 hours (P = 0.05) whereas caspase 3 and 8 significantly upregulated in non-irradiated, HSV-infected cells as compared to uninfected controls (P = 0.05). Infection with 0.0001 MOI downregulated bcl-2 in non-irradiated cells but was upregulated by 27% after irradiation when compared to non-irradiated infected cells (P = 0.05). Irradiation had no effect on HSV-1 shedding or HSV gene expression at 144 hours. Conclusions HSV-1 infection may improve the viability of immortal cells after irradiation. The effect might be related to inhibition of apoptosis. PMID:25005804

  12. The role of p38 MAP kinase and c-Jun N-terminal protein kinase signaling in the differentiation and apoptosis of immortalized neural stem cells

    International Nuclear Information System (INIS)

    Yang, Se-Ran; Cho, Sung-Dae; Ahn, Nam-Shik; Jung, Ji-Won; Park, Joon-Suk; Jo, Eun-Hye; Hwang, Jae-Woong; Kim, Sung-Hoon; Lee, Bong-Hee; Kang, Kyung-Sun; Lee, Yong-Soon

    2005-01-01

    The two distinct members of the mitogen-activated protein (MAP) kinase family c-Jun N-terminal protein kinase (JNK) and p38 MAP kinase, play an important role in central nervous system (CNS) development and differentiation. However, their role and functions are not completely understood in CNS. To facilitate in vitro study, we have established an immortal stem cell line using SV40 from fetal rat embryonic day 17. In these cells, MAP kinase inhibitors (SP600125, SB202190, and PD98059) were treated for 1, 24, 48, and 72 h to examine the roles of protein kinases. Early inhibition of JNK did not alter phenotypic or morphological changes of immortalized cells, however overexpression of Bax and decrease of phosphorylated AKT was observed. The prolonged inhibition of JNK induced polyploidization of immortalized cells, and resulted in differentiation and inhibition of cell proliferation. Moreover, JNK and p38 MAP kinase but not ERK1/2 was activated, and p21, p53, and Bax were overexpressed by prolonged inhibition of JNK. These results indicate that JNK and p38 MAP kinase could play dual roles on cell survival and apoptosis. Furthermore, this established cell line could facilitate study of the role of JNK and p38 MAP kinase on CNS development or differentiation/apoptosis

  13. Specific regulation of point-mutated K-ras-immortalized cell proliferation by a photodynamic antisense strategy.

    Science.gov (United States)

    Higuchi, Maiko; Yamayoshi, Asako; Kato, Kiyoko; Kobori, Akio; Wake, Norio; Murakami, Akira

    2010-02-01

    It has been reported that point mutations in genes are responsible for various cancers, and the selective regulation of gene expression is an important factor in developing new types of anticancer drugs. To develop effective drugs for the regulation of point-mutated genes, we focused on photoreactive antisense oligonucleotides. Previously, we reported that photoreactive oligonucleotides containing 2'-O-psoralenylmethoxyethyl adenosine (2'-Ps-eom) showed drastic photoreactivity in a strictly sequence-specific manner. Here, we demonstrated the specific gene regulatory effects of 2'-Ps-eom on [(12)Val]K-ras mutant (GGT --> GTT). Photo-cross-linking between target mRNAs and 2'-Ps-eom was sequence-specific, and the effect was UVA irradiation-dependent. Furthermore, 2'-Ps-eom was able to inhibit K-ras-immortalized cell proliferation (K12V) but not Vco cells that have the wild-type K-ras gene. These results suggest that the 2'-Ps-eom will be a powerful nucleic acid drug to inhibit the expression of disease-causing point mutation genes, and has great therapeutic potential in the treatment of cancer.

  14. Ski protein levels increase during in vitro progression of HPV16-immortalized human keratinocytes and in cervical cancer

    International Nuclear Information System (INIS)

    Chen, Yi; Pirisi, Lucia; Creek, Kim E.

    2013-01-01

    We compared the levels of the Ski oncoprotein, an inhibitor of transforming growth factor-beta (TGF-β) signaling, in normal human keratinocytes (HKc), HPV16 immortalized HKc (HKc/HPV16), and differentiation resistant HKc/HPV16 (HKc/DR) in the absence and presence of TGF-β. Steady-state Ski protein levels increased in HKc/HPV16 and even further in HKc/DR, compared to HKc. TGF-β treatment of HKc, HKc/HPV16, and HKc/DR dramatically decreased Ski. TGF-β-induced Ski degradation was delayed in HKc/DR. Ski and phospho-Ski protein levels are cell cycle dependent with maximal Ski expression and localization to centrosomes and mitotic spindles during G2/M. ShRNA knock down of Ski in HKc/DR inhibited cell proliferation. More intense nuclear and cytoplasmic Ski staining and altered Ski localization were found in cervical cancer samples compared to adjacent normal tissue in a cervical cancer tissue array. Overall, these studies demonstrate altered Ski protein levels, degradation and localization in HPV16-transformed human keratinocytes and in cervical cancer. - Highlights: • Ski oncoprotein levels increase during progression of HPV16-transformed cells. • Ski and phospho-Ski protein levels are cell cycle dependent. • Ski knock-down in HPV16-transformed keratinocytes inhibited cell proliferation. • Cervical cancer samples overexpress Ski

  15. Induction of chromosomal aberrations in human primary fibroblasts and immortalized cancer cells exposed to extremely-low-frequency electromagnetic fields

    International Nuclear Information System (INIS)

    Seyyedi, S. S.; Mozdarani, H.; Rezaei Tavirani, M.; Heydari, S.

    2010-01-01

    Rapidly increasing possibilities of exposure to environmental extremely low-frequency electromagnetic fields have become a topic of worldwide investigation. Epidemiological and laboratory studies suggest that exposure to extremely low-frequency electromagnetic fields may increase cancer risk therefore assessment of chromosomal damage in various cell lines might be of predictive value for future risk estimation. Materials and Methods: Primary cultures of fibroblasts from human skin biopsy were exposed to continuous extremely low-frequency electromagnetic fields (3, 50 and 60 Hz, sinusoidal, 3h, and 4 m T). Also immortalized cell lines, SW480, MCF-7 and 1321N1 were exposed to continuous extremely low-frequency electromagnetic fields (50 Hz, sinusoidal, 3 h, 4 m T). Metaphase plates Were prepared according to standard methods and stained in 5% Giemsa solution. Chromosomal aberrations of both chromosome and chromatid types were scored to evaluate the effects of extremely low-frequency electromagnetic fields on primary or established cell lines. Results: Results indicate that by increasing the frequency of extremely low-frequency electromagnetic fields, chromosomal aberrations were increased up to 7-fold above background levels in primary human fibroblast cells. In addition, continuous exposure to a 50 Hz electromagnetic field led to a significant increase in chromosomal aberrations in SW480, MCF-7 and 1321N1 cell lines compared to sham control. Conclusion: Results obtained indicate that extremely low-frequency electromagnetic fields has the potential for induction of chromosomal aberrations in all cell types.

  16. Aneuploidy in immortalized human mesenchymal stem cells with non-random loss of chromosome 13 in culture.

    Science.gov (United States)

    Takeuchi, Masao; Takeuchi, Kikuko; Ozawa, Yutaka; Kohara, Akihiro; Mizusawa, Hiroshi

    2009-01-01

    Aneuploidy (an abnormal number of chromosomes) is commonly observed in most human cancer cells, highlighting the need to examine chromosomal instability in tumorigenesis. Previously, the immortalized human mesenchymal stem cell line UE6E7T-3 was shown to undergo a preferential loss of one copy of chromosome 13 after prolonged culture. Here, the loss of chromosome 13 was found to be caused by chromosome missegregation during mitosis, which involved unequal segregation, exclusion of the misaligned chromosome 13 on the metaphase plate, and trapping of chromosome 13 in the midbody region, as observed by fluorescence in situ hybridization. Near-diploid aneuploidy, not tetraploidy, was the direct result. The loss of chromosome 13 was non-random, and was detected by analysis of microsatellites and single nucleotide polymorphism-based loss of heterozygosity (LOH). Of the five microsatellite loci on chromosome 13, four loci showed microsatellite instability at an early stage in culture, and LOH was apparent at a late stage in culture. These results suggest that the microsatellite mutations cause changes in centromere integrity provoking loss of this chromosome in the UE6E7T-3 cell line. Thus, these results support the use of this cell line as a useful model for understanding the mechanism of aneuploid formation in cell cultures.

  17. A contemplation in negation and emphasizes of outstanding philosophers of Tehran philosophy school in immortality of subject in substantial movement.

    Directory of Open Access Journals (Sweden)

    mohamad khosravi farsani

    2015-03-01

    Full Text Available Agha Ali and Jelveh ,two of outstanding of Tehran philosophy school, have reconsidered Sandra's opinions in two opposite sides. Agha Ali is the claimant of negation and ambiguity in most of Sandra's opinions while emphasizing on transcendent theosophy foundations ,and he tries to make these ambiguities clear .However , Jelveh follows Avicenna's way and has the idea of criticizing Sandra .This article has chosen the problem Of immortality of subject in substantial movement between all debates of these two philosophers of the same age.in this essay we are going to survey Agha Ali's claims in his new explantation in one hand ,and survey and criticize the new explanation of Jelveh in negation Of substantial movement .One of the consequences of surveying and criticizing these two philosophers is that we recognize Agha Ali has succeeded in making Sadra's opinions clear by presenting a new explanation of substantial movement subject. However ,Jelveh has merged Sadra's opinions with Avicenna's instead of debilitating Sadra's opinions and stabilizing Avicenna's opinions.

  18. Evaluating the immortal strand hypothesis in cancer stem cells: symmetric/self-renewal as the relevant surrogate marker of tumorigenicity.

    Science.gov (United States)

    Winquist, Raymond J; Hall, Amy B; Eustace, Brenda K; Furey, Brinley F

    2014-09-15

    Stem cells subserve repair functions for the lifetime of the organism but, as a consequence of this responsibility, are candidate cells for accumulating numerous genetic and/or epigenetic aberrations leading to malignant transformation. However, given the importance of this guardian role, stem cells likely harbor some process for maintaining their precious genetic code such as non-random segregation of chromatid strands as predicted by the Immortal Strand Hypothesis (ISH). Discerning such non-random chromosomal segregation and asymmetric cell division in normal or cancer stem cells has been complicated by methodological shortcomings but also by differing division kinetics amongst tissues and the likelihood that both asymmetric and symmetric cell divisions, dictated by local extrinsic factors, are operant in these cells. Recent data suggest that cancer stem cells demonstrate a higher incidence of symmetric versus asymmetric cell division with both daughter cells retaining self-renewal characteristics, a profile which may underlie poorly differentiated morphology and marked clonal diversity in tumors. Pathways and targets are beginning to emerge which may provide opportunities for preventing such a predilection in cancer stem cells and that will hopefully translate into new classes of chemotherapeutics in oncology. Thus, although the existence of the ISH remains controversial, the shift of cell division dynamics to symmetric random chromosome segregation/self-renewal, which would negate any likelihood of template strand retention, appears to be a surrogate marker for the presence of highly malignant tumorigenic cell populations. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs

    Directory of Open Access Journals (Sweden)

    Choo Andre

    2011-04-01

    Full Text Available Abstract Background Exosomes or secreted bi-lipid vesicles from human ESC-derived mesenchymal stem cells (hESC-MSCs have been shown to reduce myocardial ischemia/reperfusion injury in animal models. However, as hESC-MSCs are not infinitely expansible, large scale production of these exosomes would require replenishment of hESC-MSC through derivation from hESCs and incur recurring costs for testing and validation of each new batch. Our aim was therefore to investigate if MYC immortalization of hESC-MSC would circumvent this constraint without compromising the production of therapeutically efficacious exosomes. Methods The hESC-MSCs were transfected by lentivirus carrying a MYC gene. The transformed cells were analyzed for MYC transgene integration, transcript and protein levels, and surface markers, rate of cell cycling, telomerase activity, karyotype, genome-wide gene expression and differentiation potential. The exosomes were isolated by HPLC fractionation and tested in a mouse model of myocardial ischemia/reperfusion injury, and infarct sizes were further assessed by using Evans' blue dye injection and TTC staining. Results MYC-transformed MSCs largely resembled the parental hESC-MSCs with major differences being reduced plastic adherence, faster growth, failure to senesce, increased MYC protein expression, and loss of in vitro adipogenic potential that technically rendered the transformed cells as non-MSCs. Unexpectedly, exosomes from MYC-transformed MSCs were able to reduce relative infarct size in a mouse model of myocardial ischemia/reperfusion injury indicating that the capacity for producing therapeutic exosomes was preserved. Conclusion Our results demonstrated that MYC transformation is a practical strategy in ensuring an infinite supply of cells for the production of exosomes in the milligram range as either therapeutic agents or delivery vehicles. In addition, the increased proliferative rate by MYC transformation reduces the time

  20. Establishment of c-myc-immortalized Kupffer cell line from a C57BL/6 mouse strain

    Directory of Open Access Journals (Sweden)

    Hiroshi Kitani

    2014-01-01

    Full Text Available We recently demonstrated in several mammalian species, a novel procedure to obtain liver-macrophages (Kupffer cells in sufficient numbers and purity using a mixed primary culture of hepatocytes. In this study, we applied this method to the C57BL/6 mouse liver and established an immortalized Kupffer cell line from this mouse strain. The hepatocytes from the C57BL/6 adult mouse liver were isolated by a two-step collagenase perfusion method and cultured in T25 culture flasks. Similar to our previous studies, the mouse hepatocytes progressively changed their morphology into a fibroblastic appearance after a few days of culture. After 7–10 days of culture, Kupffer-like cells, which were contaminants in the hepatocyte fraction at the start of the culture, actively proliferated on the mixed fibroblastic cell sheet. At this stage, a retroviral vector containing the human c-myc oncogene and neomycin resistance gene was introduced into the mixed culture. Gentle shaking of the culture flask, followed by the transfer and brief incubation of the culture supernatant, resulted in a quick and selective adhesion of Kupffer cells to a plastic dish surface. After selection with G418 and cloning by limiting dilutions, a clonal cell line (KUP5 was established. KUP5 cells displayed typical macrophage morphology and were stably passaged at 4–5 days intervals for more than 5 months, with a population doubling time of 19 h. KUP5 cells are immunocytochemically positive for mouse macrophage markers, such as Mac-1, F4/80. KUP5 cells exhibited substantial phagocytosis of polystyrene microbeads and the release of inflammatory cytokines upon lipopolysaccharide stimulation. Taken together, KUP5 cells provide a useful means to study the function of Kupffer cells in vitro.

  1. Telomerase-immortalized non-malignant human prostate epithelial cells retain the properties of multipotent stem cells

    International Nuclear Information System (INIS)

    Li Hongzhen; Zhou Jianjun; Miki, Jun; Furusato, Bungo; Gu Yongpeng; Srivastava, Shiv; McLeod, David G.; Vogel, Jonathan C.; Rhim, Johng S.

    2008-01-01

    Understanding prostate stem cells may provide insight into the origin of prostate cancer. Primary cells have been cultured from human prostate tissue but they usually survive only 15-20 population doublings before undergoing senescence. We report here that RC-170N/h/clone 7 cells, a clonal cell line from hTERT-immortalized primary non-malignant tissue-derived human prostate epithelial cell line (RC170N/h), retain multipotent stem cell properties. The RC-170N/h/clone 7 cells expressed a human embryonic stem cell marker, Oct-4, and potential prostate epithelial stem cell markers, CD133, integrin α2β1 hi and CD44. The RC-170N/h/clone 7 cells proliferated in KGM and Dulbecco's Modified Eagle Medium with 10% fetal bovine serum and 5 μg/ml insulin (DMEM + 10% FBS + Ins.) medium, and differentiated into epithelial stem cells that expressed epithelial cell markers, including CK5/14, CD44, p63 and cytokeratin 18 (CK18); as well as the mesenchymal cell markers, vimentin, desmin; the neuron and neuroendocrine cell marker, chromogranin A. Furthermore the RC170 N/h/clone 7 cells differentiated into multi tissues when transplanted into the sub-renal capsule and subcutaneously of NOD-SCID mice. The results indicate that RC170N/h/clone 7 cells retain the properties of multipotent stem cells and will be useful as a novel cell model for studying the mechanisms of human prostate stem cell differentiation and transformation

  2. Balancing Benefits and Risks of Immortal Data: Participants' Views of Open Consent in the Personal Genome Project.

    Science.gov (United States)

    Zarate, Oscar A; Brody, Julia Green; Brown, Phil; Ramirez-Andreotta, Mónica D; Perovich, Laura; Matz, Jacob

    2016-01-01

    An individual's health, genetic, or environmental-exposure data, placed in an online repository, creates a valuable shared resource that can accelerate biomedical research and even open opportunities for crowd-sourcing discoveries by members of the public. But these data become "immortalized" in ways that may create lasting risk as well as benefit. Once shared on the Internet, the data are difficult or impossible to redact, and identities may be revealed by a process called data linkage, in which online data sets are matched to each other. Reidentification (re-ID), the process of associating an individual's name with data that were considered deidentified, poses risks such as insurance or employment discrimination, social stigma, and breach of the promises often made in informed-consent documents. At the same time, re-ID poses risks to researchers and indeed to the future of science, should re-ID end up undermining the trust and participation of potential research participants. The ethical challenges of online data sharing are heightened as so-called big data becomes an increasingly important research tool and driver of new research structures. Big data is shifting research to include large numbers of researchers and institutions as well as large numbers of participants providing diverse types of data, so the participants' consent relationship is no longer with a person or even a research institution. In addition, consent is further transformed because big data analysis often begins with descriptive inquiry and generation of a hypothesis, and the research questions cannot be clearly defined at the outset and may be unforeseeable over the long term. In this article, we consider how expanded data sharing poses new challenges, illustrated by genomics and the transition to new models of consent. We draw on the experiences of participants in an open data platform-the Personal Genome Project-to allow study participants to contribute their voices to inform ethical consent

  3. MicroRNA-4739 regulates osteogenic and adipocytic differentiation of immortalized human bone marrow stromal cells via targeting LRP3

    Directory of Open Access Journals (Sweden)

    Mona Elsafadi

    2017-04-01

    Full Text Available Understanding the regulatory networks underlying lineage differentiation and fate determination of human bone marrow stromal cells (hBMSC is a prerequisite for their therapeutic use. The goal of the current study was to unravel the novel role of the low-density lipoprotein receptor-related protein 3 (LRP3 in regulating the osteogenic and adipogenic differentiation of immortalized hBMSCs. Gene expression profiling revealed significantly higher LRP3 levels in the highly osteogenic hBMSC clone imCL1 than in the less osteogenic clone imCL2, as well as a significant upregulation of LRP3 during the osteogenic induction of the imCL1 clone. Data from functional and gene expression assays demonstrated the role of LRP3 as a molecular switch promoting hBMSC lineage differentiation into osteoblasts and inhibiting differentiation into adipocytes. Interestingly, microRNA (miRNA expression profiling identified miR-4739 as the most under-represented miRNA (−36.11 fold in imCL1 compared to imCL2. The TargetScan prediction algorithm, combined with functional and biochemical assays, identified LRP3 mRNA as a novel target of miR-4739, with a single potential binding site for miR-4739 located in the LRP3 3′ UTR. Regulation of LRP3 expression by miR-4739 was subsequently confirmed by qRT-PCR, western blotting, and luciferase assays. Over-expression of miR-4739 mimicked the effects of LRP3 knockdown on promoting adipogenic and suppressing osteogenic differentiation of hBMSCs. Hence, we report for the first time a novel biological role for the LRP3/hsa-miR-4739 axis in balancing osteogenic and adipocytic differentiation of hBMSCs. Our data support the potential utilization of miRNA-based therapies in regenerative medicine.

  4. Hepatocyte nuclear factor 4A improves hepatic differentiation of immortalized adult human hepatocytes and improves liver function and survival.

    Science.gov (United States)

    Hang, Hua-Lian; Liu, Xin-Yu; Wang, Hai-Tian; Xu, Ning; Bian, Jian-Min; Zhang, Jian-Jun; Xia, Lei; Xia, Qiang

    2017-11-15

    Immortalized human hepatocytes (IHH) could provide an unlimited supply of hepatocytes, but insufficient differentiation and phenotypic instability restrict their clinical application. This study aimed to determine the role of hepatocyte nuclear factor 4A (HNF4A) in hepatic differentiation of IHH, and whether encapsulation of IHH overexpressing HNF4A could improve liver function and survival in rats with acute liver failure (ALF). Primary human hepatocytes were transduced with lentivirus-mediated catalytic subunit of human telomerase reverse transcriptase (hTERT) to establish IHH. Cells were analyzed for telomerase activity, proliferative capacity, hepatocyte markers, and tumorigenicity (c-myc) expression. Hepatocyte markers, hepatocellular functions, and morphology were studied in the HNF4A-overexpressing IHH. Hepatocyte markers and karyotype analysis were completed in the primary hepatocytes using shRNA knockdown of HNF4A. Nuclear translocation of β-catenin was assessed. Rat models of ALF were treated with encapsulated IHH or HNF4A-overexpressing IHH. A HNF4A-positive IHH line was established, which was non-tumorigenic and conserved properties of primary hepatocytes. HNF4A overexpression significantly enhanced mRNA levels of genes related to hepatic differentiation in IHH. Urea levels were increased by the overexpression of HNF4A, as measured 24h after ammonium chloride addition, similar to that of primary hepatocytes. Chromosomal abnormalities were observed in primary hepatocytes transfected with HNF4A shRNA. HNF4α overexpression could significantly promote β-catenin activation. Transplantation of HNF4A overexpressing IHH resulted in better liver function and survival of rats with ALF compared with IHH. HNF4A improved hepatic differentiation of IHH. Transplantation of HNF4A-overexpressing IHH could improve the liver function and survival in a rat model of ALF. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Interaction of CtBP with adenovirus E1A suppresses immortalization of primary epithelial cells and enhances virus replication during productive infection

    Energy Technology Data Exchange (ETDEWEB)

    Subramanian, T.; Zhao, Ling-jun; Chinnadurai, G., E-mail: chinnag@slu.edu

    2013-09-01

    Adenovirus E1A induces cell proliferation, oncogenic transformation and promotes viral replication through interaction with p300/CBP, TRRAP/p400 multi-protein complex and the retinoblastoma (pRb) family proteins through distinct domains in the E1A N-terminal region. The C-terminal region of E1A suppresses E1A/Ras co-transformation and interacts with FOXK1/K2, DYRK1A/1B/HAN11 and CtBP1/2 (CtBP) protein complexes. To specifically dissect the role of CtBP interaction with E1A, we engineered a mutation (DL→AS) within the CtBP-binding motif, PLDLS, and investigated the effect of the mutation on immortalization and Ras cooperative transformation of primary cells and viral replication. Our results suggest that CtBP–E1A interaction suppresses immortalization and Ras co-operative transformation of primary rodent epithelial cells without significantly influencing the tumorigenic activities of transformed cells in immunodeficient and immunocompetent animals. During productive infection, CtBP–E1A interaction enhances viral replication in human cells. Between the two CtBP family proteins, CtBP2 appears to restrict viral replication more than CtBP1 in human cells. - Highlights: • Adenovirus E1A C-terminal region suppresses E1A/Ras co-transformation. • This E1A region binds with FOXK, DYRK1/HAN11 and CtBP cellular protein complexes. • We found that E1A–CtBP interaction suppresses immortalization and transformation. • The interaction enhances viral replication in human cells.

  6. Escape from Evil? Notes on Capacity, Tragedy, Coding and Non-Destructive Immortality Projects

    Directory of Open Access Journals (Sweden)

    Ronnie Lippens

    2015-09-01

    Full Text Available Like James Hardie-Bick’s (2015 contribution this paper elaborates on the importance for socio-legal studies of Ernest Becker’s (1924-1974 work on the destructive consequences of human … all too human forms of death denial. With Becker, it makes an attempt to think through the question, ‘Is it possible, in the light of the human condition, to escape evil?’ Terminally ill by the early 1970s, Becker himself was left no time to complete his thoughts on this matter. Focussing on the point where Becker left the discussion when he died in 1974 we make an attempt here, still with an eye on the aforementioned question, to explore the work of a number of philosophers whose work we know Becker was familiar with: Benedictus de Spinoza, Henri Bergson, and Albert Camus. In their work, it is argued here, one could find elements towards thinking through the question of evil, and the (impossibility of escaping it. Al igual que el artículo de James Hardie-Bick (2015, este artículo profundiza en la importancia que tiene para los estudios sociojurídicos el trabajo de Ernest Becker (1924-1974 sobre las consecuencias destructivas del ser humano… y la tan humana negación de la muerte. Con Becker, se realiza un intento de reflexionar sobre esta pregunta: “Es posible, a la luz de la condición humana, escapar del mal? Enfermo terminal a comienzos de los años 70, el propio Becker no tuvo tiempo de completar sus pensamientos sobre este asunto. Centrándonos en el punto en el que Becker dejó el debate, cuando murió en 1974, y sin perder de vista esta pregunta, se intenta analizar el trabajo de una serie de filósofos, con el que estaba familiarizado Becker: Benedictus de Spinoza, Henri Bergson y Albert Camus. Se defiende que en su trabajo se pueden encontrar elementos que hacen pensar sobre la cuestión del mal, y la (imposibilidad de escapar de él.DOWNLOAD THIS PAPER FROM SSRN: http://ssrn.com/abstract=2619429

  7. Bioethics in popular science: evaluating the media impact of The Immortal Life of Henrietta Lacks on the biobank debate.

    Science.gov (United States)

    Nisbet, Matthew C; Fahy, Declan

    2013-02-28

    The global expansion of biobanks has led to a range of bioethical concerns related to consent, privacy, control, ownership, and disclosure. As an opportunity to engage broader audiences on these concerns, bioethicists have welcomed the commercial success of Rebecca Skloot's 2010 bestselling book The Immortal Life of Henrietta Lacks. To assess the impact of the book on discussion within the media and popular culture more generally, we systematically analyzed the ethics-related themes emphasized in reviews and articles about the book, and in interviews and profiles of Skloot. We conducted a content analysis of a population of relevant English-language articles and transcripts (n = 125) produced by news organizations and publications in the U.S., Canada, Great Britain/Ireland, and Australia/New Zealand. We scored each article for the emphasis and appearance of 9 ethics-related themes. These were informed consent, welfare of the vulnerable, compensation, scientific progress, control/access, accountability/oversight, privacy, public education, and advocacy. The informed consent theme dominated media discussion, with almost 39.2 percent of articles/transcripts featuring the theme as a major focus and 44.8 percent emphasizing the theme as a minor focus. Other prominent themes and frames of reference focused on the welfare of the vulnerable (18.4 percent major emphasis; 36.0 percent minor emphasis), and donor compensation (19.2 percent major; 52.8 percent minor). Ethical themes that comprised a second tier of prominence included those of scientific progress, control/access, and accountability/oversight. The least prominent themes were privacy, public education, and advocacy. The book has been praised as an opportunity to elevate media discussion of bioethics, but such claims should be re-considered. The relatively narrow focus on informed consent in the media discussion generated by Skloot's book may limit the ability of ethicists and advocates to elevate attention to

  8. Expression of a TGF-{beta} regulated cyclin-dependent kinase inhibitor in normal and immortalized airway epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Tierney, L.A.; Bloomfield, C.; Johnson, N.F. [and others

    1995-12-01

    Tumors arising from epithelial cells, including lung cancers are frequently resistant to factors that regulate growth and differentiation in normal in normal cells. Once such factor is transforming growth factor-{Beta} (TGF-{Beta}). Escape from the growth-inhibitory effects of TGF-{Beta} is thought to be a key step in the transformation of airway epithelial cells. most lung cancer cell lines require serum for growth. In contrast, normal human bronchial epithelial (NHBE) cells are exquisitely sensitive to growth-inhibitory and differentiating effects of TGF-{Beta}. The recent identification of a novel cyclin-dependent kinase inhibitor, p15{sup INK4B}, which is regulated by TGF-{Beta}, suggests a mechanism by which TGF-{Beta} mediates growth arrest in NHBE cells. The purpose of this study was two-fold: (1) to determine if p15{sup INK4B} is induced by TGF-{Beta} in NHBE cells or immortalized bronchial epithelial (R.1) cells and if that induction corresponds to a G1/S cell-cycle arrest; (2) to determine the temporal relationship between p15{sup INK4B} induction, cell-cycle arrest, and the phosphorylation state of the pRB because it is thought that p15{sup INK4B} acts indirectly by preventing phosphorylation of the RB gene product. In this study, expression of p15{sup INK4B} was examined in NHBE cells and R.1 cells at different time intervals following TGF-{Beta} treatment. The expression of this kinase inhibitor and its relationship to the cell and the pRb phosphorylation state were examined in cells that were both sensitive (NHBE) and resistant (R.1) to the effects of TGF-{Beta}. These results suggest that the cyclin-dependent kinase inhibitor, p15{sup INK4B}, is involved in airway epithelial cell differentiation and that loss or reduction of expression plays a role in the resistance of transformed or neoplastic cells to the growth-inhibitory effects of TGF-{Beta}.

  9. Soma, food of the immortals according to the Bower Manuscript (Kashmir, 6th century A.D.).

    Science.gov (United States)

    Leonti, Marco; Casu, Laura

    2014-08-08

    Food is medicine and vice versa. In Hindu and Ayurvedic medicine, and among human cultures of the Indian subcontinent in general, the perception of the food-medicine continuum is especially well established. The preparation of the exhilarating, gold-coloured Soma, Amrita or Ambrosia, the elixir and food of the 'immortals'-the Hindu pantheon-by the ancient Indo-Aryans, is described in the Rigveda in poetic hymns. Different theories regarding the botanical identity of Soma circulate, but no pharmacologically and historically convincing theory exists to date. We intend to contribute to the botanical, chemical and pharmacological characterisation of Soma through an analysis of two historical Amrita recipes recorded in the Bower Manuscript. The recipes are referred therein as panaceas (clarified butter) and also as a medicine to treat nervous diseases (oil), while no exhilarating properties are mentioned. Notwithstanding this, we hypothesise, that these recipes are related to the ca. 1800 years older Rigvedic Soma. We suppose that the psychoactive Soma ingredient(s) are among the components, possibly in smaller proportions, of the Amrita recipes preserved in the Bower Manuscript. The Bower Manuscript is a medical treatise recorded in the 6th century A.D. in Sanskrit on birch bark leaves, probably by Buddhist monks, and unearthed towards the end of the 19th century in Chinese Turkestan. We analysed two Amrita recipes from the Bower Manuscript, which was translated by Rudolf Hoernle into English during the early 20th century. A database search with the updated Latin binomials of the herbal ingredients was used to gather quantitative phytochemical and pharmacological information. Together, both Amrita recipes contain around 100 herbal ingredients. Psychoactive alkaloid containing species still important in Ayurvedic, Chinese and Thai medicine and mentioned in the recipe for 'Amrita-Prâsa clarified butter' and 'Amrita Oil' are: Tinospora cordifolia (Amrita, Guduchi), three

  10. Activation of the omega-3 fatty acid receptor GPR120 mediates anti-inflammatory actions in immortalized hypothalamic neurons.

    Science.gov (United States)

    Wellhauser, Leigh; Belsham, Denise D

    2014-03-27

    Overnutrition and the ensuing hypothalamic inflammation is a major perpetuating factor in the development of metabolic diseases, such as obesity and diabetes. Inflamed neurons of the CNS fail to properly regulate energy homeostasis leading to pathogenic changes in glucose handling, feeding, and body weight. Hypothalamic neurons are particularly sensitive to pro-inflammatory signals derived locally and peripherally, and it is these neurons that become inflamed first upon high fat feeding. Given the prevalence of metabolic disease, efforts are underway to identify therapeutic targets for this inflammatory state. At least in the periphery, omega-3 fatty acids and their receptor, G-protein coupled receptor 120 (GPR120), have emerged as putative targets. The role for GPR120 in the hypothalamus or CNS in general is poorly understood. Here we introduce a novel, immortalized cell model derived from the rat hypothalamus, rHypoE-7, to study GPR120 activation at the level of the individual neuron. Gene expression levels of pro-inflammatory cytokines were studied by quantitative reverse transcriptase-PCR (qRT-PCR) upon exposure to tumor necrosis factor α (TNFα) treatment in the presence or absence of the polyunsaturated omega-3 fatty acid docosahexaenoic acid (DHA). Signal transduction pathway involvement was also studied using phospho-specific antibodies to key proteins by western blot analysis. Importantly, rHypoE-7 cells exhibit a transcriptional and translational inflammatory response upon exposure to TNFα and express abundant levels of GPR120, which is functionally responsive to DHA. DHA pretreatment prevents the inflammatory state and this effect was inhibited by the reduction of endogenous GPR120 levels. GPR120 activates both AKT (protein kinase b) and ERK (extracellular signal-regulated kinase); however, the anti-inflammatory action of this omega-3 fatty acid (FA) receptor is AKT- and ERK-independent and likely involves the GPR120-transforming growth factor

  11. Change of mitotic cycle and DNA repair in embryonic cells of rat, immortalized by E1 A oncogene and transformated by E1 A and c-Ha-Ras oncogenes under ionizing radiation action

    International Nuclear Information System (INIS)

    Kirillova, T.V.

    1997-01-01

    Comparison investigation into the repair of mitotic cycle and the reunion of DN single- and double-strand breaks in gamma-ray irradiated initial E1 A oncogene immortalized and E1 A and c-Ha-Ras oncogene transformed (mutant form) lines of rat embryonic fibroblasts was carried out. Possible involvement of Ras gene product in DNA repair speed governing and absence of tumor suppression function of p 53 protein in the embryonic and E1 A oncogene immortalized cells of rat fibroblast, as well as, presence of the mentioned function of p 53 protein in E1 A and c-Ha-Ras oncogene transformed cells were studied [ru

  12. Toxicity evaluation of chlorinated organic compounds using immortalized rat hepatocytes; Fushika rat kansaibo wo mochiita yuki enso kagobutsu no dokusei hyoka no kokoromi

    Energy Technology Data Exchange (ETDEWEB)

    Sone, H; Nakajima, M; Yonemoto, J [National Institute for Environmental Studies, Tsukuba (Japan)

    1997-11-10

    Chlorinated organic compounds has high priority for toxicity screening among environmental hazardous chemicals. In the present study, we used immortalized rat hepatocytes as a liver model in vitro to evaluate the toxicity of nine chlorinated organic compounds. Toxicity of nine chlorinated organic compounds were evaluated to cellular viability of immortalized rat hapatocytes. The potency of the toxicity based on 50% inhibitory concentration (IC50) value was in the following order: triclocalban>triclosan>3,4-dichloroaniline>2,5-diclorophenol> 2,5-dichloroanisole>p-dichlorobenzene> p-chloroaniline>o-dichlorobenzene=tris (2-chloroethyl) phosphate. The rank order of cytotoxic potency of nine chemicals was compared with toxicity information using animals. The rank order of cytotoxic potency did not relative to the order referenced mean lethal dose (LD50) as an index of acute toxicity of rats or mice. However, the rank order of cytotoxic potency relatively correlated non-observed adverse effect level (NOAEL) under the exposure duration adjusted for chronic toxicity in vivo. These data suggests that the origin of testing cell had better to make match target organ of toxic chemicals for extrapolation from data of bioassay in vitro to in vivo. 16 refs., 2 figs., 3 tabs.

  13. Interaction of CtBP with adenovirus E1A suppresses immortalization of primary epithelial cells and enhances virus replication during productive infection.

    Science.gov (United States)

    Subramanian, T; Zhao, Ling-Jun; Chinnadurai, G

    2013-09-01

    Adenovirus E1A induces cell proliferation, oncogenic transformation and promotes viral replication through interaction with p300/CBP, TRRAP/p400 multi-protein complex and the retinoblastoma (pRb) family proteins through distinct domains in the E1A N-terminal region. The C-terminal region of E1A suppresses E1A/Ras co-transformation and interacts with FOXK1/K2, DYRK1A/1B/HAN11 and CtBP1/2 (CtBP) protein complexes. To specifically dissect the role of CtBP interaction with E1A, we engineered a mutation (DL→AS) within the CtBP-binding motif, PLDLS, and investigated the effect of the mutation on immortalization and Ras cooperative transformation of primary cells and viral replication. Our results suggest that CtBP-E1A interaction suppresses immortalization and Ras co-operative transformation of primary rodent epithelial cells without significantly influencing the tumorigenic activities of transformed cells in immunodeficient and immunocompetent animals. During productive infection, CtBP-E1A interaction enhances viral replication in human cells. Between the two CtBP family proteins, CtBP2 appears to restrict viral replication more than CtBP1 in human cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Aging, fertility, and immortality.

    Science.gov (United States)

    Rauser, Casandra L; Mueller, Laurence D; Rose, Michael R

    2003-01-01

    Evolutionary theory suggests that fecundity rates will plateau late in life in the same fashion as mortality rates. We demonstrate that late-life plateaus arise for fecundity in Drosophila melanogaster. The result qualitatively fits the evolutionary theory of late life based on the force of natural selection. But there are a number of alternative interpretations. Fecundity plateaus could be secondary consequences of mortality-rate plateaus. Female fecundity plateaus might arise from diminished male sexual function. Another alternative hypothesis is analogous to male sexual inadequacy: nutritional shortfalls. These may arise later in life because of a decline in female feeding or digestion. If some females have a life-long tendency to lay eggs at a faster rate, but die earlier, then aging for fecundity could arise from the progressive loss of the fast-layers, with the late-life plateau simply the laying patterns of individual females who were slow-layers throughout adult life. If this type of model is generally applicable to late life, then we should find that the females who survive to lay at a slow but steady rate in late life have a similar laying pattern in mid-life.

  15. The Immortal Senescence.

    Science.gov (United States)

    Bianchi-Smiraglia, Anna; Lipchick, Brittany C; Nikiforov, Mikhail A

    2017-01-01

    Activation of oncogenic signaling paradoxically results in the permanent withdrawal from cell cycle and induction of senescence (oncogene-induced senescence (OIS)). OIS is a fail-safe mechanism used by the cells to prevent uncontrolled tumor growth, and, as such, it is considered as the first barrier against cancer. In order to progress, tumor cells thus need to first overcome the senescent phenotype. Despite the increasing attention gained by OIS in the past 20 years, this field is still rather young due to continuous emergence of novel pathways and processes involved in OIS. Among the many factors contributing to incomplete understanding of OIS are the lack of unequivocal markers for senescence and the complexity of the phenotypes revealed by senescent cells in vivo and in vitro. OIS has been shown to play major roles at both the cellular and organismal levels in biological processes ranging from embryonic development to barrier to cancer progression. Here we will briefly outline major advances in methodologies that are being utilized for induction, identification, and characterization of molecular processes in cells undergoing oncogene-induced senescence. The full description of such methodologies is provided in the corresponding chapters of the book.

  16. Conditionally immortalized stem cell lines from human spinal cord retain regional identity and generate functional V2a interneurons and motorneurons

    Czech Academy of Sciences Publication Activity Database

    Cocks, G.; Romanyuk, Nataliya; Amemori, Takashi; Jendelová, Pavla; Forostyak, Oksana; Jeffries, A. R.; Perfect, L.; Thuret, S.; Dayanithi, Govindan; Syková, Eva; Price, J.

    2013-01-01

    Roč. 4, č. 3 (2013), s. 69 ISSN 1757-6512 R&D Projects: GA AV ČR IAA500390902; GA ČR GAP304/11/2373; GA ČR GA13-00939S; GA ČR(CZ) GBP304/12/G069 Institutional research plan: CEZ:AV0Z50390703 Institutional support: RVO:68378041 Keywords : neural stem cells * spinal cord * motoneurons Subject RIV: FH - Neurology Impact factor: 4.634, year: 2013

  17. Determination of acute lethal and chronic lethal dose thresholds of valproic acid using 3D spheroids constructed from the immortal human hepatocyte cell line HepG2/C3A

    DEFF Research Database (Denmark)

    Fey, S. J.; Wrzesinski, K.

    2013-01-01

    describe here a culture system based on 3D spheroid culture of immortal hepatocytes which can determine the toxicity of valproic acid (or structurally or functionally related molecules) in vitro. The spheroids were used to follow changes in ATP production, glucose uptake and adenylate kinase following...

  18. Detailed cost-benefit analysis of potential impairment countermeasures. Research in the framework of the European research programme IMMORTAL (Impaired Motorists, Methods of Roadside Testing and Assessment for Licensing) Deliverable P2.

    NARCIS (Netherlands)

    Vlakveld, W. Wesemann, P. Devillers, E. Elvik, R. & Veisten, K.

    2005-01-01

    Almost all kinds of driver impairments increase accident risks. This study forms part of the European IMMORTAL (Impaired Motorists, Methods Of Roadside Testing and Assessment for Licensing) project. The study provides a cost-benefit analysis (CBA) of several possible policies of impairment

  19. Human Papillomavirus type 16 E6 and E 7 proteins alter NF-kB in cultured cervical epithelial cells and inhibition of NF-kB promotes cell growth and immortalization

    Science.gov (United States)

    Vandermark, Erik R.; Deluca, Krysta A.; Gardner, Courtney R.; Marker, Daniel F.; Schreiner, Cynthia N.; Strickland, David A.; Wilton, Katelynn M.; Mondal, Sumona; Woodworth, Craig D.

    2012-01-01

    The NF-kB family of transcription factors regulates important biological functions including cell growth, survival and the immune response. We found that Human Papillomavirus type 16 (HPV-16) E7 and E6/E7 proteins inhibited basal and TNF-alpha-inducible NF-kB activity in human epithelial cells cultured from the cervical transformation zone, the anatomic region where most cervical cancers develop. In contrast, HPV-16 E6 regulated NF-kB in a cell type- and cell growth-dependent manner. NF-kB influenced immortalization of cervical cells by HPV16. Inhibition of NF-kB by an IkB alpha repressor mutant increased colony formation and immortalization by HPV-16. In contrast, activation of NF-kB by constitutive expression of p65 inhibited proliferation and immortalization. Our results suggest that inhibition of NF-kB by HPV-16 E6/E7 contributes to immortalization of cells from the cervical transformation zone. PMID:22284893

  20. Combined introduction of Bmi-1 and hTERT immortalizes human adipose tissue-derived stromal cells with low risk of transformation

    Energy Technology Data Exchange (ETDEWEB)

    Tatrai, Peter, E-mail: peter.tatrai@biomembrane.hu [Institute of Enzymology, Research Center for Natural Sciences, Hungarian Academy of Sciences, Karolina ut 29, H-1113 Budapest (Hungary); Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Egyetem ter 1, H-4032 Debrecen (Hungary); Szepesi, Aron, E-mail: aron.szepesi@biomembrane.hu [Creative Cell Ltd., Puskas Tivadar utca 13, H-1119 Budapest (Hungary); Matula, Zsolt, E-mail: matula.zsolt@gmail.com [Creative Cell Ltd., Puskas Tivadar utca 13, H-1119 Budapest (Hungary); Szigeti, Anna, E-mail: anna.szigeti@biomembrane.hu [Creative Cell Ltd., Puskas Tivadar utca 13, H-1119 Budapest (Hungary); Buchan, Gyoengyi, E-mail: buchan@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Egyetem ter 1, H-4032 Debrecen (Hungary); Madi, Andras, E-mail: madi@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Egyetem ter 1, H-4032 Debrecen (Hungary); Stem Cell, Apoptosis and Genomics Research Group of the Hungarian Academy of Sciences, University of Debrecen, Egyetem ter 1, H-4032 Debrecen (Hungary); Uher, Ferenc, E-mail: uher@biomembrane.hu [Stem Cell Laboratory, Hungarian National Blood Transfusion Service, Dioszegi ut 64, H-1113 Budapest (Hungary); and others

    2012-05-25

    Highlights: Black-Right-Pointing-Pointer We immortalized human adipose stromal cells (ASCs) with hTERT, Bmi-1, and SV40T. Black-Right-Pointing-Pointer hTERT-only ASCs are prone to transformation, while Bmi-only ASCs become senescent. Black-Right-Pointing-Pointer SV40T introduced along with hTERT abrogates proliferation control and multipotency. Black-Right-Pointing-Pointer hTERT combined with Bmi-1 yields stable phenotype up to 140 population doublings. -- Abstract: Adipose tissue-derived stromal cells (ASCs) are increasingly being studied for their usefulness in regenerative medicine. However, limited life span and donor-dependent variation of primary cells such as ASCs present major hurdles to controlled and reproducible experiments. We therefore aimed to establish immortalized ASC cell lines that provide steady supply of homogeneous cells for in vitro work while retain essential features of primary cells. To this end, combinations of human telomerase reverse transcriptase (hTERT), murine Bmi-1, and SV40 large T antigen (SV40T) were introduced by lentiviral transduction into ASCs. The resulting cell lines ASC{sup hTERT}, ASC{sup Bmi-1}, ASC{sup Bmi-1+hTERT} and ASC{sup SV40T+hTERT} were tested for transgene expression, telomerase activity, surface immunomarkers, proliferation, osteogenic and adipogenic differentiation, karyotype, tumorigenicity, and cellular senescence. All cell lines have maintained expression of characteristic surface immunomarkers, and none was tumorigenic. However, ASC{sup Bmi-1} had limited replicative potential, while the rapidly proliferating ASC{sup SV40T+hTERT} acquired chromosomal aberrations, departed from MSC phenotype, and lost differentiation capacity. ASC{sup hTERT} and ASC{sup hTERT+Bmi-1}, on the other hand, preserved all essential MSC features and did not senesce after 100 population doublings. Notably, a subpopulation of ASC{sup hTERT} also acquired aberrant karyotype and showed signs of transformation after long-term culture

  1. Combined introduction of Bmi-1 and hTERT immortalizes human adipose tissue-derived stromal cells with low risk of transformation

    International Nuclear Information System (INIS)

    Tátrai, Péter; Szepesi, Áron; Matula, Zsolt; Szigeti, Anna; Buchan, Gyöngyi; Mádi, András; Uher, Ferenc

    2012-01-01

    Highlights: ► We immortalized human adipose stromal cells (ASCs) with hTERT, Bmi-1, and SV40T. ► hTERT-only ASCs are prone to transformation, while Bmi-only ASCs become senescent. ► SV40T introduced along with hTERT abrogates proliferation control and multipotency. ► hTERT combined with Bmi-1 yields stable phenotype up to 140 population doublings. -- Abstract: Adipose tissue-derived stromal cells (ASCs) are increasingly being studied for their usefulness in regenerative medicine. However, limited life span and donor-dependent variation of primary cells such as ASCs present major hurdles to controlled and reproducible experiments. We therefore aimed to establish immortalized ASC cell lines that provide steady supply of homogeneous cells for in vitro work while retain essential features of primary cells. To this end, combinations of human telomerase reverse transcriptase (hTERT), murine Bmi-1, and SV40 large T antigen (SV40T) were introduced by lentiviral transduction into ASCs. The resulting cell lines ASC hTERT , ASC Bmi-1 , ASC Bmi-1+hTERT and ASC SV40T+hTERT were tested for transgene expression, telomerase activity, surface immunomarkers, proliferation, osteogenic and adipogenic differentiation, karyotype, tumorigenicity, and cellular senescence. All cell lines have maintained expression of characteristic surface immunomarkers, and none was tumorigenic. However, ASC Bmi-1 had limited replicative potential, while the rapidly proliferating ASC SV40T+hTERT acquired chromosomal aberrations, departed from MSC phenotype, and lost differentiation capacity. ASC hTERT and ASC hTERT+Bmi-1 , on the other hand, preserved all essential MSC features and did not senesce after 100 population doublings. Notably, a subpopulation of ASC hTERT also acquired aberrant karyotype and showed signs of transformation after long-term culture. In conclusion, hTERT alone was sufficient to extend the life span of human ASC, but ASC hTERT are prone to transformation during extensive

  2. Introduction of a normal human chromosome 8 corrects abnormal phenotypes of Werner syndrome cells immortalized by expressing an hTERT gene

    International Nuclear Information System (INIS)

    Ariyoshi, Kentaro; Kodama, Seiji; Suzuki, Keiji; Goto, Makoto; Oshimura, Mitsuo; Ishizaki, Kanji; Watanabe, Masami

    2009-01-01

    Werner syndrome (WS) is an autosomal recessive disease characterized by premature aging and caused by mutations of the WRN gene mapped at 8p12. To examine functional complementation of WS phenotypes, we introduced a normal human chromosome 8 into a strain of WS fibroblasts (WS3RGB) immortalized by expressing a human telomerase reverse transcriptase subunit (hTERT) gene. Here, we demonstrate that the abnormal WS phenotypes including cellular sensitivities to 4-nitroquinoline-1-oxide (4NQO) and hydroxy urea (HU), and chromosomal radiosensitivity at G 2 phase are corrected by expression of the WRN gene mediated by introducing a chromosome 8. This indicates that those multiple abnormal WS phenotypes are derived from a primary, but not secondary, defect in the WRN gene. (author)

  3. Establishment of a new immortalized human corneal epithelial cell line (iHCE-NY1) for use in evaluating eye irritancy by in vitro test methods.

    Science.gov (United States)

    Yamamoto, Naoki; Kato, Yoshinao; Sato, Atsushi; Hiramatsu, Noriko; Yamashita, Hiromi; Ohkuma, Mahito; Miyachi, Ei-Ichi; Horiguchi, Masayuki; Hirano, Koji; Kojima, Hajime

    2016-08-01

    In vitro test methods that use human corneal epithelial cells to evaluate the eye irritation potency of chemical substances do not use human corneal epithelium because it has been difficult to maintain more than four passages. In this study, we make a new cell line comprising immortalized human corneal epithelial cells (iHCE-NY1). The IC50 of iHCE-NY1 cells is slightly higher than that of Statens Seruminstitut Rabbit Cornea (SIRC) cells, which are currently used in some in vitro test methods. CDKN1A in iHCE-NY1 cells was used as a marker of gene expression to indicate cell cycle activity. This enabled us to evaluate cell recovery characteristics at concentrations lower than the IC50 of cytotoxic tests.

  4. Decellularized extracellular matrices produced from immortal cell lines derived from different parts of the placenta support primary mesenchymal stem cell expansion.

    Directory of Open Access Journals (Sweden)

    Gina D Kusuma

    Full Text Available Mesenchymal stem/stromal cells (MSCs exhibit undesired phenotypic changes during ex vivo expansion, limiting production of the large quantities of high quality primary MSCs needed for both basic research and cell therapies. Primary MSCs retain many desired MSC properties including proliferative capacity and differentiation potential when expanded on decellularized extracellular matrix (dECM prepared from primary MSCs. However, the need to use low passage number primary MSCs (passage 3 or lower to produce the dECM drastically limits the utility and impact of this technology. Here, we report that primary MSCs expanded on dECM prepared from high passage number (passage 25 human telomerase reverse transcriptase (hTERT transduced immortal MSC cell lines also exhibit increased proliferation and osteogenic differentiation. Two hTERT-transduced placenta-derived MSC cell lines, CMSC29 and DMSC23 [derived from placental chorionic villi (CMSCs and decidua basalis (DMSCs, respectively], were used to prepare dECM-coated substrates. These dECM substrates showed structural and biochemical differences. Primary DMSCs cultured on dECM-DMSC23 showed a three-fold increase in cell number after 14 days expansion in culture and increased osteogenic differentiation compared with controls. Primary CMSCs cultured on the dECM-DMSC23 exhibited a two-fold increase in cell number and increased osteogenic differentiation. We conclude that immortal MSC cell lines derived from different parts of the placenta produce dECM with varying abilities for supporting increased primary MSC expansion while maintaining important primary MSC properties. Additionally, this is the first demonstration of using high passage number cells to produce dECM that can promote primary MSC expansion, and this advancement greatly increases the feasibility and applicability of dECM-based technologies.

  5. Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-κB in immortalized and malignant oral keratinocytes

    International Nuclear Information System (INIS)

    Lee, Hwa-Jeong; Lee, Jun; Lee, Sun-Kyung; Lee, Suk-Keun; Kim, Eun-Cheol

    2007-01-01

    Interleukin-8 (IL-8) is a cytokine that plays an important role in tumor progression in a variety of cancer types; however, its regulation is not well understood in oral cancer cells. In the present study, we examined the expression and mechanism of IL-8 in which it is involved by treating immortalized (IHOK) and malignant human oral keratinocytes (HN12) cells with deferoxamine (DFO). IL-8 production was measured by an enzyme-linked immunoabsorbent assay and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Electrophoretic mobility shift assays was used to determine NF-κB binding activity. Phosphorylation and degradation of the I-κB were analyized by Western blot. IHOK cells incubated with DFO showed increased expression of IL-8 mRNA, as well as higher release of the IL-8 protein. The up-regulation of DFO-induced IL-8 expression was higher in IHOK cells than in HN12 cells and was concentration-dependent. DFO acted additively with IL-1β to strongly up-regulate IL-8 in IHOK cells but not in HN12 cells. Accordingly, selective p38 and ERK1/2 inhibitors for both kinases abolished DFO-induced IL-8 expression in both IHOK and HN12 cells. Furthermore, DFO induced the degradation and phosphorylation of IκB, and activation of NF-κB. The IL-8 inducing effects of DFO were mediated by a nitric oxide donor (S-nitrosoglutathione), and by pyrrolidine dithiocarbamate, an inhibitor of NF-κB, as well as by wortmannin, which inhibits the phosphatidylinositol 3-kinase-dependent activation of NAD(P)H oxidase. This results demonstrate that DFO-induced IL-8 acts via multiple signaling pathways in immortalized and malignant oral keratinocytes, and that the control of IL-8 may be an important target for immunotheraphy against human oral premalignant lesions

  6. Direct induction of hepatocyte-like cells from immortalized human bone marrow mesenchymal stem cells by overexpression of HNF4α

    International Nuclear Information System (INIS)

    Hu, Xiaojun; Xie, Peiyi; Li, Weiqiang; Li, Zhengran; Shan, Hong

    2016-01-01

    Hepatocytes from human bone marrow-derived mesenchymal stem cells (hBM-MSCs) are expected to be a useful source for cell transplantation. However, relatively low efficiency and repeatability of hepatic differentiation of human BM-MSCs remains an obstacle for clinical translation. Hepatocyte nuclear factor 4 alpha (HNF4α), a critical transcription factor, plays an essential role in the entire process of liver development. In this study, immortalized hBM-MSCs, UE7T-13 cells were transduced with a lentiviral vector containing HNF4α. The typical fibroblast-like morphology of the MSCs changed, and polygonal, epithelioid cells grew out after HNF4α transduction. In hepatocyte culture medium, HNF4α-transduced MSCs (E7-hHNF4α cells) strongly expressed the albumin (ALB), CYP2B6, alpha-1 antitrypsin (AAT), and FOXA2 mRNA and exhibited morphology markedly similar to that of mature hepatocytes. The E7-hHNF4α cells showed hepatic functions such as Indocyanine green (ICG) uptake and release, glycogen storage, urea production and ALB secretion. Approximately 28% of E7-hHNF4α cells expressed both ALB and AAT. Furthermore, these E7-hHNF4α cells via superior mesenteric vein (SMV) injection expressed human ALB in mouse chronic injured liver. In conclusion, this study represents a novel strategy by directly inducing hepatocyte-like cells from MSCs. - Highlights: • We overexpressed HNF4α in immortalized BM-MSCs by lentiviral transduction. • HNF4α-transduced MSCs transdifferentiated into hepatocytes with mature hepatic metabolic functions. • Our study represents a novel strategy by direct induction of hepatocyte-like cells from MSCs.

  7. Herpes simplex virus-1 infection or Simian virus 40-mediated immortalization of corneal cells causes permanent translocation of NLRP3 to the nuclei

    Directory of Open Access Journals (Sweden)

    Shu-Long Wang

    2015-01-01

    Full Text Available AIM: To investigate into the potential involvement of pyrin containing 3 gene (NLRP3, a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of corneas against viruses. METHODS: The herpes viral keratitis model was utilized in BALB/c mice with inoculation of herpes simplex virus-1 (HSV-1. Corneal tissues removed during therapy of patients with viral keratitis as well as a Simian vacuolating virus 40 (SV40-immortalized human corneal epithelial cell line were also examined. Immunohistochemistry was used to detect NLRP3 in these subjects, focusing on their distribution in tissue or cells. Western blot was used to measure the level of NLRP3 and another two related molecules in NLPR3 inflammasome, namely caspase-1 and IL-1β. RESULTS: The NLRP3 activation induced by HSV-1 infection in corneas was accompanied with redistribution of NLRP3 from the cytoplasm to the nucleus in both murine and human corneal epithelial cells. Furthermore, in the SV40-immortalized human corneal epithelial cells, NLRP3 was exclusively located in the nucleus, and treatment of the cells with high concentration of extracellular potassium (known as an inhibitor of NLRP3 activation effectively drove NLRP3 back to the cytoplasm as reflected by both immunohistochemistry and Western blot. CONCLUSION: It is proposed that herpes virus infection activates and causes redistribution of NLRP3 to nuclei. Whether this NLRP3 translocation occurs with other viral infections and in other cell types merit further study.

  8. Immortalized porcine mesenchymal cells derived from nasal mucosa, lungs, lymph nodes, spleen and bone marrow retain their stemness properties and trigger the expression of siglec-1 in co-cultured blood monocytic cells.

    Science.gov (United States)

    Garba, Abubakar; Desmarets, Lowiese M B; Acar, Delphine D; Devriendt, Bert; Nauwynck, Hans J

    2017-01-01

    Mesenchymal stromal cells have been isolated from different sources. They are multipotent cells capable of differentiating into many different cell types, including osteocytes, chondrocytes and adipocytes. They possess a therapeutic potential in the management of immune disorders and the repair of damaged tissues. Previous work in our laboratory showed an increase of the percentages of CD172a+, CD14+, CD163+, Siglec-1+, CD4+ and CD8+ hematopoietic cells, when co-cultured with immortalized mesenchymal cells derived from bone marrow. The present work aimed to demonstrate the stemness properties of SV40-immortalized mesenchymal cells derived from nasal mucosa, lungs, spleen, lymph nodes and red bone marrow and their immunomodulatory effect on blood monocytes. Mesenchymal cells from nasal mucosa, lungs, spleen, lymph nodes and red bone marrow were isolated and successfully immortalized using simian virus 40 large T antigen (SV40LT) and later, co-cultured with blood monocytes, in order to examine their differentiation stage (expression of Siglec-1). Flow cytometric analysis revealed that the five mesenchymal cell lines were positive for mesenchymal cell markers CD105, CD44, CD90 and CD29, but lacked the expression of myeloid cell markers CD16 and CD11b. Growth analysis of the cells demonstrated that bone marrow derived-mesenchymal cells proliferated faster compared with those derived from the other tissues. All five mesenchymal cell lines co-cultured with blood monocytes for 1, 2 and 7 days triggered the expression of siglec-1 in the monocytes. In contrast, no siglec-1+ cells were observed in monocyte cultures without mesenchymal cell lines. Mesenchymal cells isolated from nasal mucosa, lungs, spleen, lymph nodes and bone marrow were successfully immortalized and these cell lines retained their stemness properties and displayed immunomodulatory effects on blood monocytes.

  9. PCB153 reduces telomerase activity and telomere length in immortalized human skin keratinocytes (HaCaT) but not in human foreskin keratinocytes (NFK)

    International Nuclear Information System (INIS)

    Senthilkumar, P.K.; Robertson, L.W.; Ludewig, G.

    2012-01-01

    Polychlorinated biphenyls (PCBs), ubiquitous environmental pollutants, are characterized by long term-persistence in the environment, bioaccumulation, and biomagnification in the food chain. Exposure to PCBs may cause various diseases, affecting many cellular processes. Deregulation of the telomerase and the telomere complex leads to several biological disorders. We investigated the hypothesis that PCB153 modulates telomerase activity, telomeres and reactive oxygen species resulting in the deregulation of cell growth. Exponentially growing immortal human skin keratinocytes (HaCaT) and normal human foreskin keratinocytes (NFK) were incubated with PCB153 for 48 and 24 days, respectively, and telomerase activity, telomere length, superoxide level, cell growth, and cell cycle distribution were determined. In HaCaT cells exposure to PCB153 significantly reduced telomerase activity, telomere length, cell growth and increased intracellular superoxide levels from day 6 to day 48, suggesting that superoxide may be one of the factors regulating telomerase activity, telomere length and cell growth compared to untreated control cells. Results with NFK cells showed no shortening of telomere length but reduced cell growth and increased superoxide levels in PCB153-treated cells compared to untreated controls. As expected, basal levels of telomerase activity were almost undetectable, which made a quantitative comparison of treated and control groups impossible. The significant down regulation of telomerase activity and reduction of telomere length by PCB153 in HaCaT cells suggest that any cell type with significant telomerase activity, like stem cells, may be at risk of premature telomere shortening with potential adverse health effects for the affected organism. -- Highlights: ► Human immortal (HaCaT) and primary (NFK) keratinocytes were exposed to PCB153. ► PCB153 significantly reduced telomerase activity and telomere length in HaCaT. ► No effect on telomere length and

  10. Identification of differentially expressed proteins between human esophageal immortalized and carcinomatous cell lines by two-dimensional electrophoresis and MALDI-TOF-mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    Xing-Dong Xiong; Li-Yan Xu; Zhong-Ying Shen; Wei-Jia Cai; Jian-Min Luo; Ya-Li Han; En-Min Li

    2002-01-01

    AIM: To identify the differentially expressed proteins between the human immortalized esophageal epithelial cell line (SHEE) and the malignant transformed esophageal carcinoma cell line (SHEEC), and to explore new ways for studying esophageal carcinoma associated genes. METHODS: SHEE and SHEEC cell lines were used to separate differentially expressed proteins by two-dimensional electrophoresis/The silver-stained 2-D gels was scanned with EDAS290 digital camera system and analyzed with the PDQuest 6.2 Software. Six spots in which the differentially expressed protein was more obvious were selected and analyzed with matrix-assisted laser desorption/ionization time of flying mass spectrometry (MALDI-TOF-MS).RESULTS: There were 107±4.58 and 115±9.91 protein spots observed in SHEE and SHEEC respectively, and the majority of these spots between the two cell lines matched each other (r=-0.772), only a few were expressed differentially. After analyzed by MALDI-TOF-MS and database search for the six differentially expressed proteins, One new protein as well as other five sequence-known proteins including RNPEP-like protein, human rRNA gene upstream sequence binding transcription factor, uracil DNA glycosylase,Annexin A2 and p300/CBP-associated factor were preliminarily identified.CONCLUSION: These differentially expressed proteins might play an importance role during malignant transformation of SHEEC from SHEE. The identification of these proteins may serve as a new way for studying esophageal carcinoma associated genes.

  11. An In Vitro System Comprising Immortalized Hypothalamic Neuronal Cells (GT1-7 Cells) for Evaluation of the Neuroendocrine Effects of Essential Oils.

    Science.gov (United States)

    Mizuno, Dai; Konoha-Mizuno, Keiko; Mori, Miwako; Yamazaki, Kentaro; Haneda, Toshihiro; Koyama, Hironari; Kawahara, Masahiro

    2015-01-01

    Aromatherapy and plant-based essential oils are widely used as complementary and alternative therapies for symptoms including anxiety. Furthermore, it was reportedly effective for the care of several diseases such as Alzheimer's disease and depressive illness. To investigate the pharmacological effects of essential oils, we developed an in vitro assay system using immortalized hypothalamic neuronal cells (GT1-7 cells). In this study, we evaluated the effects of essential oils on neuronal death induced by hydrogen peroxide (H2O2), aluminum, zinc, or the antagonist of estrogen receptor (tamoxifen). Among tests of various essential oils, we found that H2O2-induced neuronal death was attenuated by the essential oils of damask rose, eucalyptus, fennel, geranium, ginger, kabosu, mandarin, myrrh, and neroli. Damask rose oil had protective effects against aluminum-induced neurotoxicity, while geranium and rosemary oil showed protective activity against zinc-induced neurotoxicity. In contrast, geranium oil and ginger oil enhanced the neurotoxicity of tamoxifen. Our in vitro assay system could be useful for the neuropharmacological and endocrine pharmacological studies of essential oils.

  12. An In Vitro System Comprising Immortalized Hypothalamic Neuronal Cells (GT1–7 Cells for Evaluation of the Neuroendocrine Effects of Essential Oils

    Directory of Open Access Journals (Sweden)

    Dai Mizuno

    2015-01-01

    Full Text Available Aromatherapy and plant-based essential oils are widely used as complementary and alternative therapies for symptoms including anxiety. Furthermore, it was reportedly effective for the care of several diseases such as Alzheimer’s disease and depressive illness. To investigate the pharmacological effects of essential oils, we developed an in vitro assay system using immortalized hypothalamic neuronal cells (GT1–7 cells. In this study, we evaluated the effects of essential oils on neuronal death induced by hydrogen peroxide (H2O2, aluminum, zinc, or the antagonist of estrogen receptor (tamoxifen. Among tests of various essential oils, we found that H2O2-induced neuronal death was attenuated by the essential oils of damask rose, eucalyptus, fennel, geranium, ginger, kabosu, mandarin, myrrh, and neroli. Damask rose oil had protective effects against aluminum-induced neurotoxicity, while geranium and rosemary oil showed protective activity against zinc-induced neurotoxicity. In contrast, geranium oil and ginger oil enhanced the neurotoxicity of tamoxifen. Our in vitro assay system could be useful for the neuropharmacological and endocrine pharmacological studies of essential oils.

  13. Symbiotic Plant Peptides Eliminate Candida albicans Both In Vitro and in an Epithelial Infection Model and Inhibit the Proliferation of Immortalized Human Cells

    Directory of Open Access Journals (Sweden)

    Lilla Ördögh

    2014-01-01

    Full Text Available The increasing number of multidrug-resistant microbes now emerging necessitates the identification of novel antimicrobial agents. Plants produce a great variety of antimicrobial peptides including hundreds of small, nodule-specific cysteine-rich NCR peptides that, in the legume Medicago truncatula, govern the differentiation of endosymbiotic nitrogen fixing bacteria and, in vitro, can display potent antibacterial activities. In this study, the potential candidacidal activity of 19 NCR peptides was investigated. Cationic NCR peptides having an isoelectric point above 9 were efficient in killing Candida albicans, one of the most common fungal pathogens of humans. None of the tested NCR peptides were toxic for immortalized human epithelial cells at concentrations that effectively killed the fungus; however, at higher concentrations, some of them inhibited the division of the cells. Furthermore, the cationic peptides successfully inhibited C. albicans induced human epithelial cell death in an in vitro coculture model. These results highlight the therapeutic potential of cationic NCR peptides in the treatment of candidiasis.

  14. Type I Interferon Reaction to Viral Infection in Interferon-Competent, Immortalized Cell Lines from the African Fruit Bat Eidolon helvum

    Science.gov (United States)

    Biesold, Susanne E.; Ritz, Daniel; Gloza-Rausch, Florian; Wollny, Robert; Drexler, Jan Felix; Corman, Victor M.; Kalko, Elisabeth K. V.; Oppong, Samuel; Drosten, Christian; Müller, Marcel A.

    2011-01-01

    Bats harbor several highly pathogenic zoonotic viruses including Rabies, Marburg, and henipaviruses, without overt clinical symptoms in the animals. It has been suspected that bats might have evolved particularly effective mechanisms to suppress viral replication. Here, we investigated interferon (IFN) response, -induction, -secretion and -signaling in epithelial-like cells of the relevant and abundant African fruit bat species, Eidolon helvum (E. helvum). Immortalized cell lines were generated; their potential to induce and react on IFN was confirmed, and biological assays were adapted to application in bat cell cultures, enabling comparison of landmark IFN properties with that of common mammalian cell lines. E. helvum cells were fully capable of reacting to viral and artificial IFN stimuli. E. helvum cells showed highest IFN mRNA induction, highly productive IFN protein secretion, and evidence of efficient IFN stimulated gene induction. In an Alphavirus infection model, O'nyong-nyong virus exhibited strong IFN induction but evaded the IFN response by translational rather than transcriptional shutoff, similar to other Alphavirus infections. These novel IFN-competent cell lines will allow comparative research on zoonotic, bat-borne viruses in order to model mechanisms of viral maintenance and emergence in bat reservoirs. PMID:22140523

  15. Graminex Pollen: Phenolic Pattern, Colorimetric Analysis and Protective Effects in Immortalized Prostate Cells (PC3) and Rat Prostate Challenged with LPS.

    Science.gov (United States)

    Locatelli, Marcello; Macchione, Nicola; Ferrante, Claudio; Chiavaroli, Annalisa; Recinella, Lucia; Carradori, Simone; Zengin, Gokhan; Cesa, Stefania; Leporini, Lidia; Leone, Sheila; Brunetti, Luigi; Menghini, Luigi; Orlando, Giustino

    2018-05-11

    Prostatitis, a general term describing prostate inflammation, is a common disease that could be sustained by bacterial or non-bacterial infectious agents. The efficacy of herbal extracts with antioxidant and anti-inflammatory effects for blunting the burden of inflammation and oxidative stress, with possible improvements in clinical symptoms, is under investigation. Pollen extracts have been previously reported as promising agents in managing clinical symptoms related to prostatitis. The aim of the present work was to evaluate the protective effects of Graminex pollen (Graminex TM , Deshler, OH, USA), a commercially available product based on standardized pollen extracts, in rat prostate specimens, ex vivo. In this context, we studied the putative mechanism of action of pollen on multiple inflammatory pathways, including the reduction of prostaglandin E₂ (PGE₂), nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), and malondialdehyde (MDA), whose activities were significantly increased by inflammatory stimuli. We characterized by means of chromatographic and colorimetric studies the composition of Graminex pollen to better correlate the activity of pollen on immortalized prostate cells (PC3), and in rat prostate specimens challenged with Escherichia coli lipopolysaccharide (LPS). We found that Graminex pollen was able to reduce radical oxygen species (ROS) production by PC3 cells and MDA, NFκB mRNA, and PGE₂ levels, in rat prostate specimens. According to our experimental evidence, Graminex pollen appears to be a promising natural product for the management of the inflammatory components in the prostate.

  16. An inhibitory switch derepressed by pbx, hox, and Meis/Prep1 partners regulates DNA-binding by pbx1 and E2a-pbx1 and is dispensable for myeloid immortalization by E2a-pbx1.

    Science.gov (United States)

    Calvo, K R; Knoepfler, P; McGrath, S; Kamps, M P

    1999-12-23

    The Pbx/Exd family of homeodomain (HD) proteins contribute to the transcriptional and developmental roles of other Hox and Meis/Prep1/Hth HD proteins through heterodimer formation. E2a-Pbx1 is an oncogenic derrivative of Pbx1 produced by the t(1;19) translocation in pediatric pre-B cell acute lymphoblastic leukemia. E2a-Pbx1 heterodimerizes with Hox but not with Meis/Prep1 proteins, produces acute myeloid leukemia in mice, and blocks differentiation of cultured murine myeloid progenitors. Here, we characterize negative and positive regulatory sequences that flank the Pbx1 HD and determine their importance for myeloid immortalization by E2a-Pbx1. A 25 residue predicted alpha helix preceding the Pbx1 HD bound the HD and prevented both its binding to DNA and its ability to heterodimerize with Hox proteins. Addition of 39 residues N-terminal to this inhibitory helix exposed a Pbx dimerization interface that orchestrated cooperative DNA-binding of E2a-Pbx1 and all Pbx proteins as homodimers and heterdimers. Sequences inhibiting DNA-binding and mediating Pbx dimerization coincided with those reported to have nuclear export function. An additional 103 residues N-terminal to the Pbx dimerization interface restored heterodimerization with Hox and Meis1/Prep1 proteins. This negative switch domain - comprised of the inhibitory helix and N-terminal regions required for its partner-mediated derepression - was dispensable for myeloid immortalization by E2a-Pbx1. While stabilizing the heterodimer, the 310 helix C-terminal to the Pbx1 HD was also dispensable for the ability of E2a-Pbx1 to heterodimerize with Hox proteins and immortalize myeloblasts. Retention of myeloid immortalization by E2a-Pbx1 proteins lacking all Pbx1 sequences N- or C-terminal to the HD indicates that Hox proteins, or a yet undefined factor that binds the Pbx1 HD and derepresses DNA-binding by the HD, cooperate with E2a-Pbx1 in myeloid immortalization.

  17. Chromosomal Conditions

    Science.gov (United States)

    ... and more. Stony Point, NY 10980 Close X Home > Complications & Loss > Birth defects & other health conditions > Chromosomal conditions Chromosomal conditions ... Disorders See also: Genetic counseling , Your family health history Last reviewed: February, 2013 ... labor & premature birth The newborn intensive care unit (NICU) Birth defects & ...

  18. Up in smoke: regulatory immortality for 'grandfathered' power plants under the NSR rule changes

    Energy Technology Data Exchange (ETDEWEB)

    Conrad G. Schneider [Clean Air Task Force (USA)

    2004-01-01

    The US New Source Review (NSR) program requires power plant owners to install modern pollution control whenever they upgrade their plants in a way that will cause more pollution. The Clean Air Task Force and other environmental organizations and dozens of states and municipalities have challenged changes to the NSR rule change exempting grandfathered power plants under certain conditions. The author discussed this legislation and whether the Clear Skies Act will be effective. 9 refs.

  19. Identification of two immortalized cell lines, ECV304 and bEnd3, for in vitro permeability studies of blood-brain barrier.

    Directory of Open Access Journals (Sweden)

    Shu Yang

    Full Text Available To identify suitable cell lines for a mimetic system of in vivo blood-brain barrier (BBB for drug permeability assessment, we characterized two immortalized cell lines, ECV304 and bEnd3 in the respect of the tightness, tight junction proteins, P-glycoprotein (P-gp function and discriminative brain penetration. The ECV304 monoculture achieved higher transendothelial electrical resistance (TEER and lower permeability to Lucifer yellow than bEnd3. However, co-culture with rat glioma C6 cells impaired the integrity of ECV304 and bEnd3 cell layers perhaps due to the heterogeneity among C6 cells in inducing BBB characteristics. The immunostaining of ZO-1 delivered distinct bands along cell borders on both cell lines while those of occludin and claudin-5 were diffused and weak. P-gp functionality was only proved in bEnd3 by Rhodamine 123 (R123 uptake assay. A permeability test of reference compounds displayed a similar rank order (digoxin < R123 < quinidine, verapamil < propranolol in ECV304 and bEnd3 cells. In comparison with bEnd3, ECV304 developed tighter barrier for the passage of reference compounds and higher discrimination between transcellular and paracellular transport. However, the monoculture models of ECV304 and bEnd3 fail to achieve the sufficient tightness of in vitro BBB permeability models with high TEER and evident immunostaining of tight junction proteins. Further strategies to enhance the paracellular tightness of both cell lines to mimic in vivo BBB tight barrier deserve to be conducted.

  20. Expression of progesterone receptor membrane component-2 within the immature rat ovary and its role in regulating mitosis and apoptosis of spontaneously immortalized granulosa cells.

    Science.gov (United States)

    Griffin, Daniel; Liu, Xiufang; Pru, Cindy; Pru, James K; Peluso, John J

    2014-08-01

    Progesterone receptor membrane component 2 (Pgrmc2) mRNA was detected in the immature rat ovary. By 48 h after eCG, Pgrmc2 mRNA levels decreased by 40% and were maintained at 48 h post-hCG. Immunohistochemical studies detected PGRMC2 in oocytes and ovarian surface epithelial, interstitial, thecal, granulosa, and luteal cells. PGRMC2 was also present in spontaneously immortalized granulosa cells, localizing to the cytoplasm of interphase cells and apparently to the mitotic spindle of cells in metaphase. Interestingly, PGRMC2 levels appeared to decrease during the G1 stage of the cell cycle. Moreover, overexpression of PGRMC2 suppressed entry into the cell cycle, possibly by binding the p58 form of cyclin dependent kinase 11b. Conversely, Pgrmc2 small interfering RNA (siRNA) treatment increased the percentage of cells in G1 and M stage but did not increase the number of cells, which was likely due to an increase in apoptosis. Depleting PGRMC2 did not inhibit cellular (3)H-progesterone binding, but attenuated the ability of progesterone to suppress mitosis and apoptosis. Taken together these studies suggest that PGRMC2 affects granulosa cell mitosis by acting at two specific stages of the cell cycle. First, PGRMC2 regulates the progression from the G0 into the G1 stage of the cell cycle. Second, PGRMC2 appears to localize to the mitotic spindle, where it likely promotes the final stages of mitosis. Finally, siRNA knockdown studies indicate that PGRMC2 is required for progesterone to slow the rate of granulosa cell mitosis and apoptosis. These findings support a role for PGRMC2 in ovarian follicle development. © 2014 by the Society for the Study of Reproduction, Inc.

  1. Critical role of free cytosolic calcium, but not uncoupling, in mitochondrial permeability transition and cell death induced by diclofenac oxidative metabolites in immortalized human hepatocytes

    International Nuclear Information System (INIS)

    Lim, M.S.; Lim, Priscilla L.K.; Gupta, Rashi; Boelsterli, Urs A.

    2006-01-01

    Diclofenac is a widely used nonsteroidal anti-inflammatory drug that has been associated with rare but serious hepatotoxicity. Experimental evidence indicates that diclofenac targets mitochondria and induces the permeability transition (mPT) which leads to apoptotic cell death in hepatocytes. While the downstream effector mechanisms have been well characterized, the more proximal pathways leading to the mPT are not known. The purpose of this study was to explore the role of free cytosolic calcium (Ca 2+ c ) in diclofenac-induced cell injury in immortalized human hepatocytes. We show that exposure to diclofenac caused time- and concentration-dependent cell injury, which was prevented by the specific mPT inhibitor cyclosporin A (CsA, 5 μM). At 8 h, diclofenac caused increases in [Ca 2+ ] c (Fluo-4 fluorescence), which was unaffected by CsA. Combined exposure to diclofenac/BAPTA (Ca 2+ chelator) inhibited cell injury, indicating that Ca 2+ plays a critical role in precipitating mPT. Diclofenac decreased the mitochondrial membrane potential, ΔΨ m (JC-1 fluorescence), even in the presence of CsA or BAPTA, indicating that mitochondrial depolarization was not a consequence of the mPT or elevated [Ca 2+ ] c . The CYP2C9 inhibitor sulphaphenazole (10 μM) protected from diclofenac-induced cell injury and prevented increases in [Ca 2+ ] c , while it had no effect on the dissipation of the ΔΨ m . Finally, diclofenac exposure greatly increased the mitochondria-selective superoxide levels secondary to the increases in [Ca 2+ ] c . In conclusion, these data demonstrate that diclofenac has direct depolarizing effects on mitochondria which does not lead to cell injury, while CYP2C9-mediated bioactivation causes increases in [Ca 2+ ] c , triggering the mPT and precipitating cell death

  2. Dioxin exerts anti-estrogenic actions in a novel dioxin-responsive telomerase-immortalized epithelial cell line of the porcine oviduct (TERT-OPEC).

    Science.gov (United States)

    Hombach-Klonisch, Sabine; Pocar, Paola; Kauffold, Johannes; Klonisch, Thomas

    2006-04-01

    Oviduct epithelial cells are important for the nourishment and survival of ovulated oocytes and early embryos, and they respond to the steroid hormones estrogen and progesterone. Endocrine-disrupting polyhalogenated aromatic hydrocarbons (PHAH) are environmental toxins that act in part through the ligand-activated transcription factor arylhydrocarbon receptor (AhR; dioxin receptor), and exposure to PHAH has been shown to decrease fertility. To investigate effects of PHAHs on the oviduct epithelium as a potential target tissue of dioxin-type endocrine disruptors, we have established a novel telomerase-immortalized oviduct porcine epithelial cell line (TERT-OPEC). TERT-OPEC exhibited active telomerase and the immunoreactive epithelial marker cytokeratin but lacked the stromal marker vimentin. TERT-OPEC contained functional estrogen receptor (ER)-alpha and AhR, as determined by the detection of ER-alpha- and AhR-specific target molecules. Treatment of TERT-OPEC with the AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in a significant increase in the production of the cytochrome P-450 microsomal enzyme CYP1A1. Activated AhR caused a downregulation of ER nuclear protein fraction and significantly decreased ER-signaling in TERT-OPEC as determined by ERE-luciferase transient transfection assays. In summary, the TCDD-induced and AhR-mediated anti-estrogenic responses by TERT-OPEC suggest that PHAH affect the predominantly estrogen-dependent differentiation of the oviduct epithelium within the fallopian tube. This action then alters the local endocrine milieu, potentially resulting in a largely unexplored cause of impaired embryonic development and female infertility.

  3. Leflunomide or A77 1726 protect from acetaminophen-induced cell injury through inhibition of JNK-mediated mitochondrial permeability transition in immortalized human hepatocytes

    International Nuclear Information System (INIS)

    Latchoumycandane, Calivarathan; Seah, Quee Ming; Tan, Rachel C.H.; Sattabongkot, Jetsumon; Beerheide, Walter; Boelsterli, Urs A.

    2006-01-01

    Leflunomide, a disease-modifying anti-rheumatic drug, protects against T-cell-mediated liver injury by poorly understood mechanisms. The active metabolite of leflunomide, A77 1726 (teriflunomide) has been shown to inhibit stress-activated protein kinases (JNK pathway), which are key regulators of mitochondria-mediated cell death. Therefore, we hypothesized that leflunomide may protect from drugs that induce the mitochondrial permeability transition (mPT) by blocking the JNK signaling pathway. To this end, we exposed cultured immortalized human hepatocytes (HC-04) to the standard protoxicant drug acetaminophen (APAP), which induces CsA-sensitive mPT-mediated cell death. We determined the effects of leflunomide on the extent of APAP-induced hepatocyte injury and the upstream JNK-mediated mitochondrial signaling pathways. We found that leflunomide or A77 1726 concentration-dependently protected hepatocytes from APAP (1 mM)-induced mitochondrial permeabilization and lethal cell injury. This was not due to proximal inhibition of CYP-catalyzed APAP bioactivation to its thiol-reactive metabolite. Instead, we demonstrate that leflunomide (20 μM) inhibited the APAP-induced early (3 h) activation (phosphorylation) of JNK1/2, thus inhibiting phosphorylation of the anti-apoptotic protein Bcl-2 and preventing P-Bcl-2-mediated induction of the mPT. This greatly attenuated mitochondrial cytochrome c release, which we used as a marker for mitochondrial permeabilization. The specific JNK2 inhibitor SP600125 similarly protected from APAP-induced cell death. In conclusion, these findings are consistent with our hypothesis that leflunomide protects from protoxicant-induced hepatocyte injury by inhibiting JNK signaling and preventing mPT induction

  4. Miscellaneous conditions

    International Nuclear Information System (INIS)

    Berquist, T.H.; Hoffman, A.D.

    1989-01-01

    This paper reports on numerous conditions (systemic diseases, metabolic diseases, etc.) that may also affect the foot and ankle. In many cases, imaging of the foot and ankle is not performed for primary diagnostic purposes. However, radiographic changes do occur with these conditions. Therefore, it is important to be aware of radiographic abnormalities that these diseases may cause in the foot and ankle

  5. C-terminal cleavage of DeltaNp63alpha is associated with TSA-induced apoptosis in immortalized corneal epithelial cells.

    Science.gov (United States)

    Robertson, Danielle M; Ho, Su-Inn; Cavanagh, H Dwight

    2010-08-01

    In the central human corneal epithelium, loss of DeltaNp63 occurs in all surface epithelial cells preparing to undergo desquamation, suggesting a potential role for DeltaNp63 isoforms in mediating surface cell apoptotic shedding. In this study, the authors investigated a role for DeltaNp63 isoforms in caspase-mediated apoptosis in a telomerase-immortalized corneal epithelial cell line. For in vitro studies, hTCEpi cells were cultured in KGM-2 serum-free culture media containing 0.15 mM calcium. To assess dynamic protein interactions among individual DeltaNp63 isoforms, DeltaNp63-EGFP expression plasmids were transiently expressed in hTCEpi cells and evaluated by FRAP. Trichostatin-A (TSA; 3.31 muM) was used to induce cell death as measured by caspase activity. Cleavage and loss of endogenous DeltaNp63alpha, DeltaNp63-EGFP expression plasmids, and p53 were assessed after treatment with TSA and siRNA. Transient expression of DeltaNp63-EGFP alpha and beta isoforms resulted in the formation of a smaller isoform similar in size to DeltaNp63gamma-EGFP. FRAP demonstrated that DeltaNp63alpha-EGFP has greater immobile fraction than beta or gamma. TSA induced caspase-mediated apoptotic pathways; caspase induction was accompanied by a decrease in endogenous DeltaNp63alpha and p53. TSA upregulated DeltaNp63-EGFP plasmid expression; this was accompanied by a selective increase in cleavage of DeltaNp63alpha-EGFP. siRNA knockdown of DeltaNp63alpha correlated with a reduction in p53 independently of TSA. DeltaNp63alpha is the dominant active isoform in corneal epithelial cell nuclei. Loss of DeltaNp63alpha occurs during apoptotic signaling by cleavage at the C terminus. The corresponding loss of p53 suggests that a significant relationship appears to exist between these two regulatory proteins.

  6. Transplantation of Immortalized CD34+ and CD34- Adipose-Derived Stem Cells Improve Cardiac Function and Mitigate Systemic Pro-Inflammatory Responses.

    Directory of Open Access Journals (Sweden)

    Jong-Ho Kim

    Full Text Available Adipose-derived stem cells (ADSCs have the potential to differentiate into various cell lineages and they are easily obtainable from patients, which makes them a promising candidate for cell therapy. However, a drawback is their limited life span during in vitro culture. Therefore, hTERT-immortalized CD34+ and CD34- mouse ADSC lines (mADSCshTERT tagged with GFP were established. We evaluated the proliferation capacity, multi-differentiation potential, and secretory profiles of CD34+ and CD34- mADSCshTERT in vitro, as well as their effects on cardiac function and systemic inflammation following transplantation into a rat model of acute myocardial infarction (AMI to assess whether these cells could be used as a novel cell source for regeneration therapy in the cardiovascular field. CD34+ and CD34- mADSCshTERT demonstrated phenotypic characteristics and multi-differentiation potentials similar to those of primary mADSCs. CD34+ mADSCshTERT exhibited a higher proliferation ability compared to CD34- mADSCshTERT, whereas CD34- mADSCshTERT showed a higher osteogenic differentiation potential compared to CD34+ mADSCshTERT. Primary mADSCs, CD34+, and CD34- mADSCshTERT primarily secreted EGF, TGF-β1, IGF-1, IGF-2, MCP-1, and HGFR. CD34+ mADSCshTERT had higher secretion of VEGF and SDF-1 compared to CD34- mADSCshTERT. IL-6 secretion was severely reduced in both CD34+ and CD34- mADSCshTERT compared to primary mADSCs. Transplantation of CD34+ and CD34- mADSCshTERT significantly improved the left ventricular ejection fraction and reduced infarct size compared to AMI-induced rats after 28 days. At 28 days after transplantation, engraftment of CD34+ and CD34- mADSCshTERT was confirmed by positive Y chromosome staining, and differentiation of CD34+ and CD34- mADSCshTERT into endothelial cells was found in the infarcted myocardium. Significant decreases were observed in circulating IL-6 levels in CD34+ and CD34- mADSCshTERT groups compared to the AMI

  7. Aquatic conditions

    Science.gov (United States)

    Warren E. Heilman

    1999-01-01

    This publication provides citizens, private and public organizations, scientists, and others with information about the aquatic conditions in or near national forests in the Ozark-Ouachita Highlands: the Mark Twain in Missouri, the Ouachita in Arkansas and Oklahoma, and the Ozark-St. Francis National Forests in Arkansas. This report includes water quality analyses...

  8. Husserl, the Monad and Immortality

    African Journals Online (AJOL)

    denise

    otherwise it is little more than shorthand for a long, complex ... Husserl first uses the term “monad” in “Philosophy as. Rigorous Science” ..... its sensory perceptions and affections. But, beyond ... “lost” in memory or daydream or in any other of its.

  9. The prevalence and relative risk of drink and drug driving in the Netherlands: a case-control study in the Tilburg police district : research in the framework of the European research programme IMMORTAL (Impaired Motorists, Methods of Roadside Testing and Assessment for Licensing).

    NARCIS (Netherlands)

    Mathijssen, M.P.M. & Houwing, S.

    2005-01-01

    Drink and drug driving can have an impact on the driving performance and accident risk. This epidemiological study, which forms part of the European project IMMORTAL, investigates the prevalence of eight defined drug groups, including alcohol, among drivers in the Tilburg police district. To examine

  10. Culture Conditions Affect Expression of DUX4 in FSHD Myoblasts

    Directory of Open Access Journals (Sweden)

    Sachchida Nand Pandey

    2015-05-01

    Full Text Available Facioscapulohumeral muscular dystrophy (FSHD is believed to be caused by aberrant expression of double homeobox 4 (DUX4 due to epigenetic changes of the D4Z4 region at chromosome 4q35. Detecting DUX4 is challenging due to its stochastic expression pattern and low transcription level. In this study, we examined different cDNA synthesis strategies and the sensitivity for DUX4 detection. In addition, we investigated the effects of dexamethasone and knockout serum replacement (KOSR on DUX4 expression in culture. Our data showed that DUX4 was consistently detected in cDNA samples synthesized using Superscript III. The sensitivity of DUX4 detection was higher in the samples synthesized using oligo(dT primers compared to random hexamers. Adding dexamethasone to the culture media significantly suppressed DUX4 expression in immortalized (1.3 fold, p < 0.01 and primary (4.7 fold, p < 0.01 FSHD myoblasts, respectively. Culture medium with KOSR increased DUX4 expression and the response is concentration dependent. The findings suggest that detection strategies and culture conditions should be carefully considered when studying DUX4 in cultured cells.

  11. «El inmortal» de Jorge Luis Borges: el yo, infinitos, absolutos y vocabularios finales Jorge Luis Borges's «The Immortal»: the Self, Infinites, Absolutes, and Final Vocabularies

    Directory of Open Access Journals (Sweden)

    Jorge Sagastume

    2011-07-01

    ilosofía de la lengua.Jorge Luis Borges often consulted Mathematics and Imagination by E. Kasner and J. Newman, where they address the set theory (branch of mathematics that studies the relationship between sets proposed by Georg Cantor (18451918, and in which transfinite arithmetic (beyond finite arithmetic is established, and an epistemic system created to represent different levels of the ininite. Thus, Cantor labels the different levels of the ininite by assigning to each the irst letter of the Hebrew alphabet, the Aleph, followed by a number, depending on the level of infinite he is referring to (Aleph-zero, Aleph-one, etc.. Following these ideas, Borges weaves several narratives, discussing the ininite and the absolute. An example of such narratives is the collection of stories compiled under the title The Aleph, which opens with «The Immortal» and closes with the story that gives the collection its title. The objective of this paper is to study «The Immortal» under the Cantorian lens, so as to discuss one particular absolute, the self, and to suggest that it is impossible to establish a inal vocabulary, or a deinite deinition, about this topic. This impossibility, Borges proposes, is in part due to the apparent initude of language, on the one hand, and on the other, the fallible attributes of human memory are also crucial when it comes to deining anything. However, being the ironist Borges is, he is capable of providing through «The Immortal» a re-description of these issues by means of a transinite language that resolves some paradoxes while at the same time reveals others. Due to this way of writing, I propose Borges fosters a continuation of the dialogue among different disciplines. Though I will center my analysis on «The Immortal», to develop these ideas I will also revisit other stories in The Aleph departing from a theoretical approach rooted in the philosophy of language.

  12. Condition Indicators for Gearbox Condition Monitoring Systems

    Directory of Open Access Journals (Sweden)

    P. Večeř

    2005-01-01

    Full Text Available Condition monitoring systems for manual transmissions based on vibration diagnostics are widely applied in industry. The systems deal with various condition indicators, most of which are focused on a specific type of gearbox fault. Frequently used condition indicators (CIs are described in this paper. The ability of a selected condition indicator to describe the degree of gearing wear was tested using vibration signals acquired during durability testing of manual transmission with helical gears. 

  13. Role of Vitamin D in Maintaining Renal Epithelial Barrier Function in Uremic Conditions

    Directory of Open Access Journals (Sweden)

    Milos Mihajlovic

    2017-11-01

    Full Text Available As current kidney replacement therapies are not efficient enough for end-stage renal disease (ESRD treatment, a bioartificial kidney (BAK device, based on conditionally immortalized human proximal tubule epithelial cells (ciPTEC, could represent an attractive solution. The active transport activity of such a system was recently demonstrated. In addition, endocrine functions of the cells, such as vitamin D activation, are relevant. The organic anion transporter 1 (OAT-1 overexpressing ciPTEC line presented 1α-hydroxylase (CYP27B1, 24-hydroxylase (CYP24A1 and vitamin D receptor (VDR, responsible for vitamin D activation, degradation and function, respectively. The ability to produce and secrete 1α,25-dihydroxy-vitamin D3, was shown after incubation with the precursor, 25-hydroxy-vitamin D3. The beneficial effect of vitamin D on cell function and behavior in uremic conditions was studied in the presence of an anionic uremic toxins mixture. Vitamin D could restore cell viability, and inflammatory and oxidative status, as shown by cell metabolic activity, interleukin-6 (IL-6 levels and reactive oxygen species (ROS production, respectively. Finally, vitamin D restored transepithelial barrier function, as evidenced by decreased inulin-FITC leakage in biofunctionalized hollow fiber membranes (HFM carrying ciPTEC-OAT1. In conclusion, the protective effects of vitamin D in uremic conditions and proven ciPTEC-OAT1 endocrine function encourage the use of these cells for BAK application.

  14. Low calcium culture condition induces mesenchymal cell-like phenotype in normal human epidermal keratinocytes

    International Nuclear Information System (INIS)

    Takagi, Ryo; Yamato, Masayuki; Murakami, Daisuke; Sugiyama, Hiroaki; Okano, Teruo

    2011-01-01

    Highlights: → Normal human epidermal keratinocytes serially cultured under low calcium concentration were cytokeratin and vimentin double positive cells. → The human keratinocytes expressed some epithelial stem/progenitor cell makers, mesenchymal cell markers, and markers of epithelial-mesenchymal transition. → Mesenchymal cell-like phenotype in the keratinocytes was suppressed under high-calcium condition. -- Abstract: Epithelial-mesenchymal transition (EMT) is an important cellular phenomenon in organ developments, cancer invasions, and wound healing, and many types of transformed cell lines are used for investigating for molecular mechanisms of EMT. However, there are few reports for EMT in normal human epithelial cells, which are non-transformed or non-immortalized cells, in vitro. Therefore, normal human epidermal keratinocytes (NHEK) serially cultured in low-calcium concentration medium (LCM) were used for investigating relations between differentiation and proliferation and mesenchymal-like phenotype in the present study, since long-term cultivation of NHEK is achieved in LCM. Interestingly, NHEK serially cultured in LCM consisted essentially of cytokeratin-vimentin double positive cells (98%), although the NHEK exhibited differentiation under high-calcium culture condition with 3T3 feeder layer. The vimentin expression was suppressed under high-calcium condition. These results may indicate the importance of mesenchymal-like phenotype for serially cultivation of NHEK in vitro.

  15. The Lcn2-engineered HEK-293 cells show senescence under stressful condition

    Directory of Open Access Journals (Sweden)

    Bahareh Bahmani

    2015-05-01

    Full Text Available Objective(s: Lipocalin2 (Lcn2 gene is highly expressed in response to various types of cellular stresses. The precise role of Lcn2 has not been fully understood yet. However, it plays a key role in controlling vital cellular processes such as proliferation, apoptosis and metabolism. Recently it was shown that Lcn2 decreases senescence and increases proliferation of mesenchymal stem cells (MSC with finite life span under either normal or oxidative stress conditions. However, Lcn2 effects on immortal cell line with infinite proliferation are not defined completely.  Materials and Material and Methods: HEK-293 cells were transfected with recombinant pcDNA3.1 containing Lcn2 fragment (pcDNA3.1-Lcn2. Expression of lipocalin2 in transfected cells was evaluated by RT-PCR, real time RT-PCR, and ELISA. Different cell groups were treated with H2O2 and WST-1 assay was performed to determine their proliferation rate. Senescence was studied by β-galactosidase and gimsa staining methods as well as evaluation of the expression of senescence-related genes by real time RT-PCR. Results: Lcn2 increased cell proliferation under normal culture condition, while the proliferation slightly decreased under oxidative stress.  This decrease was further found to be attributed to senescence. Conclusion: Our findings indicated that under harmful conditions, Lcn2 gene is responsible for the regulation of cell survival through senescence.

  16. “…so much immortal wealth”: Life in the Sick-Room by Harriet Martineau as Eco-Sustainable Narrative

    Directory of Open Access Journals (Sweden)

    Loredana Salis

    2017-11-01

    Full Text Available This study reassesses Harriet Martineau’s Life in the Sick-Room as an example of Victorian eco-sustainable narrative. Based on the author’s real-life experience as a long-term patient, the volume was conceived as a normative treatise on the condition of the invalid, and contributed significantly to ongoing debates on the reform of the medical system. Though the author does not deliberately provide readers with an ecological message, she advocates a remedial process that sees nature as a refuge and a redemptive space. A re-reading of Life in the Sick-Room today shows its value from an eco-critical viewpoint.

  17. Skin Condition Finder

    Science.gov (United States)

    ... SKIN CONDITIONS HEALTH TOPICS FOR PROFESSIONALS Rash and Skin Condition Finder 1 Select Age Group Infant Child ... Toe Toe Webspace Toe Nail CLOSE About the Skin Condition Finder Have a health question or concern? ...

  18. Staphylococcus aureus alpha-toxin mediates general and cell type-specific changes in metabolite concentrations of immortalized human airway epithelial cells.

    Directory of Open Access Journals (Sweden)

    Philipp Gierok

    Full Text Available Staphylococcus aureus alpha-toxin (Hla is a potent pore-forming cytotoxin that plays an important role in the pathogenesis of S. aureus infections, including pneumonia. The impact of Hla on the dynamics of the metabolome in eukaryotic host cells has not been investigated comprehensively. Using 1H-NMR, GC-MS and HPLC-MS, we quantified the concentrations of 51 intracellular metabolites and assessed alterations in the amount of 25 extracellular metabolites in the two human bronchial epithelial cell lines S9 and 16HBE14o- under standard culture conditions and after treatment with sub-lethal amounts (2 µg/ml of recombinant Hla (rHla in a time-dependent manner. Treatment of cells with rHla caused substantial decreases in the concentrations of intracellular metabolites from different metabolic pathways in both cell lines, including ATP and amino acids. Concomitant increases in the extracellular concentrations were detected for various intracellular compounds, including nucleotides, glutathione disulfide and NAD+. Our results indicate that rHla has a major impact on the metabolome of eukaryotic cells as a consequence of direct rHla-mediated alterations in plasma membrane permeability or indirect effects mediated by cellular signalling. However, cell-specific changes also were observed. Glucose consumption and lactate production rates suggest that the glycolytic activity of S9 cells, but not of 16HBE14o- cells, is increased in response to rHla. This could contribute to the observed higher level of resistance of S9 cells against rHla-induced membrane damage.

  19. Betting on conditionals

    OpenAIRE

    Politzer , Guy; Over , David P; Baratgin , Jean

    2010-01-01

    A study is reported testing two hypotheses about a close parallel relation between indicative conditionals, if A then B, and conditional bets, I bet you that if A then B. The first is that both the indicative conditional and the conditional bet are related to the conditional probability, P(B|A). The second is that de Finetti's three-valued truth table has psychological reality for both types of conditional – true, false, or void for indicative conditionals and win, lose or void for conditiona...

  20. Regulation of taurine transport at the blood-placental barrier by calcium ion, PKC activator and oxidative stress conditions

    Directory of Open Access Journals (Sweden)

    Lee Na-Young

    2010-08-01

    Full Text Available Abstract Background In the present study, we investigated the changes of uptake and efflux transport of taurine under various stress conditions using rat conditionally immortalized syncytiotrophoblast cell line (TR-TBT cells, as in vitro blood-placental barrier (BPB model. Methods The transport of taurine in TR-TBT cells were characterized by cellular uptake study using radiolabeled taurine. The efflux of taurine was measured from the amount of radiolabeled taurine remaining in the cells after the uptake of radiolabeled taurine for 60 min. Results Taurine uptake was significantly decreased by phosphorylation of protein kinase C (PKC activator in TR-TBT cells. Also, calcium ion (Ca2+ was involved in taurine transport in TR-TBT cells. Taurine uptake was inhibited and efflux was enhanced under calcium free conditions in the cells. In addition, oxidative stress induced the change of taurine transport in TR-TBT cells, but the changes were different depending on the types of oxidative stress inducing agents. Tumor necrosis factor-α (TNF-α, lipopolysaccharide (LPS and diethyl maleate (DEM significantly increased taurine uptake, but H2O2 and nitric oxide (NO donor decreased taurine uptake in the cells. Taurine efflux was down-regulated by TNF-α in TR-TBT cells. Conclusion Taurine transport in TR-TBT cells were regulated diversely at extracellular Ca2+ level, PKC activator and oxidative stress conditions. It suggested that variable stresses affected the taurine supplies from maternal blood to fetus and taurine level of fetus.

  1. Conditional Aid Effectiveness

    DEFF Research Database (Denmark)

    Doucouliagos, Hristos; Paldam, Martin

    of the differences in results between studies. Taking all available studies in consideration, we find no support for conditionality with respect to policy, while conditionality regarding aid itself is dubious. However, the results differ depending on the authors’ institutional affiliation....

  2. Energetics Conditioning Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Energetics Conditioning Facility is used for long term and short term aging studies of energetic materials. The facility has 10 conditioning chambers of which 2...

  3. Modelling classroom conditions with different boundary conditions

    DEFF Research Database (Denmark)

    Marbjerg, Gerd Høy; Jeong, Cheol-Ho; Brunskog, Jonas

    2014-01-01

    A model that combines image source modelling and acoustical radiosity with complex boundary condition, thus including phase shifts on reflection has been developed. The model is called PARISM (Phased Acoustical Radiosity and Image Source Model). It has been developed in order to be able to model...

  4. Watershed condition [Chapter 4

    Science.gov (United States)

    Daniel G. Neary; Jonathan W. Long; Malchus B. Baker

    2012-01-01

    Managers of the Prescott National Forest are obliged to evaluate the conditions of watersheds under their jurisdiction in order to guide informed decisions concerning grazing allotments, forest and woodland management, restoration treatments, and other management initiatives. Watershed condition has been delineated by contrasts between “good” and “poor” conditions (...

  5. Conditional uncertainty principle

    Science.gov (United States)

    Gour, Gilad; Grudka, Andrzej; Horodecki, Michał; Kłobus, Waldemar; Łodyga, Justyna; Narasimhachar, Varun

    2018-04-01

    We develop a general operational framework that formalizes the concept of conditional uncertainty in a measure-independent fashion. Our formalism is built upon a mathematical relation which we call conditional majorization. We define conditional majorization and, for the case of classical memory, we provide its thorough characterization in terms of monotones, i.e., functions that preserve the partial order under conditional majorization. We demonstrate the application of this framework by deriving two types of memory-assisted uncertainty relations, (1) a monotone-based conditional uncertainty relation and (2) a universal measure-independent conditional uncertainty relation, both of which set a lower bound on the minimal uncertainty that Bob has about Alice's pair of incompatible measurements, conditioned on arbitrary measurement that Bob makes on his own system. We next compare the obtained relations with their existing entropic counterparts and find that they are at least independent.

  6. Diffused Knowledge Immortalizes Itself The LOCKSS Program

    CERN Document Server

    Reich, Victoria A

    2003-01-01

    The LOCKSS model, 'Lots of Copies Keeps Stuff Safe,' creates low-cost, persistent digital 'caches' of authoritative versions of http-delivered content. The LOCKSS software enables institutions to locally collect, store, preserve and archive authorized content, thus safeguarding their community's access to that content. The current version of LOCKSS software is restricted to electronic journals. Accuracy and completeness of LOCKSS caches are assured through a peer-to-peer polling and reputation system (operated through LCAP, LOCKSS' communication protocol), which is both robust and secure. LOCKSS replicas cooperate to detect and repair preservation failures. LOCKSS is designed to run on inexpensive hardware and to require almost no technical administration. The software has been under development since 1999 and is distributed as open source.

  7. The (not so) Immortal Strand Hypothesis

    OpenAIRE

    Tomasetti, Cristian; Bozic, Ivana

    2015-01-01

    Background: Non-random segregation of DNA strands during stem cell replication has been proposed as a mechanism to minimize accumulated genetic errors in stem cells of rapidly dividing tissues. According to this hypothesis, an “immortal” DNA strand is passed to the stem cell daughter and not the more differentiated cell, keeping the stem cell lineage replication error-free. After it was introduced, experimental evidence both in favor and against the hypothesis has been presented. Principal...

  8. Cell culture from sponges: pluripotency and immortality

    NARCIS (Netherlands)

    Caralt Bosch, de S.; Uriz, M.J.; Wijffels, R.H.

    2007-01-01

    Sponges are a source of compounds with potential pharmaceutical applications. In this article, methods of sponge cell culture for production of these bioactive compounds are reviewed, and new approaches for overcoming the problem of metabolite supply are examined. The use of embryos is proposed as a

  9. The search of a digital immortality?

    Directory of Open Access Journals (Sweden)

    Carla Landuzzi

    2015-12-01

    Full Text Available The text intends to examine how technological innovations allow the construction of web spaces for shared funeral rituals and their partecipation by those same communities that move across the network. It can be assumed a new resacralization process of rituals referring to an individual system of meanings. The web may be capable of reappropriating the experience of pain through new ways that allow flexible access and fruition without spatial or temporal limits. They are interactive rituals that build an elective sociality, as practiced by the inclusion decisions under emotionally meaningful groups. The search for a digital alter ego that will survive the earthly physicality threatens to tarnish the very identity of the dead.

  10. Suicide, Immortality, and the Method of Embarrassments

    Science.gov (United States)

    Bakan, David

    1976-01-01

    This paper, presented at Self-Destruction and Self-Creation, at Duquesne University (April, 1969) explains that the suicide, reacting to his experience of "being in question" (Heidegger), kills himself to arrogate death to his will. He allows the possibility that if he wished it, he could live forever and usurp death. (Author)

  11. Qualification of conditioning process

    International Nuclear Information System (INIS)

    Wolf, J.

    1989-01-01

    A conditioning process is qualified by the PTB if the execution of pre-treatment and conditioning occurs so that a safe and orderly final storage of the products and waste containers produced can be assumed. All the relevant operating conditions for the plant are laid down by the producer/conditioner of the waste in a handbook. The elements of product inspection by process qualification are shown in tabular form. (DG) [de

  12. Irreversibility and conditional probability

    International Nuclear Information System (INIS)

    Stuart, C.I.J.M.

    1989-01-01

    The mathematical entropy - unlike physical entropy - is simply a measure of uniformity for probability distributions in general. So understood, conditional entropies have the same logical structure as conditional probabilities. If, as is sometimes supposed, conditional probabilities are time-reversible, then so are conditional entropies and, paradoxically, both then share this symmetry with physical equations of motion. The paradox is, of course that probabilities yield a direction to time both in statistical mechanics and quantum mechanics, while the equations of motion do not. The supposed time-reversibility of both conditionals seems also to involve a form of retrocausality that is related to, but possibly not the same as, that described by Costa de Beaurgard. The retrocausality is paradoxically at odds with the generally presumed irreversibility of the quantum mechanical measurement process. Further paradox emerges if the supposed time-reversibility of the conditionals is linked with the idea that the thermodynamic entropy is the same thing as 'missing information' since this confounds the thermodynamic and mathematical entropies. However, it is shown that irreversibility is a formal consequence of conditional entropies and, hence, of conditional probabilities also. 8 refs. (Author)

  13. Lossless Conditional Schema Evolution

    DEFF Research Database (Denmark)

    Jensen, Ole Guttorm; Bøhlen, Michael Hanspeter

    2003-01-01

    The paper considers conditional schema evolution, where schema changes change the schema of the tuples that satisfy the change condition. When the schema of a relation change some tuples may no longer fit the current schema. Handling the mismatch between the intended schema of tuples and the reco......The paper considers conditional schema evolution, where schema changes change the schema of the tuples that satisfy the change condition. When the schema of a relation change some tuples may no longer fit the current schema. Handling the mismatch between the intended schema of tuples...... and the recorded schema of tuples is at the core of a DBMS that supports schema evolution. We propose to keep track of schema mismatches at the level of individual tuples, and prove that conditionally evolving schemas, in contrast to current commercial database systems, are lossless when the schema evolves...

  14. Evaporation under vacuum condition

    International Nuclear Information System (INIS)

    Mizuta, Satoshi; Shibata, Yuki; Yuki, Kazuhisa; Hashizume, Hidetoshi; Toda, Saburo; Takase, Kazuyuki; Akimoto, Hajime

    2000-01-01

    In nuclear fusion reactor design, an event of water coolant ingress into its vacuum vessel is now being considered as one of the most probable accidents. In this report, the evaporation under vacuum condition is evaluated by using the evaporation model we have developed. The results show that shock-wave by the evaporation occurs whose behavior strongly depends on the initial conditions of vacuum. And in the case of lower initial pressure and temperature, the surface temp finally becomes higher than other conditions. (author)

  15. Chronic Conditions Dashboard

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CMS Chronic Conditions Dashboard presents statistical views of information on the prevalence, utilization and Medicare spending for Medicare beneficiaries with...

  16. Chronic Condition Data Warehouse

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CMS Chronic Condition Data Warehouse (CCW) provides researchers with Medicare and Medicaid beneficiary, claims, and assessment data linked by beneficiary across...

  17. Chronic Conditions PUF

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Chronic Conditions PUFs are aggregated files in which each record is a profile or cell defined by the characteristics of Medicare beneficiaries. A profile is...

  18. National Coastal Condition Assessment

    Science.gov (United States)

    The NCCA is a collaborative, statistical survey of the nation's coastal waters and the Great Lakes. It is one of four national surveys that EPA and its partners conduct to assess the condition and health of the nation's water resources.

  19. Operant Conditioning and Education.

    Science.gov (United States)

    de Noronha, Mario

    A case study of a learning disabled 8-year-old with behavior disturbancs is presented to highlight the use of operant conditioning in cutting down educational costs and easing the teacher's class management problems. (CL)

  20. Multidimensional HAM-conditions

    DEFF Research Database (Denmark)

    Hansen, Ernst Jan de Place

    Heat, Air and Moisture (HAM) conditions, experimental data are needed. Tests were performed in the large climate simulator at SBi involving full-scale wall elements. The elements were exposed for steady-state conditions, and temperature cycles simulating April and September climate in Denmark....... The effect on the moisture and temperature conditions of the addition of a vapour barrier and an outer cladding on timber frame walls was studied. The report contains comprehensive appendices documenting the full-scale tests. The tests were performed as a part of the project 'Model for Multidimensional Heat......, Air and Moisture Conditions in Building Envelope Components' carried out as a co-project between DTU Byg and SBi....

  1. Common Childhood Orthopedic Conditions

    Science.gov (United States)

    ... Parents Parents site Sitio para padres General Health Growth & Development Infections Diseases & Conditions Pregnancy & Baby Nutrition & Fitness Emotions & ... pain. Toe Walking Toe walking is common among toddlers as they learn to walk, especially during the ...

  2. Conditional Probabilistic Population Forecasting

    OpenAIRE

    Sanderson, W.C.; Scherbov, S.; O'Neill, B.C.; Lutz, W.

    2003-01-01

    Since policy makers often prefer to think in terms of scenarios, the question has arisen as to whether it is possible to make conditional population forecasts in a probabilistic context. This paper shows that it is both possible and useful to make these forecasts. We do this with two different kinds of examples. The first is the probabilistic analog of deterministic scenario analysis. Conditional probabilistic scenario analysis is essential for policy makers it allows them to answer "what if"...

  3. Conditional probabilistic population forecasting

    OpenAIRE

    Sanderson, Warren; Scherbov, Sergei; O'Neill, Brian; Lutz, Wolfgang

    2003-01-01

    Since policy-makers often prefer to think in terms of alternative scenarios, the question has arisen as to whether it is possible to make conditional population forecasts in a probabilistic context. This paper shows that it is both possible and useful to make these forecasts. We do this with two different kinds of examples. The first is the probabilistic analog of deterministic scenario analysis. Conditional probabilistic scenario analysis is essential for policy-makers because it allows them...

  4. Conditional Probabilistic Population Forecasting

    OpenAIRE

    Sanderson, Warren C.; Scherbov, Sergei; O'Neill, Brian C.; Lutz, Wolfgang

    2004-01-01

    Since policy-makers often prefer to think in terms of alternative scenarios, the question has arisen as to whether it is possible to make conditional population forecasts in a probabilistic context. This paper shows that it is both possible and useful to make these forecasts. We do this with two different kinds of examples. The first is the probabilistic analog of deterministic scenario analysis. Conditional probabilistic scenario analysis is essential for policy-makers because...

  5. Conditional data watchpoint management

    Science.gov (United States)

    Burdick, Dean Joseph; Vaidyanathan, Basu

    2010-08-24

    A method, system and computer program product for managing a conditional data watchpoint in a set of instructions being traced is shown in accordance with illustrative embodiments. In one particular embodiment, the method comprises initializing a conditional data watchpoint and determining the watchpoint has been encountered. Upon that determination, examining a current instruction context associated with the encountered watchpoint prior to completion of the current instruction execution, further determining a first action responsive to a positive context examination; otherwise, determining a second action.

  6. LHCb distributed conditions database

    International Nuclear Information System (INIS)

    Clemencic, M

    2008-01-01

    The LHCb Conditions Database project provides the necessary tools to handle non-event time-varying data. The main users of conditions are reconstruction and analysis processes, which are running on the Grid. To allow efficient access to the data, we need to use a synchronized replica of the content of the database located at the same site as the event data file, i.e. the LHCb Tier1. The replica to be accessed is selected from information stored on LFC (LCG File Catalog) and managed with the interface provided by the LCG developed library CORAL. The plan to limit the submission of jobs to those sites where the required conditions are available will also be presented. LHCb applications are using the Conditions Database framework on a production basis since March 2007. We have been able to collect statistics on the performance and effectiveness of both the LCG library COOL (the library providing conditions handling functionalities) and the distribution framework itself. Stress tests on the CNAF hosted replica of the Conditions Database have been performed and the results will be summarized here

  7. Conditions precedent and indemnities

    International Nuclear Information System (INIS)

    Nielsen, A.D.

    1999-01-01

    The use of certain conditions which allow purchase and sale agreements to be voided without any liability to either the vendor or purchaser are discussed. The drafting issues that arise when preparing these conditions are described and some common types of conditions precedent found in oil and gas purchase and sale transactions are explained. A 'conditions precedent' was defined as being something which must happen before an interest can vest or grow or before an obligation can be performed. Vendors and purchasers use conditions precedent to provide protection against having to conclude a transaction in circumstances that are not acceptable to them. The manner in which indemnity provisions in an oil and gas purchase and sale agreement work, is also explained. These usually relate to breaches of the contract by either vendors or purchasers. Indemnity clauses are used to allocate risk between the vendor and the purchaser and to set out the mechanics by which either party may make a claim against the other. Ways in which to prepare indemnity clauses are described. 2 refs

  8. Nonprice terms and conditions

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    In this and the following chapter the authors review some of the more common provisions contained in wheeling contracts. Here they discuss nonprice terms and conditions. In the next chapter they look at the manner in which they address the pricing issue. At the outset one should note that there is a relationship between price and nonprice terms and condition. A couple of the provisions discussed here affect the risks incurred by the wheeling utility and the price it may charge for that service. These provisions include the length of the contract, the degree to which service can be interrupted and the ability to terminate the contract early, among others. These provisions are often characterized as nonprice terms and conditions. In reality, however, these factors have a direct bearing on the overall cost of wheeling services provided

  9. Lossless conditional schema evolution

    DEFF Research Database (Denmark)

    Jensen, Ole Guttorm; Böhlen, Michael

    2004-01-01

    is a precondition for a flexible semantics that allows to correctly answer general queries over evolving schemas. The key challenge is to handle attribute mismatches between the intended and recorded schema in a consistent way. We provide a parametric approach to resolve mismatches according to the needs......Conditional schema changes change the schema of the tuples that satisfy the change condition. When the schema of a relation changes some tuples may no longer fit the current schema. Handling the mismatch between the intended schema of tuples and the recorded schema of tuples is at the core...... of a DBMS that supports schema evolution. We propose to keep track of schema mismatches at the level of individual tuples, and prove that evolving schemas with conditional schema changes, in contrast to database systems relying on data migration, are lossless when the schema evolves. The lossless property...

  10. Stochastic conditional intensity processes

    DEFF Research Database (Denmark)

    Bauwens, Luc; Hautsch, Nikolaus

    2006-01-01

    model allows for a wide range of (cross-)autocorrelation structures in multivariate point processes. The model is estimated by simulated maximum likelihood (SML) using the efficient importance sampling (EIS) technique. By modeling price intensities based on NYSE trading, we provide significant evidence......In this article, we introduce the so-called stochastic conditional intensity (SCI) model by extending Russell’s (1999) autoregressive conditional intensity (ACI) model by a latent common dynamic factor that jointly drives the individual intensity components. We show by simulations that the proposed...... for a joint latent factor and show that its inclusion allows for an improved and more parsimonious specification of the multivariate intensity process...

  11. Electronic signal conditioning

    CERN Document Server

    NEWBY, BRUCE

    1994-01-01

    At technician level, brief references to signal conditioning crop up in a fragmented way in various textbooks, but there has been no single textbook, until now!More advanced texts do exist but they are more mathematical and presuppose a higher level of understanding of electronics and statistics. Electronic Signal Conditioning is designed for HNC/D students and City & Guilds Electronics Servicing 2240 Parts 2 & 3. It will also be useful for BTEC National, Advanced GNVQ, A-level electronics and introductory courses at degree level.

  12. Probabilistic conditional independence structures

    CERN Document Server

    Studeny, Milan

    2005-01-01

    Probabilistic Conditional Independence Structures provides the mathematical description of probabilistic conditional independence structures; the author uses non-graphical methods of their description, and takes an algebraic approach.The monograph presents the methods of structural imsets and supermodular functions, and deals with independence implication and equivalence of structural imsets.Motivation, mathematical foundations and areas of application are included, and a rough overview of graphical methods is also given.In particular, the author has been careful to use suitable terminology, and presents the work so that it will be understood by both statisticians, and by researchers in artificial intelligence.The necessary elementary mathematical notions are recalled in an appendix.

  13. Conditioning experiences and phobias

    NARCIS (Netherlands)

    Merckelbach, H.; de Ruiter, C.; van den Hout, M.A.; Hoekstra, R.

    1989-01-01

    A retrospective study was conducted to examine the extent to which phobias are associated with a conditioning pathway to fear. The Phobic Origin Questionnaire (Öst and Hugdahl, Behav. Res. Ther. 19, 439-477, 1981) was administered to a sample of 91 phobic outpatients (patients with panic disorder

  14. PERIODONTAL CONDITIONS IN EUROPE

    NARCIS (Netherlands)

    PILOT, T; MIYAZAKI, H

    The aim of the present overview is to evaluate the periodontal conditions in European populations. Study was made of a number of extensive surveys of periodontal diseases carried out in a number of European countries, primarily North West Europe. These surveys often provide considerable detail.

  15. Sufficiency of Bell's conditions

    Energy Technology Data Exchange (ETDEWEB)

    Gutkowski, D; Masotto, G [Istituto di Matematica della Universita di Palermo (Italy); Valdes, M V

    1979-04-11

    It is shown that, if the results of measurements of spin components of two-spin one-half particles coupled to a singlet state with respect to n=3 directions satisfy Bell's conditions, then these results are compatible with a local hidden-variable theory. The previous statement is extended to the case n=4.

  16. Benign Breast Conditions

    Science.gov (United States)

    ... breast condition refers to a lump, cyst, or nipple discharge (fluid) of the female or male breast that is not cancerous. There are numerous ... Intraductal papillomas. Small tumors can form in your nipple’s milk ducts. ... These are rare in men. Men do have undeveloped milk ducts. The most ...

  17. A Tourism Conditions Index

    NARCIS (Netherlands)

    C-L. Chang (Chia-Lin); H-K. Hsu (Hui-Kuang); M.J. McAleer (Michael)

    2014-01-01

    markdownabstract__Abstract__ This paper uses monthly data from April 2005 to August 2013 for Taiwan to propose a novel tourism indicator, namely the Tourism Conditions Index (TCI). TCI accounts for the spillover weights based on the Granger causality test and estimates of the multivariate BEKK

  18. Teachers and Operant Conditioning.

    Science.gov (United States)

    Frey, Sherman

    A survey was conducted of 406 elementary, middle, and secondary school teachers to determine their understanding, acceptance, and use of the principle of operant conditioning. The treatment of data was by percent and chi square analysis primarily according to sex, experience, degree, and position. Subjects reported that a) they believed that the…

  19. Operant Conditioning - Token Economy.

    Science.gov (United States)

    Montgomery, Jacqueline; McBurney, Raymond D.

    Described is an Operant Conditioning-Token Economy Program, teaching patients to be responsible for their own behavior, to make choices, and to be motivated to change. The program was instigated with mentally ill patients in a state hospital and was later used with institutionalized mentally handicapped groups. After two years, only four of the…

  20. Theobromine increases NAD⁺/Sirt-1 activity and protects the kidney under diabetic conditions.

    Science.gov (United States)

    Papadimitriou, Alexandros; Silva, Kamila C; Peixoto, Elisa B M I; Borges, Cynthia M; Lopes de Faria, Jacqueline M; Lopes de Faria, José B

    2015-02-01

    Reduction in sirtuin 1 (Sirt-1) is associated with extracellular matrix (ECM) accumulation in the diabetic kidney. Theobromine may reduce kidney ECM accumulation in diabetic rats. In the current study, we aimed to unravel, under diabetic conditions, the mechanism of kidney ECM accumulation induced by a reduction in Sirt-1 and the effect of theobromine in these events. In vitro, we used immortalized human mesangial cells (iHMCs) exposed to high glucose (HG; 30 mM), with or without small interfering RNA for NOX4 and Sirt-1. In vivo, spontaneously hypertensive rats (SHR) were rendered diabetic by means of streptozotocin and studied after 12 wk. The effects of treatment with theobromine were investigated under both conditions. HG leads to a decrease in Sirt-1 activity and NAD(+) levels in iHMCs. Sirt-1 activity could be reestablished by treatment with NAD(+), silencing NOX4, and poly (ADP-ribose) polymerase-1 (PARP-1) blockade, or with theobromine. HG also leads to a low AMP/ATP ratio, acetylation of SMAD3, and increased collagen IV, which is prevented by theobromine. Sirt-1 or AMPK blockade abolished these effects of theobromine. In diabetic SHR, theobromine prevented increases in albuminuria and kidney collagen IV, reduced AMPK, elevated NADPH oxidase activity and PARP-1, and reduced NAD(+) levels and Sirt-1 activity. These results suggest that in diabetes mellitus, Sirt-1 activity is reduced by PARP-1 activation and NAD(+) depletion due to low AMPK, which increases NOX4 expression, leading to ECM accumulation mediated by transforming growth factor (TGF)-β1 signaling. It is suggested that Sirt-1 activation by theobromine may have therapeutic potential for diabetic nephropathy. Copyright © 2015 the American Physiological Society.

  1. Thiamine and benfotiamine prevent apoptosis induced by high glucose-conditioned extracellular matrix in human retinal pericytes.

    Science.gov (United States)

    Beltramo, Elena; Nizheradze, Konstantin; Berrone, Elena; Tarallo, Sonia; Porta, Massimo

    2009-10-01

    Early and selective loss of pericytes and thickening of the basement membrane are hallmarks of diabetic retinopathy. We reported reduced adhesion, but no changes in apoptosis, of bovine retinal pericytes cultured on extracellular matrix (ECM) produced by endothelial cells in high glucose (HG). Since human and bovine pericytes may behave differently in conditions mimicking the diabetic milieu, we verified the behaviour of human retinal pericytes cultured on HG-conditioned ECM. Pericytes were cultured in physiological/HG on ECM produced by human umbilical vein endothelial cells in physiological/HG, alone or in the presence of thiamine and benfotiamine. Adhesion, proliferation, apoptosis, p53 and Bcl-2/Bax ratio (mRNA levels and protein concentrations) were measured in wild-type and immortalized human pericytes. Both types of pericytes adhered less to HG-conditioned ECM and plastic than to physiological glucose-conditioned ECM. DNA synthesis was impaired in pericytes cultured in HG on the three different surfaces but there were no differences in proliferation. DNA fragmentation and Bcl-2/Bax ratio were greatly enhanced by HG-conditioned ECM in pericytes kept in both physiological and HG. Addition of thiamine and benfotiamine to HG during ECM production completely prevented these damaging effects. Apoptosis is strongly increased in pericytes cultured on ECM produced by endothelium in HG, probably due to impairment of the Bcl-2/Bax ratio. Thiamine and benfotiamine completely revert this effect. This behaviour is therefore completely different from that of bovine pericytes, underlining the importance of establishing species-specific cell models to study the mechanisms of diabetic retinopathy. (c) 2009 John Wiley & Sons, Ltd.

  2. Persistent facial pain conditions

    DEFF Research Database (Denmark)

    Forssell, Heli; Alstergren, Per; Bakke, Merete

    2016-01-01

    Persistent facial pains, especially temporomandibular disorders (TMD), are common conditions. As dentists are responsible for the treatment of most of these disorders, up-to date knowledge on the latest advances in the field is essential for successful diagnosis and management. The review covers...... TMD, and different neuropathic or putative neuropathic facial pains such as persistent idiopathic facial pain and atypical odontalgia, trigeminal neuralgia and painful posttraumatic trigeminal neuropathy. The article presents an overview of TMD pain as a biopsychosocial condition, its prevalence......, clinical features, consequences, central and peripheral mechanisms, diagnostic criteria (DC/TMD), and principles of management. For each of the neuropathic facial pain entities, the definitions, prevalence, clinical features, and diagnostics are described. The current understanding of the pathophysiology...

  3. Time, rate, and conditioning.

    Science.gov (United States)

    Gallistel, C R; Gibbon, J

    2000-04-01

    The authors draw together and develop previous timing models for a broad range of conditioning phenomena to reveal their common conceptual foundations: First, conditioning depends on the learning of the temporal intervals between events and the reciprocals of these intervals, the rates of event occurrence. Second, remembered intervals and rates translate into observed behavior through decision processes whose structure is adapted to noise in the decision variables. The noise and the uncertainties consequent on it have both subjective and objective origins. A third feature of these models is their timescale invariance, which the authors argue is a very important property evident in the available experimental data. This conceptual framework is similar to the psychophysical conceptual framework in which contemporary models of sensory processing are rooted. The authors contrast it with the associative conceptual framework.

  4. Children's proximal societal conditions

    DEFF Research Database (Denmark)

    Stanek, Anja Hvidtfeldt

    2018-01-01

    that is above or outside the institutional setting or the children’s everyday life, but something that is represented through societal structures and actual persons participating (in political ways) within the institutional settings, in ways that has meaning to children’s possibilities to participate, learn...... and develop. Understanding school or kindergarten as (part of) the children’s proximal societal conditions for development and learning, means for instance that considerations about an inclusive agenda are no longer simply thoughts about the school – for economic reasons – having space for as many pupils...... as possible (schools for all). Such thoughts can be supplemented by reflections about which version of ‘the societal’ we wish to present our children with, and which version of ‘the societal’ we wish to set up as the condition for children’s participation and development. The point is to clarify or sharpen...

  5. Baseline conditions at Olkiluoto

    International Nuclear Information System (INIS)

    2003-09-01

    The main purpose of this report is to establish a reference point - defined as the data collected up until the end of year 2002 - for the coming phases of the Finnish spent nuclear fuel disposal programme. The focus is: to define the current surface and underground conditions at the site, both as regards the properties for which a change is expected and for the properties which are of particular interest for long-term safety or environmental impact; to establish, as far as possible, the natural fluctuation of properties that are potentially affected by construction of the underground laboratory, the ONKALO, and to provide references to data on parameters or use in model development and testing and to use models to assist in understanding and interpreting the data. The emphasis of the baseline description is on bedrock characteristics that are relevant to the long-term safety of a spent fuel repository and, hence, to include the hydrogeological, hydrogeochemical, rock mechanical, tectonic and seismic conditions of the site. The construction of the ONKALO will also affect some conditions on the surface, and, therefore, a description of the main characteristics of the nature and the man-made constructions at Olkiluoto is also given. This report is primarily a road map to the available information on the prevailing conditions at the Olkiluoto site and a framework for understanding of data collected. Hence, it refers to numerous available background reports and other archived information produced over the past 20 years or more, and forms a recapitulation and revaluation of the characterisation data of the Olkiluoto site. (orig.)

  6. Retrocausality and conditional probability

    International Nuclear Information System (INIS)

    Stuart, C.I.J.M.

    1989-01-01

    Costa de Beauregard has proposed that physical causality be identified with conditional probability. The proposal is shown to be vulnerable on two accounts. The first, though mathematically trivial, seems to be decisive so far as the current formulation of the proposal is concerned. The second lies in a physical inconsistency which seems to have its source in a Copenhagenlike disavowal of realism in quantum mechanics. 6 refs. (Author)

  7. On conditional decomposability

    Czech Academy of Sciences Publication Activity Database

    Komenda, Jan; Masopust, Tomáš; van Schuppen, J. H.

    2012-01-01

    Roč. 61, č. 12 (2012), s. 1260-1268 ISSN 0167-6911 R&D Projects: GA ČR(CZ) GPP202/11/P028; GA ČR(CZ) GAP103/11/0517 Institutional support: RVO:67985840 Keywords : discrete-event system * coordination control * conditional decomposability Subject RIV: BA - General Mathematics Impact factor: 1.667, year: 2012 http://www.sciencedirect.com/science/article/pii/S0167691112001612

  8. Conditional Belief Types

    Science.gov (United States)

    2016-04-19

    Rationality of a player is determined by comparing her actual expected payoff to her expected payoff when her strategy is changed , while her beliefs —and...reduced strategies, and it is possible that under such conditions, beliefs about other players’ reduced strategies change as well. Thus, independence...assumptions, whether they concern observability of moves or subjective beliefs of any other kind, can be all accommodated by changing the informational

  9. Decontamination and winter conditions

    International Nuclear Information System (INIS)

    Quenild, C.; Tveten, U.

    1984-12-01

    The report deals with two decontamonation experiments under winter conditions. A snow-covered parking lot was contaminated, and the snow was subsequently removed using standard snow-moving equipment. The snow left behind was collected and the content of contaminant was determined. A non-radioactive contaminant was used. A decontamination factor exceeding 100 was obtained. Although the eksperimental conditions were close to ideal, it is reason to believe that extremely efficient removal of deposited materials on a snow surface is achivable. In another investigation, run-off from agricultural surface, contaminated while covered with snow, was measured A lycimeter was used in this experiment. A stable layer of ice and snow was allowed to form before contamination. The run-off water was collected at each thaw period until all snow and ice was gone. Cs-134 was used as contaminant. Roughly 30% of the Cs-134 with which the area was contaminated ran off with the melt water. Following a reactor accident situation, this would have given a corresponding reduction in the long term doses. Both of these experiments show that consequence calculation assumptions, as they are currently applied to large accident assessment, tend to overestimate the consequences resulting from accidents taking place under winter conditions

  10. Plasma focus matching conditions

    International Nuclear Information System (INIS)

    Soliman, H.M.; Masoud, M.M.; Elkhalafawy, T.A.

    1988-01-01

    A snow-plough and slug models have been used to obtain the optimum matching conditions of the plasma in the focus. The dimensions of the plasma focus device are, inner electrode radius = 2 cm, outer electrode radius = 5.5 cm, and its length = 8 cm. It was found that the maximum magnetic energy of 12.26 kJ has to be delivered to plasma focus whose density is 10 19 /cm 3 at focusing time of 2.55 μs and with total external inductance of 24.2 n H. The same method is used to evaluate the optimum matching conditions for the previous coaxial discharge system which had inner electrode radius = 1.6 cm, outer electrode radius = 3.3 cm and its length = 31.5 cm. These conditions are charging voltage = 12 kV, capacity of the condenser bank = 430 μf, plasma focus density = 10 19 /cm 3 focusing time = 8 μs and total external inductance = 60.32 n H.3 fig., 2 tab

  11. Pathologic conditions in pregnancy

    International Nuclear Information System (INIS)

    Beomonte Zobel, B.; Tella, S.; Innacoli, M.; D'Archivio, C.; Cardone, G.; Masciocchi, C.; Gallucci, M.; Passariello, R.; Cappa, F.

    1991-01-01

    Soma authors suggested that MR imaging could rapresent an effective diagnostic alternative in the study of pathologic conditions of mother and fetus during pregnancy. To verify the actual role of MR imaging, we examined 20 patients in the 2nd and 3rd trimester of gestation, after a preliminary US examination. Fifteen patients presented fetal or placental pathologies; in 4 patients the onset of the pathologic condition occurred during pregnancy; in 1 case of US diagnosis of fetal ascites, MR findings were nornal and the newborn was healty. As for placental pathologies, our series included a case of placental cyst, two hematomas between placenta and uterine wall, and two cases of partial placenta previa. As for fetal malformation, we evaluated a case of omphalocele, one of Prune-Belly syndrome, a case of femoral asimmetry, one of thanatophoric dwarfism, a case of thoracopagus twins with cardiovascular abnormalities, two fetal hydrocephali, and three cases of pyelo-ureteral stenosis. As for maternal pathologies during pregnancy, we observed a case of subserous uterine fibromyoma, one of of right hydronephrosis, one of protrusion of lumbar invertebral disk, and a large ovarian cyst. In our experience, MR imaging exhibited high sensitivity and a large field of view, which were both useful in the investigation of the different conditions occurring during pregnancy. In the evaluation of fetal and placental abnormalities, especially during the 3rd trimester, the diagnostic yieldof MR imaging suggested it as a complementary technique to US for the evaluation of fetal malformation and of intrauterine growth retardation

  12. MRI of vaginal conditions

    International Nuclear Information System (INIS)

    Lopez, C.; Balogun, M.; Ganesan, R.; Olliff, J.F.

    2005-01-01

    Magnetic resonance imaging (MRI) has become an important part of the assessment of suspected vaginal pathology. This pictorial review demonstrates the MRI features and some of the histopathological findings of a variety of vaginal conditions. These may be congenital (total vaginal agenesis, partial vaginal agenesis, longitudinal vaginal septum, transverse vaginal septum), benign (Bartholin's cyst, diffuse vaginal inflammation, invasive endometriosis, ureterovaginal fistula, post-surgical appearances with the formation of a neovagina and adhesions) or malignant, usually due to extension or recurrence from another pelvic malignancy. In this paper, examples of the above are described and illustrated together with examples of the much rarer primary vaginal malignancies

  13. Learning conditional Gaussian networks

    DEFF Research Database (Denmark)

    Bøttcher, Susanne Gammelgaard

    This paper considers conditional Gaussian networks. The parameters in the network are learned by using conjugate Bayesian analysis. As conjugate local priors, we apply the Dirichlet distribution for discrete variables and the Gaussian-inverse gamma distribution for continuous variables, given...... a configuration of the discrete parents. We assume parameter independence and complete data. Further, to learn the structure of the network, the network score is deduced. We then develop a local master prior procedure, for deriving parameter priors in these networks. This procedure satisfies parameter...... independence, parameter modularity and likelihood equivalence. Bayes factors to be used in model search are introduced. Finally the methods derived are illustrated by a simple example....

  14. MRI of vaginal conditions

    Energy Technology Data Exchange (ETDEWEB)

    Lopez, C. [Department of Radiology, Birmingham Women' s Hospital, Birmingham (United Kingdom)]. E-mail: carolina.lopez@bwhct.nhs.uk; Balogun, M. [Department of Radiology, Birmingham Women' s Hospital, Birmingham (United Kingdom); Ganesan, R. [Department of Histopathology, Birmingham Women' s Hospital, Birmingham (United Kingdom); Olliff, J.F. [University Hospital Birmingham, Birmingham (United Kingdom)

    2005-06-01

    Magnetic resonance imaging (MRI) has become an important part of the assessment of suspected vaginal pathology. This pictorial review demonstrates the MRI features and some of the histopathological findings of a variety of vaginal conditions. These may be congenital (total vaginal agenesis, partial vaginal agenesis, longitudinal vaginal septum, transverse vaginal septum), benign (Bartholin's cyst, diffuse vaginal inflammation, invasive endometriosis, ureterovaginal fistula, post-surgical appearances with the formation of a neovagina and adhesions) or malignant, usually due to extension or recurrence from another pelvic malignancy. In this paper, examples of the above are described and illustrated together with examples of the much rarer primary vaginal malignancies.

  15. Conditional sterility in plants

    Science.gov (United States)

    Meagher, Richard B.; McKinney, Elizabeth; Kim, Tehryung

    2010-02-23

    The present disclosure provides methods, recombinant DNA molecules, recombinant host cells containing the DNA molecules, and transgenic plant cells, plant tissue and plants which contain and express at least one antisense or interference RNA specific for a thiamine biosynthetic coding sequence or a thiamine binding protein or a thiamine-degrading protein, wherein the RNA or thiamine binding protein is expressed under the regulatory control of a transcription regulatory sequence which directs expression in male and/or female reproductive tissue. These transgenic plants are conditionally sterile; i.e., they are fertile only in the presence of exogenous thiamine. Such plants are especially appropriate for use in the seed industry or in the environment, for example, for use in revegetation of contaminated soils or phytoremediation, especially when those transgenic plants also contain and express one or more chimeric genes which confer resistance to contaminants.

  16. Conditional Epistemic Planning

    DEFF Research Database (Denmark)

    Andersen, Mikkel Birkegaard; Bolander, Thomas; Jensen, Martin Holm

    2012-01-01

    Recent work has shown that Dynamic Epistemic Logic (DEL) offers a solid foundation for automated planning under partial observability and non-determinism. Under such circumstances, a plan must branch if it is to guarantee achieving the goal under all contingencies (strong planning). Without...... branching, plans can offer only the possibility of achieving the goal (weak planning). We show how to formulate planning in uncertain domains using DEL and give a language of conditional plans. Translating this language to standard DEL gives verification of both strong and weak plans via model checking....... In addition to plan verification, we provide a tableau-inspired algorithm for synthesising plans, and show this algorithm to be terminating, sound and complete....

  17. Remote Ischemic Conditioning

    Science.gov (United States)

    Heusch, Gerd; Bøtker, Hans Erik; Przyklenk, Karin; Redington, Andrew; Yellon, Derek

    2014-01-01

    In remote ischemic conditioning (RIC) brief, reversible episodes of ischemia with reperfusion in one vascular bed, tissue or organ confer a global protective phenotype and render remote tissues and organs resistant to ischemia/reperfusion injury. The peripheral stimulus can be chemical, mechanical or electrical and involves activation of peripheral sensory nerves. The signal transfer to the heart or other organs is through neuronal and humoral communications. Protection can be transferred, even across species, with plasma-derived dialysate and involves nitric oxide, stromal derived factor-1α, microRNA-144, but also other, not yet identified factors. Intracardiac signal transduction involves: adenosine, bradykinin, cytokines, and chemokines, which activate specific receptors; intracellular kinases; and mitochondrial function. RIC by repeated brief inflation/deflation of a blood pressure cuff protects against endothelial dysfunction and myocardial injury in percutaneous coronary interventions, coronary artery bypass grafting and reperfused acute myocardial infarction. RIC is safe and effective, noninvasive, easily feasible and inexpensive. PMID:25593060

  18. Initial Cladding Condition

    International Nuclear Information System (INIS)

    Siegmann, E.

    2000-01-01

    The purpose of this analysis is to describe the condition of commercial Zircaloy clad fuel as it is received at the Yucca Mountain Project (YMP) site. Most commercial nuclear fuel is encased in Zircaloy cladding. This analysis is developed to describe cladding degradation from the expected failure modes. This includes reactor operation impacts including incipient failures, potential degradation after reactor operation during spent fuel storage in pool and dry storage and impacts due to transportation. Degradation modes include cladding creep, and delayed hydride cracking during dry storage and transportation. Mechanical stresses from fuel handling and transportation vibrations are also included. This Analysis and Model Report (AMR) does not address any potential damage to assemblies that might occur at the YMP surface facilities. Ranges and uncertainties have been defined. This analysis will be the initial boundary condition for the analysis of cladding degradation inside the repository. In accordance with AP-2.13Q, ''Technical Product Development Planning'', a work plan (CRWMS M andO 2000c) was developed, issued, and utilized in the preparation of this document. There are constraints, caveats and limitations to this analysis. This cladding degradation analysis is based on commercial Pressurized Water Reactor (PWR) fuel with Zircaloy cladding but is applicable to Boiling Water Reactor (BWR) fuel. Reactor operating experience for both PWRs and BWRs is used to establish fuel reliability from reactor operation. It is limited to fuel exposed to normal operation and anticipated operational occurrences (i.e. events which are anticipated to occur within a reactor lifetime), and not to fuel that has been exposed to severe accidents. Fuel burnup projections have been limited to the current commercial reactor licensing environment with restrictions on fuel enrichment, oxide coating thickness and rod plenum pressures. The information provided in this analysis will be used in

  19. Magnetic conditioning in superfluid

    International Nuclear Information System (INIS)

    Caspi, S.

    1988-08-01

    Improvements in superconducting magnet technology have reduced to a handful the number of training quenches typical of dipole magnets. The number of training quenches in long (17 m) and short (1--2 m) SSC magnets are now about the same (operating at 6.6 tesla and 4.4 K). Yet the steps necessary to totally eliminate training are in the future RandD plans for magnet construction and conductor motion prevention. The accepted hypothesis is that Lorentz forces and poor mechanical properties of superconducting cables are the cause of conductor motion. Conductor motion reduces the stored energy in the cable by converting it into heat. The small amount of heat generated (millijoules) during motion is usually enough to quench the magnet when it is close to short sample. During training, the magnet performance normally improves with the number of quenches. It is not the quench itself that improves magnet performance but rather the fact that once conductor motion has occurred it will probably not repeat itself unless subjected to higher forces. Conditioning is a process that enables the magnet to reduce its stored energy without causing a premature quench. During the conditioning process the magnet is further cooled from its operating temperature of 4.4 K to 1.8 K by converting He I into He II. As a result the magnet is placed in a state where it has excess stability as well as excellent heat transfer capabilities. Although this does not eliminate motion, if the magnet is now cycled to /approximately/10% above its operating field at 4.4 K (which is above short sample) the excess stability should be enough to prevent quenching and reduce the probability of conductor motion and training once the magnet has been warmed back up to its operating temperature of 4.4 K. 3 refs., 5 figs

  20. Magnetic conditioning in superfluid

    Energy Technology Data Exchange (ETDEWEB)

    Caspi, S.

    1988-08-01

    Improvements in superconducting magnet technology have reduced to a handful the number of training quenches typical of dipole magnets. The number of training quenches in long (17 m) and short (1--2 m) SSC magnets are now about the same (operating at 6.6 tesla and 4.4 K). Yet the steps necessary to totally eliminate training are in the future RandD plans for magnet construction and conductor motion prevention. The accepted hypothesis is that Lorentz forces and poor mechanical properties of superconducting cables are the cause of conductor motion. Conductor motion reduces the stored energy in the cable by converting it into heat. The small amount of heat generated (millijoules) during motion is usually enough to quench the magnet when it is close to short sample. During training, the magnet performance normally improves with the number of quenches. It is not the quench itself that improves magnet performance but rather the fact that once conductor motion has occurred it will probably not repeat itself unless subjected to higher forces. Conditioning is a process that enables the magnet to reduce its stored energy without causing a premature quench. During the conditioning process the magnet is further cooled from its operating temperature of 4.4 K to 1.8 K by converting He I into He II. As a result the magnet is placed in a state where it has excess stability as well as excellent heat transfer capabilities. Although this does not eliminate motion, if the magnet is now cycled to /approximately/10% above its operating field at 4.4 K (which is above short sample) the excess stability should be enough to prevent quenching and reduce the probability of conductor motion and training once the magnet has been warmed back up to its operating temperature of 4.4 K. 3 refs., 5 figs.

  1. A comprehensive siRNA screen for kinases that suppress macroautophagy in optimal growth conditions

    DEFF Research Database (Denmark)

    Szyniarowski, Piotr; Corcelle-Termeau, Elisabeth; Farkas, Thomas

    2011-01-01

    , whereas CSNK1A1, BUB1, PKLR and NEK4 suppressed autophagosome formation downstream or independent of mTORC1. Importantly, all identified kinases except for BUB1 regulated macroautophagy also in immortalized MCF-10A breast epithelial cells. The kinases identified here shed light to the complex regulation...

  2. The Negated Conditional: A Litmus Test for the Suppositional Conditional?

    Science.gov (United States)

    Handley, Simon J.; Evans, Jonathan St. B. T.; Thompson, Valerie A.

    2006-01-01

    Under the suppositional account of conditionals, when people think about a conditional assertion, "if p then q," they engage in a mental simulation in which they imagine p holds and evaluate the probability that q holds under this supposition. One implication of this account is that belief in a conditional equates to conditional probability…

  3. Flue gas conditioning today

    Energy Technology Data Exchange (ETDEWEB)

    Southam, B.J.; Coe, E.L. Jr. [Wahlco Engineering International Ltd., Santa Ana, CA (United States)

    1995-12-01

    Many relatively small electrostatic precipitators (ESP`s) exist which collect fly ash at remarkably high efficiencies and have been tested consistently at correspondingly high migration velocities. But the majority of the world`s coal supplies produce ashes which are collected at much lower migration velocities for a given efficiency and therefore require correspondingly large specific collection areas to achieve acceptable results. Early trials of flue gas conditioning (FGC) showed benefits in maximizing ESP performance and minimizing expense which justified continued experimentation. Trials of several dozen ways of doing it wrong eventually developed a set of reliable rules for doing it right. One result is that the use of sulfur trioxide (SO{sub 3}) for adjustment of the resistivity of fly ash from low sulfur coal has been widely applied and has become an automatically accepted part of the option of burning low sulfur coal for compliance with the Clean Air Act of l990 in the U.S.A. Currently, over 100,000 MW of generating capacity is using FGC, and it is estimated that approximately 45,800 MW will utilize coal-switching with FGC for Clean Air Act emission compliance. Guarantees that this equipment will be available to operate at least 98 percent of the time it is called upon are routinely fulfilled.

  4. Design extension conditions

    Energy Technology Data Exchange (ETDEWEB)

    Bujor, A.; Harwood, C.; Lei, Q.; Viktorov, A., E-mail: christopher.harwood@cnsc-ccsn.gc.ca [Canadian Nuclear Safety Commission, Ottawa, Ontario (Canada)

    2013-07-01

    The CNSC has introduced the term Design Extension Conditions (DEC) in regulatory document RD-337 version 2, 'Design of New Nuclear Power Plants' which was issued for public consultation in July 2012. The primary drivers for this change compared with the earlier version of RD-337 are to maintain alignment with the equivalent International Atomic Energy Agency (IAEA) safety standard and to introduce changes resulting from lessons learned from the Fukushima Daiichi accident. RD-337 version 2 and the accompanying guidance document GD-337 establish high level design requirements and expectations for new Nuclear Power Plants (NPPs), including those pertaining to DEC. Other regulatory documents provide requirements for safety analysis and accident management as well as other aspect relevant to DEC. Nevertheless, the currently available guidance specific to DEC is not comprehensive, while the practices just begin to emerge. CNSC and industry stakeholders are actively discussing how the high level requirements and expectations will be applied in various fields. This paper is a summary of a CNSC discussion paper that is being developed to encourage substantive stakeholder discussions. The topic of DEC is being advanced rapidly both nationally and internationally. With this in mind, this paper does not intend to provide a final established position, but rather to stimulate discussion on the subject of DEC. This paper provides the definition of DEC, gives background information relating to the adoption of the term, describes the identification of DECs and the underlying principles associated with design, analysis, operational and procedural requirements. As described in this paper, DEC and associated requirements apply to new NPPs. Applicability to existing NPPs is also discussed. (author)

  5. Assessing the planet's condition.

    Science.gov (United States)

    Brown, L R

    1990-01-01

    The destruction of the environment has accelerated since the Earth Day of 1970, the world's population has increased by another 1.6 billion, and over 500 million acres of forest have been lost. Carbon dioxide levels, greenhouse gases, and chlorofluorocarbons have increased in the atmosphere with evidence that global warming has started. The ozone hole has appeared, acid rain has destroyed forests, air pollution in major northern hemisphere cities has worsened, and species are disappearing, while toxic chemicals have been dumped indiscriminately. World grain production has fallen while population has increased. In Europe 14 countries have stabilized their population, and Japan, France, and Finland are on the way to zero growth. Reduction of high fertility in 1/2 could halt the deterioration of living conditions. Japan and China achieved this within a decade. Energy efficiency has to be attained; US cars still consume too much gas. Solar energy with photovoltaic cells to provide power, fuel alcohol from plants, and solar thermal power plants have potential. Semiarid regions, such as northern Africa, could become major producers of solar energy. Various measures are mandatory to cut down on waste: to recycle paper bags, to use standardized glasses for beverages, and to utilize scrap metal in electric arc steel furnaces. Reforestation is also on the agenda, as major deforestation has occurred in the Brazilian Amazon region, in India, and in Europe because of acid rain. Australia's national plan envisions planting 1 billion trees, and the US project is of similar magnitude during the 1990s. Only the US has succeeded in erosion control and topsoil stabilization when it converted erodible cropland into grassland or woodland during 1986-90.

  6. Visualising Deteriorating Conditions

    Directory of Open Access Journals (Sweden)

    Tom Andrews, RN, B.Sc. (Hons, M.Sc., Ph.D.

    2005-03-01

    Full Text Available The research aims were to investigate the difficulties ward staff experienced in detecting deterioration and how these were resolved. The emphasis within the literature tends to be on identifying premonitory signs that may be useful in predicting deterioration. Changes in respiratory rate is the most consistent of these (Fieselmann et al. 1993; Sax and Charlson 1987; Schein et al. 1990; Smith and Wood 1998 but in common with other signs, it lacks sensitivity and specificity. The sample consisted of 44 nurses, doctors (Interns and health care support workers from a general medical and surgical ward. Data were collected by means of nonparticipant observations and interviews, using grounded theory as originated by (Glaser and Strauss 1967 and (Glaser 1978. As data were collected, the constant comparative method and theoretical sensitivity were used as outlined in grounded theory. A core category of “visualising deteriorating conditions” emerged, together with its sub-core categories of “intuitive knowing”, “baselining” and “grabbing attention”.The main concern in visualising deteriorating conditions is to ensure that patients suspected of deterioration are successfully referred to medical staff. The aim is to convince those who can treat or prevent further deterioration to intervene. Through intuitive knowing they pick up that patients have changed in a way that requires a medical assessment. To make the referral more credible, nurses attempt to contextualise any changes in patients by baselining (establishing baselines. Finally with the backup of colleagues, nurses refer patients by providing as much persuasive information as possible in a way that grabs attention. The whole process is facilitated by knowledge and experience, together with mutual trust and respect.

  7. Acute vs. chronic conditions (image)

    Science.gov (United States)

    ... describe anything from a broken bone to an asthma attack. A chronic condition, by contrast is a long- ... a broken bone, an acute condition. An acute asthma attack occurs in the midst of the chronic disease ...

  8. Klinefelter Syndrome (KS): Condition Information

    Science.gov (United States)

    ... Condition Information Share Facebook Twitter Pinterest Email Print Klinefelter Syndrome (KS): Condition Information What is KS? The term " ... such as XXYY. This is called poly-X Klinefelter syndrome, and it causes more severe symptoms. 1 Klinefelter, ...

  9. Energy conditions and spacetime singularities

    International Nuclear Information System (INIS)

    Tipler, F.J.

    1978-01-01

    In this paper, a number of theorems are proven which collectively show that singularities will occur in spacetime under weaker energy conditions than the strong energy condition. In particular, the Penrose theorem, which uses only the weak energy condition but which applies only to open universes, is extended to all closed universes which have a Cauchy surface whose universal covering manifold is not a three-sphere. Furthermore, it is shown that the strong energy condition in the Hawking-Penrose theorem can be replaced by the weak energy condition and the assumption that the strong energy condition holds only on the average. In addition, it is demonstrated that if the Universe is closed, then the existence of singularities follows from the averaged strong energy condition alone. It is argued that any globally hyperbolic spacetime which satisfies the weak energy condition and which contains a black hole must be null geodesically incomplete

  10. Petroleum investment conditions in Peru

    International Nuclear Information System (INIS)

    Garcia Schreck, M.

    1996-01-01

    This report focuses on the current petroleum investment conditions in Peru, and Peru's hydrocarbon potential. Investment conditions are examined, and political risk, internal security, the economic environment, and the legal framework for investment are considered. (UK)

  11. Reconstruction of boundary conditions from internal conditions using viability theory

    KAUST Repository

    Hofleitner, Aude; Claudel, Christian G.; Bayen, Alexandre M.

    2012-01-01

    This article presents a method for reconstructing downstream boundary conditions to a HamiltonJacobi partial differential equation for which initial and upstream boundary conditions are prescribed as piecewise affine functions and an internal condition is prescribed as an affine function. Based on viability theory, we reconstruct the downstream boundary condition such that the solution of the Hamilton-Jacobi equation with the prescribed initial and upstream conditions and reconstructed downstream boundary condition satisfies the internal value condition. This work has important applications for estimation in flow networks with unknown capacity reductions. It is applied to urban traffic, to reconstruct signal timings and temporary capacity reductions at intersections, using Lagrangian sensing such as GPS devices onboard vehicles.

  12. Reconstruction of boundary conditions from internal conditions using viability theory

    KAUST Repository

    Hofleitner, Aude

    2012-06-01

    This article presents a method for reconstructing downstream boundary conditions to a HamiltonJacobi partial differential equation for which initial and upstream boundary conditions are prescribed as piecewise affine functions and an internal condition is prescribed as an affine function. Based on viability theory, we reconstruct the downstream boundary condition such that the solution of the Hamilton-Jacobi equation with the prescribed initial and upstream conditions and reconstructed downstream boundary condition satisfies the internal value condition. This work has important applications for estimation in flow networks with unknown capacity reductions. It is applied to urban traffic, to reconstruct signal timings and temporary capacity reductions at intersections, using Lagrangian sensing such as GPS devices onboard vehicles.

  13. Conditional cooperation on three continents

    NARCIS (Netherlands)

    Kocher, M.G.; Cherry, T.; Kroll, S.; Netzer, R.; Sutter, M.

    2007-01-01

    We show in a public goods experiment on three continents that conditional cooperation is a universal behavioral regularity. Yet, the number of conditional cooperators and the extent of conditional cooperation are much higher in the U.S.A. than anywhere else.

  14. Some remarks on conditional entropy

    NARCIS (Netherlands)

    Nijst, A.G.P.M.

    1969-01-01

    Using a definition of conditional entropy given by Hanen and Neveu [5, 10, 11] we discuss in this paper some properties of conditional entropy and mean entropy, in particular an integral representation of conditional entropy (§ 2), and the decomposition theorem of the KolmogorovSina¯i invariant (§

  15. PBL and the Postmodern Condition

    DEFF Research Database (Denmark)

    Ravn, Ole; Jensen, Annie Aarup

    2016-01-01

    . Through discussions of this alleged condition for university curricula development we investigate its connections to the PBL-model. Some of the explored conditions highlight strong potentials for the PBL-model but the postmodern condition also raises a number of changes and challenges in relation...... to the original PBL-model as an educational setting....

  16. Operant Conditioning for Special Educators.

    Science.gov (United States)

    Pedrini, Bonnie C.; Pedrini, D. T.

    The paper briefly explains operant conditioning as it pertains to special educators. Operant conditioning is thought to be an efficient method for modifying student behavior. Using the B. F. Skinner frame of reference, operant conditioning is said to include behavior modification and therapy, programed instruction, and computer assisted and…

  17. Bayesian Sampling using Condition Indicators

    DEFF Research Database (Denmark)

    Faber, Michael H.; Sørensen, John Dalsgaard

    2002-01-01

    of condition indicators introduced by Benjamin and Cornell (1970) a Bayesian approach to quality control is formulated. The formulation is then extended to the case where the quality control is based on sampling of indirect information about the condition of the components, i.e. condition indicators...

  18. Serotonin and conditioning: focus on Pavlovian psychostimulant drug conditioning.

    Science.gov (United States)

    Carey, Robert J; Damianopoulos, Ernest N

    2015-04-01

    Serotonin containing neurons are located in nuclei deep in the brainstem and send axons throughout the central nervous system from the spinal cord to the cerebral cortex. The vast scope of these connections and interactions enable serotonin and serotonin analogs to have profound effects upon sensory/motor processes. In that conditioning represents a neuroplastic process that leads to new sensory/motor connections, it is apparent that the serotonin system has the potential for a critical role in conditioning. In this article we review the basics of conditioning as well as the serotonergic system and point up the number of non-associative ways in which manipulations of serotonin neurotransmission have an impact upon conditioning. We focus upon psychostimulant drug conditioning and review the contribution of drug stimuli in the use of serotonin drugs to investigate drug conditioning and the important impact drug stimuli can have on conditioning by introducing new sensory stimuli that can create or mask a CS. We also review the ways in which experimental manipulations of serotonin can disrupt conditioned behavioral effects but not the associative processes in conditioning. In addition, we propose the use of the recently developed memory re-consolidation model of conditioning as an approach to assess the possible role of serotonin in associative processes without the complexities of performance effects related to serotonin treatment induced alterations in sensory/motor systems. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Evaluative conditioning of food technologies

    DEFF Research Database (Denmark)

    Loebnitz, Natascha; Grunert, Klaus G

    2015-01-01

    Consumer attitudes play an important role in the acceptance of new technologies. The success of food innovations depends on understanding how consumers form and change attitudes toward food technologies. Earlier post hoc explanations suggest that evaluative conditioning can change consumer...... attitudes toward food technologies. The present study tests how evaluative conditioning can affect consumer acceptance of new food technologies. Furthermore, authors investigate whether evaluative conditioning is resistant to extinction after a two-month period and whether the evaluative conditioning effect...... prevails in a product-related context. Within an evaluative conditioning paradigm including between-subjects control groups in addition to standard within-subjects control conditions, participants were presented with three food technologies (conventional, enzyme, and genetic technology) paired...

  20. Evolutions of Yang Phase Under Cyclic Condition and Adiabatic Condition

    International Nuclear Information System (INIS)

    Qian Shangwu; Gu Zhiyu

    2005-01-01

    There are three non-integrable phases in literatures: Berry phase, Aharonov-Anandan phase, and Yang phase. This article discusses the evolutions of Yang phase under the cyclic condition and the adiabatic condition for the general time-dependent harmonic oscillator, thus reveals the intimate relations between these three non-integrable phases.

  1. Conditional Eddies in Plasma Turbulence

    DEFF Research Database (Denmark)

    Johnsen, H.; Pécseli, H.L.; Trulsen, J.

    1987-01-01

    Low‐frequency electrostatic turbulence generated by the ion–ion beam instability was investigated experimentally in a double‐plasma device. Real time signals were recorded and examined by a conditional statistical analysis. Conditionally averaged potential distributions reveal the formation...... and propagation of structures with a relatively long lifetime. Various methods for making a conditional analysis are discussed and compared. The results are discussed with reference to ion phase space vortices and clump formation in collisionless plasmas....

  2. Artificial changes of weather conditions

    International Nuclear Information System (INIS)

    Kozin, I.D.; Vasil'ev, I.V.; Fedulina, I.N.; Zakizhan, Z.Z.; Khalimov, R.A.

    2005-01-01

    Unfavorable weather conditions have undesirable ecological consequences, causes remarkable economical damage. In the paper authors consider physical factors and technical methods of influence on cloud formation. (author)

  3. Scaling of interfacial jump conditions

    International Nuclear Information System (INIS)

    Quezada G, S.; Vazquez R, A.; Espinosa P, G.

    2015-09-01

    To model the behavior of a nuclear reactor accurately is needed to have balance models that take into account the different phenomena occurring in the reactor. These balances have to be coupled together through boundary conditions. The boundary conditions have been studied and different treatments have been given to the interface. In this paper is a brief description of some of the interfacial jump conditions that have been proposed in recent years. Also, the scaling of an interfacial jump condition is proposed, for coupling the different materials that are in contact within a nuclear reactor. (Author)

  4. Fixed or adapted conditioning intensity for repeated conditioned pain modulation.

    Science.gov (United States)

    Hoegh, M; Petersen, K K; Graven-Nielsen, T

    2017-12-29

    Aims Conditioned pain modulation (CPM) is used to assess descending pain modulation through a test stimulation (TS) and a conditioning stimulation (CS). Due to potential carry-over effects, sequential CPM paradigms might alter the intensity of the CS, which potentially can alter the CPM-effect. This study aimed to investigate the difference between a fixed and adaptive CS intensity on CPM-effect. Methods On the dominant leg of 20 healthy subjects the cuff pressure detection threshold (PDT) was recorded as TS and the pain tolerance threshold (PTT) was assessed on the non-dominant leg for estimating the CS. The difference in PDT before and during CS defined the CPM-effect. The CPM-effect was assessed four times using a CS with intensities of 70% of baseline PTT (fixed) or 70% of PTT measured throughout the session (adaptive). Pain intensity of the conditioning stimulus was assessed on a numeric rating scale (NRS). Data were analyzed with repeated-measures ANOVA. Results No difference was found comparing the four PDTs assessed before CSs for the fixed and the adaptive paradigms. The CS pressure intensity for the adaptive paradigm was increasing during the four repeated assessments (P CPM-effect was higher using the fixed condition compared with the adaptive condition (P CPM paradigms using a fixed conditioning stimulus produced an increased CPM-effect compared with adaptive and increasing conditioning intensities.

  5. 76 FR 14600 - Dental Conditions

    Science.gov (United States)

    2011-03-17

    ... qualify for VHA dental treatment, including any claim for treatment of periodontal disease or calculus... DEPARTMENT OF VETERANS AFFAIRS 38 CFR Part 3 RIN 2900-AN28 Dental Conditions AGENCY: Department of... its adjudication regulations regarding service connection of dental conditions for treatment purposes...

  6. Paranormal weighted conditional type operators

    OpenAIRE

    Estaremi, Yousef

    2014-01-01

    In this paper, some sub-classes of paranormal weighted conditional expectation type operators, such as *-paranormal, quasi-*-paranormal and (n; k)-quasi-*-paranormal weighted conditional expectation type opera- tors on $L^2(\\Sigma)$ are investigated. Also, some applications about the spectrum, point spectrum, joint point spectrum, approximate point spectrum and joint approximate point spectrum of these classes are presented.

  7. Loading Conditions and Longitudinal Strength

    DEFF Research Database (Denmark)

    Sørensen, Herman

    1995-01-01

    Methods for the calculation of the lightweight of the ship.Loading conditions satisfying draught, trim and intact stability requirements and analysis of the corresponding stillwater longitudinal strength.......Methods for the calculation of the lightweight of the ship.Loading conditions satisfying draught, trim and intact stability requirements and analysis of the corresponding stillwater longitudinal strength....

  8. 77 FR 4469 - Dental Conditions

    Science.gov (United States)

    2012-01-30

    ... DEPARTMENT OF VETERANS AFFAIRS 38 CFR Part 3 RIN 2900-AN28 Dental Conditions AGENCY: Department of... rule the proposal to amend its adjudication regulations regarding service connection of dental... Veterans Benefits Administration (VBA) for service connection of dental conditions for the purpose of...

  9. Conditional Eddies in Plasma Turbulence

    DEFF Research Database (Denmark)

    Johnsen, Helene; Pécseli, Hans; Trulsen, J.

    1986-01-01

    Conditional structures, or eddies, in turbulent flows are discussed with special attention to electrostatic turbulence in plasmas. The potential variation of these eddies is obtained by sampling the fluctuations only when a certain condition is satisfied in a reference point. The resulting...

  10. Sectoral profiles of working conditions

    NARCIS (Netherlands)

    Houtman, I.L.D.; Andries, F.; Berg, R. van den; Dhondt, S.

    2002-01-01

    This report looks at trends in working conditions across different sectors Over the period 1995-2000. Basing its findings on the Third European Survey on Working Conditions (2000) in the 15 EU Member States and Norway, it examines the quality of working life in eighteen different sectors. It

  11. Sectoral profiles of working conditions

    NARCIS (Netherlands)

    Houtman, I.L.D.; Parent-Thirion, A.

    2003-01-01

    This report looks at trends in working conditions across different sectors over a five-year period 1995-2000. Basing its findings on the Third European Survey on Working Conditions carried out by the Foundation in 2000 in the 15 EU Member States and Norway, it examines the quality of working life in

  12. Optimising Extinction of Conditioned Disgust

    NARCIS (Netherlands)

    Bosman, Renske C.; Borg, Charmaine; de Jong, Peter J.

    2016-01-01

    Maladaptive disgust responses are tenacious and resistant to exposure-based interventions. In a similar vein, laboratory studies have shown that conditioned disgust is relatively insensitive to Conditioned Stimulus (CS)-only extinction procedures. The relatively strong resistance to extinction might

  13. Condition based spare parts supply

    NARCIS (Netherlands)

    Lin, X.; Basten, Robertus Johannes Ida; Kranenburg, A.A.; van Houtum, Geert-Jan

    2012-01-01

    We consider a spare parts stock point that serves an installed base of machines. Each machine contains the same critical component, whose degradation behavior is described by a Markov process. We consider condition based spare parts supply, and show that an optimal, condition based inventory policy

  14. Initial conditions for chaotic inflation

    International Nuclear Information System (INIS)

    Brandenberger, R.; Kung, J.; Feldman, H.

    1991-01-01

    In contrast to many other inflationary Universe models, chaotic inflation does not depend on fine tuning initial conditions. Within the context of linear perturbation theory, it is shown that chaotic inflation is stable towards both metric and matter perturbations. Neglecting gravitational perturbations, it is shown that chaotic inflation is an attractor in initial condition space. (orig.)

  15. Jump conditions in transonic equilibria

    International Nuclear Information System (INIS)

    Guazzotto, L.; Betti, R.; Jardin, S. C.

    2013-01-01

    In the present paper, the numerical calculation of transonic equilibria, first introduced with the FLOW code in Guazzotto et al.[Phys. Plasmas 11, 604 (2004)], is critically reviewed. In particular, the necessity and effect of imposing explicit jump conditions at the transonic discontinuity are investigated. It is found that “standard” (low-β, large aspect ratio) transonic equilibria satisfy the correct jump condition with very good approximation even if the jump condition is not explicitly imposed. On the other hand, it is also found that high-β, low aspect ratio equilibria require the correct jump condition to be explicitly imposed. Various numerical approaches are described to modify FLOW to include the jump condition. It is proved that the new methods converge to the correct solution even in extreme cases of very large β, while they agree with the results obtained with the old implementation of FLOW in lower-β equilibria.

  16. Remark on Trautman's Radiation Condition

    International Nuclear Information System (INIS)

    Walker, M.

    1979-01-01

    The confusion about the boundary conditions for radiating systems formulated by Trautman are discussed. The confusion has mainly to do with where in space-time the conditions are to be imposed but also with what is it that the conditions are intended to guarantee. Imposing Trautman's conditions near future null infinity allows the existence of outgoing radiation; in order to exclude incoming radiation, they must be imposed near (or at) past null infinity. Since receding to infinity in spacelike directions means that one crosses all radiation, whether in- or outgoing, it makes no sense to impose the conditions at spatial infinity. If one were to impose fall-off of the electromagnetic field in flat space-time of 1/n at spatial infinity, then the field would contain finite energy. (Auth.)

  17. The conditional in quantum logic

    International Nuclear Information System (INIS)

    Hardegree, G.M.

    1976-01-01

    In this article it is argued that orthodox quantum logic, which is represented by the lattice of projections on Hilbert space, does in fact admit an operation which possesses the essential properties of a material conditional. It is proposed that this connective can be interpreted as a Stalnaker (counter factual) conditional, where the nearness ordering among 'worlds' (in this case, QM pure states) derives in a natural way from the Hilbert space inner-product metric. It is a characteristic of the quantum logic conditional that the law of modus ponens is equivalent to the orthomodular law of conventional quantum logic. (B.R.H.)

  18. Systemic conditions affecting the breast

    International Nuclear Information System (INIS)

    Abbitt, P.L.; DeParedes, E.S.

    1987-01-01

    While the mammogram is most often used in the evaluation of diseases specific to the breast, manifestations of systemic conditions may also be recognized. Congenital systemic conditions such as neurofibromatosis and ectodermal dysplasia have graphic mammographic findings. The effects of diet, hormonal, and medication therapy can also have a dramatic impact on the appearance of the mammogram, as can common clinical states such as congestive heart failure or renal failure. Metastases to the breast from extramammary primaries may be seen mammographically as discrete masses, as causing diffusely increased density of the breast or as abnormal axillary adenopathy. The authors review a variety of conditions and their mammographic appearance

  19. National Coastal Condition Assessment (NCCA)

    Data.gov (United States)

    U.S. Environmental Protection Agency — During the summer of 2010, state and EPA crews conducted field sampling for the fifth National Coastal Condition Assessment (NCCA). The assessment is in the data...

  20. Chronic Conditions among Medicare Beneficiaries

    Data.gov (United States)

    U.S. Department of Health & Human Services — The data used in the chronic condition reports are based upon CMS administrative enrollment and claims data for Medicare beneficiaries enrolled in the...

  1. Inflation with generalized initial conditions

    International Nuclear Information System (INIS)

    Albrecht, A.; Brandenberger, R.; Matzner, R.

    1987-01-01

    In many current models of the early Universe a scalar field phi which is only very weakly coupled to other quantum fields is used to generate inflation. In such models there are no forces which could thermalize the scalar field, and previous assumptions about its preinflation ''initial'' conditions must be abandoned. In this paper the onset of inflation is studied classically for more general initial conditions of the scalar field configuration. In particular, initial conditions with a nonvanishing spatial average of phi, with phi chosen at random in each initial horizon volume, and with random initial momenta are considered. We identify and discuss several mechanisms that can drive these more general initial conditions toward an inflationary state. The analysis is done in one spatial dimension

  2. Benign Breast Problems and Conditions

    Science.gov (United States)

    ... Hyperplasia: A condition in which cells in the breast ducts or lobes are increasing in number and do not look normal under a microscope. Benign: Not cancer. Biopsy: A minor surgical procedure to remove a small ...

  3. Conditioning processes for incinerator ashes

    International Nuclear Information System (INIS)

    Jouan, A.; Ouvrier, N.; Teulon, F.

    1990-01-01

    Three conditioning processes for alpha-bearing solid waste incineration ashes were investigated and compared according to technical and economic criteria: isostatic pressing, cold-crucible direct-induction melting and cement-resin matrix embedding

  4. Conditioning biomass for microbial growth

    Science.gov (United States)

    Bodie, Elizabeth A; England, George

    2015-03-31

    The present invention relates to methods for improving the yield of microbial processes that use lignocellulose biomass as a nutrient source. The methods comprise conditioning a composition comprising lignocellulose biomass with an enzyme composition that comprises a phenol oxidizing enzyme. The conditioned composition can support a higher rate of growth of microorganisms in a process. In one embodiment, a laccase composition is used to condition lignocellulose biomass derived from non-woody plants, such as corn and sugar cane. The invention also encompasses methods for culturing microorganisms that are sensitive to inhibitory compounds in lignocellulose biomass. The invention further provides methods of making a product by culturing the production microorganisms in conditioned lignocellulose biomass.

  5. Distributed Dynamic Condition Response Structures

    DEFF Research Database (Denmark)

    Hildebrandt, Thomas; Mukkamala, Raghava Rao

    We present distributed dynamic condition response structures as a declarative process model inspired by the workflow language employed by our industrial partner and conservatively generalizing labelled event structures. The model adds to event structures the possibility to 1) finitely specify...... as a labelled transition system. Exploration of the relationship between dynamic condition response structures and traditional models for concurrency, application to more complex scenarios, and further extensions of the model is left to future work....

  6. Conditioning of nuclear reactor fuel

    International Nuclear Information System (INIS)

    1975-01-01

    A method of conditioning the fuel of a nuclear reactor core to minimize failure of the fuel cladding comprising increasing the fuel rod power to a desired maximum power level at a rate below a critical rate which would cause cladding damage is given. Such conditioning allows subsequent freedom of power changes below and up to said maximum power level with minimized danger of cladding damage. (Auth.)

  7. Discriminated conditioned suppression in rats

    OpenAIRE

    Ribeiro, Thais Arantes; Huziwara, Edson Massayuki; Montagnoli, Tathianna Amorim Souza; Souza, Deisy das Graças de

    2012-01-01

    This experiment evaluated the effects of superimposing the Estes-Skinner Conditioned Emotional Response (CER) procedure on one of two components of a multiple schedule. The question was whether CER conditioning occurred under contextual control. The procedure had four experimental phases: (1) baseline of operant responding under a two-component multiple schedule (mult VI 30 VI 30), one component correlated with the house light on and the other correlated with the house light off (light/dark c...

  8. Establishment and characterization of two human breast carcinoma cell lines by spontaneous immortalization: Discordance between Estrogen, Progesterone and HER2/neu receptors of breast carcinoma tissues with derived cell lines

    Directory of Open Access Journals (Sweden)

    Kamalidehghan Behnam

    2012-10-01

    Full Text Available Abstract Background Breast cancer is one of the most common cancers among women throughout the world. Therefore, established cell lines are widely used as in vitro experimental models in cancer research. Methods Two continuous human breast cell lines, designated MBC1 and MBC2, were successfully established and characterized from invasive ductal breast carcinoma tissues of Malaysian patients. MBC1 and MBC2 have been characterized in terms of morphology analysis, population doubling time, clonogenic formation, wound healing assay, invasion assay, cell cycle, DNA profiling, fluorescence immunocytochemistry, Western blotting and karyotyping. Results MBC1 and MBC2 exhibited adherent monolayer epithelial morphology at a passage number of 150. Receptor status of MBC1 and MBC2 show (ER+, PR+, HER2+ and (ER+, PR-, HER2+, respectively. These results are in discordance with histopathological studies of the tumoral tissues, which were triple negative and (ER-, PR-, HER2+ for MBC1 and MBC2, respectively. Both cell lines were capable of growing in soft agar culture, which suggests their metastatic potential. The MBC1 and MBC2 metaphase spreads showed an abnormal karyotype, including hyperdiploidy and complex rearrangements with modes of 52–58 chromosomes per cell. Conclusions Loss or gain in secondary properties, deregulation and specific genetic changes possibly conferred receptor changes during the culturing of tumoral cells. Thus, we hypothesize that, among heterogenous tumoral cells, only a small minority of ER+/PR+/HER2+ and ER+/PR-/HER2+ cells with lower energy metabolism might survive and adjust easily to in vitro conditions. These cell lines will pave the way for new perspectives in genetic and biological investigations, drug resistance and chemotherapy studies, and would serve as prototype models in Malaysian breast carcinogenesis investigations.

  9. Serotonergic Modulation of Conditioned Fear

    Directory of Open Access Journals (Sweden)

    Judith R. Homberg

    2012-01-01

    Full Text Available Conditioned fear plays a key role in anxiety disorders as well as depression and other neuropsychiatric conditions. Understanding how neuromodulators drive the associated learning and memory processes, including memory consolidation, retrieval/expression, and extinction (recall, is essential in the understanding of (individual differences in vulnerability to these disorders and their treatment. The human and rodent studies I review here together reveal, amongst others, that acute selective serotonin reuptake inhibitor (SSRI treatment facilitates fear conditioning, reduces contextual fear, and increases cued fear, chronic SSRI treatment reduces both contextual and cued fear, 5-HT1A receptors inhibit the acquisition and expression of contextual fear, 5-HT2A receptors facilitates the consolidation of cued and contextual fear, inactivation of 5-HT2C receptors facilitate the retrieval of cued fear memory, the 5-HT3 receptor mediates contextual fear, genetically induced increases in serotonin levels are associated with increased fear conditioning, impaired cued fear extinction, or impaired extinction recall, and that genetically induced 5-HT depletion increases fear conditioning and contextual fear. Several explanations are presented to reconcile seemingly paradoxical relationships between serotonin levels and conditioned fear.

  10. Extracranial radiotherapy in stereotaxic conditions

    International Nuclear Information System (INIS)

    Noel, Georges; Moty-Monnereau, Celine; Meyer, Aurelia; David, Pauline; Pages, Frederique; Muller, Felix; Lee-Robin, Sun Hae; David, Denis Jean

    2006-12-01

    This document reports a literature survey and the discussion of an expert group with the objective to assess the use of extracranial radiotherapy devices in stereotaxic conditions. After a brief overview of the technological context, the authors proposes a technical description of radiotherapy in stereotaxic conditions, of the CyberKnife, of others radiotherapy techniques in stereotaxic conditions for extracranial indications, and of alternate techniques. They give an overview of concerned pathologies: skeleton, hepatic, bronchopulmonary, pancreas, prostate, kidney, and paediatric tumours. They describe the present care condition in France in terms of classification of medial acts, and of patient homogeneous groups. They provide the identification of this practice in foreign nomenclature. In the next part, they report the assessment, first through a critical analysis of published data and information in terms of act feasibility, efficiency and safety, of act role in the therapeutic strategy, of conditions of execution, and of impact on public health, and secondly through a statement of opinion of the working group in terms of terminology, indications, safety, and conditions of execution

  11. Conditioned sounds enhance visual processing.

    Directory of Open Access Journals (Sweden)

    Fabrizio Leo

    Full Text Available This psychophysics study investigated whether prior auditory conditioning influences how a sound interacts with visual perception. In the conditioning phase, subjects were presented with three pure tones ( =  conditioned stimuli, CS that were paired with positive, negative or neutral unconditioned stimuli. As unconditioned reinforcers we employed pictures (highly pleasant, unpleasant and neutral or monetary outcomes (+50 euro cents, -50 cents, 0 cents. In the subsequent visual selective attention paradigm, subjects were presented with near-threshold Gabors displayed in their left or right hemifield. Critically, the Gabors were presented in synchrony with one of the conditioned sounds. Subjects discriminated whether the Gabors were presented in their left or right hemifields. Participants determined the location more accurately when the Gabors were presented in synchrony with positive relative to neutral sounds irrespective of reinforcer type. Thus, previously rewarded relative to neutral sounds increased the bottom-up salience of the visual Gabors. Our results are the first demonstration that prior auditory conditioning is a potent mechanism to modulate the effect of sounds on visual perception.

  12. Turbocharging Normalization in Highland Conditions

    Directory of Open Access Journals (Sweden)

    I. V. Filippov

    2017-01-01

    Full Text Available To ensure many production processes are used compressors of various types, including turbochargers, which produce compressed air. The actual performance values of turbochargers used in highlands are significantly different from the certified values, and parameters of compressed air do not always guarantee the smooth and efficient functioning for consumers.The paper presents research results of the turbochargers of 4CI 425MX4 type, a series of "CENTAC", manufactured by INGERSOL – RAND Company. The research has been conducted in industrial highland conditions in difficult climatic environment. There were almost no investigations of turbochargers running in highland conditions. The combination of low atmospheric pressure with high temperature of the intake air causes the abnormal operating conditions of a turbocharger. Only N. M. Barannikov in his paper shows the results of theoretical studies of such operating conditions, but as to the practical research, there is no information at all.To normalize the turbocharger operation an option of the mechanical pressurization in the suction pipe is adopted. As a result of theoretical research, a TurboMAX blower MAX500 was chosen as a supercharger. The next stage of theoretical research was to construct characteristics of the turbocharger 4CI 425MX4 with a mechanical supercharger in the suction pipe. The boost reduces to the minimum the time of using additional compressors when parameters of the intake air are changed and ensures the smooth and efficient functioning for consumers.To verify the results of theoretical studies, namely, the technique for recalculation of the turbocharger characteristics under the real conditions of suction, were carried out the experimental researches. The average error between experimental and theoretical data is 2,9783 %, which confirms the validity of the technique used for reduction of the turbocharger characteristics to those under the real conditions of suction.

  13. Lorentzian condition in holographic cosmology

    International Nuclear Information System (INIS)

    Hertog, Thomas; Monten, Ruben; Vreys, Yannick

    2017-01-01

    We derive a sufficient set of conditions on the Euclidean boundary theory in dS/CFT for it to predict classical, Lorentzian bulk evolution at large spatial volumes. Our derivation makes use of a canonical transformation to express the bulk wave function at large volume in terms of the sources of the dual partition function. This enables a sharper formulation of dS/CFT. The conditions under which the boundary theory predicts classical bulk evolution are stronger than the criteria usually employed in quantum cosmology. We illustrate this in a homogeneous isotropic minisuperspace model of gravity coupled to a scalar field in which we identify the ensemble of classical histories explicitly.

  14. Tore supra first wall conditioning

    International Nuclear Information System (INIS)

    Gauthier, E.; Achard, M.H.; Grosman, A.; Monier, P.

    1989-01-01

    The procedures and the results obtained concerning impurity and isotopic control in Tore Supra tokamak are summarized. The conditioning of the vessel, mainly achieved by glow discharges, is described. The impurity control of the discharge was monitored with a VUV-X spectrometer. The in situ blasting degassing procedure applied is explained. In the sequence of the conditioning process, the hydrogen and the helium glow discharges and the carbonization method are discussed. The He glow discharges allowed to limit the H content of the He plasma shot below 20%

  15. Working Conditions, Lifestyles and Health

    DEFF Research Database (Denmark)

    Cottini, Elena; Ghinetti, Paolo

    The aim of this paper is to investigate whether employee health is affected by the environment in which the individual works - in terms of both physical and psychosocial working conditions - and by his or her lifestyle. Health measures are computed from Danish data, and refer to both self assessed...... general health and two more objective health measures: mental health specific to work-related problems, and physical health. We find that both bad working conditions and bad lifestyles reduce health, especially in its self-assessed component. The impact of lifetsyle indicators have a more modest health...... impact on both physical and mental health....

  16. Hygienic diagnosis in extreme conditions

    International Nuclear Information System (INIS)

    Sofronov, G.A.

    1997-01-01

    Review for book by M.P. Zakharchenko, S.A. Lopatin, G.N. Novozhilov, V.I. Zakharov Hygienic diagnosis in extreme conditions is presented discussing the problem of people health preservation under extreme conditions. Hygienic diagnosis is considered illustrated by cases of hostilities (Afghan War), earthquake response in Armenia (1988) and Chernobyl accident response. Attention is paid to the estimation of radiation doses to people and characteristics of main types of dosimeters. The high scientific level of the book is marked

  17. Extreme Conditions Modeling Workshop Report

    Energy Technology Data Exchange (ETDEWEB)

    Coe, R. G.; Neary, V. S.; Lawson, M. J.; Yu, Y.; Weber, J.

    2014-07-01

    Sandia National Laboratories (SNL) and the National Renewable Energy Laboratory (NREL) hosted the Wave Energy Converter (WEC) Extreme Conditions Modeling (ECM) Workshop in Albuquerque, NM on May 13th-14th, 2014. The objective of the workshop was to review the current state of knowledge on how to model WECs in extreme conditions (e.g. hurricanes and other large storms) and to suggest how U.S. Department of Energy (DOE) and national laboratory resources could be used to improve ECM methods for the benefit of the wave energy industry.

  18. Flow in air conditioned rooms

    DEFF Research Database (Denmark)

    Nielsen, Peter V.

    1974-01-01

    Flow in air conditioned r ooms is examined by means of model experiments . The different gearnetries giving unsteady, steady three- dimensional and steady twodimensional flow are determined . Velacity profiles and temperature profiles are measured in some of the geometries. A numerical solution...... of the flow equations is demonstrated and the flow in air conditioned rooms in case of steady two dimensional flow is predi cted. Compari son with measured results is shown i n the case of small Archimedes numbers, and predictions are shown at high Archimedes numbers. A numerical prediction of f low and heat...

  19. Condition Number Regularized Covariance Estimation.

    Science.gov (United States)

    Won, Joong-Ho; Lim, Johan; Kim, Seung-Jean; Rajaratnam, Bala

    2013-06-01

    Estimation of high-dimensional covariance matrices is known to be a difficult problem, has many applications, and is of current interest to the larger statistics community. In many applications including so-called the "large p small n " setting, the estimate of the covariance matrix is required to be not only invertible, but also well-conditioned. Although many regularization schemes attempt to do this, none of them address the ill-conditioning problem directly. In this paper, we propose a maximum likelihood approach, with the direct goal of obtaining a well-conditioned estimator. No sparsity assumption on either the covariance matrix or its inverse are are imposed, thus making our procedure more widely applicable. We demonstrate that the proposed regularization scheme is computationally efficient, yields a type of Steinian shrinkage estimator, and has a natural Bayesian interpretation. We investigate the theoretical properties of the regularized covariance estimator comprehensively, including its regularization path, and proceed to develop an approach that adaptively determines the level of regularization that is required. Finally, we demonstrate the performance of the regularized estimator in decision-theoretic comparisons and in the financial portfolio optimization setting. The proposed approach has desirable properties, and can serve as a competitive procedure, especially when the sample size is small and when a well-conditioned estimator is required.

  20. Condition Number Regularized Covariance Estimation*

    Science.gov (United States)

    Won, Joong-Ho; Lim, Johan; Kim, Seung-Jean; Rajaratnam, Bala

    2012-01-01

    Estimation of high-dimensional covariance matrices is known to be a difficult problem, has many applications, and is of current interest to the larger statistics community. In many applications including so-called the “large p small n” setting, the estimate of the covariance matrix is required to be not only invertible, but also well-conditioned. Although many regularization schemes attempt to do this, none of them address the ill-conditioning problem directly. In this paper, we propose a maximum likelihood approach, with the direct goal of obtaining a well-conditioned estimator. No sparsity assumption on either the covariance matrix or its inverse are are imposed, thus making our procedure more widely applicable. We demonstrate that the proposed regularization scheme is computationally efficient, yields a type of Steinian shrinkage estimator, and has a natural Bayesian interpretation. We investigate the theoretical properties of the regularized covariance estimator comprehensively, including its regularization path, and proceed to develop an approach that adaptively determines the level of regularization that is required. Finally, we demonstrate the performance of the regularized estimator in decision-theoretic comparisons and in the financial portfolio optimization setting. The proposed approach has desirable properties, and can serve as a competitive procedure, especially when the sample size is small and when a well-conditioned estimator is required. PMID:23730197

  1. Rapid contextual conditioning in autoshaping.

    Science.gov (United States)

    Balsam, P D; Schwartz, A L

    1981-10-01

    Two experiments are reported which investigate the speed of contextual conditioning in autoshaping. In both experiments, a procedure was employed in which ring doves were magazine trained in one context prior to the manipulation of background values in a second context. In Experiment 1, subjects were exposed to 4, 8, 64, 128, or 256 US-only presentations prior to autoshaping. Acquisition speed and maintained response measures were monotonically related to the number of pretraining trials. Subjects in Group 4 acquired the key-peck response fastest, and retardation was maximal within 64 pretraining trials. In Experiment 2, subjects given 20 pretraining trials were significantly more retarded than subjects given 2 pretraining trials, but only when pretraining and testing were conducted in the same context. Overall, the results of these experiments show that in autoshaping, contextual conditioning is very rapid; this demonstrates the plausibility of theoretical accounts of Pavlovian conditioning which assert that the development of the conditioned response depends on the associative values of both the CS and background stimuli.

  2. Nested Dynamic Condition Response Graphs

    DEFF Research Database (Denmark)

    Hildebrandt, Thomas; Mukkamala, Raghava Rao; Slaats, Tijs

    2012-01-01

    We present an extension of the recently introduced declarative process model Dynamic Condition Response Graphs ( DCR Graphs) to allow nested subgraphs and a new milestone relation between events. The extension was developed during a case study carried out jointly with our industrial partner...

  3. Teat condition in dairy cows

    NARCIS (Netherlands)

    Neijenhuis, Francesca

    2004-01-01

    The dairy cow's teat is the first line of defence against mastitis pathogens. The milking process may affect the teat's condition, increasing the risk of mastitis. It is well-proven that teat-ends with severe erosions or broken skin will have an increased risk of mastitis. However, more common

  4. Teat Condition in Dairy Cows

    NARCIS (Netherlands)

    Neijenhuis, F.

    2004-01-01

    The dairy cow's teat is the first line of defence against mastitis pathogens. The milking process may affect the teat's condition, increasing the risk of mastitis. It is well-proven that teat-ends with severe erosions or broken skin will have an increased risk of mastitis. However, more common

  5. Acceptance conditions in automated negotiation

    NARCIS (Netherlands)

    Baarslag, T.; Hindriks, K.V.; Jonker, C.M.

    2011-01-01

    In every negotiation with a deadline, one of the negotiating parties has to accept an offer to avoid a break off. A break off is usually an undesirable outcome for both parties, therefore it is important that a negotiator employs a proficient mechanism to decide under which conditions to accept.

  6. Conditional Reasoning in Schizophrenic Patients.

    Science.gov (United States)

    Kornreich, Charles; Delle-Vigne, Dyna; Brevers, Damien; Tecco, Juan; Campanella, Salvatore; Noël, Xavier; Verbanck, Paul; Ermer, Elsa

    2017-01-01

    Conditional reasoning (if p then q) is used very frequently in everyday situations. Conditional reasoning is impaired in brain-lesion patients, psychopathy, alcoholism, and polydrug dependence. Many neurocognitive deficits have also been described in schizophrenia. We assessed conditional reasoning in 25 patients with schizophrenia, 25 depressive patients, and 25 controls, using the Wason selection task in three different domains: social contracts, precautionary rules, and descriptive rules. Control measures included depression, anxiety, and severity of schizophrenia measures as a Verbal Intelligence Scale. Patients with schizophrenia were significantly impaired on all conditional reasoning tasks compared to depressives and controls. However, the social contract and precautions tasks yielded better results than the descriptive tasks. Differences between groups disappeared for social contract but remained for precautions and descriptive tasks when verbal intelligence was used as a covariate. These results suggest that domain-specific reasoning mechanisms, proposed by evolutionary psychologists, are relatively resilient in the face of brain network disruptions that impair more general reasoning abilities. Nevertheless, patients with schizophrenia could encounter difficulties understanding precaution rules and social contracts in real-life situations resulting in unwise risk-taking and misunderstandings in the social world.

  7. The content of compound conditioning.

    Science.gov (United States)

    Harris, Justin A; Andrew, Benjamin J; Livesey, Evan J

    2012-04-01

    In three experiments using Pavlovian conditioning of magazine approach, rats were trained with a compound stimulus, AB, and were concurrently trained with stimulus B on its own. The reinforcement rate of B, rB, was either 1/2, 2/3, or 2/5 of rAB. After extended training, the conditioning strength of A was assessed using probe trials in which A was presented alone. Responding during A was compared with that during AB, B, and a third stimulus, C, for which rC = rAB - rB. In each experiment, the rats' response rate during A was almost identical to that during C (and during B, when rB = 1/2rAB). This suggests that, during AB conditioning, the rats had learned about rA as being equal to [rAB - rB], and implies that the content of their learning was a linear function of r. The findings provide strong support for rate-based models of conditioning (e.g., Gallistel & Gibbon, 2000). They are also consistent with the associative account of learning defined in the Rescorla and Wagner (1972) model, but only if the learning rate during reinforcement equals that during nonreinforcement. (c) 2012 APA, all rights reserved.

  8. Defining and Measuring Chronic Conditions

    Centers for Disease Control (CDC) Podcasts

    This podcast is an interview with Dr. Anand Parekh, U.S. Department of Health and Human Services Deputy Assistant Secretary for Health, and Dr. Samuel Posner, Preventing Chronic Disease Editor in Chief, about the definition and burden of multiple chronic conditions in the United States.

  9. What's wrong with fear conditioning?

    NARCIS (Netherlands)

    Beckers, T.; Krypotos, A.M.; Boddez, Y.; Effting, M.; Kindt, M.

    2013-01-01

    Fear conditioning is one of the prime paradigms of behavioural neuroscience and a source of tremendous insight in the fundamentals of learning and memory and the psychology and neurobiology of emotion. It is also widely regarded as a model for the pathogenesis of anxiety disorders in a

  10. CONDITIONS FOR EXACT CAVALIERI ESTIMATION

    Directory of Open Access Journals (Sweden)

    Mónica Tinajero-Bravo

    2014-03-01

    Full Text Available Exact Cavalieri estimation amounts to zero variance estimation of an integral with systematic observations along a sampling axis. A sufficient condition is given, both in the continuous and the discrete cases, for exact Cavalieri sampling. The conclusions suggest improvements on the current stereological application of fractionator-type sampling.

  11. Extreme conditions (p, T, H)

    Energy Technology Data Exchange (ETDEWEB)

    Mesot, J [Lab. for Neutron Scattering ETH Zurich, Zurich (Switzerland) and Paul Scherrer Institute, Villigen (Switzerland)

    1996-11-01

    The aim of this paper is to summarize the sample environment which will be accessible at the SINQ. In order to illustrate the type of experiments which will be feasible under extreme conditions of temperature, magnetic field and pressure at the SINQ a few selected examples are also given. (author) 7 figs., 14 refs.

  12. Conditioning of alpha bearing wastes

    International Nuclear Information System (INIS)

    1991-01-01

    Alpha bearing wastes are generated during the reprocessing of spent fuel, mixed oxide fuel fabrication, decommissioning and other activities. The safe and effective management of these wastes is of particular importance owing to the radiotoxicity and long lived characteristics of certain transuranic (TRU) elements. The management of alpha bearing wastes involves a number of stages which include collection, characterization, segregation, treatment, conditioning, transport, storage and disposal. This report describes the currently available matrices and technologies for the conditioning of alpha wastes and relates them to their compatibility with the other stages of the waste management process. The selection of a specific immobilization process is dependent on the waste treatment state and the subsequent handling, transport, storage and disposal requirements. The overall objectives of immobilization are similar for all waste producers and processors, which are to produce: (a) Waste forms with sufficient mechanical, physical and chemical stability to satisfy all stages of handling, transport and storage (referred to as the short term requirements), and (b) Waste forms which will satisfy disposal requirements and inhibit the release of radionuclides to the biosphere (referred to as the long term requirements). Cement and bitumen processes have already been successfully applied to alpha waste conditioning on the industrial scale in many of the IAEA Member States. Cement systems based on BFS and pozzolanic cements have emerged as the principal encapsulation matrices for the full range of alpha bearing wastes. Alternative technologies, such as polymers and ceramics, are being developed for specific waste streams but are unlikely to meet widespread application owing to cost and process complexity. The merits of alpha waste conditioning are improved performance in transport, storage and disposal combined with enhanced public perception of waste management operations. These

  13. The sodium-bicarbonate cotransporter NBCe2 (slc4a5) expressed in human renal proximal tubules shows increased apical expression under high-salt conditions.

    Science.gov (United States)

    Gildea, John J; Xu, Peng; Carlson, Julia M; Gaglione, Robert T; Bigler Wang, Dora; Kemp, Brandon A; Reyes, Camellia M; McGrath, Helen E; Carey, Robert M; Jose, Pedro A; Felder, Robin A

    2015-12-01

    The electrogenic sodium bicarbonate cotransporter (NBCe2) is encoded by SLC4A5, variants of which have been associated with salt sensitivity of blood pressure, which affects 25% of the adult population. NBCe2 is thought to mediate sodium bicarbonate cotransport primarily in the renal collecting duct, but NBCe2 mRNA is also found in the rodent renal proximal tubule (RPT). The protein expression or function of NBCe2 has not been demonstrated in the human RPT. We validated an NBCe2 antibody by shRNA and Western blot analysis, as well as overexpression of an epitope-tagged NBCe2 construct in both RPT cells (RPTCs) and human embryonic kidney 293 (HEK293) cells. Using this validated NBCe2 antibody, we found NBCe2 protein expression in the RPT of fresh and frozen human kidney slices, RPTCs isolated from human urine, and isolated RPTC apical membrane. Under basal conditions, NBCe2 was primarily found in the Golgi, while NBCe1 was primarily found at the basolateral membrane. Following an acute short-term increase in intracellular sodium, NBCe2 expression was increased at the apical membrane in cultured slices of human kidney and polarized, immortalized RPTCs. Sodium bicarbonate transport was increased by monensin and overexpression of NBCe2, decreased by NBCe2 shRNA, but not by NBCe1 shRNA, and blocked by 2,2'-(1,2-ethenediyl)bis[5-isothiocyanato-benzenesulfonic acid]. NBCe2 could be important in apical sodium and bicarbonate cotransport under high-salt conditions; the implication of the ex vivo studies to the in vivo situation when salt intake is increased remains unclear. Therefore, future studies will examine the role of NBCe2 in mediating increased renal sodium transport in humans whose blood pressures are elevated by an increase in sodium intake. Copyright © 2015 the American Physiological Society.

  14. Extreme Conditions Modeling Workshop Report

    Energy Technology Data Exchange (ETDEWEB)

    Coe, Ryan Geoffrey [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Neary, Vincent Sinclair [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Lawon, Michael J. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Yu, Yi-Hsiang [National Renewable Energy Lab. (NREL), Golden, CO (United States); Weber, Jochem [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2014-07-01

    Sandia National Laboratories (SNL) and the National Renewable Energy Laboratory (NREL) hosted the Wave Energy Converter (WEC) Extreme Conditions Modeling (ECM) Workshop in Albuquerque, New Mexico on May 13–14, 2014. The objective of the workshop was to review the current state of knowledge on how to numerically and experimentally model WECs in extreme conditions (e.g. large ocean storms) and to suggest how national laboratory resources could be used to improve ECM methods for the benefit of the wave energy industry. More than 30 U.S. and European WEC experts from industry, academia, and national research institutes attended the workshop, which consisted of presentations from W EC developers, invited keynote presentations from subject matter experts, breakout sessions, and a final plenary session .

  15. Ranking Theory and Conditional Reasoning.

    Science.gov (United States)

    Skovgaard-Olsen, Niels

    2016-05-01

    Ranking theory is a formal epistemology that has been developed in over 600 pages in Spohn's recent book The Laws of Belief, which aims to provide a normative account of the dynamics of beliefs that presents an alternative to current probabilistic approaches. It has long been received in the AI community, but it has not yet found application in experimental psychology. The purpose of this paper is to derive clear, quantitative predictions by exploiting a parallel between ranking theory and a statistical model called logistic regression. This approach is illustrated by the development of a model for the conditional inference task using Spohn's (2013) ranking theoretic approach to conditionals. Copyright © 2015 Cognitive Science Society, Inc.

  16. Acoustic multivariate condition monitoring - AMCM

    Energy Technology Data Exchange (ETDEWEB)

    Rosenhave, P E [Vestfold College, Maritime Dept., Toensberg (Norway)

    1998-12-31

    In Norway, Vestfold College, Maritime Department presents new opportunities for non-invasive, on- or off-line acoustic monitoring of rotating machinery such as off-shore pumps and diesel engines. New developments within acoustic sensor technology coupled with chemometric data analysis of complex signals now allow condition monitoring of hitherto unavailable flexibility and diagnostic specificity. Chemometrics paired with existing knowledge yields a new and powerful tool for condition monitoring. By the use of multivariate techniques and acoustics it is possible to quantify wear and tear as well as predict the performance of working components in complex machinery. This presentation describes the AMCM method and one result of a feasibility study conducted onboard the LPG/C `Norgas Mariner` owned by Norwegian Gas Carriers as (NGC), Oslo. (orig.) 6 refs.

  17. Acoustic multivariate condition monitoring - AMCM

    Energy Technology Data Exchange (ETDEWEB)

    Rosenhave, P.E. [Vestfold College, Maritime Dept., Toensberg (Norway)

    1997-12-31

    In Norway, Vestfold College, Maritime Department presents new opportunities for non-invasive, on- or off-line acoustic monitoring of rotating machinery such as off-shore pumps and diesel engines. New developments within acoustic sensor technology coupled with chemometric data analysis of complex signals now allow condition monitoring of hitherto unavailable flexibility and diagnostic specificity. Chemometrics paired with existing knowledge yields a new and powerful tool for condition monitoring. By the use of multivariate techniques and acoustics it is possible to quantify wear and tear as well as predict the performance of working components in complex machinery. This presentation describes the AMCM method and one result of a feasibility study conducted onboard the LPG/C `Norgas Mariner` owned by Norwegian Gas Carriers as (NGC), Oslo. (orig.) 6 refs.

  18. Initial conditions for cosmological perturbations

    Science.gov (United States)

    Ashtekar, Abhay; Gupt, Brajesh

    2017-02-01

    Penrose proposed that the big bang singularity should be constrained by requiring that the Weyl curvature vanishes there. The idea behind this past hypothesis is attractive because it constrains the initial conditions for the universe in geometric terms and is not confined to a specific early universe paradigm. However, the precise statement of Penrose’s hypothesis is tied to classical space-times and furthermore restricts only the gravitational degrees of freedom. These are encapsulated only in the tensor modes of the commonly used cosmological perturbation theory. Drawing inspiration from the underlying idea, we propose a quantum generalization of Penrose’s hypothesis using the Planck regime in place of the big bang, and simultaneously incorporating tensor as well as scalar modes. Initial conditions selected by this generalization constrain the universe to be as homogeneous and isotropic in the Planck regime as permitted by the Heisenberg uncertainty relations.

  19. Health effects of air conditioning

    Energy Technology Data Exchange (ETDEWEB)

    Molina, C.; Caillaud, D.

    The air conditioning used in residential or commercial buildings (offices, hotels, sterile areas of hospitals, computer and electronics industries) is responsible for a certain number of well identified ailments which can be classified in three groups: infections (legionnaires'disease, ornithosis), allergies (mainly respiratory) eg. rhinitis, asthma, alveolitis but also Monday morning illness or humidifier fever, various functional disorders grouped under the name Sick Building Syndrome. To avoid these problems, a certain number of recommendations may be made. They concern: installation of air conditioning, humidification which is the cause of bacterial and fungal contamination, filtration, monitoring of the installation by qualitative and quantitative measurements, maintenance. The legal problems relating to these illnesses, the responsibility for which is ultimately laid at the door of the installers, should also be mentioned. Allergies are recognized to be of professional origin in Table 66 of allergic illnesses issued by the Social Security.

  20. Initial conditions for cosmological perturbations

    International Nuclear Information System (INIS)

    Ashtekar, Abhay; Gupt, Brajesh

    2017-01-01

    Penrose proposed that the big bang singularity should be constrained by requiring that the Weyl curvature vanishes there. The idea behind this past hypothesis is attractive because it constrains the initial conditions for the universe in geometric terms and is not confined to a specific early universe paradigm. However, the precise statement of Penrose’s hypothesis is tied to classical space-times and furthermore restricts only the gravitational degrees of freedom. These are encapsulated only in the tensor modes of the commonly used cosmological perturbation theory. Drawing inspiration from the underlying idea, we propose a quantum generalization of Penrose’s hypothesis using the Planck regime in place of the big bang, and simultaneously incorporating tensor as well as scalar modes. Initial conditions selected by this generalization constrain the universe to be as homogeneous and isotropic in the Planck regime as permitted by the Heisenberg uncertainty relations . (paper)

  1. Sleep Behavior and Unemployment Conditions

    OpenAIRE

    Antillón, Marina; Lauderdale, Diane S.; Mullahy, John

    2014-01-01

    Recent research has reported that habitually short sleep duration is a risk factor for declining health, including increased risk of obesity, diabetes and coronary heart disease. In this study we investigate whether macroeconomic conditions are associated with variation in mean sleep time in the United States, and if so, whether the effect is procyclical or countercyclical. We merge state unemployment rates from 2003 through 2012 with the American Time Use Survey, a nationally representative ...

  2. Macroeconomic Conditions and Capital Raising

    OpenAIRE

    Isil Erel; Brandon Julio; Woojin Kim; Michael S. Weisbach

    2011-01-01

    Do macroeconomic conditions affect firms' abilities to raise capital? If so, how do they affect the manner in which the capital is raised? We address these questions using a large sample of publicly-traded debt issues, seasoned equity offers, bank loans and private placements of equity and debt. Our results suggest that a borrower's credit quality significantly affects its ability to raise capital during macroeconomic downturns. For noninvestment-grade borrowers, capital raising tends to be p...

  3. Learning strategies during fear conditioning

    OpenAIRE

    Carpenter, Russ E.; Summers, Cliff H.

    2009-01-01

    This paper describes a model of fear learning, in which subjects have an option of behavioral responses to impending social defeat. The model generates two types of learning: social avoidance and classical conditioning, dependent upon 1) escape from or 2) social subordination to an aggressor. We hypothesized that social stress provides the impetus as well as the necessary information to stimulate dichotomous goal-oriented learning. Specialized tanks were constructed to subject rainbow trout t...

  4. OPAL Netlogo Land Condition Model

    Science.gov (United States)

    2014-08-15

    ER D C/ CE RL T R- 14 -1 2 Optimal Allocation of Land for Training and Non-training Uses ( OPAL ) OPAL Netlogo Land Condition Model...Fulton, Natalie Myers, Scott Tweddale, Dick Gebhart, Ryan Busby, Anne Dain-Owens, and Heidi Howard August 2014 OPAL team measuring above and...online library at http://acwc.sdp.sirsi.net/client/default. Optimal Allocation of Land for Training and Non-training Uses ( OPAL ) ERDC/CERL TR-14-12

  5. Steel Pickling in Challenging Conditions

    OpenAIRE

    Maanonen, Mika

    2014-01-01

    The purpose of this thesis was to collect data on the pickling procedure and parameters especially in conditions where there are limited amount of power for heating, limited water treatment possibilities and equipment to maintain pickling processes. Information about steel pickling, alternative methods and processes before and after pickling was acquired. Data on most common chemicals for pickling were acquired and compared. Cleaning efficiency, ease of use, safety, price and availability...

  6. Conditionally solvable path integral problems

    International Nuclear Information System (INIS)

    Grosche, C.

    1995-05-01

    Some specific conditionally exactly solvable potentials are discussed within the path integral formalism. They generalize the usually known potentials by the incorporation of a fractional power behaviour and strongly anharmonic terms. We find four different kinds of such potentials, the first is related to the Coulomb potential, the second is an anharmonic confinement potential, and the third and the fourth are related to the Manning-Rosen potential. (orig.)

  7. Microbial Response to Spaceflight Conditions

    OpenAIRE

    Moeller, R.

    2017-01-01

    Space radiation, including Galactic Cosmic Rays (GCR) and Solar Particle Events (SPE), represents a major hazard for biological systems beyond Earth. Spores of Bacillus subtilis have been shown to be suitable dosimeters for probing extreme terrestrial and extraterrestrial environmental conditions in astrobiological and environmental studies. During dormancy spores are metabolically inactive; thus substantial DNA, protein, tRNA and ribosome damage can accumulate while the spo...

  8. EPR spectroscopy at DNP conditions

    International Nuclear Information System (INIS)

    Heckmann, J.; Goertz, St.; Meyer, W.; Radtke, E.; Reicherz, G.

    2004-01-01

    In terms of dynamic nuclear polarization (DNP) studies and systematic target material research it is crucial to know the EPR lineshape of the DNP relevant paramagnetic centers. Therefore in Bochum an EPR spectrometer has been implemented into the 4 He evaporation DNP facility in order to perform EPR studies at DNP conditions (B=2.5 T, T=1 K). The spectrometer hardware and performance as well as first results are presented

  9. Furfural stability in various conditions

    OpenAIRE

    Oreiro Muzas, Olaya

    2011-01-01

    The topic of this thesis is the study of the furfural stability to determine the influence of some conditions in furfural degradation. The aim of the study is to decrease furfural degradation and thus improve furfural yield in furfural production. The thesis consists of a literature review and laboratory experiments. Attention has been paid to the furfural description and properties as well as the background of the research and traditional methods to produce furfural. In the experiments, w...

  10. Monitoring Thermal Conditions in Footwear

    Science.gov (United States)

    Silva-Moreno, Alejandra. A.; Lopez Vela, Martín; Alcalá Ochoa, Noe

    2006-09-01

    Thermal conditions inside the foot were evaluated on a volunteer subject. We have designed and constructed an electronic system which can monitors temperature and humidity of the foot inside the shoe. The data is stored in a battery-powered device for later uploading to a host computer for data analysis. The apparatus potentially can be used to provide feedback to patients who are prone to having skin breakdowns.

  11. Analytical methods under emergency conditions

    International Nuclear Information System (INIS)

    Sedlet, J.

    1983-01-01

    This lecture discusses methods for the radiochemical determination of internal contamination of the body under emergency conditions, here defined as a situation in which results on internal radioactive contamination are needed quickly. The purpose of speed is to determine the necessity for medical treatment to increase the natural elimination rate. Analytical methods discussed include whole-body counting, organ counting, wound monitoring, and excreta analysis. 12 references

  12. Defining and Measuring Chronic Conditions

    Centers for Disease Control (CDC) Podcasts

    2013-05-20

    This podcast is an interview with Dr. Anand Parekh, U.S. Department of Health and Human Services Deputy Assistant Secretary for Health, and Dr. Samuel Posner, Preventing Chronic Disease Editor in Chief, about the definition and burden of multiple chronic conditions in the United States.  Created: 5/20/2013 by Preventing Chronic Disease (PCD), National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 5/20/2013.

  13. Reconstruction of FXR Beam Conditions

    International Nuclear Information System (INIS)

    Nexen, W E; Scarpetti, R D; Zentler, J

    2001-01-01

    Beam-envelope radius, envelope angle, and beam emittance can be derived from measurements of beam radius for at least three different transport conditions. We have used this technique to reconstruct exit parameters from the FXR injector and accelerator. We use a diamagnetic loop (DML) to measure the magnetic moment of the high current beam. With no assumptions about radial profile, we can derive the beam mean squire radius from the moment under certain easily met conditions. Since it is this parameter which is required for the reconstruction, it is evident that the DML is the ideal diagnostic for this technique. The simplest application of this technique requires at least three shots for a reconstruction but in reality requires averaging over many more shots because of shot to shot variation. Since DML measurements do not interfere with the beam, single shot time resolved measurements of the beam parameters appear feasible if one uses an array of at least three DMLs separated by known transport conditions

  14. Commission Conditions d'emploi

    CERN Multimedia

    Staff Association

    2017-01-01

    Au CERN, nous avons la formidable possibilité d’imaginer nos CONDITIONS D’EMPLOIS. Rendez-vous compte ! Nous avons le pouvoir de proposer des idées et de les défendre pour avoir des conditions d’emplois qui soient les plus attractives possibles pour le personnel en place et à venir. ---------------- L’Association du personnel du CERN, tout le monde connait ou en a entendu parler. Ce qui est moins connu, ce sont les diverses commissions internes qui traitent des sujets propres à défendre les intérêts du personnel. Les publications dans notre journal, l’Echo, sont un des moyens à notre disposition pour vous faire découvrir chacune des commissions internes de l’Association du personnel (voir Echo n°242 sur la commission juridique, et Echo n°255 sur la commission des cas particuliers). Commission Conditions d&...

  15. Ventilation-air conditioning system

    International Nuclear Information System (INIS)

    Kubokoya, Takashi.

    1991-01-01

    Heretofore, in ventilation-air conditioning systems in a nuclear power plant, exhaust gases from each of the ventilation-air conditioning systems of a reactor building, a turbine building, a waste processing building are joined and they are released into atmosphere from the top of a high main exhaustion stack. In order to build such a high main exhaustion stack, a considerable construction cost is required and, in addition, there is a worry of lacking balance with surrounding scenery. Then, in the present invention, exhaust gases are heated by waste heat in a turbine during their introduction from the ventilation-air conditioning facility in the building of a power plant to the main exhaust stack. With such a constitution, since the exhaust gases are heated and their temperature is elevated, they uprise by natural convection when they are released from the top of the main exhaustion stack to the atmosphere. Accordingly, they are released to a level higher than the conventional case in view of the volume of the blower which sends the exhaust gases under pressure, to diffuse them to the atmosphere more sufficiently compared with a conventional case. Further, the height of the main exhaustion stack can be reduced, enabling to minimize the cost for moving the blower. (T.M.)

  16. Inbreeding, energy use and condition.

    Science.gov (United States)

    Ketola, T; Kotiaho, J S

    2009-04-01

    In energetic terms, fitness may be seen to be dependent on successful allocation of energy between life-history traits. In addition, fitness will be constrained by the energy allocation ability, which has also been defined as condition. We suggest here that the allocation ability, estimated as the difference between total energy budget and maintenance metabolism, may be used as a measure of condition. We studied this possibility by measuring the resting metabolic rate and metabolism during forced exercise in Gryllodes sigillatus crickets. To verify that these metabolic traits are closely related to fitness, we experimentally manipulated the degree of inbreeding of individuals belonging to the same pedigree, hence enabling analysis of both inbreeding depression and heritability of traits. We found that inbreeding increased maintenance metabolism, whereas total energy budget was rather insensitive to inbreeding. Despite this, inbreeding led to decreased allocation ability. Overall, metabolic traits exhibited strong inbreeding depression and rather low heritabilities, a pattern that is typical of traits under strong selection. However, traditionally used condition indices were not affected by inbreeding and did not covary with metabolic traits. Moreover, in contrast to the common, but largely untested, tenet, it seems that high resting metabolic rate is indicative of low rather than high quality.

  17. Testing the Conditional Mean Function of Autoregressive Conditional Duration Models

    DEFF Research Database (Denmark)

    Hautsch, Nikolaus

    be subject to censoring structures. In an empirical study based on financial transaction data we present an application of the model to estimate conditional asset price change probabilities. Evaluating the forecasting properties of the model, it is shown that the proposed approach is a promising competitor......This paper proposes a dynamic proportional hazard (PH) model with non-specified baseline hazard for the modelling of autoregressive duration processes. A categorization of the durations allows us to reformulate the PH model as an ordered response model based on extreme value distributed errors...

  18. The epithelial-mesenchymal transition induced by keratinocyte growth conditions is overcome by E6 and E7 from HPV16, but not HPV8 and HPV38: Characterization of global transcription profiles

    International Nuclear Information System (INIS)

    Azzimonti, Barbara; Dell'Oste, Valentina; Borgogna, Cinzia; Mondini, Michele; Gugliesi, Francesca; De Andrea, Marco; Chiorino, Giovanna; Scatolini, Maria; Ghimenti, Chiara; Landolfo, Santo; Gariglio, Marisa

    2009-01-01

    The aim of this study was to evaluate the growth properties of primary human keratinocytes expressing E6 and E7 proteins, which are from either the β- or α-genotypes, under different culture conditions. We demonstrated that keratinocytes expressing E6 and E7, from both HPV8 and 38, irreversibly underwent the epithelial-mesenchymal transition (EMT) when grown on plastic with FAD medium (F12/DMEM/5%FBS). Expression of E6/E7 from HPV16 was capable of fully overcoming the FAD-induced EMT. Immortalization was only observed in HPV16-transduced cell lines, while the more proliferating phenotype of both KerHPV8 and 38 was mainly related to FAD-induced EMT. Microarray analysis of exponentially growing cells identified 146 cellular genes that were differentially regulated in HPV16 compared to HPV8- and 38-transduced cells. A large accumulation of transcripts associated with epidermal development and differentiation was observed in HPV16-transduced cells, whereas transcripts of genes involved in the extracellular matrix, multicellular organismal processes, and inflammatory response were affected in HPV8 and 38-transduced cells.

  19. William Gaddis’s Immortality: Celebration, Cartoon, or Corruption?

    Directory of Open Access Journals (Sweden)

    Crystal Alberts

    2013-11-01

    Full Text Available Although ostensibly a review of 'The Letters of William Gaddis' edited by Steven Moore (Champaign: Dalkey Archive, 2013, this article evaluates Moore’s volume in light of generally accepted practices of scholarly editions and the handling of historical documents. In particular, Alberts compares some of Moore’s edited letters to the originals housed either at Washington University in St. Louis or the Harry Ransom Center at the University of Texas, Austin and reveals issues involving the representation of the archival material, inconsistencies in editorial principles, and a misattributed letter, among other things.

  20. William Gaddis’s Immortality: Celebration, Cartoon, or Corruption?

    OpenAIRE

    Alberts, Crystal

    2013-01-01

    Although ostensibly a review of 'The Letters of William Gaddis' edited by Steven Moore (Champaign: Dalkey Archive, 2013), this article evaluates Moore’s volume in light of generally accepted practices of scholarly editions and the handling of historical documents. In particular, Alberts compares some of Moore’s edited letters to the originals housed either at Washington University in St. Louis or the Harry Ransom Center at the University of Texas, Austin and reveals issues involving the repre...

  1. Mortalizing Morality and Immortalizing Immorality in the Campaign ...

    African Journals Online (AJOL)

    Caught in the web of some kind of psychological trauma, emotional dislocation, social fracture and cultural disfigurement resulting from the health mutilation of the scourge of HIV/AIDS, science is receiving the greatest challenge in history in its attempts to provide a cure for this deadly disease. Governments in their tiers and ...

  2. Protein composition of catalytically active human telomerase from immortal cells

    DEFF Research Database (Denmark)

    Cohen, Scott B; Graham, Mark E; Lovrecz, George O

    2007-01-01

    Telomerase is a ribonucleoprotein enzyme complex that adds 5'-TTAGGG-3' repeats onto the ends of human chromosomes, providing a telomere maintenance mechanism for approximately 90% of human cancers. We have purified human telomerase approximately 10(8)-fold, with the final elution dependent on th...

  3. Technique and the Art of Immortality, 1800-1900

    NARCIS (Netherlands)

    Bol, M.A.H.

    2017-01-01

    This essay investigates how, over the course of the nineteenth and twentieth centuries, painters, art historians, and chemists fused a bond to undo the damage they believed the industrial revolution had caused the art of painting. Even though the industrial revolution produced many novelties for

  4. This immortal coil? New CT rigs duel against singles

    Energy Technology Data Exchange (ETDEWEB)

    Creighton, J.

    1998-12-01

    New competition to conventional single rigs that have changed little in the last four decades face new competition from next-generation coiled tubing (CT) units which have multi-function capabilities, ranging from driving onto leases, drilling and setting surface case to cementing. Several of these new units are ready to challenge the conventional single rigs. Their ability to perform at high penetration rates (up to twice what single rigs can do) is expected to significantly cut drill time, with corresponding cost savings for both contractors and operators. Serval Corporation and Fleet Coiled Services are just two of the drilling service companies that have launched new shallow grass roots coiled tubing drilling units recently, gambling that the new technology will win over conventional methods hands down. Some major companies, like Fracmaster Ltd. and NOWSCO Well Service Ltd., have targeted the re-entry and horizontal markets, a much more difficult technical challenge, sinking billions of dollars of research and development money into advancing the most technically difficult applications of coil technology.

  5. Phenoptosis in arthropods and immortality of social insects.

    Science.gov (United States)

    Kartsev, V M

    2014-10-01

    In general, there are no drastic differences in phenoptosis patterns in plant and animal organisms. However, there are some specific features characteristic for insects and other arthropods: 1) their development includes metamorphosis with different biochemical laws at consecutive developmental stages; 2) arthropods can reduce or stop development and aging when in a state of diapause or temporal cold immobility; 3) their life cycle often correlates with seasonal changes of surroundings; 4) polymorphism is widespread - conspecifics differ by their lifespans and phenoptosis features; 5) lifespan-related sexual dimorphism is common; 6) significant situational plasticity of life cycle organization is an important feature; for example, the German wasp (Paravespula germanica) is obligatorily univoltine in the temperate zone, while in tropical regions its lifespan increases and leads to repeated reproduction; 7) life cycles of closely related species may differ significantly, for example, in contrast to German wasp, some tropical hornets (Vespa) have only one reproduction period. Surprisingly, many insect species have been shown to be subjected to gradual aging and phenoptosis, like the highest mammals. However, queens of social insects and some long-lived arachnids can apparently be considered non-aging organisms. In some species, lifespan is limited to one season, while others live much longer or shorter. Cases of one-time reproduction are rather rare. Aphagia is common in insects (over 10,000 species). Cannibalism is an important mortality factor in insects as well as in spiders. In social insects, which exist only in colonies (families), the lifetime of a colony can be virtually unlimited. However, in case of some species the developmental cycle and death of a colony after its completion are predetermined. Most likely, natural selection in insects does not lengthen individual lifespan, but favors increase in reproduction efficiency based on fast succession of generations leading to increased evolvability.

  6. In Search of Rationality in Human Longevity and Immortality

    OpenAIRE

    Bhar, Gopal C.

    2016-01-01

    The human body is machine-like, but self-moving, self-regulating, and self-adjusting, governed by willpower and intelligence. Aging of the body is basically a maintenance problem and so it could perhaps be postponed by thorough and frequent maintenance. Aging brings on a cascade of ills and health problems leading to deterioration of physical, mental, emotional, and social dimensions of life. This paper deals with solution of the problem philosophically in the light of Indian scriptures witho...

  7. In Search of Rationality in Human Longevity and Immortality.

    Science.gov (United States)

    Bhar, Gopal C

    2016-01-01

    The human body is machine-like, but self-moving, self-regulating, and self-adjusting, governed by willpower and intelligence. Aging of the body is basically a maintenance problem and so it could perhaps be postponed by thorough and frequent maintenance. Aging brings on a cascade of ills and health problems leading to deterioration of physical, mental, emotional, and social dimensions of life. This paper deals with solution of the problem philosophically in the light of Indian scriptures without entering into traditional bioethical issues. With a meaningful reason for existence, life can be extended. Examining the scientific perspectives on aging, some common manipulations for its extension are discussed. These are calorie restriction, vitamin and antioxidant treatment, exercise and hormonal interventions, etc. Finally, the question of longevity is explored through pursuance of eternal value-based activity and spirituality in the tradition of Indian heritage.

  8. Solar air-conditioning. Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-07-01

    Within the 3rd International Conference on solar air-conditioning in Palermo (Italy) at 30th September to 2nd October, 2009 the following lectures were held: (1) Removal of non-technological barriers to solar cooling technology across Southern European islands (Stefano Rugginenti); (2) The added economic and environmental value of solar thermal systems in microgrids with combined heat and power (Chris Marney); (3) Australian solar cooling interest group (Paul Kohlenbach); (4) Designing of a technology roadmap for solar assisted air conditioning in Austria (Hilbert Focke); (5) Solar cooling in the new context of renewable policies at European level (Raffaele Piria); (6) Prototype of a solar driven steam jet ejector chiller (Clemens Pollerberg); (7) New integrated solar air conditioning system (Joan Carlos Bruno); (8) Primary energy optimised operation of solar driven desiccant evaporative cooling systems through innovative control strategies; (9) Green chiller association (Uli Jakob); (10) Climate Well {sup registered} (Olof Hallstrom); (11) Low capacity absorption chillers for solar cooling applications (Gregor Weidner); (12) Solar cooling in residential, small scale commercial and industrial applications with adsorption technology (Walter Mittelbach); (13) French solar heating and cooling development programme based on energy performance (Daniel Mugnier); (14) Mirrox fresnel process heat collectors for industrial applications and solar cooling (Christian Zahler); (15) Modelling and analyzing solar cooling systems in polysun (Seyen Hossein Rezaei); (16) Solar cooling application in Valle Susa Italy (Sufia Jung); (17) Virtual case study on small solar cooling systems within the SolarCombi+Project (Bjoern Nienborg); (18) Design of solar cooling plants under uncertainty (Fernando Dominguez-Munoz); (19) Fast pre-design of systems using solar thermally driven chillers (Hans-Martin Henning); (20) Design of a high fraction solar heating and cooling plant in southern

  9. Uranium mill tailings conditioning technology

    International Nuclear Information System (INIS)

    Dreesen, D.R.; Cokal, E.J.; Wangen, L.E.; Williams, J.M.; O'Brien, P.D.; Thode, E.F.

    1982-01-01

    Conditioning of uranium mill tailings involves the physicochemical alteration of tailings to remove or immobilize mobile radionuclides and toxic trace elements before disposal in a repository. The principal immobilization approach under investigation is sintering tailings at high temperatures (1100-1200 deg. C) to radically alter the structure of tailings. This thermal stabilization at 1200 deg. C reduced radon emanation power for tailings sands by factors of 20 to 200 and for tailings fines by factors of 300 to 1100. Substantial reductions in the leachability of most contaminants have been found for thermally conditioned tailings. Obvious mineral transformations occur, including an increase in amorphous material, the conversion of gypsum to anhydrite and its subsequent decomposition, the disappearance of clay minerals, and some decrease in quartz content. A conceptual thermal stabilization process has been developed wherein obsolete coal-fired rotary cement kilns perform the sintering. An economic analysis of this conceptual process has shown that thermal stabilization can be competitive at certain tailings sites with other remedial actions requiring the excavation, transportation, and burial of tailings in a repository. An analysis of the long-term radiological hazard posed by untreated tailings and by tailings conditioned by radionuclide removal has illustrated the necessity of extracting both 226 Ra and 230 Th to achieve long-term hazard reductions. Sulphuric acid extraction of residual mineral values and important radionuclides from tailings has been investigated. Concentrated H 2 SO 4 can extract up to 80% of the 226 Ra, 70% of the Ba, and 90% of the 230 Th from tailings in a single stage extraction. An economic analysis of a sulphuric acid leach process was made to determine whether the value of minerals recovered from tailings would offset the leaching cost. For one relatively mineral-rich tailings pile, the U and V values would more than pay for the

  10. Thermotactile perception thresholds measurement conditions.

    Science.gov (United States)

    Maeda, Setsuo; Sakakibara, Hisataka

    2002-10-01

    The purpose of this paper is to investigate the effects of posture, push force and rate of temperature change on thermotactile thresholds and to clarify suitable measuring conditions for Japanese people. Thermotactile (warm and cold) thresholds on the right middle finger were measured with an HVLab thermal aesthesiometer. Subjects were eight healthy male Japanese students. The effects of posture in measurement were examined in the posture of a straight hand and forearm placed on a support, the same posture without a support, and the fingers and hand flexed at the wrist with the elbow placed on a desk. The finger push force applied to the applicator of the thermal aesthesiometer was controlled at a 0.5, 1.0, 2.0 and 3.0 N. The applicator temperature was changed to 0.5, 1.0, 1.5, 2.0 and 2.5 degrees C/s. After each measurement, subjects were asked about comfort under the measuring conditions. Three series of experiments were conducted on different days to evaluate repeatability. Repeated measures ANOVA showed that warm thresholds were affected by the push force and the rate of temperature change and that cold thresholds were influenced by posture and push force. The comfort assessment indicated that the measurement posture of a straight hand and forearm laid on a support was the most comfortable for the subjects. Relatively high repeatability was obtained under measurement conditions of a 1 degrees C/s temperature change rate and a 0.5 N push force. Measurement posture, push force and rate of temperature change can affect the thermal threshold. Judging from the repeatability, a push force of 0.5 N and a temperature change of 1.0 degrees C/s in the posture with the straight hand and forearm laid on a support are recommended for warm and cold threshold measurements.

  11. ITER Operating Limits and Conditions

    International Nuclear Information System (INIS)

    Ciattaglia, S.; Barabaschi, P.; Carretero, J.A.

    2006-01-01

    The Operating Limits and Conditions (OLCs) are operating parameters and conditions, chosen among all system/components, which together define the domain of the safe operation of ITER in all foreseen ITER status (operation, maintenance, commissioning). At the same time they are selected to guarantee the required operation flexibility which is a critical factor for the success of an experimental machine such as ITER. System and components important for personnel or public safety (Safety Important Class, SIC) are identified from the overall plant safety analysis on functional importance to safety of the components. SIC classification has to be presented already inside the preliminary safety analysis report and approved by the licensing safety authority before the relevant construction. OLCs comprise the safety limits, i.e. that if exceeded could result in a potential safety hazard, the relevant settings that determine the intervention of SIC systems and the operational limits on equipment which warn from or stop a functional departure from a planned operational status that could challenge equipment and functions. The safety limits have to indicate clearly states that leave the nominal safety state of ITER; they are derived from the safety analysis of ITER. OLCs can represent in some cases few parameters grouping together. Some operational conditions, e.g. inventories, will be controlled through no real time measurements and procedures. Operating experience from present tokamaks, in particular JET, and from nuclear plants is considered at the maximum possible extent. This paper presents the guidelines to develop the ITER OLCs with particular reference to safety limits. A few examples are reported as well as open issues on some OLCs control and measurement and the relevant R-and-D planned to solve the issues. (author)

  12. Conditions for successful data assimilation

    Science.gov (United States)

    Morzfeld, M.; Chorin, A. J.

    2013-12-01

    Many applications in science and engineering require that the predictions of uncertain models be updated by information from a stream of noisy data. The model and the data jointly define a conditional probability density function (pdf), which contains all the information one has about the process of interest and various numerical methods can be used to study and approximate this pdf, e.g. the Kalman filter, variational methods or particle filters. Given a model and data, each of these algorithms will produce a result. We are interested in the conditions under which this result is reasonable, i.e. consistent with the real-life situation one is modeling. In particular, we show, using idealized models, that numerical data assimilation is feasible in principle only if a suitably defined effective dimension of the problem is not excessive. This effective dimension depends on the noise in the model and the data, and in physically reasonable problems it can be moderate even when the number of variables is huge. In particular, we find that the effective dimension being moderate induces a balance condition between the noises in the model and the data; this balance condition is often satisfied in realistic applications or else the noise levels are excessive and drown the underlying signal. We also study the effects of the effective dimension on particle filters in two instances, one in which the importance function is based on the model alone, and one in which it is based on both the model and the data. We have three main conclusions: (1) the stability (i.e., non-collapse of weights) in particle filtering depends on the effective dimension of the problem. Particle filters can work well if the effective dimension is moderate even if the true dimension is large (which we expect to happen often in practice). (2) A suitable choice of importance function is essential, or else particle filtering fails even when data assimilation is feasible in principle with a sequential algorithm

  13. BOUNDARY CONDITIONS IN GAP GEOMETRY

    Energy Technology Data Exchange (ETDEWEB)

    Rothenstein, W.; Helholtz, J.

    1963-11-15

    The procedure for calculnting the monoenergetic angular flux density in lattice cells including voids between fuel and moderator is discussed. Boundary conditions describThe thermal energy of a nuclear reactor may be conserved by using as the reactor coolant a hydrocarbon fraction boiling within the range 220 to 650 deg C (preferably 340 to 550 deg C) and containing not more than 5% of extraneous materials having neutron cross sections of > 10 barns. The hot coolant may either be cracked outside of the reactor or used to heat another petroleum hydrocarbon which is to be converted. (D.L.C.)

  14. Heat removing under hypersonic conditions

    Directory of Open Access Journals (Sweden)

    Semenov Mikhail E.

    2016-01-01

    Full Text Available In this paper we consider the heat transfer properties of the axially symmetric body with parabolic shape at hypersonic speeds (with a Mach number M > 5. We use the numerical methods based on the implicit difference scheme (Fedorenko method with direct method based on LU-decomposition and iterative method based on the Gauss-Seigel method. Our numerical results show that the heat removing process should be performed in accordance with the nonlinear law of heat distribution over the surface taking into account the hypersonic conditions of motion.

  15. Saddlepoint Approximations in Conditional Inference

    Science.gov (United States)

    1990-06-11

    Then the inverse transform can be written as (%, Y) = (T, q(T, Z)) for some function q. When the transform is not one to one, the domain should be...general regularity conditions described at the beginning of this section hold and that the solution t1 in (9) exists. Denote the inverse transform by (X, Y...density hn(t 0 l z) are desired. Then the inverse transform (Y, ) = (T, q(T, Z)) exists and the variable v in the cumulant generating function K(u, v

  16. CONDITIONS FOR IMPLEMENTING ORGANIZATIONAL CHANGES

    Directory of Open Access Journals (Sweden)

    Renata Winkler

    2015-12-01

    Full Text Available Changes are one of the most typical phenomena experienced by contemporary organizations and are an inherent element of their functioning. The change introduction process is complex and it is often accompanied by a phenomenon of resistance to change on the part of the employees in an organization, which is considered as the main cause of failure in the change implementation process. The purpose of the article is to discuss the basic conditions for implementing changes related both to their adequate defining and overcoming resistance to change.

  17. Perioperative Management of Neurological Conditions

    Directory of Open Access Journals (Sweden)

    Manjeet Singh Dhallu

    2017-06-01

    Full Text Available Perioperative care of the patients with neurological diseases can be challenging. Most important consideration is the management and understanding of pathophysiology of these disorders and evaluation of new neurological changes that occur perioperatively. Perioperative generally refers to 3 phases of surgery: preoperative, intraoperative, and postoperative. We have tried to address few commonly encountered neurological conditions in clinical practice, such as delirium, stroke, epilepsy, myasthenia gravis, and Parkinson disease. In this article, we emphasize on early diagnosis and management strategies of neurological disorders in the perioperative period to minimize morbidity and mortality of patients.

  18. TRANSPORTATION INDUSTRY EFFECTIVE MANAGEMENT CONDITIONS

    Directory of Open Access Journals (Sweden)

    V. I. Kuznetsov

    2011-01-01

    Full Text Available Main aspects that determine conditions of transportation industry effective management and decrease of transportation expenses are discussed. Theoretical concepts making it possible to solve the problem of scientific management of the whole country’s goods transportation costs are provided for. Main approaches are presented to the solution of motor transport operation ecological optimization problem as well as to the rise of motor transport workers’ labor productivity, to the increase of transportation vehicles use efficiency and to determine functional capacity of the motor transport complex.

  19. Conditioning of primates for experiments

    International Nuclear Information System (INIS)

    Legeay, G.; Geneste, M.; Brawers, G.

    1965-01-01

    The preparation of the monkey for experiments is one branch of zootechny applied to laboratory animals. The construction of a monkey-house at the Saclay Nuclear Research Centre has made it possible to study the hygiene rules necessary for obtaining subjects with relatively stable biological parameters. This hygiene includes: - prophylactic treatment, because the animals received lived originally in the wild state, - a balanced diet according to modern dietetic standards, - a habitat hygiene which recreates the original living conditions of the species. The possibility of reproduction has been used as a criterion of the efficiency of the methods applied. (authors) [fr

  20. Motivational condition in educational evaluation

    Directory of Open Access Journals (Sweden)

    Julio Fernando Acosta Muñoz

    2012-01-01

    Full Text Available This is a reflection article, methodologically based on research into and theoretical and conceptual review of the motivational condition in educational evaluation. At the same time, some inquiries about the motivational problems in this education process are made. The objective is to examine what the motivational condition within the process ofeducational evaluation is. On the one hand, educational evaluation is a tool that attests to the knowledge, on the other hand, however, it prevents students from strengthening their interest both in the participation in the specific testing activity and in their learning, since it lays emphasis on extrinsic factors, such as grade, which make students lose and distort their intrinsic motivation to learn. Therefore, the evaluation proposal arisen from the construct of motivation is thought to generate in students positive sensations standing even after goals are obtained. Likewise, it must promote liveliness, integration and psychological health, in order to get students to fulfill their needs and obtain psychological welfare in the classroom.

  1. Coordination of Conditional Poisson Samples

    Directory of Open Access Journals (Sweden)

    Grafström Anton

    2015-12-01

    Full Text Available Sample coordination seeks to maximize or to minimize the overlap of two or more samples. The former is known as positive coordination, and the latter as negative coordination. Positive coordination is mainly used for estimation purposes and to reduce data collection costs. Negative coordination is mainly performed to diminish the response burden of the sampled units. Poisson sampling design with permanent random numbers provides an optimum coordination degree of two or more samples. The size of a Poisson sample is, however, random. Conditional Poisson (CP sampling is a modification of the classical Poisson sampling that produces a fixed-size πps sample. We introduce two methods to coordinate Conditional Poisson samples over time or simultaneously. The first one uses permanent random numbers and the list-sequential implementation of CP sampling. The second method uses a CP sample in the first selection and provides an approximate one in the second selection because the prescribed inclusion probabilities are not respected exactly. The methods are evaluated using the size of the expected sample overlap, and are compared with their competitors using Monte Carlo simulation. The new methods provide a good coordination degree of two samples, close to the performance of Poisson sampling with permanent random numbers.

  2. SULFENTRAZONE PHYTOREMEDIATION UNDER FIELD CONDITIONS

    Directory of Open Access Journals (Sweden)

    ALESSANDRA FERREIRA BELO

    2016-01-01

    Full Text Available Phytoremediation is a technique that has been used with increasing frequency to decontaminate soils treated with herbicides that have long - term residual effects, such as sulfentrazone. The goal was to assess phytoremediation of the herbicide sulfentrazone under field conditions by the species Canavalia ensiformis and Crotalaria juncea . The treatments consisted of combinations of the plant species C. ensiformis and C. juncea plus a control treatment (with manual weeding and four doses of the herbicide sulfentrazone. The experimental design used herein was a split - plot randomized block design with four replicates per subplot. The treatments were kept in the field for 75 days. After this period, the experimental area was again furrowed and fertilized, considering the requirements for Pennisetum glaucum , a plant used as an indicator of the presence of sulfentrazone. Thirty - four days after sowing pearl millet, the fresh and dry shoot masses of the plants were assessed. At the end of the cycle, the plant height, stem diameter, internode length, number of leaves, number of panicles, and fresh and dry panicle masses were determined. Previous cultivation of phytoremediation species C. ensiformis and C. juncea promotes sulfentrazone remediation. C. ensiformis is the most efficient species for the decontamination of the herbicide sulfentrazone under field conditions.

  3. ATLAS diamond Beam Condition Monitor

    Energy Technology Data Exchange (ETDEWEB)

    Gorisek, A. [CERN (Switzerland)]. E-mail: andrej.gorisek@cern.ch; Cindro, V. [J. Stefan Institute (Slovenia); Dolenc, I. [J. Stefan Institute (Slovenia); Frais-Koelbl, H. [Fotec (Austria); Griesmayer, E. [Fotec (Austria); Kagan, H. [Ohio State University, OH (United States); Korpar, S. [J. Stefan Institute (Slovenia); Kramberger, G. [J. Stefan Institute (Slovenia); Mandic, I. [J. Stefan Institute (Slovenia); Meyer, M. [CERN (Switzerland); Mikuz, M. [J. Stefan Institute (Slovenia); Pernegger, H. [CERN (Switzerland); Smith, S. [Ohio State University, OH (United States); Trischuk, W. [University of Toronto (Canada); Weilhammer, P. [CERN (Switzerland); Zavrtanik, M. [J. Stefan Institute (Slovenia)

    2007-03-01

    The ATLAS experiment has chosen to use diamond for its Beam Condition Monitor (BCM) given its radiation hardness, low capacitance and short charge collection time. In addition, due to low leakage current diamonds do not require cooling. The ATLAS Beam Condition Monitoring system is based on single beam bunch crossing measurements rather than integrating the accumulated particle flux. Its fast electronics will allow separation of LHC collisions from background events such as beam gas interactions or beam accidents. There will be two stations placed symmetrically about the interaction point along the beam axis at z=+/-183.8cm. Timing of signals from the two stations will provide almost ideal separation of beam-beam interactions and background events. The ATLAS BCM module consists of diamond pad detectors of 1cm{sup 2} area and 500{mu}m thickness coupled to a two-stage RF current amplifier. The production of the final detector modules is almost done. A S/N ratio of 10:1 has been achieved with minimum ionizing particles (MIPs) in the test beam setup at KEK. Results from the test beams and bench measurements are presented.

  4. ATLAS diamond Beam Condition Monitor

    International Nuclear Information System (INIS)

    Gorisek, A.; Cindro, V.; Dolenc, I.; Frais-Koelbl, H.; Griesmayer, E.; Kagan, H.; Korpar, S.; Kramberger, G.; Mandic, I.; Meyer, M.; Mikuz, M.; Pernegger, H.; Smith, S.; Trischuk, W.; Weilhammer, P.; Zavrtanik, M.

    2007-01-01

    The ATLAS experiment has chosen to use diamond for its Beam Condition Monitor (BCM) given its radiation hardness, low capacitance and short charge collection time. In addition, due to low leakage current diamonds do not require cooling. The ATLAS Beam Condition Monitoring system is based on single beam bunch crossing measurements rather than integrating the accumulated particle flux. Its fast electronics will allow separation of LHC collisions from background events such as beam gas interactions or beam accidents. There will be two stations placed symmetrically about the interaction point along the beam axis at z=+/-183.8cm. Timing of signals from the two stations will provide almost ideal separation of beam-beam interactions and background events. The ATLAS BCM module consists of diamond pad detectors of 1cm 2 area and 500μm thickness coupled to a two-stage RF current amplifier. The production of the final detector modules is almost done. A S/N ratio of 10:1 has been achieved with minimum ionizing particles (MIPs) in the test beam setup at KEK. Results from the test beams and bench measurements are presented

  5. Asymptotic conditions and conserved quantities

    International Nuclear Information System (INIS)

    Koul, R.K.

    1990-01-01

    Two problems have been investigated in this dissertation. The first one deals with the relationship between stationary space-times which are flat at null infinity and stationary space-times which are asymptotic flat at space-like infinity. It is shown that the stationary space-times which are asymptotically flat, in the Penrose sense, at null infinity, are asymptotically flat at space-like infinity in the Geroch sense and metric at space like infinity is at least C 1 . In the converse it is shown that the stationary space-times which are asymptotically flat at space like infinity, in the Beig sense, are asymptotically flat at null infinity in the Penrose sense. The second problem addressed deals with the theories of arbitrary dimensions. The theories treated are the ones which have fiber bundle structure, outside some compact region. For these theories the criterion for the choice of the background metric is specified, and the boundary condition for the initial data set (q ab , P ab ) is given in terms of the background metric. Having these boundary conditions it is shown that the symplectic structure and the constraint functionals are well defined. The conserved quantities associated with internal Killing vector fields are specified. Lastly the energy relative to a fixed background and the total energy of the theory have been given. It is also shown that the total energy of the theory is independent of the choice of the background

  6. The acquisition of conditioned responding.

    Science.gov (United States)

    Harris, Justin A

    2011-04-01

    This report analyzes the acquisition of conditioned responses in rats trained in a magazine approach paradigm. Following the suggestion by Gallistel, Fairhurst, and Balsam (2004), Weibull functions were fitted to the trial-by-trial response rates of individual rats. These showed that the emergence of responding was often delayed, after which the response rate would increase relatively gradually across trials. The fit of the Weibull function to the behavioral data of each rat was equaled by that of a cumulative exponential function incorporating a response threshold. Thus, the growth in conditioning strength on each trial can be modeled by the derivative of the exponential--a difference term of the form used in many models of associative learning (e.g., Rescorla & Wagner, 1972). Further analyses, comparing the acquisition of responding with a continuously reinforced stimulus (CRf) and a partially reinforced stimulus (PRf), provided further evidence in support of the difference term. In conclusion, the results are consistent with conventional models that describe learning as the growth of associative strength, incremented on each trial by an error-correction process.

  7. ATLAS diamond Beam Condition Monitor

    CERN Document Server

    Gorišek, A; Dolenc, I; Frais-Kölbl, H; Griesmayer, E; Kagan, H; Korpar, S; Kramberger, G; Mandic, I; Meyer, M; Mikuz, M; Pernegger, H; Smith, S; Trischuk, W; Weilhammer, P; Zavrtanik, M

    2007-01-01

    The ATLAS experiment has chosen to use diamond for its Beam Condition Monitor (BCM) given its radiation hardness, low capacitance and short charge collection time. In addition, due to low leakage current diamonds do not require cooling. The ATLAS Beam Condition Monitoring system is based on single beam bunch crossing measurements rather than integrating the accumulated particle flux. Its fast electronics will allow separation of LHC collisions from background events such as beam gas interactions or beam accidents. There will be two stations placed symmetrically about the interaction point along the beam axis at . Timing of signals from the two stations will provide almost ideal separation of beam–beam interactions and background events. The ATLAS BCM module consists of diamond pad detectors of area and thickness coupled to a two-stage RF current amplifier. The production of the final detector modules is almost done. A S/N ratio of 10:1 has been achieved with minimum ionizing particles (MIPs) in the test bea...

  8. Vulvovaginitis and other common childhood gynaecological conditions.

    Science.gov (United States)

    Garden, Anne S

    2011-04-01

    Paediatric gynaecological problems, especially those involving the vulvar area, are common in childhood. The conditions frequently seen include recurrent bacterial vulvovaginitis, vulvar irritation, labial adhesions and dermatological conditions. The presentation and management of these conditions will be reviewed.

  9. Large errors and severe conditions

    CERN Document Server

    Smith, D L; Van Wormer, L A

    2002-01-01

    Physical parameters that can assume real-number values over a continuous range are generally represented by inherently positive random variables. However, if the uncertainties in these parameters are significant (large errors), conventional means of representing and manipulating the associated variables can lead to erroneous results. Instead, all analyses involving them must be conducted in a probabilistic framework. Several issues must be considered: First, non-linear functional relations between primary and derived variables may lead to significant 'error amplification' (severe conditions). Second, the commonly used normal (Gaussian) probability distribution must be replaced by a more appropriate function that avoids the occurrence of negative sampling results. Third, both primary random variables and those derived through well-defined functions must be dealt with entirely in terms of their probability distributions. Parameter 'values' and 'errors' should be interpreted as specific moments of these probabil...

  10. Shocking matter to extreme conditions

    International Nuclear Information System (INIS)

    Gupta, Y.M.; Sharma, S.M.

    1997-01-01

    A good understanding of the thermodynamic response of matter at high compression and high energy densities is important to several areas of physics. Shock-wave experiments are uniquely suited for obtaining data at extreme conditions, and a shock-compressed matter can be viewed as a condensed system with or without dissociation or as a strongly coupled plasma. This article reviews work by Da Silva et al. in which irradiances ranging from 5x10 superscript 12 to 2x10 superscript 14 W/cm 2 were used to generate 8- to 10-ns square pulses in liquid deuterium. The authors demonstrated negligible pre-heating of the sample, steady propagation of the shock wave, and direct determination of the shock wave velocity along with particle velocity and density in the shocked state. Da Silva et al. results are compared with models and other experimental information, and the usefulness of the data in other areas is assessed. 11 refs., 1 fig

  11. Bare Quantum Null Energy Condition.

    Science.gov (United States)

    Fu, Zicao; Marolf, Donald

    2018-02-16

    The quantum null energy condition (QNEC) is a conjectured relation between a null version of quantum field theory energy and derivatives of quantum field theory von Neumann entropy. In some cases, divergences cancel between these two terms and the QNEC is intrinsically finite. We study the more general case here where they do not and argue that a QNEC can still hold for bare (unrenormalized) quantities. While the original QNEC applied only to locally stationary null congruences in backgrounds that solve semiclassical theories of quantum gravity, at least in the formal perturbation theory at a small Planck length, the quantum focusing conjecture can be viewed as the special case of our bare QNEC for which the metric is on shell.

  12. Radioisotope studies under pathologic conditions

    International Nuclear Information System (INIS)

    DeRossi; Salvatori, M.; Valenza, V.

    1987-01-01

    This article presents a general discussion on salivary pathology, before dealing with the various salivary gland diseases which can draw real advantage from radioisotope studies. Clinical problems related to the salivary glands first concern diffuse or focal glandular swelling. Focal swelling includes inflammatory or metastatic deposits in preauricular or submandibular lymph nodes, cysts, abscesses, foci of inflammation, benign and malignant neoplasms of the salivary glands themselves or of surrounding blood or lymph vessels, nerves, connective tissue, and oral mucosa. Primary tumors of the salivary glands are rare and usually benign. The combination of a systemic disease with dry mouth and dry eyes due to inflamed conjunctiva and cornea because of decreased fluid production, forms Sjogren syndrome. It may also cause diffuse glandular swelling. Chronic alcoholism, cirrhosis, diabetes mellitus, hyperlipoproteinemia, and malnutrition are other pathologic conditions sometimes associated with diffuse salivary gland swelling

  13. INDIVIDUAL AGENCY AND LIFE CONDITIONS

    Directory of Open Access Journals (Sweden)

    SERGIO TRUJILLO GARCÍA

    2005-07-01

    Full Text Available As a result of the project Interpretación desde la Psicología de la calidad de vida y sus dimensiones en adultos mayores de losmunicipios de Soacha y Sibaté (Cundinamarca, Colombia [Interpretation from the psychology of the Quality of Life and itsdimensions in old age adults from the Soacha and Sibaté municipalities (Cundinamarca, Colombia] which had a theoretical modelcomposed for three axels (epistemological, ecological and temporal, emerged some tensions which constitute thequality of life dimensions of the elderly. In the present article one of those tensions is discussed: the one shaped bythe contradictions among the possibilities of the individual agency exercise and the precarious life conditions whichhad characterized the context of development of the old age participants.

  14. Macroeconomic conditions and opioid abuse.

    Science.gov (United States)

    Hollingsworth, Alex; Ruhm, Christopher J; Simon, Kosali

    2017-12-01

    We examine how deaths and emergency department (ED) visits related to use of opioid analgesics (opioids) and other drugs vary with macroeconomic conditions. As the county unemployment rate increases by one percentage point, the opioid death rate per 100,000 rises by 0.19 (3.6%) and the opioid overdose ED visit rate per 100,000 increases by 0.95 (7.0%). Macroeconomic shocks also increase the overall drug death rate, but this increase is driven by rising opioid deaths. Our findings hold when performing a state-level analysis, rather than county-level; are primarily driven by adverse events among whites; and are stable across time periods. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. LDA measurements under plasma conditions

    International Nuclear Information System (INIS)

    Lesinski, J.; Mizera-Lesinska, B.; Fanton, J.C.; Boulos, M.I.

    1979-01-01

    A study was made of the application of Laser Doppler Anemometry (LDA) for the measurement of the fluid and particle velocities under plasma conditions. The flow configuration, is that of a dc plasma jet called the principal jet, in which an alumina powder of a mean particle diameter of 115 μm and a standard deviation of 11.3 μm was injected using a secondary jet. The plasma jet immerged from a 7.1 mm ID nozzle while that of the secondary jet was 2 nm in diameter. The secondary jet was introduced at the nozzle level of the plasma jet directed 90 0 to its axis. Details of the nozzle and the gas flow system are shown in Figure 2

  16. Life conditions of Sicilian centenarians.

    Science.gov (United States)

    Receputo, G; Rapisarda, R; Mazzoleni, G; Fornaro, D; Tomasello, F B; Di Stefano, S; Savia, S; Cilmi, V; Malacuarnera, M

    1996-01-01

    Aim of the study was at furnishing a description of the socio-economic reality of Sicilian centenarians. Informations were taken from the records of Italian Multicentric Study on Centenarians. Randomly selected 28 centenarians (8 males, 20 females), in the age range 100-108 years from Eastern Sicily were examined. The following average socioeconomic profile of the centenarians was established: they are widows or widowers with 4 children; have primary education, mediocre socioeconomic conditions, have worked in the fields or had been housewives; their hobbies were before gardening or embroidering and sewing and now is watching TV; they live in their own salubrious 4 roomed house in small center in the hills. These observations reveal that the social and intellectual quality of life is better in cases of centenarian subjects living at home, in their family environment, surrounded by their children and grandchildren as they receive greater affection and physical care than those living in old peoples' homes.

  17. Working conditions in seafaring international

    DEFF Research Database (Denmark)

    Jensen, Olaf Chresten; Canals, M. Luisa

    2008-01-01

    . The average was 60-80 working hours a week. 60% had 70 hours or more per week and one third more than 80 hours. 80 % worked all the 7 days in the week. Officers were 15-30% among the Philippines and Indonesian seafarers and 80% among the seafarers from United Kingdom and Denmark. 80% of the seafarers from...... frequent involved. Seafarers from the Philippines and Indonesia had low incidence rates of injury. The self-perceived health was generally good among the seafarers, with some national exceptions Conclusions - Remarkable non-equity for work conditions between the nationalities - Working hours per week......Background The world merchant fleet comprise about 1.4 million seafarers. Multi ethnic crews make about 2/3 of the world merchant fleet. The purpose was to descripe important aspects of the working environment for seafarers. Method The seafarers have biannual health examinations and they used 5...

  18. Thermodynamic condition for ''Gamma'' flotation

    International Nuclear Information System (INIS)

    Kaoma, J.; Yarar, B.

    1989-01-01

    Using the definition of the critical surface tension of wetting solids (Γc) and Gibb's adsorption isotherm, coupled with Young-Dupre's equation, the equilibrium thermodynamic condition for 'GAMMA' flotation has been derived. It is defined by the relation, Cos Oe=Γc/Γlg. At equilibrium for 'Gamma' flotation to occur, the liquid/gas interfacial tension (9γlg) should be larger than the critical surface tension of wetting of the solid surface, meaning that the equilibrium contact angle (Oe) should be greater than Zero, or cos Oe < 1, a Pre- requisite for the solid/gas bubble attachment. This definition holds for solid surfaces in the absence of any specific adsorption at the solid/liquid and solid/gas inter faces. Contact angle and flotation data are presented to sustain this definition. (author)., 15 refs., 9 figs

  19. Uncertain deduction and conditional reasoning.

    Science.gov (United States)

    Evans, Jonathan St B T; Thompson, Valerie A; Over, David E

    2015-01-01

    There has been a paradigm shift in the psychology of deductive reasoning. Many researchers no longer think it is appropriate to ask people to assume premises and decide what necessarily follows, with the results evaluated by binary extensional logic. Most every day and scientific inference is made from more or less confidently held beliefs and not assumptions, and the relevant normative standard is Bayesian probability theory. We argue that the study of "uncertain deduction" should directly ask people to assign probabilities to both premises and conclusions, and report an experiment using this method. We assess this reasoning by two Bayesian metrics: probabilistic validity and coherence according to probability theory. On both measures, participants perform above chance in conditional reasoning, but they do much better when statements are grouped as inferences, rather than evaluated in separate tasks.

  20. On the local equilibrium condition

    International Nuclear Information System (INIS)

    Hessling, H.

    1994-11-01

    A physical system is in local equilibrium if it cannot be distinguished from a global equilibrium by ''infinitesimally localized measurements''. This should be a natural characterization of local equilibrium, but the problem is to give a precise meaning to the qualitative phrase ''infinitesimally localized measurements''. A solution is suggested in form of a Local Equilibrium Condition (LEC), which can be applied to linear relativistic quantum field theories but not directly to selfinteracting quantum fields. The concept of local temperature resulting from LEC is compared to an old approach to local temperature based on the principle of maximal entropy. It is shown that the principle of maximal entropy does not always lead to physical states if it is applied to relativistic quantum field theories. (orig.)

  1. Optimising Extinction of Conditioned Disgust.

    Science.gov (United States)

    Bosman, Renske C; Borg, Charmaine; de Jong, Peter J

    2016-01-01

    Maladaptive disgust responses are tenacious and resistant to exposure-based interventions. In a similar vein, laboratory studies have shown that conditioned disgust is relatively insensitive to Conditioned Stimulus (CS)-only extinction procedures. The relatively strong resistance to extinction might be explained by disgust's adaptive function to motivate avoidance from contamination threats (pathogens) that cannot be readily detected and are invisible to the naked eye. Therefore, the mere visual presentation of unreinforced disgust eliciting stimuli might not be sufficient to correct a previously acquired threat value of the CS+. Following this, the current study tested whether the efficacy of CS-only exposure can be improved by providing additional safety information about the CS+. For the CSs we included two neutral items a pea soup and a sausage roll, whereas for the Unconditioned Stimulus (US) we used one video clip of a woman vomiting and a neutral one about glass blowing. The additional safety information was conveyed by allowing actual contact with the CS+ or by observing an actress eating the food items representing the CS+. When additional safety information was provided via allowing direct contact with the CS+, there was a relatively strong post-extinction increase in participants' willingness-to-eat the CS+. This beneficial effect was still evident at one-week follow up. Also self-reported disgust was lower at one-week follow up when additional safety information was provided. The current findings help explain why disgust is relatively insensitive to CS-only extinction procedures, and provide helpful starting points to improve interventions that are aimed to reduce distress in disgust-related psychopathology.

  2. Personalized Support for Chronic Conditions

    Science.gov (United States)

    D’Antrassi, Pierluigi; Ajčević, Miloš; Stellato, Kira; Di Lenarda, Andrea; Marceglia, Sara; Accardo, Agostino

    2016-01-01

    Summary Objective Solutions for improving management of chronic conditions are under the attention of healthcare systems, due to the increasing prevalence caused by demographic change and better survival, and the relevant impact on healthcare expenditures. The objective of this study was to propose a comprehensive architecture of a mHealth system aimed at boosting the active and informed participation of patients in their care process, while at the same time overcoming the current technical and psychological/clinical issues highlighted by the existing literature. Methods After having studied the current challenges outlined in the literature, both in terms of technological and human requirements, we focused our attention on some specific psychological aspects with a view to providing patients with a comprehensive and personalized solution. Our approach has been reinforced through the results of a preliminary assessment we conducted on 22 patients with chronic conditions. The main goal of such an assessment was to provide a preliminary understanding of their needs in a real context, both in terms of self-awareness and of their predisposition toward the use of IT solutions. Results According to the specific needs and features, such as mindfulness and gamification, which were identified through the literature and the preliminary assessment, we designed a comprehensive open architecture able to provide a tailor-made solution linked to specific individuals’ needs. Conclusion The present study represents the preliminary step towards the development of a solution aimed at enhancing patients’ actual perception and encouraging self-management and self-awareness for a better lifestyle. Future work regards further identification of pathology-related needs and requirements through focus groups including all stakeholders in order to describe the architecture and functionality in greater detail. PMID:27452661

  3. The ATLAS Beam Conditions Monitor

    International Nuclear Information System (INIS)

    Cindro, V; Dolenc, I; Kramberger, G; Macek, B; Mandic, I; Mikuz', M; Zavrtanik, M; Dobos, D; Gorisek, A; Pernegger, H; Weilhammer, P; Frais-Koelbl, H; Griesmayer, E; Niegl, M; Kagan, H; Tardif, D; Trischuk, W

    2008-01-01

    Beam conditions and the potential detector damage resulting from their anomalies have pushed the LHC experiments to build their own beam monitoring devices. The ATLAS Beam Conditions Monitor (BCM) consists of two stations (forward and backward) of detectors each with four modules. The sensors are required to tolerate doses up to 500 kGy and in excess of 10 15 charged particles per cm 2 over the lifetime of the experiment. Each module includes two diamond sensors read out in parallel. The stations are located symmetrically around the interaction point, positioning the diamond sensors at z = ±184 cm and r = 55 mm (a pseudo- rapidity of about 4.2). Equipped with fast electronics (2 ns rise time) these stations measure time-of-flight and pulse height to distinguish events resulting from lost beam particles from those normally occurring in proton-proton interactions. The BCM also provides a measurement of bunch-by-bunch luminosities in ATLAS by counting in-time and out-of-time collisions. Eleven detector modules have been fully assembled and tested. Tests performed range from characterisation of diamond sensors to full module tests with electron sources and in proton testbeams. Testbeam results from the CERN SPS show a module median-signal to noise of 11:1 for minimum ionising particles incident at a 45-degree angle. The best eight modules were installed on the ATLAS pixel support frame that was inserted into ATLAS in the summer of 2007. This paper describes the full BCM detector system along with simulation studies being used to develop the logic in the back-end FPGA coincidence hardware

  4. The ATLAS Beam Conditions Monitor

    Energy Technology Data Exchange (ETDEWEB)

    Cindro, V; Dolenc, I; Kramberger, G; Macek, B; Mandic, I; Mikuz' , M; Zavrtanik, M [Jozef Stefan Institute and Department of Physics, University of Ljubljana, Ljubljana (Slovenia); Dobos, D; Gorisek, A; Pernegger, H; Weilhammer, P [CERN, Geneva (Switzerland); Frais-Koelbl, H; Griesmayer, E; Niegl, M [University of Applied Sciences Wiener Neustadt and Fotec, Wiener Neustadt (Austria); Kagan, H [Ohio State University, Columbus (United States); Tardif, D; Trischuk, W [University of Toronto, Toronto (Canada)], E-mail: william@physics.utoronto.ca

    2008-02-15

    Beam conditions and the potential detector damage resulting from their anomalies have pushed the LHC experiments to build their own beam monitoring devices. The ATLAS Beam Conditions Monitor (BCM) consists of two stations (forward and backward) of detectors each with four modules. The sensors are required to tolerate doses up to 500 kGy and in excess of 10{sup 15} charged particles per cm{sup 2} over the lifetime of the experiment. Each module includes two diamond sensors read out in parallel. The stations are located symmetrically around the interaction point, positioning the diamond sensors at z = {+-}184 cm and r = 55 mm (a pseudo- rapidity of about 4.2). Equipped with fast electronics (2 ns rise time) these stations measure time-of-flight and pulse height to distinguish events resulting from lost beam particles from those normally occurring in proton-proton interactions. The BCM also provides a measurement of bunch-by-bunch luminosities in ATLAS by counting in-time and out-of-time collisions. Eleven detector modules have been fully assembled and tested. Tests performed range from characterisation of diamond sensors to full module tests with electron sources and in proton testbeams. Testbeam results from the CERN SPS show a module median-signal to noise of 11:1 for minimum ionising particles incident at a 45-degree angle. The best eight modules were installed on the ATLAS pixel support frame that was inserted into ATLAS in the summer of 2007. This paper describes the full BCM detector system along with simulation studies being used to develop the logic in the back-end FPGA coincidence hardware.

  5. Optimising Extinction of Conditioned Disgust.

    Directory of Open Access Journals (Sweden)

    Renske C Bosman

    Full Text Available Maladaptive disgust responses are tenacious and resistant to exposure-based interventions. In a similar vein, laboratory studies have shown that conditioned disgust is relatively insensitive to Conditioned Stimulus (CS-only extinction procedures. The relatively strong resistance to extinction might be explained by disgust's adaptive function to motivate avoidance from contamination threats (pathogens that cannot be readily detected and are invisible to the naked eye. Therefore, the mere visual presentation of unreinforced disgust eliciting stimuli might not be sufficient to correct a previously acquired threat value of the CS+. Following this, the current study tested whether the efficacy of CS-only exposure can be improved by providing additional safety information about the CS+. For the CSs we included two neutral items a pea soup and a sausage roll, whereas for the Unconditioned Stimulus (US we used one video clip of a woman vomiting and a neutral one about glass blowing. The additional safety information was conveyed by allowing actual contact with the CS+ or by observing an actress eating the food items representing the CS+. When additional safety information was provided via allowing direct contact with the CS+, there was a relatively strong post-extinction increase in participants' willingness-to-eat the CS+. This beneficial effect was still evident at one-week follow up. Also self-reported disgust was lower at one-week follow up when additional safety information was provided. The current findings help explain why disgust is relatively insensitive to CS-only extinction procedures, and provide helpful starting points to improve interventions that are aimed to reduce distress in disgust-related psychopathology.

  6. Ocean climate and seal condition

    Directory of Open Access Journals (Sweden)

    Crocker Daniel E

    2005-03-01

    Full Text Available Abstract Background The condition of many marine mammals varies with fluctuations in productivity and food supply in the ocean basin where they forage. Prey is impacted by physical environmental variables such as cyclic warming trends. The weaning weight of northern elephant seal pups, Mirounga angustirostris, being closely linked to maternal condition, indirectly reflects prey availability and foraging success of pregnant females in deep waters of the northeastern Pacific. The aim of this study was to examine the effect of ocean climate on foraging success in this deep-diving marine mammal over the course of three decades, using cohort weaning weight as the principal metric of successful resource accrual. Results The mean annual weaning weight of pups declined from 1975 to the late 1990s, a period characterized by a large-scale, basin-wide warm decadal regime that included multiple strong or long-duration El Niños; and increased with a return to a cool decadal regime from about 1999 to 2004. Increased foraging effort and decreased mass gain of adult females, indicative of reduced foraging success and nutritional stress, were associated with high ocean temperatures. Conclusion Despite ranging widely and foraging deeply in cold waters beyond coastal thermoclines in the northeastern Pacific, elephant seals are impacted significantly by ocean thermal dynamics. Ocean warming redistributes prey decreasing foraging success of females, which in turn leads to lower weaning mass of pups. Annual fluctuations in weaning mass, in turn, reflect the foraging success of females during the year prior to giving birth and signals changes in ocean temperature cycles.

  7. Eliciting conditional and unconditional rank correlations from conditional probabilities

    International Nuclear Information System (INIS)

    Morales, O.; Kurowicka, D.; Roelen, A.

    2008-01-01

    Causes of uncertainties may be interrelated and may introduce dependencies. Ignoring these dependencies may lead to large errors. A number of graphical models in probability theory such as dependence trees, vines and (continuous) Bayesian belief nets [Cooke RM. Markov and entropy properties of tree and vine-dependent variables. In: Proceedings of the ASA section on Bayesian statistical science, 1997; Kurowicka D, Cooke RM. Distribution-free continuous Bayesian belief nets. In: Proceedings of mathematical methods in reliability conference, 2004; Bedford TJ, Cooke RM. Vines-a new graphical model for dependent random variables. Ann Stat 2002; 30(4):1031-68; Kurowicka D, Cooke RM. Uncertainty analysis with high dimensional dependence modelling. New York: Wiley; 2006; Hanea AM, et al. Hybrid methods for quantifying and analyzing Bayesian belief nets. In: Proceedings of the 2005 ENBIS5 conference, 2005; Shachter RD, Kenley CR. Gaussian influence diagrams. Manage Sci 1998; 35(5) .] have been developed to capture dependencies between random variables. The input for these models are various marginal distributions and dependence information, usually in the form of conditional rank correlations. Often expert elicitation is required. This paper focuses on dependence representation, and dependence elicitation. The techniques presented are illustrated with an application from aviation safety

  8. Hot conditioning equipment conceptual design report

    Energy Technology Data Exchange (ETDEWEB)

    Bradshaw, F.W., Westinghouse Hanford

    1996-08-06

    This report documents the conceptual design of the Hot Conditioning System Equipment. The Hot conditioning System will consist of two separate designs: the Hot Conditioning System Equipment; and the Hot Conditioning System Annex. The Hot Conditioning System Equipment Design includes the equipment such as ovens, vacuum pumps, inert gas delivery systems, etc.necessary to condition spent nuclear fuel currently in storage in the K Basins of the Hanford Site. The Hot Conditioning System Annex consists of the facility of house the Hot Conditioning System. The Hot Conditioning System will be housed in an annex to the Canister Storage Building. The Hot Conditioning System will consist of pits in the floor which contain ovens in which the spent nuclear will be conditioned prior to interim storage.

  9. Hot conditioning equipment conceptual design report

    International Nuclear Information System (INIS)

    Bradshaw, F.W.

    1996-01-01

    This report documents the conceptual design of the Hot Conditioning System Equipment. The Hot conditioning System will consist of two separate designs: the Hot Conditioning System Equipment; and the Hot Conditioning System Annex. The Hot Conditioning System Equipment Design includes the equipment such as ovens, vacuum pumps, inert gas delivery systems, etc.necessary to condition spent nuclear fuel currently in storage in the K Basins of the Hanford Site. The Hot Conditioning System Annex consists of the facility of house the Hot Conditioning System. The Hot Conditioning System will be housed in an annex to the Canister Storage Building. The Hot Conditioning System will consist of pits in the floor which contain ovens in which the spent nuclear will be conditioned prior to interim storage

  10. Sleep behavior and unemployment conditions.

    Science.gov (United States)

    Antillón, Marina; Lauderdale, Diane S; Mullahy, John

    2014-07-01

    Recent research has reported that habitually short sleep duration is a risk factor for declining health, including increased risk of obesity, diabetes and coronary heart disease. In this study we investigate whether macroeconomic conditions are associated with variation in mean sleep time in the United States, and if so, whether the effect is procyclical or countercyclical. We merge state unemployment rates from 2003 through 2012 with the American Time Use Survey, a nationally representative sample of adults with 24h time diaries. We find that higher aggregate unemployment is associated with longer mean sleep duration, with each additional point of state unemployment associated with an additional average 0.83 min of sleep (punemployment is associated with more sleeplessness. Instead, we find that higher state unemployment is associated with less frequent time use described as "sleeplessness" (marginal effect=0.05 at 4% unemployment and 0.034 at 14% unemployment, p<0.001), after controlling for a secular trend. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Pressure cylinders under fire condition

    Directory of Open Access Journals (Sweden)

    Jan Hora

    2016-03-01

    Full Text Available The presence of pressure cylinders under fire conditions significantly increases the risk rate for the intervening persons. It is considerably problematic to predict the pressure cylinders behaviour during heat exposition, its destruction progress and possible following explosion of the produced air–gas mixture because pressure cylinders and its environment generate a highly complicated dynamic system during an uncontrolled destruction. The large scale tests carried out by the Pilsen Fire and Rescue Department and the Rapid Response Unit of the Czech Republic Police in October 2012 and in May 2014 in the Military area Brdy and in the area of the former Lachema factory in Kaznějov had several objectives, namely, to record, qualify and quantify some of the aspects of an uncontrolled heat destruction procedure of an exposed pressure cylinder in an enclosed space and to qualify and describe the process of a controlled destruction of a pressure cylinder by shooting through it including basic tactical concepts. The article describes the experiments that were carried out.

  12. Alcoholism: a systemic proinflammatory condition.

    Science.gov (United States)

    González-Reimers, Emilio; Santolaria-Fernández, Francisco; Martín-González, María Candelaria; Fernández-Rodríguez, Camino María; Quintero-Platt, Geraldine

    2014-10-28

    Excessive ethanol consumption affects virtually any organ, both by indirect and direct mechanisms. Considerable research in the last two decades has widened the knowledge about the paramount importance of proinflammatory cytokines and oxidative damage in the pathogenesis of many of the systemic manifestations of alcoholism. These cytokines derive primarily from activated Kupffer cells exposed to Gram-negative intestinal bacteria, which reach the liver in supra-physiological amounts due to ethanol-mediated increased gut permeability. Reactive oxygen species (ROS) that enhance the inflammatory response are generated both by activation of Kupffer cells and by the direct metabolic effects of ethanol. The effects of this increased cytokine secretion and ROS generation lie far beyond liver damage. In addition to the classic consequences of endotoxemia associated with liver cirrhosis that were described several decades ago, important research in the last ten years has shown that cytokines may also induce damage in remote organs such as brain, bone, muscle, heart, lung, gonads, peripheral nerve, and pancreas. These effects are even seen in alcoholics without significant liver disease. Therefore, alcoholism can be viewed as an inflammatory condition, a concept which opens the possibility of using new therapeutic weapons to treat some of the complications of this devastating and frequent disease. In this review we examine some of the most outstanding consequences of the altered cytokine regulation that occurs in alcoholics in organs other than the liver.

  13. On condition based maintenance policy

    Directory of Open Access Journals (Sweden)

    Jong-Ho Shin

    2015-04-01

    Full Text Available In the case of a high-valuable asset, the Operation and Maintenance (O&M phase requires heavy charges and more efforts than the installation (construction phase, because it has long usage life and any accident of an asset during this period causes catastrophic damage to an industry. Recently, with the advent of emerging Information Communication Technologies (ICTs, we can get the visibility of asset status information during its usage period. It gives us new challenging issues for improving the efficiency of asset operations. One issue is to implement the Condition-Based Maintenance (CBM approach that makes a diagnosis of the asset status based on wire or wireless monitored data, predicts the assets abnormality, and executes suitable maintenance actions such as repair and replacement before serious problems happen. In this study, we have addressed several aspects of CBM approach: definition, related international standards, procedure, and techniques with the introduction of some relevant case studies that we have carried out.

  14. Efficient robust conditional random fields.

    Science.gov (United States)

    Song, Dongjin; Liu, Wei; Zhou, Tianyi; Tao, Dacheng; Meyer, David A

    2015-10-01

    Conditional random fields (CRFs) are a flexible yet powerful probabilistic approach and have shown advantages for popular applications in various areas, including text analysis, bioinformatics, and computer vision. Traditional CRF models, however, are incapable of selecting relevant features as well as suppressing noise from noisy original features. Moreover, conventional optimization methods often converge slowly in solving the training procedure of CRFs, and will degrade significantly for tasks with a large number of samples and features. In this paper, we propose robust CRFs (RCRFs) to simultaneously select relevant features. An optimal gradient method (OGM) is further designed to train RCRFs efficiently. Specifically, the proposed RCRFs employ the l1 norm of the model parameters to regularize the objective used by traditional CRFs, therefore enabling discovery of the relevant unary features and pairwise features of CRFs. In each iteration of OGM, the gradient direction is determined jointly by the current gradient together with the historical gradients, and the Lipschitz constant is leveraged to specify the proper step size. We show that an OGM can tackle the RCRF model training very efficiently, achieving the optimal convergence rate [Formula: see text] (where k is the number of iterations). This convergence rate is theoretically superior to the convergence rate O(1/k) of previous first-order optimization methods. Extensive experiments performed on three practical image segmentation tasks demonstrate the efficacy of OGM in training our proposed RCRFs.

  15. Boundary Conditions of Methamphetamine Craving

    Science.gov (United States)

    Lopez, Richard B.; Onyemekwu, Chukwudi; Hart, Carl L.; Ochsner, Kevin N.; Kober, Hedy

    2015-01-01

    Methamphetamine use has increased significantly and become a global health concern. Craving is known to predict methamphetamine use and relapse following abstinence. Some have suggested that cravings are automatic, generalized, and uncontrollable, but experimental work addressing these claims is lacking. In two exploratory studies we tested the boundary conditions of methamphetamine craving by asking: (1) is craving specific to users’ preferred route of administration? and (2) can craving be regulated by cognitive strategies? Two groups of methamphetamine users were recruited. In Study 1, participants were grouped by their preferred route of administration (intranasal vs. smoking), and rated their craving in response to photographs and movies depicting methamphetamine use (via the intranasal vs. smoking route). In Study 2, methamphetamine smokers implemented cognitive regulation strategies while viewing photographs depicting methamphetamine smoking. Strategies involved either focusing on the positive aspects of smoking methamphetamine or the negative consequences of doing so – the latter strategy based on treatment protocols for addiction. In Study 1, we found a significant interaction between group and route of administration, such that participants who preferred to smoke methamphetamine reported significantly stronger craving for smoking stimuli, whereas those who preferred the intranasal route reported stronger craving for intranasal stimuli. In Study 2, participants reported significantly lower craving when focusing on the negative consequences associated with methamphetamine use. Taken together, these findings suggest that strength of craving for methamphetamine is moderated by users’ route of administration and can be reduced by cognitive strategies. This has important theoretical, methodological, and clinical implications. PMID:26302338

  16. Facility engineering for Arctic conditions

    Energy Technology Data Exchange (ETDEWEB)

    Hunt, D.M.; McClusky, K.R.; Shirley, R.; Spitzenberger, R. [Mustang Engineering Inc., Houston, TX (United States)

    2001-07-01

    The Northstar Development Project is located on Seal Island in the Beaufort Sea, north of Prudhoe Bay. The design and engineering of the facilities for the Northstar Development Project was fraught with challenges. Mustang Engineering Incorporated was involved in the design and engineering of the pipe rack, pump house, process and compressor modules. All the characteristics of an offshore facility are present, even though the project is land-based on a man-made island. A number of the strategies developed for offshore platforms of the Gulf of Mexico were adapted to the fabrication, logistics and installation of the modules. To reduce yard fabrication time, a modularized design concept was adopted. Cost savings and onsite fabrication efficiencies were realized through open communication with the operator, early discussions with vendors, regulatory agencies, and local fabrication and installation contractors. Some improvisation and deviations were required to meet the stringent requirements for operation under Arctic conditions. The lessons learned on this project will be of use in future Arctic projects. 1 tab., 6 figs.

  17. Pathological Jealousy: An Interactive Condition.

    Science.gov (United States)

    Seeman, Mary V

    2016-01-01

    The aim of this review is to describe the psychopathology, antecedents, and current management of pathological jealousy from an interpersonal perspective. The Google Scholar database was searched with the following terms: delusional jealousy; morbid jealousy; paranoid jealousy; pathological jealousy; Othello syndrome; delusional disorder-jealous type; conjugal paranoia. From a total of 600 articles, 40 were selected based on their currency and pertinence to the interpersonal aspects of jealousy. Findings were that delusional jealousy is equally prevalent among men and women, with a greater prevalence in the elderly. Antecedents to this condition can be neurologic, drug related, and/or psychological, most often preceded by low self-esteem and excessive dependence on a romantic partner. Pathological jealousy can be triggered by the behavior of the partner and maintained by reasoning biases and by the psychological benefits that it initially bestows on the relationship. In the long run, however, it poses dangerous risks to the patient, the partner, and the imagined rival so that involuntary hospitalization is sometimes required. Treatment recommendations include couple therapy, a strong cognitive focus, antipsychotic medication, and interventions which enhance self-esteem of both partners and which address the solidarity of the existing relationship. Treatment effectiveness does not yet have a firm evidence base.

  18. The ATLAS beam conditions monitor

    CERN Document Server

    Mikuz, M; Dolenc, I; Kagan, H; Kramberger, G; Frais-Kölbl, H; Gorisek, A; Griesmayer, E; Mandic, I; Pernegger, H; Trischuk, W; Weilhammer, P; Zavrtanik, M

    2006-01-01

    The ATLAS beam conditions monitor is being developed as a stand-alone device allowing to separate LHC collisions from background events induced either on beam gas or by beam accidents, for example scraping at the collimators upstream the spectrometer. This separation can be achieved by timing coincidences between two stations placed symmetric around the interaction point. The 25 ns repetition of collisions poses very stringent requirements on the timing resolution. The optimum separation between collision and background events is just 12.5 ns implying a distance of 3.8 m between the two stations. 3 ns wide pulses are required with 1 ns rise time and baseline restoration in 10 ns. Combined with the radiation field of 10/sup 15/ cm/sup -2/ in 10 years of LHC operation only diamond detectors are considered suitable for this task. pCVD diamond pad detectors of 1 cm/sup 2/ and around 500 mum thickness were assembled with a two-stage RF current amplifier and tested in proton beam at MGH, Boston and SPS pion beam at...

  19. WORK CONDITIONS OF CHAINSAW OPERATORS

    Directory of Open Access Journals (Sweden)

    Jorge Roberto Malinovski

    2002-01-01

    Full Text Available The objective of this research was to analyze the human factors and the work conditions in clear-cutting operations using chainsaws in mountainous areas. Data were colected in a forestry company in Minas Gerais, Brazil, by interviews with 29 chainsaw operators. The results indicated that the operators average age was 32.3 years, height 1.68m and body weight 64.4Kg. The average job time in the company was 112 months and the average time of chainsaw operation experience was 81.5 months. Most (93.1% were dexterous and 6.9% were left-handed. The high incidence of backache (41.4% indicated that the task demands an overload of lumbar column, so that the company should take preventive measures to avoid backaches, using educational strategies or changing the opera-tional system. The high level of accidents (44.8% indicated that some precautions are needed to im-prove work safety.

  20. Noise exposure under hyperbaric conditions

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-03-01

    Objective evidence exists that divers demonstrate a hearing deficit greater than would be expected from ageing effects alone. Deafness in divers may be caused by a number of factors other than exposure to excessive noise levels, eg barotrauma, ear infection etc. This review concentrates on the concern that exposure of commercial divers to noise while at work may cause a hearing deficit. Sound pressure levels recorded both underwater and in diving chambers often exceed those allowable to workers onshore. However, the sound perceived by the diver is modified both in amplitude and in frequency when he is either underwater or in pressurised chambers. Broadly the effect of this modification is to attenuate the sound and thus offer some protection from high noise levels. The degree of attentuation varies with the frequency of the sound, however it is also possible under specific conditions associated with gas density for the sensitivity to particular frequencies to be amplified above that for normal atmospheric air. The levels of sound observed from some underwater tools are of concern even after allowing for a significant de-sensitisation of the divers` hearing. Reports of tinnitus and temporary hearing loss following a dive are sure signs that the noise levels have been harmful. It is not possible at present to describe risk criteria for hearing damage due to noise exposure associated with diving. (author)

  1. Fuel conditioning facility material accountancy

    International Nuclear Information System (INIS)

    Yacout, A.M.; Bucher, R.G.; Orechwa, Y.

    1995-01-01

    The operation of the Fuel conditioning Facility (FCF) is based on the electrometallurgical processing of spent metallic reactor fuel. It differs significantly, therefore, from traditional PUREX process facilities in both processing technology and safeguards implications. For example, the fissile material is processed in FCF only in batches and is transferred within the facility only as solid, well-characterized items; there are no liquid steams containing fissile material within the facility, nor entering or leaving the facility. The analysis of a single batch lends itself also to an analytical relationship between the safeguards criteria, such as alarm limit, detection probability, and maximum significant amount of fissile material, and the accounting system's performance, as it is reflected in the variance associated with the estimate of the inventory difference. This relation, together with the sensitivity of the inventory difference to the uncertainties in the measurements, allows a thorough evaluation of the power of the accounting system. The system for the accountancy of the fissile material in the FCF has two main components: a system to gather and store information during the operation of the facility, and a system to interpret this information with regard to meeting safeguards criteria. These are described and the precision of the inventory closure over one batch evaluated

  2. Mixed Fluid Conditions: Capillary Phenomena

    KAUST Repository

    Santamarina, Carlos

    2017-07-06

    Mixed fluid phenomena in porous media have profound implications on soil-atmosphere interaction, energy geotechnology, environmental engineering and infrastructure design. Surface tension varies with pressure, temperature, solute concentration, and surfactant concentration; on the other hand, the contact angle responds to interfacial tensions, surface topography, invasion velocity, and chemical interactions. Interfaces are not isolated but interact through the fluid pressure and respond to external fields. Jumps, snap-offs and percolating wetting liquids along edges and crevices are ubiquitous in real, non-cylindrical porous networks. Pore- and macroscale instabilities together with pore structure variability-and-correlation favor fluid trapping and hinder recovery efficiency. The saturation-pressure characteristic curve is affected by the saturation-history, flow-rate, the mechanical response of the porous medium, and time-dependent reactive and diffusive processes; in addition, there are salient differences between unsaturation by internal gas nucleation and gas invasion. Capillary forces add to other skeletal forces in the porous medium and can generate open-mode discontinuities when the capillary entry pressure is high relative to the effective stress. Time emerges as an important variable in mixed-fluid conditions and common quasi-static analyses may fail to capture the system response.

  3. Dirac's minimum degree condition restricted to claws

    NARCIS (Netherlands)

    Broersma, Haitze J.; Ryjacek, Z.; Schiermeyer, I.

    1997-01-01

    Let G be a graph on n 3 vertices. Dirac's minimum degree condition is the condition that all vertices of G have degree at least . This is a well-known sufficient condition for the existence of a Hamilton cycle in G. We give related sufficiency conditions for the existence of a Hamilton cycle or a

  4. Maximum Likelihood Learning of Conditional MTE Distributions

    DEFF Research Database (Denmark)

    Langseth, Helge; Nielsen, Thomas Dyhre; Rumí, Rafael

    2009-01-01

    We describe a procedure for inducing conditional densities within the mixtures of truncated exponentials (MTE) framework. We analyse possible conditional MTE specifications and propose a model selection scheme, based on the BIC score, for partitioning the domain of the conditioning variables....... Finally, experimental results demonstrate the applicability of the learning procedure as well as the expressive power of the conditional MTE distribution....

  5. Electrical Aversion Conditioning with Chronic Alcoholics

    Science.gov (United States)

    Vogler, Roger E.; And Others

    1970-01-01

    Pseudoconditioning (random shock delivery), sham conditioning (no shock), and ward controls (routine hospital treatment) ( were compared with two conditioning groups. Conditioning only (contingent shock) and booster Ss (additional conditioning sessions after release from hospital) were shocked for drinking and reinforced by shock termination for…

  6. Women's housing conditions in Bangladesh.

    Science.gov (United States)

    Shefali, M K

    1996-01-01

    This news article describes women's housing conditions, housing policy, and pilot programs to house poor women in Bangladesh. Although Bangladesh has a constitution that reinforces the equal status of women, in practice, men dominate and patrilineal customs determine inheritance and property rights. Religious affiliation also determines land tenure and inheritance. Muslim women can inherit 12.5% of their husband's property if there are children. 25% is inherited if wives are without children. Hindu women without sons can inherit their husband's property, but not parental property. Many families refuse to release property to women without a fight. Women, regardless of ownership of land, rarely control or use their land. The custom of requiring men to maintain wives during the marriage, and daughters until marriage, creates obstacles to women's decision making about property. Without collateral and other security women are unable to secure bank loans. Many women are also constrained by the requirement of male consent or guarantees for bank transactions. Banks do not have a gender responsive criteria for selecting loan recipients. The government does not provide sufficient housing to satisfy the growing housing needs due to population growth. Some housing is available from slum landlords. A National Housing Policy was formulated in 1993. Priority would be given to the housing needs of low income women in urban areas and women-headed households with income below the poverty line. The policy does not address the underlying factors that prevent equal access to housing for women. The government prepared a Human Settlement and Urban Development proposal for the Habitat II conference. The plan did not address gender issues. Special efforts are being made by nongovernmental groups to meet the housing needs of professional women and for some disadvantaged women.

  7. The Condition for Generous Trust.

    Directory of Open Access Journals (Sweden)

    Obayashi Shinya

    Full Text Available Trust has been considered the "cement" of a society and is much studied in sociology and other social sciences. Most studies, however, have neglected one important aspect of trust: it involves an act of forgiving and showing tolerance toward another's failure. In this study, we refer to this concept as "generous trust" and examine the conditions under which generous trust becomes a more viable option when compared to other types of trust. We investigate two settings. First, we introduce two types of uncertainties: uncertainty as to whether trustees have the intention to cooperate, and uncertainty as to whether trustees have enough competence to accomplish the entrusted tasks. Second, we examine the manner in which trust functions in a broader social context, one that involves matching and commitment processes. Since we expect generosity or forgiveness to work differently in the matching and commitment processes, we must differentiate trust strategies into generous trust in the matching process and that in the commitment process. Our analytical strategy is two-fold. First, we analyze the "modified" trust game that incorporates the two types of uncertainties without the matching process. This simplified setting enables us to derive mathematical results using game theory, thereby giving basic insight into the trust mechanism. Second, we investigate socially embedded trust relationships in contexts involving the matching and commitment processes, using agent-based simulation. Results show that uncertainty about partner's intention and competence makes generous trust a viable option. In contrast, too much uncertainty undermines the possibility of generous trust. Furthermore, a strategy that is too generous cannot stand alone. Generosity should be accompanied with moderate punishment. As for socially embedded trust relationships, generosity functions differently in the matching process versus the commitment process. Indeed, these two types of generous

  8. Heavy fermions and extreme conditions

    International Nuclear Information System (INIS)

    Cheikine, Ilia

    2000-01-01

    Three heavy electron systems, CeCu 2 Si 2 , CePd 2 Si 2 and UGe 2 , were investigated by transport, quantum oscillations (CePd 2 Si 2 ) and neutron diffraction (UGe 2 ) measurements. The experiments were performed under extreme conditions of very low temperature, high magnetic field and hydrostatic pressure. In the case of CeCu 2 Si 2 , we followed the evolution of the magnetic A-phase that is found to collapse rapidly under pressure. We found evidence for a relation between the A-phase and the presence of a maximum in the temperature dependence of H c2 . Our analysis showed that at low pressure, the sign of the exchange integral should be negative, thus superconductivity is enhanced by an increase in the paramagnetic susceptibility as in the Jaccarino-Peter effect. The anisotropy of the initial slope of H c2 and therefore that of the effective mass was found to change under pressure. For CePd 2 Si 2 , both the de Haas-van Alphen effect at ambient pressure and the electrical resistivity under pressure were studied. The latter reveals a non-Fermi liquid behavior in the vicinity of the antiferromagnetic quantum critical point, P c ∼ kbar. The analysis of H c2 at P c shows that the superconducting state is well described by a weak coupling, clean limit model with a slightly anisotropic orbital limit and a strongly anisotropic paramagnetic one. UGe 2 is shown to demonstrate the coexistence of ferromagnetism and superconductivity that develops just below the ferromagnetic quantum critical point, P c ∼16 kbar. The measurements of the resistivity under pressure point to a possible existence of another phase boundary and thus another quantum critical point, P x ∼ 12 kbar, within the ferromagnetic state. The P-T phase diagram containing both P c and P x was sketched, and a possible relation between P x and the development of superconductivity was discussed. The temperature dependence of H c2 demonstrates a variety of novel behaviors, which cannot be understood within

  9. Breast milk is conditionally perfect.

    Science.gov (United States)

    Erick, Miriam

    2018-02-01

    Breast milk is the universal preferred nutrition for the newborn human infant. New mother have been encouraged to exclusively breastfeed by health care professionals and consumer-advocacy forums for years, citing "breast milk is the perfect food". The benefits are numerous and include psychological, convenience, economical, ecological and nutritionally superior. Human milk is a composite of nutritional choices of the mother, commencing in the pre-conceptual era. Events influencing the eventual nutritional profile of breast milk for the neonate start with pre-conceptual dietary habits through pregnancy and finally to postpartum. Food choices do affect the nutritional profile of human breast milk. It is not known who coined the phrase "breast milk is the perfect food" but it is widely prevalent in the literature. While breast milk is highly nutritive, containing important immunological and growth factors, scientific investigation reveals a few short-falls. Overall, human breast milk has been found to be low in certain nutrients in developed countries: vitamin D, iodine, iron, and vitamin K. Additional nutrient deficiencies have been documented in resource-poor countries: vitamin A, vitamin B 12, zinc, and vitamin B 1/thiamin. Given these findings, isn't it more accurate to describe breast milk as "conditionally perfect"? Correcting the impression that breast milk is an inherently, automatically comprehensive enriched product would encourage women who plan to breastfeed an opportunity to concentrate on dietary improvement to optimizes nutrient benefits ultimately to the neonate. The more immediate result would improve pre-conceptual nutritional status. Here, we explore the nutritional status of groups of young women; some of whom will become pregnant and eventually produce breast milk. We will review the available literature profiling vitamin, mineral, protein and caloric content of breast milk. We highlight pre-existing situations needing correction to optimize

  10. Discharge Planning in Chronic Conditions

    Science.gov (United States)

    McMartin, K

    2013-01-01

    Background Chronically ill people experience frequent changes in health status accompanied by multiple transitions between care settings and care providers. Discharge planning provides support services, follow-up activities, and other interventions that span pre-hospital discharge to post-hospital settings. Objective To determine if discharge planning is effective at reducing health resource utilization and improving patient outcomes compared with standard care alone. Data Sources A standard systematic literature search was conducted for studies published from January 1, 2004, until December 13, 2011. Review Methods Reports, randomized controlled trials, systematic reviews, and meta-analyses with 1 month or more of follow-up and limited to specified chronic conditions were examined. Outcomes included mortality/survival, readmissions and emergency department (ED) visits, hospital length of stay (LOS), health-related quality of life (HRQOL), and patient satisfaction. Results One meta-analysis compared individualized discharge planning to usual care and found a significant reduction in readmissions favouring individualized discharge planning. A second meta-analysis compared comprehensive discharge planning with postdischarge support to usual care. There was a significant reduction in readmissions favouring discharge planning with postdischarge support. However, there was significant statistical heterogeneity. For both meta-analyses there was a nonsignificant reduction in mortality between the study arms. Limitations There was difficulty in distinguishing the relative contribution of each element within the terms “discharge planning” and “postdischarge support.” For most studies, “usual care” was not explicitly described. Conclusions Compared with usual care, there was moderate quality evidence that individualized discharge planning is more effective at reducing readmissions or hospital LOS but not mortality, and very low quality evidence that it is more

  11. [Life conditions of Togolese doctors].

    Science.gov (United States)

    Koffi-Tessio, Annick Viwalé; Oniankitan, Owonayo; Mijiyawa, Moustafa

    2010-09-01

    %) are ready to choose again the profession if they have to start everything. The little time spent with the family has been stated out by 36 medical doctors (69%), the social and family prestige that came out of it by 32 (62%), and the ability to control the health of one's family by 34 (65%). The psychological impact of the profession on the medical doctors questioned was dominated by the adoption of a philosophical attitude towards life. A better productivity of the Togolese medical doctors needs the improvement of their life conditions (adjustment of texts in force, revision of the salary scale), the renovation of the facilities, the modernization of the technical platform, the continuing education of the medical doctors and the reinforcement of the practical management of the patient on bed.

  12. Chronic Condition Public Use File (PUF)

    Data.gov (United States)

    U.S. Department of Health & Human Services — This release contains the Chronic Conditions Public Use Files (PUF) with information from Medicare claims. The CMS Chronic Conditions PUF is an aggregated file in...

  13. How Are Genetic Conditions Treated or Managed?

    Science.gov (United States)

    ... mtDNA Resources Help Me Understand Genetics Share: Email Facebook Twitter Home Help Me Understand Genetics Genetic Consultation How are genetic conditions treated or managed? How are genetic conditions treated or managed? Many ...

  14. National Coastal Condition Report I (2001)

    Science.gov (United States)

    Thousands of pieces of information on the condition of the estuarine and Great Lakes resources of the United States were collected from 1990 to 1997 with results showing estuaries to be in fair to poor condition.

  15. Deep Neuromuscular Blockade Improves Laparoscopic Surgical Conditions

    DEFF Research Database (Denmark)

    Rosenberg, Jacob; Herring, W Joseph; Blobner, Manfred

    2017-01-01

    INTRODUCTION: Sustained deep neuromuscular blockade (NMB) during laparoscopic surgery may facilitate optimal surgical conditions. This exploratory study assessed whether deep NMB improves surgical conditions and, in doing so, allows use of lower insufflation pressures during laparoscopic cholecys...

  16. Do conditional benefits reduce equilibrium unemployment?

    NARCIS (Netherlands)

    van der Ploeg, F.

    2006-01-01

    Although unconditional unemployment benefits destroy jobs in competitive and noncompetitive labor markets, conditional benefits can spur job growth in noncompetitive labor markets. Unconditional benefits reduce the penalty of shirking and misconduct, while conditional benefits increase this penalty.

  17. Quadratic Functionals with General Boundary Conditions

    International Nuclear Information System (INIS)

    Dosla, Z.; Dosly, O.

    1997-01-01

    The purpose of this paper is to give the Reid 'Roundabout Theorem' for quadratic functionals with general boundary conditions. In particular, we describe the so-called coupled point and regularity condition introduced in terms of Riccati equation solutions

  18. Scalable conditional induction variables (CIV) analysis

    KAUST Repository

    Oancea, Cosmin E.; Rauchwerger, Lawrence

    2015-01-01

    challenges to automatic parallelization. Because the complexity of such induction variables is often due to their conditional evaluation across the iteration space of loops we name them Conditional Induction Variables (CIV). This paper presents a flow

  19. Singularity theorems from weakened energy conditions

    International Nuclear Information System (INIS)

    Fewster, Christopher J; Galloway, Gregory J

    2011-01-01

    We establish analogues of the Hawking and Penrose singularity theorems based on (a) averaged energy conditions with exponential damping; (b) conditions on local stress-energy averages inspired by the quantum energy inequalities satisfied by a number of quantum field theories. As particular applications, we establish singularity theorems for the Einstein equations coupled to a classical scalar field, which violates the strong energy condition, and the nonminimally coupled scalar field, which also violates the null energy condition.

  20. A sector perspective on working conditions

    NARCIS (Netherlands)

    Jettinghoff, K.; Houtman, I.

    2009-01-01

    Every five years the European Foundation for the Improvement of Living and Working Conditions (Eurofound) conducts the European Working Conditions Survey (EWCS). The survey provides an overview of the state of working conditions throughout Europe and indicates the nature and content of changes