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  1. Targeting Tumor Oct4 to Deplete Prostate Tumor and Metastasis Initiating Cells

    Science.gov (United States)

    2017-12-01

    is associated with androgen receptor (AR). We detected Oct4 protein expression in prostate cancer cells as well as in tumor tissue specimens...unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Identification of genes driving prostate carcinogenesis will lead to new cancer treatment. The human...a pseudogene of embryonic Oct4 (POU5F1). A recent study found that tumor Oct4 found in prostate cancer cells is due to the gene expression of POU5F1B

  2. OCT4: A penetrant pluripotency inducer

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    Xuecong Wang

    2014-01-01

    Full Text Available Native OCT4 protein has the intrinsic ability of crossing cellular membranes to enter cells. This finding could revive efforts to induce pluripotency with proteins replacing nucleic acid-based approaches, and raises the intriguing question as to whether OCT4 can act non-cell-autonomously.

  3. OCT4: A penetrant pluripotency inducer.

    Science.gov (United States)

    Wang, Xuecong; Jauch, Ralf

    2014-01-01

    Native OCT4 protein has the intrinsic ability of crossing cellular membranes to enter cells. This finding could revive efforts to induce pluripotency with proteins replacing nucleic acid-based approaches, and raises the intriguing question as to whether OCT4 can act non-cell-autonomously.

  4. OCT4: A penetrant pluripotency inducer

    OpenAIRE

    Wang, Xuecong; Jauch, Ralf

    2014-01-01

    Native OCT4 protein has the intrinsic ability of crossing cellular membranes to enter cells. This finding could revive efforts to induce pluripotency with proteins replacing nucleic acid-based approaches, and raises the intriguing question as to whether OCT4 can act non-cell-autonomously.

  5. Post-translational regulation of Oct4 transcriptional activity.

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    Jonathan P Saxe

    Full Text Available Oct4 is a key component of the molecular circuitry which regulates embryonic stem cell proliferation and differentiation. It is essential for maintenance of undifferentiated, pluripotent cell populations, and accomplishes these tasks by binding DNA in multiple heterodimer and homodimer configurations. Very little is known about how formation of these complexes is regulated, or the mechanisms through which Oct4 proteins respond to complex extracellular stimuli which regulate pluripotency. Here, we provide evidence for a phosphorylation-based mechanism which regulates specific Oct4 homodimer conformations. Point mutations of a putative phosphorylation site can specifically abrogate transcriptional activity of a specific homodimer assembly, with little effect on other configurations. Moreover, we performed bioinformatic predictions to identify a subset of Oct4 target genes which may be regulated by this specific assembly, and show that altering Oct4 protein levels affects transcription of Oct4 target genes which are regulated by this assembly but not others. Finally, we identified several signaling pathways which may mediate this phosphorylation and act in combination to regulate Oct4 transcriptional activity and protein stability. These results provide a mechanism for rapid and reversible alteration of Oct4 transactivation potential in response to extracellular signals.

  6. Of Mice and Snakes: A Tail of Oct4.

    Science.gov (United States)

    Shylo, Natalia A; Weatherbee, Scott D

    2016-08-08

    The vertebrate axial skeleton comprises regions of specialized vertebrae, which vary in length between lineages. Aires et al. (2016) uncover a key role for Oct4 in determining trunk length in mice. Additionally, a heterochronic shift in Oct4 expression may underlie the extreme elongation of the trunk in snakes. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Dynamic methylation and expression of Oct4 in early neural stem cells.

    Science.gov (United States)

    Lee, Shih-Han; Jeyapalan, Jennie N; Appleby, Vanessa; Mohamed Noor, Dzul Azri; Sottile, Virginie; Scotting, Paul J

    2010-09-01

    Neural stem cells are a multipotent population of tissue-specific stem cells with a broad but limited differentiation potential. However, recent studies have shown that over-expression of the pluripotency gene, Oct4, alone is sufficient to initiate a process by which these can form 'induced pluripotent stem cells' (iPS cells) with the same broad potential as embryonic stem cells. This led us to examine the expression of Oct4 in endogenous neural stem cells, as data regarding its expression in neural stem cells in vivo are contradictory and incomplete. In this study we have therefore analysed the expression of Oct4 and other genes associated with pluripotency throughout development of the mouse CNS and in neural stem cells grown in vitro. We find that Oct4 is still expressed in the CNS by E8.5, but that this expression declines rapidly until it is undetectable by E15.5. This decline is coincident with the gradual methylation of the Oct4 promoter and proximal enhancer. Immunostaining suggests that the Oct4 protein is predominantly cytoplasmic in location. We also found that neural stem cells from all ages expressed the pluripotency associated genes, Sox2, c-Myc, Klf4 and Nanog. These data provide an explanation for the varying behaviour of cells from the early neuroepithelium at different stages of development. The expression of these genes also provides an indication of why Oct4 alone is sufficient to induce iPS formation in neural stem cells at later stages.

  8. Concurrent Expression of Oct4 and Nanog Maintains Mesenchymal Stem-Like Property of Human Dental Pulp Cells

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    Chuan-En Huang

    2014-10-01

    Full Text Available Human dental pulp stem cells (DPSCs, unique mesenchymal stem cells (MSCs type, exhibit the characteristics of self-renewal and multi-lineage differentiation capacity. Oct4 and Nanog are pluripotent genes. The aim of this study was to determine the physiological functions of Oct4 and Nanog expression in DPSCs. Herein, we determined the critical role of an Oct4/Nanog axis modulating MSCs properties of DPSCs by lentiviral-mediated co-overexpression or co-knockdown of Oct4/Nanog in DPSCs. MSCs properties including osteogenic/chondrogenic/adipogenic induction differentiation was assayed for expression of osteogenic/chondrogenic/adipogenic markers by quantitative real-time RT-PCR analysis. Initially, we observed that the expression profile of Oct4 and Nanog in dental pulp cells, which exerted properties of MSCs, was significantly up-regulated compared to that of STRO-1−CD146− dental pulp cells. Down-regulation of Oct4 and Nanog co-expression significantly reduced the cell proliferation, osteogenic differentiation capability, STRO-1, CD146, and Alkaline phosphatase (ALP activity of DPSCs. In contrast, co-overexpression of Oct4 and Nanog enhanced the expression level of STRO-1 and CD146, proliferation rate and osteogenic/chondrogenic/adipogenic induction differentiation capability, and expression of osteogenic/chondrogenic/adipogenic induction differentiation markers. Our results suggest that Oct4-Nanog signaling is a regulatory switch to maintain properties in DPSCs.

  9. Concurrent expression of Oct4 and Nanog maintains mesenchymal stem-like property of human dental pulp cells.

    Science.gov (United States)

    Huang, Chuan-En; Hu, Fang-Wei; Yu, Chuan-Hang; Tsai, Lo-Lin; Lee, Tzu-Hsin; Chou, Ming-Yung; Yu, Cheng-Chia

    2014-10-15

    Human dental pulp stem cells (DPSCs), unique mesenchymal stem cells (MSCs) type, exhibit the characteristics of self-renewal and multi-lineage differentiation capacity. Oct4 and Nanog are pluripotent genes. The aim of this study was to determine the physiological functions of Oct4 and Nanog expression in DPSCs. Herein, we determined the critical role of an Oct4/Nanog axis modulating MSCs properties of DPSCs by lentiviral-mediated co-overexpression or co-knockdown of Oct4/Nanog in DPSCs. MSCs properties including osteogenic/chondrogenic/adipogenic induction differentiation was assayed for expression of osteogenic/chondrogenic/adipogenic markers by quantitative real-time RT-PCR analysis. Initially, we observed that the expression profile of Oct4 and Nanog in dental pulp cells, which exerted properties of MSCs, was significantly up-regulated compared to that of STRO-1-CD146- dental pulp cells. Down-regulation of Oct4 and Nanog co-expression significantly reduced the cell proliferation, osteogenic differentiation capability, STRO-1, CD146, and Alkaline phosphatase (ALP) activity of DPSCs. In contrast, co-overexpression of Oct4 and Nanog enhanced the expression level of STRO-1 and CD146, proliferation rate and osteogenic/chondrogenic/adipogenic induction differentiation capability, and expression of osteogenic/chondrogenic/adipogenic induction differentiation markers. Our results suggest that Oct4-Nanog signaling is a regulatory switch to maintain properties in DPSCs.

  10. Oct-4 expression maintained stem cell properties in prostate cancer ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research ... The purpose of the present study is to isolate cancerous stem-like cells from normal healthy volunteers and ... The treatment with Oct-4 blocking antibody can specifically block the capability of ...

  11. Oct4 targets regulatory nodes to modulate stem cell function.

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    Pearl A Campbell

    2007-06-01

    Full Text Available Stem cells are characterized by two defining features, the ability to self-renew and to differentiate into highly specialized cell types. The POU homeodomain transcription factor Oct4 (Pou5f1 is an essential mediator of the embryonic stem cell state and has been implicated in lineage specific differentiation, adult stem cell identity, and cancer. Recent description of the regulatory networks which maintain 'ES' have highlighted a dual role for Oct4 in the transcriptional activation of genes required to maintain self-renewal and pluripotency while concomitantly repressing genes which facilitate lineage specific differentiation. However, the molecular mechanism by which Oct4 mediates differential activation or repression at these loci to either maintain stem cell identity or facilitate the emergence of alternate transcriptional programs required for the realization of lineage remains to be elucidated. To further investigate Oct4 function, we employed gene expression profiling together with a robust statistical analysis to identify genes highly correlated to Oct4. Gene Ontology analysis to categorize overrepresented genes has led to the identification of themes which may prove essential to stem cell identity, including chromatin structure, nuclear architecture, cell cycle control, DNA repair, and apoptosis. Our experiments have identified previously unappreciated roles for Oct4 for firstly, regulating chromatin structure in a state consistent with self-renewal and pluripotency, and secondly, facilitating the expression of genes that keeps the cell poised to respond to cues that lead to differentiation. Together, these data define the mechanism by which Oct4 orchestrates cellular regulatory pathways to enforce the stem cell state and provides important insight into stem cell function and cancer.

  12. Oct-4 expression maintained stem cell properties in prostate cancer ...

    African Journals Online (AJOL)

    Erah

    Keywords: Prostate cancer, Cancer stem-like cells, Oct-4, CD133, Multi-drug resistance1 (MDR1). Received: 7 ... mechanisms in maintaining the self-renewal and drug resistant ... (platelet-derived growth factor α receptor). This suggests that ...

  13. Analysis of nuclear reprogramming in cloned miniature pig embryos by expression of Oct-4 and Oct-4 related genes

    International Nuclear Information System (INIS)

    Lee, Eugine; Lee, So Hyun; Kim, Sue

    2006-01-01

    Xenotransplantation is a rapidly expanding field of research and cloned miniature pigs have been considered as a model animal for it. However, the efficiency of somatic cell nuclear transfer (SCNT) is extremely low, with most clones resulting in early lethality and several kinds of aberrant development. A possible explanation for the developmental failure of SCNT embryos is insufficient reprogramming of the somatic cell nucleus by the oocyte. In order to test this, we analyzed the reprogramming capacity of differentiated fibroblast cell nuclei and embryonic germ cell nuclei with Oct-4 and Oct-4 related genes (Ndp5211, Dppa2, Dppa3, and Dppa5), which are important for embryonic development, Hand1 and GATA-4, which are important for placental development, as molecular markers using RT-PCR. The Oct-4 expression level was significantly lower (P < 0.05) in cloned hatched blastocysts derived from fibroblasts and many of fibroblast-derived clones failed to reactivate at least one of the tested genes, while most of the germ cell clones and control embryos correctly expressed these genes. In conclusion, our results suggest that the reprogramming of fibroblast-derived cloned embryos is highly aberrant and this improper reprogramming could be one reason of the early lethality and post-implantation anomalies of somatic cell-derived clones

  14. Enhanced human somatic cell reprogramming efficiency by fusion of the MYC transactivation domain and OCT4

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    Ling Wang

    2017-12-01

    Full Text Available The development of human induced pluripotent stem cells (iPSCs holds great promise for regenerative medicine. However the iPSC induction efficiency is still very low and with lengthy reprogramming process. We utilized the highly potent transactivation domain (TAD of MYC protein to engineer the human OCT4 fusion proteins. Applying the MYC-TAD-OCT4 fusion proteins in mouse iPSC generation leads to shorter reprogramming dynamics, with earlier activation of pluripotent markers in reprogrammed cells than wild type OCT4 (wt-OCT4. Dramatic enhancement of iPSC colony induction efficiency and shortened reprogramming dynamics were observed when these MYC-TAD-OCT4 fusion proteins were used to reprogram primary human cells. The OCT4 fusion proteins induced human iPSCs are pluripotent. We further show that the MYC Box I (MBI is dispensable while both MBII and the linking region between MBI/II are essential for the enhanced reprogramming activity of MYC-TAD-OCT4 fusion protein. Consistent with an enhanced transcription activity, the engineered OCT4 significantly stimulated the expression of genes specifically targeted by OCT4-alone, OCT4/SOX2, and OCT4/SOX2/KLF4 during human iPSC induction, compared with the wt-OCT4. The MYC-TAD-OCT4 fusion proteins we generated will be valuable tools for studying the reprogramming mechanisms and for efficient iPSC generation for humans as well as for other species.

  15. Hierarchical Oct4 Binding in Concert with Primed Epigenetic Rearrangements during Somatic Cell Reprogramming

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    Jun Chen

    2016-02-01

    Full Text Available The core pluripotency factor Oct4 plays key roles in somatic cell reprogramming through transcriptional control. Here, we profile Oct4 occupancy, epigenetic changes, and gene expression in reprogramming. We find that Oct4 binds in a hierarchical manner to target sites with primed epigenetic modifications. Oct4 binding is temporally continuous and seldom switches between bound and unbound. Oct4 occupancy in most of promoters is maintained throughout the entire reprogramming process. In contrast, somatic cell-specific enhancers are silenced in the early and intermediate stages, whereas stem cell-specific enhancers are activated in the late stage in parallel with cell fate transition. Both epigenetic remodeling and Oct4 binding contribute to the hyperdynamic enhancer signature transitions. The hierarchical Oct4 bindings are associated with distinct functional themes at different stages. Collectively, our results provide a comprehensive molecular roadmap of Oct4 binding in concert with epigenetic rearrangements and rich resources for future reprogramming studies.

  16. OCT4 increases BIRC5 and CCND1 expression and promotes cancer progression in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Cao, Lu; Wu, Mengchao; Zhang, Ying; Su, Changqing; Li, Chunguang; Shen, Shuwen; Yan, Yan; Ji, Weidan; Wang, Jinghan; Qian, Haihua; Jiang, Xiaoqing; Li, Zhigang

    2013-01-01

    OCT4 and BIRC5 are preferentially expressed in human cancer cells and mediate cancer cell survival and tumor maintenance. However, the molecular mechanism that regulates OCT4 and BIRC5 expression is not well characterized. By manipulating OCT4 and BIRC5 expression in hepatocellular carcinoma (HCC) cell lines, the regulatory mechanism of OCT4 on BIRC5 and CCND1 were investigated. Increasing or decreasing OCT4 expression could enhance or suppress BIRC5 expression, respectively, by regulating the activity of BIRC5 promoter. Because there is no binding site for OCT4 within BIRC5 promoter, the effect of OCT4 on BIRC5 promoter is indirect. An octamer motif for OCT4 in the CCND1 promoter has directly and partly participated in the regulation of CCND1 promoter activity, suggesting that OCT4 also could upregulated the expression of CCND1. Co-suppression of OCT4 and BIRC5 induced cancer cell apoptosis and cell cycle arrest, thereby efficiently inhibiting the proliferative activity of cancer cells and suppressing the growth of HCC xenogrfts in nude mice. OCT4 can upregulate BIRC5 and CCND1 expression by increasing their promoter activity. These factors collusively promotes HCC cell proliferation, and co-suppression of OCT4 and BIRC5 is potentially beneficial for HCC treatment

  17. OCT4 and SOX2 are reliable markers in detecting stem cells in odontogenic lesions

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    Abhishek Banerjee

    2016-01-01

    Full Text Available Context (Background: Stem cells are a unique subpopulation of cells in the human body with a capacity to initiate differentiation into various cell lines. Tumor stem cells (TSCs are a unique subpopulation of cells that possess the ability to initiate a neoplasm and sustain self-renewal. Epithelial stem cell (ESC markers such as octamer-binding transcription factor 4 (OCT4 and sex-determining region Y (SRY-box 2 (SOX2 are capable of identifying these stem cells expressed during the early stages of tooth development. Aims: To detect the expression of the stem cell markers OCT4 and SOX2 in the normal odontogenic tissues and the odontogenic cysts and tumors. Materials and Methods: Paraffin sections of follicular tissue, radicular cyst, dentigerous cyst, odontogenic keratocyst, ameloblastoma, adenomatoid odontogenic tumor, and ameloblastic carcinoma were obtained from the archives. The sections were subjected to immunohistochemical assay by the use of mouse monoclonal antibodies to OCT4 and SOX2. Statistical Analysis: The results were evaluated by descriptive analysis. Results: The results show the presence of stem cells in the normal and lesional tissues with these stem cell identifying markers. SOX2 was found to be more consistent and reliable in the detection of stem cells. Conclusion: The stem cell expressions are maintained in the tumor transformation of tissue and probably suggest that there is no phenotypic change of stem cells in progression from normal embryonic state to its tumor component. The quantification and localization reveals interesting trends that indicate the probable role of the cells in the pathogenesis of the lesions.

  18. Distinctive expression pattern of OCT4 variants in different types of breast cancer.

    Science.gov (United States)

    Soheili, Saamaaneh; Asadi, Malek Hossein; Farsinejad, Alireza

    2017-01-01

    OCT4 is a key regulator of self-renewal and pluripotency in embryonic stem cells which can potentially encode three spliced variants designated OCT4A, OCT4B and OCT4B1. Based on cancer stem cell concept, it is suggested that the stemness factors misexpressed in cancer cells and potentially is involved in tumorigenesis. Accordingly, in this study, we investigated the potential expression of OCT4 variants in breast cancer tissues. A total of 94 tumoral and peritumoral breast specimens were evaluated with respect to the expression of OCT4 variants using quantitative RT-PCR and immunohistochemical (IHC) analysis. We detected the expression of OCT4 variants in breast tumor tissues with no or very low levels of expression in peritumoral samples of the same patients. While OCT4B was highly expressed in lobular type of breast cancer, OCT4A and OCTB1 variants are highly expressed in low grade (I and II) ductal tumors. Furthermore, the results of this study revealed a considerable association between the expression level of OCT4 variants and the expression of ER, PR, Her2 and P53 factors. All data demonstrated a distinctive expression pattern of OCT4 spliced variants in different types of breast cancer and provide further evidence for the involvement of embryonic genes in carcinogenesis.

  19. Overexpression of Oct4 suppresses the metastatic potential of breast cancer cells via Rnd1 downregulation.

    Science.gov (United States)

    Shen, Long; Qin, Kunhua; Wang, Dekun; Zhang, Yan; Bai, Nan; Yang, Shengyong; Luo, Yunping; Xiang, Rong; Tan, Xiaoyue

    2014-11-01

    Although Oct4 is known as a critical transcription factor involved in maintaining "stemness", its role in tumor metastasis is still controversial. Herein, we overexpressed and silenced Oct4 expression in two breast cancer cell lines, MDA-MB-231 and 4T1, separately. Our data showed that ectopic overexpression of Oct4 suppressed cell migration and invasion in vitro and the formation of metastatic lung nodules in vivo. Conversely, Oct4 downregulation increased the metastatic potential of breast cancer cells both in vitro and in vivo. Furthermore, we identified Rnd1 as the downstream target of Oct4 by ribonucleic acid sequencing (RNA-seq) analysis, which was significantly downregulated upon Oct4 overexpression. Chromatin immunoprecipitation assays revealed the binding of Oct4 to the promoter region of Rnd1 by ectopic overexpression of Oct4. Dual luciferase assays indicated that Oct4 overexpression suppressed transcriptional activity of the Rnd1 promoter. Moreover, overexpression of Rnd1 partially rescued the inhibitory effects of Oct4 on the migration and invasion of breast cancer cells. Overexpression of Rnd1 counteracted the influence of Oct4 on the formation of cell adhesion and lamellipodia, which implied a potential underlying mechanism involving Rnd1. In addition, we also found that overexpression of Oct4 led to an elevation of E-cadherin expression, even in 4T1 cells that possess a relatively high basal level of E-cadherin. Rnd1 overexpression impaired the promoting effects of Oct4 on E-cadherin expression in MDA-MB-231 cells. These results suggest that Oct4 affects the metastatic potential of breast cancer cells through Rnd1-mediated effects that influence cell motility and E-cadherin expression. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. OCT-4 expression in follicular and luteal phase endometrium: a pilot study

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    Huber Johannes C

    2010-04-01

    Full Text Available Abstract Background The stem cell marker Octamer-4 (OCT-4 is expressed in human endometrium. Menstrual cycle-dependency of OCT-4 expression has not been investigated to date. Methods In a prospective, single center cohort study of 98 women undergoing hysteroscopy during the follicular (n = 49 and the luteal (n = 40 phases of the menstrual cycle, we obtained endometrial samples. Specimens were investigated for OCT-4 expression on the mRNA and protein levels using reverse transcriptase polymerase chain reaction (RT-PCR and immunohistochemistry. Expression of OCT-4 was correlated to menstrual cycle phase. Results Of 89 women sampled, 49 were in the follicular phase and 40 were in the luteal phase. OCT-4 mRNA was detected in all samples. Increased OCT-4 mRNA levels in the follicular and luteal phases was found in 35/49 (71% and 27/40 (68% of women, respectively (p = 0.9. Increased expression of OCT-4 protein was identified in 56/89 (63% samples. Increased expression of OCT-4 protein in the follicular and luteal phases was found in 33/49 (67% and 23/40 (58% of women, respectively (p = 0.5. Conclusions On the mRNA and protein levels, OCT-4 is not differentially expressed during the menstrual cycle. Endometrial OCT-4 is not involved in or modulated by hormone-induced cyclical changes of the endometrium.

  1. Nocodazole treatment decreases expression of pluripotency markers Nanog and Oct4 in human embryonic stem cells

    DEFF Research Database (Denmark)

    Kallas, Ade; Pook, Martin; Maimets, Martti

    2011-01-01

    in the expression of transcription markers Nanog and Oct4 as well as SSEA-3 and SSEA-4 in human embryonic cells after their treatment with nocodazole. Multivariate permeabilised-cell flow cytometry was applied for characterising the expression of Nanog and Oct4 during different cell cycle phases. Among untreated h......ESC we detected Nanog-expressing cells, which also expressed Oct4, SSEA-3 and SSEA-4. We also found another population expressing SSEA-4, but without Nanog, Oct4 and SSEA-3 expression. Nocodazole treatment resulted in a decrease of cell population positive for all four markers Nanog, Oct4, SSEA-3, SSEA-4....... Nocodazole-mediated cell-cycle arrest was accompanied by higher rate of apoptosis and upregulation of p53. Twenty-four hours after the release from nocodazole block, the cell cycle of hESC normalised, but no increase in the expression of transcription markers Nanog and Oct4 was detected. In addition...

  2. OCT4B1 Regulates the Cellular Stress Response of Human Dental Pulp Cells with Inflammation

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    Lu Liu

    2017-01-01

    Full Text Available Introduction. Infection and apoptosis are combined triggers for inflammation in dental tissues. Octamer-binding transcription factor 4-B1 (OCT4B1, a novel spliced variant of OCT4 family, could respond to the cellular stress and possess antiapoptotic property. However, its specific role in dental pulpitis remains unknown. Methods. To investigate the effect of OCT4B1 on inflammation of dental pulp cells (DPCs, its expression in inflamed dental pulp tissues and DPCs was examined by in situ hybridization, real-time PCR, and FISH assay. OCT4B1 overexpressed DPCs model was established, confirmed by western blot and immunofluorescence staining, and then stimulated with Lipopolysaccharide (LPS. Apoptotic rate was determined by Hoechst/PI staining and FACS. Cell survival rate was calculated by CCK8 assay. Results. In situ hybridization, real-time PCR, and FISH assay revealed that OCT4B1 was extensively expressed in inflamed dental pulp tissues and DPCs with LPS stimulation. Western blot and immunofluorescence staining showed the expression of OCT4B1 and OCT4B increased after OCT4B1 transfection. Hoechst/PI staining and FACS demonstrated that less red/blue fluorescence was detected and apoptotic percentage decreased (3.45% after transfection. CCK8 demonstrated that the survival rate of pCDH-OCT4B1-flag cells increased. Conclusions. OCT4B1 plays an essential role in inflammation and apoptosis of DPCs. OCT4B might operate synergistically with OCT4B1 to reduce apoptosis.

  3. Structural basis for the SOX-dependent genomic redistribution of OCT4 in stem cell differentiation.

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    Merino, Felipe; Ng, Calista Keow Leng; Veerapandian, Veeramohan; Schöler, Hans Robert; Jauch, Ralf; Cojocaru, Vlad

    2014-09-02

    In pluripotent cells, OCT4 associates with SOX2 to maintain pluripotency or with SOX17 to induce primitive endoderm commitment. The OCT4-SOX2 and OCT4-SOX17 combinations bind mutually exclusive to two distinct composite DNA elements, known as the "canonical" and "compressed" motifs, respectively. The structural basis for the OCT4-SOX17 cooperativity is unknown. Whereas SOX17 has been engineered to replace SOX2 in the pluripotency circuitry, all generated SOX2 mutants have failed to act like SOX17. From molecular simulations, we revealed the OCT4-SOX17 interaction interface and elucidated the SOX-dependent motif preference of OCT4. Moreover, we designed a SOX2 mutant that we predicted and confirmed experimentally to bind cooperatively with OCT4 to the compressed motif. Ultimately, we found a strong correlation between the experimental and calculated relative cooperative-binding free energies of 12 OCT4-SOX-DNA complexes. Therefore, we validated the OCT4-SOX interfaces and demonstrated that in silico design of DNA-binding cooperativity is suitable for altering transcriptional circuitries. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Oct4 is required ~E7.5 for proliferation in the primitive streak.

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    Brian DeVeale

    2013-11-01

    Full Text Available Oct4 is a widely recognized pluripotency factor as it maintains Embryonic Stem (ES cells in a pluripotent state, and, in vivo, prevents the inner cell mass (ICM in murine embryos from differentiating into trophectoderm. However, its function in somatic tissue after this developmental stage is not well characterized. Using a tamoxifen-inducible Cre recombinase and floxed alleles of Oct4, we investigated the effect of depleting Oct4 in mouse embryos between the pre-streak and headfold stages, ~E6.0-E8.0, when Oct4 is found in dynamic patterns throughout the embryonic compartment of the mouse egg cylinder. We found that depletion of Oct4 ~E7.5 resulted in a severe phenotype, comprised of craniorachischisis, random heart tube orientation, failed turning, defective somitogenesis and posterior truncation. Unlike in ES cells, depletion of the pluripotency factors Sox2 and Oct4 after E7.0 does not phenocopy, suggesting that ~E7.5 Oct4 is required within a network that is altered relative to the pluripotency network. Oct4 is not required in extraembryonic tissue for these processes, but is required to maintain cell viability in the embryo and normal proliferation within the primitive streak. Impaired expansion of the primitive streak occurs coincident with Oct4 depletion ∼E7.5 and precedes deficient convergent extension which contributes to several aspects of the phenotype.

  5. Clinicopathological and prognostic significance of OCT4 in patients with hepatocellular carcinoma: a meta-analysis

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    Liang CJ

    2017-12-01

    Full Text Available Chaojie Liang,* Yingchen Xu,* Hua Ge, Guangming Li, Jixiang Wu Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China *These authors contributed equally to this work Background and aims: Octamer-binding transcription factor 4 (OCT4 has been implicated in the development of hepatocellular carcinoma (HCC, although the findings are controversial. We conducted a meta-analysis to assess the correlation between OCT4 and the clinicopathological characteristics and the prognostic value in HCC.Methods: An electronic search for relevant articles was conducted in PubMed, Cochrane Library, Web of Science, EMBASE database, Chinese CNKI, and Chinese WanFang database. Correlations between OCT4 expression and clinicopathological features and survival outcomes were analyzed. Pooled odds ratios and hazard ratios with 95% CIs were calculated using STATA 14.2 software.Results: A total of 10 trials with 985 patients were included. Positive OCT4 expression was correlated with tumor size, tumor numbers, differentiation, and TNM stage. OCT4 expression was not correlated with gender, age, hepatitis B surface antigen, alfa-fetoprotein, liver cirrhosis, vascular invasion, or tumor encapsulation. OCT4 expression was associated with poor 3- and 5-year overall survival, and disease-free survival rate.Conclusion: OCT4 expression was associated with tumor size, tumor numbers, differentiation, and TNM stage in HCC. OCT4 may be a useful prognostic biomarker for HCC. Keywords: octamer-binding transcription factor 4, hepatocellular carcinoma, prognosis, meta-analysis

  6. A unique Oct4 interface is crucial for reprogramming to pluripotency

    NARCIS (Netherlands)

    Esch, Daniel; Vahokoski, Juha; Groves, Matthew R; Pogenberg, Vivian; Cojocaru, Vlad; Vom Bruch, Hermann; Han, Dong; Drexler, Hannes C A; Araúzo-Bravo, Marcos J; Ng, Calista K L; Jauch, Ralf; Wilmanns, Matthias; Schöler, Hans R

    Terminally differentiated cells can be reprogrammed to pluripotency by the forced expression of Oct4, Sox2, Klf4 and c-Myc. However, it remains unknown how this leads to the multitude of epigenetic changes observed during the reprogramming process. Interestingly, Oct4 is the only factor that cannot

  7. A conserved Oct4/POUV-dependent network links adhesion and migration to progenitor maintenance

    DEFF Research Database (Denmark)

    Livigni, Alessandra; Peradziryi, Hanna; Sharov, Alexei A

    2013-01-01

    BACKGROUND: The class V POU domain transcription factor Oct4 (Pou5f1) is a pivotal regulator of embryonic stem cell (ESC) self-renewal and reprogramming of somatic cells to induced pluripotent stem (iPS) cells. Oct4 is also an important evolutionarily conserved regulator of progenitor cell differ...

  8. Expression of Oct-4 is significantly associated with the development and prognosis of colorectal cancer

    Science.gov (United States)

    ZHOU, HUAN; HU, YU; WANG, WEIPENG; MAO, YONG; ZHU, JINGJIE; ZHOU, BIN; SUN, JING; ZHANG, XUEGUANG

    2015-01-01

    Octamer-binding transcription factor 4 (Oct-4), is an essential transcription factor, which is required for pluripotency and self-renewal in embryonic stem cells and germ cells. It is also involved in maintaining cancer stem-like properties in certain types of tumor, and is an important biomarker for cancer stem cells. The present study investigated whether Oct-4 expression was associated with colorectal cancer (CRC). In order to achieve this, primary CRC tissues, matched non-tumor tissues and benign polyp tissues, representing different stages of carcinogenesis, were obtained, and Oct-4 expression was analyzed using reverse transcription-quantitative polymerase chain reaction, flow cytometry analysis and immunohistochemistry. Furthermore, the medical records of patients with CRC were reviewed, and clinicopathological analysis was performed in order to assess the association between Oct-4 expression and certain clinicopathological parameters. It was shown that the transcription and translation of Oct-4 increased in a stepwise manner, from non-tumor to benign polyp tissues, and from benign polyps to CRC tissues. Oct-4 expression in CRC was significantly correlated with histological grade (P=0.007), lymph node metastasis (P=0.027), distant metastasis (P=0.017) and TNM stage (P=0.041). Kaplan-Meier survival curve analysis demonstrated that Oct-4+ cases had a shorter median survival time (37.0 months) compared with Oct-4− cases (76.0 months; P=0.001). These results indicated that aberrant expression of Oct-4 may be involved in the development of CRC. Thus, Oct-4 may be a biomarker for the prediction, diagnosis or assessment of prognosis in CRC, in addition to a potential target for the treatment of this disease. PMID:26622555

  9. BAY11 enhances OCT4 synthetic mRNA expression in adult human skin cells.

    Science.gov (United States)

    Awe, Jason P; Crespo, Agustin Vega; Li, You; Kiledjian, Megerditch; Byrne, James A

    2013-02-06

    The OCT4 transcription factor is involved in many cellular processes, including development, reprogramming, maintaining pluripotency and differentiation. Synthetic OCT4 mRNA was recently used (in conjunction with other reprogramming factors) to generate human induced pluripotent stem cells. Here, we discovered that BAY 11-7082 (BAY11), at least partially through an NF-κB-inhibition based mechanism, could significantly increase the expression of OCT4 following transfection of synthetic mRNA (synRNA) into adult human skin cells. We tested various chemical and molecular small molecules on their ability to suppress the innate immune response seen upon synthetic mRNA transfection. Three molecules - B18R, BX795, and BAY11 - were used in immunocytochemical and proliferation-based assays. We also utilized global transcriptional meta-analysis coupled with quantitative PCR to identify relative gene expression downstream of OCT4. We found that human skin cells cultured in the presence of BAY11 resulted in reproducible increased expression of OCT4 that did not inhibit normal cell proliferation. The increased levels of OCT4 resulted in significantly increased expression of genes downstream of OCT4, including the previously identified SPP1, DUSP4 and GADD45G, suggesting the expressed OCT4 was functional. We also discovered a novel OCT4 putative downstream target gene SLC16A9 which demonstrated significantly increased expression following elevation of OCT4 levels. For the first time we have shown that small molecule-based stabilization of synthetic mRNA expression can be achieved with use of BAY11. This small molecule-based inhibition of innate immune responses and subsequent robust expression of transfected synthetic mRNAs may have multiple applications for future cell-based research and therapeutics.

  10. Conserved and divergent patterns of expression of DAZL, VASA and OCT4 in the germ cells of the human fetal ovary and testis

    Directory of Open Access Journals (Sweden)

    Coutts Shona

    2007-12-01

    Full Text Available Abstract Background Germ cells arise from a small group of cells that express markers of pluripotency including OCT4. In humans formation of gonadal compartments (cords in testis, nests in ovary takes place during the 1st trimester (6–8 weeks gestation. In the 2nd trimester germ cells can enter meiotic prophase in females whereas in males this does not occur until puberty. We have used qRTPCR, Westerns and immunohistochemical profiling to determine which of the germ cell subtypes in the human fetal gonads express OCT4, DAZL and VASA, as these have been shown to play an essential role in germ cell maturation in mice. Results OCT4 mRNA and protein were detected in extracts from both 1st and 2nd trimester ovaries and testes. In ovarian extracts a marked increase in expression of VASA and DAZL mRNA and protein occurred in the 2nd trimester. In testicular extracts VASA mRNA and protein were low/undetectable in 1st trimester and increased in the 2nd trimester whereas the total amount of DAZL did not seem to change. During the 1st trimester, germ cells were OCT4 positive but did not express VASA. These results are in contrast to the situation in mice where expression of Vasa is initiated in Oct4 positive primordial germ cells as they enter the gonadal ridge. In the 2nd trimester germ cells with intense cytoplasmic staining for VASA were present in both sexes; these cells were OCT4 negative. DAZL expression overlapped with both OCT4 and VASA and changed from the nuclear to the cytoplasmic compartment as cells became OCT4-negative. In males, OCT4-positive and VASA-positive subpopulations of germ cells coexisted within the same seminiferous cords but in the ovary there was a distinct spatial distribution of cells with OCT4 expressed by smaller, peripherally located, germ cells whereas DAZL and VASA were immunolocalised to larger (more mature centrally located cells. Conclusion OCT4, DAZL and VASA are expressed by human fetal germ cells but their

  11. Expression and prognostic value of Oct-4 in astrocytic brain tumors

    DEFF Research Database (Denmark)

    Krogh Petersen, Jeanette; Jensen, Per; Sørensen, M. D.

    2016-01-01

    .045). There was no association between survival and Oct-4 positive cell fraction, neither when combining all tumor grades nor in analysis of individual grades. Oct-4 intensity was not associated with grade, but taking IDH1 status into account we found a tendency for high Oct-4 intensity to be associated with poor prognosis...... was associated with tumor malignancy, but seemed to be without independent prognostic influence in glioblastomas. Identification of a potential prognostic value in anaplastic astrocytomas requires additional studies using larger patient cohorts. © 2016 Krogh Petersen et al. This is an open access article...

  12. Systems Analyses Reveal Shared and Diverse Attributes of Oct4 Regulation in Pluripotent Cells

    DEFF Research Database (Denmark)

    Ding, Li; Paszkowski-Rogacz, Maciej; Winzi, Maria

    2015-01-01

    We combine a genome-scale RNAi screen in mouse epiblast stem cells (EpiSCs) with genetic interaction, protein localization, and "protein-level dependency" studies-a systematic technique that uncovers post-transcriptional regulation-to delineate the network of factors that control the expression...... of Oct4, a key regulator of pluripotency. Our data signify that there are similarities, but also fundamental differences in Oct4 regulation in EpiSCs versus embryonic stem cells (ESCs). Through multiparametric data analyses, we predict that Tox4 is associating with the Paf1C complex, which maintains cell...... identity in both cell types, and validate that this protein-protein interaction exists in ESCs and EpiSCs. We also identify numerous knockdowns that increase Oct4 expression in EpiSCs, indicating that, in stark contrast to ESCs, Oct4 is under active repressive control in EpiSCs. These studies provide...

  13. A nontranscriptional role for Oct4 in the regulation of mitotic entry

    Science.gov (United States)

    Zhao, Rui; Deibler, Richard W.; Lerou, Paul H.; Ballabeni, Andrea; Heffner, Garrett C.; Cahan, Patrick; Unternaehrer, Juli J.; Kirschner, Marc W.; Daley, George Q.

    2014-01-01

    Rapid progression through the cell cycle and a very short G1 phase are defining characteristics of embryonic stem cells. This distinct cell cycle is driven by a positive feedback loop involving Rb inactivation and reduced oscillations of cyclins and cyclin-dependent kinase (Cdk) activity. In this setting, we inquired how ES cells avoid the potentially deleterious consequences of premature mitotic entry. We found that the pluripotency transcription factor Oct4 (octamer-binding transcription factor 4) plays an unappreciated role in the ES cell cycle by forming a complex with cyclin–Cdk1 and inhibiting Cdk1 activation. Ectopic expression of Oct4 or a mutant lacking transcriptional activity recapitulated delayed mitotic entry in HeLa cells. Reduction of Oct4 levels in ES cells accelerated G2 progression, which led to increased chromosomal missegregation and apoptosis. Our data demonstrate an unexpected nontranscriptional function of Oct4 in the regulation of mitotic entry. PMID:25324523

  14. Expression of the pluripotency transcription factor OCT4 in the normal and aberrant mammary gland

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    Foteini eHassiotou

    2013-04-01

    Full Text Available Breast cancers with lactating features, some of which are associated with pregnancy and lactation, are often poorly differentiated, lack estrogen receptor, progesterone receptor and HER2 expression and have high mortality. Very little is known about the molecular mechanisms that drive uncontrolled cell proliferation in these tumors and confer lactating features. We have recently reported expression of OCT4 and associated embryonic stem cell (ESC self-renewal genes in the normal lactating breast and breastmilk stem cells (hBSCs. This prompted us to examine OCT4 expression in breast cancers with lactating features and compare it with that observed during normal lactation, using rare specimens of human lactating breast. In accordance with previous literature, the normal resting breast (from non-pregnant, non-lactating women showed minimal OCT4 nuclear expression (0.9%. However, this increased in the normal lactating breast (11.4%, with further increase in lactating adenomas, lactating carcinomas and pregnancy-associated breast cancer (30.7-48.3%. OCT4 was expressed in the epithelium and at lower levels in the stroma, and was co-localized with NANOG. Comparison of normal non-tumorigenic hBSCs with OCT4-overexpressing tumorigenic breast cell lines (OTBCs demonstrated upregulation of OCT4, SOX2 and NANOG in both systems, but OTBCs expressed OCT4 at significantly higher levels than SOX2 and NANOG. Similar to hBSCs, OTBCs displayed multi-lineage differentiation potential, including the ability to differentiate into functional lactocytes synthesizing milk proteins both in vitro and in vivo. Based on these findings, we propose a hypothesis of normal and malignant transformation in the breast, which centers on OCT4 and its associated gene network. Although minimal expression of these embryonic genes can be seen in the breast in its resting state throughout life, a controlled program of upregulation of this gene network may be a potential regulator of the

  15. A novel SALL4/OCT4 transcriptional feedback network for pluripotency of embryonic stem cells.

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    Jianchang Yang

    Full Text Available BACKGROUND: SALL4 is a member of the SALL gene family that encodes a group of putative developmental transcription factors. Murine Sall4 plays a critical role in maintaining embryonic stem cell (ES cell pluripotency and self-renewal. We have shown that Sall4 activates Oct4 and is a master regulator in murine ES cells. Other SALL gene members, especially Sall1 and Sall3 are expressed in both murine and human ES cells, and deletions of these two genes in mice lead to perinatal death due to developmental defects. To date, little is known about the molecular mechanisms controlling the regulation of expressions of SALL4 or other SALL gene family members. METHODOLOGY/PRINCIPAL FINDINGS: This report describes a novel SALL4/OCT4 regulator feedback loop in ES cells in balancing the proper expression dosage of SALL4 and OCT4 for the maintenance of ESC stem cell properties. While we have observed that a positive feedback relationship is present between SALL4 and OCT4, the strong self-repression of SALL4 seems to be the "break" for this loop. In addition, we have shown that SALL4 can repress the promoters of other SALL family members, such as SALL1 and SALL3, which competes with the activation of these two genes by OCT4. CONCLUSIONS/SIGNIFICANCE: Our findings, when taken together, indicate that SALL4 is a master regulator that controls its own expression and the expression of OCT4. SALL4 and OCT4 work antagonistically to balance the expressions of other SALL gene family members. This novel SALL4/OCT4 transcription regulation feedback loop should provide more insight into the mechanism of governing the "stemness" of ES cells.

  16. Dental pulp stem cells differentiation reveals new insights in Oct4A dynamics.

    Directory of Open Access Journals (Sweden)

    Federico Ferro

    Full Text Available Although the role played by the core transcription factor network, which includes c-Myc, Klf4, Nanog, and Oct4, in the maintenance of embryonic stem cell (ES pluripotency and in the reprogramming of adult cells is well established, its persistence and function in adult stem cells are still debated. To verify its persistence and clarify the role played by these molecules in adult stem cell function, we investigated the expression pattern of embryonic and adult stem cell markers in undifferentiated and fully differentiated dental pulp stem cells (DPSC. A particular attention was devoted to the expression pattern and intracellular localization of the stemness-associated isoform A of Oct4 (Oct4A. Our data demonstrate that: Oct4, Nanog, Klf4 and c-Myc are expressed in adult stem cells and, with the exception of c-Myc, they are significantly down-regulated following differentiation. Cell differentiation was also associated with a significant reduction in the fraction of DPSC expressing the stem cell markers CD10, CD29 and CD117. Moreover, a nuclear to cytoplasm shuttling of Oct4A was identified in differentiated cells, which was associated with Oct4A phosphorylation. The present study would highlight the importance of the post-translational modifications in DPSC stemness maintenance, by which stem cells balance self-renewal versus differentiation. Understanding and controlling these mechanisms may be of great importance for stemness maintenance and stem cells clinical use, as well as for cancer research.

  17. Dissecting the role of distinct OCT4-SOX2 heterodimer configurations in pluripotency

    Science.gov (United States)

    Tapia, Natalia; MacCarthy, Caitlin; Esch, Daniel; Gabriele Marthaler, Adele; Tiemann, Ulf; Araúzo-Bravo, Marcos J.; Jauch, Ralf; Cojocaru, Vlad; Schöler, Hans R.

    2015-01-01

    The transcription factors OCT4 and SOX2 are required for generating induced pluripotent stem cells (iPSCs) and for maintaining embryonic stem cells (ESCs). OCT4 and SOX2 associate and bind to DNA in different configurations depending on the arrangement of their individual DNA binding elements. Here we have investigated the role of the different OCT4-SOX2-DNA assemblies in regulating and inducing pluripotency. To this end, we have generated SOX2 mutants that interfere with specific OCT4-SOX2 heterodimer configurations and assessed their ability to generate iPSCs and to rescue ESC self-renewal. Our results demonstrate that the OCT4-SOX2 configuration that dimerizes on a Hoxb1-like composite, a canonical element with juxtaposed individual binding sites, plays a more critical role in the induction and maintenance of pluripotency than any other OCT4-SOX2 configuration. Overall, the results of this study provide new insight into the protein interactions required to establish a de novo pluripotent network and to maintain a true pluripotent cell fate. PMID:26314899

  18. Coalition of Oct4A and β1 integrins in facilitating metastasis in ovarian cancer

    International Nuclear Information System (INIS)

    Samardzija, Chantel; Luwor, Rodney B.; Quinn, Michael A.; Kannourakis, George; Findlay, Jock K.; Ahmed, Nuzhat

    2016-01-01

    Ovarian cancer is a metastatic disease and one of the leading causes of gynaecology malignancy-related deaths in women. Cancer stem cells (CSCs) are key contributors of cancer metastasis and relapse. Integrins are a family of cell surface receptors which allow interactions between cells and their surrounding microenvironment and play a fundamental role in promoting metastasis. This study investigates the molecular mechanism which associates CSCs and integrins in ovarian cancer metastasis. The expression of Oct4A in high-grade serous ovarian tumors and normal ovaries was determined by immunofluorescence analysis. The functional role of Oct4A was evaluated by generating stable knockdown (KD) of Oct4A clones in an established ovarian cancer cell line HEY using shRNA-mediated silencing. The expression of integrins in cell lines was evaluated by flow cytometry. Spheroid forming ability, adhesion and the activities of matrix metalloproteinases 9/2 (MMP-9/2) was measured by in vitro functional assays and gelatin zymography. These observations were further validated in in vivo mouse models using Balb/c nu/nu mice. We report significantly elevated expression of Oct4A in high-grade serous ovarian tumors compared to normal ovarian tissues. The expression of Oct4A in ovarian cancer cell lines correlated with their CSC-related sphere forming abilities. The suppression of Oct4A in HEY cells resulted in a significant diminution of integrin β1 expression and associated α5 and α2 subunits compared to vector control cells. This was associated with a reduced adhesive ability on collagen and fibronectin and decreased secretion of pro-MMP2 in Oct4A KD cells compared to vector control cells. In vivo, Oct4A knock down (KD) cells produced tumors which were significantly smaller in size and weight compared to tumors derived from vector control cells. Immunohistochemical analyses of Oct4A KD tumor xenografts demonstrated a significant loss of cytokeratin 7 (CK7), Glut-1 as well as CD34

  19. O-GlcNAc transferase regulates transcriptional activity of human Oct4.

    Science.gov (United States)

    Constable, Sandii; Lim, Jae-Min; Vaidyanathan, Krithika; Wells, Lance

    2017-10-01

    O-linked β-N-acetylglucosamine (O-GlcNAc) is a single sugar modification found on many different classes of nuclear and cytoplasmic proteins. Addition of this modification, by the enzyme O-linked N-acetylglucosamine transferase (OGT), is dynamic and inducible. One major class of proteins modified by O-GlcNAc is transcription factors. O-GlcNAc regulates transcription factor properties through a variety of different mechanisms including localization, stability and transcriptional activation. Maintenance of embryonic stem (ES) cell pluripotency requires tight regulation of several key transcription factors, many of which are modified by O-GlcNAc. Octamer-binding protein 4 (Oct4) is one of the key transcription factors required for pluripotency of ES cells and more recently, the generation of induced pluripotent stem (iPS) cells. The action of Oct4 is modulated by the addition of several post-translational modifications, including O-GlcNAc. Previous studies in mice found a single site of O-GlcNAc addition responsible for transcriptional regulation. This study was designed to determine if this mechanism is conserved in humans. We mapped 10 novel sites of O-GlcNAc attachment on human Oct4, and confirmed a role for OGT in transcriptional activation of Oct4 at a site distinct from that found in mouse that allows distinction between different Oct4 target promoters. Additionally, we uncovered a potential new role for OGT that does not include its catalytic function. These results confirm that human Oct4 activity is being regulated by OGT by a mechanism that is distinct from mouse Oct4. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. OCT4 expression in outgrowth colonies derived from porcine inner cell masses and epiblasts

    DEFF Research Database (Denmark)

    Rasmussen, M A; Wolf, X A; Schauser, K

    2011-01-01

    on the relationship between OCT4 expression and embryonic stem cell (ESC)-like morphology. A total of 104 zona pellucida-enclosed and 101 hatched blastocysts were subjected to four different methods of ICM and epiblast isolation, respectively: Manual isolation, immunosurgery, immunosurgery with manual cleaning......, or whole blastocyst culture. OCs were established on mouse embryonic fibroblast (MEF) cells and categorized according to morphology and OCT4 staining. Although all isolation methods resulted in ESC-like OCs, immunosurgery with manual cleaning yielded significantly higher rates of ICM/epiblast attachment...

  1. Establishment of a rabbit Oct4 promoter-based EGFP reporter system.

    Directory of Open Access Journals (Sweden)

    Longquan Quan

    Full Text Available Rabbits are commonly used as laboratory animal models to investigate human diseases and phylogenetic development. However, pluripotent stem cells that contribute to germline transmission have yet to be established in rabbits. The transcription factor Oct4, also known as Pou5f1, is considered essential for the maintenance of the pluripotency of stem cells. Hence, pluripotent cells can be identified by monitoring Oct4 expression using a well-established Oct4 promoter-based reporter system. This study developed a rabbit Oct4 promoter-based enhanced green fluorescent protein (EGFP reporter system by transfecting pROP2-EGFP into rabbit fetal fibroblasts (RFFs. The transgenic RFFs were used as donor cells for somatic cell nuclear transfer (SCNT. The EGFP expression was detected in the blastocysts and genital ridges of SCNT fetuses. Fibroblasts and neural stem cells (NSCs were derived from the SCNT fetuses. EGFP was also reactivated in blastocysts after the second SCNT, and induced pluripotent stem cells (iPSCs were obtained after reprogramming using Yamanaka's factors. The results above indicated that a rabbit reporter system used to monitor the differentiating status of cells was successfully developed.

  2. Estrogen-related receptor beta interacts with Oct4 to positively regulate Nanog gene expression

    NARCIS (Netherlands)

    D.L.C. van den Berg (Debbie); W. Zhang (Wensheng); A. Yates (Adam); M.P. Engelen (Erik); K. Takacs (Katalin); K. Bezstarosti (Karel); J.A.A. Demmers (Jeroen); I. Chambers (Ian); R.A. Poor (Raymond)

    2008-01-01

    textabstractEmbryonic stem (ES) cell self-renewal is regulated by transcription factors, including Oct4, Sox2, and Nanog. A number of additional transcriptional regulators of ES cell self-renewal have recently been identified, including the orphan nuclear receptor estrogen-related receptor beta

  3. An Oct4-Centered Protein Interaction Network in Embryonic Stem Cells

    NARCIS (Netherlands)

    D.L.C. van den Berg (Debbie); T. Snoek (Tim); N.P. Mullin (Nick); A. Yates (Adam); K. Bezstarosti (Karel); J.A.A. Demmers (Jeroen); I. Chambers (Ian); R.A. Poot (Raymond)

    2010-01-01

    textabstractTranscription factors, such as Oct4, are critical for establishing and maintaining pluripotent cell identity. Whereas the genomic locations of several pluripotency transcription factors have been reported, the spectrum of their interaction partners is underexplored. Here, we use an

  4. Confinement and clearance of OCT4 in the porcine embryo at stereomicroscopically defined stages around gastrulation

    DEFF Research Database (Denmark)

    Vejlsted, Morten; Offenberg, Hanne Kjær; Thorup, Flemming

    2006-01-01

    was selectively observed in the epiblast. A prominent crescent-shaped thickening at the posterior region of the embryonic disk marked the first polarization within this structure reflecting incipient cell ingression. Following differentiation of the epiblast, clearance of OCT4 from the three germ layers......In the areas of developmental biology and embryonic stem cell research, reliable molecular markers of pluripotency and early lineage commitment are sparse in large animal species. In this study, we present morphological and immunohistochemical findings on the porcine embryo in the period around...... gastrulation, days 8-17 postinsemination, introducing a steromicroscopical staging system in this species. In embryos at the expanding hatched blastocyst stage, OCT4 is confined to the inner cell mass. Following detachment of the hypoblast, and formation of the embryonic disk, this marker of pluripotency...

  5. OCT4 and downstream factors are expressed in human somatic urogenital epithelia and in culture of epididymal spheres

    DEFF Research Database (Denmark)

    Audouze, Karine Marie Laure; Brunak, Søren; Kristensen, DM

    2010-01-01

    and microdissected tissues, in situ hybridisation, immunohistochemistry, and Western blotting to show that OCT4 and SOX2 together with downstream targets, UTF1 and REX1, are expressed in the human male urogenital tract. We further supported these results by analysis of DNA methylation of a region in the OCT4...

  6. Scalable topographies to support proliferation and Oct4 expression by human induced pluripotent stem cells.

    Science.gov (United States)

    Reimer, Andreas; Vasilevich, Aliaksei; Hulshof, Frits; Viswanathan, Priyalakshmi; van Blitterswijk, Clemens A; de Boer, Jan; Watt, Fiona M

    2016-01-13

    It is well established that topographical features modulate cell behaviour, including cell morphology, proliferation and differentiation. To define the effects of topography on human induced pluripotent stem cells (iPSC), we plated cells on a topographical library containing over 1000 different features in medium lacking animal products (xeno-free). Using high content imaging, we determined the effect of each topography on cell proliferation and expression of the pluripotency marker Oct4 24 h after seeding. Features that maintained Oct4 expression also supported proliferation and cell-cell adhesion at 24 h, and by 4 days colonies of Oct4-positive, Sox2-positive cells had formed. Computational analysis revealed that small feature size was the most important determinant of pluripotency, followed by high wave number and high feature density. Using this information we correctly predicted whether any given topography within our library would support the pluripotent state at 24 h. This approach not only facilitates the design of substrates for optimal human iPSC expansion, but also, potentially, identification of topographies with other desirable characteristics, such as promoting differentiation.

  7. Genome editing reveals a role for OCT4 in human embryogenesis.

    Science.gov (United States)

    Fogarty, Norah M E; McCarthy, Afshan; Snijders, Kirsten E; Powell, Benjamin E; Kubikova, Nada; Blakeley, Paul; Lea, Rebecca; Elder, Kay; Wamaitha, Sissy E; Kim, Daesik; Maciulyte, Valdone; Kleinjung, Jens; Kim, Jin-Soo; Wells, Dagan; Vallier, Ludovic; Bertero, Alessandro; Turner, James M A; Niakan, Kathy K

    2017-10-05

    Despite their fundamental biological and clinical importance, the molecular mechanisms that regulate the first cell fate decisions in the human embryo are not well understood. Here we use CRISPR-Cas9-mediated genome editing to investigate the function of the pluripotency transcription factor OCT4 during human embryogenesis. We identified an efficient OCT4-targeting guide RNA using an inducible human embryonic stem cell-based system and microinjection of mouse zygotes. Using these refined methods, we efficiently and specifically targeted the gene encoding OCT4 (POU5F1) in diploid human zygotes and found that blastocyst development was compromised. Transcriptomics analysis revealed that, in POU5F1-null cells, gene expression was downregulated not only for extra-embryonic trophectoderm genes, such as CDX2, but also for regulators of the pluripotent epiblast, including NANOG. By contrast, Pou5f1-null mouse embryos maintained the expression of orthologous genes, and blastocyst development was established, but maintenance was compromised. We conclude that CRISPR-Cas9-mediated genome editing is a powerful method for investigating gene function in the context of human development.

  8. Tryptophan derivatives regulate the transcription of Oct4 in stem-like cancer cells.

    Science.gov (United States)

    Cheng, Jie; Li, Wenxin; Kang, Bo; Zhou, Yanwen; Song, Jiasheng; Dan, Songsong; Yang, Ying; Zhang, Xiaoqian; Li, Jingchao; Yin, Shengyong; Cao, Hongcui; Yao, Hangping; Zhu, Chenggang; Yi, Wen; Zhao, Qingwei; Xu, Xiaowei; Zheng, Min; Zheng, Shusen; Li, Lanjuan; Shen, Binghui; Wang, Ying-Jie

    2015-06-10

    The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that responds to environmental toxicants, is increasingly recognized as a key player in embryogenesis and tumorigenesis. Here we show that a variety of tryptophan derivatives that act as endogenous AhR ligands can affect the transcription level of the master pluripotency factor Oct4. Among them, ITE enhances the binding of the AhR to the promoter of Oct4 and suppresses its transcription. Reduction of endogenous ITE levels in cancer cells by tryptophan deprivation or hypoxia leads to Oct4 elevation, which can be reverted by administration with synthetic ITE. Consequently, synthetic ITE induces the differentiation of stem-like cancer cells and reduces their tumorigenic potential in both subcutaneous and orthotopic xenograft tumour models. Thus, our results reveal a role of tryptophan derivatives and the AhR signalling pathway in regulating cancer cell stemness and open a new therapeutic avenue to target stem-like cancer cells.

  9. Expression of OCT4A: The First Step to the Next Stage of Urothelial Bladder Cancer Progression

    Directory of Open Access Journals (Sweden)

    Wojciech Jóźwicki

    2014-09-01

    Full Text Available OCT4 (octamer-binding transcription factor is a transcription factor responsible for maintaining the pluripotent properties of embryonic stem cells. In this paper, we present the results of studies to investigate the role of the OCT4 splicing variant in urothelial bladder cancer and the relationship between the OCT4 phenotype and the morphological parameters of tumor malignancy. Ninety patients who received a cystectomy for bladder cancer were enrolled. The expression of OCT4 protein was analyzed by immunohistochemistry. The ratio of OCT4-positive cells was the lowest in pT1 (pathological assessment (p—tumor extent confined to mucosa (T1 tumors and the highest in pTis (non-papillary tumor extent confined to urothelium and pT2 (tumor extent including muscularis propria tumors. Information about the percentage of OCT4A-positive tumor cells could facilitate choosing the treatment mode in borderline pTis–pT1 (crossing the border of the basement membrane; the first stage of progression and pT1–pT2 (crossing the border of the muscularis propria; the second stage of progression cases: a higher percentage of OCT4A-positive cells should support more radical therapy. A significantly higher percentage of cases with moderate OCT4 intensity was found in metastasizing (the third stage of progression cases with >2 positive lymph nodes. The percentage of OCT4-positive cells was significantly higher for cancers with a high grade, higher non-classic differentiation number and greater aggressiveness of invasion. The differentiation, maturation and aggressiveness of tumor invasion appear to depend on the expression of the OCT4 phenotype in cancer cells, similar to the successive stages of malignancy progression in urothelial cancer.

  10. Heat shock instructs hESCs to exit from the self-renewal program through negative regulation of OCT4 by SAPK/JNK and HSF1 pathway.

    Science.gov (United States)

    Byun, Kyunghee; Kim, Taek-Kyun; Oh, Jeehyun; Bayarsaikhan, Enkhjargal; Kim, Daesik; Lee, Min Young; Pack, Chan-Gi; Hwang, Daehee; Lee, Bonghee

    2013-11-01

    Environmental factors affect self-renewal of stem cells by modulating the components of self-renewal networks. Heat shock, an environmental factor, induces heat shock factors (HSFs), which up-regulate stress response-related genes. However, the link of heat shock to self-renewal of stem cells has not been elucidated yet. Here, we present the direct link of heat shock to a core stem cell regulator, OCT4, in the self-renewal network through SAPK/JNK and HSF1 pathway. We first showed that heat shock initiated differentiation of human embryonic stem cells (hESCs). Gene expression analysis revealed that heat shock increased the expression of many genes involved in cellular processes related to differentiation of stem cells. We then examined the effects of HSFs induced by heat shock on core self-renewal factors. Among HSFs, heat shock induced mainly HSF1 in hESCs. The HSF1 repressed the expression of OCT4, leading to the differentiation of hESCs and the above differentiation-related gene expression change. We further examined the effects of the upstream MAP (mitogen-activated protein) kinases of HSF1 on the repression of OCT4 expression by HSF1. Among the MAP kinases, SAPK/JNK controlled predominantly the repression of the OCT4 expression by HSF1. The direct link of heat shock to the core self-renewal regulator through SAPK/JNK and HSF1 provides a fundamental basis for understanding the effect of heat and other stresses involving activation of HSF1 on the self-renewal program and further controlling differentiation of hESCs in a broad spectrum of stem cell applications using these stresses. © 2013.

  11. Study on the relationship of abnormal transcription factors OCT4, HBP1 and Snail expression with progression of osteosarcoma

    Directory of Open Access Journals (Sweden)

    Li Li

    2016-09-01

    Full Text Available Objective: To study the relationship of abnormal transcription factors OCT4, HBP1 and Snail expression with progression of osteosarcoma. Methods: Surgical removed osteosarcoma tissue specimens were selected as pathology group, surgically removed osteoid osteoma specimens were selected as control group, and the expression levels of gene transcription factors OCT4, HBP1 and Snail, proliferation genes, epithelial-mesenchymal transition marker molecules in tissue specimens were determined. Results: Oct4 and Snail protein levels of pathology group were significantly higher than those of control group and HBP1 protein level was significantly lower than that of control group; C-myc and cyclinD1 protein levels of pathology group were significantly higher than those of control group, positively correlated with OCT4 and negatively correlated with HBP1; p16 and p53 protein levels were significantly lower than those of control group, negatively correlated with OCT4 and positively correlated with HBP1; N-cadherin and Vimentin protein levels of pathology group were significantly higher than those of control group and positively correlated with Snail while E-cadherin and Occludin protein levels were significantly lower than those of control group and negatively correlated with Snail. Conclusion: Oct4 and Snail are highly expressed and HBP1 is lowly expressed in osteosarcoma tissue, Oct4 and Snail can participate in the regulation of cell proliferation, and HBP1 can participate in the regulation of epithelial-mesenchymal transition of cells.

  12. MiR-145 regulates epithelial to mesenchymal transition of breast cancer cells by targeting Oct4.

    Directory of Open Access Journals (Sweden)

    Jiajia Hu

    Full Text Available MiR-145 could regulate tumor growth, apoptosis, migration, and invasion. In our present study, we investigated its role in epithelial-mesenchymal transition (EMT. Expression of miR-145 was decreased in breast tumor tissues at T3&4 stages in comparison with those at T1&2. Over-expression of miR-145 mimics enhanced protein levels of E-cadherin and dampened those of α-SMA and Fibronectin, indicative of its inhibitory role in EMT occurrence. Mechanistic studies showed that miR-145 mimics inhibited Oct4 expression and miR-145 inhibitor enhanced it. Over-expression of Oct4 reversed miR-145-regulated expression of EMT markers, suggesting that Oct4 mediated the inhibitory effects of miR-145. MiR-145 could inhibite the expression of Snail, ZEB1, and ZEB2, while over-expression of Oct4 rescued the effects. Furthermore, Oct-4 induced over-expression of transcription factor Snail, ZEB1 and ZEB2 was mediated by β-catenin. Expression of Slug and Twist were not altered by miR-145/Oct4. Taken together, our results have revealed a novel role of miR-145 on EMT. It inhibits EMT by blocking the expression of Oct4, and downstream transcriptional factors, Snail, ZEB1 and ZEB2.

  13. Recruitment of Oct4 protein to UV-damaged chromatin in embryonic stem cells

    Czech Academy of Sciences Publication Activity Database

    Bártová, Eva; Šustáčková, Gabriela; Stixová, Lenka; Kozubek, Stanislav; Legartová, Soňa; Foltánková, Veronika

    2011-01-01

    Roč. 6, č. 12 (2011), e27281 E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) LC535; GA MŠk(CZ) LC06027; GA MŠk(CZ) ME 919; GA ČR(CZ) GAP302/10/1022; GA MŠk(CZ) LD11020 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : embryonic stem cells * epigenetics * Oct4 Subject RIV: BO - Biophysics Impact factor: 4.092, year: 2011

  14. Transdifferentiation of Human Hair Follicle Mesenchymal Stem Cells into Red Blood Cells by OCT4

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    Zhijing Liu

    2015-01-01

    Full Text Available Shortage of red blood cells (RBCs, erythrocytes can have potentially life-threatening consequences for rare or unusual blood type patients with massive blood loss resulting from various conditions. Erythrocytes have been derived from human pluripotent stem cells (PSCs, but the risk of potential tumorigenicity cannot be ignored, and a majority of these cells produced from PSCs express embryonic ε- and fetal γ-globins with little or no adult β-globin and remain nucleated. Here we report a method to generate erythrocytes from human hair follicle mesenchymal stem cells (hHFMSCs by enforcing OCT4 gene expression and cytokine stimulation. Cells generated from hHFMSCs expressed mainly the adult β-globin chain with minimum level of the fetal γ-globin chain. Furthermore, these cells also underwent multiple maturation events and formed enucleated erythrocytes with a biconcave disc shape. Gene expression analyses showed that OCT4 regulated the expression of genes associated with both pluripotency and erythroid development during hHFMSC transdifferentiation toward erythroid cells. These findings show that mature erythrocytes can be generated from adult somatic cells, which may serve as an alternative source of RBCs for potential autologous transfusion.

  15. Down-regulation of HSP40 gene family following OCT4B1 suppression in human tumor cell lines

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    Mohammad Reza Mirzaei

    2016-02-01

    Full Text Available Objective(s: The OCT4B1, as one of OCT4 variants, is expressed in cancer cell lines and tissues more than other variants and plays an important role in apoptosis and stress (heat shock protein pathways. The present study was designed to determine the effects of OCT4B1 silencing on expressional profile of HSP40 gene family expression in three different human tumor cell lines. Materials and Methods: The OCT4B1 expression was suppressed by specific siRNA transfection in AGS (gastric adenocarcinoma, 5637 (bladder tumor and U-87MG (brain tumor cell lines employing Lipofectamine reagent. Real-time PCR array technique was employed for RNA qualification. The fold changes were calculated using RT2 Profiler PCR array data analysis software version 3.5. Results: Our results indicated that fifteen genes (from 36 studied genes were down-regulated and two genes (DNAJC11 and DNAJC5B were up-regulated in all three studied tumor cell lines by approximately more than two folds. The result of other studied genes (19 genes showed different expressional pattern (up or down-expression based on tumor cell lines. Conclusion: According to the findings of the present study, we may suggest that there is a direct correlation between OCT4B1 expression in tumor cell lines (and tissues and HSP40 family gene expressions to escape from apoptosis and cancer expansion.

  16. XPC Promotes Pluripotency of Human Dental Pulp Cells through Regulation of Oct-4/Sox2/c-Myc

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    Lu Liu

    2016-01-01

    Full Text Available Introduction. Xeroderma pigmentosum group C (XPC, essential component of multisubunit stem cell coactivator complex (SCC, functions as the critical factor modulating pluripotency and genome integrity through interaction with Oct-4/Sox2. However, its specific role in regulating pluripotency and multilineage differentiation of human dental pulp cells (DPCs remains unknown. Methods. To elucidate the functional role XPC played in pluripotency and multilineage differentiation of DPCs, expressions of XPC in DPCs with long-term culture were examined by real-time PCR and western blot. DPCs were transfected with lentiviral-mediated human XPC gene; then transfection rate was investigated by real-time PCR and western blot. Cell cycle, apoptosis, proliferation, senescence, multilineage differentiation, and expression of Oct-4/Sox2/c-Myc in transfected DPCs were examined. Results. XPC, Oct-4, Sox2, and c-Myc were downregulated at P7 compared with P3 in DPCs with long-term culture. XPC genes were upregulated in DPCs at P2 after transfection and maintained high expression level at P3 and P7. Cell proliferation, PI value, and telomerase activity were enhanced, whereas apoptosis was suppressed in transfected DPCs. Oct-4/Sox2/c-Myc were significantly upregulated, and multilineage differentiation in DPCs with XPC overexpression was enhanced after transfection. Conclusions. XPC plays an essential role in the modulation of pluripotency and multilineage differentiation of DPCs through regulation of Oct-4/Sox2/c-Myc.

  17. XPC Promotes Pluripotency of Human Dental Pulp Cells through Regulation of Oct-4/Sox2/c-Myc.

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    Liu, Lu; Peng, Zhengjun; Xu, Zhezhen; Wei, Xi

    2016-01-01

    Introduction. Xeroderma pigmentosum group C (XPC), essential component of multisubunit stem cell coactivator complex (SCC), functions as the critical factor modulating pluripotency and genome integrity through interaction with Oct-4/Sox2. However, its specific role in regulating pluripotency and multilineage differentiation of human dental pulp cells (DPCs) remains unknown. Methods. To elucidate the functional role XPC played in pluripotency and multilineage differentiation of DPCs, expressions of XPC in DPCs with long-term culture were examined by real-time PCR and western blot. DPCs were transfected with lentiviral-mediated human XPC gene; then transfection rate was investigated by real-time PCR and western blot. Cell cycle, apoptosis, proliferation, senescence, multilineage differentiation, and expression of Oct-4/Sox2/c-Myc in transfected DPCs were examined. Results. XPC, Oct-4, Sox2, and c-Myc were downregulated at P7 compared with P3 in DPCs with long-term culture. XPC genes were upregulated in DPCs at P2 after transfection and maintained high expression level at P3 and P7. Cell proliferation, PI value, and telomerase activity were enhanced, whereas apoptosis was suppressed in transfected DPCs. Oct-4/Sox2/c-Myc were significantly upregulated, and multilineage differentiation in DPCs with XPC overexpression was enhanced after transfection. Conclusions. XPC plays an essential role in the modulation of pluripotency and multilineage differentiation of DPCs through regulation of Oct-4/Sox2/c-Myc.

  18. Mass spectrometry for identification of proteins that specifically bind to a distal enhancer of the Oct4 gene

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    Bakhmet, E. I.; Nazarov, I. B.; Artamonova, T. O.; Khodorkovsky, M. A.; Tomilin, A. N.

    2017-11-01

    Transcription factor Oct4 is a marker of pluripotent stem cells and has a significant role in their self-renewal. Oct4 gene is controlled by three cis-regulatory elements - proximal promoter, proximal enhancer and distal enhancer. All of these elements are targets for binding of regulatory proteins. Distal enhancer is in our research focus because of its activity in early stages of embryonic development. There are two main sequences called site 2A and site 2B that are presented in distal enhancer. For this moment proteins which bind to a site 2A (CCCCTCCCCCC) remain unknown. Using combination of in vitro method electrophoretic mobility shift assay (EMSA) and mass spectromery we identified several candidates that can regulate Oct4 gene expression through site 2A.

  19. Direct activation of human and mouse Oct4 genes using engineered TALE and Cas9 transcription factors.

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    Hu, Jiabiao; Lei, Yong; Wong, Wing-Ki; Liu, Senquan; Lee, Kai-Chuen; He, Xiangjun; You, Wenxing; Zhou, Rui; Guo, Jun-Tao; Chen, Xiongfong; Peng, Xianlu; Sun, Hao; Huang, He; Zhao, Hui; Feng, Bo

    2014-04-01

    The newly developed transcription activator-like effector protein (TALE) and clustered regularly interspaced short palindromic repeats/Cas9 transcription factors (TF) offered a powerful and precise approach for modulating gene expression. In this article, we systematically investigated the potential of these new tools in activating the stringently silenced pluripotency gene Oct4 (Pou5f1) in mouse and human somatic cells. First, with a number of TALEs and sgRNAs targeting various regions in the mouse and human Oct4 promoters, we found that the most efficient TALE-VP64s bound around -120 to -80 bp, while highly effective sgRNAs targeted from -147 to -89-bp upstream of the transcription start sites to induce high activity of luciferase reporters. In addition, we observed significant transcriptional synergy when multiple TFs were applied simultaneously. Although individual TFs exhibited marginal activity to up-regulate endogenous gene expression, optimized combinations of TALE-VP64s could enhance endogenous Oct4 transcription up to 30-fold in mouse NIH3T3 cells and 20-fold in human HEK293T cells. More importantly, the enhancement of OCT4 transcription ultimately generated OCT4 proteins. Furthermore, examination of different epigenetic modifiers showed that histone acetyltransferase p300 could enhance both TALE-VP64 and sgRNA/dCas9-VP64 induced transcription of endogenous OCT4. Taken together, our study suggested that engineered TALE-TF and dCas9-TF are useful tools for modulating gene expression in mammalian cells.

  20. Curcumin Effect on the Expressional Profile of OCT4, Nanog and Nucleostemin Genes in AGS (Adenocarcinoma Cancer Cell Line

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    Fahmideh Bagrezaei

    2016-07-01

    Full Text Available Background Curcumin is the natural yellow pigment in turmeric isolated from the rhizome of the plant Curcuma longa. Curcumin inhibits formation and invasive cancer cells and destroys cancer cells resistant to chemotherapeutic drugs. Objectives The purpose of this study was the survey of effects of different concentrations of alcoholic curcumin on the octamer-binding transcription factor 4 (OCT4 Nanog and Nucleostemin genes in the AGS (human gastric adenocarcinoma cell line. Materials and Methods In this experimental study the AGS cell line was cultured in RPMI-1640, supplemented with penicillin/streptomycin (100 U/mL and 100 mg/mL, respectively and 10% fetal bovine serum, at 37°C in a humidified atmosphere of 5% CO2. In 60 - 70% cell confluence, the cells were treated with curcumin concentration (20, 40, 100 μL and incubated for 24, 48 and 72 hours. Finally, total RNA were extracted and cDNA were synthesized and the expression of mentioned genes was detected. The data were analyzed by excel software. Results Expression rate of OCT4A, OCT4B, Nanog and Nucleostemin (GLN3 at concentrations less than 20 μg/mL were reduced but OCT4B1 expression showed increased by hours respectively. Conclusions The results showed that curcumin inhibited cell division; also, this study could be the basis for more extensive studies on the anti-cancer effect of the combined plants.

  1. Transient exposure to proteins SOX2, Oct-4, and NANOG immortalizes exhausted tumor-infiltrating CTLs

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    Bhadurihauck, Anjuli; Li, Lei [Department of Animal and Avian Sciences, University of Maryland, College Park, 20742, MD (United States); Li, Qianqian; Wang, Jianjun [Department of Biochemistry and Molecular Biology, Wayne State University, Detroit, 48201 (United States); Xiao, Zhengguo, E-mail: xiao0028@umd.edu [Department of Animal and Avian Sciences, University of Maryland, College Park, 20742, MD (United States)

    2016-05-13

    Adoptive cell transfer therapy (ACT) is one of the most promising immunotherapies against cancer, using tumor-infiltrating lymphocytes (TILs) expanded in vitro. Tumor-infiltrating cytotoxic T lymphocytes (TICTLs) play a prominent role in cancer control. TILs terminally differentiate in response to immunosuppressive environments within tumors, and thus are slow to expand and challenging to maintain both in vitro and in patients. To reverse this exhaustion, we utilize a nuclear protein delivery system that exposes TICTLs to the SOX2, Oct-4, and NANOG (SON) proteins. Unlike activated naïve CTLs (effector CTLs), TICTLs respond favorably to SON treatment, exhibiting steady proliferation and extended survivability independent of cytokine and antigen stimulation. Though TICTLs treated with SON (STICTLs) still express T cell receptors as well as other critical downstream components, they are unresponsive to antigen challenge, suggesting that SON treatment regresses TICTLs into a state similar to that of an early double negative T cell. Our findings indicate the TICTL response to SON proteins is unique when compared to effector CTLs, suggesting TICTLs may be sensitive to regulation by other lineage-specific transcription factors and opening a promising new avenue into cancer immunotherapy. To our knowledge, this is the first report on lineage reprogramming of TILs using protein stem cell transcription factors delivered directly to the nucleus. -- Highlights: •TICTLs are sensitive to reprogramming by proteins of stem cell transcription factors, but effector CTLs were not. •TICTLs are regressed back to an early double negative T cell stage. •TCR signaling is deregulated by these transcription factors.

  2. Quiescent Oct4+ Neural Stem Cells (NSCs) Repopulate Ablated Glial Fibrillary Acidic Protein+ NSCs in the Adult Mouse Brain.

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    Reeve, Rachel L; Yammine, Samantha Z; Morshead, Cindi M; van der Kooy, Derek

    2017-09-01

    Adult primitive neural stem cells (pNSCs) are a rare population of glial fibrillary acidic protein (GFAP) - Oct4 + cells in the mouse forebrain subependymal zone bordering the lateral ventricles that give rise to clonal neurospheres in leukemia inhibitory factor in vitro. pNSC neurospheres can be passaged to self-renew or give rise to GFAP + NSCs that form neurospheres in epidermal growth factor and fibroblast growth factor 2, which we collectively refer to as definitive NSCs (dNSCs). Label retention experiments using doxycycline-inducible histone-2B (H2B)-green fluorescent protein (GFP) mice and several chase periods of up to 1 year quantified the adult pNSC cell cycle time as 3-5 months. We hypothesized that while pNSCs are not very proliferative at baseline, they may exist as a reserve pool of NSCs in case of injury. To test this function of pNSCs, we obtained conditional Oct4 knockout mice, Oct4 fl/fl ;Sox1 Cre (Oct4 CKO ), which do not yield adult pNSC-derived neurospheres. When we ablated the progeny of pNSCs, namely all GFAP + dNSCs, in these Oct4 CKO mice, we found that dNSCs did not recover as they do in wild-type mice, suggesting that pNSCs are necessary for dNSC repopulation. Returning to the H2B-GFP mice, we observed that the cytosine β-d-arabinofuranoside ablation of proliferating cells including dNSCs-induced quiescent pNSCs to proliferate and significantly dilute their H2B-GFP label. In conclusion, we demonstrate that pNSCs are the most quiescent stem cells in the adult brain reported to date and that their lineage position upstream of GFAP + dNSCs allows them to repopulate a depleted neural lineage. Stem Cells 2017;35:2071-2082. © 2017 AlphaMed Press.

  3. Correlation of HIF-2α, ABCG2 and OCT-4 with chemotherapy resistance in human gastric cancer

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    Hong-mei ZHANG

    2015-11-01

    Full Text Available Objective To investigate the correlation of HIF-2α, ABCG2 and OCT-4 with chemotherapy resistant gastric cancer in humans. Methods Fifty-two patients who were confirmed to have advanced gastric cancer with the aid of electronic endoscopy and pathology in the Department of Gastroenterology, Affiliated Hospital of Weifang Medical College, were enrolled in the study. According to the effect of FOL-FOX4 chemotherapy that these patients had experienced, they were divided into three groups: CR+PR (complete remission+partial remission group, SD (stable disease group and PD (progressive disease group. The expression levels of HIF-2α, ABCG2, and OCT-4 mRNA and protein were assessed in different groups by using RT-PCR and immunocytochemistry. Results Two patients achieved CR , 19 achieved PR , 25 showed SD, and 6 showed PD. In other words, CR+PR were seen in 21 patients (40.4%, SD in 25(48.1%, PD in 6(11.5%. In CR+PR group, the expression levels of HIF-2α, ABCG2 and OCT4 mRNA and protein were low, but the above mentioned expressions were significantly increased in SD group and PD group. The expression levels of HIF-2α, ABCG2 and Oct-4 mRNA and protein were highest in the PD group, lower in the SD group, and lowest in the CR + PR groups (all P<0.05. Conclusions The expression of the markers HIF-2α, ABCG2 and OCT4 in human tumor tissues is related to the effect of chemotherapy for gastric cancer. A high expression of tumor markers is perhaps the main reason for low efficacy of chemotherapy due to drug resistance. DOI: 10.11855/j.issn.0577-7402.2015.10.09

  4. Association of differential β-catenin expression with Oct-4 and Nanog in oral squamous cell carcinoma and their correlation with clinicopathological factors and prognosis.

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    Ravindran, Gokulan; Sawant, Sharada S; Hague, Angela; Kingsley, Karl; Devaraj, Halagowder

    2015-07-01

    The re-expression of pluripotent markers (Oct-4 and Nanog) and the reactivation of stem cell-related pathways in oral carcinoma have been well researched. However, the relationship between the stem cell signaling molecule β-catenin and pluripotent markers Oct-4 and Nanog in oral cancer is yet to be studied in detail. Therefore, we have investigated the correlation among Oct-4, Nanog, and β-catenin in oral squamous cell carcinoma, which, in turn, could provide valuable insight into its prognostic significance. The immunohistochemical analysis was performed for 60 cases of oral cancer to study the expression pattern of Oct-4, Nanog, and β-catenin. Whereas immunofluorescence analysis was used to investigate the co-localization of β-catenin with Oct-4 and Nanog in oral carcinoma tissues and H314 cell line. Finally, co-immunoprecipitation analysis was used to study the possible interaction between β-catenin and Oct-4 in oral carcinoma cells. β-catenin, Oct-4, and Nanog showed significant correlation with lymph node metastasis, stage, grade, and prognosis in oral squamous cell carcinoma. Interestingly, a significant positive correlation was found among the expression of Oct-4, Nanog, and β-catenin. Moreover, the interaction between β-catenin and Oct-4 was observed in oral cancer. The positive correlation among Oct-4, Nanog, and β-catenin suggests their coordinated role in maintaining proliferation in oral carcinoma cells. The interaction between β-catenin and Oct-4 may be a crucial event in oral carcinogenesis. On the other hand, β-catenin, Oct-4, and Nanog could be used as independent prognostic markers of oral squamous cell carcinoma. © 2014 Wiley Periodicals, Inc.

  5. Nuclear delivery of recombinant OCT4 by chitosan nanoparticles for transgene-free generation of protein-induced pluripotent stem cells.

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    Tammam, Salma; Malak, Peter; Correa, Daphne; Rothfuss, Oliver; Azzazy, Hassan M E; Lamprecht, Alf; Schulze-Osthoff, Klaus

    2016-06-21

    Protein-based reprogramming of somatic cells is a non-genetic approach for the generation of induced pluripotent stem cells (iPSCs), whereby reprogramming factors, such as OCT4, SOX2, KLF4 and c-MYC, are delivered as functional proteins. The technique is considered safer than transgenic methods, but, unfortunately, most protein-based protocols provide very low reprogramming efficiencies. In this study, we developed exemplarily a nanoparticle (NP)-based delivery system for the reprogramming factor OCT4. To this end, we expressed human OCT4 in Sf9 insect cells using a baculoviral expression system. Recombinant OCT4 showed nuclear localization in Sf9 cells indicating proper protein folding. In comparison to soluble OCT4 protein, encapsulation of OCT4 in nuclear-targeted chitosan NPs strongly stabilized its DNA-binding activity even under cell culture conditions. OCT4-loaded NPs enabled cell treatment with high micromolar concentrations of OCT4 and successfully delivered active OCT4 into human fibroblasts. Chitosan NPs therefore provide a promising tool for the generation of transgene-free iPSCs.

  6. Single-cell duplex RT-LATE-PCR reveals Oct4 and Xist RNA gradients in 8-cell embryos

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    Hartung Odelya

    2007-12-01

    Full Text Available Abstract Background The formation of two distinctive cell lineages in preimplantation mouse embryos is characterized by differential gene expression. The cells of the inner cell mass are pluripotent and express high levels of Oct4 mRNA, which is down-regulated in the surrounding trophectoderm. In contrast, the trophectoderm of female embryos contains Xist mRNA, which is absent from cells of the inner mass. Prior to blastocyst formation, all blastomeres of female embryos still express both of these RNAs. We, thus, postulated that simultaneous quantification of Oct4 and Xist transcripts in individual blastomeres at the 8-cell stage could be informative as to their subsequent fate. Testing this hypothesis, however, presented numerous technical challenges. We overcame these difficulties by combining PurAmp, a single-tube method for RNA preparation and quantification, with LATE-PCR, an advanced form of asymmetric PCR. Results We constructed a duplex RT-LATE-PCR assay for real-time measurement of Oct4 and Xist templates and confirmed its specificity and quantitative accuracy with different methods. We then undertook analysis of sets of blastomeres isolated from embryos at the 8-cell stage. At this stage, all cells in the embryo are still pluripotent and morphologically equivalent. Our results demonstrate, however, that both Oct4 and Xist RNA levels vary in individual blastomeres comprising the same embryo, with some cells having particularly elevated levels of either transcript. Analysis of multiple embryos also shows that Xist and Oct4 expression levels are not correlated at the 8-cell stage, although transcription of both genes is up-regulated at this time in development. In addition, comparison of data from males and females allowed us to determine that the efficiency of the Oct4/Xist assay is unaffected by sex-related differences in gene expression. Conclusion This paper describes the first example of multiplex RT-LATE-PCR and its utility, when

  7. Expression of early transcription factors Oct-4, Sox-2 and Nanog by porcine umbilical cord (PUC matrix cells

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    Schultz Bruce

    2006-02-01

    Full Text Available Abstract Background Three transcription factors that are expressed at high levels in embryonic stem cells (ESCs are Nanog, Oct-4 and Sox-2. These transcription factors regulate the expression of other genes during development and are found at high levels in the pluripotent cells of the inner cell mass. The downregulation of these three transcription factors correlates with the loss of pluripotency and self-renewal, and the beginning of subsequent differentiation steps. The roles of Nanog, Oct-4 and Sox-2 have not been fully elucidated. They are important in embryonic development and maintenance of pluripotency in ESCs. We studied the expression of these transcription factors in porcine umbilical cord (PUC matrix cells. Methods Cells were isolated from Wharton's jelly of porcine umbilical cords (PUC and histochemically assayed for the presence of alkaline phosphatase and the presence of Nanog, Oct-4 and Sox-2 mRNA and protein. PCR amplicons were sequenced and compared with known sequences. The synthesis of Oct-4 and Nanog protein was analyzed using immunocytochemistry. FACS analysis was utilized to evaluate Hoechst 33342 dye-stained cells. Results PUC isolates were maintained in culture and formed colonies that express alkaline phosphatase. FACS analysis revealed a side population of Hoechst dye-excluding cells, the Hoechst exclusion was verapamil sensitive. Quantitative and non-quantitative RT-PCR reactions revealed expression of Nanog, Oct-4 and Sox-2 in day 15 embryonic discs, PUC cell isolates and porcine fibroblasts. Immunocytochemical analysis detected Nanog immunoreactivity in PUC cell nuclei, and faint labeling in fibroblasts. Oct-4 immunoreactivity was detected in the nuclei of some PUC cells, but not in fibroblasts. Conclusion Cells isolated from PUC express three transcription factors found in pluripotent stem cell markers both at the mRNA and protein level. The presence of these transcription factors, along with the other

  8. Human Ocular Epithelial Cells Endogenously Expressing SOX2 and OCT4 Yield High Efficiency of Pluripotency Reprogramming.

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    Ming-Wai Poon

    Full Text Available A variety of pluripotency reprogramming frequencies from different somatic cells has been observed, indicating cell origin is a critical contributor for efficiency of pluripotency reprogramming. Identifying the cell sources for efficient induced pluripotent stem cells (iPSCs generation, and defining its advantages or disadvantages on reprogramming, is therefore important. Human ocular tissue-derived conjunctival epithelial cells (OECs exhibited endogenous expression of reprogramming factors OCT4A (the specific OCT 4 isoform on pluripotency reprogramming and SOX2. We therefore determined whether OECs could be used for high efficiency of iPSCs generation. We compared the endogenous expression levels of four pluripotency factors and the pluripotency reprograming efficiency of human OECs with that of ocular stromal cells (OSCs. Real-time PCR, microarray analysis, Western blotting and immunostaining assays were employed to compare OECiPSCs with OSCiPSCs on molecular bases of reprogramming efficiency and preferred lineage-differentiation potential. Using the traditional KMOS (KLF4, C-MYC, OCT4 and SOX2 reprogramming protocol, we confirmed that OECs, endogenously expressing reprogramming factors OCT4A and SOX2, yield very high efficiency of iPSCs generation (~1.5%. Furthermore, higher efficiency of retinal pigmented epithelial differentiation (RPE cells was observed in OECiPSCs compared to OSCiPSCs or skin fibroblast iMR90iPSCs. The findings in this study suggest that conjunctival-derived epithelial (OECs cells can be easier converted to iPSCs than conjunctival-derived stromal cells (OSCs. This cell type may also have advantages in retinal pigmented epithelial differentiation.

  9. Human Ocular Epithelial Cells Endogenously Expressing SOX2 and OCT4 Yield High Efficiency of Pluripotency Reprogramming.

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    Poon, Ming-Wai; He, Jia; Fang, Xiaowei; Zhang, Zhao; Wang, Weixin; Wang, Junwen; Qiu, Fangfang; Tse, Hung-Fat; Li, Wei; Liu, Zuguo; Lian, Qizhou

    2015-01-01

    A variety of pluripotency reprogramming frequencies from different somatic cells has been observed, indicating cell origin is a critical contributor for efficiency of pluripotency reprogramming. Identifying the cell sources for efficient induced pluripotent stem cells (iPSCs) generation, and defining its advantages or disadvantages on reprogramming, is therefore important. Human ocular tissue-derived conjunctival epithelial cells (OECs) exhibited endogenous expression of reprogramming factors OCT4A (the specific OCT 4 isoform on pluripotency reprogramming) and SOX2. We therefore determined whether OECs could be used for high efficiency of iPSCs generation. We compared the endogenous expression levels of four pluripotency factors and the pluripotency reprograming efficiency of human OECs with that of ocular stromal cells (OSCs). Real-time PCR, microarray analysis, Western blotting and immunostaining assays were employed to compare OECiPSCs with OSCiPSCs on molecular bases of reprogramming efficiency and preferred lineage-differentiation potential. Using the traditional KMOS (KLF4, C-MYC, OCT4 and SOX2) reprogramming protocol, we confirmed that OECs, endogenously expressing reprogramming factors OCT4A and SOX2, yield very high efficiency of iPSCs generation (~1.5%). Furthermore, higher efficiency of retinal pigmented epithelial differentiation (RPE cells) was observed in OECiPSCs compared to OSCiPSCs or skin fibroblast iMR90iPSCs. The findings in this study suggest that conjunctival-derived epithelial (OECs) cells can be easier converted to iPSCs than conjunctival-derived stromal cells (OSCs). This cell type may also have advantages in retinal pigmented epithelial differentiation.

  10. OCT4A contributes to the stemness and multi-potency of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs)

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    Seo, Kwang-Won; Lee, Sae-Rom; Bhandari, Dilli Ram; Roh, Kyoung-Hwan; Park, Sang-Bum; So, Ah-Young; Jung, Ji-Won; Seo, Min-Soo [Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University 151-742, Seoul (Korea, Republic of); Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine, and BK21 Program for Veterinary Science, Seoul National University 151-742, Seoul (Korea, Republic of); Kang, Soo-Kyung [Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University 151-742, Seoul (Korea, Republic of); Laboratory of Biotechnology, College of Veterinary Medicine, and BK21 Program for Veterinary Science, Seoul National University 151-742, Seoul (Korea, Republic of); Lee, Yong-Soon [Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University 151-742, Seoul (Korea, Republic of); Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine, and BK21 Program for Veterinary Science, Seoul National University 151-742, Seoul (Korea, Republic of); Kang, Kyung-Sun, E-mail: kangpub@snu.ac.kr [Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University 151-742, Seoul (Korea, Republic of); Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine, and BK21 Program for Veterinary Science, Seoul National University 151-742, Seoul (Korea, Republic of)

    2009-06-19

    The OCT4A gene, a POU homeodomain transcription factor, has been shown to be expressed in embryonic stem cells (ESC) as well as hUCB-MSCs. In this study, the roles played by OCT4A in hUCB-MSCs were determined by stably inhibiting OCT4A with lenti-viral vector-based small hairpin RNA (shRNA). A decreased rate of cell proliferation was observed in OCT4-inhibited hUCB-MSCs. Down-regulation of CCNA2 expression in OCT4-inhibited hUCB-MSCs was confirmed by RT-PCR and real-time RT-PCR analysis in three genetically independent hUCB-MSC clones. Adipogenic differentiation was also suppressed in OCT4-inhibited hUCB-MSCs. The up-regulation of DTX1 and down-regulation of HDAC1, 2, and 4 expressions may be related to this differentiation deformity. The expression of other transcription factors, including SOX2, REX1 and c-MYC, was also affected by OCT4 inhibition in hUCB-MSCs. In conclusion, these finding suggest that OCT4A performs functionally conserved roles in hUCB-MSCs, making its expression biologically important for ex vivo culture of hUCB-MSCs.

  11. OCT4A contributes to the stemness and multi-potency of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs)

    International Nuclear Information System (INIS)

    Seo, Kwang-Won; Lee, Sae-Rom; Bhandari, Dilli Ram; Roh, Kyoung-Hwan; Park, Sang-Bum; So, Ah-Young; Jung, Ji-Won; Seo, Min-Soo; Kang, Soo-Kyung; Lee, Yong-Soon; Kang, Kyung-Sun

    2009-01-01

    The OCT4A gene, a POU homeodomain transcription factor, has been shown to be expressed in embryonic stem cells (ESC) as well as hUCB-MSCs. In this study, the roles played by OCT4A in hUCB-MSCs were determined by stably inhibiting OCT4A with lenti-viral vector-based small hairpin RNA (shRNA). A decreased rate of cell proliferation was observed in OCT4-inhibited hUCB-MSCs. Down-regulation of CCNA2 expression in OCT4-inhibited hUCB-MSCs was confirmed by RT-PCR and real-time RT-PCR analysis in three genetically independent hUCB-MSC clones. Adipogenic differentiation was also suppressed in OCT4-inhibited hUCB-MSCs. The up-regulation of DTX1 and down-regulation of HDAC1, 2, and 4 expressions may be related to this differentiation deformity. The expression of other transcription factors, including SOX2, REX1 and c-MYC, was also affected by OCT4 inhibition in hUCB-MSCs. In conclusion, these finding suggest that OCT4A performs functionally conserved roles in hUCB-MSCs, making its expression biologically important for ex vivo culture of hUCB-MSCs.

  12. Conversion of Sox17 into a pluripotency reprogramming factor by reengineering its association with Oct4 on DNA.

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    Jauch, Ralf; Aksoy, Irene; Hutchins, Andrew Paul; Ng, Calista Keow Leng; Tian, Xian Feng; Chen, Jiaxuan; Palasingam, Paaventhan; Robson, Paul; Stanton, Lawrence W; Kolatkar, Prasanna R

    2011-06-01

    Very few proteins are capable to induce pluripotent stem (iPS) cells and their biochemical uniqueness remains unexplained. For example, Sox2 cooperates with other transcription factors to generate iPS cells, but Sox17, despite binding to similar DNA sequences, cannot. Here, we show that Sox2 and Sox17 exhibit inverse heterodimerization preferences with Oct4 on the canonical versus a newly identified compressed sox/oct motif. We can swap the cooperativity profiles of Sox2 and Sox17 by exchanging single amino acids at the Oct4 interaction interface resulting in Sox2KE and Sox17EK proteins. The reengineered Sox17EK now promotes reprogramming of somatic cells to iPS, whereas Sox2KE has lost this potential. Consistently, when Sox2KE is overexpressed in embryonic stem cells it forces endoderm differentiation similar to wild-type Sox17. Together, we demonstrate that strategic point mutations that facilitate Sox/Oct4 dimer formation on variant DNA motifs lead to a dramatic swap of the bioactivities of Sox2 and Sox17. Copyright © 2011 AlphaMed Press.

  13. Immunohistochemical analysis of the role and relationship between Notch-1 and Oct-4 expression in urinary bladder carcinoma.

    Science.gov (United States)

    Abdou, Asmaa Gaber; El-Wahed, Moshira Mohammed Abd; Kandil, Mona Abd-Elhalim; Samaka, Rehab Monir; Elkady, Noha

    2013-10-01

    Most tumors contain a minor population of cancer stem cells that are responsible for tumor heterogeneity, resistance to therapy and recurrence. Oct-4 is a transcription factor responsible for self-renewal of stem cells, whereas the Notch family of receptors and ligands may play a pivotal role in the regulation of stem cell maintenance and differentiation. This study aimed at an evaluation of Oct-4 and Notch-1 expression in both carcinoma and stromal cells of 83 cases of primary bladder carcinoma and to study the relationship between them. Notch-1 was expressed in carcinoma and stromal cells of all malignant cases, where expression in both cell types was correlated with parameters indicating differentiation, such as low grade (p bladder carcinoma, such as poor differentiation (p = 0.001), high proliferation (p bladder carcinoma, where they may cooperate in the progression of bladder carcinoma by acquiring aggressive features, such as a liability for recurrence and dissemination. Notch-1 is also expressed in both carcinoma cells and stromal cells of bladder carcinoma. Although they could share in enhancing differentiation, stromal expression of Notch-1 may have a bad impact, possibly through up-regulation of the active nuclear form of Oct-4 in carcinoma cells. © 2013 APMIS Published by Blackwell Publishing Ltd.

  14. Comparison of Oct4, Sox2 and Nanog Expression in Pancreatic Cancer Cell Lines and Human Pancreatic Tumor

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    Vahideh Assadollahi

    2015-12-01

    Full Text Available Background: Genes are involved in the control of stem cell self-renewal as a new class of molecular markers of cancer. Objectives: In this study, the expression of Oct4, Nanog and Sox2 in cell lines MIA Paca-2, PA-TU-8902 and AsPC-1 and pancreatic cancer tissue were examined. Materials and Methods: In this experimental study, cell lines, MIA Paca-2, PA-TU-8902 and AsPC-1, were cultured in DMEM (Dulbecco’s Modified Eagles Medium and RPMI-1640 (Roswell Park Memorial Institute containing FBS 10% (fetal bovine serum in a 37°C incubator containing Co2 5% and humidity 90%. Samples of tumor and non-cancer pancreatic tumor were purchased Iran tumor bank. Extraction of RNA and synthesis of cDNA was performed. Expression levels of Oct4, Nanog and Sox2 were determined using Real-time PCR. The protein expression levels of target genes in the cell lines were studied by flow cytometry and immunocytochemistry. Results: The expression rate of Oct4, Nanog and Sox2 is more in the cancer cell lines than those in the control (normal tissue samples. The protein expression levels of target genes in the cell lines were confirmed by flow cytometry and immunocytochemistry. Conclusions: The genes are involved in stem cell self-renewal as a new class of molecular markers of cancer that detected in the pancreatic cell lines. Maybe, these genes play important role in the uncontrolled proliferation of cancer cells.

  15. Manganese Superoxide Dismutase Gene Expression Is Induced by Nanog and Oct4, Essential Pluripotent Stem Cells’ Transcription Factors

    Science.gov (United States)

    Solari, Claudia; Vázquez Echegaray, Camila; Cosentino, María Soledad; Petrone, María Victoria; Waisman, Ariel; Luzzani, Carlos; Francia, Marcos; Villodre, Emilly; Lenz, Guido; Miriuka, Santiago; Barañao, Lino; Guberman, Alejandra

    2015-01-01

    Pluripotent stem cells possess complex systems that protect them from oxidative stress and ensure genomic stability, vital for their role in development. Even though it has been reported that antioxidant activity diminishes along stem cell differentiation, little is known about the transcriptional regulation of the involved genes. The reported modulation of some of these genes led us to hypothesize that some of them could be regulated by the transcription factors critical for self-renewal and pluripotency in embryonic stem cells (ESCs) and in induced pluripotent stem cells (iPSCs). In this work, we studied the expression profile of multiple genes involved in antioxidant defense systems in both ESCs and iPSCs. We found that Manganese superoxide dismutase gene (Mn-Sod/Sod2) was repressed during diverse differentiation protocols showing an expression pattern similar to Nanog gene. Moreover, Sod2 promoter activity was induced by Oct4 and Nanog when we performed a transactivation assay using two different reporter constructions. Finally, we studied Sod2 gene regulation by modulating the expression of Oct4 and Nanog in ESCs by shRNAs and found that downregulation of any of them reduced Sod2 expression. Our results indicate that pluripotency transcription factors positively modulate Sod2 gene transcription. PMID:26642061

  16. Chemotherapy-Induced Depletion of OCT4-Positive Cancer Stem Cells in a Mouse Model of Malignant Testicular Cancer.

    Science.gov (United States)

    Pierpont, Timothy M; Lyndaker, Amy M; Anderson, Claire M; Jin, Qiming; Moore, Elizabeth S; Roden, Jamie L; Braxton, Alicia; Bagepalli, Lina; Kataria, Nandita; Hu, Hilary Zhaoxu; Garness, Jason; Cook, Matthew S; Capel, Blanche; Schlafer, Donald H; Southard, Teresa; Weiss, Robert S

    2017-11-14

    Testicular germ cell tumors (TGCTs) are among the most responsive solid cancers to conventional chemotherapy. To elucidate the underlying mechanisms, we developed a mouse TGCT model featuring germ cell-specific Kras activation and Pten inactivation. The resulting mice developed malignant, metastatic TGCTs composed of teratoma and embryonal carcinoma, the latter of which exhibited stem cell characteristics, including expression of the pluripotency factor OCT4. Consistent with epidemiological data linking human testicular cancer risk to in utero exposures, embryonic germ cells were susceptible to malignant transformation, whereas adult germ cells underwent apoptosis in response to the same oncogenic events. Treatment of tumor-bearing mice with genotoxic chemotherapy not only prolonged survival and reduced tumor size but also selectively eliminated the OCT4-positive cancer stem cells. We conclude that the chemosensitivity of TGCTs derives from the sensitivity of their cancer stem cells to DNA-damaging chemotherapy. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  17. Chemotherapy-Induced Depletion of OCT4-Positive Cancer Stem Cells in a Mouse Model of Malignant Testicular Cancer

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    Timothy M. Pierpont

    2017-11-01

    Full Text Available Summary: Testicular germ cell tumors (TGCTs are among the most responsive solid cancers to conventional chemotherapy. To elucidate the underlying mechanisms, we developed a mouse TGCT model featuring germ cell-specific Kras activation and Pten inactivation. The resulting mice developed malignant, metastatic TGCTs composed of teratoma and embryonal carcinoma, the latter of which exhibited stem cell characteristics, including expression of the pluripotency factor OCT4. Consistent with epidemiological data linking human testicular cancer risk to in utero exposures, embryonic germ cells were susceptible to malignant transformation, whereas adult germ cells underwent apoptosis in response to the same oncogenic events. Treatment of tumor-bearing mice with genotoxic chemotherapy not only prolonged survival and reduced tumor size but also selectively eliminated the OCT4-positive cancer stem cells. We conclude that the chemosensitivity of TGCTs derives from the sensitivity of their cancer stem cells to DNA-damaging chemotherapy. : Using a mouse testicular germ cell tumor model, Pierpont et al. establish that male germ cells are susceptible to malignant transformation during a restricted window of embryonic development. The cancer stem cells of the resulting testicular cancers demonstrate genotoxin hypersensitivity, rendering these malignancies highly responsive to conventional chemotherapy. Keywords: testicular germ cell tumor, TGCT, cancer stem cells, CSCs, chemotherapy, embryonal carcinoma, EC, DNA damage response, DDR

  18. Are Mesenchymal Cells Indeed Pluripotent Stem Cells or Just Stromal Cells? OCT-4 and VSELs Biology Has Led to Better Understanding

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    Deepa Bhartiya

    2013-01-01

    Full Text Available Stem cells have excited researchers because of their potential to regenerate. However, which stem cells will be the best candidate for regenerative medicine remains an enigma. Compared to pluripotent stem cells with associated risks of immune rejection and teratoma formation, adult stem cells especially the mesenchymal stem cells (MSCs are hyped to be a suitable alternate since they also exhibit pluripotent properties. This review shows that there is a subpopulation of pluripotent very small embryonic-like stem cells (VSELs among MSCs culture. The two populations differ from each other in expression pattern of OCT-4. VSELs exhibit nuclear OCT-4A, whereas the MSCs have cytoplasmic OCT-4B, similar to our earlier findings in testis and ovary. Pluripotent VSELs with nuclear OCT-4A exist in various adult body organs, and the immediate progenitors express cytoplasmic OCT-4B which is eventually lost as the cell differentiates further. To conclude it is essential to discriminate between nuclear and cytoplasmic OCT-4 expression and also to acknowledge the presence of VSELs.

  19. SOX2 and OCT4 mRNA-expressing cells, detected by molecular beacons, localize to the center of neurospheres during differentiation.

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    Mirolyuba Ilieva

    Full Text Available Neurospheres are used as in vitro assay to measure the properties of neural stem cells. To investigate the molecular and phenotypic heterogeneity of neurospheres, molecular beacons (MBs targeted against the stem cell markers OCT4 and SOX2 were designed, and synthesized with a 2'-O-methyl RNA backbone. OCT4 and SOX2 MBs were transfected into human embryonic mesencephalon derived cells, which spontaneously form neurospheres when grown on poly-L-ornitine/fibronectin matrix and medium complemented with bFGF. OCT4 and SOX2 gene expression were tracked in individual cell using the MBs. Quantitative image analysis every day for seven days showed that the OCT4 and SOX2 mRNA-expressing cells clustered in the centre of the neurospheres cultured in differentiation medium. By contrast, cells at the periphery of the differentiating spheres developed neurite outgrowths and expressed the tyrosine hydroxylase protein, indicating terminal differentiation. Neurospheres cultured in growth medium contained OCT4 and SOX2-positive cells distributed throughout the entire sphere, and no differentiating neurones. Gene expression of SOX2 and OCT4 mRNA detected by MBs correlated well with gene and protein expression measured by qRT-PCR and immunostaining, respectively. These experimental data support the theoretical model that stem cells cluster in the centre of neurospheres, and demonstrate the use of MBs for the spatial localization of specific gene-expressing cells within heterogeneous cell populations.

  20. VIH from the mud crab is specifically expressed in the eyestalk and potentially regulated by transactivator of Sox9/Oct4/Oct1.

    Science.gov (United States)

    Liu, Chunyun; Jia, Xiwei; Zou, Zhihua; Wang, Xiaowei; Wang, Yilei; Zhang, Ziping

    2018-01-01

    Vitellogenesis-inhibiting hormone (VIH) is known to regulate ovarian maturation by suppressing the synthesis of vitellogenin (Vtg) in crustaceans, which belongs to a member of crustacean hyperglycemic hormone (CHH) family synthesized and secreted from the X-organ/sinus gland complex of eyestalks. In this study, the cDNA, genomic DNA (gDNA) and the 5'-upstream regulatory (promoter region) sequences of VIH gene were obtained by conventional PCR, genome walker and tail-PCR techniques according to our transcriptomic database of Scylla paramamosain. The full-length cDNA of SpVIH is 634bp including 105bp 5'UTR, 151bp 3'UTR and 378bp ORF that encodes a peptide of 125 amino acids. The full length gDNA of SpVIH is 790bp containing two exons and one intron. The 5'-flanking promoter regions of SpVIH we isolated are 3070bp from the translation initiation (ATG) and 2398bp from the predicted transcription initiation (A), which consists of putative core promoter region and multiple potential transcription factor binding sites. SpVIH was only expressed in eyestalk. The expression level of SpVIH in eyestalk of female crab decreased gradually along with the development of ovary. As there is not cell line of crabs available, we chose the mature transfection system HEK293FT cell lines to explore the mechanism of transcription regulation of SpVIH in crabs. Sequential deletion assays using luciferase reporter gene in HEK293FT cells revealed that the possible promoter activity regions (including positive and negative transcription factors binding sites simultaneously) presented between pSpVIH-4 and pSpVIH-6. In order to further identify the crucial transcription factors binding site in this region, the site-directed mutagenesis of Sox9/Oct4/Oct1 binding site of pSpVIH-4 was created. The results demonstrated that the transcriptional activity of pSpVIH-4△ decreased significantly (p<0.05). Thus, it is reasonable to deduce that the Sox9/Oct4/Oct1 may be the essential positive transcription

  1. The effect of steroid hormones on the mRNA expression of oct4 and sox2 in uterine tissue of the ovariectomized mice model of menopause

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    Marzieh Davoudi

    2016-07-01

    Full Text Available Background: The uterus is a dynamic tissue responding to hormonal changes during reproductive cycles. As such, uterine stem cells have been studied in recent years. Transcription factors oct4 and sox2 are critical for effective maintenance of pluripotent cell identity. Objective: The present research evaluated the mRNA expression of oct4 and sox2 in the uterine tissues of ovariectomized mice treated with steroid hormones. Materials and Methods: In this experimental study, adult virgin female mice were ovariectomized and treated with estradiol 17β (E2, progesterone (P4, and a combination of E2 and P4 (E2 & P4 for 5 days. Uterine tissues were removed, and immunofluorescent (IF staining and quantitative real-time PCR of oct4 and sox2 markers were performed. Results: IF showed oct4 and sox2 expression in the uterine endometrium and myometrium among all groups. The mRNA expression of oct4 (p=0.022 and sox2 (p=0.042 in the E2-treated group significantly were decreased compared to that in the control group. By contrast, the mRNA expression of oct4 and sox2 in the P4 (p=0.641 and 0.489 respectively and E2 & P4-treated groups (p=0.267 and 0.264 respectively did not show significant differences compared to the control group. Conclusion: The results indicate ovarian steroid hormones change the expression of oct4 and sox2 in the mice uterine tissues, which suggest the involvement of steroid hormonal regulation in uterine stem cells.

  2. Enhanced expression of the stemness-related factors OCT4, SOX15 and TWIST1 in ectopic endometrium of endometriosis patients

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    Katharina Proestling

    2016-11-01

    Full Text Available Abstract Background Current evidence suggests that endometrial-derived stem cells, spilled in the peritoneal cavity via retrograde menstruation, are key players in the establishment of endometriotic lesions. The aim of this study was to determine the presence and distribution of the stemness-related factors OCT4, SOX15, TWIST1 and DCAMLK1 in women with and without endometriosis. Methods Immunohistochemical analysis was used to determine stromal and epithelial expression of OCT4, SOX15, TWIST1 and DCAMLK1 in endometriosis patient (EP endometrium (n = 69 and endometriotic tissue (n = 90 and in control endometrium (n = 50. Quantitative Real-Time PCR of OCT4, SOX15 TWIST1 and DCAMLK1 was performed in paired samples of EP endometrium and endometriotic tissue. Co-immunofluorescence staining was performed for OCT4 and SOX15. For statistical analyses we used unpaired t-test, Fisher combination test and Spearman test. For paired analyses, paired t-test and McNemar test were used. Results We detected a significant correlation between the expression of the established stem cell marker OCT4 and the stemness-related markers SOX15 (p < 0.001 and TWIST1 (p = 0.002 but not DCAMLK1. We showed a colocalization of SOX15 and OCT4 in epithelial and stromal cells of endometriotic tissue by coimmunofluorescence. A concordant expression of OCT4 and SOX15 in the same sample was observed in epithelial cells of the endometriotic tissue (71.7%. The expression of stemness-related factors was not associated with proliferative or secretory phase of the menstrual cycle in endometriosis patients but was found to be differentially expressed during the menstrual cycle in the control group. Increased expression of epithelial OCT4, SOX15 and TWIST1 was detected in endometriotic tissue compared to EP endometrium in paired (p = 0.021, p < 0.001 and p < 0.001 and unpaired analysis (p = 0.040, p < 0.001 and p = 0.001. Conclusion Our findings

  3. SOX2 and OCT4 mRNA-Expressing Cells, Detected by Molecular Beacons, Localize to the Center of Neurospheres during Differentiation

    DEFF Research Database (Denmark)

    Ilieva, Mirolyuba; Dufva, Martin

    2013-01-01

    Neurospheres are used as in vitro assay to measure the properties of neural stem cells. To investigate the molecular and phenotypic heterogeneity of neurospheres, molecular beacons (MBs) targeted against the stem cell markers OCT4 and SOX2 were designed, and synthesized with a 2'-O-methyl RNA...

  4. Oct4 Methylation-Mediated Silencing As an Epigenetic Barrier Preventing Müller Glia Dedifferentiation in a Murine Model of Retinal Injury.

    Science.gov (United States)

    Reyes-Aguirre, Luis I; Lamas, Monica

    2016-01-01

    Müller glia (MG) is the most abundant glial type in the vertebrate retina. Among its many functions, it is capable of responding to injury by dedifferentiating, proliferating, and differentiating into every cell types lost to damage. This regenerative ability is notoriously absent in mammals. We have previously reported that cultured mammalian MG undergoes a partial dedifferentiation, but fails to fully acquire a progenitor phenotype and differentiate into neurons. This might be explained by a mnemonic mechanism comprised by epigenetic traits, such as DNA methylation. To achieve a better understanding of this epigenetic memory, we studied the expression of pluripotency-associated genes, such as Oct4, Nanog , and Lin28 , which have been reported as necessary for regeneration in fish, at early times after NMDA-induced retinal injury in a mouse experimental model. We found that although Oct4 is expressed rapidly after damage (4 hpi), it is silenced at 24 hpi. This correlates with a significant decrease in the DNA methyltransferase Dnmt3b expression, which returns to basal levels at 24 hpi. By MS-PCR, we observed a decrease in Oct4 methylation levels at 4 and 12 hpi, before returning to a fully methylated state at 24 hpi. To demonstrate that these changes are restricted to MG, we separated these cells using a GLAST antibody coupled with magnetic beads. Finally, intravitreous administration of the DNA-methyltransferase inhibitor SGI-1027 induced Oct4 expression at 24 hpi in MG. Our results suggest that mammalian MG injury-induced dedifferentiation could be restricted by DNA methylation, which rapidly silences Oct4 expression, preventing multipotency acquisition.

  5. Differential expression of ID4 and its association with TP53 mutation, SOX2, SOX4 and OCT-4 expression levels.

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    Thais Fernanda de Almeida Galatro

    Full Text Available Inhibitor of DNA Binding 4 (ID4 is a member of the helix-loop-helix ID family of transcription factors, mostly present in the central nervous system during embryonic development, that has been associated with TP53 mutation and activation of SOX2. Along with other transcription factors, ID4 has been implicated in the tumorigenic process of astrocytomas, contributing to cell dedifferentiation, proliferation and chemoresistance. In this study, we aimed to characterize the ID4 expression pattern in human diffusely infiltrative astrocytomas of World Health Organization (WHO grades II to IV of malignancy (AGII-AGIV; to correlate its expression level to that of SOX2, SOX4, OCT-4 and NANOG, along with TP53 mutational status; and to correlate the results with the clinical end-point of overall survival among glioblastoma patients. Quantitative real time PCR (qRT-PCR was performed in 130 samples of astrocytomas for relative expression, showing up-regulation of all transcription factors in tumor cases. Positive correlation was found when comparing ID4 relative expression of infiltrative astrocytomas with SOX2 (r = 0.50; p<0.005, SOX4 (r = 0.43; p<0.005 and OCT-4 (r = 0.39; p<0.05. The results from TP53 coding exon analysis allowed comparisons between wild-type and mutated status only in AGII cases, demonstrating significantly higher levels of ID4, SOX2 and SOX4 in mutated cases (p<0.05. This pattern was maintained in secondary GBM and further confirmed by immunohistochemistry, suggesting a role for ID4, SOX2 and SOX4 in early astrocytoma tumorigenesis. Combined hyperexpression of ID4, SOX4 and OCT-4 conferred a much lower (6 months median survival than did hypoexpression (18 months. Because both ID4 alone and a complex of SOX4 and OCT-4 activate SOX2 transcription, it is possible that multiple activation of SOX2 impair the prognosis of GBM patients. These observational results of associated expression of ID4 with SOX4 and OCT-4 may be used as a

  6. Differentially expressed genes: OCT-4, SOX2, STAT3, CDH1 and CDH2, in cultured mesenchymal stem cells challenged with serum of women with endometriosis

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    Ehab Salama

    2018-06-01

    Full Text Available Endometriosis is a common chronic gynecological disorder defined as the presence of ectopic functional endometrial tissues, outside uterine cavity, primarily on the pelvic peritoneum and the ovaries. Several studies revealed a correlation between aberrant stem-cell activity in the endometrium and endometriosis. Yet the molecular and cellular behaviors of mesnchymal stem cells in development of endometriosis are hampered by lack of invitro experiments. Our aim was to explore morphological and molecular changes associated with mesenchymal stem cells (MSCs exposition to serum derived from women with severe endometriosis. Two cell cultures of MSCs isolated from endometrial tissues of two endometriosis-free women. Each cell culture was treated individually with the serum of women with endometriosis (experimental group/n = 7, and serum of women without endometriosis (control group/ n = 4 for 14 days. Quantitative Real-Time PCR was performed later to reveal expression of OCT-4, CDH1 and CDH2, STAT3 and SOX2 genes. Morphologically, cells showed no significant changes. However from molecular point of view, we found increased expression in OCT-4, CDH1 and CDH2. For STAT3 and SOX2 we did not find a significant difference. This study shows that endometriosis serum induced molecular changes in human endometrial MSCs (EnMSCs that might be related to altered cell behavior which may be a step in differentiation that may be completed invivo by other factors to complete the process of transition. Further researches are needed for optimization to reach differentiation. Keywords: Endometriosis, Mesnchymal stem cells, OCT-4, SOX2, STAT3, E-cadherin, N-cadherin

  7. YAP1 Regulates OCT4 Activity and SOX2 Expression to Facilitate Self-Renewal and Vascular Mimicry of Stem-Like Cells.

    Science.gov (United States)

    Bora-Singhal, Namrata; Nguyen, Jonathan; Schaal, Courtney; Perumal, Deepak; Singh, Sandeep; Coppola, Domenico; Chellappan, Srikumar

    2015-06-01

    Non-small cell lung cancer (NSCLC) is highly correlated with smoking and has very low survival rates. Multiple studies have shown that stem-like cells contribute to the genesis and progression of NSCLC. Our results show that the transcriptional coactivator yes-associated protein 1 (YAP1), which is the oncogenic component of the Hippo signaling pathway, is elevated in the stem-like cells from NSCLC and contributes to their self-renewal and ability to form angiogenic tubules. Inhibition of YAP1 by a small molecule or depletion of YAP1 by siRNAs suppressed self-renewal and vascular mimicry of stem-like cells. These effects of YAP1 were mediated through the embryonic stem cell transcription factor, Sox2. YAP1 could transcriptionally induce Sox2 through a physical interaction with Oct4; Sox2 induction occurred independent of TEAD2 transcription factor, which is the predominant mediator of YAP1 functions. The binding of Oct4 to YAP1 could be detected in cell lines as well as tumor tissues; the interaction was elevated in NSCLC samples compared to normal tissue as seen by proximity ligation assays. YAP1 bound to Oct4 through the WW domain, and a peptide corresponding to this region could disrupt the interaction. Delivery of the WW domain peptide to stem-like cells disrupted the interaction and abrogated Sox2 expression, self-renewal, and vascular mimicry. Depleting YAP1 reduced the expression of multiple epithelial-mesenchymal transition genes and prevented the growth and metastasis of tumor xenografts in mice; overexpression of Sox2 in YAP1 null cells rescued these functions. These results demonstrate a novel regulation of stem-like functions by YAP1, through the modulation of Sox2 expression. © 2015 AlphaMed Press.

  8. Craniopharyngiomas express embryonic stem cell markers (SOX2, OCT4, KLF4, and SOX9) as pituitary stem cells but do not coexpress RET/GFRA3 receptors.

    Science.gov (United States)

    Garcia-Lavandeira, Montserrat; Saez, Carmen; Diaz-Rodriguez, Esther; Perez-Romero, Sihara; Senra, Ana; Dieguez, Carlos; Japon, Miguel A; Alvarez, Clara V

    2012-01-01

    Adult stem cells maintain some markers expressed by embryonic stem cells and express other specific markers depending on the organ where they reside. Recently, stem/progenitor cells in the rodent and human pituitary have been characterized as expressing GFRA2/RET, PROP1, and stem cell markers such as SOX2 and OCT4 (GPS cells). Our objective was to detect other specific markers of the pituitary stem cells and to investigate whether craniopharyngiomas (CRF), a tumor potentially derived from Rathke's pouch remnants, express similar markers as normal pituitary stem cells. We conducted mRNA and Western blot studies in pituitary extracts, and immunohistochemistry and immunofluorescence on sections from normal rat and human pituitaries and 20 CRF (18 adamantinomatous and two papillary). Normal pituitary GPS stem cells localized in the marginal zone (MZ) express three key embryonic stem cell markers, SOX2, OCT4, and KLF4, in addition to SOX9 and PROP1 and β-catenin overexpression. They express the RET receptor and its GFRA2 coreceptor but also express the coreceptor GFRA3 that could be detected in the MZ of paraffin pituitary sections. CRF maintain the expression of SOX2, OCT4, KLF4, SOX9, and β-catenin. However, RET and GFRA3 expression was altered in CRF. In 25% (five of 20), both RET and GFRA3 were detected but not colocalized in the same cells. The other 75% (15 of 20) lose the expression of RET, GFRA3, or both proteins simultaneously. Human pituitary adult stem/progenitor cells (GPS) located in the MZ are characterized by expression of embryonic stem cell markers SOX2, OCT4, and KLF4 plus the specific pituitary embryonic factor PROP1 and the RET system. Redundancy in RET coreceptor expression (GFRA2 and GFRA3) suggest an important systematic function in their physiological behavior. CRF share the stem cell markers suggesting a common origin with GPS. However, the lack of expression of the RET/GFRA system could be related to the cell mislocation and deregulated

  9. Elimination of proliferating cells from CNS grafts using a Ki67 promoter-driven thymidine kinase

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    Vannary Tieng

    2016-01-01

    Full Text Available Pluripotent stem cell (PSC-based cell therapy is an attractive concept for neurodegenerative diseases, but can lead to tumor formation. This is particularly relevant as proliferating neural precursors rather than postmitotic mature neurons need to be transplanted. Thus, safety mechanisms to eliminate proliferating cells are needed. Here, we propose a suicide gene approach, based on cell cycle-dependent promoter Ki67-driven expression of herpes simplex virus thymidine kinase (HSV-TK. We generated a PSC line expressing this construct and induced neural differentiation. In vitro, proliferating PSC and early neural precursor cells (NPC were killed by exposure to ganciclovir. In vivo, transplantation of PSC led to tumor formation, which was prevented by early ganciclovir treatment. Transplanted NPC did not lead to tumor formation and their survival and neural maturation were not affected by ganciclovir. In conclusion, the cell cycle promoter-driven suicide gene approach described in this study allows killing of proliferating undifferentiated precursor cells without expression of the suicide gene in mature neurons. This approach could also be of use for other stem cell-based therapies where the final target consists of postmitotic cells.

  10. Dmp1 Promoter-Driven Diphtheria Toxin Receptor Transgene Expression Directs Unforeseen Effects in Multiple Tissues

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    Ahmed Al-Jazzar

    2016-12-01

    Full Text Available Mice harbouring a dentin matrix protein 1 (Dmp1 promoter-driven human diphtheria toxin (DT receptor (HDTR transgene (Tg have recently been used to attain targeted ablation of osteocytes by diphtheria toxin (DT treatment in order to define osteocyte function. Use of these Tg mice has asserted mechano- and novel paracrine regulatory osteocyte functions. To explore osteocyte roles fully, we sought to confirm the selectivity of DT effects in these transgenic mice. However, our findings revealed incomplete DT-induced osteocyte ablation, prevalent HDTR misexpression, as well as more prominent histopathological DT-induced changes in multiple organs in Tg than in wild-type (WT littermate mice. Mechanistic evidence for DT action, via prominent regulation of phosphorylation status of elongation factor-2 (EF-2, was also found in many non-skeletal tissues in Tg mice; indicative of direct “off-target” DT action. Finally, very rapid deterioration in health and welfare status in response to DT treatment was observed in these Tg when compared to WT control mice. Together, these data lead us to conclude that alternative models for osteocyte ablation should be sought and caution be exercised when drawing conclusions from experiments using these Tg mice alone.

  11. Over-expression of Oct4 and Sox2 transcription factors enhances differentiation of human umbilical cord blood cells in vivo

    International Nuclear Information System (INIS)

    Guseva, Daria; Rizvanov, Albert A.; Salafutdinov, Ilnur I.; Kudryashova, Nezhdana V.; Palotás, András; Islamov, Rustem R.

    2014-01-01

    Highlights: • Gene and cell-based therapies comprise innovative aspects of regenerative medicine. • Genetically modified hUCB-MCs enhanced differentiation of cells in a mouse model of ALS. • Stem cells successfully transformed into micro-glial and endothelial lines in spinal cords. • Over-expressing oct4 and sox2 also induced production of neural marker PGP9.5. • Formation of new nerve cells, secreting trophic factors and neo-vascularisation could improve symptoms in ALS. - Abstract: Gene and cell-based therapies comprise innovative aspects of regenerative medicine. Even though stem cells represent a highly potential therapeutic strategy, their wide-spread exploitation is marred by ethical concerns, potential for malignant transformation and a plethora of other technical issues, largely restricting their use to experimental studies. Utilizing genetically modified human umbilical cord blood mono-nuclear cells (hUCB-MCs), this communication reports enhanced differentiation of transplants in a mouse model of amyotrophic lateral sclerosis (ALS). Over-expressing Oct4 and Sox2 induced production of neural marker PGP9.5, as well as transformation of hUCB-MCs into micro-glial and endothelial lines in ALS spinal cords. In addition to producing new nerve cells, providing degenerated areas with trophic factors and neo-vascularisation might prevent and even reverse progressive loss of moto-neurons and skeletal muscle paralysis

  12. Over-expression of Oct4 and Sox2 transcription factors enhances differentiation of human umbilical cord blood cells in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Guseva, Daria [Kazan State Medical University, Kazan, Republic of Tatarstan (Russian Federation); Hannover Medical School, Hannover (Germany); Rizvanov, Albert A.; Salafutdinov, Ilnur I.; Kudryashova, Nezhdana V. [Kazan Federal University, Kazan, Republic of Tatarstan (Russian Federation); Palotás, András, E-mail: palotas@asklepios-med.eu [Kazan Federal University, Kazan, Republic of Tatarstan (Russian Federation); Asklepios-Med (Private Medical Practice and Research Center), Szeged (Hungary); Islamov, Rustem R., E-mail: islamru@yahoo.com [Kazan State Medical University, Kazan, Republic of Tatarstan (Russian Federation)

    2014-09-05

    Highlights: • Gene and cell-based therapies comprise innovative aspects of regenerative medicine. • Genetically modified hUCB-MCs enhanced differentiation of cells in a mouse model of ALS. • Stem cells successfully transformed into micro-glial and endothelial lines in spinal cords. • Over-expressing oct4 and sox2 also induced production of neural marker PGP9.5. • Formation of new nerve cells, secreting trophic factors and neo-vascularisation could improve symptoms in ALS. - Abstract: Gene and cell-based therapies comprise innovative aspects of regenerative medicine. Even though stem cells represent a highly potential therapeutic strategy, their wide-spread exploitation is marred by ethical concerns, potential for malignant transformation and a plethora of other technical issues, largely restricting their use to experimental studies. Utilizing genetically modified human umbilical cord blood mono-nuclear cells (hUCB-MCs), this communication reports enhanced differentiation of transplants in a mouse model of amyotrophic lateral sclerosis (ALS). Over-expressing Oct4 and Sox2 induced production of neural marker PGP9.5, as well as transformation of hUCB-MCs into micro-glial and endothelial lines in ALS spinal cords. In addition to producing new nerve cells, providing degenerated areas with trophic factors and neo-vascularisation might prevent and even reverse progressive loss of moto-neurons and skeletal muscle paralysis.

  13. Goat activin receptor type IIB knockdown by muscle specific promoter driven artificial microRNAs.

    Science.gov (United States)

    Patel, Amrutlal K; Shah, Ravi K; Patel, Utsav A; Tripathi, Ajai K; Joshi, Chaitanya G

    2014-10-10

    Activin receptor type IIB (ACVR2B) is a transmembrane receptor which mediates signaling of TGF beta superfamily ligands known to function in regulation of muscle mass, embryonic development and reproduction. ACVR2B antagonism has shown to enhance the muscle growth in several disease and transgenic models. Here, we show ACVR2B knockdown by RNA interference using muscle creatine kinase (MCK) promoter driven artificial microRNAs (amiRNAs). Among the various promoter elements tested, the ∼1.26 kb MCK promoter region showed maximum transcriptional activity in goat myoblasts cells. We observed up to 20% silencing in non-myogenic 293T cells and up to 32% silencing in myogenic goat myoblasts by MCK directed amiRNAs by transient transfection. Goat myoblasts stably integrated with MCK directed amiRNAs showed merely 8% silencing in proliferating myoblasts which was increased to 34% upon induction of differentiation at transcript level whereas up to 57% silencing at protein level. Knockdown of ACVR2B by 5'-UTR derived amiRNAs resulted in decreased SMAD2/3 signaling, increased expression of myogenic regulatory factors (MRFs) and enhanced proliferation and differentiation of myoblasts. Unexpectedly, knockdown of ACVR2B by 3'-UTR derived amiRNAs resulted in increased SMAD2/3 signaling, reduced expression of MRFs and suppression of myogenesis. Our study offers muscle specific knockdown of ACVR2B as a potential strategy to enhance muscle mass in the farm animal species. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Protein arginine methyltransferase 7-mediated microRNA-221 repression maintains Oct4, Nanog, and Sox2 levels in mouse embryonic stem cells.

    Science.gov (United States)

    Chen, Tsai-Yu; Lee, Sung-Hun; Dhar, Shilpa S; Lee, Min Gyu

    2018-03-16

    The stemness maintenance of embryonic stem cells (ESCs) requires pluripotency transcription factors, including Oct4, Nanog, and Sox2. We have previously reported that protein arginine methyltransferase 7 (PRMT7), an epigenetic modifier, is an essential pluripotency factor that maintains the stemness of mouse ESCs, at least in part, by down-regulating the expression of the anti-stemness microRNA (miRNA) miR-24-2. To gain greater insight into the molecular basis underlying PRMT7-mediated maintenance of mouse ESC stemness, we searched for new PRMT7-down-regulated anti-stemness miRNAs. Here, we show that miR-221 gene-encoded miR-221-3p and miR-221-5p are anti-stemness miRNAs whose expression levels in mouse ESCs are directly repressed by PRMT7. Notably, both miR-221-3p and miR-221-5p targeted the 3' untranslated regions of mRNA transcripts of the major pluripotency factors Oct4, Nanog, and Sox2 to antagonize mouse ESC stemness. Moreover, miR-221-5p silenced also the expression of its own transcriptional repressor PRMT7. Transfection of miR-221-3p and miR-221-5p mimics induced spontaneous differentiation of mouse ESCs. CRISPR-mediated deletion of the miR-221 gene, as well as specific antisense inhibitors of miR-221-3p and miR-221-5p, inhibited the spontaneous differentiation of PRMT7-depleted mouse ESCs. Taken together, these findings reveal that the PRMT7-mediated repression of miR-221-3p and miR-221-5p expression plays a critical role in maintaining mouse ESC stemness. Our results also establish miR-221-3p and miR-221-5p as anti-stemness miRNAs that target Oct4 , Nanog , and Sox2 mRNAs in mouse ESCs. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Murine bone marrow Lin⁻Sca⁻1⁺CD45⁻ very small embryonic-like (VSEL cells are heterogeneous population lacking Oct-4A expression.

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    Krzysztof Szade

    Full Text Available Murine very small embryonic-like (VSEL cells, defined by the Lin(-Sca-1(+CD45(- phenotype and small size, were described as pluripotent cells and proposed to be the most primitive hematopoietic precursors in adult bone marrow. Although their isolation and potential application rely entirely on flow cytometry, the immunophenotype of VSELs has not been extensively characterized. Our aim was to analyze the possible heterogeneity of Lin(-Sca(+CD45(- population and investigate the extent to which VSELs characteristics may overlap with that of hematopoietic stem cells (HSCs or endothelial progenitor cells (EPCs. The study evidenced that murine Lin(-Sca-1(+CD45(- population was heterogeneous in terms of c-Kit and KDR expression. Accordingly, the c-Kit(+KDR(-, c-Kit(-KDR(+, and c-Kit(-KDR(- subpopulations could be distinguished, while c-Kit(+KDR(+ events were very rare. The c-Kit(+KDR(- subset contained almost solely small cells, meeting the size criterion of VSELs, in contrast to relatively bigger c-Kit(-KDR(+ cells. The c-Kit(-KDR(-FSC(low subset was highly enriched in Annexin V-positive, apoptotic cells, hence omitted from further analysis. Importantly, using qRT-PCR, we evidenced lack of Oct-4A and Oct-4B mRNA expression either in whole adult murine bone marrow or in the sorted of Lin(-Sca-1(+CD45(-FSC(low population, even by single-cell qRT-PCR. We also found that the Lin(-Sca-1(+CD45(-c-Kit(+ subset did not exhibit hematopoietic potential in a single cell-derived colony in vitro assay, although it comprised the Sca-1(+c-Kit(+Lin(- (SKL CD34(-CD45(-CD105(+ cells, expressing particular HSC markers. Co-culture of Lin(-Sca-1(+CD45(-FSC(low with OP9 cells did not induce hematopoietic potential. Further investigation revealed that SKL CD45(-CD105(+ subset consisted of early apoptotic cells with fragmented chromatin, and could be contaminated with nuclei expelled from erythroblasts. Concluding, murine bone marrow Lin(-Sca-1(+CD45(-FSC(low cells are

  16. CD133(+)/CD44(+)/Oct4(+)/Nestin(+) stem-like cells isolated from Panc-1 cell line may contribute to multi-resistance and metastasis of pancreatic cancer.

    Science.gov (United States)

    Wang, Dongqing; Zhu, Haitao; Zhu, Ying; Liu, Yanfang; Shen, Huiling; Yin, Ruigen; Zhang, Zhijian; Su, Zhaoliang

    2013-05-01

    Pancreatic cancer is an aggressive malignant disease. Owing to the lack of early symptoms, accompanied by extensive metastasis and high resistance to chemotherapy, pancreatic adenocarcinoma becomes the fourth leading cause of cancer-related deaths. In this study, we identified a subpopulation of cells isolated from the Panc-1 cell line and named pancreatic cancer stem-like cells. These Panc-1 stem-like cells expressed high levels of CD133/CD44/Oct4/Nestin. Compared to Panc-1 cells, Panc-1 stem-like cells were resistant to gemcitabine and expressed high levels of MDR1; furthermore, Panc-1 stem-like cells have high anti-apoptotic, but weak proliferative potential. These results indicated that Panc-1 stem-like cells, as a novel group, may be a potential major cause of pancreatic cancer multidrug resistance and extensive metastasis. Copyright © 2012 Elsevier GmbH. All rights reserved.

  17. Soluble expression of recomb inant cMyc, Klf4, Oct4, and Sox2 proteins in bacteria and transduction into living cells

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    Guo-Dan Liu

    2017-04-01

    Full Text Available AIM: To develop a new method to produce recombinant reprogramming proteins, cMyc, Klf4, Oct4, and Sox2, in soluble format with low cost for the generation of induced pluripotent stem cells (iPSCs. METHODS: A short polypeptide sequence derived from the HIV trans-activator of transcription protein (TAT and the nucleus localization signal (NLS polypeptide were fused to the N terminus of the reprogramming proteins and they were constructed into pCold-SUMO vector which can extremely improve the solubility of recombinant proteins. Then these vector plasmids were transformed into E. coli BL21 (DE3 Chaperone competent cells for amplification. The solubility of these recombinant proteins was determined by SDS-PAGE and Coomassie brilliant blue staining. The recombinant proteins were purified by Ni-NTA resin and identified by Western blot. The transduction of these proteins into HEK 293T cells were evaluated by immunofluorescence staining. RESULTS: These four reprogramming proteins could be produced in soluble format in pCold-SUMO expression vector system with the assistance of chaperone proteins in bacteria. The proteins were purified successfully with a purity of over 70% with a relative high transduction rate into 293 cells. CONCLUSION: The results in the present study indicate the four important reprogramming proteins, cMyc, Klf4, Oct4, and Sox2, can be produced in soluble format in bacteria with low cost. Our new method thus might be expected to greatly contribute to the future study of iPSCs.

  18. On contribution of energetic and heavy ions to the plasma pressure: Storm Sept 27 - Oct 4, 2002

    Science.gov (United States)

    Kronberg, E. A.; Mouikis, C.; Kistler, L. M.; Dandouras, I. S.; Daly, P. W.; Welling, D. T.; Grigorenko, E. E.

    2015-12-01

    Contribution of the energetic ions (>> 40 keV) and of heavy ions into the total plasma pressure is often neglected. In this study we evaluate the contribution of these components for the storm observed from September 27 to October 4 in 2002. The thermal component of the pressure for the protons, helium and oxygen at 0--40 keV/q is measured by the Cluster/CIS/CODIF sensor. The contribution of the energetic ions at energies >> 40 keV is calculated from the Cluster/RAPID/IIMS observations. The results show that before the storm has initiated, the contribution of the energetic ions in to the total pressure is indeed negligible in the tail plasma sheet, less than ˜1%. However, with the storm development contribution of the energetic part becomes significant, up to ˜30%, towards the recovery phase and cannot be neglected. Heavy ions contribute to the 27% of the total pressure and half of them are energetic. The contribution of energetic ions to the pressure of the ring current (L≃5) is significant. The heavy ions play a dominant role in the plasma pressure, about 62% during the main phase of the magnetic storm. Half of them are energetic ions. The SWMF/BATS-R-US MHD model underestimates the contribution of the energetic and heavy ions in to the ion distribution in the magnetotail plasma sheet and the ring current. The ring current plasma pressure distorts the terrestrial internal magnetic field and defines magnetic storm. Therefore, it is essential to take in to account the contribution of the energetic and heavy ions.

  19. TALEN/CRISPR-mediated eGFP knock-in add-on at the OCT4 locus does not impact differentiation of human embryonic stem cells towards endoderm.

    Directory of Open Access Journals (Sweden)

    Nicole A J Krentz

    Full Text Available Human embryonic stem cells (hESCs have great promise as a source of unlimited transplantable cells for regenerative medicine. However, current progress on producing the desired cell type for disease treatment has been limited due to an insufficient understanding of the developmental processes that govern their differentiation, as well as a paucity of tools to systematically study differentiation in the lab. In order to overcome these limitations, cell-type reporter hESC lines will be required. Here we outline two strategies using Transcription Activator Like Effector Nucleases (TALENs and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR-CRISPR-Associated protein (Cas to create OCT4-eGFP knock-in add-on hESC lines. Thirty-one and forty-seven percent of clones were correctly modified using the TALEN and CRISPR-Cas9 systems, respectively. Further analysis of three correctly targeted clones demonstrated that the insertion of eGFP in-frame with OCT4 neither significantly impacted expression from the wild type allele nor did the fusion protein have a dramatically different biological stability. Importantly, the OCT4-eGFP fusion was easily detected using microscopy, flow cytometry and western blotting. The OCT4 reporter lines remained equally competent at producing CXCR4+ definitive endoderm that expressed a panel of endodermal genes. Moreover, the genomic modification did not impact the formation of NKX6.1+/SOX9+ pancreatic progenitor cells following directed differentiation. In conclusion, these findings demonstrate for the first time that CRISPR-Cas9 can be used to modify OCT4 and highlight the feasibility of creating cell-type specific reporter hESC lines utilizing genome-editing tools that facilitate homologous recombination.

  20. IGF-1R Promotes Symmetric Self-Renewal and Migration of Alkaline Phosphatase+ Germ Stem Cells through HIF-2α-OCT4/CXCR4 Loop under Hypoxia

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    Yung-Che Kuo

    2018-02-01

    Full Text Available Summary: Hypoxia cooperates with endocrine signaling to maintain the symmetric self-renewal proliferation and migration of embryonic germline stem cells (GSCs. However, the lack of an appropriate in vitro cell model has dramatically hindered the understanding of the mechanism underlying this cooperation. Here, using a serum-free system, we demonstrated that hypoxia significantly induced the GSC mesenchymal transition, increased the expression levels of the pluripotent transcription factor OCT4 and migration-associated proteins (SDF-1, CXCR4, IGF-1, and IGF-1R, and activated the cellular expression and translocalization of the CXCR4-downstream proteins ARP3/pFAK. The underlying mechanism involved significant IGF-1/IGF-1R activation of OCT4/CXCR4 expression through HIF-2α regulation. Picropodophyllin-induced inhibition of IGF-1R phosphorylation significantly suppressed hypoxia-induced SDF-1/CXCR4 expression and cell migration. Furthermore, transactivation between IGF-1R and CXCR4 was involved. In summary, we demonstrated that niche hypoxia synergistically cooperates with its associated IGF-1R signaling to regulate the symmetric division (self-renewal proliferation and cell migration of alkaline phosphatase-positive GSCs through HIF-2α-OCT4/CXCR4 during embryogenesis. : In this article, Huang and colleagues demonstrate that niche hypoxia promotes symmetric self-renewal proliferation and migration of PGC-like CD49f+AP+GSCs through IGF-IR regulation. Using a serum-free culture system, the crosstalk between IGF-1R and CXCR4 signaling was discovered. This work demonstrated that embryonic hypoxia synergistically cooperated with IGF-1R signaling to regulate the symmetric self-renewal and migration of PGC-like GSCs through a HIF-2α–OCT4/CXCR4 loop. Keywords: hypoxia, niche, germline stem cells, self-renewal, migration, IGF-1R, HIF-2α, OCT4, SDF-1, CXCR4

  1. IGF-1R Promotes Symmetric Self-Renewal and Migration of Alkaline Phosphatase+ Germ Stem Cells through HIF-2α-OCT4/CXCR4 Loop under Hypoxia.

    Science.gov (United States)

    Kuo, Yung-Che; Au, Heng-Kien; Hsu, Jue-Liang; Wang, Hsiao-Feng; Lee, Chiung-Ju; Peng, Syue-Wei; Lai, Ssu-Chuan; Wu, Yu-Chih; Ho, Hong-Nerng; Huang, Yen-Hua

    2018-02-13

    Hypoxia cooperates with endocrine signaling to maintain the symmetric self-renewal proliferation and migration of embryonic germline stem cells (GSCs). However, the lack of an appropriate in vitro cell model has dramatically hindered the understanding of the mechanism underlying this cooperation. Here, using a serum-free system, we demonstrated that hypoxia significantly induced the GSC mesenchymal transition, increased the expression levels of the pluripotent transcription factor OCT4 and migration-associated proteins (SDF-1, CXCR4, IGF-1, and IGF-1R), and activated the cellular expression and translocalization of the CXCR4-downstream proteins ARP3/pFAK. The underlying mechanism involved significant IGF-1/IGF-1R activation of OCT4/CXCR4 expression through HIF-2α regulation. Picropodophyllin-induced inhibition of IGF-1R phosphorylation significantly suppressed hypoxia-induced SDF-1/CXCR4 expression and cell migration. Furthermore, transactivation between IGF-1R and CXCR4 was involved. In summary, we demonstrated that niche hypoxia synergistically cooperates with its associated IGF-1R signaling to regulate the symmetric division (self-renewal proliferation) and cell migration of alkaline phosphatase-positive GSCs through HIF-2α-OCT4/CXCR4 during embryogenesis. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  2. [LincRNA-ROR functions as a ceRNA to regulate Oct4, Sox2, and Nanog expression by sponging miR-145 and its effect on biologic characteristics of colonic cancer stem cells].

    Science.gov (United States)

    Yan, Z Y; Sun, X C

    2018-04-08

    Objective: To investigate the impact of lincRNA-ROR, a ceRNA by binding miR-145 on the expression of the downstream genes Oct4, Sox2 and Nanog, and related biological characteristics of colon cancer stem cells, and to elucidate the clinical significance of this molecular regulatory network. Methods: Fifty-two cases of colorectal cancer tissue and adjacent tissue were collected at Nanyang City Central Hospital and Nanyang Second Hospital, Henan Province, from 2014 to 2016. Real-time quantitative polymerase chain reaction (qPCR) was used to detect the expression of lincRNA-ROR and miR-145 in colorectal cancer tissue and isolated colon cancer cells. The correlation between the expression of lincRNA-ROR, miR-145 and the clinicopathologic features of colon cancer was performed. CD44(-)CD133(-) and CD44(+) CD133(+) cells were isolated from SW1116 by using flow cytometry. The expression of CD44, CD133, Oct4, Sox2, Nanog, lincRNA-ROR and miR-145 in cells were detected by qPCR. The relationship between lincRNA-ROR, miR-145, Oct4, Sox2 and Nanog was analyzed by bioinformatics, dual luciferase reporter assay, qPCR and Western blot. The effects of silencing lincRNA-ROR on the proliferation and chemosensitivity of colon cancer stem cells were detected by MTT, colony formation. Results: LincRNA-ROR was frequently up-regulated and inversely correlated with miR-145 down-regulation in the colon cancer specimens( P cells were successfully isolated from SW1116 by flow cytometry. The levels of CD44, CD133, Oct4, Sox2, Nanog, lincRNA-ROR in CD44(+) CD133(+) cells were significantly increased, while miR-145 was decreased compared with CD44(-)CD133(-)cells( P cells were significantly reduced upon cell adherence, while miR-145 was significantly increased( P cancer stem cells proliferation and increased the sensitivity to chemotherapy. Conclusions: Linc-ROR functions as a key ceRNA to prevent core TFs, e. g., Oct4, Sox2, Nanog, from miR-145-mediated suppression in colon cancer stem cells

  3. Hyaluronan-CD44v3 Interaction with Oct4-Sox2-Nanog Promotes miR-302 Expression Leading to Self-renewal, Clonal Formation, and Cisplatin Resistance in Cancer Stem Cells from Head and Neck Squamous Cell Carcinoma*

    Science.gov (United States)

    Bourguignon, Lilly Y. W.; Wong, Gabriel; Earle, Christine; Chen, Liqun

    2012-01-01

    Human head and neck squamous cell carcinoma (HNSCC) is a highly malignant cancer associated with major morbidity and mortality. In this study, we determined that human HNSCC-derived HSC-3 cells contain a subpopulation of cancer stem cells (CSCs) characterized by high levels of CD44v3 and aldehyde dehydrogenase-1 (ALDH1) expression. These tumor cells also express several stem cell markers (the transcription factors Oct4, Sox2, and Nanog) and display the hallmark CSC properties of self-renewal/clonal formation and the ability to generate heterogeneous cell populations. Importantly, hyaluronan (HA) stimulates the CD44v3 (an HA receptor) interaction with Oct4-Sox2-Nanog leading to both a complex formation and the nuclear translocation of three CSC transcription factors. Further analysis reveals that microRNA-302 (miR-302) is controlled by an upstream promoter containing Oct4-Sox2-Nanog-binding sites, whereas chromatin immunoprecipitation (ChIP) assays demonstrate that stimulation of miR-302 expression by HA-CD44 is Oct4-Sox2-Nanog-dependent in HNSCC-specific CSCs. This process results in suppression of several epigenetic regulators (AOF1/AOF2 and DNMT1) and the up-regulation of several survival proteins (cIAP-1, cIAP-2, and XIAP) leading to self-renewal, clonal formation, and cisplatin resistance. These CSCs were transfected with a specific anti-miR-302 inhibitor to silence miR-302 expression and block its target functions. Our results demonstrate that the anti-miR-302 inhibitor not only enhances the expression of AOF1/AOF2 and DNMT1 but also abrogates the production of cIAP-1, cIAP-2, and XIAP and HA-CD44v3-mediated cancer stem cell functions. Taken together, these findings strongly support the contention that the HA-induced CD44v3 interaction with Oct4-Sox2-Nanog signaling plays a pivotal role in miR-302 production leading to AOF1/AOF2/DNMT1 down-regulation and survival of protein activation. All of these events are critically important for the acquisition of cancer

  4. Hyaluronan-CD44v3 interaction with Oct4-Sox2-Nanog promotes miR-302 expression leading to self-renewal, clonal formation, and cisplatin resistance in cancer stem cells from head and neck squamous cell carcinoma.

    Science.gov (United States)

    Bourguignon, Lilly Y W; Wong, Gabriel; Earle, Christine; Chen, Liqun

    2012-09-21

    Human head and neck squamous cell carcinoma (HNSCC) is a highly malignant cancer associated with major morbidity and mortality. In this study, we determined that human HNSCC-derived HSC-3 cells contain a subpopulation of cancer stem cells (CSCs) characterized by high levels of CD44v3 and aldehyde dehydrogenase-1 (ALDH1) expression. These tumor cells also express several stem cell markers (the transcription factors Oct4, Sox2, and Nanog) and display the hallmark CSC properties of self-renewal/clonal formation and the ability to generate heterogeneous cell populations. Importantly, hyaluronan (HA) stimulates the CD44v3 (an HA receptor) interaction with Oct4-Sox2-Nanog leading to both a complex formation and the nuclear translocation of three CSC transcription factors. Further analysis reveals that microRNA-302 (miR-302) is controlled by an upstream promoter containing Oct4-Sox2-Nanog-binding sites, whereas chromatin immunoprecipitation (ChIP) assays demonstrate that stimulation of miR-302 expression by HA-CD44 is Oct4-Sox2-Nanog-dependent in HNSCC-specific CSCs. This process results in suppression of several epigenetic regulators (AOF1/AOF2 and DNMT1) and the up-regulation of several survival proteins (cIAP-1, cIAP-2, and XIAP) leading to self-renewal, clonal formation, and cisplatin resistance. These CSCs were transfected with a specific anti-miR-302 inhibitor to silence miR-302 expression and block its target functions. Our results demonstrate that the anti-miR-302 inhibitor not only enhances the expression of AOF1/AOF2 and DNMT1 but also abrogates the production of cIAP-1, cIAP-2, and XIAP and HA-CD44v3-mediated cancer stem cell functions. Taken together, these findings strongly support the contention that the HA-induced CD44v3 interaction with Oct4-Sox2-Nanog signaling plays a pivotal role in miR-302 production leading to AOF1/AOF2/DNMT1 down-regulation and survival of protein activation. All of these events are critically important for the acquisition of cancer

  5. HIF-2α mediates a marked increase in migration and stemness characteristics in a subset of glioma cells under hypoxia by activating an Oct-4/Sox-2-Mena (INV) axis.

    Science.gov (United States)

    Bhagat, Mohita; Palanichamy, Jayanth Kumar; Ramalingam, Pradeep; Mudassir, Madeeha; Irshad, Khushboo; Chosdol, Kunzang; Sarkar, Chitra; Seth, Pankaj; Goswami, Sumanta; Sinha, Subrata; Chattopadhyay, Parthaprasad

    2016-05-01

    Hypoxia is a salient feature of most solid tumors and plays a central role in tumor progression owing to its multiple contributions to therapeutic resistance, metastasis, angiogenesis and stemness properties. Reports exist in literature about hypoxia increasing stemness characteristics and invasiveness potential of malignant cells. In order to delineate molecular crosstalk among factors driving glioma progression, we used knockdown and overexpression strategies. We have demonstrated that U87MG and A172 glioma cells inherently have a subset of cells with high migratory potential due to migration-inducing Mena transcripts. These cells also have elevated stemness markers (Sox-2 and Oct-4). There was a significant increase of number in this subset of migratory cells on exposure to hypoxia with corresponding elevation (over 1000 fold) in migration-inducing Mena transcripts. We were able to demonstrate that a HIF-2α-Sox-2/Oct-4-Mena (INV) axis that is strongly activated in hypoxia and markedly increases the migratory potential of the cells. Such cells also formed tumor spheres with greater efficiency. We have correlated our in-vitro results with human glioblastoma samples and found that hypoxia, invasiveness and stemness markers correlated well in native tumor samples. This study identifies a novel signaling mechanism mediated by HIF-2α in regulating invasiveness and stemness characteristics, suggesting that under hypoxic conditions, some tumor cells acquire more migratory potential by increased Pan Mena and Mena INV expression as a consequence of this HIF-2α mediated increase in Oct-4 and Sox-2. These properties would help the cells to form a new nidus after local invasion or metastasis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Assessment of the Potential of CDK2 Inhibitor NU6140 to Influence the Expression of Pluripotency Markers NANOG, OCT4, and SOX2 in 2102Ep and H9 Cells

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    Ade Kallas

    2014-01-01

    Full Text Available As cyclin-dependent kinases (CDKs regulate cell cycle progression and RNA transcription, CDKs are attractive targets for creating cancer cell treatments. In this study we investigated the effects of the small molecular agent NU6140 (inhibits CDK2 and cyclin A interaction on human embryonic stem (hES cells and embryonal carcinoma-derived (hEC cells via the expression of transcription factors responsible for pluripotency. A multiparameter flow cytometric method was used to follow changes in the expression of NANOG, OCT4, and SOX2 together in single cells. Both hES and hEC cells responded to NU6140 treatment by induced apoptosis and a decreased expression of NANOG, OCT4, and SOX2 in surviving cells. A higher sensitivity to NU6140 application in hES than hEC cells was detected. NU6140 treatment arrested hES and hEC cells in the G2 phase and inhibited entry into the M phase as evidenced by no significant increase in histone 3 phosphorylation. When embryoid bodies (EBs formed from NU6104 treated hES cells were compared to EBs from untreated hES cells differences in ectodermal, endodermal, and mesodermal lineages were found. The results of this study highlight the importance of CDK2 activity in maintaining pluripotency of hES and hEC cells and in differentiation of hES cells.

  7. Development of HSPA1A promoter-driven luciferase reporter gene assays in human cells for assessing the oxidative damage induced by silver nanoparticles

    International Nuclear Information System (INIS)

    Xin, Lili; Wang, Jianshu; Zhang, Leshuai W.; Che, Bizhong; Dong, Guangzhu; Fan, Guoqiang; Cheng, Kaiming

    2016-01-01

    The exponential increase in the total number of engineered nanoparticles in consumer products requires novel tools for rapid and cost-effective toxicology screening. In order to assess the oxidative damage induced by nanoparticles, toxicity test systems based on a human HSPA1A promoter-driven luciferase reporter in HepG2, LO2, A549, and HBE cells were established. After treated with heat shock and a group of silver nanoparticles (AgNPs) with different primary particle sizes, the cell viability, oxidative damage, and luciferase activity were determined. The time-dependent Ag + ions release from AgNPs in cell medium was also evaluated. Our results showed that heat shock produced a strong time-dependent induction of relative luciferase activity in the four luciferase reporter cells. Surprisingly, at 4 h of recovery, the relative luciferase activity was > 98 × the control level in HepG2-luciferase cells. Exposure to different sizes of AgNPs resulted in activation of the HSPA1A promoter in a dose-dependent manner, even at low cytotoxic or non-cytotoxic doses. The smaller (5 nm) AgNPs were more potent in luciferase induction than the larger (50 and 75 nm) AgNPs. These results were generally in accordance with the oxidative damage indicated by malondialdehyde concentration, reactive oxygen species induction and glutathione depletion, and Ag + ions release in cell medium. Compared with the other three luciferase reporter cells, the luciferase signal in HepG2-luciferase cells is obviously more sensitive and stable. We conclude that the luciferase reporter cells, especially the HepG2-luciferase cells, could provide a valuable tool for rapid screening of the oxidative damage induced by AgNPs. - Highlights: • We established the stable HSPA1A promoter-driven luciferase reporter cells. • Silver nanoparticles induced dose-dependent increases in luciferase activity. • HSPA1A promoter activity is a sensitive and responsive indicator of oxidative stress. • HepG2-luciferase

  8. Delivery of a survivin promoter-driven antisense survivin-expressing plasmid DNA as a cancer therapeutic: a proof-of-concept study

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    Lin KY

    2016-05-01

    Full Text Available Kun-Yuan Lin,1 Siao Muk Cheng,2 Shing-Ling Tsai,2 Ju-Ya Tsai,1 Chun-Hui Lin,1 Chun Hei Antonio Cheung1,2 1Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC; 2Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC Abstract: Survivin is a member of the inhibitor-of-apoptosis proteins family. It is overexpressed in many different cancer types but not in the differentiated normal tissue. In addition, overexpression of survivin promotes cancer cell survival and induces chemotherapeutic drug resistance, making it an attractive target for new anticancer interventions. Despite survivin being a promising molecular target for anticancer treatment, it is widely accepted that survivin is only a “semi-druggable” target. Therefore, it is important to develop a new strategy to target survivin for anticancer treatment. In this study, we constructed a novel survivin promoter-driven full-length antisense survivin (pSur/AS-Sur expression plasmid DNA. Promoter activity assay revealed that the activity of the survivin promoter of pSur/AS-Sur correlated with the endogenous expression of survivin at the transcriptional level in the transfected A549, MDA-MB-231, and PANC-1 cancer cells. Western blot analysis showed that liposomal delivery of pSur/AS-Sur successfully downregulated the expression of survivin in A549, MBA-MB-231, and PANC-1 cells in vitro. In addition, delivery of pSur/AS-Sur induced autophagy, caspase-dependent apoptosis, and caspase-independent apoptosis as indicated by the increased LC3B-II conversion, autophagosome formation, caspase-9/-3 and poly(ADP-ribose polymerase-1 cleavage, and apoptosis-inducing factor nuclear translocation in A549, MBA-MB-231, and PANC-1 cells. Importantly, liposomal delivery of pSur/AS-Sur was also capable of decreasing the proliferation of the survivin/MDR1 coexpressing multidrug-resistant KB-TAX50 cancer cells and

  9. Development of HSPA1A promoter-driven luciferase reporter gene assays in human cells for assessing the oxidative damage induced by silver nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Xin, Lili, E-mail: llxin@suda.edu.cn [School of Public Health, Medical College of Soochow University, 199 Renai Road, Suzhou 215123, Jiangsu (China); Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou 215123 (China); Wang, Jianshu [Suzhou Center for Disease Prevention and Control, 72 Sanxiang Road, Suzhou, Jiangsu (China); Zhang, Leshuai W. [School of Radiation Medicine and Protection & School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, 215123 (China); Che, Bizhong; Dong, Guangzhu [School of Public Health, Medical College of Soochow University, 199 Renai Road, Suzhou 215123, Jiangsu (China); Fan, Guoqiang; Cheng, Kaiming [Suzhou Industrial Park Centers for Disease Control and Prevention, 58 Suqian Road, Suzhou, Jiangsu (China)

    2016-08-01

    The exponential increase in the total number of engineered nanoparticles in consumer products requires novel tools for rapid and cost-effective toxicology screening. In order to assess the oxidative damage induced by nanoparticles, toxicity test systems based on a human HSPA1A promoter-driven luciferase reporter in HepG2, LO2, A549, and HBE cells were established. After treated with heat shock and a group of silver nanoparticles (AgNPs) with different primary particle sizes, the cell viability, oxidative damage, and luciferase activity were determined. The time-dependent Ag{sup +} ions release from AgNPs in cell medium was also evaluated. Our results showed that heat shock produced a strong time-dependent induction of relative luciferase activity in the four luciferase reporter cells. Surprisingly, at 4 h of recovery, the relative luciferase activity was > 98 × the control level in HepG2-luciferase cells. Exposure to different sizes of AgNPs resulted in activation of the HSPA1A promoter in a dose-dependent manner, even at low cytotoxic or non-cytotoxic doses. The smaller (5 nm) AgNPs were more potent in luciferase induction than the larger (50 and 75 nm) AgNPs. These results were generally in accordance with the oxidative damage indicated by malondialdehyde concentration, reactive oxygen species induction and glutathione depletion, and Ag{sup +} ions release in cell medium. Compared with the other three luciferase reporter cells, the luciferase signal in HepG2-luciferase cells is obviously more sensitive and stable. We conclude that the luciferase reporter cells, especially the HepG2-luciferase cells, could provide a valuable tool for rapid screening of the oxidative damage induced by AgNPs. - Highlights: • We established the stable HSPA1A promoter-driven luciferase reporter cells. • Silver nanoparticles induced dose-dependent increases in luciferase activity. • HSPA1A promoter activity is a sensitive and responsive indicator of oxidative stress. • HepG2

  10. P1 promoter-driven HNF4α isoforms are specifically repressed by β-catenin signaling in colorectal cancer cells.

    Science.gov (United States)

    Babeu, Jean-Philippe; Jones, Christine; Geha, Sameh; Carrier, Julie C; Boudreau, François

    2018-06-13

    HNF4α is a key nuclear receptor for regulating gene expression in the gut. While both P1 and P2 isoform classes of HNF4α are expressed in colonic epithelium, specific inhibition of P1 isoforms is commonly found in colorectal cancer. Previous studies have suggested that P1 and P2 isoforms may regulate different cellular functions. Despite these advances, it remains unclear whether these isoform classes are functionally divergent in the context of human biology. Here, the consequences of specific inhibition of P1 or P2 isoform expression was measured in a human colorectal cancer cell transcriptome. Results indicate that P1 isoforms were specifically associated with the control of cell metabolism while P2 isoforms globally supported aberrant oncogenic signalization, promoting cancer cell survival and progression. P1 promoter-driven isoform expression was found to be repressed by β-catenin, one of the earliest oncogenic pathways to be activated during colon tumorigenesis. These findings identify a novel cascade by which the expression of P1 isoforms are rapidly shut down in the early stages of colon tumorigenesis, allowing a change in HNF4α-dependent transcriptome thereby promoting colorectal cancer progression. © 2018. Published by The Company of Biologists Ltd.

  11. G-quadruplex formation in the Oct4 promoter positively regulates Oct4 expression

    Czech Academy of Sciences Publication Activity Database

    Renčiuk, Daniel; Ryneš, J.; Kejnovská, Iva; Foldynova-Trantirkova, S.; Andaeng, M.; Trantírek, L.; Vorlíčková, Michaela

    2017-01-01

    Roč. 1860, č. 2 (2017), s. 175-183 ISSN 1874-9399 R&D Projects: GA ČR(CZ) GP14-33947P; GA ČR GAP205/12/0466; GA ČR(CZ) GA15-06785S Institutional support: RVO:68081707 Keywords : linked polymorphic region * guanine quadruplexes * transcription factor Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 5.018, year: 2016

  12. Manufacturing Initiative

    Data.gov (United States)

    National Aeronautics and Space Administration — The Advanced Manufacturing Technologies (AMT) Project supports multiple activities within the Administration's National Manufacturing Initiative. A key component of...

  13. Unilateral initiatives

    International Nuclear Information System (INIS)

    Anon.

    1988-01-01

    This paper reports on arms control which is generally thought of in terms of formal negotiations with an opponent, with the resulting agreements embodied in a treaty. This is not surprising, since arms control discussions between opponents are both important and politically visible. There are, however, strong reasons for countries to consider and frequently take unilateral initiatives. To do so is entirely consistent with the established major precepts of arms control which state that arms control is designed to reduce the risk of war, the costs of preparing for war, and the death and destruction if war should come. Unilateral initiatives on what weapons are purchased, which ones are eliminated and how forces are deployed can all relate to these objectives. There are two main categories of motives for unilateral initiatives in arms control. In one category, internal national objectives are the dominant, often sole, driving force; the initiative is undertaken for our own good

  14. Ports Initiative

    Science.gov (United States)

    EPA's Ports Initiative works in collaboration with the port industry, communities, and government to improve environmental performance and increase economic prosperity. This effort helps people near ports breath cleaner air and live better lives.

  15. Initial Study

    DEFF Research Database (Denmark)

    Torp, Kristian

    2009-01-01

    increased. In the initial study presented here, the time it takes to pass an intersection is studied in details. Two major signal-controlled four-way intersections in the center of the city Aalborg are studied in details to estimate the congestion levels in these intersections, based on the time it takes...

  16. Characterisation of mesothelioma-initiating cells and their susceptibility to anti-cancer agents.

    Directory of Open Access Journals (Sweden)

    Elham Alizadeh Pasdar

    Full Text Available Malignant mesothelioma (MM is an aggressive type of tumour causing high mortality. One reason for this paradigm may be the existence of a subpopulation of tumour-initiating cells (TICs that endow MM with drug resistance and recurrence. The objective of this study was to identify and characterise a TIC subpopulation in MM cells, using spheroid cultures, mesospheres, as a model of MM TICs. Mesospheres, typified by the stemness markers CD24, ABCG2 and OCT4, initiated tumours in immunodeficient mice more efficiently than adherent cells. CD24 knock-down cells lost the sphere-forming capacity and featured lower tumorigenicity. Upon serial transplantation, mesospheres were gradually more efficiently tumrigenic with increased level of stem cell markers. We also show that mesospheres feature mitochondrial and metabolic properties similar to those of normal and cancer stem cells. Finally, we show that mesothelioma-initiating cells are highly susceptible to mitochondrially targeted vitamin E succinate. This study documents that mesospheres can be used as a plausible model of mesothelioma-initiating cells and that they can be utilised in the search for efficient agents against MM.

  17. Openness initiative

    International Nuclear Information System (INIS)

    Duncan, S.S.

    1995-01-01

    Although antinuclear campaigns seem to be effective, public communication and education efforts on low-level radioactive waste have mixed results. Attempts at public information programs on low-level radioactive waste still focus on influencing public opinion. A question then is: open-quotes Is it preferable to have a program focus on public education that will empower individuals to make informed decisions rather than trying to influence them in their decisions?close quotes To address this question, a case study with both quantitative and qualitative data will be used. The Ohio Low-Level Radioactive Waste Education Program has a goal to provide people with information they want/need to make their own decisions. The program initiated its efforts by conducting a statewide survey to determine information needed by people and where they turned for that information. This presentation reports data from the survey and then explores the program development process in which programs were designed and presented using the information. Pre and post data from the programs reveal attitude and knowledge shifts

  18. Openness initiative

    Energy Technology Data Exchange (ETDEWEB)

    Duncan, S.S. [Los Alamos National Lab., NM (United States)

    1995-12-31

    Although antinuclear campaigns seem to be effective, public communication and education efforts on low-level radioactive waste have mixed results. Attempts at public information programs on low-level radioactive waste still focus on influencing public opinion. A question then is: {open_quotes}Is it preferable to have a program focus on public education that will empower individuals to make informed decisions rather than trying to influence them in their decisions?{close_quotes} To address this question, a case study with both quantitative and qualitative data will be used. The Ohio Low-Level Radioactive Waste Education Program has a goal to provide people with information they want/need to make their own decisions. The program initiated its efforts by conducting a statewide survey to determine information needed by people and where they turned for that information. This presentation reports data from the survey and then explores the program development process in which programs were designed and presented using the information. Pre and post data from the programs reveal attitude and knowledge shifts.

  19. Initiative hard coal; Initiative Steinkohle

    Energy Technology Data Exchange (ETDEWEB)

    Leonhardt, J.

    2007-08-02

    In order to decrease the import dependence of hard coal in the European Union, the author has submitted suggestions to the director of conventional sources of energy (directorate general for energy and transport) of the European community, which found a positive resonance. These suggestions are summarized in an elaboration 'Initiative Hard Coal'. After clarifying the starting situation and defining the target the presupposition for a better use of hard coal deposits as raw material in the European Union are pointed out. On that basis concrete suggestions for measures are made. Apart from the conditions of the deposits it concerns thereby also new mining techniques and mining-economical developments, connected with tasks for the mining-machine industry. (orig.)

  20. KLF4 Nuclear Export Requires ERK Activation and Initiates Exit from Naive Pluripotency.

    Science.gov (United States)

    Dhaliwal, Navroop K; Miri, Kamelia; Davidson, Scott; Tamim El Jarkass, Hala; Mitchell, Jennifer A

    2018-04-10

    Cooperative action of a transcription factor complex containing OCT4, SOX2, NANOG, and KLF4 maintains the naive pluripotent state; however, less is known about the mechanisms that disrupt this complex, initiating exit from pluripotency. We show that, as embryonic stem cells (ESCs) exit pluripotency, KLF4 protein is exported from the nucleus causing rapid decline in Nanog and Klf4 transcription; as a result, KLF4 is the first pluripotency transcription factor removed from transcription-associated complexes during differentiation. KLF4 nuclear export requires ERK activation, and phosphorylation of KLF4 by ERK initiates interaction of KLF4 with nuclear export factor XPO1, leading to KLF4 export. Mutation of the ERK phosphorylation site in KLF4 (S132) blocks KLF4 nuclear export, the decline in Nanog, Klf4, and Sox2 mRNA, and differentiation. These findings demonstrate that relocalization of KLF4 to the cytoplasm is a critical first step in exit from the naive pluripotent state and initiation of ESC differentiation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Initiation devices, initiation systems including initiation devices and related methods

    Energy Technology Data Exchange (ETDEWEB)

    Daniels, Michael A.; Condit, Reston A.; Rasmussen, Nikki; Wallace, Ronald S.

    2018-04-10

    Initiation devices may include at least one substrate, an initiation element positioned on a first side of the at least one substrate, and a spark gap electrically coupled to the initiation element and positioned on a second side of the at least one substrate. Initiation devices may include a plurality of substrates where at least one substrate of the plurality of substrates is electrically connected to at least one adjacent substrate of the plurality of substrates with at least one via extending through the at least one substrate. Initiation systems may include such initiation devices. Methods of igniting energetic materials include passing a current through a spark gap formed on at least one substrate of the initiation device, passing the current through at least one via formed through the at least one substrate, and passing the current through an explosive bridge wire of the initiation device.

  2. Mouse Model of Human Breast Cancer Initiated by a Fusion Oncogene

    National Research Council Canada - National Science Library

    Orkin, Stuart H

    2006-01-01

    .... When TN is activated in mammary glands by whey acidic protein (WAP) promoter-driven Ore, all female mice exhibit extensive lobuloalveolar hyperplasia and develop multifocal mammary tumors as early as 4-month of age...

  3. Initialized Fractional Calculus

    Science.gov (United States)

    Lorenzo, Carl F.; Hartley, Tom T.

    2000-01-01

    This paper demonstrates the need for a nonconstant initialization for the fractional calculus and establishes a basic definition set for the initialized fractional differintegral. This definition set allows the formalization of an initialized fractional calculus. Two basis calculi are considered; the Riemann-Liouville and the Grunwald fractional calculi. Two forms of initialization, terminal and side are developed.

  4. Hedgehog-GLI signaling drives self-renewal and tumorigenicity of human melanoma-initiating cells.

    Science.gov (United States)

    Santini, Roberta; Vinci, Maria C; Pandolfi, Silvia; Penachioni, Junia Y; Montagnani, Valentina; Olivito, Biagio; Gattai, Riccardo; Pimpinelli, Nicola; Gerlini, Gianni; Borgognoni, Lorenzo; Stecca, Barbara

    2012-09-01

    The question of whether cancer stem/tumor-initiating cells (CSC/TIC) exist in human melanomas has arisen in the last few years. Here, we have used nonadherent spheres and the aldehyde dehydrogenase (ALDH) enzymatic activity to enrich for CSC/TIC in a collection of human melanomas obtained from a broad spectrum of sites and stages. We find that melanomaspheres display extensive in vitro self-renewal ability and sustain tumor growth in vivo, generating human melanoma xenografts that recapitulate the phenotypic composition of the parental tumor. Melanomaspheres express high levels of Hedgehog (HH) pathway components and of embryonic pluripotent stem cell factors SOX2, NANOG, OCT4, and KLF4. We show that human melanomas contain a subset of cells expressing high ALDH activity (ALDH(high)), which is endowed with higher self-renewal and tumorigenic abilities than the ALDH(low) population. A good correlation between the number of ALDH(high) cells and sphere formation efficiency was observed. Notably, both pharmacological inhibition of HH signaling by the SMOOTHENED (SMO) antagonist cyclopamine and GLI antagonist GANT61 and stable expression of shRNA targeting either SMO or GLI1 result in a significant decrease in melanoma stem cell self-renewal in vitro and a reduction in the number of ALDH(high) melanoma stem cells. Finally, we show that interference with the HH-GLI pathway through lentiviral-mediated silencing of SMO and GLI1 drastically diminishes tumor initiation of ALDH(high) melanoma stem cells. In conclusion, our data indicate an essential role of the HH-GLI1 signaling in controlling self-renewal and tumor initiation of melanoma CSC/TIC. Targeting HH-GLI1 is thus predicted to reduce the melanoma stem cell compartment. Copyright © 2012 AlphaMed Press.

  5. Three-dimensional localisation of NANOG, OCT4, and E-CADHERIN in porcine pre- and peri-implantation embryos

    DEFF Research Database (Denmark)

    Wolf, Xenia Asbæk; Serup, Palle; Hyttel, Poul

    2011-01-01

    . The expression of NANOG differed remarkably from that reported in other species. NANOG was not detected in the inner cell mass of hatched porcine blastocysts, but later appeared in the epiblast and hypoblast of spherical blastocysts where Rauber's layer had disintegrated. In pre-gastrulating, filamentous embryos...

  6. β-Catenin Regulates Primitive Streak Induction through Collaborative Interactions with SMAD2/SMAD3 and OCT4

    DEFF Research Database (Denmark)

    Funa, Nina Sofi Ayumi; Schachter, Karen; Lerdrup, Mads

    2015-01-01

    Canonical Wnt and Nodal signaling are both required for induction of the primitive streak (PS), which guides organization of the early embryo. The Wnt effector b-catenin is thought to function in these early lineage specification decisions via transcriptional activation of Nodal signaling. Here, we...... specification. This study provides mechanistic insight into how Wnt signaling controls early cell lineage decisions....

  7. Dioxin Exposure Initiative

    Science.gov (United States)

    The Dioxin Exposure Initiative (DEI) is no longer active. This page contains a summary of the dioxin exposure initiative with illustrations, contact and background information.Originally supported by scientist Matthew Lorber, who retired in Mar 2017.

  8. Construction of a Dual-Fluorescence Reporter System to Monitor the Dynamic Progression of Pluripotent Cell Differentiation.

    Science.gov (United States)

    Sun, Wu-Sheng; Chun, Ju-Lan; Do, Jeong-Tae; Kim, Dong-Hwan; Ahn, Jin-Seop; Kim, Min-Kyu; Hwang, In-Sul; Kwon, Dae-Jin; Hwang, Seong-Soo; Lee, Jeong-Woong

    2016-01-01

    Oct4 is a crucial germ line-specific transcription factor expressed in different pluripotent cells and downregulated in the process of differentiation. There are two conserved enhancers, called the distal enhancer (DE) and proximal enhancer (PE), in the 5' upstream regulatory sequences (URSs) of the mouse Oct4 gene, which were demonstrated to control Oct4 expression independently in embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs). We analyzed the URSs of the pig Oct4 and identified two similar enhancers that were highly consistent with the mouse DE and PE. A dual-fluorescence reporter was later constructed by combining a DE-free- Oct4 -promoter-driven EGFP reporter cassette with a PE-free- Oct4 -promoter-driven mCherry reporter cassette. Then, it was tested in a mouse ESC-like cell line (F9) and a mouse EpiSC-like cell line (P19) before it is formally used for pig. As a result, a higher red fluorescence was observed in F9 cells, while green fluorescence was primarily detected in P19 cells. This fluorescence expression pattern in the two cell lines was consistent with that in the early naïve pluripotent state and late primed pluripotent state during differentiation of mouse ESCs. Hence, this reporter system will be a convenient tool for screening out ESC-like naïve pluripotent stem cells from other metastable state cells in a heterogenous population.

  9. Construction of a Dual-Fluorescence Reporter System to Monitor the Dynamic Progression of Pluripotent Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Wu-Sheng Sun

    2016-01-01

    Full Text Available Oct4 is a crucial germ line-specific transcription factor expressed in different pluripotent cells and downregulated in the process of differentiation. There are two conserved enhancers, called the distal enhancer (DE and proximal enhancer (PE, in the 5′ upstream regulatory sequences (URSs of the mouse Oct4 gene, which were demonstrated to control Oct4 expression independently in embryonic stem cells (ESCs and epiblast stem cells (EpiSCs. We analyzed the URSs of the pig Oct4 and identified two similar enhancers that were highly consistent with the mouse DE and PE. A dual-fluorescence reporter was later constructed by combining a DE-free-Oct4-promoter-driven EGFP reporter cassette with a PE-free-Oct4-promoter-driven mCherry reporter cassette. Then, it was tested in a mouse ESC-like cell line (F9 and a mouse EpiSC-like cell line (P19 before it is formally used for pig. As a result, a higher red fluorescence was observed in F9 cells, while green fluorescence was primarily detected in P19 cells. This fluorescence expression pattern in the two cell lines was consistent with that in the early naïve pluripotent state and late primed pluripotent state during differentiation of mouse ESCs. Hence, this reporter system will be a convenient tool for screening out ESC-like naïve pluripotent stem cells from other metastable state cells in a heterogenous population.

  10. Tall Buildings Initiative

    Science.gov (United States)

    Initiative 2017 TBI Guidelines Version 2.03 Now Available Screen Shot 2017-10-10 at 3.05.10 PM PEER has just initiative to develop design criteria that will ensure safe and usable tall buildings following future earthquakes. Download the primary product of this initiative: Guidelines for Performance-Based Seismic Design

  11. Emerging Pathogens Initiative (EPI)

    Data.gov (United States)

    Department of Veterans Affairs — The Emerging Pathogens Initiative (EPI) database contains emerging pathogens information from the local Veterans Affairs Medical Centers (VAMCs). The EPI software...

  12. AC Initiation System.

    Science.gov (United States)

    An ac initiation system is described which uses three ac transmission signals interlocked for safety by frequency, phase, and power discrimination...The ac initiation system is pre-armed by the application of two ac signals have the proper phases, and activates a load when an ac power signal of the proper frequency and power level is applied. (Author)

  13. Sustainable Agricultural Marketing Initiatives

    Directory of Open Access Journals (Sweden)

    Hakan Adanacıoğlu

    2015-07-01

    Full Text Available Sustainable marketing is a holistic approach that puts equal emphasis on environmental, social equity, and economic concerns in the development of marketing strategies. The purpose of the study is to examine and discuss the sustainable agricultural marketing initiatives practiced throughout the World and Turkey, and to put forth suggestions to further improve the performance of agricultural marketing initiatives in Turkey. Some of the sustainable agricultural marketing initiatives practiced around the world are carried out through civil organizations. Furthermore; some of these initiatives have also launched by farmers, consumers, food processors and retailers. The long-term strategies to increase these initiatives should be determined due to the fact that examples of successful sustainable agricultural marketing initiatives are inadequate and cannot be spread in Turkey. In this context, first of all, the supports provided by the government to improve agricultural marketing systems, such as EU funds for rural development should be compatible with the goals of sustainable marketing. For this purpose, it should be examined whether all proposed projects related to agricultural marketing meet the social, economic, and environmental principles of sustainable marketing. It is important that supporting organizations, especially civil society organisations, should take an active role for faster dissemination and adoption of sustainable agricultural marketing practices in Turkey. These organizations may provide technical assistance in preparing successful project proposals and training to farm groups. In addition, the other organizations, such as local administrations, producers' associations, cooperatives, can contribute to the success of sustainable agricultural marketing initiatives. The use of direct marketing strategies and vertical integration attempts in sustainable agricultural marketing initiatives that will likely be implemented in Turkey is

  14. 1996 environmental initiatives report

    International Nuclear Information System (INIS)

    1996-01-01

    Progress by Consumers Gas in addressing environmental challenges were reviewed. Proposed environmental initiatives for the next fiscal year and beyond were introduced. Proposed initiatives were placed into three priority categories, high, medium or low, which together with the environmental management framework form the the utility's overall environmental agenda. High on the list of environmental priorities for the company are atmospheric air emissions, planning and construction practices, energy conservation and efficiency, environmental compliance, and methane emissions. The present state of the initiatives by the various company divisions and regions, compiled from the respective business plans, were reported. 21 figs

  15. Research Programs & Initiatives

    Science.gov (United States)

    CGH develops international initiatives and collaborates with other NCI divisions, NCI-designated Cancer Centers, and other countries to support cancer control planning, encourage capacity building, and support cancer research and research networks.

  16. Nursing Home Quality Initiative

    Data.gov (United States)

    U.S. Department of Health & Human Services — This Nursing Home Quality Initiative (NHQI) website provides consumer and provider information regarding the quality of care in nursing homes. NHQI discusses quality...

  17. Surgical Critical Care Initiative

    Data.gov (United States)

    Federal Laboratory Consortium — The Surgical Critical Care Initiative (SC2i) is a USU research program established in October 2013 to develop, translate, and validate biology-driven critical care....

  18. Global Methane Initiative

    Science.gov (United States)

    The Global Methane Initiative promotes cost-effective, near-term methane recovery through partnerships between developed and developing countries, with participation from the private sector, development banks, and nongovernmental organizations.

  19. Medical Errors Reduction Initiative

    National Research Council Canada - National Science Library

    Mutter, Michael L

    2005-01-01

    The Valley Hospital of Ridgewood, New Jersey, is proposing to extend a limited but highly successful specimen management and medication administration medical errors reduction initiative on a hospital-wide basis...

  20. RAS Initiative - Community Outreach

    Science.gov (United States)

    Through community and technical collaborations, workshops and symposia, and the distribution of reference reagents, the RAS Initiative seeks to increase the sharing of knowledge and resources essential to defeating cancers caused by mutant RAS genes.

  1. RAS Initiative - Events

    Science.gov (United States)

    The NCI RAS Initiative has organized multiple events with outside experts to discuss how the latest scientific and technological breakthroughs can be applied to discover vulnerabilities in RAS-driven cancers.

  2. PESP Landscaping Initiative

    Science.gov (United States)

    Landscaping practices can positively or negatively affect local environments and human health. The Landscaping Initiative seeks to enhance benefits of landscaping while reducing need for pesticides, fertilizers, etc., by working with partners.

  3. About the RAS Initiative

    Science.gov (United States)

    The RAS Initiative, a "hub and spoke" model, connects researchers to better understand and target the more than 30% of cancers driven by mutations in RAS genes. Includes oversight and contact information.

  4. The Yekaterinburg headache initiative

    DEFF Research Database (Denmark)

    Lebedeva, Elena R; Olesen, Jes; Osipova, Vera V

    2013-01-01

    for a demonstrational interventional project in Russia, undertaken within the Global Campaign against Headache. The initiative proposes three actions: 1) raise awareness of need for improvement; 2) design and implement a three-tier model (from primary care to a single highly specialized centre with academic affiliation......) for efficient and equitable delivery of headache-related health care; 3) develop a range of educational initiatives aimed at primary-care physicians, non-specialist neurologists, pharmacists and the general public to support the second action. RESULTS AND CONCLUSION: We set these proposals in a context...... of a health-care needs assessment, and as a model for all Russia. We present and discuss early progress of the initiative, justify the investment of resources required for implementation and call for the political support that full implementation requires. The more that the Yekaterinburg headache initiative...

  5. The RAS Initiative

    Science.gov (United States)

    NCI established the RAS Initiative to explore innovative approaches for attacking the proteins encoded by mutant forms of RAS genes and to ultimately create effective, new therapies for RAS-related cancers.

  6. Piezoelectrically Initiated Pyrotechnic Igniter

    Science.gov (United States)

    Quince, Asia; Dutton, Maureen; Hicks, Robert; Burnham, Karen

    2013-01-01

    This innovation consists of a pyrotechnic initiator and piezoelectric initiation system. The device will be capable of being initiated mechanically; resisting initiation by EMF, RF, and EMI (electromagnetic field, radio frequency, and electromagnetic interference, respectively); and initiating in water environments and space environments. Current devices of this nature are initiated by the mechanical action of a firing pin against a primer. Primers historically are prone to failure. These failures are commonly known as misfires or hang-fires. In many cases, the primer shows the dent where the firing pin struck the primer, but the primer failed to fire. In devices such as "T" handles, which are commonly used to initiate the blowout of canopies, loss of function of the device may result in loss of crew. In devices such as flares or smoke generators, failure can result in failure to spot a downed pilot. The piezoelectrically initiated ignition system consists of a pyrotechnic device that plugs into a mechanical system (activator), which on activation, generates a high-voltage spark. The activator, when released, will strike a stack of electrically linked piezo crystals, generating a high-voltage, low-amperage current that is then conducted to the pyro-initiator. Within the initiator, an electrode releases a spark that passes through a pyrotechnic first-fire mixture, causing it to combust. The combustion of the first-fire initiates a primary pyrotechnic or explosive powder. If used in a "T" handle, the primary would ramp the speed of burn up to the speed of sound, generating a shock wave that would cause a high explosive to go "high order." In a flare or smoke generator, the secondary would produce the heat necessary to ignite the pyrotechnic mixture. The piezo activator subsystem is redundant in that a second stack of crystals would be struck at the same time with the same activation force, doubling the probability of a first strike spark generation. If the first

  7. Supply Chain Initiatives Database

    Energy Technology Data Exchange (ETDEWEB)

    None

    2012-11-01

    The Supply Chain Initiatives Database (SCID) presents innovative approaches to engaging industrial suppliers in efforts to save energy, increase productivity and improve environmental performance. This comprehensive and freely-accessible database was developed by the Institute for Industrial Productivity (IIP). IIP acknowledges Ecofys for their valuable contributions. The database contains case studies searchable according to the types of activities buyers are undertaking to motivate suppliers, target sector, organization leading the initiative, and program or partnership linkages.

  8. International EUREKA: Initialization Segment

    International Nuclear Information System (INIS)

    1982-02-01

    The Initialization Segment creates the starting description of the uranium market. The starting description includes the international boundaries of trade, the geologic provinces, resources, reserves, production, uranium demand forecasts, and existing market transactions. The Initialization Segment is designed to accept information of various degrees of detail, depending on what is known about each region. It must transform this information into a specific data structure required by the Market Segment of the model, filling in gaps in the information through a predetermined sequence of defaults and built in assumptions. A principal function of the Initialization Segment is to create diagnostic messages indicating any inconsistencies in data and explaining which assumptions were used to organize the data base. This permits the user to manipulate the data base until such time the user is satisfied that all the assumptions used are reasonable and that any inconsistencies are resolved in a satisfactory manner

  9. Initiating events frequency determination

    International Nuclear Information System (INIS)

    Simic, Z.; Mikulicic, V.; Vukovic, I.

    2004-01-01

    The paper describes work performed for the Nuclear Power Station (NPS). Work is related to the periodic initiating events frequency update for the Probabilistic Safety Assessment (PSA). Data for all relevant NPS initiating events (IE) were reviewed. The main focus was on events occurring during most recent operating history (i.e., last four years). The final IE frequencies were estimated by incorporating both NPS experience and nuclear industry experience. Each event was categorized according to NPS individual plant examination (IPE) initiating events grouping approach. For the majority of the IE groups, few, or no events have occurred at the NPS. For those IE groups with few or no NPS events, the final estimate was made by means of a Bayesian update with general nuclear industry values. Exceptions are rare loss-of-coolant-accidents (LOCA) events, where evaluation of engineering aspects is used in order to determine frequency.(author)

  10. RCRA facility stabilization initiative

    International Nuclear Information System (INIS)

    1995-02-01

    The RCRA Facility Stabilization Initiative was developed as a means of implementing the Corrective Action Program's management goals recommended by the RIS for stabilizing actual or imminent releases from solid waste management units that threaten human health and the environment. The overall goal of stabilization is to, as situations warrant, control or abate threats to human health and/or the environment from releases at RCRA facilities, and/or to prevent or minimize the further spread of contamination while long-term remedies are pursued. The Stabilization initiative is a management philosophy and should not be confused with stabilization technologies

  11. The SEED Initiative

    Science.gov (United States)

    Teich, Carolyn R.

    2011-01-01

    Committed to fulfilling the promise of the green economy, the American Association of Community Colleges (AACC) launched the Sustainability Education and Economic Development (SEED) initiative (www.theseedcenter.org) in October 2010. The project advances sustainability and clean energy workforce development practices at community colleges by…

  12. Major New Initiatives

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Major New Initiatives. Multi-party multi-rate video conferencing OOPS. Live Lecture OOPS. Rural ATM Machine Vortex. Finger print detection HP-IITM. Medical Diagnostic kit NeuroSynaptic. LCD projection system TeNeT. Web Terminal MeTeL Midas. Entertainment ...

  13. Mixed-Initiative Clustering

    Science.gov (United States)

    Huang, Yifen

    2010-01-01

    Mixed-initiative clustering is a task where a user and a machine work collaboratively to analyze a large set of documents. We hypothesize that a user and a machine can both learn better clustering models through enriched communication and interactive learning from each other. The first contribution or this thesis is providing a framework of…

  14. Monolithic exploding foil initiator

    Science.gov (United States)

    Welle, Eric J; Vianco, Paul T; Headley, Paul S; Jarrell, Jason A; Garrity, J. Emmett; Shelton, Keegan P; Marley, Stephen K

    2012-10-23

    A monolithic exploding foil initiator (EFI) or slapper detonator and the method for making the monolithic EFI wherein the exploding bridge and the dielectric from which the flyer will be generated are integrated directly onto the header. In some embodiments, the barrel is directly integrated directly onto the header.

  15. Next generation initiation techniques

    Science.gov (United States)

    Warner, Tom; Derber, John; Zupanski, Milija; Cohn, Steve; Verlinde, Hans

    1993-01-01

    Four-dimensional data assimilation strategies can generally be classified as either current or next generation, depending upon whether they are used operationally or not. Current-generation data-assimilation techniques are those that are presently used routinely in operational-forecasting or research applications. They can be classified into the following categories: intermittent assimilation, Newtonian relaxation, and physical initialization. It should be noted that these techniques are the subject of continued research, and their improvement will parallel the development of next generation techniques described by the other speakers. Next generation assimilation techniques are those that are under development but are not yet used operationally. Most of these procedures are derived from control theory or variational methods and primarily represent continuous assimilation approaches, in which the data and model dynamics are 'fitted' to each other in an optimal way. Another 'next generation' category is the initialization of convective-scale models. Intermittent assimilation systems use an objective analysis to combine all observations within a time window that is centered on the analysis time. Continuous first-generation assimilation systems are usually based on the Newtonian-relaxation or 'nudging' techniques. Physical initialization procedures generally involve the use of standard or nonstandard data to force some physical process in the model during an assimilation period. Under the topic of next-generation assimilation techniques, variational approaches are currently being actively developed. Variational approaches seek to minimize a cost or penalty function which measures a model's fit to observations, background fields and other imposed constraints. Alternatively, the Kalman filter technique, which is also under investigation as a data assimilation procedure for numerical weather prediction, can yield acceptable initial conditions for mesoscale models. The

  16. Adult stem cell theory of the multi-stage, multi-mechanism theory of carcinogenesis: role of inflammation on the promotion of initiated stem cells.

    Science.gov (United States)

    Trosko, James E; Tai, Mei-Hui

    2006-01-01

    Inflammation, induced by microbial agents, radiation, endogenous or exogenous chemicals, has been associated with chronic diseases, including cancer. Since carcinogenesis has been characterized as consisting of the 'initiation', 'promotion' and 'progression' phases, the inflammatory process could affect any or all three phases. The stem cell theory of carcinogenesis has been given a revival, in that isolated human adult stem cells have been isolated and shown to be 'targets' for neoplastic transformation. Oct4, a transcription factor, has been associated with adult stem cells, as well as their immortalized and tumorigenic derivatives, but not with the normal differentiated daughters. These data are consistent with the stem cell theory of carcinogenesis. In addition, Gap Junctional Intercellular Communication (GJIC) seems to play a major role in cell growth. Inhibition of GJIC by non-genotoxic chemicals or various oncogenes seems to be the mechanism for the tumor promotion and progression phases of carcinogenesis. Many of the toxins, synthetic non-genotoxicants, and endogenous inflammatory factors have been shown to inhibit GJIC and act as tumor promoters. The inhibition of GJIC might be the mechanism by which the inflammatory process affects cancer and that to intervene during tumor promotion with anti-inflammatory factors might be the most efficacious anti-cancer strategy.

  17. Funding Initiatives | Women in Science | Initiatives | Indian Academy ...

    Indian Academy of Sciences (India)

    Home; Initiatives; Women in Science; Funding Initiatives ... The Fellowship Scheme for Women Scientists for societal programmes is initiative of the ... at a young age of 52, after a valiant battle with cancer, today on 29th March 2016 in Delhi.

  18. Sustaining Participatory Design Initiatives

    DEFF Research Database (Denmark)

    Iversen, Ole Sejer; Dindler, Christian

    2014-01-01

    While many participatory design (PD) projects succeed in establishing new organisational initiatives or creating technology that is attuned to the people affected, the issue of how such results are sustained after the project ends remains an important challenge. We explore the challenge...... these various forms of sustainability may be pursued in PD practice and how they can become a resource in reflecting on PD activities. Finally, we discuss implications for PD practice, suggesting that a nuanced conception of sustainability and how it may relate to PD practice are useful resources for designers...... of sustaining PD initiatives beyond the individual project and discuss implications for PD practice. First, based on current PD literature, we distinguish between four ideal typical forms of sustainability: maintaining, scaling, replicating and evolving. Second, we demonstrate from a case study how...

  19. Initial management of breastfeeding.

    Science.gov (United States)

    Sinusas, K; Gagliardi, A

    2001-09-15

    Breast milk is widely accepted as the ideal source of nutrition for infants. In order to ensure success in breastfeeding, it is important that it be initiated as early as possible during the neonatal period. This is facilitated by skin-to-skin contact between the mother and infant immediately following birth. When possible, the infant should be allowed to root and latch on spontaneously within the first hour of life. Many common nursery routines such as weighing the infant, administration of vitamin K and application of ocular antibiotics can be safely delayed until after the initial breastfeeding. Postpartum care practices that improve breastfeeding rates include rooming-in, anticipatory guidance about breastfeeding problems and the avoidance of formula supplementation and pacifiers.

  20. Self-initiated expatriates

    DEFF Research Database (Denmark)

    Selmer, Jan; Lauring, Jakob

    2014-01-01

    Purpose – As it has been suggested that adult third-culture kids may be more culturally adaptable than others, they have been labelled “the ideal” expatriates. In this article, we explore the adjustment of self-initiated expatriate academics in Hong Kong, comparing adult third-culture kids...... with adult mono-culture kids. Design/methodology/approach – We use survey results from 267 self-initiated expatriate academics in Hong Kong. Findings – Exploratory results show that adult third-culture kids had a higher extent of general adjustment. No significant results were found in relation...... to interaction adjustment and job adjustment. We also found that recent expatriate experiences generally had a positive association with the adjustment of adult mono-culture kids, but this association only existed in terms of general adjustment for adult third-culture kids. Originality/value – Once corroborated...

  1. INITIAL TRAINING OF RESEARCHERS

    Directory of Open Access Journals (Sweden)

    Karina Alejandra Cruz-Pallares

    2015-07-01

    Full Text Available The document presents results of a research that used as strategy a complementary training project with thirty-three students of a Bachelors Degree in Primary School 1997(DPS,1997 of an Education Faculty for the initial training of investigators, applied by four teachers members of the academic research group in Mexico; that develops through process of action research methodology. Highlighted in results is the strengthening of the competition of reading, understanding and writing scientific texts, which is analogous to the first feature of the graduate profile called intellectual skills. Among the conclusions it is emphasized that the initial training of teachers in a task that is quite interesting, challenging and complex, as is the educational complex phenomenon.

  2. Hanford tanks initiative plan

    International Nuclear Information System (INIS)

    McKinney, K.E.

    1997-01-01

    Abstract: The Hanford Tanks Initiative (HTI) is a five-year project resulting from the technical and financial partnership of the U.S. Department of Energy's Office of Waste Management (EM-30) and Office of Science and Technology Development (EM-50). The HTI project accelerates activities to gain key technical, cost performance, and regulatory information on two high-level waste tanks. The HTI will provide a basis for design and regulatory decisions affecting the remainder of the Tank Waste Remediation System's tank waste retrieval Program

  3. UNLV Nuclear Hydrogen Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Hechanova, Anthony E.; Johnson, Allen; O' Toole, Brendan; Trabia, Mohamed; Peterson, Per

    2012-10-25

    Evaluation of the Crack growth rate (CGR) of Alloy 617 and Alloy 276 under constant K at ambient temperature has been completed. Creep deformation of Alloy 230 at different temperature range and load level has been completed and heat to heat variation has been noticed. Creep deformation study of Alloy 276 has been completed under an applied initial stress level of 10% of yield stress at 950ºC. The grain size evaluation of the tested creep specimens of Alloy 276 has been completed.

  4. Feedback stabilization initiative

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-06-01

    Much progress has been made in attaining high confinement regimes in magnetic confinement devices. These operating modes tend to be transient, however, due to the onset of MHD instabilities, and their stabilization is critical for improved performance at steady state. This report describes the Feedback Stabilization Initiative (FSI), a broad-based, multi-institutional effort to develop and implement methods for raising the achievable plasma betas through active MHD feedback stabilization. A key element in this proposed effort is the Feedback Stabilization Experiment (FSX), a medium-sized, national facility that would be specifically dedicated to demonstrating beta improvement in reactor relevant plasmas by using a variety of MHD feedback stabilization schemes.

  5. Feedback stabilization initiative

    International Nuclear Information System (INIS)

    1997-06-01

    Much progress has been made in attaining high confinement regimes in magnetic confinement devices. These operating modes tend to be transient, however, due to the onset of MHD instabilities, and their stabilization is critical for improved performance at steady state. This report describes the Feedback Stabilization Initiative (FSI), a broad-based, multi-institutional effort to develop and implement methods for raising the achievable plasma betas through active MHD feedback stabilization. A key element in this proposed effort is the Feedback Stabilization Experiment (FSX), a medium-sized, national facility that would be specifically dedicated to demonstrating beta improvement in reactor relevant plasmas by using a variety of MHD feedback stabilization schemes

  6. Initiation of slug flow

    Energy Technology Data Exchange (ETDEWEB)

    Hanratty, T.J.; Woods, B.D. [Univ. of Illinois, Urbana, IL (United States)

    1995-12-31

    The initiation of slug flow in a horizontal pipe can be predicted either by considering the stability of a slug or by considering the stability of a stratified flow. Measurements of the shedding rate of slugs are used to define necessary conditions for the existence of a slug. Recent results show that slugs develop from an unstable stratified flow through the evolution of small wavelength waves into large wavelength waves that have the possibility of growing to form a slug. The mechanism appears to be quite different for fluids with viscosities close to water than for fluids with large viscosities (20 centipoise).

  7. Stirling to Flight Initiative

    Science.gov (United States)

    Hibbard, Kenneth E.; Mason, Lee S.; Ndu, Obi; Smith, Clayton; Withrow, James P.

    2016-01-01

    Flight (S2F) initiative with the objective of developing a 100-500 We Stirling generator system. Additionally, a different approach is being devised for this initiative to avoid pitfalls of the past, and apply lessons learned from the recent ASRG experience. Two key aspects of this initiative are a Stirling System Technology Maturation Effort, and a Surrogate Mission Team (SMT) intended to provide clear mission pull and requirements context. The S2F project seeks to lead directly into a DOE flight system development of a new SRG. This paper will detail the proposed S2F initiative, and provide specifics on the key efforts designed to pave a forward path for bringing Stirling technology to flight.

  8. Initiating statistical maintenance optimization

    International Nuclear Information System (INIS)

    Doyle, E. Kevin; Tuomi, Vesa; Rowley, Ian

    2007-01-01

    Since the 1980 s maintenance optimization has been centered around various formulations of Reliability Centered Maintenance (RCM). Several such optimization techniques have been implemented at the Bruce Nuclear Station. Further cost refinement of the Station preventive maintenance strategy includes evaluation of statistical optimization techniques. A review of successful pilot efforts in this direction is provided as well as initial work with graphical analysis. The present situation reguarding data sourcing, the principle impediment to use of stochastic methods in previous years, is discussed. The use of Crowe/AMSAA (Army Materials Systems Analysis Activity) plots is demonstrated from the point of view of justifying expenditures in optimization efforts. (author)

  9. The LHCb Starterkit initiative

    CERN Document Server

    Puig Navarro, Albert

    2017-01-01

    The vast majority of high-energy physicists use and produce software every day. Software skills are usually acquired on the go and dedicated training courses are rare. The LHCb Starterkit is a new training format for getting LHCb collaborators started in effectively using software to perform their research. The initiative, combining courses and online tutorials, focuses on teaching basic skills for research computing, as well as LHCb software specifics. Unlike traditional tutorials we focus on starting with basics, performing all the material live, with a high degree of interactivity, giving priority to understanding the tools as opposed to handing out recipes that work “as if by magic”. The LHCb Starterkit was started by young members of the collaboration inspired by the principles of Software Carpentry, and the material is created in a collaborative fashion using the tools we teach. Three successful entry-level workshops, as well as two advanced ones, have taken place since the start of the initiative i...

  10. Combat Wound Initiative program.

    Science.gov (United States)

    Stojadinovic, Alexander; Elster, Eric; Potter, Benjamin K; Davis, Thomas A; Tadaki, Doug K; Brown, Trevor S; Ahlers, Stephen; Attinger, Christopher E; Andersen, Romney C; Burris, David; Centeno, Jose; Champion, Hunter; Crumbley, David R; Denobile, John; Duga, Michael; Dunne, James R; Eberhardt, John; Ennis, William J; Forsberg, Jonathan A; Hawksworth, Jason; Helling, Thomas S; Lazarus, Gerald S; Milner, Stephen M; Mullick, Florabel G; Owner, Christopher R; Pasquina, Paul F; Patel, Chirag R; Peoples, George E; Nissan, Aviram; Ring, Michael; Sandberg, Glenn D; Schaden, Wolfgang; Schultz, Gregory S; Scofield, Tom; Shawen, Scott B; Sheppard, Forest R; Stannard, James P; Weina, Peter J; Zenilman, Jonathan M

    2010-07-01

    The Combat Wound Initiative (CWI) program is a collaborative, multidisciplinary, and interservice public-private partnership that provides personalized, state-of-the-art, and complex wound care via targeted clinical and translational research. The CWI uses a bench-to-bedside approach to translational research, including the rapid development of a human extracorporeal shock wave therapy (ESWT) study in complex wounds after establishing the potential efficacy, biologic mechanisms, and safety of this treatment modality in a murine model. Additional clinical trials include the prospective use of clinical data, serum and wound biomarkers, and wound gene expression profiles to predict wound healing/failure and additional clinical patient outcomes following combat-related trauma. These clinical research data are analyzed using machine-based learning algorithms to develop predictive treatment models to guide clinical decision-making. Future CWI directions include additional clinical trials and study centers and the refinement and deployment of our genetically driven, personalized medicine initiative to provide patient-specific care across multiple medical disciplines, with an emphasis on combat casualty care.

  11. Initiatives for proliferation prevention

    International Nuclear Information System (INIS)

    1997-04-01

    Preventing the proliferation of weapons of mass destruction is a central part of US national security policy. A principal instrument of the Department of Energy's (DOE's) program for securing weapons of mass destruction technology and expertise and removing incentives for scientists, engineers and technicians in the newly independent states (NIS) of the former Soviet Union to go to rogue countries or assist terrorist groups is the Initiatives for Proliferation Prevention (IPP). IPP was initiated pursuant to the 1994 Foreign Operations Appropriations Act. IPP is a nonproliferation program with a commercialization strategy. IPP seeks to enhance US national security and to achieve nonproliferation objectives by engaging scientists, engineers and technicians from former NIS weapons institutes; redirecting their activities in cooperatively-developed, commercially viable non-weapons related projects. These projects lead to commercial and economic benefits for both the NIS and the US IPP projects are funded in Russian, Ukraine, Kazakhstan and Belarus. This booklet offers an overview of the IPP program as well as a sampling of some of the projects which are currently underway

  12. Evaluation Program initiative

    International Nuclear Information System (INIS)

    Rich, B.L.

    1987-01-01

    The purpose of this paper is to provide the Department of Energy's (DOE) safeguards and security community with some insights on an important management initiative by the Office of Security Evaluations (OSE). The paper will present the ''what, where, who, when, and why'' of a new Evaluation Program. The Evaluation Program will be comprised of a continuing series of regular and special evaluations of DOE safeguards and security programs and policies. The evaluations will be integrative and ''crosscutting,'' i.e. will extend across DOE organizational lines. Evaluations will be offered as positive advisories to DOE managers with safeguards and security responsibilities and will not be rated. They will complement the ongoing OSE Inspection Program of inspections conducted by OSE's Inspection Division. The purpose for the evaluations is to establish an accurate and current assessment of the effectiveness and status of safeguards and security programs and policies and to provide DOE managers with required information on program and policy effectiveness

  13. Breckinridge Project, initial effort

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    1982-09-01

    Report III, Volume 1 contains those specifications numbered A through J, as follows: General Specifications (A); Specifications for Pressure Vessels (C); Specifications for Tanks (D); Specifications for Exchangers (E); Specifications for Fired Heaters (F); Specifications for Pumps and Drivers (G); and Specifications for Instrumentation (J). The standard specifications of Bechtel Petroleum Incorporated have been amended as necessary to reflect the specific requirements of the Breckinridge Project, and the more stringent specifications of Ashland Synthetic Fuels, Inc. These standard specifications are available to the Initial Effort (Phase Zero) work performed by all contractors and subcontractors. Report III, Volume 1 also contains the unique specifications prepared for Plants 8, 15, and 27. These specifications will be substantially reviewed during Phase I of the project, and modified as necessary for use during the engineering, procurement, and construction of this project.

  14. The climate technology initiative

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Adam [International Energy Agency, Climate Technology Initiative, Paris (France)

    2000-12-01

    The CTI (Climate Technology Initiative) aims to promote those technologies which cause the minimum of harm to the environment: reducing emissions of greenhouse gases and supporting those countries most vulnerable to climate change are priorities. A strong case for cogeneration is made and it is pointed out that both the European Union and the USA aim to double their cogeneration capacity by 2010. The CTI holds training courses and seminars all over the world where the barriers to the expansion of climate-friendly technology are discussed. The article also mentions the CTI Co-operation Technology Implementation Plan, research and development, its website and search engine, its presence at all UNFCCC events and its awards programme.

  15. The climate technology initiative

    International Nuclear Information System (INIS)

    Smith, Adam

    2000-01-01

    The CTI (Climate Technology Initiative) aims to promote those technologies which cause the minimum of harm to the environment: reducing emissions of greenhouse gases and supporting those countries most vulnerable to climate change are priorities. A strong case for cogeneration is made and it is pointed out that both the European Union and the USA aim to double their cogeneration capacity by 2010. The CTI holds training courses and seminars all over the world where the barriers to the expansion of climate-friendly technology are discussed. The article also mentions the CTI Co-operation Technology Implementation Plan, research and development, its website and search engine, its presence at all UNFCCC events and its awards programme

  16. Initial brain aging

    DEFF Research Database (Denmark)

    Thomsen, Kirsten; Yokota, Takashi; Hasan-Olive, Md Mahdi

    2018-01-01

    Brain aging is accompanied by declining mitochondrial respiration. We hypothesized that mitochondrial morphology and dynamics would reflect this decline. Using hippocampus and frontal cortex of a segmental progeroid mouse model lacking Cockayne syndrome protein B (CSB(m/m)) and C57Bl/6 (WT......) controls and comparing young (2-5 months) to middle-aged mice (13-14 months), we found that complex I-linked state 3 respiration (CI) was reduced at middle age in CSB(m/m) hippocampus, but not in CSB(m/m) cortex or WT brain. In hippocampus of both genotypes, mitochondrial size heterogeneity increased....... Mitochondrial DNA content was lower, and hypoxia-induced factor 1α mRNA was greater at both ages in CSB(m/m) compared to WT brain. Our findings show that decreased CI and increased mitochondrial size heterogeneity are highly associated and point to declining mitochondrial quality control as an initial event...

  17. Materials Genome Initiative

    Science.gov (United States)

    Vickers, John

    2015-01-01

    The Materials Genome Initiative (MGI) project element is a cross-Center effort that is focused on the integration of computational tools to simulate manufacturing processes and materials behavior. These computational simulations will be utilized to gain understanding of processes and materials behavior to accelerate process development and certification to more efficiently integrate new materials in existing NASA projects and to lead to the design of new materials for improved performance. This NASA effort looks to collaborate with efforts at other government agencies and universities working under the national MGI. MGI plans to develop integrated computational/experimental/ processing methodologies for accelerating discovery and insertion of materials to satisfy NASA's unique mission demands. The challenges include validated design tools that incorporate materials properties, processes, and design requirements; and materials process control to rapidly mature emerging manufacturing methods and develop certified manufacturing processes

  18. The Ombudperson Initiative Group

    CERN Multimedia

    Laura Stewart

    Following many discussions that took place at some of the ATLAS Women's Network lunch gatherings, a few ATLAS women joined forces with similarly concerned CERN staff women to form a small group last Fall to discuss the need for a CERN-wide Ombudsperson. This has since evolved into the Ombudsperson Initiative Group (OIG) currently composed of the following members: Barbro Asman, Stockholm University; Pierre Charrue, CERN AB; Anna Cook, CERN IT; Catherine Delamare, CERN and IT Ombudsperson; Paula Eerola, Lund University; Pauline Gagnon, Indiana University; Eugenia Hatziangeli, CERN AB; Doreen Klem, CERN IT; Bertrand Nicquevert, CERN TS and Laura Stewart, CERN AT. On June 12, members of the OIG met with representatives of Human Resources (HR) and the Equal Opportunity Advisory Panel (EOAP) to discuss the proposal drafted by the OIG. The meeting was very positive. Everybody agreed that the current procedures at CERN applicable in the event of conflict required a thorough review, and that a professionnally trai...

  19. Instrumented Pipeline Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Thomas Piro; Michael Ream

    2010-07-31

    This report summarizes technical progress achieved during the cooperative agreement between Concurrent Technologies Corporation (CTC) and U.S. Department of Energy to address the need for a for low-cost monitoring and inspection sensor system as identified in the Department of Energy (DOE) National Gas Infrastructure Research & Development (R&D) Delivery Reliability Program Roadmap.. The Instrumented Pipeline Initiative (IPI) achieved the objective by researching technologies for the monitoring of pipeline delivery integrity, through a ubiquitous network of sensors and controllers to detect and diagnose incipient defects, leaks, and failures. This report is organized by tasks as detailed in the Statement of Project Objectives (SOPO). The sections all state the objective and approach before detailing results of work.

  20. The Enzyme Function Initiative.

    Science.gov (United States)

    Gerlt, John A; Allen, Karen N; Almo, Steven C; Armstrong, Richard N; Babbitt, Patricia C; Cronan, John E; Dunaway-Mariano, Debra; Imker, Heidi J; Jacobson, Matthew P; Minor, Wladek; Poulter, C Dale; Raushel, Frank M; Sali, Andrej; Shoichet, Brian K; Sweedler, Jonathan V

    2011-11-22

    The Enzyme Function Initiative (EFI) was recently established to address the challenge of assigning reliable functions to enzymes discovered in bacterial genome projects; in this Current Topic, we review the structure and operations of the EFI. The EFI includes the Superfamily/Genome, Protein, Structure, Computation, and Data/Dissemination Cores that provide the infrastructure for reliably predicting the in vitro functions of unknown enzymes. The initial targets for functional assignment are selected from five functionally diverse superfamilies (amidohydrolase, enolase, glutathione transferase, haloalkanoic acid dehalogenase, and isoprenoid synthase), with five superfamily specific Bridging Projects experimentally testing the predicted in vitro enzymatic activities. The EFI also includes the Microbiology Core that evaluates the in vivo context of in vitro enzymatic functions and confirms the functional predictions of the EFI. The deliverables of the EFI to the scientific community include (1) development of a large-scale, multidisciplinary sequence/structure-based strategy for functional assignment of unknown enzymes discovered in genome projects (target selection, protein production, structure determination, computation, experimental enzymology, microbiology, and structure-based annotation), (2) dissemination of the strategy to the community via publications, collaborations, workshops, and symposia, (3) computational and bioinformatic tools for using the strategy, (4) provision of experimental protocols and/or reagents for enzyme production and characterization, and (5) dissemination of data via the EFI's Website, http://enzymefunction.org. The realization of multidisciplinary strategies for functional assignment will begin to define the full metabolic diversity that exists in nature and will impact basic biochemical and evolutionary understanding, as well as a wide range of applications of central importance to industrial, medicinal, and pharmaceutical efforts.

  1. Green Power Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Butler, Patrick Barry [Univ. of Iowa, Iowa City, IA (United States)

    2013-01-28

    National energy policy supports the gathering of more detailed and authoritative data on the introduction of renewable bio-based fuels into new and existing district energy systems via the application of biomass gasification. The University of Iowa developed a biomass-fueled, university-scale steam generation system based on biomass gasification technologies. The system serves as a state-of-the-art research and educational facility in the emerging application of gasification in steam generation. The facility, which includes a smaller down-draft gasifier and a larger multi-stage biomass boiler, was designed to operate primarily on wood-based fuels, but has provisions for testing other biomass fuel sources produced within a 100-mile radius, providing enough flexibility to meet the fluctuating local supply of biomass from industry and Midwest agriculture. The equipment was installed in an existing, staffed facility. The down-draft gasifier unit is operated by College of Engineering staff and students, under the direct technical supervision of qualified Utilities plant staff. The Green Power Initiative also includes a substantial, innovative educational component. In addition to an onsite, graduate-level research program in biomass fuels, the investigators have integrated undergraduate and graduate level teaching – through classroom studies and experiential learning – and applied research into a biomass-based, university-scale, functioning power plant. University of Iowa is unique in that it currently has multiple renewable energy technologies deployed, including significant biomass combustion (oat hulls) at its Main Power Plant and a new reciprocating engine based renewable district energy system. This project complements and supports the national energy policy and State of Iowa initiatives in ethanol and biodiesel. Byproducts of ethanol and biodiesel processes (distiller grains) as well as industry residues (oat hulls, wood chips, construction and demolition

  2. Initial Egyptian ECMO experience

    Directory of Open Access Journals (Sweden)

    Akram Abdelbary

    2016-04-01

    Results: A total of twelve patients received ECMO between January 2014 and June 2015. The mean age was 35.9 years. (range 13–65 years, 8 males, with VV ECMO in 10 patients, and VA ECMO in 2 patients. Out of ten patients of VV ECMO, one had H1N1 pneumonia, one had advanced vasculitic lung, four had bacterial pneumonia, two traumatic lung contusions and one with organophosphorus poisoning, and one undiagnosed etiology leading to severe ARDS. Lung injury score range was 3–3.8, PaO2/FiO2 (20–76 mechanical ventilation duration before ECMO 1–14 days, Femoro-jugular cannulation in 7 patients and femoro-femoral in 2 patients and femoro-subclavian in 1 patient; all patients were initially sedated and paralyzed for (2–4 days and ventilated on pressure controlled ventilation with Pmax of 25 cm H2O and PEEP of 10 cm H2O. In VA ECMO patients were cannulated percutaneously using femoro-femoral approach. One patient showed no neurologic recovery and died after 24 h, the other had CABG on ECMO however the heart didn’t recover and died after 9 days. Heparin intravenous infusion was used initially in all patients and changed to Bivalirudin in 2 patients due to possible HIT. Pump flow ranged from 2.6 to 6.5 L/min. Average support time was 12 days (range 2–24 days. Seven patients (63.3% were successfully separated from ECMO and survived to hospital discharge. Hospital length of stay ranged from 3 to 42 days, tracheostomy was done percutaneously in 5 patients and surgically in 3. Gastrointestinal bleeding occurred in 6 patients, VAP in 7 patients, neurologic complications in 1 patient with complete recovery, cardiac arrhythmias in 3 patients, pneumothorax in 9 patients, and deep venous thrombosis in 2 patients.

  3. MONTANA PALLADIUM RESEARCH INITIATIVE

    Energy Technology Data Exchange (ETDEWEB)

    Peters, John; McCloskey, Jay; Douglas, Trevor; Young, Mark; Snyder, Stuart; Gurney, Brian

    2012-05-09

    Project Objective: The overarching objective of the Montana Palladium Research Initiative is to perform scientific research on the properties and uses of palladium in the context of the U.S. Department of Energy's Hydrogen, Fuel Cells and Infrastructure Technologies Program. The purpose of the research will be to explore possible palladium as an alternative to platinum in hydrogen-economy applications. To achieve this objective, the Initiatives activities will focus on several cutting-edge research approaches across a range of disciplines, including metallurgy, biomimetics, instrumentation development, and systems analysis. Background: Platinum-group elements (PGEs) play significant roles in processing hydrogen, an element that shows high potential to address this need in the U.S. and the world for inexpensive, reliable, clean energy. Platinum, however, is a very expensive component of current and planned systems, so less-expensive alternatives that have similar physical properties are being sought. To this end, several tasks have been defined under the rubric of the Montana Palladium Research Iniative. This broad swath of activities will allow progress on several fronts. The membrane-related activities of Task 1 employs state-of-the-art and leading-edge technologies to develop new, ceramic-substrate metallic membranes for the production of high-purity hydrogen, and develop techniques for the production of thin, defect-free platinum group element catalytic membranes for energy production and pollution control. The biomimetic work in Task 2 explores the use of substrate-attached hydrogen-producing enzymes and the encapsulation of palladium in virion-based protein coats to determine their utility for distributed hydrogen production. Task 3 work involves developing laser-induced breakdown spectroscopy (LIBS) as a real-time, in situ diagnostic technique to characterize PGEs nanoparticles for process monitoring and control. The systems engineering work in task 4

  4. TFTR initial operations

    International Nuclear Information System (INIS)

    Young, K.M.; Bell, M.; Blanchard, W.R.

    1984-01-01

    TFTR (Tokamak Fusion Test Reactor) has operated since December 1982 with ohmically heated plasmas. Routine operation with feedback control of plasma current, position and density has been obtained for plasmas with Isub(p) approx.= 800 kA, a = 68 cm, R = 250 cm, and Bsub(t) = 27 kG. A maximum plasma current of 1 MA was achieved with q approx.= 2.5. Energy confinement times of approx. 150 msec were measured for hydrogen and deuterium plasmas with n-barsub(e) approx.= 2 x 10 13 cm -3 , Tsub(e)(O) approx.= 1.5 keV, Tsub(i)(O) approx.= 1.5 keV and Zsub(eff) approx.= 3. The preliminary results suggest a size-cubed scaling from PLT, and are consistent with Alcator C scaling where tau approx. nR 2 a. Initial measurements of plasma disruption characteristics indicate current decay rates of approx. 800 kA in 8 ms which is within the TFTR design requirement of 3 MA in 3 ms. (author)

  5. The new childcare initiative

    CERN Multimedia

    Cigdem Issever

    The ATLAS Women's Network recently sent out a general mailing to all ATLAS and CMS members to announce a new initiative aimed at improving childcare facilities for Users coming to CERN. Several people have expressed the need that CERN should provide or facilitate affordable day care for children of temporary visitors at CERN. The ATLAS Women's Network is now forming a child care task force from concerned people and invites all those interested to join this effort. You can do so by either adding your name to the mailing list cern-users-childcare@cern.ch in Simba or by contacting Cigdem.Issever@cern.NOSPAM.ch and Pauline.Gagnon@cern.NOSPAM.ch. More than 50 people have already joined this effort. Those who have joined the mailing list will soon receive all the details about the next conference call meeting which has been scheduled for Thursday October 25th from 16:30 to 18:00 CERN time. The preliminary agenda is the following: Summary of our first contact of ATLAS and CMS (5 min) Discussion about the co-conv...

  6. AECL's new environmental initiatives

    International Nuclear Information System (INIS)

    McDonnell, F.N.

    1993-01-01

    AECL's research and development expenditures in environmental sciences and waste management technology are about $50 M per year. The main focus of these programs is the Nuclear Fuel Waste Management Program. This research is supplemented by activities in support of laboratory, Environmental Authority and internal waste management requirements, as well as provision of non-nuclear services. AECL intends to become more involved in performing environmental research and development with broader application. The goal is to achieve a relationship with Canadian industry that would involve a substantial portion of AECL's environmental research capabilities. The research directions and priorities of the resulting partnership would be set by the private sector in accordance with their needs and requirements. It is expected that the activities associated with this new environmental initiative will start small and grow in response to perceived needs. AECL is now increasing its non-nuclear research efforts by targeting those markets that appear most attractive. The thrust can be divided into three broad categories: environmental research, environmental services, and environmental products. (Author)

  7. TFTR initial operations

    International Nuclear Information System (INIS)

    Young, K.M.; Bell, M.; Blanchard, W.R.

    1983-11-01

    The Tokamak Fusion Test Reactor (TFTR) has operated since December 1982 with ohmically heated plasmas. Routine operation with feedback control of plasma current, position, and density has been obtained for plasmas with I/sub p/ approx. = 800 kA, a = 68 cm, R = 250 cm, and B/sub t/ = 27 kG. A maximum plasma current of 1 MA was achieved with q approx. = 2.5. Energy confinement times of approx. 150 msec were measured for hydrogen and deuterium plasmas with anti n/sub e/ approx. = 2 x 10 13 cm -3 , T/sub e/ (0) approx. = 1.5 keV, T/sub i/ (0) approx. = 1.5 keV, and Z/sub eff/ approx. = 3. The preliminary results suggest a size-cubed scaling from PLT and are consistent with Alcator C scaling where tau approx. nR 2 a. Initial measurements of plasma disruption characteristics indicate current decay rates of approx. 800 kA in 8 ms which is within the TFTR design requirement of 3 MA in 3 ms

  8. European nuclear education initiatives

    International Nuclear Information System (INIS)

    Glatz, Jean-Paul

    2011-01-01

    Whatever option regarding their future nuclear energy development is chosen by European Union Member States, the availability of a sufficient number of well trained and experienced staff is key for the responsible use of nuclear energy. This is true in all areas including design, construction, operation, decommissioning, fuel cycle and waste management as well as radiation protection. Given the high average age of existing experts leading to a significant retirement induce a real risk of the loss of nuclear competencies in the coming years. Therefore the demand of hiring skilled employees is rising. The challenge of ensuring a sufficient number of qualified staff in the nuclear sector has been acknowledged widely among the different stakeholders, in particular the nuclear industry, national regulatory authorities and Technical Support Organisations (TSOs). Already the EURATOM Treaty refers explicitly to the obligation for the Commission to carry out training actions. Recently initiatives have been launched at EU level to facilitate and strengthen the efforts of national stakeholders. The European Nuclear Education Network (ENEN) Association aims at preservation and further development of expertise in the nuclear field by higher education and training. The goal of the European Nuclear Energy Leadership Academy (ENELA) is to educate future leaders in the nuclear field to ensure the further development of sustainable European nuclear energy solutions The European Nuclear Energy Forum (ENEF) is a platform operated by the European Commission for a broad discussion on the opportunities and risks of nuclear energy. The nuclear programs under investigation in the Joint Research Center (JRC) are increasingly contributing to Education and Training (E and T) initiatives, promoting a better cooperation between key players and universities as well as operators and regulatory bodies in order to mutually optimise their training programmes. Another objective is to increase

  9. The MEGAPIE Initiative

    International Nuclear Information System (INIS)

    Salvatores, M.; Bauer, G.S.; Heusener, G.

    2000-10-01

    MEGAPIE (Megawatt Pilot Experiment) is a joint initiative by Commissariat a l'Energie Atomique (CEA), France, Forschungszentrum Karlsruhe (FZK), Germany, and Paul Scherrer Institut (PSI), Switzerland, to design, build, operate and explore a liquid lead-bismuth spallation target for 1MW of beam power, taking advantage of the existing spallation neutron facility SINQ at PSI. Such a target based on an eutectic mixture with a melting point as low as 125 o C and a boiling point as high as 1670 o C is the preferred concept in several studies aiming at utilising accelerators to drive subcritical assemblies in order to transmute long lived nuclear waste into shorter lived isotopes in an effort to ease problems of long term storage and final disposal. MEGAPIE will be an essential step towards demonstrating the feasibility of the coupling of a high power accelerator, a spallation target and a subcritical assembly. It will specifically address one of the most critical issues, namely the behaviour of a liquid metal target under realistic operating conditions. As an intensely instrumented pilot experiment it will provide valuable data for benchmarking of frequently used computer codes and will allow to gain important experience in the safe handling of components that have been irradiated with PbBi. It will be installed at the ring cyclotron at PSI with 590 MeV proton energy and a continuous current of 1.8 mA. The basic concept of the MEGAPIE target as well as the definition of the project phases and of the supporting research and development activities at the participating laboratories are described in the present report

  10. 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

  11. Hazardous material reduction initiative

    International Nuclear Information System (INIS)

    Nichols, D.H.

    1995-02-01

    The Hazardous Material Reduction Initiative (HMRI) explores using the review of purchase requisitions to reduce both the use of hazardous materials and the generation of regulated and nonregulated wastes. Based on an 11-month program implemented at the Hanford Site, hazardous material use and waste generation was effectively reduced by using a centralized procurement control program known as HMRI. As expected, several changes to the original proposal were needed during the development/testing phase of the program to accommodate changing and actual conditions found at the Hanford Site. The current method requires a central receiving point within the Procurement Organization to review all purchase requisitions for potentially Occupational Safety and Health Administration (OSHA) hazardous products. Those requisitions (approximately 4% to 6% of the total) are then forwarded to Pollution Prevention personnel for evaluation under HMRI. The first step is to determine if the requested item can be filled by existing or surplus material. The requisitions that cannot filled by existing or surplus material are then sorted into two groups based on applicability to the HMRI project. For example, laboratory requests for analytical reagents or standards are excluded and the purchase requisitions are returned to Procurement for normal processing because, although regulated, there is little opportunity for source reduction due to the strict protocols followed. Each item is then checked to determine if it is regulated or not. Regulated items are prioritized based on hazardous contents, quantity requested, and end use. Copies of these requisitions are made and the originals are returned to Procurement within 1-hr. Since changes to the requisition can be made at later stages during procurement, the HMRI fulfills one of its original premises in that it does not slow the procurement process

  12. Nursing Facility Initiative Annual Report

    Data.gov (United States)

    U.S. Department of Health & Human Services — This annual report summarizes impacts from the Initiative to Reduce Avoidable Hospitalizations among Nursing Facility Residents in 2014. This initiative is designed...

  13. National Take-Back Initiative

    Science.gov (United States)

    ... Disposal Information Drug and Chemical Information E-commerce Initiatives Federal Agencies & Related Links Federal Register Notices National ... Disposal Information Drug and Chemical Information E-commerce Initiatives Federal Agencies & Related Links Federal Register Notices National ...

  14. The national geomagnetic initiative

    Science.gov (United States)

    1993-01-01

    The Earth's magnetic field, through its variability over a spectrum of spatial and temporal scales, contains fundamental information on the solid Earth and geospace environment (the latter comprising the atmosphere, ionosphere, and magnetosphere). Integrated studies of the geomagnetic field have the potential to address a wide range of important processes in the deep mantle and core, asthenosphere, lithosphere, oceans, and the solar-terrestrial environment. These studies have direct applications to important societal problems, including resource assessment and exploration, natural hazard mitigation, safe navigation, and the maintenance and survivability of communications and power systems on the ground and in space. Studies of the Earth's magnetic field are supported by a variety of federal and state agencies as well as by private industry. Both basic and applied research is presently supported by several federal agencies, including the National Science Foundation (NSF), U.S. Geological Survey (USGS), U.S. Department of Energy (DOE), National Oceanic and Atmospheric Administration (NOAA), National Aeronautics and Space Administration (NASA), and U.S. Department of Defense (DOD) (through the Navy, Air Force, and Defense Mapping Agency). Although each agency has a unique, well-defined mission in geomagnetic studies, many areas of interest overlap. For example, NASA, the Navy, and USGS collaborate closely in the development of main field reference models. NASA, NSF, and the Air Force collaborate in space physics. These interagency linkages need to be strengthened. Over the past decade, new opportunities for fundamental advances in geomagnetic research have emerged as a result of three factors: well-posed, first-order scientific questions; increased interrelation of research activities dealing with geomagnetic phenomena; and recent developments in technology. These new opportunities can be exploited through a national geomagnetic initiative to define objectives and

  15. Initial Radionuclide Inventories

    Energy Technology Data Exchange (ETDEWEB)

    H. Miller

    2004-09-19

    The purpose of this analysis is to provide an initial radionuclide inventory (in grams per waste package) and associated uncertainty distributions for use in the Total System Performance Assessment for the License Application (TSPA-LA) in support of the license application for the repository at Yucca Mountain, Nevada. This document is intended for use in postclosure analysis only. Bounding waste stream information and data were collected that capture probable limits. For commercially generated waste, this analysis considers alternative waste stream projections to bound the characteristics of wastes likely to be encountered using arrival scenarios that potentially impact the commercial spent nuclear fuel (CSNF) waste stream. For TSPA-LA, this radionuclide inventory analysis considers U.S. Department of Energy (DOE) high-level radioactive waste (DHLW) glass and two types of spent nuclear fuel (SNF): CSNF and DOE-owned (DSNF). These wastes are placed in two groups of waste packages: the CSNF waste package and the codisposal waste package (CDSP), which are designated to contain DHLW glass and DSNF, or DHLW glass only. The radionuclide inventory for naval SNF is provided separately in the classified ''Naval Nuclear Propulsion Program Technical Support Document'' for the License Application. As noted previously, the radionuclide inventory data presented here is intended only for TSPA-LA postclosure calculations. It is not applicable to preclosure safety calculations. Safe storage, transportation, and ultimate disposal of these wastes require safety analyses to support the design and licensing of repository equipment and facilities. These analyses will require radionuclide inventories to represent the radioactive source term that must be accommodated during handling, storage and disposition of these wastes. This analysis uses the best available information to identify the radionuclide inventory that is expected at the last year of last emplacement

  16. Citizen participation and citizen initiatives

    International Nuclear Information System (INIS)

    Matthoefer, H.

    1977-01-01

    Contents: Social conditions for citizen initiatives - technical change and employment - crisis behaviour - socio-psychological analysis of political planning; legitimation - presentation and criticism - conditions for citizen initiatives coming into being within the field of tension citizen : administration - legal problems of citizen initiatives - environmental protection in the energy discussion; participation; models. (HP) [de

  17. NLM Emergency Access Initiative: FAQs

    Science.gov (United States)

    Facebook Visit us on Twitter Visit us on Youtube Emergency Access Initiative Home | Journals | Books | Online Databases | FAQs Take Short Survey FAQ What is the Emergency Access Initiative? The Emergency Access Initiative (EAI) is a collaborative partnership between NLM and participating publishers to

  18. Community Rates of Breastfeeding Initiation.

    Science.gov (United States)

    Grubesic, Tony H; Durbin, Kelly M

    2016-11-01

    Breastfeeding initiation rates vary considerably across racial and ethnic groups, maternal age, and education level, yet there are limited data concerning the influence of geography on community rates of breastfeeding initiation. This study aimed to describe how community rates of breastfeeding initiation vary in geographic space, highlighting "hot spots" and "cool spots" of initiation and exploring the potential connections between race, socioeconomic status, and urbanization levels on these patterns. Birth certificate data from the Kentucky Department of Health for 2004-2010 were combined with county-level geographic base files, Census 2010 demographic and socioeconomic data, and Rural-Urban Continuum Codes to conduct a spatial statistical analysis of community rates of breastfeeding initiation. Between 2004 and 2010, the average rate of breastfeeding initiation for Kentucky increased from 43.84% to 49.22%. Simultaneously, the number of counties identified as breastfeeding initiation hot spots also increased, displaying a systematic geographic pattern in doing so. Cool spots of breastfeeding initiation persisted in rural, Appalachian Kentucky. Spatial regression results suggested that unemployment, income, race, education, location, and the availability of International Board Certified Lactation Consultants are connected to breastfeeding initiation. Not only do spatial analytics facilitate the identification of breastfeeding initiation hot spots and cool spots, but they can be used to better understand the landscape of breastfeeding initiation and help target breastfeeding education and/or support efforts.

  19. Florida Hydrogen Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Block, David L

    2013-06-30

    The Florida Hydrogen Initiative (FHI) was a research, development and demonstration hydrogen and fuel cell program. The FHI program objectives were to develop Florida?s hydrogen and fuel cell infrastructure and to assist DOE in its hydrogen and fuel cell activities The FHI program funded 12 RD&D projects as follows: Hydrogen Refueling Infrastructure and Rental Car Strategies -- L. Lines, Rollins College This project analyzes strategies for Florida's early stage adaptation of hydrogen-powered public transportation. In particular, the report investigates urban and statewide network of refueling stations and the feasibility of establishing a hydrogen rental-car fleet based in Orlando. Methanol Fuel Cell Vehicle Charging Station at Florida Atlantic University ? M. Fuchs, EnerFuel, Inc. The project objectives were to design, and demonstrate a 10 kWnet proton exchange membrane fuel cell stationary power plant operating on methanol, to achieve an electrical energy efficiency of 32% and to demonstrate transient response time of less than 3 milliseconds. Assessment of Public Understanding of the Hydrogen Economy Through Science Center Exhibits, J. Newman, Orlando Science Center The project objective was to design and build an interactive Science Center exhibit called: ?H2Now: the Great Hydrogen Xchange?. On-site Reformation of Diesel Fuel for Hydrogen Fueling Station Applications ? A. Raissi, Florida Solar Energy Center This project developed an on-demand forecourt hydrogen production technology by catalytically converting high-sulfur hydrocarbon fuels to an essentially sulfur-free gas. The removal of sulfur from reformate is critical since most catalysts used for the steam reformation have limited sulfur tolerance. Chemochromic Hydrogen Leak Detectors for Safety Monitoring ? N. Mohajeri and N. Muradov, Florida Solar Energy Center This project developed and demonstrated a cost-effective and highly selective chemochromic (visual) hydrogen leak detector for safety

  20. 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

  1. EXPERIENCES WITH IDEA PROMOTING INITIATIVES

    DEFF Research Database (Denmark)

    Gish, Liv

    2011-01-01

    In new product development a central activity is to provide new ideas. Over the last decades experiences with stimulating employee creativity and establishing idea promoting initiatives have been made in industrial practice. Such initiatives are often labeled Idea Management – a research field...... with a growing interest. In this paper I examine three different idea promoting initiatives carried out in Grundfos, a leading pump manufacturer. In the analysis I address what understandings of idea work are inscribed in the initiatives and what role these initiatives play in the organization with respect...... understandings of idea work are inscribed in the idea promoting initiatives as they to some degree have to fit with the understandings embedded in practice in order to work....

  2. Initiation into Adolescent Marijuana Use.

    Science.gov (United States)

    Brook, Judith S.; And Others

    1980-01-01

    This longitudinal study examined the relationship of three domains (personality/attitudinal orientations, peer relationships, and family socialization factors) with initiation into adolescent marihuana use. (Author/DB)

  3. Student initiative: A conceptual analysis

    Directory of Open Access Journals (Sweden)

    Polovina Nada

    2014-01-01

    Full Text Available In the description and scientific consideration of the attitude of children and youth towards their education and development, the concept of student initiative has been gaining ground lately, and it is hence the subject of analysis in this paper. The analysis is important because of the discrepancy between the increased efforts of the key educational policy holders to promote the idea about the importance of the development of student initiative and rare acceptance of this idea among theoreticians, researchers and practitioners dealing with the education and development of children and youth. By concretising the features of initiative student behaviour, our aim was, on the one hand, to observe the structural determinants and scientific status of the very concept of an initiative student, and, on the other, to contribute to the understanding of the initiative behaviour in practice. In the first part of the paper we deal with different notions and concretisations of the features of initiative behaviour of children and youth, which includes the consideration of: basic student initiative, academic student initiative, individual student initiative, the capacity for initiative and personal development initiative. In the second part of the paper, we discuss the relations of the concept of student initiative with the similar general concepts (activity/passivity, proactivity, agency and the concepts immediately related to school environment (student involvement, student participation. The results of our analysis indicate that the concept of student initiative has: particular features that differentiate it from similar concepts; the potential to reach the status of a scientific concept, bearing in mind the initial empirical specifications and general empirical verifiability of the yet unverified determinants of the concept. In the concluding part of the paper, we discuss the implications of the conceptual analysis for further research, as well as for

  4. Career Technical Education Pathways Initiative

    Science.gov (United States)

    California Community Colleges, Chancellor's Office, 2013

    2013-01-01

    California's education system--the largest in the United States--is an essential resource for ensuring strong economic growth in the state. The Career Technical Education Pathways Initiative (referred to as the Initiative in this report), which became law in 2005, brings together community colleges, K-12 school districts, employers, organized…

  5. The metabolomics standards initiative (MSI)

    NARCIS (Netherlands)

    Fiehn, O.; Robertson, D.; Griffin, J.; Werf, M. van der; Nikolau, B.; Morrison, N.; Sumner, L.W.; Goodacre, R.; Hardy, N.W.; Taylor, C.; Fostel, J.; Kristal, B.; Kaddurah-Daouk, R.; Mendes, P.; Ommen, B. van; Lindon, J.C.; Sansone, S.-A.

    2007-01-01

    In 2005, the Metabolomics Standards Initiative has been formed. An outline and general introduction is provided to inform about the history, structure, working plan and intentions of this initiative. Comments on any of the suggested minimal reporting standards are welcome to be sent to the open

  6. Behavioral Initiatives in Broad Perspective.

    Science.gov (United States)

    California Univ., Los Angeles. Center for Mental Health in Schools.

    This booklet is a technical assistance sampler addressing the issues of student misbehavior, discipline problems, and behavioral initiatives. The term behavioral initiative is defined, disciplining children with disabilities is discussed, and a cautionary note concerning ignoring students' reasons for misbehavior is presented. A brief entitled…

  7. Local initiative extrapolated to nation

    DEFF Research Database (Denmark)

    Wittchen, Kim Bjarne; Kragh, Jesper; Brøgger, Morten

    In the municipality of Sønderborg, in the southern part of Jutland, there is a shining example initiated in 2007, ProjectZero, of a local initiative that have resulted in extensive energy savings in residential buildings and at the same time created local workplaces. The intension with the pilot...

  8. Northern Eurasia Future Initiative (NEFI)

    DEFF Research Database (Denmark)

    Groisman, Pavel; Shugart, Herman; Kicklighter, David

    2017-01-01

    . The Northern Eurasia Future Initiative (NEFI) has been designed as an essential continuation of the Northern Eurasia Earth Science Partnership Initiative (NEESPI), which was launched in 2004. NEESPI sought to elucidate all aspects of ongoing environmental change, to inform societies and, thus, to better...

  9. Comprehensive School Safety Initiative Report

    Science.gov (United States)

    National Institute of Justice, 2014

    2014-01-01

    The National Institute of Justice (NIJ) developed the Comprehensive School Safety Initiative in consultation with federal partners and Congress. It is a research-focused initiative designed to increase the safety of schools nationwide through the development of knowledge regarding the most effective and sustainable school safety interventions and…

  10. 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.)

  11. Self-initiated expatriate academics

    DEFF Research Database (Denmark)

    Selmer, Jan; Lauring, Jakob

    2013-01-01

    In this chapter we examine self-initiated expatriate academics. Universities are to an increasing extent looking for talent beyond national boundaries. Accordingly, self-initiated expatriate academics represent a fast growing group of highly educated professionals who gain employment abroad...

  12. In vitro culture of bovine embryos in murine ES cell conditioned media negatively affects expression of pluripotency-related markers OCT4, SOX2 and SSEA1.

    Science.gov (United States)

    Oliveira, C S; de Souza, M M; Saraiva, N Z; Tetzner, T A D; Lima, M R; Lopes, F L; Garcia, J M

    2012-06-01

    Despite extensive efforts, establishment of bovine embryonic stem (ES) cell lines has not been successful. We hypothesized that culture conditions for in vitro-produced (IVP) embryos, the most used source of inner cell mass (ICM) to obtain ES cells, might affect their undifferentiated state. Therefore, the aim of this work was to improve pluripotency of IVP blastocysts to produce suitable ICM for further culturing. We tested KSR and foetal calf serum (FCS) supplements in SOF medium and ES cell conditioned medium (CM) on IVC (groups: KSR, KSR CM, FCS and FCS CM). Cleavage and blastocyst rates were similar between all groups. Also, embryonic quality, assessed by apoptosis rates (TUNEL assay), total cell number and ICM percentage did not differ between experimental groups. However, expression of pluripotency-related markers was affected. We detected down-regulation of OCT3/4, SOX2 and SSEA1 in ICM of FCS CM blastocysts (p < 0.05). SOX2 gene expression revealed lower levels (p < 0.05) on KSR CM blastocysts and a remarkable variation in SOX2 mRNA levels on FCS-supplemented blastocysts. In conclusion, pluripotency-related markers tend to decrease after supplementation with ES cell CM, suggesting different mechanisms regulating mouse and bovine pluripotency. KSR supplementation did not differ from FCS, but FCS replacement by KSR may produce blastocysts with stable SOX2 gene expression levels. © 2011 Blackwell Verlag GmbH.

  13. Defense Acquisition Initiatives Review: An Assessment of Extant Initiatives

    National Research Council Canada - National Science Library

    Porter, Gene; Berteau, David; Christle, Gary; Mandelbaum, Jay; Diehl, Richard

    2005-01-01

    ...) to identify and analyze a subset of initiatives that the team finds to have potential for near term management emphasis that could provide visible improvements to the much criticized Defense acquisition system...

  14. Initial Assessment of Whiplash Patients

    Directory of Open Access Journals (Sweden)

    R Gunzburg

    2003-01-01

    Full Text Available The article looks at how for severe trauma, the outcome of treatment depends on the initial medical care. This has now also been accepted for whiplash associated disorders, underlining the importance of a proper initial assessment. Once major injury has been excluded and the diagnosis of whiplash associated disorder has been established, the initial treatment of whiplash in the emergency room can be started. The four key points to remember are described, including reassuring the patient about evolution, no soft collar, nonsteroidal anti-inflammatory drugs and early mobilisation.

  15. Canada's family violence initiative: partnerships

    Directory of Open Access Journals (Sweden)

    Elaine Scott

    1994-01-01

    Full Text Available Under Canada's four-year, $136 million Family Violence Initiative, the federal government is calling upon all Canadians to work in partnerships towards the elimination of family violence - child abuse, violence against women, and elder (senior abuse. Family violence is a complex problem and requires the efforts of all Canadians to resolve it. One of the key themes of the Initiative - a multidisciplinary approach to the problem of family violence - is reflected in the selection and development of projects. Activities funded by the seven federal departments and agencies involved in the Initiative emphasize partnerships with the professional, voluntary, corporate, non-government and government sectors.

  16. Learning from the Ilulissat Initiative

    DEFF Research Database (Denmark)

    Rahbek-Clemmensen, Jon; Thomasen, Gry

    In May 2018, ten years will have passed since the representatives from the five Arctic coastal states (Canada, Denmark, Norway, Russia) and the Home Rule government of Greenland met in Ilulissat. Learning from the Ilulissat Initiative examines how the initiative came about, and how it has affected...... strong economic interests in maintaining peaceful Arctic relations. Northern forums therefore give policymakers a rare opportunity to meet, communicate, and influence a key region. The Ilulissat meeting was the result of a joint Danish‒Greenlandic initiative and is often hailed as one of the most...

  17. The Luxembourg Space Resources Initiative

    Science.gov (United States)

    Link, M.

    2017-09-01

    This keynote talk by M. Link from the Directorate of ICT and Space Affairs, Ministry of the Economy, The Government of the Grand Duchy of Luxembourg, will provide an overview of Luxembourg's ins-space resource utilization initiative.

  18. Integrated landscape initiatives in Europe

    DEFF Research Database (Denmark)

    García-Martín, María; Bieling, Claudia; Hart, Abigail

    2016-01-01

    Landscapes are linked to human well-being in a multitude of ways, some of which are challenged by global market forces and traditional management approaches. In response to this situation there has been a rise in local initiatives to sustain the values of landscape. The aim of this paper is to pr......Landscapes are linked to human well-being in a multitude of ways, some of which are challenged by global market forces and traditional management approaches. In response to this situation there has been a rise in local initiatives to sustain the values of landscape. The aim of this paper...... searches and canvassing of European umbrella organisations; followed by an online survey of representatives from the identified initiatives (n??=??71). Our results show that the most relevant characteristics of integrated landscape initiatives in Europe are: a holistic approach to landscape management...

  19. FY 10 Multifamily Initial Endorsements

    Data.gov (United States)

    Department of Housing and Urban Development — In FY 2010, HUD's Multifamily's 18 Hubs initially endorsed 1011 loans totaling $11.3 billion and providing 170,672 units/ beds. FY 10's $11.3 billion is the highest...

  20. Smart roadside initiative : user manual.

    Science.gov (United States)

    2015-09-01

    This document provides the user instructions for the Smart Roadside Initiative (SRI) applications including mobile and web-based SRI applications. These applications include smartphone-enabled information exchange and notification, and software compo...

  1. Smart roadside initiative : final report.

    Science.gov (United States)

    2015-09-01

    This is the Final Report for the Smart Roadside Initiative (SRI) prototype system deployment project. The SRI prototype was implemented at weigh stations in Grass Lake, Michigan and West Friendship, Maryland. The prototype was developed to integrate ...

  2. Global Peace Operations Initiative (GPOI)

    National Research Council Canada - National Science Library

    Kim-Mitchell, Elena

    2005-01-01

    .... In terms of manpower, the initiative aims at deploying 75,000 peace support operations (PSO) troops worldwide over the next 5 years, primarily to Africa, but also to Latin America, Europe, and Asia...

  3. Canada's family violence initiative: partnerships

    OpenAIRE

    Scott,Elaine

    1994-01-01

    Under Canada's four-year, $136 million Family Violence Initiative, the federal government is calling upon all Canadians to work in partnerships towards the elimination of family violence - child abuse, violence against women, and elder (senior) abuse. Family violence is a complex problem and requires the efforts of all Canadians to resolve it. One of the key themes of the Initiative - a multidisciplinary approach to the problem of family violence - is reflected in the selection and developmen...

  4. Student initiative: A conceptual analysis

    OpenAIRE

    Polovina Nada

    2014-01-01

    In the description and scientific consideration of the attitude of children and youth towards their education and development, the concept of student initiative has been gaining ground lately, and it is hence the subject of analysis in this paper. The analysis is important because of the discrepancy between the increased efforts of the key educational policy holders to promote the idea about the importance of the development of student initiative and rare a...

  5. Teachers’ perceptions of their own initiative: Collective initiative vs. personal initiative

    Directory of Open Access Journals (Sweden)

    Džinović Vladimir

    2013-01-01

    Full Text Available Current trends in education demand from teachers to exhibit proactive behaviour and assume responsibility for the implementation of changes in school practice. In that sense, it is important to study how teachers perceive their own initiative and to gain insight into the activities where such initiative is demonstrated. This study has been conceived as a mixed-methods research. The qualitative study implied forming four focus groups with subject teachers and class teachers (N=38, while the quantitative study entailed surveying 1441 teachers in forty primary schools in Serbia using the questionnaire constructed based on qualitative data. Data from focus groups were processed by qualitative thematic analysis, while the questionnaire data were processed by principal component analysis and univariate analysis of variance. The findings of the study have shown that teachers mostly demonstrate initiative through co­operative activities that include planning of joint teaching as well as conducting joint projects within school and with the local community actors. Teachers are least ready to demonstrate personal initiative and the initiative aimed at accomplishing considerable changes in school work. The concluding part includes the recommendations for encouraging teachers’ personal initiative and building organizational culture that would support such initiative. [Projekat Ministarstva nauke Republike Srbije, br. br. 47008: Unapređivanje kvaliteta i dostupnosti obrazovanja u procesima modernizacije Srbije i br. 179034: Od podsticanja inicijative, saradnje i stvaralaštva u obrazovanju do novih uloga i identiteta u društvu

  6. Integrated Initiating Event Performance Indicators

    International Nuclear Information System (INIS)

    S. A. Eide; Dale M. Rasmuson; Corwin L. Atwood

    2005-01-01

    The U.S. Nuclear Regulatory Commission Industry Trends Program (ITP) collects and analyses industry-wide data, assesses the safety significance of results, and communicates results to Congress and other stakeholders. This paper outlines potential enhancements in the ITP to comprehensively cover the Initiating Events Cornerstone of Safety. Future work will address other cornerstones of safety. The proposed Tier 1 activity involves collecting data on ten categories of risk-significant initiating events, trending the results, and comparing early performance with prediction limits (allowable numbers of events, above which NRC action may occur). Tier 1 results would be used to monitor industry performance at the level of individual categories of initiating events. The proposed Tier 2 activity involves integrating the information for individual categories of initiating events into a single risk-based indicator, termed the Baseline Risk Index for Initiating Events or BRIIE. The BRIIE would be evaluated yearly and compared against a threshold. BRIIE results would be reported to Congress on a yearly basis

  7. Characteristics of patients initiating raloxifene compared to those initiating bisphosphonates

    Directory of Open Access Journals (Sweden)

    Wang Sara

    2008-12-01

    Full Text Available Abstract Background Both raloxifene and bisphosphonates are indicated for the prevention and treatment of postmenopausal osteoporosis, however these medications have different efficacy and safety profiles. It is plausible that physicians would prescribe these agents to optimize the benefit/risk profile for individual patients. The objective of this study was to compare demographic and clinical characteristics of patients initiating raloxifene with those of patients initiating bisphosphonates for the prevention and treatment of osteoporosis. Methods This study was conducted using a retrospective cohort design. Female beneficiaries (45 years and older with at least one claim for raloxifene or a bisphosphonate in 2003 through 2005 and continuous enrollment in the previous 12 months and subsequent 6 months were identified using a collection of large national commercial, Medicare supplemental, and Medicaid administrative claims databases (MarketScan®. Patients were divided into two cohorts, a combined commercial/Medicare cohort and a Medicaid cohort. Within each cohort, characteristics (demographic, clinical, and resource utilization of patients initiating raloxifene were compared to those of patients initiating bisphosphonate therapy. Group comparisons were made using chi-square tests for proportions of categorical measures and Wilcoxon rank-sum tests for continuous variables. Logistic regression was used to simultaneously examine factors independently associated with initiation of raloxifene versus a bisphosphonate. Results Within both the commercial/Medicare and Medicaid cohorts, raloxifene patients were younger, had fewer comorbid conditions, and fewer pre-existing fractures than bisphosphonate patients. Raloxifene patients in both cohorts were less likely to have had a bone mineral density (BMD screening in the previous year than were bisphosphonate patients, and were also more likely to have used estrogen or estrogen/progestin therapy in the

  8. The sustainable wood production initiative.

    Science.gov (United States)

    Robert. Deal

    2004-01-01

    To address concerns about sustainable forestry in the region, the Focused Science Delivery Program is sponsoring a three year Sustainable Wood Production Initiative. The Pacific Northwest is one of the world's major timber producing regions, and the ability of this region to produce wood on a sustained yield basis is widely recognized. Concerns relating to the...

  9. Intelligent vehicle initiative : business plan

    Science.gov (United States)

    1997-11-01

    The U.S. Department of Transportation (USDOT) is embarking on a new program called the Intelligent Vehicle Initiative (IVI). The USDOT intends to jointly define the program plan and conduct the IVI in cooperation with the motor vehicle, trucking, and...

  10. Nuclear materials facility safety initiative

    International Nuclear Information System (INIS)

    Peddicord, K.L.; Nelson, P.; Roundhill, M.; Jardine, L.J.; Lazarev, L.; Moshkov, M.; Khromov, V.V.; Kruchkov, E.; Bolyatko, V.; Kazanskij, Yu.; Vorobeva, I.; Lash, T.R.; Newton, D.; Harris, B.

    2000-01-01

    Safety in any facility in the nuclear fuel cycle is a fundamental goal. However, it is recognized that, for example, should an accident occur in either the U.S. or Russia, the results could seriously delay joint activities to store and disposition weapons fissile materials in both countries. To address this, plans are underway jointly to develop a nuclear materials facility safety initiative. The focus of the initiative would be to share expertise which would lead in improvements in safety and safe practices in the nuclear fuel cycle.The program has two components. The first is a lab-to-lab initiative. The second involves university-to-university collaboration.The lab-to-lab and university-to-university programs will contribute to increased safety in facilities dealing with nuclear materials and related processes. These programs will support important bilateral initiatives, develop the next generation of scientists and engineers which will deal with these challenges, and foster the development of a safety culture

  11. Initial heating in cold cars

    NARCIS (Netherlands)

    Daanen, H.A.M.; Teunissen, L.P.J.; Hoogh, I.M. de

    2012-01-01

    During the initial minutes after entering a cold car, people feel uncomfortably cold. Six different warming systems were investigated in a small car in order to find out how to improve the feeling of comfort using 16 volunteers. The methods were: no additional warming next to a standard heating

  12. Does the cerebellum initiate movement?

    Science.gov (United States)

    Thach, W T

    2014-02-01

    Opinion is divided on what the exact function of the cerebellum is. Experiments are summarized that support the following views: (1) the cerebellum is a combiner of multiple movement factors; (2) it contains anatomically fixed permanent focal representation of individual body parts (muscles and segments) and movement modes (e.g., vestibular driven vs. cognitive driven); (3) it contains flexible changing representations/memory of physical properties of the body parts including muscle strength, segment inertia, joint viscosity, and segmental interaction torques (dynamics); (4) it contains mechanisms for learning and storage of the properties in item no. 3 through trial-and-error practice; (5) it provides for linkage of body parts, motor modes, and motordynamics via the parallel fiber system; (6) it combines and integrates the many factors so as to initiate coordinated movements of the many body parts; (7) it is thus enabled to play the unique role of initiating coordinated movements; and (8) this unique causative role is evidenced by the fact that: (a) electrical stimulation of the cerebellum can initiate compound coordinated movements; (b) in naturally initiated compound movements, cerebellar discharge precedes that in downstream target structures such as motor cerebral cortex; and (c) cerebellar ablation abolishes the natural production of compound movements in the awake alert individuals.

  13. Light-initiated detonation systems

    Science.gov (United States)

    Cooper, Stafford S.; Malone, Philip G.; Bartholomew, Stephen W.; Necker, William J.

    1986-09-01

    Numerous light sources could be employed in detonation systems, but lasers have the most efficient coupling to optical fibers and can generate energetic light pulses required for detonation. Flash lamp-pumped, solid state lasers are presently the most useful light source for explosive initiation. Laser diodes in current production cannot generate enough energy for practical applications. The most useful optical fiber for blast line application is a step index fiber with a large core-to-cladding ratio. The large core minimizes energy losses due to misalignment core of fibers in connectors. Couplers that involve mechanically crimped connectors and cleaved fibers, rather than the epoxy-cemented connectors with polished fibers, provide superior energy transmission due to the reduced carbonization at the fiber end. Detonators for optical initiation systems are similar in basic construction to those employed in electrical initiation systems. Explosive and pyrotechnic charges can also be similar. Either primary or secondary explosives can be initiated in present laser-based systems. Two laser detonation systems are presently accessible; a multiple-shot laser with a single-shot, single fiber system designed for use with detonators containing primary explosives. Additional research related to development of low-energy, photoreactive detonators, continuity checking techniques and improved connectors and fibers can produce significant improvements in presently fielded systems.

  14. Big Data Initiatives for Agroecosystems

    Science.gov (United States)

    NAL has developed a workspace for research groups associated with the i5k initiative, which aims to sequence the genomes of all insesct species known to be important to worldwide agriculture, food safety, medicine, and energy production; all those used as models in biology; the most abundant in worl...

  15. Smoking Initiation: Peers and Personality

    NARCIS (Netherlands)

    C-S. Hsieh (Chih-Sheng); J.L.W. van Kippersluis (Hans)

    2016-01-01

    textabstractSocial interactions are widely recognized to play an important role in smoking initiation among adolescents. In this paper we hypothesize that individual with `stronger' personalities (i.e. emotionally stable, conscientious individuals) are better able to resist peer pressure in the

  16. Vacuum type D initial data

    Science.gov (United States)

    García-Parrado Gómez-Lobo, Alfonso

    2016-09-01

    A vacuum type D initial data set is a vacuum initial data set of the Einstein field equations whose data development contains a region where the space–time is of Petrov type D. In this paper we give a systematic characterisation of a vacuum type D initial data set. By systematic we mean that the only quantities involved are those appearing in the vacuum constraints, namely the first fundamental form (Riemannian metric) and the second fundamental form. Our characterisation is a set of conditions consisting of the vacuum constraints and some additional differential equations for the first and second fundamental forms These conditions can be regarded as a system of partial differential equations on a Riemannian manifold and the solutions of the system contain all possible regular vacuum type D initial data sets. As an application we particularise our conditions for the case of vacuum data whose data development is a subset of the Kerr solution. This has applications in the formulation of the nonlinear stability problem of the Kerr black hole.

  17. Initial drug resistance in India

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Initial drug resistance in India. There is gradual increase in primary MDR all over India : Pondi= Pondicherry 1985; Bangalore =1986; Jaipur = 1991; Jaipur =2000. Overall the MDR is less than 3% (TRC studies).

  18. Parenting and Adolescents' Sexual Initiation

    Science.gov (United States)

    Longmore, Monica A.; Eng, Abbey L.; Giordano, Peggy C.; Manning, Wendy D.

    2009-01-01

    This study draws on social control and social learning theories to examine the role of dating-specific attitudes and practices as predictors of adolescents' sexual initiation. We include attention to the adolescent's reaction to control attempts as a further means of assessing family dynamics (i.e., frequency of dating disagreements). The study…

  19. Russian Initiatives in Internet Governance

    Directory of Open Access Journals (Sweden)

    Sergey Sergeevich Shirin

    2014-01-01

    Full Text Available The article is devoted to the research of Russian initiatives concerning its participation in international system of Internet governance. In the research, conceptual and theoretic basis for participation of state governments in Internet governance is given, academic discourse of this issue is assessed, the review of main Russian initiatives made from 2005 (since the second stage of the World Summit on Information Society till the present day is carried out. The conclusion is made that the most successful Internet governance initiative of Russia is the implementation of cyrillic top level domains. Much less successful are Russian attempts to reconstruct existing organizational structure of Internet governance. Russian policy is assessed as a policy of preferring loud statements and PR rather than real influence on development of Internet technologies. Russia consideres Internet as political resource and tries to increase its influence on decision making process on a political, not operational level of Internet governance. The author states that federal government of the United States of America has fully lost the control on the domain name systems. These functions are going to be given to the private sector, while ICANN, which was established according to the Memorandum of Understanding/Joint Project Agreement with U.S. Department of Commerce, is becoming a truly independent international organization. Considering this, the author comes to the conclusion that political transformations for the sake of Russia are already made. He also forecast that next initiatives of Russia will be directed to the segmentation of the Internet.

  20. Fayette County Better Buildings Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Capella, Arthur [County of Fayette, Uniontown, PA (United States)

    2015-03-04

    The Fayette County Better Buildings Initiative represented a comprehensive and collaborative approach to promoting and implementing energy efficiency improvements. The initiative was designed to focus on implementing energy efficiency improvements in residential units, while simultaneously supporting general marketing of the benefits of implementing energy efficiency measures. The ultimate goal of Fayette County’s Better Buildings Initiative was to implement a total of 1,067 residential energy efficiency retrofits with a minimum 15% estimated energy efficiency savings per unit. Program partners included: United States Department of Energy, Allegheny Power, and Private Industry Council of Westmoreland-Fayette, Fayette County Redevelopment Authority, and various local partners. The program was open to any Fayette County residents who own their home and meet the prequalifying conditions. The level of assistance offered depended upon household income and commitment to undergo a BPI – Certified Audit and implement energy efficiency measures, which aimed to result in at least a 15% reduction in energy usage. The initiative was designed to focus on implementing energy efficiency improvements in residential units, while simultaneously supporting general marketing of the benefits of implementing energy efficiency measures. Additionally, the program had components that involved recruitment and training for employment of persons in the energy sector (green jobs), as well as marketing and implementation of a commercial or community facilities component. The residential component of Fayette County’s Better Buildings Initiative involved a comprehensive approach, providing assistance to low- moderate- and market-rate homeowners. The initiative will also coordinate activities with local utility providers to further incentivize energy efficiency improvements among qualifying homeowners. The commercial component of Fayette County’s Better Building Initiative involved grants

  1. Initiation disruptor systems and methods of initiation disruption

    Science.gov (United States)

    Baum, Dennis W

    2014-09-23

    A system that may be used as an initiation disruption system (IDS) according to one embodiment includes an explosive charge; a plurality of particles in a layer at least partially surrounding the explosive charge; and a fire suppressant adjacent the plurality of particles. A method for disabling an object according to one embodiment includes placing the system as recited above near an object; and causing the explosive charge to initiate, thereby applying mechanical loading to the object such that the object becomes disabled. Additional systems and methods are also presented. A device according to another embodiment includes a plurality of particles bound by a binder thereby defining a sidewall having an interior for receiving an explosive; and a fire suppressant adjacent the plurality of particles and binder. Additional systems and methods are also presented.

  2. Energy efficiency initiatives: Indian experience

    Energy Technology Data Exchange (ETDEWEB)

    Dey, Dipankar [ICFAI Business School, Kolkata, (IBS-K) (India)

    2007-07-01

    India, with a population of over 1.10 billion is one of the fastest growing economies of the world. As domestic sources of different conventional commercial energy are drying up, dependence on foreign energy sources is increasing. There exists a huge potential for saving energy in India. After the first 'oil shock' (1973), the government of India realized the need for conservation of energy and a 'Petroleum Conservation Action Group' was formed in 1976. Since then many initiatives aiming at energy conservation and improving energy efficiency, have been undertaken (the establishment of Petroleum Conservation Research Association in 1978; the notification of Eco labelling scheme in 1991; the formation of Bureau of Energy Efficiency in 2002). But no such initiative was successful. In this paper an attempt has been made to analyze the changing importance of energy conservation/efficiency measures which have been initiated in India between 1970 and 2005.The present study tries to analyze the limitations and the reasons of failure of those initiatives. The probable reasons are: fuel pricing mechanism (including subsidies), political factors, corruption and unethical practices, influence of oil and related industry lobbies - both internal and external, the economic situation and the prolonged protection of domestic industries. Further, as India is opening its economy, the study explores the opportunities that the globally competitive market would offer to improve the overall energy efficiency of the economy. The study suggests that the Bureau of Energy Efficiency (BEE) - the newly formed nodal agency for improving energy efficiency of the economy may be made an autonomous institution where intervention from the politicians would be very low. For proper implementation of different initiatives to improve energy efficiency, BEE should involve more the civil societies (NGO) from the inception to the implementation stage of the programs. The paper also

  3. Initial Semantics for Strengthened Signatures

    Directory of Open Access Journals (Sweden)

    André Hirschowitz

    2012-02-01

    Full Text Available We give a new general definition of arity, yielding the companion notions of signature and associated syntax. This setting is modular in the sense requested by Ghani and Uustalu: merging two extensions of syntax corresponds to building an amalgamated sum. These signatures are too general in the sense that we are not able to prove the existence of an associated syntax in this general context. So we have to select arities and signatures for which there exists the desired initial monad. For this, we follow a track opened by Matthes and Uustalu: we introduce a notion of strengthened arity and prove that the corresponding signatures have initial semantics (i.e. associated syntax. Our strengthened arities admit colimits, which allows the treatment of the λ-calculus with explicit substitution.

  4. Blasting agents and initiation systems

    Energy Technology Data Exchange (ETDEWEB)

    Fiscor, S.

    2000-01-01

    Although blasting differs between and within each industry, as a whole, the mines and quarries are making a shift from a purely ammonium nitrate/fuel oil (ANFO) mixture to a blend of emulsion and ANFO on a straight emulsion. Non-electric (shock tube) initiation systems have provided a viable alternative to the electric detonator (blasting cap). Explosives manufacturers are seeing their roles changes to being blasting contractors or consultants rather than just suppliers. The article discusses these trends and gives examples of typical blasting techniques and amounts of blasting agent used at large USA surface coal mines. Electric caps are still used in blasting underground coal. The Ensign Bickford Co. (EBCo) is developing electronic detonators and has been field testing an electronic initiator, the DIGIDET detonator, for the last four years. When commercially available, electronic detonators will be accurate but will come with a hefty price tag. 2 photos.

  5. Global nuclear cleanout initiative 2004

    International Nuclear Information System (INIS)

    Edlow, J.; Gruber, G.

    2004-01-01

    Full text: During more than 50 years of Atoms for Peace programmes nuclear materials were spread out worldwide. Stranded nuclear materials from nuclear research are left over without any safe back-end solution. 'Dirty Bombs' or so-called 'Radioactive Dispersal Devices (RDD)' are no longer science fiction since the world experienced the 9/11 attack. Governmental, NGO's and private industry organizations having discussed Global Nuclear Cleanout since then and start to take actions. The US Department of Energy (DOE) has announced to establish a dedicated organization in cooperation with IAEA and start the 'Global Threat Reduction Initiative (GTRI)'. The US government will allocate to that program USD 450 M over the next 10 years. Besides the historical development the paper will focus on the progress of the different initiatives and perspectives to threat reduction. (author)

  6. 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.

  7. 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)

  8. Initial occupational exposure to lead

    Energy Technology Data Exchange (ETDEWEB)

    Forni, A.; Cambiaghi, G.; Secchi, G.C.

    1976-01-01

    Serial chromosome and biochemical studies were carried out in 11 subjects before and during initial occupational exposure to moderate quantities of lead fumes in a storage battery plant. The rate of abnormal metaphases, mostly with chromatid and one-break chromosome aberrations, was approximately doubled after one month of work; it further increased after two months of work; remained in this range up to seven months of exposure; and then tended to decrease somewhat. Blood lead levels increased progressively in the first few months, then reached a steady state. Urinary lead and coproporphyrin levels increased sharply after one month of work, while urinary delta-aminolevulinic acid (ALA) levels increased moderately. The ALA dehydratase (ALAD) activity of red blood cells (RBCs) was reduced to almost 50 percent of the initial values after one month, decreased further in subsequent months, and remained decreased through the remainder of the study.

  9. Guam Initial Technical Assessment Report

    Energy Technology Data Exchange (ETDEWEB)

    Baring-Gould, I.; Conrad, M.; Haase, S.; Hotchkiss, E.; McNutt, P.

    2011-04-01

    Under an interagency agreement, funded by the Department of Interior's (DOI) Office of Insular Affairs (OIA), the National Renewable Energy Laboratory (NREL) was tasked to deliver technical assistance to the island of Guam by conducting an island initial technical assessment that would lay out energy consumption and production data and establish a baseline. This assessment will be used to conduct future analysis and studies by NREL that will estimate energy efficiency and renewable energy potential for the island of Guam.

  10. CubeSat Launch Initiative

    Science.gov (United States)

    Higginbotham, Scott

    2016-01-01

    The National Aeronautics and Space Administration (NASA) recognizes the tremendous potential that CubeSats (very small satellites) have to inexpensively demonstrate advanced technologies, collect scientific data, and enhance student engagement in Science, Technology, Engineering, and Mathematics (STEM). The CubeSat Launch Initiative (CSLI) was created to provide launch opportunities for CubeSats developed by academic institutions, non-profit entities, and NASA centers. This presentation will provide an overview of the CSLI, its benefits, and its results.

  11. Air sea ratio reduction initiative

    Energy Technology Data Exchange (ETDEWEB)

    Oberle, Jean

    2010-09-15

    Airfreight is the most expensive mode of transportation as well as the most impacting in terms of CO{sup 2} emissions. It is 7 times more expensive on average to ship by air than shipping by sea 1. Airfreight transportation mode emits 30 times more CO{sup 2} than sea freight mode 2. These elements provided a compelling platform to design a global logistics program to initiate a modal shift from air to sea freight without compromising service to customers.

  12. Industry's Commercial Initiatives on ISS

    Science.gov (United States)

    Shields, C. E.; Kessler, C.; Lavitola, M. S.

    2002-01-01

    For more than ten years, private industry has worked to develop a commercial human space market and to create a sustainable ISS commercial utilization customer base. Before ISS assembly was underway - and long before NASA and the international space agencies began to craft ISS commercial business terms and conditions - industry planted and nurtured the seeds of interest in exploiting human space utilization for commerce. These early initiatives have yielded the impetus and framework for industry approaches to ISS commercial utilization today and for NASA's and the International Partners' planned accommodation of private sector interests and desires on the ISS. This paper chronicles major industry initiatives for commercial ISS utilization, emphasizing successful marketing and business approaches and why these approaches have a higher likelihood of success than others. It provides an overview of individual companies' initiatives, as well as collaborative efforts that cross company lines and country borders; and it assesses the relative success of each. Rather than emphasize negative issues and barriers, this paper characterizes and prioritizes actionable success factors for industry and government to make ISS commercial utilization a sustainable reality.

  13. The next generation safeguards initiative

    International Nuclear Information System (INIS)

    Tobey, William

    2008-01-01

    NGSI or the Next Generation Safeguards Initiative is designed to revitalize the U.S. safeguards technical base, as well as invest in human resources, and to mobilize our primary asset - the U.S. National Laboratories - as well as industry and academia to restore capabilities. While NGSI is a U.S. effort it is intended to serve as a catalyst for a much broader commitment to international safeguards in partnership with the IAEA and other countries. Initiatives over the last years include such as the Proliferation Security Initiative, UN Security Council Resolution 1540, the Global Initiative to Combat Nuclear Terrorism, and initiatives of the G-8 and NSG to discourage the spread of enrichment and reprocessing. NGSI augments this agenda by providing a means to strengthen the technical and political underpinnings of IAEA safeguards. Priorities and envisioned activities under NGSI are the following. (1) Cooperation with IAEA and others to promote universal adoption of safeguards agreements and the Additional Protocol including greater information sharing between member states and the IAEA, investigation of weaponization and procurement activities, and options to strengthen the state-level approach to safeguards. (2) NGSI anticipates the deployment of new types of reactors and fuel cycle facilities, as well as the need to use limited safeguards resources effectively and efficiently, especially in plants that pose the largest burden specifically complex, bulk-handling facilities. (3) NGSI will encourage a generational improvement in current safeguards technologies including improvement of precision and speed of nuclear measurements, performance of real-time process monitoring and surveillance in unattended mode, enabling in-field, pre-screening and analysis of nuclear and environmental samples, and collection, integration, analysis and archiving safeguards-relevant information from all available sources.(4) NGSI will address human capital management. Training and

  14. Women's Health Initiative (WHI) Background and Overview

    Science.gov (United States)

    ... Back To The Science / Women’s Health Initiative (WHI) Women’s Health Initiative (WHI) Project began 1991 Point of ... What is the goal of the WHI? The Women's Health Initiative (WHI), sponsored by the National Heart, ...

  15. 75 FR 11837 - Chesapeake Bay Watershed Initiative

    Science.gov (United States)

    2010-03-12

    ... DEPARTMENT OF AGRICULTURE Commodity Credit Corporation Chesapeake Bay Watershed Initiative AGENCY...: Notice of availability of program funds for the Chesapeake Bay Watershed Initiative. SUMMARY: The... through the Chesapeake Bay Watershed Initiative for agricultural producers in the Chesapeake Bay watershed...

  16. Cold inducible promoter driven Cre-lox system proved to be highly efficient for marker gene excision in transgenic barley.

    Science.gov (United States)

    Éva, Csaba; Téglás, Flóra; Zelenyánszki, Helga; Tamás, Cecília; Juhász, Angéla; Mészáros, Klára; Tamás, László

    2018-01-10

    A Cre-lox based auto-excision strategy has been adapted for barley, capable of cre and selectable marker gene (SMG) removal. The cold inducible wheat promoter called wcs120 was utilised for driving Cre expression. The binary vector was carrying the transgene (uidA) and a so called 'recombination cassette' flanked by the lox sequences. This part included both the recombinase gene and the SMG (bar) under the control of a constitutive promoter. T 0 , T 1 and T 2 transgenic plants were subjected to low temperature (at 4°C, 10°C and 12°C) at different developmental stages to induce recombination. The presence of uidA, cre, and bar genes and recombination footprints were studied by PCR and DNA sequencing, while cre transcription was followed by qRT-PCR. These analyses indicated that, cold treatment of the germinating seeds (4°C for 3days) followed by plant growing at higher temperature (24°C) has been the most efficient (90-100%), and this treatment lead to heritable changes in the genome. Thermal separation of Cre accumulation (at low temperature) from Cre enzyme activity (at higher temperature) could have prevented the premature excision of its own encoding gene, and lead to high expression level thereby increasing recombination frequency. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. An AAV promoter-driven neuropeptide Y gene delivery system using Sendai virosomes for neurons and rat brain.

    Science.gov (United States)

    Wu, P; de Fiebre, C M; Millard, W J; King, M A; Wang, S; Bryant, S O; Gao, Y P; Martin, E J; Meyer, E M

    1996-03-01

    An adeno-associated virus (AAV)-derived construct (pJDT95npy) containing rat neuropeptide Y (NPY) cDNA inserted downstream of endogenous AAV promoters was used to investigate AAV-driven NPY expression in postmitotic neurons in vitro and in the brain. NPY mRNA was expressed in NT2/N and rat brain primary neuronal cultures after transfection. There was a corresponding increase in the number of neurons staining for NPY-like immunoreactivity and an increase in NPY release during depolarization in the primary cultures. Injections of Sendai-virosome encapsulated pJDT95npy into neocortex increased NPY-like immunoreactivity in neurons but not glia indicating that the latter cell type did not have the translational, post-translational or storage capacity to accumulate the peptide. Injections into the rat hypothalamic para-ventricular nucleus increased body weight and food intake for 21 days, though NPY-like immunoreactivity remained elevated for at least 50 days. These studies demonstrate that AAV-derived constructs may be useful for delivering genes into post-mitotic neurons, and that Sendai virosomes are effective for delivering these constructs in vivo.

  18. High efficiency of targeted mutagenesis in arabidopsis via meiotic promoter-driven expression of Cas9 endonuclease

    KAUST Repository

    Eid, Ayman; Ali, Zahir; Mahfouz, Magdy M.

    2016-01-01

    of eukaryotic genomes, including plants; however, CRISPR/Cas9 efficiency varies considerably in different plant tissues and species. In Arabidopsis, the generation of homozygous or bi-allelic mutants in the first (T1) generation is inefficient. Here, we used

  19. High efficiency of targeted mutagenesis in arabidopsis via meiotic promoter-driven expression of Cas9 endonuclease

    KAUST Repository

    Eid, Ayman

    2016-05-28

    Key message: The use of a meiosis I-specific promoter increased the efficiency of targeted mutagenesis and will facilitate the manipulation of homologous recombination. Abstract: The CRISPR/Cas9 system has been harnessed for targeted engineering of eukaryotic genomes, including plants; however, CRISPR/Cas9 efficiency varies considerably in different plant tissues and species. In Arabidopsis, the generation of homozygous or bi-allelic mutants in the first (T1) generation is inefficient. Here, we used specific promoters to drive the expression of Cas9 during meiosis to maximize the efficiency of recovering heritable mutants in T1 plants. Our data reveal that the use of a promoter active in meiosis I resulted in high-efficiency (28 %) recovery of targeted mutants in the T1 generation. Moreover, this method enabled efficient simultaneous targeting of three genes for mutagenesis. Taken together, our results show that the use of meiosis-specific promoters will improve methods for functional genomic analysis and studying the molecular underpinnings of homologous recombination. © 2016, Springer-Verlag Berlin Heidelberg.

  20. GFAP promoter driven transgenic expression of PDGFB in the mouse brain leads to glioblastoma in a Trp53 null background

    NARCIS (Netherlands)

    Hede, Sanna-Maria; Hansson, Inga; Afink, Gijs B.; Eriksson, Anna; Nazarenko, Inga; Andrae, Johanna; Genove, Guillem; Westermark, Bengt; Nistér, Monica

    2009-01-01

    Glioblastomas are the most common and malignant astrocytic brain tumors in human adults. The tumor suppressor gene TP53 is commonly mutated and/or lost in astrocytic brain tumors and the TP53 alterations are often found in combination with excessive growth factor signaling via PDGF/PDGFRalpha. Here,

  1. HST Replacement Battery Initial Performance

    Science.gov (United States)

    Krol, Stan; Waldo, Greg; Hollandsworth, Roger

    2009-01-01

    The Hubble Space Telescope (HST) original Nickel-Hydrogen (NiH2) batteries were replaced during the Servicing Mission 4 (SM4) after 19 years and one month on orbit.The purpose of this presentation is to highlight the findings from the assessment of the initial sm4 replacement battery performance. The batteries are described, the 0 C capacity is reviewed, descriptions, charts and tables reviewing the State Of Charge (SOC) Performance, the Battery Voltage Performance, the battery impedance, the minimum voltage performance, the thermal performance, the battery current, and the battery system recharge ratio,

  2. Initial CAD investigations for NET

    International Nuclear Information System (INIS)

    Katz, F.; Leinemann, K.; Ludwig, A.; Marek, U.; Olbrich, W.; Schlechtendahl, E.G.

    1985-11-01

    This report summarizes the work done under contract no. 164/84-7/FU-D-/NET between the Commission of the European Communities and KfK during the period from June 1, 1984, through May 31, 1985. The following topics are covered in this report: Initial modelling of NET version NET2A, CAD system extension for remote handling studies, analysis of the CAD information structure, work related to the transfer of CAD information between KfK and the NET team. (orig.) [de

  3. Powering the Space Exploration Initiative

    International Nuclear Information System (INIS)

    Bennett, G.L.

    1991-01-01

    The Space Exploration Initiative (SEI) establishes the long-term goal of returning to the Moon and then exploring Mars. One of the prerequisites of SEI is the Exploration Technology Program which includes program elements on space nuclear power and surface solar power. These program elements in turn build upon the ongoing NASA research and technology base program in space energy conversion. There is a wide range of missions in NASA's strategic planning and most would benefit from power sources with improved efficiency, lighter weight and reduced cost

  4. Initial treatment of Parkinson's disease.

    Science.gov (United States)

    Tarsy, Daniel

    2006-05-01

    Initial treatment of early idiopathic Parkinson's disease (PD) begins with diagnosis based on clinical evaluation supplemented by laboratory studies and brain imaging to exclude causes of secondary parkinsonism. In most cases, testing is normal and the diagnosis of PD rests on clinical criteria. In patients with mild symptoms and signs, the diagnosis of PD may not initially be apparent, and follow-up evaluation is needed to arrive at a diagnosis. Once the diagnosis is made, pharmacologic treatment may not be the first step. First, patient education is essential, especially because PD is a high-profile disease for which information and misinformation are readily available to patients and families. Counseling concerning prognosis, future symptoms, future disability, and treatment must be provided. Questions from patients concerning diet, lifestyle, and exercise are especially common at this point. The decision of when to initiate treatment is the next major consideration. Much controversy but relatively little light has been brought to bear on this issue. L-dopa was the first major antiparkinson medication to be introduced and remains the "gold standard" of treatment. Next in efficacy are the dopamine agonists (DAs). A debate has raged concerning whether initial dopaminergic treatment should be with L-dopa or DAs. Physicians have been concerned about forestalling the appearance of dyskinesias and motor fluctuations, whereas patients have incorrectly understood that L-dopa and possibly other antiparkinson drugs have a finite duration of usefulness, making it important to defer treatment for as long as possible. This has created "L-dopa phobia," which may stand in the way of useful treatment. In spite of this controversy, there is uniform agreement that the appropriate time to treat is when the patient is beginning to be disabled. This varies from patient to patient and depends on age, employment status, nature of job, level of physical activity, concern about

  5. Interstellar Initiative Web Page Design

    Science.gov (United States)

    Mehta, Alkesh

    1999-01-01

    This summer at NASA/MSFC, I have contributed to two projects: Interstellar Initiative Web Page Design and Lenz's Law Relative Motion Demonstration. In the Web Design Project, I worked on an Outline. The Web Design Outline was developed to provide a foundation for a Hierarchy Tree Structure. The Outline would help design a Website information base for future and near-term missions. The Website would give in-depth information on Propulsion Systems and Interstellar Travel. The Lenz's Law Relative Motion Demonstrator is discussed in this volume by Russell Lee.

  6. [Initial stages of steel biocorrosion].

    Science.gov (United States)

    Zhigletsova, S K; Rodin, V B; Kobelev, V S; Aleksandrova, N V; Rasulova, G E; Kholodenko, V P

    2000-01-01

    Initial stages of corrosion of mild steel induced by Klebsiela rhinoscleromatis BO2 were studied in various media. The effect of the microorganism was detected 8-10 h after inoculation. The number of viable cells were virtually unchanged within one month in all media, but the corrosive activity of the strain decreased. The corrosive activity of microorganisms can be determined by spectrophotometry even only after incubation for 24 h. At a low level of organic substrate, even strong colonization with microorganisms does not inevitably result in a significant damage to metals.

  7. Radiation safety without borders initiative

    International Nuclear Information System (INIS)

    Dibblee, Martha; Dickson, Howard; Krieger, Ken; Lopez, Jose; Waite, David; Weaver, Ken

    2008-01-01

    The Radiation Safety Without Borders (RSWB) initiative provides peer support to radiation safety professionals in developing countries, which bolsters the country's infrastructure and may lead the way for IRPA Associate membership. The Health Physics Society (HPS) recognizes that many nations do not possess the infrastructure to adequately control and beneficially use ionizing radiation. In a substantial number of countries, organized radiation protection programs are minimal. The RSWB initiative relies on HPS volunteers to assist their counterparts in developing countries with emerging health physics and radiation safety programs, but whose resources are limited, to provide tools that promote and support infrastructure and help these professionals help themselves. RSWB experience to date has shown that by providing refurbished instruments, promoting visits to a HPS venue, or visiting a country just to look provide valuable technical and social infrastructure experiences often missing in the developing nation's cadre of radiation safety professionals. HPS/RSWB with the assistance of the International Atomic Energy Agency (IAEA) pairs chapters with a country, with the expectation that the country's professional radiation safety personnel will form a foreign HPS chapter, and the country eventually will become an IRPA Associate. Although still in its formative stage, RSWB nonetheless has gotten valuable information in spite of the small number of missions. The RSWB initiative continues to have significant beneficial impacts, including: Improving the radiation safety infrastructure of the countries that participate; Assisting those countries without professional radiation safety societies to form one; Strengthening the humanitarian efforts of the United States; Enhancing Homeland Security efforts through improved control of radioactive material internationally. Developing countries, including those in Latin America, underwritten by IAEA, may take advantage of resources

  8. University involvement in sustainability initiatives

    DEFF Research Database (Denmark)

    Lehmann, Martin; Christensen, Per; Thrane, Mikkel

    2007-01-01

    With an outset in the case of Aalborg University, the linkages (actual, potential and missing) between academic work in research & education and sustainability initiatives are explored. The focus is both on the university's core activities as a provider of research and education and on the univer......With an outset in the case of Aalborg University, the linkages (actual, potential and missing) between academic work in research & education and sustainability initiatives are explored. The focus is both on the university's core activities as a provider of research and education...... and on the university's activities as an organisation, i.e. its own operation and its accounting for this. Sustainability is defined as a continuous process requiring balance between (the emergence of) problems and our ability and capability to solve them. Some core questions that this paper seeks to answer are: "How...... is Sustainable Development understood at executive level at the university? How (if at all) is sustainable development integrated in the core activities of the university? How is the university attached to ‘real life outside the ivory tower', e.g. through the establishing of Public-Private-Academic Partnerships...

  9. Phillips Laboratory small satellite initiatives

    Science.gov (United States)

    Lutey, Mark K.; Imler, Thomas A.; Davis, Robert J.

    1993-09-01

    The Phillips Laboratory Space Experiments Directorate in conjunction with the Air Force Space Test Program (AF STP), Defense Advanced Research and Projects Agency (DARPA) and Strategic Defense Initiative Organization (SDIO), are managing five small satellite program initiatives: Lightweight Exo-Atmospheric Projectile (LEAP) sponsored by SDIO, Miniature Sensor Technology Integration (MSTI) sponsored by SDIO, Technology for Autonomous Operational Survivability (TAOS) sponsored by Phillips Laboratory, TechSat sponsored by SDIO, and the Advanced Technology Standard Satellite Bus (ATSSB) sponsored by DARPA. Each of these spacecraft fulfills a unique set of program requirements. These program requirements range from a short-lived `one-of-a-kind' mission to the robust multi- mission role. Because of these diverging requirements, each program is driven to use a different design philosophy. But regardless of their design, there is the underlying fact that small satellites do not always equate to small missions. These spacecraft with their use of or ability to insert new technologies provide more capabilities and services for their respective payloads which allows the expansion of their mission role. These varying program efforts culminate in an ATSSB spacecraft bus approach that will support moderate size payloads, up to 500 pounds, in a large set of orbits while satisfying the `cheaper, faster, better' method of doing business. This technical paper provides an overview of each of the five spacecraft, focusing on the objectives, payoffs, technologies demonstrated, and program status.

  10. The Saudi Initiative for asthma

    Directory of Open Access Journals (Sweden)

    Al-Moamary Mohamed

    2009-01-01

    Full Text Available The Saudi Initiative for Asthma (SINA provides up-to-date guidelines for healthcare workers managing patients with asthma. SINA was developed by a panel of Saudi experts with respectable academic backgrounds and long-standing experience in the field. SINA is founded on the latest available evidence, local literature, and knowledge of the current setting in Saudi Arabia. Emphasis is placed on understanding the epidemiology, pathophysiology, medications, and clinical presentation. SINA elaborates on the development of patient-doctor partnership, self-management, and control of precipitating factors. Approaches to asthma treatment in SINA are based on disease control by the utilization of Asthma Control Test for the initiation and adjustment of asthma treatment. This guideline is established for the treatment of asthma in both children and adults, with special attention to children 5 years and younger. It is expected that the implementation of these guidelines for treating asthma will lead to better asthma control and decrease patient utilization of the health care system.

  11. The international surface temperature initiative

    Science.gov (United States)

    Thorne, P. W.; Lawrimore, J. H.; Willett, K. M.; Allan, R.; Chandler, R. E.; Mhanda, A.; de Podesta, M.; Possolo, A.; Revadekar, J.; Rusticucci, M.; Stott, P. A.; Strouse, G. F.; Trewin, B.; Wang, X. L.; Yatagai, A.; Merchant, C.; Merlone, A.; Peterson, T. C.; Scott, E. M.

    2013-09-01

    The aim of International Surface Temperature Initiative is to create an end-to-end process for analysis of air temperature data taken over the land surface of the Earth. The foundation of any analysis is the source data. Land surface air temperature records have traditionally been stored in local, organizational, national and international holdings, some of which have been available digitally but many of which are available solely on paper or as imaged files. Further, economic and geopolitical realities have often precluded open sharing of these data. The necessary first step therefore is to collate readily available holdings and augment these over time either through gaining access to previously unavailable digital data or through data rescue and digitization activities. Next, it must be recognized that these historical measurements were made primarily in support of real-time weather applications where timeliness and coverage are key. At almost every long-term station it is virtually certain that changes in instrumentation, siting or observing practices have occurred. Because none of the historical measures were made in a metrologically traceable manner there is no unambiguous way to retrieve the true climate evolution from the heterogeneous raw data holdings. Therefore it is desirable for multiple independent groups to produce adjusted data sets (so-called homogenized data) to adequately understand the data characteristics and estimate uncertainties. Then it is necessary to benchmark the performance of the contributed algorithms (equivalent to metrological software validation) through development of realistic benchmark datasets. In support of this, a series of successive benchmarking and assessment cycles are envisaged, allowing continual improvement while avoiding over-tuning of algorithms. Finally, a portal is proposed giving access to related data-products, utilizing the assessment results to provide guidance to end-users on which product is the most suited to

  12. Utilisation of factorial experiments for the UV/H O process in a batch ...

    African Journals Online (AJOL)

    drinie

    2001-10-04

    Oct 4, 2001 ... The predictions given by the factorial experiments model were confirmed by the ... studies have given the effect of initial H2O2 concentration, initial concentration of the ... This mathematical model may be utilised to explain.

  13. 36 CFR 902.60 - Initial determination.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Initial determination. 902.60... INFORMATION ACT Time Limitations § 902.60 Initial determination. (a) An initial determination whether or not... workdays in accordance with § 902.62. (b) Upon making initial determination, the Administrative Officer...

  14. 42 CFR 405.803 - Initial determination.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Initial determination. 405.803 Section 405.803....803 Initial determination. (a) Carriers make initial determinations regarding claims for benefits under Medicare Part B. (b) An initial determination for purposes of this subpart includes determinations...

  15. ACHP | Summary of the Preserve America Initiative

    Science.gov (United States)

    Initiative Preserve America: Explore and Enjoy Our Heritage (logo) Summary of the Preserve America Initiative Preserve America is a White House initiative that encourages and supports community efforts to preserve and enjoy our priceless cultural and natural heritage. The goals of the initiative include a greater shared

  16. Global threat reduction initiative (GTRI)

    International Nuclear Information System (INIS)

    Chamberlain, Travis

    2009-01-01

    The Global Threat Reduction Initiative (GTRI) is a vital part of the global efforts to combat nuclear terrorism. GTRI's unique mission to reduce and protect vulnerable nuclear and radiological material located at civilian sites both in the United States and abroad directly addresses recommendations of the bipartisan 9/11 Commission. GTRI efforts are focused on the first line of defense, namely securing or removing vulnerable nuclear and radiological material at the source. The international community has promulgated guidance on the best practice on the technical and administrative aspects of radiological source security, and the GTRI seeks to provide technical assistance to national bodies and individual facilities to adopt this best practice. This presentation will discuss security concepts that are implemented by the GTRI in cooperation with the Australian Nuclear Science and Technology Organization's Regional Security of Radioactive Sources Project. (author)

  17. Teaching Evaluation: Waiting for Initiatives

    Directory of Open Access Journals (Sweden)

    Alejandro Canales Sánchez

    2008-08-01

    Full Text Available In this text, it is sustained that, despite the fact that the teaching activity is one of the main functions of higher education institutions or even the only one in most of them, it hasn’t been reflected in the leading initiatives that have been set in motion in this area for the last two decades. In particular, it points out that the wide evaluation politics established in the education system during the late eighties, didn’t consider the teaching activity as a concern issue for the mechanisms or rewards in the evaluation system. Even though the implementation of new actions tried to repair the situation, mainly by improving the quality of working time and the qualifications of the personnel performing these activities; teaching, in strict sense, and the design or application of a new evaluation scheme to strengthen it, didn’t get better.

  18. The hydrogen mine introduction initiative

    Energy Technology Data Exchange (ETDEWEB)

    Betournay, M.C.; Howell, B. [Natural Resources Canada, Ottawa, ON (Canada). CANMET Mining and Mineral Sciences Laboratories

    2009-07-01

    In an effort to address air quality concerns in underground mines, the mining industry is considering the use fuel cells instead of diesel to power mine production vehicles. The immediate issues and opportunities associated with fuel cells use include a reduction in harmful greenhouse gas emissions; reduction in ventilation operating costs; reduction in energy consumption; improved health benefits; automation; and high productivity. The objective of the hydrogen mine introduction initiative (HMII) is to develop and test the range of fundamental and needed operational technology, specifications and best practices for underground hydrogen power applications. Although proof of concept studies have shown high potential for fuel cell use, safety considerations must be addressed, including hydrogen behaviour in confined conditions. This presentation highlighted the issues to meet operational requirements, notably hydrogen production; delivery and storage; mine regulations; and hydrogen behaviour underground. tabs., figs.

  19. Somerset County Renewable Energy Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Katula, Denise [County of Somerset, Somervile, NJ (United States)

    2014-05-07

    The County of Somerset, New Jersey, through the Somerset County Improvement Authority (SCIA), applied Federal funding through the U.S. Department of Energy to will apply project funds to buy-down the capital costs of equipment associated with the installation of solar photovoltaic (PV) systems at two sites owned by the County. This Renewable Energy Initiative allows the County to take advantage of clean renewable energy, without any adverse debt impacts, and at a price that results in operating budget savings beyond what is presently available in the marketplace. This project addressed the objectives of the Office of Energy Efficiency and Renewable Energy by making the acquisition of renewable energy more affordable for the County, thereby, encouraging other counties and local units to develop similar programs and increase the deployment of solar energy technologies. The two sites that were funded by the DOE grant are part of a much larger, ambitious, and unique renewable energy project, described in the next section.

  20. DIPS space exploration initiative safety

    International Nuclear Information System (INIS)

    Dix, T.E.

    1991-01-01

    The Dynamic Isotope Power Subsystem has been identified for potential applications for the Space Exploration Initiative. A qualitative safety assessment has been performed to demonstrate the overall safety adequacy of the Dynamic Isotope Power Subsystem for these applications. Mission profiles were defined for reference lunar and martian flights. Accident scenarios were qualitatively defined for all mission phases. Safety issues were then identified. The safety issues included radiation exposure, fuel containment, criticality, diversion, toxic materials, heat flux to the extravehicular mobility unit, and disposal. The design was reviewed for areas where safety might be further improved. Safety would be improved by launching the fuel separate from the rest of the subsystem on expendable launch vehicles, using a fuel handling tool during unloading of the hot fuel canister, and constructing a cage-like structure around the reversible heat removal system lithium heat pipes. The results of the safety assessment indicate that the DIPS design with minor modifications will produce a low risk concept

  1. Plug-in Hybrid Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, Angie; Moore, Ray; Rowden, Tim

    2013-09-27

    Our main project objective was to implement Plug-in Electric Vehicles (PEV) and charging infrastructure into our electric distribution service territory and help reduce barriers in the process. Our research demonstrated the desire for some to be early adopters of electric vehicles and the effects lack of education plays on others. The response of early adopters was tremendous: with the initial launch of our program we had nearly 60 residential customers interested in taking part in our program. However, our program only allowed for 15 residential participants. Our program provided assistance towards purchasing a PEV and installation of Electric Vehicle Supply Equipment (EVSE). The residential participants have all come to love their PEVs and are more than enthusiastic about promoting the many benefits of driving electric.

  2. Initial performance parameters on FXR

    International Nuclear Information System (INIS)

    Kulke, B.; Innes, T.G.; Kihara, R.; Scarpetti, R.D.

    1982-01-01

    Construction of the new flash x-ray induction LINAC (FXR) at Lawrence Livermore National Laboratory has been completed. Initial tuning of the machine has produced stable current pulses in excess of 2 kA at the design energy of 20 MeV, with an 80 ns FWHM pulse width, producing single-pulse radiation doses near 500 Roentgen at one meter from the target. The electronic spot size on the bremsstrahlung target is estimated at 3 to 5 mm. In this paper we will discuss the basic FXR design; running-in and tuning of the machine; emittance measurements; beam stability; switch gap synchronization; and measurements of the radiation dose and angular distribution

  3. Montana BioDiesel Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Peyton, Brent [Montana State Univ., Bozeman, MT (United States)

    2017-01-29

    This initiative funding helped put Montana State University (MSU) in a position to help lead in the development of biodiesel production strategies. Recent shortages in electrical power and rising gasoline prices have focused much attention on the development of alternative energy sources that will end our dependence on fossil fuels. In addition, as the concern for environmental impact of utilizing fossil fuels increases, effective strategies must be implemented to reduce emissions or the increased regulations imposed on fossil fuel production will cause economic barriers for their use to continue to increase. Biodiesel has been repeatedly promoted as a more environmentally sound and renewable source of fuel and may prove to be a highly viable solution to provide, at the least, a proportion of our energy needs. Currently there are both practical and economic barriers to the implementation of alternative energy however the advent of these technologies is inevitable. Since many of the same strategies for the storage, transport, and utilization of biodiesel are common with that of fossil fuels, the practical barriers for biodiesel are comparatively minimal. Strategies were developed to harness the CO2 as feedstock to support the growth of biodiesel producing algae. The initiative funding led to the successful funding of highly rated projects in competitive national grant programs in the National Science Foundation and the Department of Energy. This funding put MSU in a key position to develop technologies to utilize the CO2 rich emissions produced in fossil fuel utilization and assembled world experts concerning the growth characteristics of photosynthetic microorganisms capable of producing biodiesel.

  4. Cultural initiation of medical doctors.

    Science.gov (United States)

    Zsinkó-Szabó, Zoltán; Lázár, Imre

    2013-12-01

    Eighteen years experience of teaching medical anthropology at a Hungarian medical school offers insight into the dynamics of interference between the rationalist epistemological tradition of biomedicine as one of the central paradigms of modernism and the cultural relativism of medical anthropology, as cultural anthropology is considered to be one of the generators of postmodern thinking. Tracing back the informal "prehistory" of our Institute, we can reveal its psychosomatic, humanistic commitment and critical basis as having represented a kind of counterculture compared with the technocrats of state-socialist Hungary's health ideology. The historical change and socio-cultural transition in Hungary after 1989 was accompanied by changes in the medical system as well as in philosophy and in the structure of the teaching of social sciences. The developing pluralism in the medical system together with the pluralism of social ideologies allowed the substitution of the dogmatic Marxist-Leninist framework with the more pragmatic and empiricist behavioral sciences including medical sociology and medical anthropology. The conflict between the initiation function of the hard preclinical training of the first two years, and the reflective, relativistic and critical narrative on "biomedicine as culture bound entity" constructed by medical anthropology during the second year of medical training is discussed. We also submit our fieldwork data gained as a result of a two year investigation period focusing on diverse initiation types of "would be" physicians. The main proportion of our data derives from individual semi structured deep interviews together with focus group interviews carried out with medical students of upper years. Finally, the role of medical anthropology in the "rite of passage" of becoming a medical doctor is summarized, paying attention to their field work reports and the risks and gains in this process.

  5. Initial report of the osteogenesis imperfecta adult natural history initiative.

    Science.gov (United States)

    Tosi, Laura L; Oetgen, Matthew E; Floor, Marianne K; Huber, Mary Beth; Kennelly, Ann M; McCarter, Robert J; Rak, Melanie F; Simmonds, Barbara J; Simpson, Melissa D; Tucker, Carole A; McKiernan, Fergus E

    2015-11-14

    A better understanding of the natural history of osteogenesis imperfecta (OI) in adulthood should improve health care for patients with this rare condition. The Osteogenesis Imperfecta Foundation established the Adult Natural History Initiative (ANHI) in 2010 to give voice to the health concerns of the adult OI community and to begin to address existing knowledge gaps for this condition. Using a web-based platform, 959 adults with self-reported OI, representing a wide range of self-reported disease severity, reported symptoms and health conditions, estimated the impact of these concerns on present and future health-related quality of life (QoL) and completed a Patient-Reported Outcomes Measurement Information System (PROMIS®) survey of health issues. Adults with OI report lower general physical health status (p report generally similar mental health status. Musculoskeletal, auditory, pulmonary, endocrine, and gastrointestinal issues are particular future health-related QoL concerns for these adults. Numerous other statistically significant differences exist among adults with OI as well as between adults with OI and the referent PROMIS® population, but the clinical significance of these differences is uncertain. Adults with OI report lower general health status but are otherwise more similar to the general population than might have been expected. While reassuring, further analysis of the extensive OI-ANHI databank should help identify areas of unique clinical concern and for future research. The OI-ANHI survey experience supports an internet-based strategy for successful patient-centered outcomes research in rare disease populations.

  6. Initial data sets for the Schwarzschild spacetime

    International Nuclear Information System (INIS)

    Gomez-Lobo, Alfonso Garcia-Parrado; Kroon, Juan A. Valiente

    2007-01-01

    A characterization of initial data sets for the Schwarzschild spacetime is provided. This characterization is obtained by performing a 3+1 decomposition of a certain invariant characterization of the Schwarzschild spacetime given in terms of concomitants of the Weyl tensor. This procedure renders a set of necessary conditions--which can be written in terms of the electric and magnetic parts of the Weyl tensor and their concomitants--for an initial data set to be a Schwarzschild initial data set. Our approach also provides a formula for a static Killing initial data set candidate--a KID candidate. Sufficient conditions for an initial data set to be a Schwarzschild initial data set are obtained by supplementing the necessary conditions with the requirement that the initial data set possesses a stationary Killing initial data set of the form given by our KID candidate. Thus, we obtain an algorithmic procedure of checking whether a given initial data set is Schwarzschildean or not

  7. Simulation of Initiation in Hexanitrostilbene

    Science.gov (United States)

    Thompson, Aidan; Shan, Tzu-Ray; Yarrington, Cole; Wixom, Ryan

    We report on the effect of isolated voids and pairs of nearby voids on hot spot formation, growth and chemical reaction initiation in hexanitrostilbene (HNS) crystals subjected to shock loading. Large-scale, reactive molecular dynamics simulations are performed using the reactive force field (ReaxFF) as implemented in the LAMMPS software. The ReaxFF force field description for HNS has been validated previously by comparing the isothermal equation of state to available diamond anvil cell (DAC) measurements and density function theory (DFT) calculations. Micron-scale molecular dynamics simulations of a supported shockwave propagating in HNS crystal along the [010] orientation are performed (up = 1.25 km/s, Us =4.0 km/s, P = 11GPa.) We compare the effect on hot spot formation and growth rate of isolated cylindrical voids up to 0.1 µm in size with that of two 50nm voids set 100nm apart. Results from the micron-scale atomistic simulations are compared with hydrodynamics simulations. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lock- heed Martin Corporation, for the U.S. DOE National Nuclear Security Administration under Contract DE-AC04-94AL85000.

  8. German innovation initiative for nanotechnology

    Science.gov (United States)

    Rieke, Volker; Bachmann, Gerd

    2004-10-01

    In many areas of nanotechnology, Germany can count on a good knowledge basis due to its diverse activities in nanosciences. This knowledge basis, when paired with the production and sales structures needed for implementation and the internationally renowned German talent for system integration, should consequently lead to success in the marketplace. And this is exactly the field of application for the innovation initiative "Nanotechnologie erobert Märkte" (nanotechnology conquers markets) and for the new BMBF strategy in support of nanotechnology. Until now, aspects of nanotechnology have been advanced within the confines of their respective technical subject areas. However, the primary aim of incorporating them into an overall national strategy is to build on Germany's well-developed and internationally competitive research in science and technology to tap the potential of Germany's important industrial sectors for the application of nanotechnology through joint research projects (leading-edge innovations) that strategically target the value-added chain. This development is to be supported by government education policy to remedy a threatening shortage of skilled professionals. To realize that goal, forward-looking political policymaking must become oriented to a uniform concept of innovation, one that takes into consideration all facets of new technological advances that can contribute to a new culture of innovation in Germany. And that includes education and research policy as well as a climate that encourages and supports innovation in science, business and society.

  9. German innovation initiative for nanotechnology

    International Nuclear Information System (INIS)

    Rieke, Volker; Bachmann, Gerd

    2004-01-01

    In many areas of nanotechnology, Germany can count on a good knowledge basis due to its diverse activities in nanosciences. This knowledge basis, when paired with the production and sales structures needed for implementation and the internationally renowned German talent for system integration, should consequently lead to success in the marketplace. And this is exactly the field of application for the innovation initiative 'Nanotechnologie erobert Maerkte' (nanotechnology conquers markets) and for the new BMBF strategy in support of nanotechnology. Until now, aspects of nanotechnology have been advanced within the confines of their respective technical subject areas. However, the primary aim of incorporating them into an overall national strategy is to build on Germany's well-developed and internationally competitive research in science and technology to tap the potential of Germany's important industrial sectors for the application of nanotechnology through joint research projects (leading-edge innovations) that strategically target the value-added chain. This development is to be supported by government education policy to remedy a threatening shortage of skilled professionals. To realize that goal, forward-looking political policymaking must become oriented to a uniform concept of innovation, one that takes into consideration all facets of new technological advances that can contribute to a new culture of innovation in Germany. And that includes education and research policy as well as a climate that encourages and supports innovation in science, business and society

  10. Clean coal initiatives in Indiana

    Science.gov (United States)

    Bowen, B.H.; Irwin, M.W.; Sparrow, F.T.; Mastalerz, Maria; Yu, Z.; Kramer, R.A.

    2007-01-01

    Purpose - Indiana is listed among the top ten coal states in the USA and annually mines about 35 million short tons (million tons) of coal from the vast reserves of the US Midwest Illinois Coal Basin. The implementation and commercialization of clean coal technologies is important to the economy of the state and has a significant role in the state's energy plan for increasing the use of the state's natural resources. Coal is a substantial Indiana energy resource and also has stable and relatively low costs, compared with the increasing costs of other major fuels. This indigenous energy source enables the promotion of energy independence. The purpose of this paper is to outline the significance of clean coal projects for achieving this objective. Design/methodology/approach - The paper outlines the clean coal initiatives being taken in Indiana and the research carried out at the Indiana Center for Coal Technology Research. Findings - Clean coal power generation and coal for transportation fuels (coal-to-liquids - CTL) are two major topics being investigated in Indiana. Coking coal, data compilation of the bituminous coal qualities within the Indiana coal beds, reducing dependence on coal imports, and provision of an emissions free environment are important topics to state legislators. Originality/value - Lessons learnt from these projects will be of value to other states and countries.

  11. Electrical initiation of an energetic nanolaminate film

    Science.gov (United States)

    Tringe, Joseph W.; Gash, Alexander E.; Barbee, Jr., Troy W.

    2010-03-30

    A heating apparatus comprising an energetic nanolaminate film that produces heat when initiated, a power source that provides an electric current, and a control that initiates the energetic nanolaminate film by directing the electric current to the energetic nanolaminate film and joule heating the energetic nanolaminate film to an initiation temperature. Also a method of heating comprising providing an energetic nanolaminate film that produces heat when initiated, and initiating the energetic nanolaminate film by directing an electric current to the energetic nanolaminate film and joule heating the energetic nanolaminate film to an initiation temperature.

  12. Shock Initiation of Damaged Explosives

    Energy Technology Data Exchange (ETDEWEB)

    Chidester, S K; Vandersall, K S; Tarver, C M

    2009-10-22

    Explosive and propellant charges are subjected to various mechanical and thermal insults that can increase their sensitivity over the course of their lifetimes. To quantify this effect, shock initiation experiments were performed on mechanically and thermally damaged LX-04 (85% HMX, 15% Viton by weight) and PBX 9502 (95% TATB, 5% Kel-F by weight) to obtain in-situ manganin pressure gauge data and run distances to detonation at various shock pressures. We report the behavior of the HMX-based explosive LX-04 that was damaged mechanically by applying a compressive load of 600 psi for 20,000 cycles, thus creating many small narrow cracks, or by cutting wedge shaped parts that were then loosely reassembled, thus creating a few large cracks. The thermally damaged LX-04 charges were heated to 190 C for long enough for the beta to delta solid - solid phase transition to occur, and then cooled to ambient temperature. Mechanically damaged LX-04 exhibited only slightly increased shock sensitivity, while thermally damaged LX-04 was much more shock sensitive. Similarly, the insensitive explosive PBX 9502 was mechanically damaged using the same two techniques. Since PBX 9502 does not undergo a solid - solid phase transition but does undergo irreversible or 'rachet' growth when thermally cycled, thermal damage to PBX 9502 was induced by this procedure. As for LX-04, the thermally damaged PBX 9502 demonstrated a greater shock sensitivity than mechanically damaged PBX 9502. The Ignition and Growth reactive flow model calculated the increased sensitivities by igniting more damaged LX-04 and PBX 9502 near the shock front based on the measured densities (porosities) of the damaged charges.

  13. Process Engineering Technology Center Initiative

    Science.gov (United States)

    Centeno, Martha A.

    2002-01-01

    NASA's Kennedy Space Center (KSC) is developing as a world-class Spaceport Technology Center (STC). From a process engineering (PE) perspective, the facilities used for flight hardware processing at KSC are NASA's premier factories. The products of these factories are safe, successful shuttle and expendable vehicle launches carrying state-of-the-art payloads. PE is devoted to process design, process management, and process improvement, rather than product design. PE also emphasizes the relationships of workers with systems and processes. Thus, it is difficult to speak of having a laboratory for PE at K.S.C. because the entire facility is practically a laboratory when observed from a macro level perspective. However, it becomes necessary, at times, to show and display how K.S.C. has benefited from PE and how K.S.C. has contributed to the development of PE; hence, it has been proposed that a Process Engineering Technology Center (PETC) be developed to offer a place with a centralized focus on PE projects, and a place where K.S.C.'s PE capabilities can be showcased, and a venue where new Process Engineering technologies can be investigated and tested. Graphics for showcasing PE capabilities have been designed, and two initial test beds for PE technology research have been identified. Specifically, one test bed will look into the use of wearable computers with head mounted displays to deliver work instructions; the other test bed will look into developing simulation models that can be assembled into one to create a hierarchical model.

  14. Open Geodata Initiative for Romania

    Science.gov (United States)

    Craciunescu, Vasile; Iosifescu, Ionut; Ilie, Codrina Maria; Gaitanaru, Dragos; Radu Gogu, Constantin; Hurni, Lorenz

    2013-04-01

    The concept of open data access is a very important topic nowadays. The concept assumes that all data collected or generated by public sector bodies (excepting personal data and data protected under existing privacy protection or accessibility rules) is made publicly accessible in commonly-used, machine-readable formats and can be re-used for any purpose, commercial or non-commercial. Governmental agencies are considered to be the most significant data owners and providers in modern societies. The sheer volume and wealth of this data makes apparent the potential benefits of reusing, combining, and processing governmental data. Even though metadata (information about the data) is sometimes published, administrations typically express reluctance to making their data available, for various reasons, cultural, political, legal, institutional and technical. The governmental spatial information (also called geospatial data, georeferenced data or geodata) producers in Romania are no exception -with the additional situation that even metadata is not usually available. Starting from 2013 a joint program between a Swiss partner (The Swiss Federal Institute of Technology ETH- Zurich - Institute of Cartography and Geoinformation) and a Romanian partner (Technical University of Civil Engineering - UTCB) is developed in order to establish a new approach on the open geodata topic. The main objective of the project GEOIDEA.RO (GEodata Openness Initiative for Development and Economic Advancement in ROmania) is to improve the scientific basis for open geodata model adoption in Romania. Is our believe that publishing government geodata in Romania over the Internet,under an open license and in a reusable format can strengthen citizen engagement and yield new innovative businesses, bringing substantial social and economic gains.

  15. Initiation of protein synthesis in bacteria

    DEFF Research Database (Denmark)

    Laursen, Brian Søgaard; Sørensen, Hans Peter; Mortensen, Kim Kusk

    2005-01-01

    Valuable information on translation initiation is available from biochemical data and recently solved structures. We present a detailed description of current knowledge about the structure, function, and interactions of the individual components involved in bacterial translation initiation. The f...

  16. Surgeon General's Family Health History Initiative

    Science.gov (United States)

    ... Source Code The Surgeon General's Family Health History Initiative To help focus attention on the importance of ... health campaign, called the Surgeon General's Family History Initiative, to encourage all American families to learn more ...

  17. Multifamily Hubs' Initial Endorsements FY12

    Data.gov (United States)

    Department of Housing and Urban Development — Describes the program, geographic & lender distribution of multifamily loans initially endorsed for FHA insurance or risk sharing in FY 12. A loan is initially...

  18. Project Lifescape | Initiatives | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    This project is part of the Academy initiative to enhance the quality of science education. It is pursued in ... database through a website. Project Lifescape has also initiated work using some Indian languages. ... and Outreach. Math and Finance ...

  19. Overview of Organic Marketing Initiatives in Europe

    DEFF Research Database (Denmark)

    Nielsen, Thorkild; Kristensen, Niels Heine; Hansen, Mette Weinreich

    2004-01-01

    Nielsen T, Kristensen NH, Hansen MW (2004): Overview of Organic Marketing Initiatives in Europe. Chapter in: Organic Marketing Initiatives and Rural Development. Volume 7, from the OMIaRD project. University of Wales, Aberystwyth, UK. ISBN: 0-9543279-7-1......Nielsen T, Kristensen NH, Hansen MW (2004): Overview of Organic Marketing Initiatives in Europe. Chapter in: Organic Marketing Initiatives and Rural Development. Volume 7, from the OMIaRD project. University of Wales, Aberystwyth, UK. ISBN: 0-9543279-7-1...

  20. Initial value formulation of higher derivative gravity

    International Nuclear Information System (INIS)

    Noakes, D.R.

    1983-01-01

    The initial value problem is considered for the conformally coupled scalar field and higher derivative gravity, by expressing the equations of each theory in harmonic coordinates. For each theory it is shown that the (vacuum) equations can take the form of a diagonal hyperbolic system with constraints on the initial data. Consequently these theories possess well-posed initial value formulations

  1. National Strategic Computing Initiative Strategic Plan

    Science.gov (United States)

    2016-07-01

    23 A.6 National Nanotechnology Initiative...program, lack the memory capacity to perform current and anticipated new classes of scientific and engineering applications, and be potentially...Initiative: https://www.nitrd.gov/nitrdgroups/index.php?title=Big_Data_(BD_SSG)  National Nanotechnology Initiative: http://www.nano.gov  Precision

  2. 6 CFR 13.37 - Initial Decision.

    Science.gov (United States)

    2010-01-01

    ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Initial Decision. 13.37 Section 13.37 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY PROGRAM FRAUD CIVIL REMEDIES § 13.37 Initial Decision. (a) The ALJ will issue an Initial Decision based only on the record, which will contain...

  3. Motivation and Training Initiation: Evidence from Poland

    Science.gov (United States)

    Mielniczuk, Emilia; Laguna, Mariola

    2017-01-01

    Purpose: Based on the self-determination theory and the model of action phases, the present study aims to provide insight into motivational factors that are important for training initiation. It investigates the relations between three types of motivation (intrinsic, extrinsic and amotivation) and training initiation: intention to initiate new…

  4. 75 FR 18472 - Cooperative Conservation Partnership Initiative

    Science.gov (United States)

    2010-04-12

    ... Initiative AGENCY: Commodity Credit Corporation and Natural Resources Conservation Service, Department of... Energy Act of 2008 (2008 Act) establishes the Cooperative Conservation Partnership Initiative (CCPI) by... of Agriculture (USDA). The CCPI is a voluntary conservation initiative that enables the use of...

  5. 40 CFR 610.12 - Program initiative.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Program initiative. 610.12 Section 610... RETROFIT DEVICES Test Procedures and Evaluation Criteria General Provisions § 610.12 Program initiative. A... being marketed may be inadequate, (b) At the EPA Administrator's initiative, or (c) Upon the application...

  6. 75 FR 12433 - National Export Initiative

    Science.gov (United States)

    2010-03-16

    ... Order 13534 of March 11, 2010 National Export Initiative By the authority vested in me as President by... performance will, in turn, create good high-paying jobs. The National Export Initiative (NEI) shall be an Administration initiative to improve conditions that directly affect the private sector's ability to export. The...

  7. Initiation of CMEs by Magnetic Flux Emergence

    Indian Academy of Sciences (India)

    The initiation of solar Coronal Mass Ejections (CMEs) is studied in the framework of numerical magnetohydrodynamics (MHD). The initial CME model includes a magnetic flux rope in spherical, axisymmetric geometry. The initial configuration consists of a magnetic flux rope embedded in a gravitationally stratified solar ...

  8. Clean Energy Infrastructure Educational Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Hallinan, Kevin; Menart, James; Gilbert, Robert

    2012-08-31

    The Clean Energy Infrastructure Educational Initiative represents a collaborative effort by the University of Dayton, Wright State University and Sinclair Community College. This effort above all aimed to establish energy related programs at each of the universities while also providing outreach to the local, state-wide, and national communities. At the University of Dayton, the grant has aimed at: solidfying a newly created Master's program in Renewable and Clean Energy; helping to establish and staff a regional sustainability organization for SW Ohio. As well, as the prime grantee, the University of Dayton was responsible for insuring curricular sharing between WSU and the University of Dayton. Finally, the grant, through its support of graduate students, and through cooperation with the largest utilities in SW Ohio enabled a region-wide evaluation of over 10,000 commercial building buildings in order to identify the priority buildings in the region for energy reduction. In each, the grant has achieved success. The main focus of Wright State was to continue the development of graduate education in renewable and clean energy. Wright State has done this in a number of ways. First and foremost this was done by continuing the development of the new Renewable and Clean Energy Master's Degree program at Wright State . Development tasks included: continuing development of courses for the Renewable and Clean Energy Master's Degree, increasing the student enrollment, and increasing renewable and clean energy research work. The grant has enabled development and/or improvement of 7 courses. Collectively, the University of Dayton and WSU offer perhaps the most comprehensive list of courses in the renewable and clean energy area in the country. Because of this development, enrollment at WSU has increased from 4 students to 23. Secondly, the grant has helped to support student research aimed in the renewable and clean energy program. The grant helped to solidify

  9. Initial value gravitational quadrupole radiation theorem

    International Nuclear Information System (INIS)

    Winicour, J.

    1987-01-01

    A rigorous version of the quadrupole radiation formula is derived using the characteristic initial value formulation of a general relativistic fluid space-time. Starting from initial data for a Newtonian fluid, an algorithm is presented that determines characteristic initial data for a one-parameter family of general relativistic fluid space-times. At the initial time, a one-parameter family of space-times with this initial data osculates the evolution of the Newtonian fluid and has leading order news function equal to the third time derivative of the transverse Newtonian quadrupole moment

  10. Genetically engineered rat gliomas: PDGF-driven tumor initiation and progression in tv-a transgenic rats recreate key features of human brain cancer.

    Directory of Open Access Journals (Sweden)

    Nina P Connolly

    Full Text Available Previously rodent preclinical research in gliomas frequently involved implantation of cell lines such as C6 and 9L into the rat brain. More recently, mouse models have taken over, the genetic manipulability of the mouse allowing the creation of genetically accurate models outweighed the disadvantage of its smaller brain size that limited time allowed for tumor progression. Here we illustrate a method that allows glioma formation in the rat using the replication competent avian-like sarcoma (RCAS virus / tumor virus receptor-A (tv-a transgenic system of post-natal cell type-specific gene transfer. The RCAS/tv-a model has emerged as a particularly versatile and accurate modeling technology by enabling spatial, temporal, and cell type-specific control of individual gene transformations and providing de novo formed glial tumors with distinct molecular subtypes mirroring human GBM. Nestin promoter-driven tv-a (Ntv-a transgenic Sprague-Dawley rat founder lines were created and RCAS PDGFA and p53 shRNA constructs were used to initiate intracranial brain tumor formation. Tumor formation and progression were confirmed and visualized by magnetic resonance imaging (MRI and spectroscopy. The tumors were analyzed using histopathological and immunofluorescent techniques. All experimental animals developed large, heterogeneous brain tumors that closely resembled human GBM. Median survival was 92 days from tumor initiation and 62 days from the first point of tumor visualization on MRI. Each tumor-bearing animal showed time dependent evidence of malignant progression to high-grade glioma by MRI and neurological examination. Post-mortem tumor analysis demonstrated the presence of several key characteristics of human GBM, including high levels of tumor cell proliferation, pseudopalisading necrosis, microvascular proliferation, invasion of tumor cells into surrounding tissues, peri-tumoral reactive astrogliosis, lymphocyte infiltration, presence of numerous tumor

  11. Organic Marketing Initiatives and Rural Development

    OpenAIRE

    Schmid, Otto; Sanders, Jürn; Midmore, Peter

    2004-01-01

    Over recent decades, organic farmers have come together to form collective marketing initiatives. To begin with, such schemes were often essential as the only means of finding markets for organic products, but farmers today participate in them to pool ideas, capital and skills, and to collectively increase added value of products and market power in the supply chain. However, Organic Marketing Initiatives (OMIs) are not only initiated and managed by farmers but also by consumers, processors o...

  12. Targeted Radiation Therapy for Cancer Initiative

    Science.gov (United States)

    2017-11-01

    AWARD NUMBER: W81XWH-08-2-0174 TITLE: Targeted Radiation Therapy for Cancer Initiative PRINCIPAL INVESTIGATOR: Dusten Macdonald, MD...for Cancer Initiative 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Dusten Macdonald, MD 5d. PROJECT NUMBER...Cancer Initiative Final Report INTRODUCTION: The full potential of radiation therapy has not been realized due to the inability to locate and

  13. Initialization Errors in Quantum Data Base Recall

    OpenAIRE

    Natu, Kalyani

    2016-01-01

    This paper analyzes the relationship between initialization error and recall of a specific memory in the Grover algorithm for quantum database search. It is shown that the correct memory is obtained with high probability even when the initial state is far removed from the correct one. The analysis is done by relating the variance of error in the initial state to the recovery of the correct memory and the surprising result is obtained that the relationship between the two is essentially linear.

  14. Gaseous detonation initiation via wave implosion

    Science.gov (United States)

    Jackson, Scott Irving

    Efficient detonation initiation is a topic of intense interest to designers of pulse detonation engines. This experimental work is the first to detonate propane-air mixtures with an imploding detonation wave and to detonate a gas mixture with a non-reflected, imploding shock. In order to do this, a unique device has been developed that is capable of generating an imploding toroidal detonation wave inside of a tube from a single ignition point without any obstruction to the tube flow path. As part of this study, an initiator that creates a large-aspect-ratio planar detonation wave in gas-phase explosive from a single ignition point has also been developed. The effectiveness of our initiation devices has been evaluated. The minimum energy required by the imploding shock for initiation was determined to scale linearly with the induction zone length, indicating the presence of a planar initiation mode. The imploding toroidal detonation initiator was found to be more effective at detonation initiation than the imploding shock initiator, using a comparable energy input to that of current initiator tubes.

  15. The Dynamics of Initiative in Communication Networks.

    Directory of Open Access Journals (Sweden)

    Anders Mollgaard

    Full Text Available Human social interaction is often intermittent. Two acquainted persons can have extended periods without social interaction punctuated by periods of repeated interaction. In this case, the repeated interaction can be characterized by a seed initiative by either of the persons and a number of follow-up interactions. The tendency to initiate social interaction plays an important role in the formation of social networks and is in general not symmetric between persons. In this paper, we study the dynamics of initiative by analysing and modeling a detailed call and text message network sampled from a group of 700 individuals. We show that in an average relationship between two individuals, one part is almost twice as likely to initiate communication compared to the other part. The asymmetry has social consequences and ultimately might lead to the discontinuation of a relationship. We explain the observed asymmetry by a positive feedback mechanism where individuals already taking initiative are more likely to take initiative in the future. In general, people with many initiatives receive attention from a broader spectrum of friends than people with few initiatives. Lastly, we compare the likelihood of taking initiative with the basic personality traits of the five factor model.

  16. Rotary mode system initial instrument calibration

    International Nuclear Information System (INIS)

    Johns, B.R.

    1994-01-01

    The attached report contains the vendor calibration procedures used for the initial instrument calibration of the rotary core sampling equipment. The procedures are from approved vendor information files

  17. Falls among pregnant women in Enugu, Southeast Nigeria

    African Journals Online (AJOL)

    2013-10-04

    Oct 4, 2013 ... Key words: Enugu, falls, Nigeria, pregnant women, prevalence, risk factors .... in which someone is paid some wages (salary) at specific intervals, for example .... initiated the process of filling the existing gap on falls during.

  18. Food insecurity and coping strategies among people living with HIV ...

    African Journals Online (AJOL)

    2011-10-04

    Oct 4, 2011 ... 2Clinton Health Access Initiative, P.O. Box 7727, Dar es Salaam, Tanzania ... Food insecurity raises risks of HIV infection as people adopt behaviours to ..... Relatives. Friends. Neighbours. CBO/NGO/FBO. Others. 238. 210.

  19. Implementing Patient Safety Initiatives in Rural Hospitals

    Science.gov (United States)

    Klingner, Jill; Moscovice, Ira; Tupper, Judith; Coburn, Andrew; Wakefield, Mary

    2009-01-01

    Implementation of patient safety initiatives can be costly in time and energy. Because of small volumes and limited resources, rural hospitals often are not included in nationally driven patient safety initiatives. This article describes the Tennessee Rural Hospital Patient Safety Demonstration project, whose goal was to strengthen capacity for…

  20. Career Technical Education Pathways Initiative Annual Report

    Science.gov (United States)

    California Community Colleges, Chancellor's Office, 2014

    2014-01-01

    California's education system--the largest in the United States--is an essential resource for ensuring strong economic growth in the state. The Career Technical Education Pathways Initiative (the Initiative) became law in 2005 with Senate Bills 70 and 1133 and provided more than $380 million over eight years to improve career technical education…

  1. European Initiatives in Postgraduate Education in Gerontology

    Science.gov (United States)

    van Rijsselt, Rene J. T.; Parkatti, Terttu; Troisi, Joseph

    2007-01-01

    This paper describes three innovative European initiatives in postgraduate education in gerontology. The first is the European Masters Program in Gerontology (EuMaG), developed as an interdisciplinary joint program, supported and delivered by 22 European universities. Second, the Nordplus initiative to increase mobility of students and staff in…

  2. European initiatives in postgraduate education in gerontology

    NARCIS (Netherlands)

    van Rijsselt, R.J.T.; Parkatti, T.; Troisi, J.

    2007-01-01

    This paper describes three innovative European initiatives in postgraduate education in gerontology. The first is the European Masters Program in Gerontology (EuMaG), developed as an interdisciplinary joint program, supported and delivered by 22 European universities. Second, the Nordplus initiative

  3. College and Career Counseling Training Initiative

    Science.gov (United States)

    Southern Regional Education Board (SREB), 2014

    2014-01-01

    The Southern Regional Education Board's (SREB) College and Career Counseling Training Initiative works to increase the knowledge and skills of counselors who advise students on their postsecondary aspirations. Membership in the initiative provides access to Strategies in College and Career Counseling, a series of online training modules that can…

  4. Movement initiation in groups of feral horses

    NARCIS (Netherlands)

    Krueger, Konstanze; Flauger, Birgit; Farmer, Kate; Hemelrijk, Charlotte

    Herds of ungulates, flocks of birds, swarms of insects and schools of fish move in coordinated groups. Computer models show that only one or very few animals are needed to initiate and direct movement. To investigate initiation mechanisms further, we studied two ways in which movement can be

  5. Framework for Evaluation of Equity Initiatives

    Science.gov (United States)

    Bexley, Emmaline; Harris, Kerri-Lee; James, Richard

    2010-01-01

    The Framework for Evaluation of Equity Initiatives has been prepared to support the Go8 Equity Strategy. Its purpose is to assist Group of Eight (Go8) universities to evaluate the effectiveness of their equity initiatives and interventions in the context of federal policies and the distinctive missions and responsibilities of the individual Go8…

  6. 28 CFR 301.305 - Initial determination.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Initial determination. 301.305 Section... COMPENSATION Compensation for Work-Related Physical Impairment or Death § 301.305 Initial determination. A... determination, including the reasons therefore, together with notification of the right to appeal the...

  7. View all initiatives | IDRC - International Development Research ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    View all initiatives. You are looking at projects supported by The William and Flora Hewlett Foundation. Displaying 1 - 2 of 2. Growth and Economic Opportunities for Women. Initiative. Women around the world increasingly participate in economic activities, but they continue to face significant challenges in pursuing better ...

  8. Science Granting Councils Initiative: Research uptake | CRDI ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The initiative's activities include training, regional exchanges and forums, online training, on-site coaching, and collaborative research. The initiative was developed jointly by IDRC, the United Kingdom's Department for International Development, and South Africa's National Research Foundation. Its ultimate goal is ...

  9. 12 CFR 404.15 - Initial determination.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Initial determination. 404.15 Section 404.15 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Access to Records Under the Privacy Act of 1974 § 404.15 Initial determination. (a) Time for processing. The Freedom of...

  10. 12 CFR 404.8 - Initial determination.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Initial determination. 404.8 Section 404.8 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Procedures for Disclosure of Records Under the Freedom of Information Act. § 404.8 Initial determination. (a) Authority to...

  11. Current Editorial Initiatives: A Progress Report

    Directory of Open Access Journals (Sweden)

    Werner Ulrich

    2013-01-01

    Full Text Available This editorial article reports on the progress that the Journal of Research Practice (JRP has achieved in its ongoing development since November 2011, when a number of editorial initiatives were announced. Several new initiatives are also proposed. In addition, there are some current announcements, including a number of recent awards, distinctions, and nominations.

  12. 75 FR 49510 - Credit Watch Termination Initiative

    Science.gov (United States)

    2010-08-13

    ... DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT [Docket No. FR-5411-N-02] Credit Watch Termination Initiative AGENCY: Office of the Assistant Secretary for Housing--Federal Housing Commissioner, HUD. ACTION... FHA Credit Watch Termination Initiative. This notice includes a list of mortgagees which have had...

  13. 76 FR 47240 - ``Add Us In'' Initiative

    Science.gov (United States)

    2011-08-04

    ... DEPARTMENT OF LABOR Office of Disability Employment Policy ``Add Us In'' Initiative AGENCY: Office of Disability Employment Policy, Department of Labor. Announcement Type: New Notice of Availability... Add Us In initiative is to identify and develop strategies to increase the capacity of small...

  14. 75 FR 17944 - Credit Watch Termination Initiative

    Science.gov (United States)

    2010-04-08

    ... DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT [Docket No. FR-5411-N-01] Credit Watch Termination Initiative AGENCY: Office of the Assistant Secretary for Housing--Federal Housing Commissioner, HUD. ACTION... FHA Credit Watch Termination Initiative. This notice includes a list of mortgagees which have had...

  15. Institutional Support : Agricultural and Rural Forecasting Initiative ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Initiative Prospective Agricole et Rural (IPAR), Sénégal, began in 2004 and was formally registered in October 2008 as an independent, nonprofit research organization. The Initiative is committed to promoting dialogue and informing debate between policymakers, researchers and research users in the areas of agriculture, ...

  16. Unraveling networked learning initiatives: an analytic framework

    NARCIS (Netherlands)

    Rusman, Ellen; Prinsen, Fleur; Vermeulen, Marjan

    2016-01-01

    Networked learning happens naturally within the social systems of which we are all part. However, in certain circumstances individuals may want to actively take initiative to initiate interaction with others they are not yet regularly in exchange with. This may be the case when external influences

  17. Symbolic initiative and its application to computers

    Energy Technology Data Exchange (ETDEWEB)

    Hellerman, L

    1982-01-01

    The author reviews the role of symbolic initiative in mathematics and then defines a sense in which computers compute mathematical functions. This allows a clarification of the semantics of computer and communication data. Turing's view of machine intelligence is examined in terms of its use of symbolic initiative. 12 references.

  18. Embedding initial data for black hole collisions

    OpenAIRE

    Romano, Joseph D.; Price, Richard H.

    1994-01-01

    We discuss isometric embedding diagrams for the visualization of initial data for the problem of the head-on collision of two black holes. The problem of constructing the embedding diagrams is explicitly presented for the best studied initial data, the Misner geometry. We present a partial solution of the embedding diagrams and discuss issues related to completing the solution.

  19. Multimedia Instruction Initiative: Building Faculty Competence.

    Science.gov (United States)

    Haile, Penelope J.

    Hofstra University began a university-wide initiative to enhance classroom instruction with multimedia technology and foster collaborative approaches to learning. The Multimedia Instruction Initiative emphasized teamwork among faculty, students, and computer center support staff to develop a technology-enriched learning environment supported by…

  20. Children's Alcohol Initiation: An Analytic Overview

    Science.gov (United States)

    Ward, Bernadette; Snow, Pamela; Aroni, Rosalie

    2010-01-01

    Many parents support the "supervised introduction" of alcohol to children. While initiation to regular alcohol consumption in early adolescence has been linked with alcohol-related problems in adult life, the findings from these studies cannot be extrapolated to early childhood. The definition of initiation to alcohol in early childhood is often…

  1. Direct laser initiation of open secondary explosives

    International Nuclear Information System (INIS)

    Assovskiy, I G; Melik-Gaikazov, G V; Kuznetsov, G P

    2015-01-01

    The goal of this paper is experimental study of the mechanism of initiation of secondary explosives (SE) by short laser pulse. Laser initiation of SE is much more difficult in comparison with initiation of primary explosives. Using of some special methods is typically requested to realize laser initiation of SE: using of porous SE, putting it in a closed envelope, and using some optically dense additives. In this paper we consider interaction of laser pulse with open surface of non-porous, optically uniform SE. Only pure chemical methods were used to control the light sensitivity of SE. Implementation of the method of laser initiation is reduced to the optimization of composition and molecular structure of the explosives, along with the optimization of the laser pulse (its duration, energy density and wavelength). (paper)

  2. Subsidiary Initiative Taking in Multinational Corporations

    DEFF Research Database (Denmark)

    Dörrenbacher, Christoph; Gammelgaard, Jens

    2016-01-01

    This paper investigates the political maneuvering that accompanies subsidiary initiative taking in multinational corporations. On the basis of an explorative empirical investigation of subsidiary initiative taking in the French subsidiaries of six German MNCs, the paper explores the activities...... that subsidiaries undertake to sell their initiatives, and the relationships among issue selling, subsidiary power and headquarters’ hierarchical power. The findings suggest that the use of issue-selling tactics is common when subsidiaries engage in initiative taking. In addition, the paper demonstrates that a low...... degree of issue selling is needed to obtain approval of an initiative in less asymmetrical headquarters–subsidiary power relationships (i.e. relationships in which subsidiaries are relatively powerful). In cases where power relationships are highly asymmetrical, issue selling is a necessity...

  3. NPV-LDE-225 (Erismodegib) inhibits epithelial mesenchymal transition and self-renewal of glioblastoma initiating cells by regulating miR-21, miR-128, and miR-200.

    Science.gov (United States)

    Fu, Junsheng; Rodova, Mariana; Nanta, Rajesh; Meeker, Daniel; Van Veldhuizen, Peter J; Srivastava, Rakesh K; Shankar, Sharmila

    2013-06-01

    Glioblastoma multiforme is the most common form of primary brain tumor, often characterized by poor survival. Glioblastoma initiating cells (GICs) regulate self-renewal, differentiation, and tumor initiation properties and are involved in tumor growth, recurrence, and resistance to conventional treatments. The sonic hedgehog (SHH) signaling pathway is essential for normal development and embryonic morphogenesis. The objectives of this study were to examine the molecular mechanisms by which GIC characteristics are regulated by NPV-LDE-225 (Smoothened inhibitor; (2,2'-[[dihydro-2-(4-pyridinyl)-1,3(2H,4H)-pyrimidinediyl]bis(methylene)]bis[N,N-dimethylbenzenamine). Cell viability and apoptosis were measured by XTT and annexin V-propidium iodide assay, respectively. Gli translocation and transcriptional activities were measured by immunofluorescence and luciferase assay, respectively. Gene and protein expressions were measured by quantitative real-time PCR and Western blot analyses, respectively. NPV-LDE-225 inhibited cell viability, neurosphere formation, and Gli transcriptional activity and induced apoptosis by activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase. NPV-LDE-225 increased the expression of tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-R1/DR4, TRAIL-R2/DR5, and Fas and decreased the expression of platelet derived growth factor receptor-α and Bcl2, and these effects were abrogated by Gli1 plus Gli2 short hairpin RNAs. NPV-LDE-225 enhanced the therapeutic potential of FasL and TRAIL by upregulating Fas and DR4/5, respectively. Interestingly, NPV-LDE-225 induced expression of programmed cell death 4 and apoptosis and inhibited cell viability by suppressing micro RNA (miR)-21. Furthermore, NPV-LDE-225 inhibited pluripotency-maintaining factors Nanog, Oct4, Sox2, and cMyc. The inhibition of Bmi1 by NPV-LDE-225 was regulated by induction of miR-128. Finally, NPV-LDE-225 suppressed epithelial-mesenchymal transition by

  4. A mechanical energy analysis of gait initiation

    Science.gov (United States)

    Miller, C. A.; Verstraete, M. C.

    1999-01-01

    The analysis of gait initiation (the transient state between standing and walking) is an important diagnostic tool to study pathologic gait and to evaluate prosthetic devices. While past studies have quantified mechanical energy of the body during steady-state gait, to date no one has computed the mechanical energy of the body during gait initiation. In this study, gait initiation in seven normal male subjects was studied using a mechanical energy analysis to compute total body energy. The data showed three separate states: quiet standing, gait initiation, and steady-state gait. During gait initiation, the trends in the energy data for the individual segments were similar to those seen during steady-state gait (and in Winter DA, Quanbury AO, Reimer GD. Analysis of instantaneous energy of normal gait. J Biochem 1976;9:253-257), but diminished in amplitude. However, these amplitudes increased to those seen in steady-state during the gait initiation event (GIE), with the greatest increase occurring in the second step due to the push-off of the foundation leg. The baseline level of mechanical energy was due to the potential energy of the individual segments, while the cyclic nature of the data was indicative of the kinetic energy of the particular leg in swing phase during that step. The data presented showed differences in energy trends during gait initiation from those of steady state, thereby demonstrating the importance of this event in the study of locomotion.

  5. Cigarette advertising and teen smoking initiation.

    Science.gov (United States)

    Hanewinkel, Reiner; Isensee, Barbara; Sargent, James D; Morgenstern, Matthis

    2011-02-01

    To test the specificity of the association between cigarette advertising and adolescent smoking initiation. A longitudinal survey of 2102 adolescents, aged 10 to 17 years at baseline, who never smoked was conducted by using masked images of 6 cigarette advertisements and 8 other commercial products with all brand information digitally removed. The exposure variable was a combination of contact frequency and cued recall of brands for cigarette and other advertisements. Multilevel mixed-effects Poisson regressions were used to assess smoking initiation 9 months after the baseline assessment as a function of cigarette-advertisement exposure, other advertisement exposure, and baseline covariates. Thirteen percent (n = 277) of students initiated smoking during the observation period. Although the incidence of trying smoking was associated with increased exposure to cigarette advertisements (10% in the low, 12% in the medium, and 19% in the high cigarette-advertisement exposure tertile initiated smoking), exposure to other advertisements did not predict smoking initiation. Compared with low exposure to cigarette advertisements, high exposure remained a significant predictor of adolescent smoking initiation after controlling for baseline covariates (adjusted relative risk: 1.46 [95% confidence interval: 1.08-1.97]; P content-related effect of cigarette advertisements and underlines the specificity of the relationship between tobacco marketing and teen smoking; exposure to cigarette advertisements, but not other advertisements, is associated with smoking initiation.

  6. Health professionals' attitudes towards suicide prevention initiatives.

    Science.gov (United States)

    Brunero, S; Smith, J; Bates, E; Fairbrother, G

    2008-09-01

    Preventing suicide can depend upon the ability of a range of different health professionals to make accurate suicide risk assessments and treatment plans. The attitudes that clinicians hold towards suicide prevention initiatives may influence their suicide risk assessment and management skills. This study measures a group of non-mental health professionals' attitude towards suicide prevention initiatives. Health professionals that had attended suicide prevention education showed significantly more positive attitudes towards suicide prevention initiatives. The findings in this study further support the effectiveness of educating non-mental health professionals in suicide risk awareness and management.

  7. Initiation of anticoagulation in atrial fibrillation

    DEFF Research Database (Denmark)

    Gundlund, A.; Staerk, L.; Fosbøl, E. L.

    2017-01-01

    Background: The use of non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prophylaxis in atrial fibrillation (AF) is increasing rapidly. We compared characteristics of AF patients initiated on NOACs versus vitamin K antagonists (VKAs). Methods: Using Danish nationwide registry data, we...... compared with a VKA [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.28–1.43]. By contrast, patients with a history of myocardial infarction were less likely to be initiated on a NOAC compared with a VKA (OR 0.72, 95% CI 0.67–0.77). Conclusions: Atrial fibrillation patients who were initiated...

  8. Initial singularity and pure geometric field theories

    Science.gov (United States)

    Wanas, M. I.; Kamal, Mona M.; Dabash, Tahia F.

    2018-01-01

    In the present article we use a modified version of the geodesic equation, together with a modified version of the Raychaudhuri equation, to study initial singularities. These modified equations are used to account for the effect of the spin-torsion interaction on the existence of initial singularities in cosmological models. Such models are the results of solutions of the field equations of a class of field theories termed pure geometric. The geometric structure used in this study is an absolute parallelism structure satisfying the cosmological principle. It is shown that the existence of initial singularities is subject to some mathematical (geometric) conditions. The scheme suggested for this study can be easily generalized.

  9. Higher-dimensional puncture initial data

    International Nuclear Information System (INIS)

    Zilhao, Miguel; Ansorg, Marcus; Cardoso, Vitor; Gualtieri, Leonardo; Herdeiro, Carlos; Sperhake, Ulrich; Witek, Helvi

    2011-01-01

    We calculate puncture initial data, corresponding to single and binary black holes with linear momenta, which solve the constraint equations of D-dimensional vacuum gravity. The data are generated by a modification of the pseudospectral code presented in [M. Ansorg, B. Bruegmann, and W. Tichy, Phys. Rev. D 70, 064011 (2004).] and made available as the TwoPunctures thorn inside the Cactus computational toolkit. As examples, we exhibit convergence plots, the violation of the Hamiltonian constraint as well as the initial data for D=4,5,6,7. These initial data are the starting point to perform high-energy collisions of black holes in D dimensions.

  10. Mobile computing initiatives within pharmacy education.

    Science.gov (United States)

    Cain, Jeff; Bird, Eleanora R; Jones, Mikael

    2008-08-15

    To identify mobile computing initiatives within pharmacy education, including how devices are obtained, supported, and utilized within the curriculum. An 18-item questionnaire was developed and delivered to academic affairs deans (or closest equivalent) of 98 colleges and schools of pharmacy. Fifty-four colleges and schools completed the questionnaire for a 55% completion rate. Thirteen of those schools have implemented mobile computing requirements for students. Twenty schools reported they were likely to formally consider implementing a mobile computing initiative within 5 years. Numerous models of mobile computing initiatives exist in terms of device obtainment, technical support, infrastructure, and utilization within the curriculum. Responders identified flexibility in teaching and learning as the most positive aspect of the initiatives and computer-aided distraction as the most negative, Numerous factors should be taken into consideration when deciding if and how a mobile computing requirement should be implemented.

  11. Hybrid Black-Hole Binary Initial Data

    Science.gov (United States)

    Mundim, Bruno C.; Kelly, Bernard J.; Nakano, Hiroyuki; Zlochower, Yosef; Campanelli, Manuela

    2010-01-01

    "Traditional black-hole binary puncture initial data is conformally flat. This unphysical assumption is coupled with a lack of radiation signature from the binary's past life. As a result, waveforms extracted from evolutions of this data display an abrupt jump. In Kelly et al. [Class. Quantum Grav. 27:114005 (2010)], a new binary black-hole initial data with radiation contents derived in the post-Newtonian (PN) calculations was adapted to puncture evolutions in numerical relativity. This data satisfies the constraint equations to the 2.5PN order, and contains a transverse-traceless "wavy" metric contribution, violating the standard assumption of conformal flatness. Although the evolution contained less spurious radiation, there were undesired features; the unphysical horizon mass loss and the large initial orbital eccentricity. Introducing a hybrid approach to the initial data evaluation, we significantly reduce these undesired features."

  12. Augmenting Probabilistic Risk Assesment with Malevolent Initiators

    International Nuclear Information System (INIS)

    Smith, Curtis; Schwieder, David

    2011-01-01

    As commonly practiced, the use of probabilistic risk assessment (PRA) in nuclear power plants only considers accident initiators such as natural hazards, equipment failures, and human error. Malevolent initiators are ignored in PRA, but are considered the domain of physical security, which uses vulnerability assessment based on an officially specified threat (design basis threat). This paper explores the implications of augmenting and extending existing PRA models by considering new and modified scenarios resulting from malevolent initiators. Teaming the augmented PRA models with conventional vulnerability assessments can cost-effectively enhance security of a nuclear power plant. This methodology is useful for operating plants, as well as in the design of new plants. For the methodology, we have proposed an approach that builds on and extends the practice of PRA for nuclear power plants for security-related issues. Rather than only considering 'random' failures, we demonstrated a framework that is able to represent and model malevolent initiating events and associated plant impacts.

  13. 16 CFR 238.2 - Initial offer.

    Science.gov (United States)

    2010-01-01

    ... § 238.2 Initial offer. (a) No statement or illustration should be used in any advertisement which creates a false impression of the grade, quality, make, value, currency of model, size, color, usability...

  14. Initiation of Meiotic Recombination in Mammals

    Directory of Open Access Journals (Sweden)

    Rajeev Kumar

    2010-12-01

    Full Text Available Meiotic recombination is initiated by the induction of programmed DNA double strand breaks (DSBs. DSB repair promotes homologous interactions and pairing and leads to the formation of crossovers (COs, which are required for the proper reductional segregation at the first meiotic division. In mammals, several hundred DSBs are generated at the beginning of meiotic prophase by the catalytic activity of SPO11. Currently it is not well understood how the frequency and timing of DSB formation and their localization are regulated. Several approaches in humans and mice have provided an extensive description of the localization of initiation events based on CO mapping, leading to the identification and characterization of preferred sites (hotspots of initiation. This review presents the current knowledge about the proteins known to be involved in this process, the sites where initiation takes place, and the factors that control hotspot localization.

  15. Profiles of an initially perturbed electron beam

    International Nuclear Information System (INIS)

    Abdelsalam, F.W.

    1991-01-01

    This paper discusses the solutions for the profiles of an electron beam which is launched into a constant magnetic field with an initial boundary slope and injected with a radius which is greater or less than the cathode radius. It has been found that the outermost electron traces sine waves and executes limited excursions when the initial boundary slope corresponds to angles up to 1 degree, no matter whether the initial radius is 0.90 or 1.10 times the radius of the cathode. For initial inclination angles close to 2 degrees, the beam boundary does not preserve a sinusoidal shape, this statement holds true for focusing magnetic flux densities varying from 200x10 -4 to 700x10 -4 weber per square meter

  16. Initiation of Replication in Escherichia coli

    DEFF Research Database (Denmark)

    Frimodt-Møller, Jakob

    The circular chromosome of Escherichia coli is replicated by two replisomes assembled at the unique origin and moving in the opposite direction until they meet in the less well defined terminus. The key protein in initiation of replication, DnaA, facilitates the unwinding of double-stranded DNA...... to single-stranded DNA in oriC. Although DnaA is able to bind both ADP and ATP, DnaA is only active in initiation when bound to ATP. Although initiation of replication, and the regulation of this, is thoroughly investigated it is still not fully understood. The overall aim of the thesis was to investigate...... the regulation of initiation, the effect on the cell when regulation fails, and if regulation was interlinked to chromosomal organization. This thesis uncovers that there exists a subtle balance between chromosome replication and reactive oxygen species (ROS) inflicted DNA damage. Thus, failure in regulation...

  17. Data Center Optimization Initiative Strategic Plans

    Data.gov (United States)

    Social Security Administration — On August 1, 2016, the Office of Management and Budget issued memorandum M-16-19, establishing the Data Center Optimization Initiative (DCOI). The DCOI, as described...

  18. Science Granting Councils Initiative: Research uptake | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The Science Granting Councils Initiative in sub-Saharan Africa aims to ... The strategy identifies a wide range of activities to collect, package, and share lessons ... Organization for Women in Science for the Developing World (OWSD), IDRC is ...

  19. Pacific Northwest Laboratory's Solid Waste Initiative

    International Nuclear Information System (INIS)

    Holter, G.M.

    1993-09-01

    In fiscal year 1992 (FY-92), a Solid Waste Initiative was undertaken within the Pacific Northwest Laboratory (PNL). This action was partly in response to a perceived increase in the frequency and severity of impacts associated with solid waste issues at all levels. It also recognized the limited attention of previous efforts in addressing the broader impacts resulting from solid waste and, thus, dealing with solid waste issues in a holistic fashion. This paper provides a description of the Solid Waste Initiative at PNL, including a historical perspective on PNL's involvement in solid waste issues, the goals and objectives of the Solid Waste Initiative, and a discussion of selected activities being conducted under the Initiative

  20. Implementing Knowledge Management as a Strategic Initiative

    National Research Council Canada - National Science Library

    DiGiacomo, Joseph

    2003-01-01

    ... are: leadership, organization, technology and leaning. Knowledge management was one of five strategic initiatives in the overall strategic plan, which was developed using Kaplan and Norton's Balanced Scorecard methodology...

  1. Hawaii Energy and Environmental Technologies (HEET) Initiative

    National Research Council Canada - National Science Library

    Rocheleau, Richard E; Moore, Robert M; Turn, Scott Q; Antal, Jr., Michael J; Cooney, Michael J; Liaw, Bor-Yann; Masutani, Stephen M

    2007-01-01

    This report covers efforts by the Hawaii Natural Energy Institute of the University of Hawaii under the ONR-funded HEET Initiative that addresses critical technology needs for exploration/utilization...

  2. African Health Systems Initiative (AHSI) | IDRC - International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The African Health Systems Initiative (AHSI) is a 10-year Canadian International ... for strengthening African-led health systems and human resources for health. ... IDRC congratulates first cohort of Women in Climate Change Science Fellows.

  3. 2010 Administrative Law Judge Initial Decisions

    Data.gov (United States)

    Securities and Exchange Commission — The initial decisions issued by administrative law judges in 2010 that contains findings of fact, legal conclusions, and an order that often contains a sanction....

  4. 2009 Administrative Law Judge Initial Decisions

    Data.gov (United States)

    Securities and Exchange Commission — The initial decisions issued by administrative law judges in 2009 that contains findings of fact, legal conclusions, and an order that often contains a sanction....

  5. Cabozantinib for Initial Treatment of Kidney Cancer

    Science.gov (United States)

    FDA has approved cabozantinib (Cabometyx®) as an initial treatment for patients with advanced renal cell carcinoma. The approval adds another tyrosine kinase inhibitor to the available options for patients with advanced kidney cancer.

  6. 19 CFR 354.14 - Initial decision.

    Science.gov (United States)

    2010-04-01

    ... submissions. The initial decision will be based solely on evidence received into the record, and the pleadings... sanctions to impose, the presiding official or the Deputy Under Secretary will consider the nature of the...

  7. NECTAR: initiatives and development 2008-2016

    OpenAIRE

    Dimmock, Nick; Hibbert, Dawn

    2017-01-01

    A poster illustrating the development of NECTAR, the University of Northampton's research repository, since its launch in 2008. Key initiatives and projects are highlighted, along with statistics on deposit activity and downloads.

  8. African Tobacco Control Research Initiative Scoping Exercise ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The African Tobacco Control Research Initiative (ATCRI) was established in ... of taxation, advertising bans, smoke-free places and graphic health warnings. ... Special journal issue highlights IDRC-supported findings on women's paid work.

  9. Single Family Loan Sale Initiative - National Offering

    Data.gov (United States)

    Department of Housing and Urban Development — The FHA Office of Housing is conducting a series of mortgage loan sales under the Single Family Loan Sale (SFLS) Initiative. The current sales structure consists of...

  10. Nonfasting Versus Initial Fasting Ketogenic Diet

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-02-01

    Full Text Available A retrospective evaluation of the ketogenic diet (KD was conducted comparing efficacy and tolerability of the diet with or without initial fasting and fluid restriction and involving university centers in Seoul, Korea.

  11. THE RISK FACTORS FOR INITIAL REPRODUCTIVE LOSS

    Directory of Open Access Journals (Sweden)

    Екатерина Игоревна Лебедева

    2017-09-01

    Conclusion. Mixed somatic and gynecological pathology, abnormalities in hemostasis, combination of inherited and acquired thrombogenic risk factors dominates in women with initial reproductive loss, though only 37,3 % such pregnancies have favorable outcome.

  12. National Aerospace Leadership Initiative - Phase 2

    Science.gov (United States)

    2010-03-01

    BNB Manufacturing, HMR Associates, PWA, UTRC, Sikorsky Helicopter, TCI MRO, Schwerdtle, Unilever , University of Hartford. In several cases parts were...HMR Associates, PWA, UTRC, Sikorsky Helicopter, TCI MRO, Schwerdtle, Unilever , University of Hartford National Aerospace Leadership Initiative

  13. Lilavatis Daughters | Women in Science | Initiatives | Indian ...

    Indian Academy of Sciences (India)

    Home; Initiatives; Women in Science; Lilavatis Daughters ... The book 'Lilavati's Daughters: The Women Scientists of India' was successfully ... Charusita Chakravarty, one of the stars of our community of women scientists, at a young age of 52, ...

  14. Innovation Initiatives in Large Software Companies

    DEFF Research Database (Denmark)

    Edison, Henry; Wang, Xiaofeng; Jabangwe, Ronald

    2018-01-01

    empirical studies on innovation initiative in the context of large software companies. A total of 7 studies are conducted in the context of large software companies, which reported 5 types of initiatives: intrapreneurship, bootlegging, internal venture, spin-off and crowdsourcing. Our study offers three......Context: To keep the competitive advantage and adapt to changes in the market and technology, companies need to innovate in an organised, purposeful and systematic manner. However, due to their size and complexity, large companies tend to focus on the structure in maintaining their business, which...... can potentially lower their agility to innovate. Objective:The aims of this study are to provide an overview of the current research on innovation initiatives and to identify the challenges of implementing those initiatives in the context of large software companies. Method: The investigation...

  15. Partners and initiatives | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Results 1 - 10 of 20 ... A longstanding partner, Global Affairs Canada collaborates with us on maternal and ... Collaborative Adaptation Research Initiative in Africa and Asia ... These investments in scientific breakthroughs will improve the health.

  16. Initial response of a rock penetrator

    International Nuclear Information System (INIS)

    Longcope, D.B.; Grady, D.E.

    1977-12-01

    An analysis based on elastic rod theory is given for the early-time axisymmetric response of pointed penetrators. Results of measurements by laser interferometry of the back surface particle velocity of laboratory scale penetrators impacted by sandstone targets are presented. Values of the initial pressure on the penetrator tip are determined which give good agreement between the analytical and experimental results. These initial tip pressures are found to be approximated by the stress-particle velocity Hugoniot for the target material

  17. Global initiatives to prevent nuclear terrorism

    International Nuclear Information System (INIS)

    2010-01-01

    The fight against nuclear and radiological terrorism - someone to blow up a nuclear weapon or spread radioactive material as a 'dirty bomb' that act of terrorism - is one of the most serious threats to international security. The Global Initiative to prevent nuclear terrorism is a Norwegian-sponsored initiative that is aimed directly at combating terrorism by non-state actors. NRPA follow up Norwegian measures, including in Kazakhstan, and verifies that they are implemented and functioning as intended. (AG)

  18. Inhomogeneous inflation: The initial-value problem

    International Nuclear Information System (INIS)

    Laguna, P.; Kurki-Suonio, H.; Matzner, R.A.

    1991-01-01

    We present a spatially three-dimensional study for solving the initial-value problem in general relativity for inhomogeneous cosmologies. We use York's conformal approach to solve the constraint equations of Einstein's field equations for scalar field sources and find the initial data which will be used in the evolution. This work constitutes the first stage in the development of a code to analyze the effects of matter and spacetime inhomogeneities on inflation

  19. Network support for system initiated checkpoints

    Science.gov (United States)

    Chen, Dong; Heidelberger, Philip

    2013-01-29

    A system, method and computer program product for supporting system initiated checkpoints in parallel computing systems. The system and method generates selective control signals to perform checkpointing of system related data in presence of messaging activity associated with a user application running at the node. The checkpointing is initiated by the system such that checkpoint data of a plurality of network nodes may be obtained even in the presence of user applications running on highly parallel computers that include ongoing user messaging activity.

  20. Initial States: IR and Collinear Divergences

    International Nuclear Information System (INIS)

    Lavelle, Martin; McMullan, David

    2007-01-01

    The standard approach to the infra-red problem is to use the Bloch-Nordsieck trick to handle soft divergences and the Lee-Nauenberg (LN) theorem for collinear singularities. We show that this is inconsistent in the presence of massless initial particles. Furthermore, we show that using the LN theorem with such initial states introduces a non-convergent infinite series of diagrams at any fixed order in perturbation theory

  1. Motivators to Adopt Green Supply Chain Initiatives

    OpenAIRE

    Amarpreet S. Kohli; Ellen Hawkins

    2015-01-01

    There are several factors that drive organizations to consider implementing green supply chain (GSC) initiatives. This paper refines an instrument to empirically test the significance of the following drivers for participation in GSC initiatives: Government Regulation, Buyer/Supply Chain Influence, Internal Readiness, Competitive Advantage, and Corporate Social Responsibility. Corporate Social Responsibility emerged as the most significant variable that effected the decision making of the org...

  2. Southwest Regional Clean Energy Incubation Initiative (SRCEII)

    Energy Technology Data Exchange (ETDEWEB)

    Webber, Michael [Univ. of Texas, Austin, TX (United States)

    2017-10-31

    The Austin Technology Incubator’s (ATI’s) Clean Energy Incubator at the University of Texas at Austin (ATI-CEI) utilized the National Incubator Initiative for Clean Energy (NIICE) funding to establish the Southwest Regional Clean Energy Incubation Initiative, composed of clean energy incubators from The University of Texas at Austin (UT-Austin), The University of Texas at El Paso (UTEP), The University of Texas at San Antonio (UTSA), and Texas A&M University (TAMU).

  3. The State of the NIH BRAIN Initiative.

    Science.gov (United States)

    Koroshetz, Walter; Gordon, Joshua; Adams, Amy; Beckel-Mitchener, Andrea; Churchill, James; Farber, Gregory; Freund, Michelle; Gnadt, Jim; Hsu, Nina; Langhals, Nicholas; Lisanby, Sarah; Liu, Guoying; Peng, Grace; Ramos, Khara; Steinmetz, Michael; Talley, Edmund; White, Samantha

    2018-06-19

    The BRAIN Initiative® arose from a grand challenge to "accelerate the development and application of new technologies that will enable researchers to produce dynamic pictures of the brain that show how individual brain cells and complex neural circuits interact at the speed of thought." The BRAIN Initiative is a public-private effort focused on the development and use of powerful tools for acquiring fundamental insights about how information processing occurs in the central nervous system. As the Initiative enters its fifth year, NIH has supported over 500 principal investigators, who have answered the Initiative's challenge via hundreds of publications describing novel tools, methods, and discoveries that address the Initiative's seven scientific priorities. We describe scientific advances produced by individual labs, multi-investigator teams, and entire consortia that, over the coming decades, will produce more comprehensive and dynamic maps of the brain, deepen our understanding of how circuit activity can produce a rich tapestry of behaviors, and lay the foundation for understanding how its circuitry is disrupted in brain disorders. Much more work remains to bring this vision to fruition, and NIH continues to look to the diverse scientific community, from mathematics, to physics, chemistry, engineering, neuroethics, and neuroscience, to ensure that the greatest scientific benefit arises from this unique research Initiative. Copyright © 2018 the authors.

  4. Systematic Review about Personal Growth Initiative

    Directory of Open Access Journals (Sweden)

    Clarissa Pinto Pizarro de Freitas

    Full Text Available The present study aimed to realize a systematic review of publications about personal growth initiative. A literature review was realized in Bireme, Index Psi, LILACS, PePSIC, Pubmed - Publisher's Medlme, Wiley Online Library, PsycINFO, OneFile, SciVerse ScienceDirect, ERIC, Emerald Journals, PsycARTICLES - American Psychological Association, Directory of Open Access Journals - DOAJ, SAGE Journals, SpringerLink, PLoS, IngentaConnect, IEEE Journals & Magazines and SciELO databases. The literature review was performed from December of 2014 to January of 2015, without stipulating date limits for the publication of the articles. It was found 53 studies, excluded seven, and analyzed 46 researches. The studies aimed to investigate the psychometric properties of personal growth initiative scale and personal growth initiative scale II. The relations of personal initiative growth and others constructs were also evaluated. Furthermore the studies investigated the impact of interventions to promote personal growth initiative. Results of these studies showed that personal growth initiative was positively related to levels of well-being, selfesteem and others positive dimensions, and negatively to anxiety, depression and others negative factors.

  5. INITIATION AND CONDUCT OF ADMINISTRATIVE PROCEDURE

    Directory of Open Access Journals (Sweden)

    Milan Stipic

    2013-12-01

    Full Text Available General administrative procedure act contains legal norms that are valid for all identical cases. In addition to the general, there are special administrative procedures, customized to the specific administrative areas. Procedure initiation is regulated. Administrative procedure can be initiated at the request of the proponent and ex officio. When the official determines that the conditions for the conduct of administrative procedure are met, before making a decision, all the facts and circumstances relevant to the resolution of administrative matter have to be identified. When there are no legal requirements for the initiation of procedures, the official shall make a decision to reject the application of the party. The procedure is initiated ex officio when stipulated by law or when protection of public interest requires it. When initiating procedure ex officio, the public authority shall take into consideration the petition or other information that indicate the need to protect the public interest. In such cases the applicant is not a party, and the official is obliged to notify the applicant, if initiation of procedures is not accepted ex officio. Based on the notification, the applicant has a right to complain, including the situation when there is no response within the prescribed period of 30 days. Public authority may, therefore it is not obliged to, initiate administrative procedure by public announcement only in a situation where the parties are unknown, while it is obliged to initiate procedure by public announcement when this method of initiating the procedure is prescribed by law. Initiation of procedure with public announcement occurs in rare cases. Due to the application of efficiency and cost-effectiveness principle, two or more administrative procedures can be merged into one procedure by a conclusion. The condition for this is that the rights or obligations of the parties are based on the same legal basis and on the same or

  6. Correlates of sexual initiation among European adolescents

    Science.gov (United States)

    Carli, Vladimir; Hadlaczky, Gergö; Sarchiapone, Marco; Apter, Alan; Balazs, Judit; Banzer, Raphaela; Bobes, Julio; Brunner, Romuald; Cosman, Doina; Farkas, Luca; Haring, Christian; Hoven, Christina W.; Kaess, Michael; Kahn, Jean Pierre; McMahon, Elaine; Postuvan, Vita; Sisask, Merike; Värnik, Airi; Zadravec Sedivy, Nusa; Wasserman, Danuta

    2018-01-01

    Background Sexuality is a physiological component of adolescent development, though early initiation is associated with reproductive health risk. This study aimed at identifying correlates and predictors of sexual initiation in a large multinational cohort of European adolescents. Methods A questionnaire addressing socio-demographics, behaviours, mental health and sexual activity, was delivered to 11,110 adolescents recruited from 168 randomly selected schools in 10 European countries between 2009 and 2011. A follow-up questionnaire was delivered after 12 months. The longitudinal association of baseline risk behaviors, psychological attributes and contextual vulnerabilities, with sexual initiation during follow-up was evaluated through simple and multivariable age/sex stratified logistic regression. Multinomial logistic regression measured the association between predictors and sexual initiation with or without coexisting reproductive risk factors, such as multiple partners or infrequent condom use. Results Baseline sexual experience was reported by 19.2% of 10,757 respondents (median age 15; IQR 14–15; females 59.6%). This was significantly more frequent among pupils older than 15 (41%) and males (20.8%). Of 7,111 pupils without previous experience who were available at follow-up (response rate 81.8%), 17% reported sexual initiation, without differences between females and males. Baseline smoking (age/sex adjusted odds ratio [aOR] 3.63), alcohol use (aOR 2.95), illegal drugs use (aOR 2.72), and poor sleep (aOR 1.71) predicted sexual initiation. Stratified analyses showed a particularly strong association in case of younger and female pupils, and, among girls, when initiation was reported together with multiple partners and/or infrequent condom use. Externalizing (i.e. conduct and hyperactivity) symptoms independently predicted sexual initiation. Internalizing difficulties (i.e. emotional and peer problems) were negatively associated with early and risky sexual

  7. Correlates of sexual initiation among European adolescents.

    Directory of Open Access Journals (Sweden)

    Pietro Gambadauro

    Full Text Available Sexuality is a physiological component of adolescent development, though early initiation is associated with reproductive health risk. This study aimed at identifying correlates and predictors of sexual initiation in a large multinational cohort of European adolescents.A questionnaire addressing socio-demographics, behaviours, mental health and sexual activity, was delivered to 11,110 adolescents recruited from 168 randomly selected schools in 10 European countries between 2009 and 2011. A follow-up questionnaire was delivered after 12 months. The longitudinal association of baseline risk behaviors, psychological attributes and contextual vulnerabilities, with sexual initiation during follow-up was evaluated through simple and multivariable age/sex stratified logistic regression. Multinomial logistic regression measured the association between predictors and sexual initiation with or without coexisting reproductive risk factors, such as multiple partners or infrequent condom use.Baseline sexual experience was reported by 19.2% of 10,757 respondents (median age 15; IQR 14-15; females 59.6%. This was significantly more frequent among pupils older than 15 (41% and males (20.8%. Of 7,111 pupils without previous experience who were available at follow-up (response rate 81.8%, 17% reported sexual initiation, without differences between females and males. Baseline smoking (age/sex adjusted odds ratio [aOR] 3.63, alcohol use (aOR 2.95, illegal drugs use (aOR 2.72, and poor sleep (aOR 1.71 predicted sexual initiation. Stratified analyses showed a particularly strong association in case of younger and female pupils, and, among girls, when initiation was reported together with multiple partners and/or infrequent condom use. Externalizing (i.e. conduct and hyperactivity symptoms independently predicted sexual initiation. Internalizing difficulties (i.e. emotional and peer problems were negatively associated with early and risky sexual initiation among boys

  8. Mobile Health Initiatives in Vietnam: Scoping Study.

    Science.gov (United States)

    Lam, Jeffrey A; Dang, Linh Thuy; Phan, Ngoc Tran; Trinh, Hue Thi; Vu, Nguyen Cong; Nguyen, Cuong Kieu

    2018-04-24

    Mobile health (mHealth) offers a promising solution to the multitude of challenges the Vietnamese health system faces, but there is a scarcity of published information on mHealth in Vietnam. The objectives of this scoping study were (1) to summarize the extent, range, and nature of mHealth initiatives in Vietnam and (2) to examine the opportunities and threats of mHealth utilization in the Vietnamese context. This scoping study systematically identified and extracted relevant information from 20 past and current mHealth initiatives in Vietnam. The study includes multimodal information sources, including published literature, gray literature (ie, government reports and unpublished literature), conference presentations, Web-based documents, and key informant interviews. We extracted information from 27 records from the electronic search and conducted 14 key informant interviews, allowing us to identify 20 mHealth initiatives in Vietnam. Most of the initiatives were primarily funded by external donors (n=15), while other initiatives were government funded (n=1) or self-funded (n=4). A majority of the initiatives targeted vulnerable and hard-to-reach populations (n=11), aimed to prevent the occurrence of disease (n=12), and used text messaging (short message service, SMS) as part of their intervention (n=14). The study revealed that Vietnamese mHealth implementation has been challenged by factors including features unique to the Vietnamese language (n=4) and sociocultural factors (n=3). The largest threats to the popularity of mHealth initiatives are the absence of government policy, lack of government interest, heavy dependence on foreign funding, and lack of technological infrastructure. Finally, while current mHealth initiatives have already demonstrated promising opportunities for alternative models of funding, such as social entrepreneurship or private business models, sustainable mHealth initiatives outside of those funded by external donors have not yet been

  9. Report of Committee for JAEA Internationalization Initiative

    International Nuclear Information System (INIS)

    2013-03-01

    In global circumstances surrounding nuclear energy, the role expected to Japan Atomic Energy Agency (JAEA) is becoming increasingly important. JAEA has been promoted an initiative for the international hub in order to increase the scientific competitiveness of Japan and make international contributions, by gathering excellent researchers from the entire world with the latest facilities. Also, JAEA established 'Committee for JAEA Internationalization Initiative', which will discuss issues such as environmental improvement for accepted foreigners, direction of efforts for internationalization initiative and strategies to improve current situation. This report mentions the results of the committee's discussion including current issues for the initiative and recommendations for their solution, as well as the issues to be discussed in order to enhance international awareness of JAEA staff. The following is the summary of the recommendations for the initiative: Set up local teams that focus on the situation of each site in order to provide detailed support for foreigners from diversified backgrounds. Develop systems for emergency situations to provide information for safety swiftly for foreigners and confirm their safety, in addition to preparing emergency goods. Prepare bilingual documents and systems that foreigners need to use for their work based on importance and frequency of use of such systems and documents. (author)

  10. Industrial initiatives in the wind industry

    International Nuclear Information System (INIS)

    Edworthy, J.

    1992-01-01

    Industrial initiatives are methods of lobbying and marketing to increase the activity, revenues, profits, and commercial viability of an industry. They may be undertaken by industry individuals or firms, industry groups, government agencies, or combinations of all these. In Canada, one example of an industrial initiative is the Canadian Wind Energy Association. Other initiatives relevant to the wind power industry include Technology Inflow Programs sponsored by External Affairs Canada, used for visiting foreign firms with the view to licensing foreign technology, and Industrial Research Assistance Programs to develop or adapt new technologies in partnership with government. The Conservation/Renewable Energy Council, Small Power Producers of Alberta, and Independent Power Producers Society of Ontario are also active in supporting wind energy initiatives. In other countries, notable initiatives for wind energy include the Danish wind turbine warranty guarantee program. The Western Wind Industry Network of Canada conducts regional lobbying. It is suggested that in Canada, more such networks are needed, as well as joint ventures with utilities and governments, and more work with the regulatory agencies, to promote wind energy

  11. Semiclassical initial value approximation for Green's function.

    Science.gov (United States)

    Kay, Kenneth G

    2010-06-28

    A semiclassical initial value approximation is obtained for the energy-dependent Green's function. For a system with f degrees of freedom the Green's function expression has the form of a (2f-1)-dimensional integral over points on the energy surface and an integral over time along classical trajectories initiated from these points. This approximation is derived by requiring an integral ansatz for Green's function to reduce to Gutzwiller's semiclassical formula when the integrations are performed by the stationary phase method. A simpler approximation is also derived involving only an (f-1)-dimensional integral over momentum variables on a Poincare surface and an integral over time. The relationship between the present expressions and an earlier initial value approximation for energy eigenfunctions is explored. Numerical tests for two-dimensional systems indicate that good accuracy can be obtained from the initial value Green's function for calculations of autocorrelation spectra and time-independent wave functions. The relative advantages of initial value approximations for the energy-dependent Green's function and the time-dependent propagator are discussed.

  12. MAGI: many-component galaxy initializer

    Science.gov (United States)

    Miki, Yohei; Umemura, Masayuki

    2018-04-01

    Providing initial conditions is an essential procedure for numerical simulations of galaxies. The initial conditions for idealized individual galaxies in N-body simulations should resemble observed galaxies and be dynamically stable for time-scales much longer than their characteristic dynamical times. However, generating a galaxy model ab initio as a system in dynamical equilibrium is a difficult task, since a galaxy contains several components, including a bulge, disc, and halo. Moreover, it is desirable that the initial-condition generator be fast and easy to use. We have now developed an initial-condition generator for galactic N-body simulations that satisfies these requirements. The developed generator adopts a distribution-function-based method, and it supports various kinds of density models, including custom-tabulated inputs and the presence of more than one disc. We tested the dynamical stability of systems generated by our code, representing early- and late-type galaxies, with N = 2097 152 and 8388 608 particles, respectively, and we found that the model galaxies maintain their initial distributions for at least 1 Gyr. The execution times required to generate the two models were 8.5 and 221.7 seconds, respectively, which is negligible compared to typical execution times for N-body simulations. The code is provided as open-source software and is publicly and freely available at https://bitbucket.org/ymiki/magi.

  13. [WHO Healthy City Initiative in Japan].

    Science.gov (United States)

    Yoshizawa, Kazuko

    2013-01-01

    City environmental conditions are associated with health outcomes in people living there. World Health Organization (WHO) initiated Healthy City in 1986. To promote the networking, Alliance for Healthy Cities (AFHC) was launched in 2003 with local offices including AFHC Japan. As of 2010, 26 cities are members of AFHC Japan. A questionnaire was sent to those member cities. It includes questions on why they became an AFHC member, which section is in charge of the initiatives, what factors are important for promotion, and others. Out of the 26 cities, 13 cities returned the completed questionnaire. As for factors important for promoting the initiatives, 10 (77%) out of the 13 cities answered "consciousness of residents", while five (38%) chose "budget". This result suggests that community participation is a more important factor than budget for promoting and succeeding in the initiatives. Aging is a problem in any of the member cities, and six cities out the 13 falls under the category of superaged society, which is defined as a society with the proportion of aged people cities (85%) agreed that bicycles are an alternative means of transportation to cars; however, infrastructure for ensuring safety needs further improvement. In the promotion of Healthy City, networking among the member cities in Japan and worldwide should be promoted. Community participation with empowerment from the planning stage should lead to sustainable initiatives. The function of AFHC in collaboration among the members should be strengthened to cope with the rapidly changing city environment.

  14. Initial conditions for critical Higgs inflation

    Science.gov (United States)

    Salvio, Alberto

    2018-05-01

    It has been pointed out that a large non-minimal coupling ξ between the Higgs and the Ricci scalar can source higher derivative operators, which may change the predictions of Higgs inflation. A variant, called critical Higgs inflation, employs the near-criticality of the top mass to introduce an inflection point in the potential and lower drastically the value of ξ. We here study whether critical Higgs inflation can occur even if the pre-inflationary initial conditions do not satisfy the slow-roll behavior (retaining translation and rotation symmetries). A positive answer is found: inflation turns out to be an attractor and therefore no fine-tuning of the initial conditions is necessary. A very large initial Higgs time-derivative (as compared to the potential energy density) is compensated by a moderate increase in the initial field value. These conclusions are reached by solving the exact Higgs equation without using the slow-roll approximation. This also allows us to consistently treat the inflection point, where the standard slow-roll approximation breaks down. Here we make use of an approach that is independent of the UV completion of gravity, by taking initial conditions that always involve sub-planckian energies.

  15. Initial conditions and entanglement sudden death

    International Nuclear Information System (INIS)

    Qian, Xiao-Feng; Eberly, J.H.

    2012-01-01

    We report results bearing on the behavior of non-local decoherence and its potential for being managed or even controlled. The decoherence process known as entanglement sudden death (ESD) can drive prepared entanglement to zero at the same time that local coherences and fidelity remain non-zero. For a generic ESD-susceptible Bell superposition state, we provide rules restricting the occurrence and timing of ESD, amounting to management tools over a continuous variation of initial conditions. These depend on only three parameters: initial purity, entanglement and excitation. Knowledge or control of initial phases is not needed. -- Highlights: ► We study the possibility of managing disentanglement through initial conditions. ► The initial parameters are the amount of entanglement, excitation, and purity. ► Entanglement sudden death (ESD) free and ESD susceptible phases are identified. ► ESD onset time is also presented in the ESD susceptible phase. ► Our results may guide experiments to prepare ESD free or delayed ESD states.

  16. Crack initiation under generalized plane strain conditions

    International Nuclear Information System (INIS)

    Shum, D.K.M.; Merkle, J.G.

    1991-01-01

    A method for estimating the decrease in crack-initiation toughness, from a reference plane strain value, due to positive straining along the crack front of a circumferential flaw in a reactor pressure vessel is presented in this study. This method relates crack initiation under generalized plane strain conditions with material failure at points within a distance of a few crack-tip-opening displacements ahead of a crack front, and involves the formulation of a micromechanical crack-initiation model. While this study is intended to address concerns regarding the effects of positive out-of- plane straining on ductile crack initiation, the approach adopted in this work can be extended in a straightforward fashion to examine conditions of macroscopic cleavage crack initiation. Provided single- parameter dominance of near-tip fields exists in the flawed structure, results from this study could be used to examine the appropriateness of applying plane strain fracture toughness to the evaluation of circumferential flaws, in particular to those in ring-forged vessels which have no longitudinal welds. In addition, results from this study could also be applied toward the analysis of the effects of thermal streaming on the fracture resistance of circumferentially oriented flaws in a pressure vessel. 37 refs., 8 figs., 1 tab

  17. The Trilateral Initiative: The Legal Framework

    International Nuclear Information System (INIS)

    Rockwood, L.

    2015-01-01

    The Trilateral Initiative was a six-year effort undertaken by the IAEA, the United States and the Russian Federation between 1996 to 2002 to identify verification arrangements and technologies for IAEA verification of classified forms of Pu and HEU from nuclear warheads or components. As part of that Initiative, between 1999 and 2001, the parties succeeded in negotiating a model agreement for such verification (the Model Agreement). Although the Trilateral Initiative ended in 2002, the Model Agreement produced as a result of those negotiations could still serve as the basis for bilateral agreements between the IAEA and nuclear-weapon States wishing to demonstrate, in a verifiable manner, the release of weapon origin and other fissile material from defence programmes. This presentation will describe the legal framework for the Model Agreement and the major issues addressed during its negotiation

  18. State nuclear initiatives in the United States

    International Nuclear Information System (INIS)

    Strauss, P.L.; Stoiber, C.R.

    1977-01-01

    The paper deals with State nuclear initiatives regarding the role of nuclear power in the energy future of the United States. The question of whether and under what circumstances nuclear facilities should be used to generate electricity was put to the popular vote in several States in 1976. Some general principles of Federal-State relations are discussed with specific reference to nuclear regulations. The initiative mechanism itself is described as well as its legal form and background. The parallel developments in the State and Federal legislative consideration of nuclear issues is reviewed and the suggested reasons for the defeat of the proposals in the seven States concerned are discussed. Finally, the author draws some conclusions on the effects of the 1976 initiatives on future decision-making in the US on energy policy in general and nuclear power in particular. (NEA) [fr

  19. Polyhomogeneous expansions from time symmetric initial data

    Science.gov (United States)

    Gasperín, E.; Valiente Kroon, J. A.

    2017-10-01

    We make use of Friedrich’s construction of the cylinder at spatial infinity to relate the logarithmic terms appearing in asymptotic expansions of components of the Weyl tensor to the freely specifiable parts of time symmetric initial data sets for the Einstein field equations. Our analysis is based on the assumption that a particular type of formal expansions near the cylinder at spatial infinity corresponds to the leading terms of actual solutions to the Einstein field equations. In particular, we show that if the Bach tensor of the initial conformal metric does not vanish at the point at infinity then the most singular component of the Weyl tensor decays near null infinity as O(\\tilde{r}-3\\ln \\tilde{r}) so that spacetime will not peel. We also provide necessary conditions on the initial data which should lead to a peeling spacetime. Finally, we show how to construct global spacetimes which are candidates for non-peeling (polyhomogeneous) asymptotics.

  20. Cosmological constant and general isocurvature initial conditions

    International Nuclear Information System (INIS)

    Trotta, R.; Riazuelo, A.; Durrer, R.

    2003-01-01

    We investigate in detail the question of whether a nonvanishing cosmological constant is required by the present-day cosmic microwave background and large scale structure data when general isocurvature initial conditions are taken into account. We also discuss the differences between the usual Bayesian and the frequentist approaches in data analysis. We show that the Cosmic Background Explorer (COBE)-normalized matter power spectrum is dominated by the adiabatic mode and therefore breaks the degeneracy between initial conditions which is present in the cosmic microwave background anisotropies. We find that in a flat universe the Bayesian analysis requires Ω Λ =e0 to more than 3σ, while in the frequentist approach Ω Λ =0 is still within 3σ for a value of h≤0.48. Both conclusions hold regardless of the initial conditions

  1. Aquarius: The Instrument and Initial Results

    Science.gov (United States)

    Vine, David M Le; Lagerloef, G.S.E.; Ruf, C.; Wentz, F.; Yueh, S.; Piepmeier, J.; Lindstrom, E.; Dinnat, E.

    2012-01-01

    Aquarius was launched on June 10, 2011 aboard the Aquarius/SAC-D observatory and the instrument has been operating continuously since the initial turned-on was completed on August 25. The initial observed antenna temperatures were close to predicted and the first salinity map was released in September. In order to map the ocean salinity field, Aquarius includes several special features such as the inclusion of a scatterometer to provide a roughness correction, measurement of the third Stokes parameter to correct for Faraday rotation, and fast sampling to mitigate the effects of RFI. This paper provides an overview of the instrument and an example of initial results. Details are covered in subsequent papers in the session on Aquarius

  2. How initial representations shape coupled learning processes

    DEFF Research Database (Denmark)

    Puranam, Phanish; Swamy, M.

    2016-01-01

    Coupled learning processes, in which specialists from different domains learn how to make interdependent choices among alternatives, are common in organizations. We explore the role played by initial representations held by the learners in coupled learning processes using a formal agent-based model....... We find that initial representations have important consequences for the success of the coupled learning process, particularly when communication is constrained and individual rates of learning are high. Under these conditions, initial representations that generate incorrect beliefs can outperform...... one that does not discriminate among alternatives, or even a mix of correct and incorrect representations among the learners. We draw implications for the design of coupled learning processes in organizations. © 2016 INFORMS....

  3. Initial value problem for plasma oscillations

    International Nuclear Information System (INIS)

    Li, J.; Spies, G.O.

    1991-01-01

    The solution of the initial value problem for the linearized one-dimensional electron Vlasov--Poisson equations in a field-free homogeneous equilibrium is examined for small and for large ratios κ of Debye length and wavelength, assuming initial perturbing distribution functions varying on the same velocity scale as the equilibrium. Previously known approximations of the initial evolution (which, unlike the time-asymptotic one, does not depend on analyticity assumptions) are extended to longer times, and to arbitrary stable or unstable equilibria: In the quasifluid regime (small κ), the electric field, within an additive error O(κ 2 ), and independently of the initial data, performs an oscillation near the plasma frequency that corresponds to an eigenmode if it is unstable or marginal, but to an approximate eigenmode arising from the continuous spectrum otherwise. If other unstable or marginal modes are present, these influence only the time-asymptotic behavior because their amplitudes are O(κ 2 ) initially. In the ballistic regime (large κ), there are no instabilities and the perturbing density, now within an error O(κ -2 ), is the Fourier transform of the initial perturbing distribution function, thus following an arbitrary decay law that is independent of the equilibrium. The errors are shown to be time-independent, implying that either approximation is relevant at least until the perturbing density has essentially damped out. Hence the dominating damping mechanism (in the stable case) is Landau damping if κ much-lt 1, but ballistic particle mixing if κ much-gt 1

  4. NMR imaging of the brain: initial impressions

    International Nuclear Information System (INIS)

    Spencer, D.H.; Bydder, G.M.

    1983-01-01

    An NMR imaging system designed and built by Thorn-EMI Ltd was installed at Hammersmith Hospital in March 1981. In the first year of operation 180 patients and 40 volunteers have had cranial examinations and initial impressions bases on this experience are presented. Patients with a wide variety of neurological diseases have been studied to provide a basis for diagnostic interpretation, to define distinctive features, and to evaluate different types of scanning sequences. NMR imaging appears to be of considerable value in neurological diagnosis and has a number of advantages over CT. The detailed evaluation of NMR imaging will require much more work but the initial results are very promising

  5. Inclusion-initiated fracture model for ceramics

    International Nuclear Information System (INIS)

    Sung, J.; Nicholson, P.S.

    1990-01-01

    The fracture of ceramics initiating from a typical inclusion is analyzed. The inclusion is considered to have a thermal expansion coefficient and fracture toughness lower than those of the matrix and a Young's modulus higher than that of the matrix. Inclusion-initiated fracture is modeled for a spherical inclusion using a weight function method to compute the residual stress intensity factor for a part-through elliptical crack. The results are applied to an α-Al 2 O 3 inclusion embedded in a tetragonal ZrO 2 ceramic. The strength predictions agree well with experimental data

  6. The Windscale piles initial decommissioning programme

    International Nuclear Information System (INIS)

    Boorman, T.; Woodacre, A.

    1992-01-01

    The two Windscale Piles, the first large scale nuclear reactors built in the UK were constructed in the late 1940's and operated until the accident in Pile No 1 caused their permanent shutdown in 1957. Following a period of care and maintenance, a programme of initial decommissioning has begun aimed at establishing a satisfactory long-term safe condition for the Windscale Piles Complex with minimum maintenance commitments. For the chimneys this involves the removal of the top filter sections. The pond will be emptied and cleaned. For the Piles the initial phase includes the consideration of options for long-term decommissioning solutions. (author)

  7. Initiative and responsibility; Veranlassung und Verantwortung

    Energy Technology Data Exchange (ETDEWEB)

    Loewer, Wolfgang (ed.)

    2012-07-01

    The 6th Bonner Dialogue to energy law picks up the trend of increasing regulation of the energy sector on a more fundamental level. Under this aspect, the book under consideration contains four contributions: (1) Initiative and responsibility from a constitutional point of view (Hans-Jueergen Papier); (2) Obligations to invest in the development of transmission networks between initiative and responsibility (Juergen Kuehling); (3) Antitrust unbundling of companies from comparative law perspective (Wulf-Henning Roth); (4) Unbundling of companies outside of fusion control according to valid and future law (Andreas Roehling).

  8. Modular initiator with integrated optical diagnostic

    Science.gov (United States)

    Alam, M Kathleen [Cedar Crest, NM; Schmitt, Randal L [Tijeras, NM; Welle, Eric J [Niceville, FL; Madden, Sean P [Arlington, MA

    2011-05-17

    A slapper detonator which integrally incorporates an optical wavequide structure for determining whether there has been degradation of the explosive in the explosive device that is to be initiated by the detonator. Embodiments of this invention take advantage of the barrel-like character of a typical slapper detonator design. The barrel assembly, being in direct contact with the energetic material, incorporates an optical diagnostic device into the barrel assembly whereby one can monitor the state of the explosive material. Such monitoring can be beneficial because the chemical degradation of the explosive plays an important in achieving proper functioning of a detonator/initiator device.

  9. Brane decay and an initial spacelike singularity.

    Science.gov (United States)

    Kawai, Shinsuke; Keski-Vakkuri, Esko; Leigh, Robert G; Nowling, Sean

    2006-01-27

    We present a novel string theory scenario where matter in a spacetime originates from a decaying brane at the origin of time. The decay could be considered as a big-bang-like event at X0=0. The closed string interpretation is a time-dependent spacetime with a semi-infinite time direction, with the initial energy of the brane converted into energy flux from the origin. The open string interpretation can be viewed as a string theoretic nonsingular initial condition.

  10. The high-risk plaque initiative

    DEFF Research Database (Denmark)

    Falk, Erling; Sillesen, Henrik; Muntendam, Pieter

    2011-01-01

    The High-Risk Plaque (HRP) Initiative is a research and development effort to advance the understanding, recognition, and management of asymptomatic individuals at risk for a near-term atherothrombotic event such as myocardial infarction or stroke. Clinical studies using the newest technologies...... have been initiated, including the BioImage Study in which novel approaches are tested in a typical health plan population. Asymptomatic at-risk individuals were enrolled, including a survey-only group (n = 865), a group undergoing traditional risk factor scoring (n = 718), and a group in which all...

  11. Evaluation and Evaluating the Community Initiative "URBAN"

    DEFF Research Database (Denmark)

    Alves, Sonia

    2013-01-01

    focus on a more open and democratic process of evaluation. This paper presents and compares different conceptual and methodological frameworks created for the assessment of the European initiative Urban II, including the one that was used by the author in the context of an academic evaluation...... in the city of Porto. The comparative analysis of the results leads us to the recommendation for more democratic processes of evaluation and intervention, in order to improve their quality and accountability and promote the important goal of learning with this type of experimental initiatives....

  12. Initial performance of the PIGMI prototype

    International Nuclear Information System (INIS)

    Stovall, J.E.

    1979-01-01

    The PIGMI (Pion Generator for Medical Irradiations) program at LASL is an accelerator development program aimed at completing the design of an accelerator suitable for use as a pion generator in a hospital-based radiotherapy program. The major thrust of the program has been the design of a 7 MeV prototype accelerator which emphasizes compactness, economy of construction, and operation and reliability. To achieve these goals the design of the prototype has exploited a number of innovations in proton linac technology. An overview of the program discussing the major innovative features of the prototype is presented. The initial operating experience is discussed and initial performance measurements are presented

  13. Statistical distribution of time to crack initiation and initial crack size using service data

    Science.gov (United States)

    Heller, R. A.; Yang, J. N.

    1977-01-01

    Crack growth inspection data gathered during the service life of the C-130 Hercules airplane were used in conjunction with a crack propagation rule to estimate the distribution of crack initiation times and of initial crack sizes. A Bayesian statistical approach was used to calculate the fraction of undetected initiation times as a function of the inspection time and the reliability of the inspection procedure used.

  14. Research on Initiation Sensitivity of Solid Explosive and Planer Initiation System

    OpenAIRE

    N Matsuo; M Otuka; H Hamasima; K Hokamoto; S Itoh

    2016-01-01

    Firstly, recently, there are a lot of techniques being demanded for complex process, various explosive initiation method and highly accurate control of detonation are needed. In this research, the metal foil explosion using high current is focused attention on the method to obtain linear or planate initiation easily, and the main evaluation of metal foil explosion to initiate explosive was conducted. The explosion power was evaluated by observing optically the underwater shock wave generated ...

  15. Who is a self-initiated expatriate?

    DEFF Research Database (Denmark)

    Cerdin, Jean-Luc; Selmer, Jan

    2014-01-01

    The purpose of this article is to enhance the conceptual coherence of the notion of a self-initiated expatriate (SIE). We propose a definition based on a set of conceptual criteria which differentiates SIEs from other types of international movers. This article defines who an SIE is according...

  16. Criteria for initiation of tokamak disruptions

    International Nuclear Information System (INIS)

    Hopcraft, K.I.; Turner, M.F.

    1986-01-01

    The process by which a tokamak plasma evolves from an equilibrium state containing a saturated magnetic island to one which is disruptively unstable is discussed and illustrated by numerical simulation of a resistive magnetoplasma. Those elements which are required to initiate a disruption are delineated

  17. Stakeholder initiatives in flood risk management

    NARCIS (Netherlands)

    Edelenbos, Jurian; Buuren, Van Arwin; Roth, Dik; Winnubst, Madelinde

    2017-01-01

    In recent years stakeholder participation has become a popular topic in flood management. Little is known about how and under which circumstances local stakeholders initiate and develop successful flood management strategies and how governmental actors respond to them. Drawing on theories of

  18. 16 CFR 5.64 - Initial decision.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Initial decision. 5.64 Section 5.64 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE STANDARDS OF... this subpart, except that the determination of the Administrative Law Judge must be supported by a...

  19. Orchestration of Floral Initiation by APETALA1

    NARCIS (Netherlands)

    Kaufmann, K.; Muino Acuna, J.M.

    2010-01-01

    The MADS-domain transcription factor APETALA1 (AP1) is a key regulator of Arabidopsis flower development. To understand the molecular mechanisms underlying AP1 function, we identified its target genes during floral initiation using a combination of gene expression profiling and genome-wide binding

  20. International Research Chairs Initiative | IDRC - International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The International Research Chairs Initiative (IRCI) is a seven-year, CA$8 million research program that pairs top research talent from universities in Canada with their counterparts in developing countries to address key ... The results of this joint effort: world-class discoveries and healthier, wealthier, fairer societies.

  1. Test set for initial value problem solvers

    NARCIS (Netherlands)

    W.M. Lioen (Walter); J.J.B. de Swart (Jacques)

    1998-01-01

    textabstractThe CWI test set for IVP solvers presents a collection of Initial Value Problems to test solvers for implicit differential equations. This test set can both decrease the effort for the code developer to test his software in a reliable way, and cross the bridge between the application

  2. Robustness of inflation to inhomogeneous initial conditions

    Energy Technology Data Exchange (ETDEWEB)

    Clough, Katy; Lim, Eugene A. [Theoretical Particle Physics and Cosmology Group, Physics Department, Kings College London, Strand, London WC2R 2LS (United Kingdom); DiNunno, Brandon S.; Fischler, Willy; Flauger, Raphael; Paban, Sonia, E-mail: katy.clough@kcl.ac.uk, E-mail: eugene.a.lim@gmail.com, E-mail: bsd86@physics.utexas.edu, E-mail: fischler@physics.utexas.edu, E-mail: flauger@physics.utexas.edu, E-mail: paban@physics.utexas.edu [Department of Physics, The University of Texas at Austin, Austin, TX, 78712 (United States)

    2017-09-01

    We consider the effects of inhomogeneous initial conditions in both the scalar field profile and the extrinsic curvature on different inflationary models. In particular, we compare the robustness of small field inflation to that of large field inflation, using numerical simulations with Einstein gravity in 3+1 dimensions. We find that small field inflation can fail in the presence of subdominant gradient energies, suggesting that it is much less robust to inhomogeneities than large field inflation, which withstands dominant gradient energies. However, we also show that small field inflation can be successful even if some regions of spacetime start out in the region of the potential that does not support inflation. In the large field case, we confirm previous results that inflation is robust if the inflaton occupies the inflationary part of the potential. Furthermore, we show that increasing initial scalar gradients will not form sufficiently massive inflation-ending black holes if the initial hypersurface is approximately flat. Finally, we consider the large field case with a varying extrinsic curvature K , such that some regions are initially collapsing. We find that this may again lead to local black holes, but overall the spacetime remains inflationary if the spacetime is open, which confirms previous theoretical studies.

  3. Diagonal Pade approximations for initial value problems

    International Nuclear Information System (INIS)

    Reusch, M.F.; Ratzan, L.; Pomphrey, N.; Park, W.

    1987-06-01

    Diagonal Pade approximations to the time evolution operator for initial value problems are applied in a novel way to the numerical solution of these problems by explicitly factoring the polynomials of the approximation. A remarkable gain over conventional methods in efficiency and accuracy of solution is obtained. 20 refs., 3 figs., 1 tab

  4. Chapter 1: The Appalachian regional reforestation initiative

    Science.gov (United States)

    Patrick Angel; Vic Davis; Jim Burger; Don Graves; Carl. Zipper

    2017-01-01

    The Appalachian Regional Reforestation Initiative (ARRI) is a cooperative effort by the States of the Appalachian region with the U.S. Department of the Interior's Office of Surface Mining Reclamation and Enforcement (OSMRE) to encourage restoration of high-quality forests on reclaimed coal mines in the eastern United States. The goals of ARRI are to communicate...

  5. Valuing Initial Teacher Education at Master's Level

    Science.gov (United States)

    Brooks, Clare; Brant, Jacek; Abrahams, Ian; Yandell, John

    2012-01-01

    The future of Master's-level work in initial teacher education (ITE) in England seems uncertain. Whilst the coalition government has expressed support for Master's-level work, its recent White Paper focuses on teaching skills as the dominant form of professional development. This training discourse is in tension with the view of professional…

  6. Initial conditions for turbulent mixing simulations

    Directory of Open Access Journals (Sweden)

    T. Kaman

    2010-01-01

    Full Text Available In the context of the classical Rayleigh-Taylor hydrodynamical instability, we examine the much debated question of models for initial conditions and the possible influence of unrecorded long wave length contributions to the instability growth rate α.

  7. 19 CFR 210.42 - Initial determinations.

    Science.gov (United States)

    2010-04-01

    ... Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION INVESTIGATIONS OF UNFAIR PRACTICES IN IMPORT TRADE ADJUDICATION AND ENFORCEMENT Determinations and Actions Taken § 210.42 Initial determinations. (a... Justice, the Federal Trade Commission, the U.S. Customs Service, and such other departments and agencies...

  8. E-Government: Initiatives, Developments, and Issues.

    Science.gov (United States)

    Aldrich, Duncan; Bertot, John Carlo; McClure, Charles R.

    2002-01-01

    Provides a background of government efforts to incorporate telecommunication and computer technologies to improve government performance and enhance citizen access to government information and services. Describes this symposium issue which discusses key issues that affect the success and implementation of electronic government initiatives. (LRW)

  9. Rethinking managerial roles in change initiatives

    NARCIS (Netherlands)

    B.A.S. Koene (Bas)

    2017-01-01

    textabstractOrganisational change that is initiated by middle management rather than top management is more likely to gain employee support. This is the conclusion of a recent study co-authored by Bas Koene, assistant professor in RSM’s Department of Organisation and Personnel Management.

  10. Nanostructure-initiator mass spectrometry biometrics

    Science.gov (United States)

    Leclerc, Marion; Bowen, Benjamin; Northen, Trent

    2015-09-08

    Several embodiments described herein are drawn to methods of identifying an analyte on a subject's skin, methods of generating a fingerprint, methods of determining a physiological change in a subject, methods of diagnosing health status of a subject, and assay systems for detecting an analyte and generating a fingerprint, by nanostructure-initiator mass spectrometry (NIMS).

  11. Research award: Collaborative Adaptation Research Initiative in ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2017-09-06

    Sep 6, 2017 ... The Collaborative Adaptation Research Initiative in Africa and Asia (CARIAA) builds resilience in these hot spots by supporting collaborative research on climate change adaptation to inform adaptation policy and practice. Specifically, CARIAA supports four consortia that research geographic and social ...

  12. Project Lifescape | Initiatives | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Project Lifescape. This project is part of the Academy initiative to enhance the quality of science education. It is pursued in collaboration with the Centre for Ecological Sciences at the Indian Institute of Science to spread biodiversity literacy, expecially within the high school and college student community, and to involve them ...

  13. RSA Monitoring Redesign Initiative Informational Booklet #1

    Science.gov (United States)

    US Department of Education, 2005

    2005-01-01

    This informational booklet contains background materials regarding the Rehabilitation Services Administration (RSA) initiative to redesign its monitoring system. The booklet is intended to expand the knowledge and understanding of those individuals selected to participate in the RSA-sponsored monitoring conference that was held August 24 and 25,…

  14. RSA Monitoring Redesign Initiative Informational Booklet #2

    Science.gov (United States)

    US Department of Education, 2005

    2005-01-01

    The U.S. Department of Education's Rehabilitation Services Administration (RSA) is undertaking a major initiative to substantially redesign its program monitoring and improvement system. The overriding goal is to improve vocational rehabilitation (VR) services and employment outcomes for individuals with disabilities through the development of a…

  15. Urban Social initiatives and Co-creation

    DEFF Research Database (Denmark)

    Geert Jensen, Birgitte; Rasmussen, Jørgen

    2016-01-01

    As part of the 2014 fall semester study programme, Studio Design and Social Innovation, from Aarhus School of Architecture, collaborated with DemokraCity on a community initiative project to revitalize TILST, a town located on the outskirts of Aarhus, Denmark. Demokracity focuses on urban social...... and story for the site, thereby building a new identity and creating value for the area....

  16. 32 CFR 989.4 - Initial considerations.

    Science.gov (United States)

    2010-07-01

    ... alternatives analyzed in the environmental documents. (f) Pursue the objective of furthering foreign policy and... ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.4 Initial considerations. Air Force personnel will: (a... CATEX from environmental impact analysis (appendix B). (c) Make environmental documents, comments, and...

  17. 16 CFR 2.1 - How initiated.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false How initiated. 2.1 Section 2.1 Commercial... General; upon referrals by the courts; upon complaint by members of the public; or by the Commission upon..., authority to open investigations in response to requests pursuant to an agreement under the International...

  18. Initial data for N black holes

    International Nuclear Information System (INIS)

    York, J.W. Jr.

    1984-01-01

    In the present work I focus attention on the construction of suitably general initial data, with particular attention to some new results that enable consideration of black holes that can possess spin (and electric charge) as well as orbital motion. (orig.)

  19. International Metadata Initiatives: Lessons in Bibliographic Control.

    Science.gov (United States)

    Caplan, Priscilla

    This paper looks at a subset of metadata schemes, including the Text Encoding Initiative (TEI) header, the Encoded Archival Description (EAD), the Dublin Core Metadata Element Set (DCMES), and the Visual Resources Association (VRA) Core Categories for visual resources. It examines why they developed as they did, major point of difference from…

  20. View all initiatives | IDRC - International Development Research ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Initiative. The Cultivate Africa's Future research partnership is designed to support applied research to combat hunger in sub-Saharan Africa by harnessing the potential for innovation among the region's smallholder farmers, the majority of whom are women. We fund researchers driving global change. Careers · Contact Us ...

  1. View all initiatives | IDRC - International Development Research ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The Science Granting Councils Initiative in Sub-Saharan Africa is focused on strengthening the capacities of science granting councils in order to support research and evidence-based policies that will contribute to economic and social development in Sub-Saharan Africa. We fund researchers driving global change.

  2. View all initiatives | IDRC - International Development Research ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The Open Data for Development program's global network will facilitate and scale innovative approaches to open data to ensure benefits reach citizens in developing countries. Combining research and action to address scaling and sustainability of open data for development initiatives is key to the network's success.

  3. Initial Encounters : The Lived Experiences of Buyers

    NARCIS (Netherlands)

    G. Wright; J.J. Dekker

    2012-01-01

    The initial encounter between a buyer and a seller has received much attention among practitioners. The first time a buyer interacts with a seller is thought to be highly influential. The premise is that buyers form an opinion during this first encounter, or even the first minutes of this encounter.

  4. Return to Experience and Initial Wage Level

    DEFF Research Database (Denmark)

    Sørensen, Kenneth Lykke; Vejlin, Rune Majlund

    This paper estimates the relationship between initial wage and return to experience. We use a Mincer-like wage model to nonparametrically estimate this relationship allowing for an unobservable individual permanent effect in wages and unobservable individual return to experience. The relationship...

  5. Return to experience and initial wage level

    DEFF Research Database (Denmark)

    Sørensen, K.L.; Vejlin, R.

    2014-01-01

    This paper estimates the relationship between initial wage and return to experience. We use a Mincer-like wage model to non-parametrically estimate this relationship allowing for an unobservable individual permanent effect in wages and unobservable individual return to experience. The relationshi...

  6. Think Tank Initiative - Hewlett Foundation | IDRC - International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    IDRC and the William and Flora Hewlett Foundation are collaborating on the Think Tank Initiative, a new program to strengthen independent think tanks and policy research centres in the developing world. These organizations provide critical input for the creation of effective public policy to promote growth and reduce ...

  7. Tubular Initial Conditions and Ridge Formation

    Directory of Open Access Journals (Sweden)

    M. S. Borysova

    2013-01-01

    Full Text Available The 2D azimuth and rapidity structure of the two-particle correlations in relativistic A+A collisions is altered significantly by the presence of sharp inhomogeneities in superdense matter formed in such processes. The causality constraints enforce one to associate the long-range longitudinal correlations observed in a narrow angular interval, the so-called (soft ridge, with peculiarities of the initial conditions of collision process. This study's objective is to analyze whether multiform initial tubular structures, undergoing the subsequent hydrodynamic evolution and gradual decoupling, can form the soft ridges. Motivated by the flux-tube scenarios, the initial energy density distribution contains the different numbers of high density tube-like boost-invariant inclusions that form a bumpy structure in the transverse plane. The influence of various structures of such initial conditions in the most central A+A events on the collective evolution of matter, resulting spectra, angular particle correlations and vn-coefficients is studied in the framework of the hydrokinetic model (HKM.

  8. Service-Learning Initiatives in Nursing Education

    Science.gov (United States)

    O'Shea, Eileen; Planas, Jessica; Quan, Melissa; Greiner, Lydia; Kazer, Meredith; Babington, Lynn

    2013-01-01

    In response to the changing demands of the U.S. healthcare system and the needs of the nursing profession, the Institute of Medicine, in collaboration with the Robert Wood Johnson Foundation, spearheaded a two-year initiative to develop recommendations for the future of nursing. Discussions of these recommendations within nursing education led to…

  9. transnational initiatives towards natural resource governance

    African Journals Online (AJOL)

    RAYAN_

    a comparative analysis of heterogeneous governance initiatives originating in Africa ... Botswana-inspired, democratic developmental state model for such administration .... Community (EAC), and Common Market for Eastern and Southern ..... In an era still characterized by a single superpower, the mix of fragile or failed ...

  10. Kennesaw State University Classroom Technology Initiative.

    Science.gov (United States)

    McHaney, Jane; Wallace, Deborah; Taylor, Beverley

    The purpose of the Kennesaw State University (KSU) Coca Cola/Board of Regents Classroom Technology Initiative was to develop preservice and inservice teachers' expertise in educational technology such as computers, presentation software, and multimedia and to teach educators to apply those skills to content instruction. Project goals were to…

  11. Venture Capital Initiative: Ohio's School Improvement Effort.

    Science.gov (United States)

    Yoo, Soonhwa; Loadman, William E.

    In 1994 the Ohio State Legislature established Venture Capital to support school restructuring. The Venture Capital school initiative is a concept borrowed from the business community in which the corporate entity provides risk capital to parts of the organization to stimulate creative ideas and to provide opportunities for local entities to try…

  12. Achieving Sustainability in Learning and Teaching Initiatives

    Science.gov (United States)

    Brew, Angela; Cahir, Jayde

    2014-01-01

    Universities have a long history of change in learning and teaching to suit various government initiatives and institutional priorities. Academic developers now are frequently required to address strategic learning and teaching priorities. This paper asks how, in such a context, academic developers can ensure that work they do in relation to one…

  13. Status Report on the MCNP 2020 Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Forrest B. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Rising, Michael Evan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-10-02

    The discussion below provides a status report on the MCNP 2020 initiative. It includes discussion of the history of MCNP 2020, accomplishments during 2013-17, priorities for near-term development, other related efforts, a brief summary, and a list of references for the plans and work accomplished.

  14. Structural Basis of Mitochondrial Transcription Initiation.

    Science.gov (United States)

    Hillen, Hauke S; Morozov, Yaroslav I; Sarfallah, Azadeh; Temiakov, Dmitry; Cramer, Patrick

    2017-11-16

    Transcription in human mitochondria is driven by a single-subunit, factor-dependent RNA polymerase (mtRNAP). Despite its critical role in both expression and replication of the mitochondrial genome, transcription initiation by mtRNAP remains poorly understood. Here, we report crystal structures of human mitochondrial transcription initiation complexes assembled on both light and heavy strand promoters. The structures reveal how transcription factors TFAM and TFB2M assist mtRNAP to achieve promoter-dependent initiation. TFAM tethers the N-terminal region of mtRNAP to recruit the polymerase to the promoter whereas TFB2M induces structural changes in mtRNAP to enable promoter opening and trapping of the DNA non-template strand. Structural comparisons demonstrate that the initiation mechanism in mitochondria is distinct from that in the well-studied nuclear, bacterial, or bacteriophage transcription systems but that similarities are found on the topological and conceptual level. These results provide a framework for studying the regulation of gene expression and DNA replication in mitochondria. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. View all initiatives | IDRC - International Development Research ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The International Research Chairs Initiative pairs top research talent from universities in Canada with their counterparts in developing countries to address key development challenges. We fund researchers driving global change. Careers · Contact Us · Subscribe · Unsubscribe · Site map. Follow us; Facebook · Twitter ...

  16. Using action research for complex research initiatives

    CSIR Research Space (South Africa)

    Greeff, M

    2009-12-01

    Full Text Available the research process of such a complex research initiative. Action research is one research method that lends itself to these complex projects. The paper uses the Ability Based Technology Interventions (AbTi) research project as a case study to analyse...

  17. Winning relationships through customer service: initial contact.

    Science.gov (United States)

    Levin, R P

    1994-08-01

    First impressions last, and can have an impact on all future contact with a new patient. By using each initial contact with a new patient to begin building a strong relationship, a practice can be positioned for success. This article explores relationship building techniques.

  18. The Danish 22q11 research initiative

    DEFF Research Database (Denmark)

    Schmock, Henriette; Vangkilde, Anders; Larsen, Kit Melissa

    2015-01-01

    mechanisms may come from studies of subjects with homogenous etiologies. Breakthroughs in psychiatric genetics have shown that several genetic anomalies predispose for neurodevelopmental brain disorders. We have established a Danish research initiative to study the common microdeletion at chromosome 22q11...

  19. The Overture Initiative Integrating Tools for VDM

    DEFF Research Database (Denmark)

    Larsen, Peter Gorm; Battle, Nick; Ferreira, Miguel

    2010-01-01

    Overture is a community-based initiative that aims to develop a common open-source platform integrating a range of tools for constructing and analysing formal models of systems using VDM. The mission is to both provide an industrial-strength tool set for VDM and also to provide an environment...

  20. 76 FR 49508 - ``Add Us In'' Initiative

    Science.gov (United States)

    2011-08-10

    ... DEPARTMENT OF LABOR Office of Disability Employment Program ``Add Us In'' Initiative AGENCY: Office of Disability Employment Policy, Department of Labor. ACTION: Correction to the Funding Opportunity Number and Closing Date. SUMMARY: The Office of Disability Employment Policy, Department of Labor...

  1. Porting Initiation and Failure into Linked CHEETAH

    Science.gov (United States)

    Souers, Clark; Vitello, Peter

    2007-06-01

    Linked CHEETAH is a thermo-chemical code coupled to a 2-D hydrocode. Initially, a quadratic-pressure dependent kinetic rate was used, which worked well in modeling prompt detonation of explosives of large size, but does not work on other aspects of explosive behavior. The variable-pressure Tarantula reactive flow rate model was developed with JWL++ in order to also describe failure and initiation, and we have moved this model into Linked CHEETAH. The model works by turning on only above a pressure threshold, where a slow turn-on creates initiation. At a higher pressure, the rate suddenly leaps to a large value over a small pressure range. A slowly failing cylinder will see a rapidly declining rate, which pushes it quickly into failure. At a high pressure, the detonation rate is constant. A sequential validation procedure is used, which includes metal-confined cylinders, rate-sticks, corner-turning, initiation and threshold, gap tests and air gaps. The size (diameter) effect is central to the calibration. This work was performed under the auspices of the U.S. Department of Energy by the University of California Lawrence Livermore National Laboratory under contract No. W-7405-Eng-48.

  2. 10 CFR 824.13 - Initial decision.

    Science.gov (United States)

    2010-01-01

    ... all material issues of law, as well as reasons therefor. If the Hearing Officer determines that a... other matters as justice may require. (b) The Hearing Officer shall serve all parties with the initial... Notice of Review. If the Secretary files a notice of Notice of Review, he shall file a final order as...

  3. Small Spacecraft Technology Initiative Education Program

    Science.gov (United States)

    1995-01-01

    A NASA engineer with the Commercial Remote Sensing Program (CRSP) at Stennis Space Center works with students from W.P. Daniels High School in New Albany, Miss., through NASA's Small Spacecraft Technology Initiative Program. CRSP is teaching students to use remote sensing to locate a potential site for a water reservoir to offset a predicted water shortage in the community's future.

  4. Philadelphia's Renaissance Schools Initiative after Four Years

    Science.gov (United States)

    Stratos, Kati; Wolford, Tonya; Reitano, Adrienne

    2015-01-01

    In 2010-2011, the School District of Philadelphia (the District) launched its Renaissance Schools Initiative, a program designed to dramatically improve student achievement in the District's lowest performing schools. Some schools became Promise Academies, based on the federal turnaround model, and remained District-operated neighborhood schools.…

  5. Initial growth of Pterygota macrocarpa Schumann (Sterculiaceae ...

    African Journals Online (AJOL)

    Objective: A study on the growth of Pterygota macrocarpa (Sterculiaceae), in the nursery depending on the intensity of the light, was conducted within the Forest Management Unit of Bossematié. The main objective is to seek additional information on the initial growth of Pterygota macrocarpa , an overexploited and ...

  6. Fundamental study of crack initiation and propagation

    International Nuclear Information System (INIS)

    Norris, D.M. Jr.; Reaugh, J.E.; Moran, B.; Quinones, D.F.; Wilkins, M.L.

    1977-01-01

    Objective is to determine the fracture toughness of A533B-1 steel by computer modeling Charpy V-notch tests. A computer model of ductile fracture was developed that predicts fracture initiation. The model contains a set of material-dependent parameters obtained by computer simulations of small specimen tests. The computer calculations give detailed stress and strain histories up to the time of fracture, which are used to determine the model parameter values. The calibrated fracture model, that correctly predicts fracture initiation (and initiation energy) in the Charpy specimen, may then be used to simulate tests of accepted fracture-toughness specimens and hence obtain fracture toughness. The model parameters were calibrated to predict fracture in four different test specimens: two different notched-tension specimens, a simple tension specimen, and a precracked compact-tension specimen. The model was then used in a computer simulation of the Charpy V-notch specimen to initiate and advance a flat fracture. Results were compared with interrupted Charpy tests. Calibration of the model for two additional heat treatments of A533B-1 steel is in progress

  7. Educational Technology: Effective Leadership and Current Initiatives

    Science.gov (United States)

    Courville, Keith

    2011-01-01

    (Purpose) This article describes the basis for effective educational technology leadership and a few of the current initiatives and impacts that are a result of the aforementioned effective leadership. (Findings) Topics addressed in this paper include: (1) the role of the educational technology leader in an educational setting; (2) an examination…

  8. SunShot Initiative Portfolio Book 2014

    Energy Technology Data Exchange (ETDEWEB)

    Solar Energy Technologies Office

    2014-05-01

    The 2014 SunShot Initiative Portfolio Book outlines the progress towards the goals outlined in the SunShot Vision Study. Contents include overviews of each of SunShot’s five subprogram areas, as well as a description of every active project in the SunShot’s project portfolio as of May 2014.

  9. Energy Transition Initiative: Islands Playbook (Book)

    Energy Technology Data Exchange (ETDEWEB)

    2015-01-01

    The Island Energy Playbook (the Playbook) provides an action-oriented guide to successfully initiating, planning, and completing a transition to an energy system that primarily relies on local resources to eliminate a dependence on one or two imported fuels. It is intended to serve as a readily available framework that any community can adapt to organize its own energy transition effort.

  10. Understanding the Sustainability of Private Development Initiatives

    NARCIS (Netherlands)

    Kinsbergen, Sara; Schulpen, Lau; Ruben, Ruerd

    2017-01-01

    In the Netherlands, there is a large group of small-scale, voluntary development organisations, referred to as Private Development Initiatives (PDIs). By classifying PDI interventions based on their potential sustainability, we aim to enhance our understanding of PDIs as alternative development

  11. Tasman frontier subduction initiation and paleogene climate

    NARCIS (Netherlands)

    Sutherland, Rupert; Dickens, Gerald R.; Blum, Peter; Agnini, Claudia; Alegret, Laia; Bhattacharya, Joyeeta; Bordenave, Aurelien; Chang, Liao; Collot, Julien; Cramwinckel, Margot J.; Dallanave, Edoardo; Drake, Michelle K.; Etienne, Samuel J.G.; Giorgioni, Martino; Gurnis, Michael; Harper, Dustin T.; Huang, Huai Hsuan May; Keller, Allison L.; Lam, Adriane R.; Li, He; Matsui, Hiroki; Newsam, Cherry; Park, Yu Hyeon; Pascher, Kristina M.; Pekar, Stephen F.; Penman, Donald E.; Saito, Saneatsu; Stratford, Wanda R.; Westerhold, Thomas; Zhou, Xiaoli

    International Ocean Discovery Program (IODP) Expedition 371 drilled six sites in the Tasman Sea of the southwest Pacific between 27 July and 26 September 2017. The primary goal was to understand Tonga-Kermadec subduction initiation through recovery of Paleogene sediment records. Secondary goals

  12. Nuclear propulsion for the space exploration initiative

    International Nuclear Information System (INIS)

    Stanley, M.L.

    1991-01-01

    President Bush's speech of July 20, 1989, outlining a goal to go back to the moon and then Mars initiated the Space Exploration Initiative (SEI). The US Department of Defense (DOD), US Department of Energy (DOE), and NASA have been working together in the planning necessary to initiate a program to develop a nuclear propulsion system. Applications of nuclear technology for in-space transfer of personnel and cargo between Earth orbit and lunar or Martian orbit are being considered as alternatives to chemical propulsion systems. Mission and system concept studies conducted over the past 30 yr have consistently indicated that use of nuclear technology can substantially reduce in-space propellant requirements. A variety of nuclear technology options are currently being studied, including nuclear thermal rockets, nuclear electrical propulsion systems, and hybrid nuclear thermal rockets/nuclear electric propulsion concepts. Concept performance in terms of thrust, weight, power, and efficiency are dependent, and appropriate concept application is mission dependent (i.e., lunar, Mars, cargo, personnel, trajectory, transit time, payload). A comprehensive evaluation of mission application, technology performance capability and maturity, technology development programmatics, and safety characteristics is required to optimize both technology and mission selection to support the Presidential initiative

  13. EDITORIAL Drugs for Neglected Diseases Initiative

    African Journals Online (AJOL)

    Dr.Kofi-Tsekpo

    disease, and malaria have a devastating impact on humanity, yet R&D for new drugs for these diseases has been progressively marginalised because they are not considered a lucrative investment. DNDi, a needs-driven initiative, keeps the needs of patients suffering from neglected diseases paramount in its search for.

  14. Understanding the Early Years (UEY) Initiative

    Science.gov (United States)

    Human Resources and Social Development Canada, 2007

    2007-01-01

    Internal Audit Services conducted an Early Implementation Review of the Understanding the Early Years (UEY) Initiative in 2006-07. This review is intended to provide assurance to senior management that program delivery has been established appropriately in order to meet its objectives and highlight any areas that require focused management…

  15. 1 | Page PROSPECTUS INITIATIVE DES CONSEILS ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    khaled fourati

    INITIATIVE DES CONSEILS SUBVENTIONNAIRES DE LA RECHERCHE ... années environ ont créé un contexte dans lequel la science, la technologie et .... précis. La nature de cette collaboration transfrontalière sera déterminée et appuyée.

  16. Independence of Movement Preparation and Movement Initiation.

    Science.gov (United States)

    Haith, Adrian M; Pakpoor, Jina; Krakauer, John W

    2016-03-09

    Initiating a movement in response to a visual stimulus takes significantly longer than might be expected on the basis of neural transmission delays, but it is unclear why. In a visually guided reaching task, we forced human participants to move at lower-than-normal reaction times to test whether normal reaction times are strictly necessary for accurate movement. We found that participants were, in fact, capable of moving accurately ∼80 ms earlier than their reaction times would suggest. Reaction times thus include a seemingly unnecessary delay that accounts for approximately one-third of their duration. Close examination of participants' behavior in conventional reaction-time conditions revealed that they generated occasional, spontaneous errors in trials in which their reaction time was unusually short. The pattern of these errors could be well accounted for by a simple model in which the timing of movement initiation is independent of the timing of movement preparation. This independence provides an explanation for why reaction times are usually so sluggish: delaying the mean time of movement initiation relative to preparation reduces the risk that a movement will be initiated before it has been appropriately prepared. Our results suggest that preparation and initiation of movement are mechanistically independent and may have a distinct neural basis. The results also demonstrate that, even in strongly stimulus-driven tasks, presentation of a stimulus does not directly trigger a movement. Rather, the stimulus appears to trigger an internal decision whether to make a movement, reflecting a volitional rather than reactive mode of control. Copyright © 2016 the authors 0270-6474/16/363007-10$15.00/0.

  17. Reduction of initial shock in decadal predictions using a new initialization strategy

    Science.gov (United States)

    He, Yujun; Wang, Bin; Liu, Mimi; Liu, Li; Yu, Yongqiang; Liu, Juanjuan; Li, Ruizhe; Zhang, Cheng; Xu, Shiming; Huang, Wenyu; Liu, Qun; Wang, Yong; Li, Feifei

    2017-08-01

    A novel full-field initialization strategy based on the dimension-reduced projection four-dimensional variational data assimilation (DRP-4DVar) is proposed to alleviate the well-known initial shock occurring in the early years of decadal predictions. It generates consistent initial conditions, which best fit the monthly mean oceanic analysis data along the coupled model trajectory in 1 month windows. Three indices to measure the initial shock intensity are also proposed. Results indicate that this method does reduce the initial shock in decadal predictions by Flexible Global Ocean-Atmosphere-Land System model, Grid-point version 2 (FGOALS-g2) compared with the three-dimensional variational data assimilation-based nudging full-field initialization for the same model and is comparable to or even better than the different initialization strategies for other fifth phase of the Coupled Model Intercomparison Project (CMIP5) models. Better hindcasts of global mean surface air temperature anomalies can be obtained than in other FGOALS-g2 experiments. Due to the good model response to external forcing and the reduction of initial shock, higher decadal prediction skill is achieved than in other CMIP5 models.

  18. On Surface-Initiated Atom Transfer Radical Polymerization Using Diazonium Chemistry To Introduce the Initiator Layer

    DEFF Research Database (Denmark)

    Iruthayaraj, Joseph; Chernyy, Sergey; Lillethorup, Mie

    2011-01-01

    This work features the controllability of surface-initiated atom transfer radical polymerization (SI-ATRP) of methyl methacrylate, initiated by a multilayered 2-bromoisobutyryl moiety formed via diazonium chemistry. The thickness as a function of polymerization time has been studied by varying di...

  19. Initiation precursors and initiators in laser-induced copolymerization of styrene and maleic anhydride in acetone

    Science.gov (United States)

    Miner, Gilda A.; Meador, Willard E.; Chang, C. Ken

    1990-01-01

    The initiation step of photopolymerized styrene/maleic anhydride copolymer was investigated at 365 nm. UV absorption measurements provide decisive evidence that the styrene/maleic anhydride charge transfer complex is the sole absorbing species; however, key laser experiments suggest intermediate reactions lead to a monoradical initiating species. A mechanism for the photoinitiation step of the copolymer is proposed.

  20. Initiation of Gaseous Detonation by Conical Projectiles

    Science.gov (United States)

    Verreault, Jimmy

    Initiation and stabilization of detonation by hypersonic conical projectiles launched into combustible gas mixtures is investigated. This phenomenon must be understood for the design and optimization of specific hypersonic propulsion devices, such as the oblique detonation wave engine and the ram accelerator. The criteria for detonation initiation by a projectile is also related to fundamental aspects of detonation research, such as the requirement for direct initiation of a detonation by a blast wave. Experimental results of this problem also offer useful references for validation of numerical and theoretical modeling. Projectiles with cone half angles varying from 15° to 60° were launched into stoichiometric mixtures of hydrogen/oxygen with 70% argon dilution at initial pressures between 10 and 200 kPa. The projectiles were launched from a combustion-driven gas gun at velocities up to 2.2 km/s (corresponding to 133% of the Chapman Jouguet velocity). Pictures of the flowfields generated by the projectiles were taken via Schlieren photography. Five combustion regimes were observed about the projectile ranging from prompt and delayed oblique detonation wave formation, combustion instabilities, a wave splitting, and an inert shock wave. Two types of transition from the prompt oblique detonation wave regime to the inert shock regime were observed. The first (the delayed oblique detonation wave regime) showed an inert shock attached to the tip of the projectile followed by a sharp kink at the onset of an oblique detonation wave; this regime occurred by decreasing the cone angle at high mixture pressures. The second (the combustion instabilities regime) exhibited large density gradients due to combustion ignition and quenching phenomena; this regime occurred by decreasing the mixture pressure at large cone angles. A number of theoretical models were considered to predict critical conditions for the initiation of oblique detonations. The Lee-Vasiljev model agreed

  1. A methodology for analyzing precursors to earthquake-initiated and fire-initiated accident sequences

    International Nuclear Information System (INIS)

    Budnitz, R.J.; Lambert, H.E.; Apostolakis, G.

    1998-04-01

    This report covers work to develop a methodology for analyzing precursors to both earthquake-initiated and fire-initiated accidents at commercial nuclear power plants. Currently, the U.S. Nuclear Regulatory Commission sponsors a large ongoing project, the Accident Sequence Precursor project, to analyze the safety significance of other types of accident precursors, such as those arising from internally-initiated transients and pipe breaks, but earthquakes and fires are not within the current scope. The results of this project are that: (1) an overall step-by-step methodology has been developed for precursors to both fire-initiated and seismic-initiated potential accidents; (2) some stylized case-study examples are provided to demonstrate how the fully-developed methodology works in practice, and (3) a generic seismic-fragility date base for equipment is provided for use in seismic-precursors analyses. 44 refs., 23 figs., 16 tabs

  2. Considerations about mediative in initial petition

    Directory of Open Access Journals (Sweden)

    Maria das Vitórias Nunes Silva Lourenço

    2013-12-01

    Full Text Available This paper presents considerations about Initial Petition, textual/discursive genre, which is a genre circumscribed in the judicial domain with relation to the Commitment. For this purpose, this article exposes the text plan of the Initial Petition from the postulations of Adam (2011. In the same way, it studies the mediative frameworks based on Guentchéva (1994, 1996, which develop the notion of mediative grammatical categories, that permits the linguistic marking of distance and engagement of the enunciator with regard to the information expressed. It evidences the relevance of the use of mediated constructions in the judicial text, as they function as attenuated strategies to the responsibility of the producer of the text with what is said, and at the same time points to a discourse of authority through the entrance of the sources of law.

  3. The US proliferation security initiative (PSI)

    International Nuclear Information System (INIS)

    Gregoire, B.

    2004-01-01

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

  4. Initial conditions of radiative shock experiments

    International Nuclear Information System (INIS)

    Kuranz, C. C.; Drake, R. P.; Krauland, C. M.; Marion, D. C.; Grosskopf, M. J.; Rutter, E.; Torralva, B.; Holloway, J. P.; Bingham, D.; Goh, J.; Boehly, T. R.; Sorce, A. T.

    2013-01-01

    We performed experiments at the Omega Laser Facility to characterize the initial, laser-driven state of a radiative shock experiment. These experiments aimed to measure the shock breakout time from a thin, laser-irradiated Be disk. The data are then used to inform a range of valid model parameters, such as electron flux limiter and polytropic γ, used when simulating radiative shock experiments using radiation hydrodynamics codes. The characterization experiment and the radiative shock experiment use a laser irradiance of ∼7 × 10 14 W cm −2 to launch a shock in the Be disk. A velocity interferometer and a streaked optical pyrometer were used to infer the amount of time for the shock to move through the Be disk. The experimental results were compared with simulation results from the Hyades code, which can be used to model the initial conditions of a radiative shock system using the CRASH code

  5. On the initial condition of inflationary fluctuations

    International Nuclear Information System (INIS)

    Jiang, Hongliang; Wang, Yi; Zhou, Siyi

    2016-01-01

    It is usually assumed that the inflationary fluctuations start from the Bunch-Davies (BD) vacuum and the iε prescription is used when interactions are calculated. We show that those assumptions can be verified explicitly by calculating the loop corrections to the inflationary two-point and three-point correlation functions. Those loop corrections can be resummed to exponential factors, which suppress non-BD coefficients and behave as the iε factor for the case of the BD initial condition. A new technique of loop chain diagram resummation is developed for this purpose. For the non-BD initial conditions which is setup at finite time and has not fully decayed, explicit correction to the two-point and three-point correlation functions are calculated. Especially, non-Gaussianity in the folded limit is regularized due to the interactions.

  6. The SPIRIT Telescope Initiative: six years on

    Science.gov (United States)

    Luckas, Paul

    2017-06-01

    Now in its sixth year of operation, the SPIRIT initiative remains unique in Australia, as a robust web-enabled robotic telescope initiative funded for education and outreach. With multiple modes of operation catering for a variety of usage scenarios and a fully supported education program, SPIRIT provides free access to contemporary astronomical tools for students and educators in Western Australia and beyond. The technical solution itself provides an excellent model for low cost robotic telescope installations, and the education program has evolved over time to include a broad range of student experiences-from engagement activities to authentic science. This paper details the robotic telescope solution, student interface and educational philosophy, summarises achievements and lessons learned and examines the possibilities for future enhancement including spectroscopy.

  7. Initial conditioning of the TFTR vacuum vessel

    International Nuclear Information System (INIS)

    Dylla, H.F.; Blanchard, W.R.; Krawchuk, R.B.; Hawryluk, R.J.; Owens, D.K.

    1984-01-01

    We report on the initial conditioning of the Tokamak Fusion Test Reactor (TFTR) vacuum vessel prior to the initiation of first plasma discharges, and during subsequent operation with high power ohmically-heated plasmas. Following evacuation of the 86 m 3 vessel with the 10 4 1/s high vacuum pumping system, the vessel was conditioned by a 15 A dc glow discharge in H 2 at a pressure of 5 mTorr. Rapid-pulse discharge cleaning was used subsequently to preferentially condition the graphite plasma limiters. The effectiveness of the discharge cleaning was monitored by measuring the exhaust rates of the primary discharge products (CO/C 2 H 4 , CH 4 , and H 2 O). After 175 hours of glow discharge treatment, the equivalent of 50 monolayers of C and O was removed from the vessel, and the partial pressures of impurity gases were reduced to the range of 10 -9 -10 -10 Torr

  8. Hanford Tanks Initiative quality assurance implementation plan

    International Nuclear Information System (INIS)

    Huston, J.J.

    1998-01-01

    Hanford Tanks Initiative (HTI) Quality Assurance Implementation Plan for Nuclear Facilities defines the controls for the products and activities developed by HTI. Project Hanford Management Contract (PHMC) Quality Assurance Program Description (QAPD)(HNF-PRO599) is the document that defines the quality requirements for Nuclear Facilities. The QAPD provides direction for compliance to 10 CFR 830.120 Nuclear Safety Management, Quality Assurance Requirements. Hanford Tanks Initiative (HTI) is a five-year activity resulting from the technical and financial partnership of the US Department of Energy's Office of Waste Management (EM-30), and Office of Science and Technology Development (EM-50). HTI will develop and demonstrate technologies and processes for characterization and retrieval of single shell tank waste. Activities and products associated with HTI consist of engineering, construction, procurement, closure, retrieval, characterization, and safety and licensing

  9. Runaway breakdown and hydrometeors in lightning initiation.

    Science.gov (United States)

    Gurevich, A V; Karashtin, A N

    2013-05-03

    The particular electric pulse discharges are observed in thunderclouds during the initiation stage of negative cloud-to-ground lightning. The discharges are quite different from conventional streamers or leaders. A detailed analysis reveals that the shape of the pulses is determined by the runaway breakdown of air in the thundercloud electric field initiated by extensive atmospheric showers (RB-EAS). The high amplitude of the pulse electric current is due to the multiple microdischarges at hydrometeors stimulated and synchronized by the low-energy electrons generated in the RB-EAS process. The series of specific pulse discharges leads to charge reset from hydrometeors to the free ions and creates numerous stretched ion clusters, both positive and negative. As a result, a wide region in the thundercloud with a sufficiently high fractal ion conductivity is formed. The charge transport by ions plays a decisive role in the lightning leader preconditioning.

  10. Environmental management initiatives and stakeholder influences

    DEFF Research Database (Denmark)

    Madsen, Henning; Ulhøi, John Parm

    1999-01-01

    in Danish industrial companies. These findings are discussed in the light of similar reported results and case studies of companies which are reportedly pioneers in the introduction of environmental initiatives from a number of EU countries. Implications for theory, practice and training are addressed...... of change, from the point of view of stakeholder theory, from a merely reactive attitude in industry, where companies only tend to respond to stakeholder pressure which cannot be ignored (e.g. ex post responses to one or two stakeholders, such as regulators and customers), towards an increasingly proactive...... attitude characterised by ex ante responses to several strategic groups of stakeholders (including NGOs, employees, neighbours, etc.). The present situation is illustrated by the findings in two recent surveys concerning perceived stakeholder influence in relation to environmental management initiatives...

  11. International and national initiatives in biobanking.

    Science.gov (United States)

    Ectors, N

    2011-01-01

    Translational research and biobanking are "in", also in Flanders and in Belgium. In Flanders the Advice report 120 from the Flemish Council for Science and innovation, entitled "Extension of translational research in Flanders" paved the way for the Center for Medical Innovation. The Center for Medical Innovation aims at promoting collaboration between Flemish Universities, university hospitals, pharma and biotech industry and the Flemish Government specifically in the domain of translational research. The Initiative # 27 of the Cancer plan from the Federal Government aims at financing a virtual interuniversity tumor bank in order to promote "cancer" translational research in a collaborative network between academic structures, general hospitals en different industrial partners (pharmacy, biotechnology, diagnostics, ...) active in research in Belgium. However, the scientific interest in the human tissues is not new, at all. This text aims at giving an overview of the development and evolutions of "biobanking" initiatives.

  12. Initial Multidisciplinary Design and Analysis Framework

    Science.gov (United States)

    Ozoroski, L. P.; Geiselhart, K. A.; Padula, S. L.; Li, W.; Olson, E. D.; Campbell, R. L.; Shields, E. W.; Berton, J. J.; Gray, J. S.; Jones, S. M.; hide

    2010-01-01

    Within the Supersonics (SUP) Project of the Fundamental Aeronautics Program (FAP), an initial multidisciplinary design & analysis framework has been developed. A set of low- and intermediate-fidelity discipline design and analysis codes were integrated within a multidisciplinary design and analysis framework and demonstrated on two challenging test cases. The first test case demonstrates an initial capability to design for low boom and performance. The second test case demonstrates rapid assessment of a well-characterized design. The current system has been shown to greatly increase the design and analysis speed and capability, and many future areas for development were identified. This work has established a state-of-the-art capability for immediate use by supersonic concept designers and systems analysts at NASA, while also providing a strong base to build upon for future releases as more multifidelity capabilities are developed and integrated.

  13. Initial design process of the repository

    International Nuclear Information System (INIS)

    Osmanlioglu, A.E.

    2001-01-01

    The concept of the final disposal of high level wastes is to isolate the waste from the biosphere for extremely long periods of time by emplacement of wastes into deep stable geological formations. Several geological formations have been considered as candidate host environments for high level waste disposal and several techniques have been developed for repository design. In this study, interrelationships of main parameters of a general repository design have been defined and effective parameters are shown at each step. Initial design process is based on the long term stability of underground openings as disposal galleries. For this reason, this design process includes two main analyses: mechanical analysis and thermal analysis. Each of the analysis systems is directly related to each other by technical precautions. As a result of this design process, general information about the acceptable depth of the repository, layout and emplacement pattern can be taken. Final design study can be established on the result of initial design process. (author)

  14. Technology transfer from the space exploration initiative

    International Nuclear Information System (INIS)

    Buden, D.

    1991-01-01

    Space exploration has demonstrated that it stimulates the national economy by creating new and improved products, increased employment, and provides a stimulus to education. The exploration of the Moon and Mars under the Space Exploration Initiative has the potential of accelerating this stimulates to the economy. It is difficult to identify all of the concrete ways this will be accomplished. However, many areas can be identified. The space exploration building blocks of power, propulsion, spacecraft, robotics, rovers, mining and manufacturing, communications, navigation, habitats, life support and infrastructures are reviewed to identify possible technology areas. For example, better means for working in hazardous areas and handling hazardous waste are potential outcomes of this initiative. Methods to produce higher quality goods and improve America's competitiveness in manufacturing will undoubtedly evolve from the need to produce products that must last many years in the harsh environments of space and planetary surfaces. Some ideas for technology transfer are covered in this paper

  15. Multiagency Initiative to Provide Greenhouse Gas Information

    Science.gov (United States)

    Boland, Stacey W.; Duren, Riley M.

    2009-11-01

    Global Greenhouse Gas Information System Workshop; Albuquerque, New Mexico, 20-22 May 2009; The second Greenhouse Gas Information System (GHGIS) workshop brought together 74 representatives from 28 organizations including U.S. government agencies, national laboratories, and members of the academic community to address issues related to the understanding, operational monitoring, and tracking of greenhouse gas emissions and carbon offsets. The workshop was held at Sandia National Laboratories and organized by an interagency collaboration among NASA centers, Department of Energy laboratories, and the U.S. National Oceanic and Atmospheric Administration. It was motivated by the perceived need for an integrated interagency, community-wide initiative to provide information about greenhouse gas sources and sinks at policy-relevant temporal and spatial scales. Such an initiative could significantly enhance the ability of national and regional governments, industry, and private citizens to implement and evaluate effective climate change mitigation policies.

  16. Care initiation area yields dramatic results.

    Science.gov (United States)

    2009-03-01

    The ED at Gaston Memorial Hospital in Gastonia, NC, has achieved dramatic results in key department metrics with a Care Initiation Area (CIA) and a physician in triage. Here's how the ED arrived at this winning solution: Leadership was trained in and implemented the Kaizen method, which eliminates redundant or inefficient process steps. Simulation software helped determine additional space needed by analyzing arrival patterns and other key data. After only two days of meetings, new ideas were implemented and tested.

  17. Security analysis of session initiation protocol

    OpenAIRE

    Dobson, Lucas E.

    2010-01-01

    Approved for public release; distribution is unlimited The goal of this thesis is to investigate the security of the Session Initiation Protocol (SIP). This was accomplished by researching previously discovered protocol and implementation vulnerabilities, evaluating the current state of security tools and using those tools to discover new vulnerabilities in SIP software. The CVSS v2 system was used to score protocol and implementation vulnerabilities to give them a meaning that was us...

  18. Leading and managing organizational change initiatives

    OpenAIRE

    Peus, Claudia; Frey, Dieter; Gerkhardt, Marit; Fischer, Peter; Traut-Mattausch, Eva

    2009-01-01

    Although indispensable for long-term economic growth, organizational changes are usually met with resistance. This article draws on psychological theories and empirical evidence to highlight why and under what conditions changes lead to resistance and what likely consequences of resistance are. Furthermore, the article discusses the variables that have been identified as success factors for organizational change initiatives. These include individual difference variables and objective characte...

  19. Hanford Tanks Initiative risk management guide

    International Nuclear Information System (INIS)

    Schaus, P.S.

    1997-01-01

    This project-specific Risk Management Guide describes the general approach and process being used by the HTI Project to manage risk associated with execution of the HTI mission. It includes the initial identification of risk and the quantification of its likelihood and severity of its consequences. It further addresses the formulation of risk mitigation plans, periodic statusing of the Risk Management List, and risk closure

  20. University Research Initiative Program for Combat Readiness

    Science.gov (United States)

    1999-05-01

    microscope image of one of the lenses. This array was selected for testing because it is fabricated in a relatively inexpensive polyacrylic material, the...potent analogues of the potassium -sparing diuretic, amiloride. However, our results 179 University Reasearch Initiative for Combat Readiness Annual Report...for Combat Readiness Annual Report for the period June 1, 1998 - June 30, 1999 Roger H. Sawyer University of South Carolina Columbia, SC 29208 May