WorldWideScience

Sample records for regions links notch-1

  1. Characterization of Notch1 antibodies that inhibit signaling of both normal and mutated Notch1 receptors.

    Directory of Open Access Journals (Sweden)

    Miguel Aste-Amézaga

    2010-02-01

    Full Text Available Notch receptors normally play a key role in guiding a variety of cell fate decisions during development and differentiation of metazoan organisms. On the other hand, dysregulation of Notch1 signaling is associated with many different types of cancer as well as tumor angiogenesis, making Notch1 a potential therapeutic target.Here we report the in vitro activities of inhibitory Notch1 monoclonal antibodies derived from cell-based and solid-phase screening of a phage display library. Two classes of antibodies were found, one directed against the EGF-repeat region that encompasses the ligand-binding domain (LBD, and the second directed against the activation switch of the receptor, the Notch negative regulatory region (NRR. The antibodies are selective for Notch1, inhibiting Jag2-dependent signaling by Notch1 but not by Notch 2 and 3 in reporter gene assays, with EC(50 values as low as 5+/-3 nM and 0.13+/-0.09 nM for the LBD and NRR antibodies, respectively, and fail to recognize Notch4. While more potent, NRR antibodies are incomplete antagonists of Notch1 signaling. The antagonistic activity of LBD, but not NRR, antibodies is strongly dependent on the activating ligand. Both LBD and NRR antibodies bind to Notch1 on human tumor cell lines and inhibit the expression of sentinel Notch target genes, including HES1, HES5, and DTX1. NRR antibodies also strongly inhibit ligand-independent signaling in heterologous cells transiently expressing Notch1 receptors with diverse NRR "class I" point mutations, the most common type of mutation found in human T-cell acute lymphoblastic leukemia (T-ALL. In contrast, NRR antibodies failed to antagonize Notch1 receptors bearing rare "class II" or "class III" mutations, in which amino acid insertions generate a duplicated or constitutively sensitive metalloprotease cleavage site. Signaling in T-ALL cell lines bearing class I mutations is partially refractory to inhibitory antibodies as compared to cell

  2. Gauging NOTCH1 Activation in Cancer Using Immunohistochemistry.

    Directory of Open Access Journals (Sweden)

    Michael J Kluk

    Full Text Available Fixed, paraffin-embedded (FPE tissues are a potentially rich resource for studying the role of NOTCH1 in cancer and other pathologies, but tests that reliably detect activated NOTCH1 (NICD1 in FPE samples have been lacking. Here, we bridge this gap by developing an immunohistochemical (IHC stain that detects a neoepitope created by the proteolytic cleavage event that activates NOTCH1. Following validation using xenografted cancers and normal tissues with known patterns of NOTCH1 activation, we applied this test to tumors linked to dysregulated Notch signaling by mutational studies. As expected, frequent NICD1 staining was observed in T lymphoblastic leukemia/lymphoma, a tumor in which activating NOTCH1 mutations are common. However, when IHC was used to gauge NOTCH1 activation in other human cancers, several unexpected findings emerged. Among B cell tumors, NICD1 staining was much more frequent in chronic lymphocytic leukemia than would be predicted based on the frequency of NOTCH1 mutations, while mantle cell lymphoma and diffuse large B cell lymphoma showed no evidence of NOTCH1 activation. NICD1 was also detected in 38% of peripheral T cell lymphomas. Of interest, NICD1 staining in chronic lymphocytic leukemia cells and in angioimmunoblastic lymphoma was consistently more pronounced in lymph nodes than in surrounding soft tissues, implicating factors in the nodal microenvironment in NOTCH1 activation in these diseases. Among carcinomas, diffuse strong NICD1 staining was observed in 3.8% of cases of triple negative breast cancer (3 of 78 tumors, but was absent from 151 non-small cell lung carcinomas and 147 ovarian carcinomas. Frequent staining of normal endothelium was also observed; in line with this observation, strong NICD1 staining was also seen in 77% of angiosarcomas. These findings complement insights from genomic sequencing studies and suggest that IHC staining is a valuable experimental tool that may be useful in selection of

  3. Notch-1 mediates hypoxia-induced angiogenesis in rheumatoid arthritis.

    Science.gov (United States)

    Gao, Wei; Sweeney, Catherine; Connolly, Mary; Kennedy, Aisling; Ng, Chin Teck; McCormick, Jennifer; Veale, Douglas J; Fearon, Ursula

    2012-07-01

    To examine the effect of hypoxia on Notch-1 signaling pathway components and angiogenesis in inflammatory arthritis. The expression and regulation of Notch-1, its ligand delta-like protein 4 (DLL-4) and downstream signaling components (hairy-related transcription factor 1 [HRT-1], HRT-2), and hypoxia-inducible factor 1α (HIF-1α) under normoxic and hypoxic conditions (1-3%) were assessed in synovial tissue specimens from patients with inflammatory arthritis and controls and in human dermal microvascular endothelial cells (HDMECs) by immunohistology, dual immunofluorescence staining (Notch-1/factor VIII), Western blotting, and real-time polymerase chain reaction. In vivo synovial tissue oxygen levels (tissue PO2) were measured under direct visualization at arthroscopy. HDMEC activation under hypoxic conditions in the presence of Notch-1 small interfering RNA (siRNA), the γ-secretase inhibitor DAPT, or dimethyloxalylglycine (DMOG) was assessed by Matrigel tube formation assay, migration assay, invasion assay, and matrix metalloproteinase 2 (MMP-2)/MMP-9 zymography. Expression of Notch-1, its ligand DLL-4, and HRT-1 was demonstrated in synovial tissue, with the strongest expression localized to perivascular/vascular regions. Localization of Notch-1 to synovial endothelium was confirmed by dual immunofluorescence staining. Notch-1 intracellular domain (NICD) expression was significantly higher in synovial tissue from patients with tissue PO2 of PO2 of >20 mm Hg (>3% O2). Exposure of HDMECs to 3% hypoxia induced HIF-1α and NICD protein expression and DLL-4, HRT-1, and HRT-2 messenger RNA expression. DMOG directly induced NICD expression, while Notch-1 siRNA inhibited hypoxia-induced HIF-1α expression, suggesting that Notch-1/HIF-1α signaling is bidirectional. Finally, 3% hypoxia-induced angiogenesis, endothelial cell migration, endothelial cell invasion, and proMMP-2 and proMMP-9 activities were inhibited by Notch-1 siRNA and/or the γ-secretase inhibitor DAPT. Our

  4. Evidence of Aortopathy in Mice with Haploinsufficiency of Notch1 in Nos3-Null Background

    Directory of Open Access Journals (Sweden)

    Sara N. Koenig

    2015-03-01

    Full Text Available Thoracic aortic aneurysms (TAA are a significant cause of morbidity and mortality in humans. While the exact etiology is unknown, genetic factors play an important role. Mutations in NOTCH1 have been linked to bicuspid aortic valve (BAV and aortopathy in humans. The aim of this study was to determine if haploinsufficiency of Notch1 contributes to aortopathy using Notch1+/−; Nos3−/− mice. Echocardiographic analysis of Notch1+/−; Nos3−/− mice reveals effacement of the sinotubular junction and a trend toward dilation of the aortic sinus. Furthermore, examination of the proximal aorta of Notch1+/−; Nos3−/− mice reveals elastic fiber degradation, a trend toward increased matrix metalloproteinase 2 expression, and increased smooth muscle cell apoptosis, features characteristic of aneurysmal disease. Although at a lower penetrance, we also found features consistent with aortopathic changes in Notch1 heterozygote mice and in Nos3-null mice. Our findings implicate a novel role for Notch1 in aortopathy of the proximal aorta.

  5. miR-935 suppresses gastric signet ring cell carcinoma tumorigenesis by targeting Notch1 expression

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Chao [Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730 (China); Yu, Jianchun, E-mail: yu_jchpumch@163.com [Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730 (China); Kang, Weiming [Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730 (China); Liu, Yuqin [Cell Culture Center, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005 (China); Ma, Zhiqiang; Zhou, Li [Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730 (China)

    2016-01-29

    Gastric signet ring cell carcinoma (GSRCC) is a unique pathological type of gastric carcinoma that is extremely invasive and has a poor prognosis. Expression of microRNAs (miRNAs) has been closely linked to the carcinogenesis of gastric cancer and has been considered as a powerful prognostic marker. The function of miR-935 has never been reported in cancer before. We found, using microRNA array, that expression of miR-935 in GSRCC cell lines is lower than in non-GSRCC cell lines, and enhanced expression of miR-935 in GSRCC cell-lines inhibit cell proliferation, migration and invasion. We also identified Notch1 as a direct target of miR-935. Knockdown of Notch1 reduced proliferation, migration/invasion of GSRCC cells, and overexpression Notch1's activated form (Notch intracellular domain) could rescue miR-935's tumor suppressive effect on GSRCC. Expression of miR-935 was lower in gastric carcinoma tissue than in paired normal tissue samples, and lower in GSRCC than in non-GSRCC. Our results demonstrate the inverse correlation between the expression of miR-935 and Notch1 in gastric tissues. We conclude that miR-935 inhibits gastric carcinoma cell proliferation, migration and invasion by targeting Notch1, suggesting potential applications of the miR-935-Notch1 pathway in gastric cancer clinical diagnosis and therapeutics, especially in gastric signet ring cell carcinoma. - Highlights: • The expression of miR-935 is lower in GC tissue than in paired normal tissue. • The expression of miR-935 is lower in GSRCC tissue than in non-GSRCC. • Enhanced expression of miR-935 suppresses tumorigenesis of GSRCC. • Notch1 is a direct target of miR-935.

  6. Analysis list: NOTCH1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NOTCH1 Blood + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/NOTCH1.1....tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/NOTCH1.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/NOTC...H1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/NOTCH1.Blood.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Blood.gml ...

  7. Common nonmutational NOTCH1 activation in chronic lymphocytic leukemia.

    Science.gov (United States)

    Fabbri, Giulia; Holmes, Antony B; Viganotti, Mara; Scuoppo, Claudio; Belver, Laura; Herranz, Daniel; Yan, Xiao-Jie; Kieso, Yasmine; Rossi, Davide; Gaidano, Gianluca; Chiorazzi, Nicholas; Ferrando, Adolfo A; Dalla-Favera, Riccardo

    2017-04-04

    Activating mutations of NOTCH1 (a well-known oncogene in T-cell acute lymphoblastic leukemia) are present in ∼4-13% of chronic lymphocytic leukemia (CLL) cases, where they are associated with disease progression and chemorefractoriness. However, the specific role of NOTCH1 in leukemogenesis remains to be established. Here, we report that the active intracellular portion of NOTCH1 (ICN1) is detectable in ∼50% of peripheral blood CLL cases lacking gene mutations. We identify a "NOTCH1 gene-expression signature" in CLL cells, and show that this signature is significantly enriched in primary CLL cases expressing ICN1, independent of NOTCH1 mutation. NOTCH1 target genes include key regulators of B-cell proliferation, survival, and signal transduction. In particular, we show that NOTCH1 transactivates MYC via binding to B-cell-specific regulatory elements, thus implicating this oncogene in CLL development. These results significantly extend the role of NOTCH1 in CLL pathogenesis, and have direct implications for specific therapeutic targeting.

  8. Essential Role of Endothelial Notch1 in Angiogenesis

    Science.gov (United States)

    Limbourg, Florian P.; Takeshita, Kyosuke; Radtke, Freddy; Bronson, Roderick T.; Chin, Michael T.; Liao, James K.

    2009-01-01

    Background Notch signaling influences binary cell fate decisions in a variety of tissues. The Notch1 receptor is widely expressed during embryogenesis and is essential for embryonic development. Loss of global Notch1 function results in early embryonic lethality, but the cell type responsible for this defect is not known. Here, we identify the endothelium as the primary target tissue affected by Notch1 signaling. Methods and Results We generated an endothelium-specific deletion of Notch1 using Tie2Cre and conditional Notch1flox/flox mice. Mutant embryos lacking endothelial Notch1 died at approximately embryonic day 10.5 with profound vascular defects in placenta, yolk sac, and embryo proper, whereas heterozygous deletion had no effect. In yolk sacs of mutant embryos, endothelial cells formed a primary vascular plexus indicative of intact vasculogenesis but failed to induce the secondary vascular remodeling required to form a mature network of well-organized large and small blood vessels, which demonstrates a defect in angiogenesis. These vascular defects were also evident in the placenta, where blood vessels failed to invade the placental labyrinth, and in the embryo proper, where defective blood vessel maturation led to pericardial and intersomitic hemorrhage. Enhanced activation of caspase-3 was detected in endothelial and neural cells of mutant mice, which resulted in enhanced apoptotic degeneration of somites and the neural tube. Conclusions These findings recapitulate the vascular phenotype of global Notch1-/- mutants and indicate an essential cell-autonomous role of Notch1 signaling in the endothelium during vascular development. These results may have important clinical implications with regard to Notch1 signaling in adult angiogenesis. PMID:15809373

  9. dlk acts as a negative regulator of Notch1 activation through interactions with specific EGF-like repeats

    International Nuclear Information System (INIS)

    Baladron, Victoriano; Ruiz-Hidalgo, Maria Jose; Nueda, Maria Luisa; Diaz-Guerra, Maria Jose M.; Garcia-Ramirez, Jose Javier; Bonvini, Ezio; Gubina, Elena; Laborda, Jorge

    2005-01-01

    The protein dlk, encoded by the Dlk1 gene, belongs to the Notch epidermal growth factor (EGF)-like family of receptors and ligands, which participate in cell fate decisions during development. The molecular mechanisms by which dlk regulates cell differentiation remain unknown. By using the yeast two-hybrid system, we found that dlk interacts with Notch1 in a specific manner. Moreover, by using luciferase as a reporter gene under the control of a CSL/RBP-Jk/CBF-1-dependent promoter in the dlk-negative, Notch1-positive Balb/c 14 cell line, we found that addition of synthetic dlk EGF-like peptides to the culture medium or forced expression of dlk decreases endogenous Notch activity. Furthermore, the expression of the gene Hes-1, a target for Notch1 activation, diminishes in confluent Balb/c14 cells transfected with an expression construct encoding for the extracellular EGF-like region of dlk. The expression of Dlk1 and Notch1 increases in 3T3-L1 cells maintained in a confluent state for several days, which is associated with a concomitant decrease in Hes-1 expression. On the other hand, the decrease of Dlk1 expression in 3T3-L1 cells by antisense cDNA transfection is associated with an increase in Hes-1 expression. These results suggest that dlk functionally interacts in vivo with Notch1, which may lead to the regulation of differentiation processes modulated by Notch1 activation and signaling, including adipogenesis

  10. Notch 1 as a potential therapeutic target in cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Kamstrup, Maria Rørbæk; Gjerdrum, Lise Mette Rahbek; Biskup, Edyta Urszula

    2010-01-01

    Deregulation of Notch signaling has been linked to the development of T-cell leukemias and several solid malignancies. Yet, it is unknown whether Notch signalling is involved in the pathogenesis of mycosis fungoides and Sezary syndrome, the most common subtypes of cutaneous T cell lymphoma....... By immunohistochemistry of 40 biopsies taken from skin lesions of mycosis fungoides and Sezary syndrome we demonstrated prominent expression of Notch1 on tumor cells, especially in the more advanced stages. The gamma-secretase inhibitor I blocked Notch signaling and potently induced apoptosis in cell lines derived from...... mycosis fungoides (MyLa) and Sezary syndrome (SeAx, HuT-78)and in primary leukemic Sézary cells. Specific downregulation of Notch1 (but not Notch2 and Notch3) by siRNA induced apoptosis in SeAx. The mechanism of apoptosis involved the inhibition of NF-kappaB, which is the most important prosurvival...

  11. The common oncogenomic program of NOTCH1 and NOTCH3 signaling in T-cell acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Sung Hee Choi

    Full Text Available Notch is a major oncogenic driver in T cell acute lymphoblastic leukemia (T-ALL, in part because it binds to an enhancer that increases expression of MYC. Here, we exploit the capacity of activated NOTCH1 and NOTCH3 to induce T-ALL, despite substantial divergence in their intracellular regions, as a means to elucidate a broad, common Notch-dependent oncogenomic program through systematic comparison of the transcriptomes and Notch-bound genomic regulatory elements of NOTCH1- and NOTCH3-dependent T-ALL cells. ChIP-seq studies show a high concordance of functional NOTCH1 and NOTCH3 genomic binding sites that are enriched in binding motifs for RBPJ, the transcription factor that recruits activated Notch to DNA. The interchangeability of NOTCH1 and NOTCH3 was confirmed by rescue of NOTCH1-dependent T-ALL cells with activated NOTCH3 and vice versa. Despite remarkable overall similarity, there are nuanced differences in chromatin landscapes near critical common Notch target genes, most notably at a Notch-dependent enhancer that regulates MYC, which correlates with responsiveness to Notch pathway inhibitors. Overall, a common oncogenomic program driven by binding of either Notch is sufficient to maintain T-ALL cell growth, whereas cell-context specific differences appear to influence the response of T-ALL cells to Notch inhibition.

  12. Inhibitory role of Notch1 in calcific aortic valve disease.

    Directory of Open Access Journals (Sweden)

    Asha Acharya

    Full Text Available Aortic valve calcification is the most common form of valvular heart disease, but the mechanisms of calcific aortic valve disease (CAVD are unknown. NOTCH1 mutations are associated with aortic valve malformations and adult-onset calcification in families with inherited disease. The Notch signaling pathway is critical for multiple cell differentiation processes, but its role in the development of CAVD is not well understood. The aim of this study was to investigate the molecular changes that occur with inhibition of Notch signaling in the aortic valve. Notch signaling pathway members are expressed in adult aortic valve cusps, and examination of diseased human aortic valves revealed decreased expression of NOTCH1 in areas of calcium deposition. To identify downstream mediators of Notch1, we examined gene expression changes that occur with chemical inhibition of Notch signaling in rat aortic valve interstitial cells (AVICs. We found significant downregulation of Sox9 along with several cartilage-specific genes that were direct targets of the transcription factor, Sox9. Loss of Sox9 expression has been published to be associated with aortic valve calcification. Utilizing an in vitro porcine aortic valve calcification model system, inhibition of Notch activity resulted in accelerated calcification while stimulation of Notch signaling attenuated the calcific process. Finally, the addition of Sox9 was able to prevent the calcification of porcine AVICs that occurs with Notch inhibition. In conclusion, loss of Notch signaling contributes to aortic valve calcification via a Sox9-dependent mechanism.

  13. NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells

    Directory of Open Access Journals (Sweden)

    Mauro Di Ianni

    2018-04-01

    Full Text Available To investigate chronic lymphocytic leukemia (CLL-initiating cells, we assessed NOTCH1 mutation/expression in hematopoietic stem cells (HSCs. In NOTCH1-mutated CLL, we detected subclonal mutations in 57% CD34+/CD38− HSCs. NOTCH1 mutation was present in 66% CD34+/CD38+ progenitor cells displaying an increased mutational burden compared to HSCs. Flow cytometric analysis revealed significantly higher NOTCH1 activation in CD34+/CD38− and CD34+/CD38+ cells from CLL patients, regardless NOTCH1 mutation compared to healthy donors. Activated NOTCH1 resulted in overexpression of the NOTCH1 target c-MYC. We conclude that activated NOTCH1 is an early event in CLL that may contribute to aberrant HSCs in this disease.

  14. NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells.

    Science.gov (United States)

    Di Ianni, Mauro; Baldoni, Stefano; Del Papa, Beatrice; Aureli, Patrizia; Dorillo, Erica; De Falco, Filomena; Albi, Elisa; Varasano, Emanuela; Di Tommaso, Ambra; Giancola, Raffaella; Accorsi, Patrizia; Rotta, Gianluca; Rompietti, Chiara; Silva Barcelos, Estevão Carlos; Campese, Antonio Francesco; Di Bartolomeo, Paolo; Screpanti, Isabella; Rosati, Emanuela; Falzetti, Franca; Sportoletti, Paolo

    2018-01-01

    To investigate chronic lymphocytic leukemia (CLL)-initiating cells, we assessed NOTCH1 mutation/expression in hematopoietic stem cells (HSCs). In NOTCH1- mutated CLL, we detected subclonal mutations in 57% CD34+/CD38- HSCs. NOTCH1 mutation was present in 66% CD34+/CD38+ progenitor cells displaying an increased mutational burden compared to HSCs. Flow cytometric analysis revealed significantly higher NOTCH1 activation in CD34+/CD38- and CD34+/CD38+ cells from CLL patients, regardless NOTCH1 mutation compared to healthy donors. Activated NOTCH1 resulted in overexpression of the NOTCH1 target c-MYC. We conclude that activated NOTCH1 is an early event in CLL that may contribute to aberrant HSCs in this disease.

  15. Down-regulation of Notch-1 by γ-secretase inhibitor suppress the ...

    African Journals Online (AJOL)

    Notch-1 signaling is crucial for stem cell maintenance and in a variety of tissues. Previous research has demonstrated that Notch-1 activity plays a key role in prostate tumorigenesis. However, the function of Notch-1 signaling in tumorigenesis can be either oncogene or suppressor gene. In our paper, γ- secretase inhibitor ...

  16. Inhibition of Notch1 increases paclitaxel sensitivity to human breast cancer

    Institute of Scientific and Technical Information of China (English)

    Zhao Li; Ma Yongjie; Gu Feng; Fu Li

    2014-01-01

    Background Paclitaxel (PAC) is the first-line chemotherapy drug for most breast cancer patients,but clinical studies showed that some breast cancer patients were insensitive to PAC,which led to chemotherapy failure.It was reported that Notch1 signaling participated in drug resistance of breast cancer.Here,we show whether Notch1 expression is related to PAC sensitivity of breast cancer.Methods We employed Notch1 siRNA and Notch1 inhibitor,N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester (DAPT),to down regulate Notch1 expression in human breast cancer cells MDA-MB-231,and detected the inhibition effect by Western blotting and reverse trans cription-polymerase chain reaction,respectively.After 24 hours exposure to different concentration of PAC (0,1,5,10,15,20,and 25 μg/ml),the viability of the control group and experimental group cells was tested by MTT.We also examined the expression of Notch1 in PAC sensitive and nonsensitive breast cancer patients,respectively by immunohistochemistry (IHC).The PAC sensitivity of breast cancer patients were identified by collagen gel droplet embedded culture-drug sensitivity test (CD-DST).Results Down regulation of Notch1 expression by Notch1siRNA interference or Notch1 inhibitor increased the PAC sensitivity in MDA-MB-231 cells (P <0.05).Also,the expression of Notch1 in PAC sensitive patients was much lower than that of PAC non-sensitive patients (P <0.01).Conclusion Notch1 expression has an effect on PAC sensitivity in breast cancer patients,and the inhibition of Notch1 increases paclitaxel sensitivity to human breast cancer.

  17. Molecular Characterization of Notch1 Positive Progenitor Cells in the Developing Retina.

    Directory of Open Access Journals (Sweden)

    Galina Dvoriantchikova

    Full Text Available The oscillatory expression of Notch signaling in neural progenitors suggests that both repressors and activators of neural fate specification are expressed in the same progenitors. Since Notch1 regulates photoreceptor differentiation and contributes (together with Notch3 to ganglion cell fate specification, we hypothesized that genes encoding photoreceptor and ganglion cell fate activators would be highly expressed in Notch1 receptor-bearing (Notch1+ progenitors, directing these cells to differentiate into photoreceptors or into ganglion cells when Notch1 activity is diminished. To identify these genes, we used microarray analysis to study expression profiles of whole retinas and isolated from them Notch1+ cells at embryonic day 14 (E14 and postnatal day 0 (P0. To isolate Notch1+ cells, we utilized immunomagnetic cell separation. We also used Notch3 knockout (Notch3KO animals to evaluate the contribution of Notch3 signaling in ganglion cell differentiation. Hierarchical clustering of 6,301 differentially expressed genes showed that Notch1+ cells grouped near the same developmental stage retina cluster. At E14, we found higher expression of repressors (Notch1, Hes5 and activators (Dll3, Atoh7, Otx2 of neuronal differentiation in Notch1+ cells compared to whole retinal cell populations. At P0, Notch1, Hes5, and Dll1 expression was significantly higher in Notch1+ cells than in whole retinas. Otx2 expression was more than thirty times higher than Atoh7 expression in Notch1+ cells at P0. We also observed that retinas of wild type animals had only 14% (P < 0.05 more ganglion cells compared to Notch3KO mice. Since this number is relatively small and Notch1 has been shown to contribute to ganglion cell fate specification, we suggested that Notch1 signaling may play a more significant role in RGC development than the Notch3 signaling cascade. Finally, our findings suggest that Notch1+ progenitors--since they heavily express both pro-ganglion cell (Atoh7

  18. Far infrared promotes wound healing through activation of Notch1 signaling.

    Science.gov (United States)

    Hsu, Yung-Ho; Lin, Yuan-Feng; Chen, Cheng-Hsien; Chiu, Yu-Jhe; Chiu, Hui-Wen

    2017-11-01

    The Notch signaling pathway is critically involved in cell proliferation, differentiation, development, and homeostasis. Far infrared (FIR) has an effect that promotes wound healing. However, the underlying molecular mechanisms are unclear. In the present study, we employed in vivo and HaCaT (a human skin keratinocyte cell line) models to elucidate the role of Notch1 signaling in FIR-promoted wound healing. We found that FIR enhanced keratinocyte migration and proliferation. FIR induced the Notch1 signaling pathway in HaCaT cells and in a microarray dataset from the Gene Expression Omnibus database. We next determined the mRNA levels of NOTCH1 in paired normal and wound skin tissues derived from clinical patients using the microarray dataset and Ingenuity Pathway Analysis software. The result indicated that the Notch1/Twist1 axis plays important roles in wound healing and tissue repair. In addition, inhibiting Notch1 signaling decreased the FIR-enhanced proliferation and migration. In a full-thickness wound model in rats, the wounds healed more rapidly and the scar size was smaller in the FIR group than in the light group. Moreover, FIR could increase Notch1 and Delta1 in skin tissues. The activation of Notch1 signaling may be considered as a possible mechanism for the promoting effect of FIR on wound healing. FIR stimulates keratinocyte migration and proliferation. Notch1 in keratinocytes has an essential role in FIR-induced migration and proliferation. NOTCH1 promotes TWIST1-mediated gene expression to assist wound healing. FIR might promote skin wound healing in a rat model. FIR stimulates keratinocyte migration and proliferation. Notch1 in keratinocytes has an essential role in FIR-induced migration and proliferation. NOTCH1 promotes TWIST1-mediated gene expression to assist wound healing. FIR might promote skin wound healing in a rat model.

  19. Droplet digital PCR analysis of NOTCH1 gene mutations in chronic lymphocytic leukemia.

    Science.gov (United States)

    Minervini, Angela; Francesco Minervini, Crescenzio; Anelli, Luisa; Zagaria, Antonella; Casieri, Paola; Coccaro, Nicoletta; Cumbo, Cosimo; Tota, Giuseppina; Impera, Luciana; Orsini, Paola; Brunetti, Claudia; Giordano, Annamaria; Specchia, Giorgina; Albano, Francesco

    2016-12-27

    In chronic lymphocytic leukemia (CLL), NOTCH1 gene mutations (NOTCH1mut) have been associated with adverse prognostic features but the independence of these as a prognostic factor is still controversial. In our study we validated a c.7541-7542delCT NOTCH1 mutation assay based on droplet digital PCR (ddPCR); we also analyzed the NOTCH1mut allelic burden, expressed as fractional abundance (FA), in 88 CLL patients at diagnosis to assess its prognostic role and made a longitudinal ddPCR analysis in 10 cases harboring NOTCH1mut to verify the FA variation over time. Our data revealed that with the ddPCR approach the incidence of NOTCH1mut in CLL was much higher (53.4%) than expected. However, longitudinal ddPCR analysis of CLL cases showed a statistically significant reduction of the NOTCH1mut FA detected at diagnosis after treatment (median FA 11.67 % vs 0.09 %, respectively, p = 0.01); the same difference, in terms of NOTCH1mut FA, was observed in the relapsed cases compared to the NOTCH1mut allelic fraction observed in patients in complete or partial remission (median FA 4.75% vs 0.43%, respectively, p = 0.007). Our study demonstrated a much higher incidence of NOTCH1mut in CLL than has previously been reported, and showed that the NOTCH1mut allelic burden evaluation by ddPCR might identify patients in need of a closer clinical follow-up during the "watch and wait" interval and after standard chemotherapy.

  20. PI3K/AKT signaling inhibits NOTCH1 lysosome-mediated degradation.

    Science.gov (United States)

    Platonova, Natalia; Manzo, Teresa; Mirandola, Leonardo; Colombo, Michela; Calzavara, Elisabetta; Vigolo, Emilia; Cermisoni, Greta Chiara; De Simone, Daria; Garavelli, Silvia; Cecchinato, Valentina; Lazzari, Elisa; Neri, Antonino; Chiaramonte, Raffaella

    2015-06-06

    The pathways of NOTCH and PI3K/AKT are dysregulated in about 60% and 48% of T-cell acute lymphoblastic leukemia (T-ALL) patients, respectively. In this context, they interact and cooperate in controlling tumor cell biology. Here, we propose a novel mechanism by which the PI3K/AKT pathway regulates NOTCH1 in T-ALL, starting from the evidence that the inhibition of PI3K/AKT signaling induced by treatment with LY294002 or transient transfection with a dominant negative AKT mutant downregulates NOTCH1 protein levels and activity, without affecting NOTCH1 transcription. We showed that the withdrawal of PI3K/AKT signaling was associated to NOTCH1 phosphorylation in tyrosine residues and monoubiquitination of NOTCH1 detected by Ubiquitin capture assay. Co-immunoprecipitation assay and colocalization analysis further showed that the E3 ubiquitin ligase c-Cbl interacts and monoubiquitinates NOTCH1, activating its lysosomal degradation. These results suggest that the degradation of NOTCH1 could represent a mechanism of control by which NOTCH1 receptors are actively removed from the cell surface. This mechanism is finely regulated by the PI3K/AKT pathway in physiological conditions. In pathological conditions characterized by PI3K/AKT hyperactivation, such as T-ALL, the excessive AKT signaling could lead to NOTCH1 signaling dysregulation. Therefore, a therapeutic strategy directed to PI3K/AKT in T-ALL could contemporaneously inhibit the dysregulated NOTCH1 signaling. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  1. Perivascular delivery of Notch 1 siRNA inhibits injury-induced arterial remodeling.

    Directory of Open Access Journals (Sweden)

    Eileen M Redmond

    Full Text Available To determine the efficacy of perivascular delivery of Notch 1 siRNA in preventing injury-induced arterial remodeling.Carotid artery ligation was performed to induce arterial remodeling. After 14 days, morphometric analysis confirmed increased vSMC growth and subsequent media thickening and neointimal formation. Laser capture microdissection, quantitative qRT-PCR and immunoblot analysis of medial tissue revealed a significant increase in Notch1 receptor and notch target gene, Hrt 1 and 2 expression in the injured vessels. Perivascular delivery of Notch 1 siRNA by pluronic gel inhibited the injury-induced increase in Notch 1 receptor and target gene expression when compared to scrambled siRNA controls while concomitantly reducing media thickening and neointimal formation to pre-injury, sham-operated levels. Selective Notch 1 knockdown also reversed the injury-induced inhibition of pro-apoptotic Bax expression while decreasing injury-induced anti-apoptotic Bcl-XL expression to sham-operated control levels. In parallel experiments, proliferative cyclin levels, as measured by PCNA expression, were reversed to sham-operated control levels following selective Notch 1 knockdown.These results suggest that injury-induced arterial remodeling can be successfully inhibited by localized perivascular delivery of Notch 1 siRNA.

  2. Glioma cell fate decisions mediated by Dll1-Jag1-Fringe in Notch1 signaling pathway.

    Science.gov (United States)

    Shi, Xiaofei; Wang, Ruiqi

    2017-09-21

    The Notch family of proteins plays a vital role in determining cell fates, such as proliferation, differentiation, and apoptosis. It has been shown that Notch1 and its ligands, Dll1 and Jag1, are overexpressed in many glioma cell lines and primary human gliomas. The roles of Notch1 in some cancers have been firmly established, and recent data implicate that it plays important roles in glioma cell fate decisions. This paper focuses on devising a specific theoretical framework that incorporates Dll1, Jag1, and Fringe in Notch1 signaling pathway to explore their functional roles of these proteins in glioma cells in the tumorigenesis and progression of human gliomas, and to study how glioma cell fate decisions are modulated by both trans-activation and cis-inhibition. This paper presents a computational model for Notch1 signaling pathway in glioma cells. Based on the bifurcation analysis of the model, we show that how the glioma cell fate decisions are modulated by both trans-activation and cis-inhibition mediated by the Fringe protein, providing insight into the design and control principles of the Notch signaling system and the gliomas. This paper presents a computational model for Notch1 signaling pathway in glioma cells based on intertwined dynamics with cis-inhibition and trans-activation involving the proteins Notch1, Dll1, Jag1, and Fringe. The results show that how the glioma cell fate transitions are performed by the Notch1 signaling. Transition from grade III ∼ IV with significantly high Notch1 to grade I ∼ II with high Notch1, and then to normal cells by repressing the Fringe levels or decreasing the strength of enhancement induced by Fringe.

  3. Roles of Notch1 Signaling in Regulating Satellite Cell Fates Choices and Postnatal Skeletal Myogenesis.

    Science.gov (United States)

    Shan, Tizhong; Xu, Ziye; Wu, Weiche; Liu, Jiaqi; Wang, Yizhen

    2017-11-01

    Adult skeletal muscle stem cells, also called satellite cells, are indispensable for the growth, maintenance, and regeneration of the postnatal skeletal muscle. Satellite cells, predominantly quiescent in mature resting muscles, are activated after skeletal muscle injury or degeneration. Notch1 signaling is an evolutionarily conserved pathway that plays crucial roles in satellite cells homeostasis and postnatal skeletal myogenesis and regeneration. Activation of Notch1 signaling promotes the muscle satellite cells quiescence and proliferation, but inhibits differentiation of muscle satellite cells. Notably, the new roles of Notch1 signaling during late-stage of skeletal myogenesis including in post-differentiation myocytes and post-fusion myotubes have been recently reported. Here, we mainly review and discuss the regulatory roles of Notch1 in regulating satellite cell fates choices and skeletal myogenesis. J. Cell. Physiol. 232: 2964-2967, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. Prognostic value of Notch-1 expression in hepatocellular carcinoma: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Wu T

    2015-10-01

    Full Text Available Tao Wu,1 Min Jiao,1 Li Jing,1 Min-Cong Wang,1 Hai-Feng Sun,2 Qing Li,1 Yi-Yang Bai,1 Yong-Chang Wei,1 Ke-Jun Nan,1 Hui Guo1 1Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, 2Department of Oncology, Shaanxi Cancer Hospital, Xi’an, People’s Republic of China Abstract: Association of Notch-1 expression with prognosis of patients with hepatocellular carcinoma (HCC remains controversial. We conducted a meta-analysis to reevaluate the association of Notch-1 expression with clinicopathological characteristics and prognosis of HCC. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure were searched to look for relevant studies. The association between Notch-1 expression and clinicopathological parameters and overall survival (OS was then reassessed using the meta-analysis for odds ratio (OR or hazard ratio (HR and 95% confidence interval (CI. A total of seven studies, including 810 HCC patients, were eligible for the meta-analysis. Our data showed that high Notch-1 expression was able to predict poor OS (HR 1.50, 95% CI 1.17–1.83, P=0.0001. The pooled OR showed that high Notch-1 expression was significantly associated with tumor metastasis (OR 0.37, 95% CI 0.16–0.86, P=0.02 and tumor size >5 cm (OR 0.48, 95% CI 0.26–0.88, P=0.02. In contrast, there was no association between high Notch-1 expression and tumor differentiation, late TNM stage, tumor number, and portal vein invasion of HCC. In conclusion, Notch-1 overexpression might predict poorer survival and more aggressive behavior in patients with HCC. Keywords: hepatocellular carcinoma, Notch-1, prognosis, clinicopathological features, meta-analysis

  5. Expression of Notch1 Correlates with Breast Cancer Progression and Prognosis.

    Directory of Open Access Journals (Sweden)

    Xun Yuan

    Full Text Available Various studies have evaluated the significance of Notch1 expression in breast cancer, but the results have ever been disputed. By using 21 studies involving 3867 patients, this meta-analysis revealed that the expression of Notch1 was significantly higher in breast cancer than in normal tissues (OR=7.21; 95%CI, 4.7-11.07 and that higher Notch1 expression was associated with transition from ductal carcinoma in situ (DCIS to invasive cancer (OR=3.75; 95% CI, 1.8-7.78. Higher Notch1 activity was observed in the basal subtype of breast cancer (OR=2.53; 95% CI, 1.18-5.43. Moreover, patients with Notch1 overexpression exhibited significantly worse overall and recurrence-free survival. Our meta-analysis suggests that Notch inhibitors may be useful in blocking the early progression of DCIS and that the outcomes of clinical trials for Notch1-targeting therapeutics could be improved by the molecular stratification of breast cancer patients.

  6. The pathological significance of Notch1 in oral squamous cell carcinoma.

    Science.gov (United States)

    Yoshida, Ryoji; Nagata, Masashi; Nakayama, Hideki; Niimori-Kita, Kanako; Hassan, Wael; Tanaka, Takuji; Shinohara, Masanori; Ito, Takaaki

    2013-10-01

    Notch signaling has been reported to be involved in several types of malignant tumors; however, the role and activation mechanism of Notch signaling in oral squamous cell carcinoma (OSCC) remains poorly characterized. The purpose of this study was to elucidate the pathological significance of Notch signaling and its activation mechanism in the development and progression of OSCC. In this study, we showed that the expression of Notch1 and intracellular Notch domain (NICD) are upregulated in OSCCs. In addition, Notch1 and NICD were found to be characteristically localized at the invasive tumor front. TNF-α, a major inflammatory cytokine, significantly activated Notch signaling in vitro. In a clinicopathological analysis, Notch1 expression correlated with both the T-stage and the clinical stage. Furthermore, loss of Notch1 expression correlated with the inhibition of cell proliferation and TNF-α-dependent invasiveness in an OSCC cell line. In addition, γ-secretase inhibitor (GSI) prevented cell proliferation and TNF-α-dependent invasion of OSCC cells in vitro. These results indicate that altered expression of Notch1 is associated with increased cancer progression and that Notch1 regulates the steps involved in cell metastasis in OSCC. Moreover, inactivating Notch signaling with GSI could therefore be a useful approach for treating patients with OSCC.

  7. FOXP3 expression is modulated by TGF-β1/NOTCH1 pathway in human melanoma

    Science.gov (United States)

    Skarmoutsou, Eva; Bevelacqua, Valentina; D'Amico, Fabio; Russo, Angela; Spandidos, Demetrios A.; Scalisi, Aurora

    2018-01-01

    Forkhead box protein 3 (FOXP3) transcription factor is expressed by immune cells and several human cancers and is associated with tumor aggressiveness and unfavorable clinical outcomes. NOTCH and transforming growth factor-β (TGF-β) protumorigenic effects are mediated by FOXP3 expression in several cancer models; however, their interaction and role in melanoma is unknown. We investigated TGF-β-induced FOXP3 gene expression during NOTCH1 signaling inactivation. Primary (WM35) and metastatic melanoma (A375 and A2058) cell lines and normal melanocytes (NHEM) were used. FOXP3 subcellular distribution was evaluated by immuno cytochemical analysis. Gene expression levels were assessed by reverse transcription-quantitative polymerase chain reaction. Protein levels were assessed by western blot analysis. The γ-secretase inhibitor (GSI) was used for NOTCH1 inhibition and recombinant human (rh)TGF-β was used for melanoma cell stimulation. Cell proliferation and viability were respectively assessed by MTT and Trypan blue dye assays. FOXP3 mRNA and protein levels were progressively higher in WM35, A375 and A2058 cell lines compared to NHEM and their levels were further increased after stimulation with rh-TGF-β. TGF-β-mediated FOXP3 expression was mediated by NOTCH1 signaling. Inhibition of NOTCH1 with concomitant rh-TGF-β stimulation determined the reduction in gene expression and protein level of FOXP3. Finally, melanoma cell line proliferation and viability were reduced by NOTCH1 inhibition. The results show that nn increase in FOXP3 expression in metastatic melanoma cell lines is a potential marker of tumor aggressiveness and metastasis. NOTCH1 is a central mediator of TGF-β-mediated FOXP3 expression and NOTCH1 inhibition produces a significant reduction of melanoma cell proliferation and viability. PMID:29620159

  8. Notch1 deficiency in postnatal neural progenitor cells in the dentate gyrus leads to emotional and cognitive impairment.

    Science.gov (United States)

    Feng, Shufang; Shi, Tianyao; Qiu, Jiangxia; Yang, Haihong; Wu, Yan; Zhou, Wenxia; Wang, Wei; Wu, Haitao

    2017-10-01

    It is well known that Notch1 signaling plays a crucial role in embryonic neural development and adult neurogenesis. The latest evidence shows that Notch1 also plays a critical role in synaptic plasticity in mature hippocampal neurons. So far, deeper insights into the function of Notch1 signaling during the different steps of adult neurogenesis are still lacking, and the mechanisms by which Notch1 dysfunction is associated with brain disorders are also poorly understood. In the current study, we found that Notch1 was highly expressed in the adult-born immature neurons in the hippocampal dentate gyrus. Using a genetic approach to selectively ablate Notch1 signaling in late immature precursors in the postnatal hippocampus by cross-breeding doublecortin (DCX) + neuron-specific proopiomelanocortin (POMC)-α Cre mice with floxed Notch1 mice, we demonstrated a previously unreported pivotal role of Notch1 signaling in survival and function of adult newborn neurons in the dentate gyrus. Moreover, behavioral and functional studies demonstrated that POMC-Notch1 -/- mutant mice showed anxiety and depressive-like behavior with impaired synaptic transmission properties in the dentate gyrus. Finally, our mechanistic study showed significantly compromised phosphorylation of cAMP response element-binding protein (CREB) in Notch1 mutants, suggesting that the dysfunction of Notch1 mutants is associated with the disrupted pCREB signaling in postnatally generated immature neurons in the dentate gyrus.-Feng, S., Shi, T., Qiu, J., Yang, H., Wu, Y., Zhou, W., Wang, W., Wu, H. Notch1 deficiency in postnatal neural progenitor cells in the dentate gyrus leads to emotional and cognitive impairment. © FASEB.

  9. Inhibition of fibroblast growth by Notch1 signaling is mediated by induction of Wnt11-dependent WISP-1.

    Directory of Open Access Journals (Sweden)

    Zhao-Jun Liu

    Full Text Available Fibroblasts are an integral component of stroma and important source of growth factors and extracellular matrix (ECM. They play a prominent role in maintaining tissue homeostasis and in wound healing and tumor growth. Notch signaling regulates biological function in a variety of cells. To elucidate the physiological function of Notch signaling in fibroblasts, we ablated Notch1 in mouse (Notch1(Flox/Flox embryonic fibroblasts (MEFs. Notch1-deficient (Notch1(-/- MEFs displayed faster growth and motility rate compared to Notch1(Flox/Flox MEFs. Such phenotypic changes, however, were reversible by reconstitution of Notch1 activation via overexpression of the intracellular domain of Notch1 (NICD1 in Notch1-deficient MEFs. In contrast, constitutive activation of Notch1 signaling by introducing NICD1 into primary human dermal fibroblasts (FF2441, which caused pan-Notch activation, inhibited cell growth and motility, whereas cellular inhibition was relievable when the Notch activation was countered with dominant-negative mutant of Master-mind like 1 (DN-MAML-1. Functionally, "Notch-activated" stromal fibroblasts could inhibit tumor cell growth/invasion. Moreover, Notch activation induced expression of Wnt-induced secreted proteins-1 (WISP-1/CCN4 in FF2441 cells while deletion of Notch1 in MEFs resulted in an opposite effect. Notably, WISP-1 suppressed fibroblast proliferation, and was responsible for mediating Notch1's inhibitory effect since siRNA-mediated blockade of WISP-1 expression could relieve cell growth inhibition. Notch1-induced WISP-1 expression appeared to be Wnt11-dependent, but Wnt1-independent. Blockade of Wnt11 expression resulted in decreased WISP-1 expression and liberated Notch-induced cell growth inhibition. These findings indicated that inhibition of fibroblast proliferation by Notch pathway activation is mediated, at least in part, through regulating Wnt1-independent, but Wnt11-dependent WISP-1 expression.

  10. Epidermal Notch1 recruits RORγ + group 3 innate lymphoid cells to orchestrate normal skin repair

    NARCIS (Netherlands)

    Z. Li (Zhi); T. Hodgkinson (Tom); E.J. Gothard (Elizabeth J.); S. Boroumand (Soulmaz); R. Lamb (Rebecca); I. Cummins (Ian); P. Narang (Priyanka); A. Sawtell (Amy); J. Coles (Jenny); G. Leonov (German); A. Reboldi (Andrea); C.D. Buckley; T. Cupedo (Tom); C. Siebel (Christian); A. Bayat (Ardeshir); M. Coles (Mark); C.A. Ambler (Carrie A.)

    2016-01-01

    textabstractNotch has a well-defined role in controlling cell fate decisions in the embryo and the adult epidermis and immune systems, yet emerging evidence suggests Notch also directs non-cell-autonomous signalling in adult tissues. Here, we show that Notch1 works as a damage response signal.

  11. Notch1 regulates hippocampal plasticity through interaction with the Reelin pathway, glutamatergic transmission and CREB signaling

    Directory of Open Access Journals (Sweden)

    Emanuele eBrai

    2015-11-01

    Full Text Available Notch signaling plays a crucial role in adult brain function such as synaptic plasticity, memory and olfaction. Several reports suggest an involvement of this pathway in neurodegenerative dementia. Yet, to date, the mechanism underlying Notch activity in mature neurons remains unresolved. In this work, we investigate how Notch regulates synaptic potentiation and contributes to the establishment of memory in mice. We observe that Notch1 is a postsynaptic receptor with functional interactions with the Reelin receptor, ApoER2, and the ionotropic receptor, NMDAR. Targeted loss of Notch1 in the hippocampal CA fields affects Reelin signaling by influencing Dab1 expression and impairs the synaptic potentiation achieved through Reelin stimulation. Further analysis indicates that loss of Notch1 affects the expression and composition of the NMDAR but not AMPAR. Glutamatergic signaling is further compromised through downregulation of CamKII and its secondary and tertiary messengers resulting in reduced CREB signaling. Our results identify Notch1 as an important regulator of mechanisms involved in synaptic plasticity and memory formation. These findings emphasize the possible involvement of this signaling receptor in dementia.

  12. Notch1 Signaling Regulates the Th17/Treg Immune Imbalance in Patients with Psoriasis Vulgaris.

    Science.gov (United States)

    Ma, Lei; Xue, HaiBo; Gao, Tianqin; Gao, MeiLan; Zhang, YuJie

    2018-01-01

    To evaluate the regulating effect of Notch1 signaling on Th17/Treg immune imbalance in psoriasis vulgaris (PV). Notch1, Hes-1, ROR γ t, Foxp3, IL-17, and IL-10 mRNA expression, as well as Th17 and Treg cell percentages in peripheral CD4 + T cells, were detected by real-time quantitative RT-PCR and flow cytometry, and serum concentrations of IL-17 and IL-10 were detected by ELISA in 36 PV patients and 32 healthy controls. Additionally, CD4 + T cells from 12 PV patients were treated with γ -secretase inhibitor DAPT, and the above indexes were measured. PV patients presented distinct Th17/Treg immune imbalance and highly expressed Notch1 and Hes-1 mRNA levels, which were positively correlated with psoriasis area and severity index (PASI) and the ratios of Th17/Treg and ROR γ t/Foxp3. DAPT treatment resulted in the obvious downregulation of Th17 cell percentage in cocultured CD4 + T cells, ROR γ t and IL-17 mRNA levels, and IL-17 concentration in cell-free supernatant from cocultured CD4 + T cells of PV patients in a dose-dependent manner, while there was no significant influence on Treg cell percentage, Foxp3, and IL-10 expression, therefore leading to the recovery of Th17/Treg immune imbalance. Notch1 signaling may contribute to the pathogenesis of PV by regulating Th17/Treg immune imbalance.

  13. Identification of a Paralog-Specific Notch1 Intracellular Domain Degron

    Directory of Open Access Journals (Sweden)

    Matthew R. Broadus

    2016-05-01

    Full Text Available Upon Notch pathway activation, the receptor is cleaved to release the Notch intracellular domain (NICD, which translocates to the nucleus to activate gene transcription. Using Xenopus egg extracts, we have identified a Notch1-specific destruction signal (N1-Box. We show that mutations in the N1-Box inhibit NICD1 degradation and that the N1-Box is transferable for the promotion of degradation of heterologous proteins in Xenopus egg extracts and in cultured human cells. Mutation of the N1-Box enhances Notch1 activity in cultured human cells and zebrafish embryos. Human cancer mutations within the N1-Box enhance Notch1 signaling in transgenic zebrafish, highlighting the physiological relevance of this destruction signal. We find that binding of the Notch nuclear factor, CSL, to the N1-Box blocks NICD1 turnover. Our studies reveal a mechanism by which degradation of NICD1 is regulated by the N1-Box to minimize stochastic flux and to establish a threshold for Notch1 pathway activation.

  14. Down-regulation of Notch-1 by γ-secretase inhibitor suppress the ...

    African Journals Online (AJOL)

    ajl yemi

    2011-11-30

    Nov 30, 2011 ... Notch-1 signaling is crucial for stem cell maintenance and in a variety of tissues. Previous ... family of transcription factors (CBF-1/RBP-Jk, Su (h) and. LAG-1) .... prostate stem cell renew and cell differentiation (Chhipa,. 2011).

  15. Role of Notch-1 signaling in ethanol induced PC12 apoptosis | Li ...

    African Journals Online (AJOL)

    Chronic alcoholic dementia has crucial role in progress of neurodegenerative disease and affects a large portion of our aging population. Neuronal cell apoptosis may be a contributing factor of neurodegenerative disease (ND) and Alzheimer's disease (AD). Previous researches have indicated that Notch-1 signaling ...

  16. Role of Notch-1 signaling in ethanol induced PC12 apoptosis

    African Journals Online (AJOL)

    DR. NJ TONUKARI

    2012-04-17

    Apr 17, 2012 ... Key words: Neuronal PC12 cell, neurodegenerative disease, ethanol, Notch-1. INTRODUCTION. Neurodegenerative disorders (ND) such as Alzheimer's disease (AD) and Parkinson's disease (PD) are pro- gressive, age-dependent neurodegenerative disorder affecting the cortex and hippocampus, and ...

  17. Chemotherapeutic treatment is associated with Notch1 induction in cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Kamstrup, Maria R; Biskup, Edyta; Manfè, Valentina

    2017-01-01

    with doxorubicin, etoposide, or gemcitabine compared to chemotherapy alone decreased cell viability by 12, 20, and 26%, respectively (p UVA (PUVA) (in MyLa2000, Hut78, and SeAx) increased the expression of Notch1 family members. Our results...

  18. Constitutively active Notch1 induces growth arrest of HPV-positive cervical cancer cells via separate signaling pathways

    International Nuclear Information System (INIS)

    Talora, Claudio; Cialfi, Samantha; Segatto, Oreste; Morrone, Stefania; Kim Choi, John; Frati, Luigi; Paolo Dotto, Gian; Gulino, Alberto; Screpanti, Isabella

    2005-01-01

    Notch signaling plays a key role in cell-fate determination and differentiation in different organisms and cell types. Several reports suggest that Notch signaling may be involved in neoplastic transformation. However, in primary keratinocytes, Notch1 can function as a tumor suppressor. Similarly, in HPV-positive cervical cancer cells, constitutively active Notch1 signaling was found to cause growth suppression. Activated Notch1 in these cells represses viral E6/E7 expression through AP-1 down-modulation, resulting in increased p53 expression and a block of pRb hyperphosphorylation. Here we show that in cervical cancer cell lines in which Notch1 ability to repress AP-1 activity is impaired, Notch1-enforced expression elicits an alternative pathway leading to growth arrest. Indeed, activated Notch1 signaling suppresses activity of the helix-loop-helix transcription factor E47, via ERK1/2 activation, resulting in inhibition of cell cycle progression. Moreover, we found that RBP-Jκ-dependent Notch signaling is specifically repressed in cervical cancer cells and this repression could provide one such mechanism that needs to be activated for cervical carcinogenesis. Finally, we show that inhibition of endogenous Notch1 signaling, although results in a proliferative advantage, sensitizes cervical cancer cell lines to drug-induced apoptosis. Together, our results provide novel molecular insights into Notch1-dependent growth inhibitory effects, counteracting the transforming potential of HPV

  19. LPL gene expression is associated with poor prognosis in CLL and closely related to NOTCH1 mutations

    DEFF Research Database (Denmark)

    Kristensen, Louise; Kielsgaard Kristensen, Thomas; Abildgaard, Niels

    2016-01-01

    these markers. AIM: To evaluate LPL gene expression together with the well-established prognostic markers of CLL and investigate correlations with more recently identified prognostic markers, NOTCH1 and TP53 mutations. METHODS: On 149 patients LPL gene expression was analyzed by real-time RT-PCR. Exon 34...... of NOTCH1 was PCR amplified and directly sequenced. RESULTS: LPL gene expression could be measured as a categorical variable (LPL+/LPL-) and was associated with time to treatment (p... and new prognostic markers, 3 out of 4 patients, who received treatment within 24 months after diagnosis, were LPL+ (p=0.03). There was a strong correlation between NOTCH1 mutation and LPL+ (p=0.005). The unfavorable prognosis of LPL+ was maintained in CLL with wild-type NOTCH1. CONCLUSIONS: NOTCH1...

  20. Sequential mutations in Notch1, Fbxw7, and Tp53 in radiation-induced mouse thymic lymphomas.

    Science.gov (United States)

    Jen, Kuang-Yu; Song, Ihn Young; Banta, Karl Luke; Wu, Di; Mao, Jian-Hua; Balmain, Allan

    2012-01-19

    T-cell acute lymphoblastic lymphomas commonly demonstrate activating Notch1 mutations as well as mutations or deletions in Fbxw7. However, because Fbxw7 targets Notch1 for degradation, genetic alterations in these genes are expected to be mutually exclusive events in lymphomagenesis. Previously, by using a radiation-induced Tp53-deficient mouse model for T-cell acute lymphoblastic lymphoma, we reported that loss of heterozygosity at the Fbxw7 locus occurs frequently in a Tp53-dependent manner. In the current study, we show that these thymic lymphomas also commonly exhibit activating Notch1 mutations in the proline-glutamic acid-serine-threonine (PEST) domain. Moreover, concurrent activating Notch1 PEST domain mutations and single-copy deletions at the Fbxw7 locus occur with high frequency in the same individual tumors, indicating that these changes are not mutually exclusive events. We further demonstrate that although Notch1 PEST domain mutations are independent of Tp53 status, they are completely abolished in mice with germline Fbxw7 haploinsufficiency. Therefore, Notch1 PEST domain mutations only occur when Fbxw7 expression levels are intact. These data suggest a temporal sequence of mutational events involving these important cancer-related genes, with Notch1 PEST domain mutations occurring first, followed by Fbxw7 deletion, and eventually by complete loss of Tp53.

  1. Luteolin suppresses angiogenesis and vasculogenic mimicry formation through inhibiting Notch1-VEGF signaling in gastric cancer.

    Science.gov (United States)

    Zang, Mingde; Hu, Lei; Zhang, Baogui; Zhu, Zhenglun; Li, Jianfang; Zhu, Zhenggang; Yan, Min; Liu, Bingya

    2017-08-26

    Gastric cancer is a great threat to the health of the people worldwide and lacks effective therapeutic regimens. Luteolin is one of Chinese herbs and presents in many fruits and green plants. In our previous study, we observed that luteolin inhibited cell migration and promoted cell apoptosis in gastric cancer. In the present study, luteolin significantly inhibited tube formation of human umbilical vein endothelial cells (HUVECs) through decreasing cell migration and proliferation of HUVECs in a dose-dependent manner. Vasculogenic mimicry (VM) tubes formed by gastric cancer cells were also inhibited with luteolin treatment. To explore how luteolin inhibited tubes formation, ELISA assay for VEGF was performed. Both of the VEGF secretion from Hs-746T cells and HUVECs were significantly decreased subsequent to luteolin treatment. In addition, cell migration was increased with the interaction between gastric cancer cells and HUVECs in co-culture assays. However, the promoting effects were abolished subsequent to luteolin treatment. Furthermore, luteolin inhibited VEGF secretion through suppressing Notch1 expression in gastric cancer. Overexpression of Notch1 in gastric cancer cells partially rescued the effects on cell migration, proliferation, HUVECs tube formation, and VM formation induced by luteolin treatment. In conclusion, luteolin inhibits angiogenesis and VM formation in gastric cancer through suppressing VEGF secretion dependent on Notch1 expression. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Notch1 is required for hypoxia-induced proliferation, invasion and chemoresistance of T-cell acute lymphoblastic leukemia cells

    Directory of Open Access Journals (Sweden)

    Zou Jie

    2013-01-01

    Full Text Available Abstract Background Notch1 is a potent regulator known to play an oncogenic role in many malignancies including T-cell acute lymphoblastic leukemia (T-ALL. Tumor hypoxia and increased hypoxia-inducible factor-1α (HIF-1α activity can act as major stimuli for tumor aggressiveness and progression. Although hypoxia-mediated activation of the Notch1 pathway plays an important role in tumor cell survival and invasiveness, the interaction between HIF-1α and Notch1 has not yet been identified in T-ALL. This study was designed to investigate whether hypoxia activates Notch1 signalling through HIF-1α stabilization and to determine the contribution of hypoxia and HIF-1α to proliferation, invasion and chemoresistance in T-ALL. Methods T-ALL cell lines (Jurkat, Sup-T1 transfected with HIF-1α or Notch1 small interference RNA (siRNA were incubated in normoxic or hypoxic conditions. Their potential for proliferation and invasion was measured by WST-8 and transwell assays. Flow cytometry was used to detect apoptosis and assess cell cycle regulation. Expression and regulation of components of the HIF-1α and Notch1 pathways and of genes related to proliferation, invasion and apoptosis were assessed by quantitative real-time PCR or Western blot. Results Hypoxia potentiated Notch1 signalling via stabilization and activation of the transcription factor HIF-1α. Hypoxia/HIF-1α-activated Notch1 signalling altered expression of cell cycle regulatory proteins and accelerated cell proliferation. Hypoxia-induced Notch1 activation increased the expression of matrix metalloproteinase-2 (MMP2 and MMP9, which increased invasiveness. Of greater clinical significance, knockdown of Notch1 prevented the protective effect of hypoxia/HIF-1α against dexamethasone-induced apoptosis. This sensitization correlated with losing the effect of hypoxia/HIF-1α on Bcl-2 and Bcl-xL expression. Conclusions Notch1 signalling is required for hypoxia/HIF-1α-induced proliferation

  3. SCL, LMO1 and Notch1 Reprogram Thymocytes into Self-Renewing Cells

    Science.gov (United States)

    Rojas-Sutterlin, Shanti; Herblot, Sabine; Hébert, Josée; Sauvageau, Guy; Lemieux, Sébastien; Lécuyer, Eric; Veiga, Diogo F. T.; Hoang, Trang

    2014-01-01

    The molecular determinants that render specific populations of normal cells susceptible to oncogenic reprogramming into self-renewing cancer stem cells are poorly understood. Here, we exploit T-cell acute lymphoblastic leukemia (T-ALL) as a model to define the critical initiating events in this disease. First, thymocytes that are reprogrammed by the SCL and LMO1 oncogenic transcription factors into self-renewing pre-leukemic stem cells (pre-LSCs) remain non-malignant, as evidenced by their capacities to generate functional T cells. Second, we provide strong genetic evidence that SCL directly interacts with LMO1 to activate the transcription of a self-renewal program coordinated by LYL1. Moreover, LYL1 can substitute for SCL to reprogram thymocytes in concert with LMO1. In contrast, inhibition of E2A was not sufficient to substitute for SCL, indicating that thymocyte reprogramming requires transcription activation by SCL-LMO1. Third, only a specific subset of normal thymic cells, known as DN3 thymocytes, is susceptible to reprogramming. This is because physiological NOTCH1 signals are highest in DN3 cells compared to other thymocyte subsets. Consistent with this, overexpression of a ligand-independent hyperactive NOTCH1 allele in all immature thymocytes is sufficient to sensitize them to SCL-LMO1, thereby increasing the pool of self-renewing cells. Surprisingly, hyperactive NOTCH1 cannot reprogram thymocytes on its own, despite the fact that NOTCH1 is activated by gain of function mutations in more than 55% of T-ALL cases. Rather, elevating NOTCH1 triggers a parallel pathway involving Hes1 and Myc that dramatically enhances the activity of SCL-LMO1 We conclude that the acquisition of self-renewal and the genesis of pre-LSCs from thymocytes with a finite lifespan represent a critical first event in T-ALL. Finally, LYL1 and LMO1 or LMO2 are co-expressed in most human T-ALL samples, except the cortical T subtype. We therefore anticipate that the self-renewal network

  4. Medial/skeletal linking structures for multi-region configurations

    CERN Document Server

    Damon, James

    2018-01-01

    The authors consider a generic configuration of regions, consisting of a collection of distinct compact regions \\{ \\Omega_i\\} in \\mathbb{R}^{n+1} which may be either regions with smooth boundaries disjoint from the others or regions which meet on their piecewise smooth boundaries \\mathcal{B}_i in a generic way. They introduce a skeletal linking structure for the collection of regions which simultaneously captures the regions' individual shapes and geometric properties as well as the "positional geometry" of the collection. The linking structure extends in a minimal way the individual "skeletal structures" on each of the regions. This allows the authors to significantly extend the mathematical methods introduced for single regions to the configuration of regions.

  5. FBXW7 and NOTCH1 mutations in childhood T cell acute lymphoblastic leukaemia and T cell non-Hodgkin lymphoma.

    Science.gov (United States)

    Park, Myoung-Ja; Taki, Tomohiko; Oda, Megumi; Watanabe, Tomoyuki; Yumura-Yagi, Keiko; Kobayashi, Ryoji; Suzuki, Nobuhiro; Hara, Junichi; Horibe, Keizo; Hayashi, Yasuhide

    2009-04-01

    Mutation analysis of FBXW7 and NOTCH1 genes was performed in 55 T cell acute lymphoblastic leukaemia (T-ALL) and 14 T cell non-Hodgkin lymphoma (T-NHL) patients who were treated on the Japan Association of Childhood Leukaemia Study (JACLS) protocols ALL-97 and NHL-98. FBXW7 and/or NOTCH1 mutations were found in 22 (40.0%) of 55 T-ALL and 7 (50.0%) of 14 T-NHL patients. FBXW7 mutations were found in 8 (14.6%) of 55 T-ALL and 3 (21.4%) of 14 T-NHL patients, and NOTCH1 mutations in 17 (30.9%) of 55 T-ALL and 6 (42.9%) of 14 T-NHL patients. Three (5.4%) T-ALL and two (1.4%) T-NHL patients had mutations in both FBXW7 and NOTCH1. FBXW7 mutations included one insertion, one deletion, one deletion/insertion and nine missense mutations. NOTCH1 mutations were detected in the heterodimerization domain (HD) in 15 cases, in the PEST domain in seven cases, and in both the HD and PEST domains in one case. Five-year event-free survival and overall survival for patients with FBXW7 and/or NOTCH1 mutations were 95.5% (95% CI, 71.9-99.4%) and 100% respectively, suggesting that T-ALL patients with FBXW7 and/or NOTCH1 mutation represent a good prognosis compared to those without FBXW7 and/or NOTCH1 mutations (63.6%, P = 0.007 and 78.8%, P = 0.023, respectively).

  6. Notch1 is a 5-fluorouracil resistant and poor survival marker in human esophagus squamous cell carcinomas.

    Directory of Open Access Journals (Sweden)

    Jian Liu

    Full Text Available Notch signaling involves the processes that govern cell proliferation, cell fate decision, cell differentiation and stem cell maintenance. Due to its fundamental role in stem cells, it has been speculated during the recent years that Notch family may have critical functions in cancer stem cells or cancer cells with a stem cell phenotype, therefore playing an important role in the process of oncogenesis. In this study, expression of Notch family in KYSE70, KYSE140 and KYSE450 squamous esophageal cancer cell lines and virus transformed squamous esophageal epithelial cell line Het-1A was examined by quantitative RT-PCR. Compared to the Het-1A cells, higher levels of Nocth1 and Notch3 expression in the cancer cell lines were identified. Due to the finding that NOTCH3 mainly mediates squamous cell differentiation, NOTCH1 expression was further studied in these cell lines. By Western blot analyses, the KYSE70 cell line which derived from a poorly differentiated tumor highly expressed Notch1, and the Notch1 expression in this cell line was hypoxia inducible, while the KYSE450 cell line which derived from a well differentiated tumor was always negative for Notch1, even in hypoxia. Additional studies demonstrated that the KYSE70 cell line was more 5-FU resistant than the KYSE450 cell line and such 5-FU resistance is correlated to Notch1 expression verified by Notch1 knockdown experiments. In clinical samples, Notch1 protein expression was detected in the basal cells of human esophagus epithelia, and its expression in squamous cell carcinomas was significantly associated with higher pathological grade and shorter overall survival. We conclude that Notch1 expression is associated with cell aggressiveness and 5-FU drug resistance in human esophageal squamous cell carcinoma cell lines in vitro and is significantly associated with a poor survival in human esophageal squamous cell carcinomas.

  7. Intracellular-activated Notch1 can reactivate Kaposi's sarcoma-associated herpesvirus from latency

    International Nuclear Information System (INIS)

    Lan, Ke; Murakami, Masanao; Choudhuri, Tathagata; Kuppers, Daniel A.; Robertson, Erle S.

    2006-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) establishes a predominantly latent infection in the infected host. Importantly, during latency, only a small number of viral encoded genes are expressed. This viral gene expression pattern contributes to the establishment of long-term infection as well as the ability of the virus to evade the immune system. Previous studies have been shown that the replication and transcription activator (RTA) encoded by ORF50 activates it downstream genes and initiates viral lytic reactivation through functional interaction with RBP-Jκ, the major downstream effector of the Notch signaling pathway. This indicates that RTA can usurp the conserved Notch signaling pathway and mimic the activities of intracellular Notch1 to modulate gene expression. In this report, we show that the activated intracellular domain of Notch1 (ICN) is aberrantly accumulated in KSHV latently infected pleural effusion lymphoma (PEL) cells. ICN activated the RTA promoter in a dose-dependent manner, and forced expression of ICN in latently infected KSHV-positive cells initiated full blown lytic replication with the production of infectious viral progeny. However, latency-associated nuclear antigen (LANA) which is predominantly expressed during latency can specifically down-modulate ICN-mediated transactivation of RTA and so control KSHV for lytic reactivation. These results demonstrate that LANA can inhibit viral lytic replication by antagonizing ICN function and suggest that LANA is a critical component of the regulatory control mechanism for switching between viral latent and lytic replication by directly interacting with effectors of the conserved cellular Notch1 pathway

  8. Identification of a Paralog-Specific Notch1 Intracellular Domain Degron

    OpenAIRE

    Broadus, Matthew R.; Chen, Tony W.; Neitzel, Leif R.; Ng, Victoria H.; Jodoin, Jeanne; Lee, Laura A.; Salic, Adrian; Robbins, David J.; Capobianco, Anthony J.; Patton, James G.; Huppert, Stacey S.; Lee, Ethan

    2016-01-01

    Upon Notch pathway activation, the receptor is cleaved to release the Notch intracellular domain (NICD), which translocates to the nucleus to activate gene transcription. Using Xenopus egg extracts, we have identified a Notch1-specific destruction signal (N1-Box). We show that mutations in the N1-Box inhibit NICD1 degradation and that the N1-Box is transferable for the promotion of degradation of heterologous proteins in Xenopus egg extracts and in cultured human cells. Mutation of the N1-Box...

  9. The Research Progress of SiRNA Targeting Notch1 on Tumor Cells: A Mini Review of the State of the Art

    Directory of Open Access Journals (Sweden)

    Lanfen Huo

    2016-09-01

    Full Text Available Notch signaling is a highly conserved signaling pathway, playing an important role in a variety of cell differentiation, development and regulation. Notch signaling includes Notch1-4; Notch1 gene encodes Notch1 signaling that can shorten cell cycle, enhance cell proliferation, inhibit cell differentiation, and promote apoptosis. Mutation and overexpression of the Notch1 gene may induce tumorigenesis, which plays an important role in the development of tumors across a variety of signaling pathways. Currently, using RNA interference technology (RNAi synthesizing small interference RNA (siRNA targeting Notch1 gene(siNotch1)has become a hot topic, and clinical application of gene silencing has also obtained a certain therapeutic effect. In this paper, the application of Notch1 gene silencing in tumor progress was reviewed.

  10. NADPH Oxidase 1 Modulates WNT and NOTCH1 Signaling To Control the Fate of Proliferative Progenitor Cells in the Colon▿

    Science.gov (United States)

    Coant, Nicolas; Ben Mkaddem, Sanae; Pedruzzi, Eric; Guichard, Cécile; Tréton, Xavier; Ducroc, Robert; Freund, Jean-Noel; Cazals-Hatem, Dominique; Bouhnik, Yoram; Woerther, Paul-Louis; Skurnik, David; Grodet, Alain; Fay, Michèle; Biard, Denis; Lesuffleur, Thécla; Deffert, Christine; Moreau, Richard; Groyer, André; Krause, Karl-Heinz; Daniel, Fanny; Ogier-Denis, Eric

    2010-01-01

    The homeostatic self-renewal of the colonic epithelium requires coordinated regulation of the canonical Wnt/β-catenin and Notch signaling pathways to control proliferation and lineage commitment of multipotent stem cells. However, the molecular mechanisms by which the Wnt/β-catenin and Notch1 pathways interplay in controlling cell proliferation and fate in the colon are poorly understood. Here we show that NADPH oxidase 1 (NOX1), a reactive oxygen species (ROS)-producing oxidase that is highly expressed in colonic epithelial cells, is a pivotal determinant of cell proliferation and fate that integrates Wnt/β-catenin and Notch1 signals. NOX1-deficient mice reveal a massive conversion of progenitor cells into postmitotic goblet cells at the cost of colonocytes due to the concerted repression of phosphatidylinositol 3-kinase (PI3K)/AKT/Wnt/β-catenin and Notch1 signaling. This conversion correlates with the following: (i) the redox-dependent activation of the dual phosphatase PTEN, causing the inactivation of the Wnt pathway effector β-catenin, and (ii) the downregulation of Notch1 signaling that provokes derepression of mouse atonal homolog 1 (Math1) expression. We conclude that NOX1 controls the balance between goblet and absorptive cell types in the colon by coordinately modulating PI3K/AKT/Wnt/β-catenin and Notch1 signaling. This finding provides the molecular basis for the role of NOX1 in cell proliferation and postmitotic differentiation. PMID:20351171

  11. Constitutively active Notch1 converts cranial neural crest-derived frontonasal mesenchyme to perivascular cells in vivo

    Directory of Open Access Journals (Sweden)

    Sophie R. Miller

    2017-03-01

    Full Text Available Perivascular/mural cells originate from either the mesoderm or the cranial neural crest. Regardless of their origin, Notch signalling is necessary for their formation. Furthermore, in both chicken and mouse, constitutive Notch1 activation (via expression of the Notch1 intracellular domain is sufficient in vivo to convert trunk mesoderm-derived somite cells to perivascular cells, at the expense of skeletal muscle. In experiments originally designed to investigate the effect of premature Notch1 activation on the development of neural crest-derived olfactory ensheathing glial cells (OECs, we used in ovo electroporation to insert a tetracycline-inducible NotchΔE construct (encoding a constitutively active mutant of mouse Notch1 into the genome of chicken cranial neural crest cell precursors, and activated NotchΔE expression by doxycycline injection at embryonic day 4. NotchΔE-targeted cells formed perivascular cells within the frontonasal mesenchyme, and expressed a perivascular marker on the olfactory nerve. Hence, constitutively activating Notch1 is sufficient in vivo to drive not only somite cells, but also neural crest-derived frontonasal mesenchyme and perhaps developing OECs, to a perivascular cell fate. These results also highlight the plasticity of neural crest-derived mesenchyme and glia.

  12. Potential involvement of Notch1 signalling in the pathogenesis of primary cutaneous CD30-positive lymphoproliferative disorders

    DEFF Research Database (Denmark)

    Kamstrup, M.R.; Ralfkiaer, E.; Skovgaard, G.L.

    2008-01-01

    Background The central role of Notch signalling in T-cell development and oncogenesis raises the question of the importance of this pathway in cutaneous T-cell lymphomas. Objectives To investigate the pattern of expression of Notch and its ligands, Jagged and Delta, in skin samples of primary...... obtained from three patients with LyP and two patients with primary cutaneous ALCL. Results We identified single Notch1-positive cells or small clusters of atypical cells in LyP. Similarly, strongly positive Jagged1 cells tended to be localized in clusters. Primary cutaneous ALCL had higher expression...... of Notch1 and Jagged1 compared with LyP. Cells expressing Notch1 and Jagged1 were colocalized and a subset of cells expressed both the receptor and the ligand. The expression of the ligand Delta1 was low to undetectable in both types of lymphoproliferations. A subpopulation of lymphoma cells was found...

  13. Angiogenesis-related protein expression in bevacizumab-treated metastatic colorectal cancer: NOTCH1 detrimental to overall survival

    International Nuclear Information System (INIS)

    Paiva, Tadeu Ferreira Jr.; Jesus, Victor Hugo Fonseca de; Marques, Raul Amorim; Costa, Alexandre André Balieiro Anastácio da; Macedo, Mariana Petaccia de; Peresi, Patricia Maria; Damascena, Aline; Rossi, Benedito Mauro; Begnami, Maria Dirlei; Lima, Vladmir Cláudio Cordeiro de

    2015-01-01

    The development of targeted therapies has undoubtedly broadened therapeutic options for patients with colorectal cancer (CRC). The use of bevacizumab to reduce angiogenesis has been associated with improved clinical outcomes. However, an urgent need for prognostic/predictive biomarkers for anti-angiogenic therapies still exists. Clinical data of 105 CRC patients treated with bevacizumab in conjunction with chemotherapy were analyzed. The expression of vascular endothelial growth factor (VEGF) receptors, NOTCH1 receptor and its ligand DLL4 were determined by immunohistochemistry. Tumor samples were arranged on a tissue microarray. The association between protein expression and clinicopathological characteristics and outcomes was determined. Bevacizumab was administered as a first-line of treatment in 70.5 % of our cases. The median progression-free survival (PFS) was 10.2 months. The median overall survival (OS) of the total cohort was 24.4 months. Bevacizumab, as the first-line of treatment, and the presence of liver metastasis were independently associated with objective response rate. Membrane VEGFR1 and VEGFR3 expressions were associated with the presence of lung metastasis; interestingly, VEGFR3 was associated with less liver metastasis. NOTCH1 expression was associated with lymph node metastasis. There was a trend toward association between improved PFS and lower NOTCH1 expression (p = 0.06). Improved OS was significantly associated with lower NOTCH1 expression (p = 0.01). In a multivariate analysis, ECOG (Eastern Cooperative Oncology Group) performance status, liver metastasis, histological grade, and NOTCH1 expression were independently associated with OS. Our findings illustrated the expression profile of angiogenesis-related proteins and their association with clinicopathological characteristics and outcomes. NOTCH1 expression is a detrimental prognostic factor in metastatic CRC patients treated with chemotherapy plus bevacizumab. The online version of

  14. Induced pluripotent stem cells with NOTCH1 gene mutation show impaired differentiation into smooth muscle and endothelial cells: Implications for bicuspid aortic valve-related aortopathy.

    Science.gov (United States)

    Jiao, Jiao; Tian, Weihua; Qiu, Ping; Norton, Elizabeth L; Wang, Michael M; Chen, Y Eugene; Yang, Bo

    2018-03-12

    The NOTCH1 gene mutation has been identified in bicuspid aortic valve patients. We developed an in vitro model with human induced pluripotent stem cells (iPSCs) to evaluate the role of NOTCH1 in smooth muscle and endothelial cell (EC) differentiation. The iPSCs were derived from a patient with a normal tricuspid aortic valve and aorta. The NOTCH1 gene was targeted in iPSCs with the Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9 nuclease (Cas9) system. The NOTCH1 -/- (NOTCH1 homozygous knockout) and isogenic control iPSCs (wild type) were differentiated into neural crest stem cells (NCSCs) and into cardiovascular progenitor cells (CVPCs). The NCSCs were differentiated into smooth muscle cells (SMCs). The CVPCs were differentiated into ECs. The differentiations of SMCs and ECs were compared between NOTCH1 -/- and wild type cells. The expression of NCSC markers (SRY-related HMG-box 10 and transcription factor AP-2 alpha) was significantly lower in NOTCH1 -/- NCSCs than in wild type NCSCs. The SMCs derived from NOTCH1 -/- NCSCs showed immature morphology with smaller size and decreased expression of all SMC-specific contractile proteins. In NOTCH1 -/- CVPCs, the expression of ISL1, NKX2.5, and MYOCD was significantly lower than that in isogenic control CVPCs, indicating impaired differentiation from iPSCs to CVPCs. The NOTCH1 -/- ECs derived from CVPCs showed significantly lower expression of cluster of differentiation 105 and cluster of differentiation 31 mRNA and protein, indicating a defective differentiation process. NOTCH1 is critical in SMC and EC differentiation of iPSCs through NCSCs and CVPCs, respectively. NOTCH1 gene mutations might potentially contribute to the development of thoracic aortic aneurysms by affecting SMC differentiation in some patients with bicuspid aortic valve. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  15. β-Elemene-Attenuated Tumor Angiogenesis by Targeting Notch-1 in Gastric Cancer Stem-Like Cells

    Directory of Open Access Journals (Sweden)

    Bing Yan

    2013-01-01

    Full Text Available Emerging evidence suggests that cancer stem cells are involved in tumor angiogenesis. The Notch signaling pathway is one of the most important regulators of these processes. β-Elemene, a naturally occurring compound extracted from Curcumae Radix, has been used as an antitumor drug for various cancers in China. However, its underlying mechanism in the treatment of gastric cancer remains largely unknown. Here, we report that CD44+ gastric cancer stem-like cells (GCSCs showed enhanced proliferation capacity compared to their CD44− counterparts, and this proliferation was accompanied by the high expression of Notch-1 (in vitro. These cells were also more superior in spheroid colony formation (in vitro and tumorigenicity (in vivo and positively associated with microvessel density (in vivo. β-Elemene was demonstrated to effectively inhibit the viability of GCSCs in a dose-dependent manner, most likely by suppressing Notch-1 (in vitro. β-Elemene also contributed to growth suppression and attenuated the angiogenesis capacity of these cells (in vivo most likely by interfering with the expression of Notch-1 but not with Dll4. Our findings indicated that GCSCs play an important role in tumor angiogenesis, and Notch-1 is one of the most likely mediators involved in these processes. β-Elemene was effective at attenuating angiogenesis by targeting the GCSCs, which could be regarded as a potential mechanism for its efficacy in gastric cancer management in the future.

  16. 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.

  17. Linking regional stakeholder scenarios and shared socioeconomic pathways

    DEFF Research Database (Denmark)

    Palazzo, Amanda; Vervoort, Joost M.; Mason-D'Croz, Daniel

    2017-01-01

    levels, they have to be connected to an exploration of drivers and challenges informed by regional expertise.In this paper, we present scenarios for West Africa developed by regional stakeholders and quantified using two global economic models, GLOBIOM and IMPACT, in interaction with stakeholder......-generated narratives and scenario trends and SSP assumptions. We present this process as an example of linking comparable scenarios across levels to increase coherence with global contexts, while presenting insights about the future of agriculture and food security under a range of future drivers including climate...... change.In these scenarios, strong economic development increases food security and agricultural development. The latter increases crop and livestock productivity leading to an expansion of agricultural area within the region while reducing the land expansion burden elsewhere. In the context of a global...

  18. Notch1 Mediates Preconditioning Protection Induced by GPER in Normotensive and Hypertensive Female Rat Hearts

    Directory of Open Access Journals (Sweden)

    Carmine Rocca

    2018-05-01

    Full Text Available G protein-coupled estrogen receptor (GPER is an estrogen receptor expressed in the cardiovascular system. G1, a selective GPER ligand, exerts cardiovascular effects through activation of the PI3K-Akt pathway and Notch signaling in normotensive animals. Here, we investigated whether the G1/GPER interaction is involved in the limitation of infarct size, and improvement of post-ischemic contractile function in female spontaneous hypertensive rat (SHR hearts. In this model, we also studied Notch signaling and key components of survival pathway, namely PI3K-Akt, nitric oxide synthase (NOS and mitochondrial K+-ATP (MitoKATP channels. Rat hearts isolated from female SHR underwent 30 min of global, normothermic ischemia and 120 min of reperfusion. G1 (10 nM alone or specific inhibitors of GPER, PI3K/NOS and MitoKATP channels co-infused with G1, just before I/R, were studied. The involvement of Notch1 was studied by Western blotting. Infarct size and left ventricular pressure were measured. To confirm endothelial-independent G1-induced protection by Notch signaling, H9c2 cells were studied with specific inhibitor, N-[N-(3,5 difluorophenacetyl-L-alanyl]-S-phenylglycine t-butyl ester (DAPT, 5 μM, of this signaling. Using DAPT, we confirmed the involvement of G1/Notch signaling in limiting infarct size in heart of normotensive animals. In the hypertensive model, G1-induced reduction in infarct size and improvement of cardiac function were prevented by the inhibition of GPER, PI3K/NOS, and MitoKATP channels. The involvement of Notch was confirmed by western blot in the hypertensive model and by the specific inhibitor in the normotensive model and cardiac cell line. Our results suggest that GPERs play a pivotal role in mediating preconditioning cardioprotection in normotensive and hypertensive conditions. The G1-induced protection involves Notch1 and is able to activate the survival pathway in the presence of comorbidity. Several pathological conditions

  19. Inhibition of Notch1 promotes hedgehog signalling in a HES1-dependent manner in chondrocytes and exacerbates experimental osteoarthritis.

    Science.gov (United States)

    Lin, Neng-Yu; Distler, Alfiya; Beyer, Christian; Philipi-Schöbinger, Ariella; Breda, Silvia; Dees, Clara; Stock, Michael; Tomcik, Michal; Niemeier, Andreas; Dell'Accio, Francesco; Gelse, Kolja; Mattson, Mark P; Schett, Georg; Distler, Jörg Hw

    2016-11-01

    Notch ligands and receptors have recently been shown to be differentially expressed in osteoarthritis (OA). We aim to further elucidate the functional role of Notch signalling in OA using Notch1 antisense transgenic (Notch1 AS) mice. Notch and hedgehog signalling were analysed by real-time PCR and immunohistochemistry. Notch-1 AS mice were employed as a model of impaired Notch signalling in vivo. Experimental OA was induced by destabilisation of the medial meniscus (DMM). The extent of cartilage destruction and osteophyte formation was analysed by safranin-O staining with subsequent assessment of the Osteoarthritis Research Society International (OARSI) and Mankin scores and µCT scanning. Collagen X staining was used as a marker of chondrocyte hypertrophy. The role of hairy/enhancer of split 1 (Hes-1) was investigated with knockdown and overexpression experiments. Notch signalling was activated in human and murine OA with increased expression of Jagged1, Notch-1, accumulation of the Notch intracellular domain 1 and increased transcription of Hes-1. Notch1 AS mice showed exacerbated OA with increases in OARSI scores, osteophyte formation, increased subchondral bone plate density, collagen X and osteocalcin expression and elevated levels of Epas1 and ADAM-TS5 mRNA. Inhibition of the Notch pathway induced activation of hedgehog signalling with induction of Gli-1 and Gli-2 and increased transcription of hedgehog target genes. The regulatory effects of Notch signalling on Gli-expression were mimicked by Hes-1. Inhibition of Notch signalling activates hedgehog signalling, enhances chondrocyte hypertrophy and exacerbates experimental OA including osteophyte formation. These data suggest that the activation of the Notch pathway may limit aberrant hedgehog signalling in OA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  20. Cardiovascular malformations caused by NOTCH1 mutations do not keep left : data on 428 probands with left-sided CHD and their families

    NARCIS (Netherlands)

    Kerstjens-Frederikse, Wilhelmina S.; van de Laar, Ingrid M. B. H.; Vos, Yvonne J.; Verhagen, Judith M. A.; Berger, Rolf M. F.; Lichtenbelt, Klaske D.; Wassink-Ruiter, Jolien S. Klein; van der Zwaag, Paul A.; Sarvaas, Gideon J. du Marchie; Bergman, Klasien A.; Bilardo, Catia M.; Roos-Hesselink, Jolien W.; Janssen, Johan H. P.; Frohn-Mulder, Ingrid M.; van Spaendonck-Zwarts, Karin Y.; Melle, van Joost P.; Hofstra, Robert M. W.; Wessels, M. W.

    Purpose: We aimed to determine the prevalence and phenotypic spectrum of NOTCH1 mutations in left-sided congenital heart disease (LS-CHD). LS-CHD includes aortic valve stenosis, a bicuspid aortic valve, coarctation of the aorta, and hypoplastic left heart syndrome. Methods: NOTCH1 was screened for

  1. Interactions of Notch1 and TLR4 signaling pathways in DRG neurons of in vivo and in vitro models of diabetic neuropathy.

    Science.gov (United States)

    Chen, Tianhua; Li, Hao; Yin, Yiting; Zhang, Yuanpin; Liu, Zhen; Liu, Huaxiang

    2017-11-02

    Understanding the interactions between Notch1 and toll-like receptor 4 (TLR4) signaling pathways in the development of diabetic peripheral neuropathy may lead to interpretation of the mechanisms and novel approaches for preventing diabetic neuropathic pain. In the present study, the interactions between Notch1 and TLR4 signaling pathways were investigated by using dorsal root ganglion (DRG) from diabetic neuropathic pain rats and cultured DRG neurons under high glucose challenge. The results showed that high glucose induced not only Notch1 mRNA, HES1 mRNA, and TLR4 mRNA expression, but also Notch1 intracellular domain (NICD1) and TLR4 protein expression in DRG neurons. The proportion of NICD1-immunoreactive (IR) and TLR4-IR neurons in DRG cultures was also increased after high glucose challenge. The above alterations could be partially reversed by inhibition of either Notch1 or TLR4 signaling pathway. Inhibition of either Notch1 or TLR4 signaling pathway could improve mechanical allodynia and thermal hyperalgesia thresholds. Inhibition of Notch1 or TLR4 signaling also decreased tumor necrosis factor-α (TNF-α) levels in DRG from diabetic neuropathic rats. These data imply that the interaction between Notch1 and TLR4 signaling pathways is one of the important mechanisms in the development or progression of diabetic neuropathy.

  2. Notch3 is dispensable for thymocyte β-selection and Notch1-induced T cell leukemogenesis.

    Directory of Open Access Journals (Sweden)

    Sara Suliman

    Full Text Available Notch1 (N1 signaling induced by intrathymic Delta-like (DL ligands is required for T cell lineage commitment as well as self-renewal during "β-selection" of TCRβ⁺CD4⁻CD8⁻ double negative 3 (DN3 T cell progenitors. However, over-expression of the N1 intracellular domain (ICN1 renders N1 activation ligand-independent and drives leukemic transformation during β-selection. DN3 progenitors also express Notch3 (N3 mRNA, and over-expression of ligand-independent mutant N3 (ICN3 influences β-selection and drives T cell leukemogenesis. However, the importance of ligand-activated N3 in promoting β-selection and ICN1-induced T cell leukemogenesis has not been examined. To address these questions we generated mice lacking functional N3. We confirmed that DN3 progenitors express N3 protein using a N3-specific antibody. Surprisingly however, N3-deficient DN3 thymocytes were not defective in generating DP thymocytes under steady state conditions or in more stringent competition assays. To determine if N3 co-operates with N1 to regulate β-selection, we generated N1;N3 compound mutants. However, N3 deficiency did not exacerbate the competitive defect of N1⁺/⁻ DN3 progenitors, demonstrating that N3 does not compensate for limiting N1 during T cell development. Finally, N3 deficiency did not attenuate T cell leukemogenesis induced by conditional expression of ICN1 in DN3 thymocytes. Importantly, we showed that in contrast to N1, N3 has a low binding affinity for DL4, the most abundant intrathymic DL ligand. Thus, despite the profound effects of ectopic ligand-independent N3 activation on T cell development and leukemogenesis, physiologically activated N3 is dispensable for both processes, likely because N3 interacts poorly with intrathymic DL4.

  3. MicroRNA-101 regulates T-cell acute lymphoblastic leukemia progression and chemotherapeutic sensitivity by targeting Notch1.

    Science.gov (United States)

    Qian, Lu; Zhang, Wanggang; Lei, Bo; He, Aili; Ye, Lianhong; Li, Xingzhou; Dong, Xin

    2016-11-01

    The present study aimed to investigate the role of microRNA (miR)-101 in acute lymphoblastic leukemia progression and chemoresistance. Furthermore, a novel target gene of miR-101 was identified. Here, we confirmed that miR-101 was significantly downregulated in the blood samples of patients with T-cell acute lymphoblastic leukemia (T-ALL) compared with the healthy controls, as determined by reverse transcription quantitative polymerase chain reaction (RTqPCR) analysis. The in vitro experiments demonstrated that miR-101 significantly repressed the proliferation and invasion, and induced potent apoptosis in Jurkat cells, as determined by CCK-8, flow cytometer and cell invasion assays. Luciferase assay confirmed that Notch1 was a target gene of miR-101, and western blotting showed that miR-101 suppressed the expression of Notch1 at the protein level. Moreover, functional restoration assays revealed that Notch1 mediates the effects of miR-101 on Jurkat cell proliferation, apoptosis and invasion. miR-101 enhanced the sensitivity of Jurkat cells to the chemotherapeutic agent adriamycin. Taken together, our results show for the first time that miR-101 acts as a tumor suppressor in T-cell acute lymphoblastic leukaemia and it could enhance chemotherapeutic sensitivity. Furthermore, Notch1 was identified to be a novel target of miR-101. This study indicates that miR-101 may represent a potential therapeutic target for T-cell acute lymphoblastic leukemia intervention.

  4. The jagged-2/notch-1/hes-1 pathway is involved in intestinal epithelium regeneration after intestinal ischemia-reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Guoqing Chen

    Full Text Available Notch signaling plays a critical role in the maintenance of intestinal crypt epithelial cell proliferation. The aim of this study was to investigate the role of Notch signaling in the proliferation and regeneration of intestinal epithelium after intestinal ischemia reperfusion (I/R injury.Male Sprague-Dawley rats were subjected to sham operation or I/R by occlusion of the superior mesenteric artery (SMA for 20 min. Intestinal tissue samples were collected at 0, 1, 2, 4, and 6 h after reperfusion. Proliferation of the intestinal epithelium was evaluated by immunohistochemical staining of proliferating nuclear antigen (PCNA. The mRNA and protein expression levels of Notch signaling components were examined using Real-time PCR and Western blot analyses. Immunofluorescence was also performed to detect the expression and location of Jagged-2, cleaved Notch-1, and Hes-1 in the intestine. Finally, the γ-secretase inhibitor DAPT and the siRNA for Jagged-2 and Hes-1 were applied to investigate the functional role of Notch signaling in the proliferation of intestinal epithelial cells in an in vitro IEC-6 culture system.I/R injury caused increased intestinal crypt epithelial cell proliferation and increased mRNA and protein expression of Jagged-2, Notch-1, and Hes-1. The immunofluorescence results further confirmed increased protein expression of Jagged-2, cleaved Notch-1, and Hes-1 in the intestinal crypts. The inhibition of Notch signaling with DAPT and the suppression of Jagged-2 and Hes-1 expression using siRNA both significantly inhibited the proliferation of IEC-6 cells.The Jagged-2/Notch-1/Hes-1 signaling pathway is involved in intestinal epithelium regeneration early after I/R injury by increasing crypt epithelial cell proliferation.

  5. Efficient delivery of Notch1 siRNA to SKOV3 cells by cationic cholesterol derivative-based liposome

    Directory of Open Access Journals (Sweden)

    Zhao Y

    2016-10-01

    Full Text Available Yun-Chun Zhao,1 Li Zhang,2 Shi-Sen Feng,3 Lu Hong,3 Hai-Li Zheng,3 Li-Li Chen,4 Xiao-Ling Zheng,1 Yi-Qing Ye,1 Meng-Dan Zhao,1 Wen-Xi Wang,3 Cai-Hong Zheng1 1Pharmacy Department, Women’s Hospital, 2Pharmacy Department, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 3Department of Pharmaceutic Preparation, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 4Department of Gynecologic Oncology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China Abstract: A novel cationic cholesterol derivative-based small interfering RNA (siRNA interference strategy was suggested to inhibit Notch1 activation in SKOV3 cells for the gene therapy of ovarian cancer. The cationic cholesterol derivative, N-(cholesterylhemisuccinoyl-amino-3-propyl-N, N-dimethylamine (DMAPA-chems liposome, was incubated with siRNA at different nitrogen-to-phosphate ratios to form stabilized, near-spherical siRNA/DMAPA-chems nanoparticles with sizes of 100–200 nm and zeta potentials of 40–50 mV. The siRNA/DMAPA-chems nanoparticles protected siRNA from nuclease degradation in 25% fetal bovine serum. The nanoparticles exhibited high cell uptake and Notch1 gene knockdown efficiency in SKOV3 cells at an nitrogen-to-phosphate ratio of 100 and an siRNA concentration of 50 nM. They also inhibited the growth and promoted the apoptosis of SKOV3 cells. These results may provide the potential for using cationic cholesterol derivatives as efficient nonviral siRNA carriers for the suppression of Notch1 activation in ovarian cancer cells. Keywords: siRNA, cationic cholesterol derivative, Notch1, ovarian cancer cells

  6. Deletion of Notch1 converts pro-T cells to dendritic cells and promotes thymic B cells by cell-extrinsic and cell-intrinsic mechanisms.

    Science.gov (United States)

    Feyerabend, Thorsten B; Terszowski, Grzegorz; Tietz, Annette; Blum, Carmen; Luche, Hervé; Gossler, Achim; Gale, Nicholas W; Radtke, Freddy; Fehling, Hans Jörg; Rodewald, Hans-Reimer

    2009-01-16

    Notch1 signaling is required for T cell development and has been implicated in fate decisions in the thymus. We showed that Notch1 deletion in progenitor T cells (pro-T cells) revealed their latent developmental potential toward becoming conventional and plasmacytoid dendritic cells. In addition, Notch1 deletion in pro-T cells resulted in large numbers of thymic B cells, previously explained by T-to-B cell fate conversion. Single-cell genotyping showed, however, that the majority of these thymic B cells arose from Notch1-sufficient cells by a cell-extrinsic pathway. Fate switching nevertheless exists for a subset of thymic B cells originating from Notch1-deleted pro-T cells. Chimeric mice lacking the Notch ligand delta-like 4 (Dll4) in thymus epithelium revealed an essential role for Dll4 in T cell development. Thus, Notch1-Dll4 signaling fortifies T cell commitment by suppressing non-T cell lineage potential in pro-T cells, and normal Notch1-driven T cell development repels excessive B cells in the thymus.

  7. Activation of Notch1 inhibits medial edge epithelium apoptosis in all-trans retinoic acid-induced cleft palate in mice

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yadong; Dong, Shiyi; Wang, Weicai; Wang, Jianning [Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055 (China); Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055 (China); Wang, Miao [Department of Oral and Maxillofacial Surgery, Kiang Wu Hospital, Macao (China); Chen, Mu [Department of Stomatology, Nanshan Affiliated Hospital of Guangdong Medical College, Shenzhen (China); Hou, Jinsong [Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055 (China); Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055 (China); Huang, Hongzhang, E-mail: drhuang52@163.com [Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055 (China); Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055 (China)

    2016-08-26

    Administration of all-trans retinoic acid (atRA) on E12.0 (embryonic day 12.0) leads to failure of medial edge epithelium (MEE) disappearance and cleft palate. However, the molecular mechanism underlying the relationship between atRA and MEE remains to be identified. In this study, atRA (200 mg/kg) administered by gavage induced a 75% incidence of cleft palate in C57BL/6 mice. Notch1 was up-regulated in MEE cells in the atRA-treated group compared with the controls at E15.0, together with reduced apoptosis and elevated proliferation. Next, we investigated the mechanisms underlying atRA, Notch1 and MEE degradation in palate organ culture. Our results revealed that down-regulation of Notch1 partially rescued the inhibition of atRA-induced palate fusion. Molecular analysis indicated that atRA increased the expression of Notch1 and Rbpj and decreased the expression of P21. In addition, depletion of Notch1 expression decreased the expression of Rbpj and increased the expression of P21. Moreover, inhibition of Rbpj expression partially reversed atRA-induced MEE persistence and increased P21 expression. These findings demonstrate that atRA inhibits MEE degradation, which in turn induces a cleft palate, possibly through the Notch1/RBPjk/P21 signaling pathway. - Highlights: • atRA exposure on E12.0 induced MEE persistence and cleft palate. • Notch1 was up-regulated in MEE cells in the atRA-treated embryos. • atRA inhibits MEE degradation, which in turn induces cleft palate, possibly through the Notch1/RBPjk/P21 signaling pathway.

  8. Activation of Notch1 inhibits medial edge epithelium apoptosis in all-trans retinoic acid-induced cleft palate in mice

    International Nuclear Information System (INIS)

    Zhang, Yadong; Dong, Shiyi; Wang, Weicai; Wang, Jianning; Wang, Miao; Chen, Mu; Hou, Jinsong; Huang, Hongzhang

    2016-01-01

    Administration of all-trans retinoic acid (atRA) on E12.0 (embryonic day 12.0) leads to failure of medial edge epithelium (MEE) disappearance and cleft palate. However, the molecular mechanism underlying the relationship between atRA and MEE remains to be identified. In this study, atRA (200 mg/kg) administered by gavage induced a 75% incidence of cleft palate in C57BL/6 mice. Notch1 was up-regulated in MEE cells in the atRA-treated group compared with the controls at E15.0, together with reduced apoptosis and elevated proliferation. Next, we investigated the mechanisms underlying atRA, Notch1 and MEE degradation in palate organ culture. Our results revealed that down-regulation of Notch1 partially rescued the inhibition of atRA-induced palate fusion. Molecular analysis indicated that atRA increased the expression of Notch1 and Rbpj and decreased the expression of P21. In addition, depletion of Notch1 expression decreased the expression of Rbpj and increased the expression of P21. Moreover, inhibition of Rbpj expression partially reversed atRA-induced MEE persistence and increased P21 expression. These findings demonstrate that atRA inhibits MEE degradation, which in turn induces a cleft palate, possibly through the Notch1/RBPjk/P21 signaling pathway. - Highlights: • atRA exposure on E12.0 induced MEE persistence and cleft palate. • Notch1 was up-regulated in MEE cells in the atRA-treated embryos. • atRA inhibits MEE degradation, which in turn induces cleft palate, possibly through the Notch1/RBPjk/P21 signaling pathway.

  9. NOTCH1 Inhibits Activation of ATM by Impairing the Formation of an ATM-FOXO3a-KAT5/Tip60 Complex.

    Science.gov (United States)

    Adamowicz, Marek; Vermezovic, Jelena; d'Adda di Fagagna, Fabrizio

    2016-08-23

    The DNA damage response (DDR) signal transduction pathway is responsible for sensing DNA damage and further relaying this signal into the cell. ATM is an apical DDR kinase that orchestrates the activation and the recruitment of downstream DDR factors to induce cell-cycle arrest and repair. We have previously shown that NOTCH1 inhibits ATM activation upon DNA damage, but the underlying mechanism remains unclear. Here, we show that NOTCH1 does not impair ATM recruitment to DNA double-strand breaks (DSBs). Rather, NOTCH1 prevents binding of FOXO3a and KAT5/Tip60 to ATM through a mechanism in which NOTCH1 competes with FOXO3a for ATM binding. Lack of FOXO3a binding to ATM leads to the loss of KAT5/Tip60 association with ATM. Moreover, expression of NOTCH1 or depletion of ATM impairs the formation of the FOXO3a-KAT5/Tip60 protein complex. Finally, we show that pharmacological induction of FOXO3a nuclear localization sensitizes NOTCH1-driven cancers to DNA-damage-induced cell death. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Relay Placement for FSO Multihop DF Systems With Link Obstacles and Infeasible Regions

    KAUST Repository

    Zhu, Bingcheng; Cheng, Julian; Alouini, Mohamed-Slim; Wu, Lenan

    2015-01-01

    Optimal relay placement is studied for free-space optical multihop communication with link obstacles and infeasible regions. An optimal relay placement scheme is proposed to achieve the lowest outage probability, enable the links to bypass obstacles

  11. Nuclear Factor Erythroid 2 Regulates Human HSC Self-Renewal and T Cell Differentiation by Preventing NOTCH1 Activation.

    Science.gov (United States)

    Di Tullio, Alessandro; Passaro, Diana; Rouault-Pierre, Kevin; Purewal, Sukhveer; Bonnet, Dominique

    2017-07-11

    Nuclear factor erythroid-derived 2 (NF-E2) has been associated with megakaryocyte maturation and platelet production. Recently, an increased in NF-E2 activity has been implicated in myeloproliferative neoplasms. Here, we investigate the role of NF-E2 in normal human hematopoiesis. Knockdown of NF-E2 in the hematopoietic stem and progenitor cells (HSPCs) not only reduced the formation of megakaryocytes but also drastically impaired hematopoietic stem cell activity, decreasing human engraftment in immunodeficient (NSG) mice. This phenotype is likely to be related to both increased cell proliferation (p21-mediated) and reduced Notch1 protein expression, which favors HSPC differentiation over self-renewal. Strikingly, although NF-E2 silencing in HSPCs did not affect their myeloid and B cell differentiation in vivo, it almost abrogated T cell production in primary hosts, as confirmed by in vitro studies. This effect is at least partly due to Notch1 downregulation in NF-E2-silenced HSPCs. Together these data reveal that NF-E2 is an important driver of human hematopoietic stem cell maintenance and T lineage differentiation. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  12. Nuclear Factor Erythroid 2 Regulates Human HSC Self-Renewal and T Cell Differentiation by Preventing NOTCH1 Activation

    Directory of Open Access Journals (Sweden)

    Alessandro Di Tullio

    2017-07-01

    Full Text Available Nuclear factor erythroid-derived 2 (NF-E2 has been associated with megakaryocyte maturation and platelet production. Recently, an increased in NF-E2 activity has been implicated in myeloproliferative neoplasms. Here, we investigate the role of NF-E2 in normal human hematopoiesis. Knockdown of NF-E2 in the hematopoietic stem and progenitor cells (HSPCs not only reduced the formation of megakaryocytes but also drastically impaired hematopoietic stem cell activity, decreasing human engraftment in immunodeficient (NSG mice. This phenotype is likely to be related to both increased cell proliferation (p21-mediated and reduced Notch1 protein expression, which favors HSPC differentiation over self-renewal. Strikingly, although NF-E2 silencing in HSPCs did not affect their myeloid and B cell differentiation in vivo, it almost abrogated T cell production in primary hosts, as confirmed by in vitro studies. This effect is at least partly due to Notch1 downregulation in NF-E2-silenced HSPCs. Together these data reveal that NF-E2 is an important driver of human hematopoietic stem cell maintenance and T lineage differentiation.

  13. The non-canonical NOTCH1 ligand Delta-like 1 homolog (DLK1) self interacts in mammals

    DEFF Research Database (Denmark)

    Traustadóttir, Gunnhildur Ásta; Jensen, Charlotte Harken; Garcia Ramirez, Jose Javier

    2017-01-01

    the proposed DLK1-IGFBP1 interaction was not supported by MTH. Very little has previously been described on the DLK1 self-interaction. Herein, we showed by immunoprecipitation as well as Sulfo-SBED label transfer that the DLK1-DLK1 interaction likely is part of Dlk1's function in preadipocytes. Furthermore our......Delta-like 1 homolog (DLK1) is an imprinted gene, which is widely expressed during mammalian development and plays a pivotal role in differentiation of various tissue types. Most recently, we have shown that DLK1 interacts with NOTCH1, yet several Notch independent mechanisms have previously been...... suggested as well, but only poorly confirmed in a mammalian context. In the present study, we employed the mammalian two-hybrid (MTH) system, a genetic in vivo protein-protein interaction system, to show robust DLK1-DLK1, DLK1-FnI (Fibronectin) and DLK1-CFR (cysteine-rich FGF receptor) interactions, whereas...

  14. β-Elemene Selectively Inhibits the Proliferation of Glioma Stem-Like Cells Through the Downregulation of Notch1.

    Science.gov (United States)

    Feng, Hai-Bin; Wang, Jing; Jiang, Hao-Ran; Mei, Xin; Zhao, Yi-Ying; Chen, Fu-Rong; Qu, Yue; Sai, Ke; Guo, Cheng-Cheng; Yang, Qun-Ying; Zhang, Zong-Ping; Chen, Zhong-Ping

    2017-03-01

    Glioma is the most frequent primary central nervous system tumor. Although the current first-line medicine, temozolomide (TMZ), promotes patient survival, drug resistance develops easily. Thus, it is important to investigate novel therapeutic reagents to solidify the treatment effect. β-Elemene (bELE) is a compound from a Chinese herb whose anticancer effect has been shown in various types of cancer. However, its role in the inhibition of glioma stem-like cells (GSLCs) has not yet been reported. We studied both the in vitro and the in vivo inhibitory effect of bELE and TMZ in GSLCs and parental cells and their combined effects. The molecular mechanisms were also investigated. We also optimized the delivery methods of bELE. We found that bELE selectively inhibits the proliferation and sphere formation of GSLCs, other than parental glioma cells, and TMZ exerts its effects on parental cells instead of GSLCs. The in vivo data confirmed that the combination of bELE and TMZ worked better in the xenografts of GSLCs, mimicking the situation of tumorigenesis of human cancer. Notch1 was downregulated with bELE treatment. Our data also demonstrated that the continuous administration of bELE produces an ideal effect to control tumor progression. Our findings have demonstrated, for the first time, that bELE could compensate for TMZ to kill both GSLCs and nonstem-like cancer cells, probably improving the prognosis of glioma patients tremendously. Notch1 might be a downstream target of bELE. Therefore, our data shed light on improving the outcomes of glioma patients by combining bELE and TMZ. Stem Cells Translational Medicine 2017;6:830-839. © 2016 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  15. β‐Elemene Selectively Inhibits the Proliferation of Glioma Stem‐Like Cells Through the Downregulation of Notch1

    Science.gov (United States)

    Feng, Hai‐bin; Wang, Jing; Jiang, Hao‐ran; Mei, Xin; Zhao, Yi‐ying; Chen, Fu‐rong; Qu, Yue; Sai, Ke; Guo, Cheng‐cheng; Yang, Qun‐ying; Zhang, Zong‐ping

    2016-01-01

    Abstract Glioma is the most frequent primary central nervous system tumor. Although the current first‐line medicine, temozolomide (TMZ), promotes patient survival, drug resistance develops easily. Thus, it is important to investigate novel therapeutic reagents to solidify the treatment effect. β‐Elemene (bELE) is a compound from a Chinese herb whose anticancer effect has been shown in various types of cancer. However, its role in the inhibition of glioma stem‐like cells (GSLCs) has not yet been reported. We studied both the in vitro and the in vivo inhibitory effect of bELE and TMZ in GSLCs and parental cells and their combined effects. The molecular mechanisms were also investigated. We also optimized the delivery methods of bELE. We found that bELE selectively inhibits the proliferation and sphere formation of GSLCs, other than parental glioma cells, and TMZ exerts its effects on parental cells instead of GSLCs. The in vivo data confirmed that the combination of bELE and TMZ worked better in the xenografts of GSLCs, mimicking the situation of tumorigenesis of human cancer. Notch1 was downregulated with bELE treatment. Our data also demonstrated that the continuous administration of bELE produces an ideal effect to control tumor progression. Our findings have demonstrated, for the first time, that bELE could compensate for TMZ to kill both GSLCs and nonstem‐like cancer cells, probably improving the prognosis of glioma patients tremendously. Notch1 might be a downstream target of bELE. Therefore, our data shed light on improving the outcomes of glioma patients by combining bELE and TMZ. Stem Cells Translational Medicine 2017;6:830–839 PMID:28297578

  16. All-trans-retinoic Acid Modulates the Plasticity and Inhibits the Motility of Breast Cancer Cells: ROLE OF NOTCH1 AND TRANSFORMING GROWTH FACTOR (TGFβ).

    Science.gov (United States)

    Zanetti, Adriana; Affatato, Roberta; Centritto, Floriana; Fratelli, Maddalena; Kurosaki, Mami; Barzago, Maria Monica; Bolis, Marco; Terao, Mineko; Garattini, Enrico; Paroni, Gabriela

    2015-07-17

    All-trans-retinoic acid (ATRA) is a natural compound proposed for the treatment/chemoprevention of breast cancer. Increasing evidence indicates that aberrant regulation of epithelial-to-mesenchymal transition (EMT) is a determinant of the cancer cell invasive and metastatic behavior. The effects of ATRA on EMT are largely unknown. In HER2-positive SKBR3 and UACC812 cells, showing co-amplification of the ERBB2 and RARA genes, ATRA activates a RARα-dependent epithelial differentiation program. In SKBR3 cells, this causes the formation/reorganization of adherens and tight junctions. Epithelial differentiation and augmented cell-cell contacts underlie the anti-migratory action exerted by the retinoid in cells exposed to the EMT-inducing factors EGF and heregulin-β1. Down-regulation of NOTCH1, an emerging EMT modulator, is involved in the inhibition of motility by ATRA. Indeed, the retinoid blocks NOTCH1 up-regulation by EGF and/or heregulin-β1. Pharmacological inhibition of γ-secretase and NOTCH1 processing also abrogates SKBR3 cell migration. Stimulation of TGFβ contributes to the anti-migratory effect of ATRA. The retinoid switches TGFβ from an EMT-inducing and pro-migratory determinant to an anti-migratory mediator. Inhibition of the NOTCH1 pathway not only plays a role in the anti-migratory action of ATRA; it is relevant also for the anti-proliferative activity of the retinoid in HCC1599 breast cancer cells, which are addicted to NOTCH1 for growth/viability. This effect is enhanced by the combination of ATRA and the γ-secretase inhibitor N-(N-(3,5-difluorophenacetyl)-l-alanyl)-S-phenylglycine t-butyl ester, supporting the concept that the two compounds act at the transcriptional and post-translational levels along the NOTCH1 pathway. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. The adaptor SASH1 acts through NOTCH1 and its inhibitor DLK1 in a 3D model of lumenogenesis involving CEACAM1.

    Science.gov (United States)

    Stubblefield, Kandis; Chean, Jennifer; Nguyen, Tung; Chen, Charng-Jui; Shively, John E

    2017-10-15

    CEACAM1 transfection into breast cancer cells restores lumen formation in a 3D culture model. Among the top up-regulated genes that were associated with restoration of lumen formation, the adaptor protein SASH1 was identified. Furthermore, SASH1 was shown to be critical for lumen formation by RNAi inhibition. Upon analyzing the gene array from CEACAM1/MCF7 cells treated with SASH1 RNAi, DLK1, an inhibitor of NOTCH1 signaling, was found to be down-regulated to the same extent as SASH1. Subsequent treatment of CEACAM1/MCF7 cells with RNAi to DLK1 also inhibited lumen formation, supporting its association with SASH1. In agreement with the role of DLK1 as a NOTCH1 inhibitor, NOTCH1, as well as its regulated genes HES1 and HEY1, were down-regulated in CEACAM1/MCF7 cells by the action of DLK1 RNAi, and up-regulated by SASH1 RNAi. When CEACAM1/MCF7 cells were treated with a γ-secretase inhibitor known to inhibit NOTCH signaling, lumen formation was inhibited. We conclude that restoration of lumen formation by CEACAM1 regulates the NOTCH1 signaling pathway via the adaptor protein SASH1 and the NOTCH1 inhibitor DLK1. These data suggest that the putative involvement of NOTCH1 as a tumor-promoting gene in breast cancer may depend on its lack of regulation in cancer, whereas its involvement in normal lumen formation requires activation of its expression, and subsequently, inhibition of its signaling. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. An Exploratory Study Linking Turkish Regional Food with Cultural Destinations

    OpenAIRE

    Mehmet Ergul; Colin Johnson; Ali Sukru Cetinkaya; Jale Boga Robertson

    2011-01-01

    Food and tourism may be considered as two interrelated elements that bring people and cultures together on many different occasions. Research indicates that food could be viewed as a peak touristic experience and a major tourist attraction. The main purpose of this paper is to identify and evaluate the significance of food tourism for Turkey and to create a number of innovative regional food related itineraries that would be replicable. Four main results emerged from the analysis of the inter...

  19. Mediator 1 contributes to enamel mineralization as a coactivator for Notch1 signaling and stimulates transcription of the alkaline phosphatase gene.

    Science.gov (United States)

    Yoshizaki, Keigo; Hu, Lizhi; Nguyen, Thai; Sakai, Kiyoshi; Ishikawa, Masaki; Takahashi, Ichiro; Fukumoto, Satoshi; DenBesten, Pamela K; Bikle, Daniel D; Oda, Yuko; Yamada, Yoshihiko

    2017-08-18

    Tooth enamel is mineralized through the differentiation of multiple dental epithelia including ameloblasts and the stratum intermedium (SI), and this differentiation is controlled by several signaling pathways. Previously, we demonstrated that the transcriptional coactivator Mediator 1 (MED1) plays a critical role in enamel formation. For instance, conditional ablation of Med1 in dental epithelia causes functional changes in incisor-specific dental epithelial stem cells, resulting in mineralization defects in the adult incisors. However, the molecular mechanism by which Med1 deficiency causes these abnormalities is not clear. Here, we demonstrated that Med1 ablation causes early SI differentiation defects resulting in enamel hypoplasia of the Med1 -deficient molars. Med1 deletion prevented Notch1-mediated differentiation of the SI cells resulting in decreased alkaline phosphatase (ALPL), which is essential for mineralization. However, it does not affect the ability of ameloblasts to produce enamel matrix proteins. Using the dental epithelial SF2 cell line, we demonstrated that MED1 directly activates transcription of the Alpl gene through the stimulation of Notch1 signaling by forming a complex with cleaved Notch1-RBP-Jk on the Alpl promoter. These results suggest that MED1 may be essential for enamel matrix mineralization by serving as a coactivator for Notch1 signaling regulating transcription of the Alpl gene.

  20. Notch1/3 and p53/p21 are a potential therapeutic target for APS-induced apoptosis in non-small cell lung carcinoma cell lines.

    Science.gov (United States)

    Zhang, Jing-Xi; Han, Yi-Ping; Bai, Chong; Li, Qiang

    2015-01-01

    Previous studies have shown that Astragalus polysaccharide (APS) can be applied to anti-cancer. However, the mechanism by which APS mediate this effect is unclear. In the present study, APS-mediated NSCLC cell apoptosis was investigated through the regulation of the notch signaling pathway. The cell viability was detected by the CCK8 assay. The mRNA and protein expression of notch1/3 and tumor suppressors were analyzed by RT-PCR and western blotting, respectively. The mRNA and protein of notch1 and notch3 were significantly up-regulated in tumor tissues as compared to non-tumor adjacent tissues. Treatment of human NSCLC cells with APS induced cell death in a dose-and time-dependent manner by using CCK8 assay. The mRNA and protein expression of notch1 and notch3 were significantly lower in NSCLC cells with APS treatment than that in control group. Moreover, western blotting analysis showed that treatment of H460 cells with APS significantly increased the pro-apoptotic Bax and caspase 8 levels, decreased the anti-apoptotic Bcl-2 level. Furthermore, p53, p21 and p16 were obviously up-regulated by APS treatment in H460 cell. This study demonstrated that APS-treated could inhibit proliferation and promote cell apoptosis, at least partially, through suppressing the expression of notch1 and notch3 and up-regulating the expression of tumor suppressors in H460 NSCLC cell lines.

  1. Pathways linking regional hyperintensities in the brain and slower gait.

    Science.gov (United States)

    Bolandzadeh, Niousha; Liu-Ambrose, Teresa; Aizenstein, Howard; Harris, Tamara; Launer, Lenore; Yaffe, Kristine; Kritchevsky, Stephen B; Newman, Anne; Rosano, Caterina

    2014-10-01

    Cerebral white matter hyperintensities (WMHs) are involved in the evolution of impaired mobility and executive functions. Executive functions and mobility are also associated. Thus, WMHs may impair mobility directly, by disrupting mobility-related circuits, or indirectly, by disrupting circuits responsible for executive functions. Understanding the mechanisms underlying impaired mobility in late life will increase our capacity to develop effective interventions. To identify regional WMHs most related to slower gait and to examine whether these regional WMHs directly impact mobility, or indirectly by executive functions. Cross-sectional study. Twenty-one WMH variables (i.e., total WMH volume and WMHs in 20 tracts), gait speed, global cognition (Modified Mini-Mental State Examination; 3MS), and executive functions and processing speed (Digit-Symbol Substitution Test; DSST) were assessed. An L1-L2 regularized regression (i.e., Elastic Net model) identified the WMH variables most related to slower gait. Multivariable linear regression models quantified the association between these WMH variables and gait speed. Formal tests of mediation were also conducted. Community-based sample. Two hundred fifty-three adults (mean age: 83years, 58% women, 41% black). Gait speed. In older adults with an average gait speed of 0.91m/sec, total WMH volume, WMHs located in the right anterior thalamic radiation (ATRR) and frontal corpuscallosum (CCF) were most associated with slower gait. There was a >10% slower gait for each standard deviation of WMH in CCF, ATRR or total brain (standardized beta in m/sec [p value]: -0.11 [p=0.046], -0.15 [p=0.007] and -0.14 [p=0.010], respectively). These associations were substantially and significantly attenuated after adjustment for DSST. This effect was stronger for WMH in CCF than for ATRR or total WMH (standardized beta in m/sec [p value]: -0.07 [p=0.190], -0.12 [p=0.024] and -0.10 [p=0.049], respectively). Adjustment for 3MS did not change these

  2. Guidance system monitors regional link network; Leitsystem ueberwacht regionales Verbundleitungsnetz

    Energy Technology Data Exchange (ETDEWEB)

    Gorgas, O. [IDS GmbH, Ettlingen (Germany)

    2002-07-01

    The Harzwasserwerke GmbH, as a regional supplier in Lower Saxony, treat drinking water in dam and ground water works. An approximately 500 km long supply network supplies water to around 70 towns and communities in Northern Germany. This means around one and a half million people are supplied with the life elixir in renowned towns such as Hannover, Wolfsburg (with the Volkswagen AG), Braunschweig, Hildesheim, Goettingen and Bremen. A new network guidance system has been installed to monitor the pipeline system and the feed to water works and feed in and out of high-level reservoirs. (orig.) [German] Die Harzwasserwerke GmbH als Regionalversorger in Niedersachsen bereiten Trinkwasser in Talsperren- und Grundwasserwerken auf. Ueber ein rund 500 km langes Leitungsnetz werden im Norden Deutschlands etwa 70 Staedte und Gemeinden versorgt. Damit werden rund eineinhalb Millionen Menschen mit dem Lebensmittel Nummer Eins, unter anderem in namhaften Staedten wie Hannover, Wolfsburg mit der Volkswagen AG, Braunschweig, Hildesheim, Goettingen und Bremen beliefert. Zur Ueberwachung des Leitungssystems und der Einspeisung an Wasserwerken bzw. Ein- und Ausspeisungen an Hochbehaeltern wurde ein neues Netzleitsystem installiert. (orig.)

  3. Identification of epidermal Pdx1 expression discloses different roles of Notch1 and Notch2 in murine Kras(G12D-induced skin carcinogenesis in vivo.

    Directory of Open Access Journals (Sweden)

    Pawel K Mazur

    Full Text Available BACKGROUND: The Ras and Notch signaling pathways are frequently activated during development to control many diverse cellular processes and are often dysregulated during tumorigenesis. To study the role of Notch and oncogenic Kras signaling in a progenitor cell population, Pdx1-Cre mice were utilized to generate conditional oncogenic Kras(G12D mice with ablation of Notch1 and/or Notch2. METHODOLOGY/PRINCIPAL FINDINGS: Surprisingly, mice with activated Kras(G12D and Notch1 but not Notch2 ablation developed skin papillomas progressing to squamous cell carcinoma providing evidence for Pdx1 expression in the skin. Immunostaining and lineage tracing experiments indicate that PDX1 is present predominantly in the suprabasal layers of the epidermis and rarely in the basal layer. Further analysis of keratinocytes in vitro revealed differentiation-dependent expression of PDX1 in terminally differentiated keratinocytes. PDX1 expression was also increased during wound healing. Further analysis revealed that loss of Notch1 but not Notch2 is critical for skin tumor development. Reasons for this include distinct Notch expression with Notch1 in all layers and Notch2 in the suprabasal layer as well as distinctive p21 and β-catenin signaling inhibition capabilities. CONCLUSIONS/SIGNIFICANCE: Our results provide strong evidence for epidermal expression of Pdx1 as of yet not identified function. In addition, this finding may be relevant for research using Pdx1-Cre transgenic strains. Additionally, our study confirms distinctive expression and functions of Notch1 and Notch2 in the skin supporting the importance of careful dissection of the contribution of individual Notch receptors.

  4. Acupuncture inhibits Notch1 and Hes1 protein expression in the basal ganglia of rats with cerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    Wei Zou

    2015-01-01

    Full Text Available Notch pathway activation maintains neural stem cells in a proliferating state and increases nerve repair capacity. To date, studies have rarely focused on changes or damage to signal transduction pathways during cerebral hemorrhage. Here, we examined the effect of acupuncture in a rat model of cerebral hemorrhage. We examined four groups: in the control group, rats received no treatment. In the model group, cerebral hemorrhage models were established by infusing non-heparinized blood into the brain. In the acupuncture group, modeled rats had Baihui (DU20 and Qubin (GB7 acupoints treated once a day for 30 minutes. In the DAPT group, modeled rats had 0.15 μg/mL DAPT solution (10 mL infused into the brain. Immunohistochemistry and western blot results showed that acupuncture effectively inhibits Notch1 and Hes1 protein expression in rat basal ganglia. These inhibitory effects were identical to DAPT, a Notch signaling pathway inhibitor. Our results suggest that acupuncture has a neuroprotective effect on cerebral hemorrhage by inhibiting Notch-Hes signaling pathway transduction in rat basal ganglia after cerebral hemorrhage.

  5. MiR-146a modulates macrophage polarization by inhibiting Notch1 pathway in RAW264.7 macrophages.

    Science.gov (United States)

    Huang, Cheng; Liu, Xue-Jiao; QunZhou; Xie, Juan; Ma, Tao-Tao; Meng, Xiao-Ming; Li, Jun

    2016-03-01

    Macrophages are heterogeneous and plastic cells which are able to undergo dynamic transition between M1 and M2 polarized phenotypes in response to the microenvironment signals. However, the underlying molecular mechanisms of macrophage polarization are still obscure. In the current study, it was revealed that miR-146a might play a pivotal role in macrophage polarization. As our results indicated, miR-146a was highly expressed in M2 macrophages rather than M1 macrophages. Over-expression of miR-146a resulted in significantly decreased production of pro-inflammatory cytokines including iNOS and TNF-α in M1 macrophages, while increased production of M2 marker genes such as Arg1 and CD206 in M2 macrophages. In contrast, knockdown of miR-146a promoted M1 macrophage polarization but diminished M2 macrophage polarization. Mechanistically, it was revealed that miR-146a modulated macrophage polarization by targeting Notch1. Of note, PPARγ was responsible as another target for miR-146a-mediated macrophage polarization. Taken together, it was suggested that miR-146a might serve as a molecular regulator in macrophage polarization and is a potential therapeutic target for inflammatory diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Pien Tze Huang inhibits the proliferation, and induces the apoptosis and differentiation of colorectal cancer stem cells via suppression of the Notch1 pathway.

    Science.gov (United States)

    Qi, Fei; Wei, Lihui; Shen, Aling; Chen, Youqin; Lin, Jiumao; Chu, Jianfeng; Cai, Qiaoyan; Pan, Jie; Peng, Jun

    2016-01-01

    Cancer stem cells (CSCs) possess properties of continuous self-renewal, multi-directional differentiation and natural chemoresistance, leading to the initiation, progression and relapse of cancer. The characteristics of CSCs are strongly associated with multiple cellular pathways such as Notch1 signaling. Therefore, targeting CSCs via suppressing the Notch1 pathway might represent a promising strategy for cancer treatment. The well-known traditional Chinese medicine (TCM) formula Pien Tze Huang (PZH) has long been used as an alternative remedy for various cancers including colorectal cancer (CRC). We previously reported that PZH contains a broad range of anticancer activities including an inhibitory effect on CSCs. To further elucidate the mode of action of PZH, in this study we isolated the stem-like side population (SP) from the human CRC SW480 cell line to investigate its effect on CSCs as well as the possible molecular mechanisms. As compared with non-SP cells, the isolated SW480 SP cells displayed stronger capacities of spheroid formation in vitro and tumorigenicity in vivo, demonstrating the stem cell-like features of SP cells. However, PZH treatment significantly decreased the percentage of SP cells in a dose-dependent manner. In addition, PZH significantly and does-dependently inhibited the viability and promoted the apoptosis and differentiation of the isolated SW480 SP cells. Moreover, PZH treatment profoundly reduced the mRNA and protein expression of Notch1 and Hes1 in the SP cells. Our findings suggest that PZH negatively modulates the characteristics of CSCs through suppression of the Notch1 signaling pathway.

  7. Utility of LRF/Pokemon and NOTCH1 protein expression in the distinction between nodular lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphoma.

    Science.gov (United States)

    Bohn, Olga; Maeda, Takahiro; Filatov, Alexander; Lunardi, Andrea; Pandolfi, Pier Paolo; Teruya-Feldstein, Julie

    2014-02-01

    Classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) are considered separate entities with different prognosis and treatment. However, morphologic features can be similar and immunohistochemical studies are essential in the distinction; thus, determination of additional biomarkers is of utmost importance. LRF/Pokemon is a proto-oncogene, an interacting partner co-expressed with BCL6 in germinal centers and highly expressed in diffuse large B-cell lymphoma and follicular lymphoma. Conversely, loss of the LRF gene in mouse hematopoietic stem cells results in complete block of early B cell development with concomitant Notch de-repression, indicating its critical role in B versus T cell fate decision at the hematopoietic stem cell stage. For the first time, we show that LRF/Pokemon is predominantly expressed in NLPHL cases as is BCL6 with low to absent NOTCH1 protein expression; while Hodgkin Reed-Sternberg (HRS) cells in CHL show low to absent BCL6 and LRF/Pokemon expression with higher NOTCH1 expression. We illustrate a potential functional interaction between LRF and BCL6 in NLPHL pathogenesis, and differential expression of LRF/Pokemon and NOTCH1 proteins in CHL thus showing differential expression, making for an additional diagnostic marker and therapeutic target.

  8. Utility of LRF/Pokemon and NOTCH1 Protein Expression in the Distinction of Nodular Lymphocyte-Predominant Hodgkin Lymphoma and Classical Hodgkin Lymphoma

    Science.gov (United States)

    Bohn, Olga; Maeda, Takahiro; Filatov, Alexander; Lunardi, Andrea; Pandolfi, Pier Paolo; Teruya-Feldstein, Julie

    2014-01-01

    Classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) are considered separate entities with different prognosis and treatment. However, morphologic features can be similar and immunohistochemical studies are essential in the distinction; thus, determination of additional biomarkers is of utmost importance. LRF/Pokemon is a protooncogene, an interacting partner co-expressed with BCL6 in germinal centers and highly expressed in diffuse large B-cell lymphoma and follicular lymphoma. Conversely, loss of the LRF gene in mouse hematopoietic stem cells results in complete block of early B cell development with concomitant Notch derepression, indicating its critical role in B versus T cell fate decision at the hematopoietic stem cell stage. For the first time, we show that LRF/Pokemon is predominantly expressed in NLPHL cases as is BCL6 with low to absent NOTCH1 protein expression; while Hodgkin Reed-Sternberg (HRS) cells in CHL show low to absent BCL6 and LRF/Pokemon expression with higher NOTCH1 expression. We illustrate a potential functional interaction between LRF and BCL6 in NLPHL pathogenesis, and differential expression of LRF/Pokemon and NOTCH1 proteins in CHL thus showing differential expression, making for an additional diagnostic marker and therapeutic target. PMID:24326827

  9. TNF inhibits Notch-1 in skeletal muscle cells by Ezh2 and DNA methylation mediated repression: implications in duchenne muscular dystrophy.

    Directory of Open Access Journals (Sweden)

    Swarnali Acharyya

    2010-08-01

    Full Text Available Classical NF-kappaB signaling functions as a negative regulator of skeletal myogenesis through potentially multiple mechanisms. The inhibitory actions of TNFalpha on skeletal muscle differentiation are mediated in part through sustained NF-kappaB activity. In dystrophic muscles, NF-kappaB activity is compartmentalized to myofibers to inhibit regeneration by limiting the number of myogenic progenitor cells. This regulation coincides with elevated levels of muscle derived TNFalpha that is also under IKKbeta and NF-kappaB control.Based on these findings we speculated that in DMD, TNFalpha secreted from myotubes inhibits regeneration by directly acting on satellite cells. Analysis of several satellite cell regulators revealed that TNFalpha is capable of inhibiting Notch-1 in satellite cells and C2C12 myoblasts, which was also found to be dependent on NF-kappaB. Notch-1 inhibition occurred at the mRNA level suggesting a transcriptional repression mechanism. Unlike its classical mode of action, TNFalpha stimulated the recruitment of Ezh2 and Dnmt-3b to coordinate histone and DNA methylation, respectively. Dnmt-3b recruitment was dependent on Ezh2.We propose that in dystrophic muscles, elevated levels of TNFalpha and NF-kappaB inhibit the regenerative potential of satellite cells via epigenetic silencing of the Notch-1 gene.

  10. TNF Inhibits Notch-1 in Skeletal Muscle Cells by Ezh2 and DNA Methylation Mediated Repression: Implications in Duchenne Muscular Dystrophy

    Science.gov (United States)

    Acharyya, Swarnali; Sharma, Sudarshana M.; Cheng, Alfred S.; Ladner, Katherine J.; He, Wei; Kline, William; Wang, Huating; Ostrowski, Michael C.; Huang, Tim H.; Guttridge, Denis C.

    2010-01-01

    Background Classical NF-κB signaling functions as a negative regulator of skeletal myogenesis through potentially multiple mechanisms. The inhibitory actions of TNFα on skeletal muscle differentiation are mediated in part through sustained NF-κB activity. In dystrophic muscles, NF-κB activity is compartmentalized to myofibers to inhibit regeneration by limiting the number of myogenic progenitor cells. This regulation coincides with elevated levels of muscle derived TNFα that is also under IKKβ and NF-κB control. Methodology/Principal Findings Based on these findings we speculated that in DMD, TNFα secreted from myotubes inhibits regeneration by directly acting on satellite cells. Analysis of several satellite cell regulators revealed that TNFα is capable of inhibiting Notch-1 in satellite cells and C2C12 myoblasts, which was also found to be dependent on NF-κB. Notch-1 inhibition occurred at the mRNA level suggesting a transcriptional repression mechanism. Unlike its classical mode of action, TNFα stimulated the recruitment of Ezh2 and Dnmt-3b to coordinate histone and DNA methylation, respectively. Dnmt-3b recruitment was dependent on Ezh2. Conclusions/Significance We propose that in dystrophic muscles, elevated levels of TNFα and NF-κB inhibit the regenerative potential of satellite cells via epigenetic silencing of the Notch-1 gene. PMID:20814569

  11. Epidermal growth factor receptor inhibition reduces angiogenesis via hypoxia-inducible factor-1α and Notch1 in head neck squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Wei-Ming Wang

    Full Text Available Angiogenesis, a marker of cancer development, affects response to radiotherapy sensibility. This preclinical study aims to understand the receptor tyrosine kinase-mediated angiogenesis in head neck squamous cell carcinoma (HNSCC. The receptor tyrosine kinase activity in a transgenic mouse model of HNSCC was assessed. The anti-tumorigenetic and anti-angiogenetic effects of cetuximab-induced epidermal growth factor receptor (EGFR inhibition were investigated in xenograft and transgenic mouse models of HNSCC. The signaling transduction of Notch1 and hypoxia-inducible factor-1α (HIF-1α was also analyzed. EGFR was overexpressed and activated in the Tgfbr1/Pten deletion (2cKO mouse model of HNSCC. Cetuximab significantly delayed tumor onset by reducing tumor angiogenesis. This drug exerted similar effects on heterotopic xenograft tumors. In the human HNSCC tissue array, increased EGFR expression correlated with increased HIF-1α and micro vessel density. Cetuximab inhibited tumor-induced angiogenesis in vitro and in vivo by significantly downregulating HIF-1α and Notch1. EGFR is involved in the tumor angiogenesis of HNSCC via the HIF-1α and Notch1 pathways. Therefore, targeting EGFR by suppressing hypoxia- and Notch-induced angiogenesis may benefit HNSCC therapy.

  12. Developmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin attenuates later-life Notch1-mediated T cell development and leukemogenesis

    International Nuclear Information System (INIS)

    Ahrenhoerster, Lori S.; Leuthner, Tess C.; Tate, Everett R.; Lakatos, Peter A.; Laiosa, Michael D.

    2015-01-01

    Over half of T cell acute lymphoblastic leukemia (T-ALL) patients have activating mutations in the Notch gene. Moreover, the contaminant 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) is a known carcinogen that mediates its toxicity through the aryl hydrocarbon receptor (AHR), and crosstalk between activated AHR and Notch signaling pathways has previously been observed. Given the importance of Notch signaling in thymocyte development and T-ALL disease progression, we hypothesized that the activated AHR potentiates disease initiation and progression in an in vivo model of Notch1-induced thymoma. This hypothesis was tested utilizing adult and developmental exposure paradigms to TCDD in mice expressing a constitutively active Notch1 transgene (Notch ICN-TG ). Following exposure of adult Notch ICN-TG mice to a single high dose of TCDD, we observed a significant increase in the efficiency of CD8 thymocyte generation. We next exposed pregnant mice to 3 μg/kg of TCDD throughout gestation and lactation to elucidate effects of developmental AHR activation on later-life T cell development and T-ALL-like thymoma susceptibility induced by Notch1. We found that the vehicle-exposed Notch ICN-TG offspring have a peripheral T cell pool heavily biased toward the CD4 lineage, while TCDD-exposed Notch ICN-TG offspring were biased toward the CD8 lineage. Furthermore, while the vehicle-exposed NotchICN-TG mice showed increased splenomegaly and B to T cell ratios indicative of disease, mice developmentally exposed to TCDD were largely protected from disease. These studies support a model where developmental AHR activation attenuates later-life Notch1-dependent impacts on thymocyte development and disease progression. - Highlights: • Adult mice exposed to 30 μg/kg TCDD have higher efficiency of CD8 thymocyte generation. • Mice carrying a constitutively active Notch transgene were exposed to 3 μg/kg TCDD throughout development. • Progression of Notch-induced thymoma was different in

  13. Developmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin attenuates later-life Notch1-mediated T cell development and leukemogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Ahrenhoerster, Lori S.; Leuthner, Tess C.; Tate, Everett R.; Lakatos, Peter A.; Laiosa, Michael D., E-mail: laiosa@uwm.edu

    2015-03-01

    Over half of T cell acute lymphoblastic leukemia (T-ALL) patients have activating mutations in the Notch gene. Moreover, the contaminant 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) is a known carcinogen that mediates its toxicity through the aryl hydrocarbon receptor (AHR), and crosstalk between activated AHR and Notch signaling pathways has previously been observed. Given the importance of Notch signaling in thymocyte development and T-ALL disease progression, we hypothesized that the activated AHR potentiates disease initiation and progression in an in vivo model of Notch1-induced thymoma. This hypothesis was tested utilizing adult and developmental exposure paradigms to TCDD in mice expressing a constitutively active Notch1 transgene (Notch{sup ICN-TG}). Following exposure of adult Notch{sup ICN-TG} mice to a single high dose of TCDD, we observed a significant increase in the efficiency of CD8 thymocyte generation. We next exposed pregnant mice to 3 μg/kg of TCDD throughout gestation and lactation to elucidate effects of developmental AHR activation on later-life T cell development and T-ALL-like thymoma susceptibility induced by Notch1. We found that the vehicle-exposed Notch{sup ICN-TG} offspring have a peripheral T cell pool heavily biased toward the CD4 lineage, while TCDD-exposed Notch{sup ICN-TG} offspring were biased toward the CD8 lineage. Furthermore, while the vehicle-exposed NotchICN-TG mice showed increased splenomegaly and B to T cell ratios indicative of disease, mice developmentally exposed to TCDD were largely protected from disease. These studies support a model where developmental AHR activation attenuates later-life Notch1-dependent impacts on thymocyte development and disease progression. - Highlights: • Adult mice exposed to 30 μg/kg TCDD have higher efficiency of CD8 thymocyte generation. • Mice carrying a constitutively active Notch transgene were exposed to 3 μg/kg TCDD throughout development. • Progression of Notch

  14. Shengui Sansheng San extraction is an angiogenic switch via regulations of AKT/mTOR, ERK1/2 and Notch1 signal pathways after ischemic stroke.

    Science.gov (United States)

    Liu, Bowen; Luo, Cheng; Zheng, Zhaoguang; Xia, Zhenyan; Zhang, Qian; Ke, Chienchih; Liu, Renshyan; Zhao, Yonghua

    2018-05-15

    As a traditional Chinese herbal formula, Shengui Sansheng San (SSS) has been employed for stroke treatment more than 300 years. We hypothesize that SSS extraction is an angiogenic switch in penumbra post-stroke, and corresponding mechanisms are investigated. In present study, rats were subjected to permanent middle cerebral artery occlusion model (MCAo) and were treated with low, middle and high doses of SSS extraction. We assessed neurological function and survival rate, and measured infarct volume by 2,3,5-triphenyltetrazolium chloride staining on day 7 after ischemia. von Willebrand factor (vWF), stromal cell-derived factor-1 alpha (SDF-1α) /chemokine (C-X-C motif) receptor 4 (CXCR4) axis, vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) as well as protein kinase B (AKT)/mammalian target of rapamycin (mTOR) /hypoxia-inducible factor-1 alpha (HIF-1α), extracellular signal-regulated kinase 1/2 (ERK1/2) and Notch1 signaling pathways were respectively investigated by immunofluorescence assay or western blotting in vivo and oxygen-glucose-deprived (OGD) brain microvascular endothelial cells (BMECs); simultaneously, wound healing of BMECs and tube formation assay were administrated. Compared to MCAo group, SSS extraction could significantly improve neurological functional scores, survival rate and cerebral infarct volume, enhance vWF + vascular density and perimeter, SDF-1α/CXCR4 axis, VEGF expression, as well as activate AKT/mTOR/HIF-1α and ERK1/2 and inhibit Notch1 pathways in penumbra. In vitro, containing SSS extraction serum increased BMEC migration, capillary formation and VEGF expression via up-regulations of AKT/mTOR and ERK1/2 pathways in OGD BMECs, but ERK inhibitor (U0126) reversed the result of VEGF expression in high dose of SSS group. Additionally, VEGFR2 and Notch1 expressions were suppressed by containing SSS extraction serum. All results were in dose dependent manner. Our study firstly demonstrates that SSS extraction is an

  15. [Notch1 signaling participates in the release of inflammatory mediators in mouse RAW264.7 cells via activating NF-κB pathway].

    Science.gov (United States)

    Zhao, Hongwei; Xu, Che Nan; Huang, Chao; Jiang, Jinzhi; Li, Liangchang

    2017-10-01

    Objective To study the effect of Notch1 signaling on the release of inflammatory mediators in lipopolysaccharide (LPS)-induced macrophages and the related mechanism. Methods The expressions of Notch1 and hairy and enhancer of split 1 (Hes1) mRNAs were investigated by reverse transcription PCR (RT-PCR) in mouse RAW264.7 cells after stimulated with 100 ng/mL LPS for 8 hours. Prior to stimulation with LPS, mouse RAW264.7 cells were treated with DAPT (10 μmol/L), an inhibitor of Notch1 signaling, for 1 hour. The concentrations of tumor necrosis factor (TNF-α), interleukin 1β (IL-1β), IL-6, nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) in cell culture media were measured by ELISA. The mRNA levels of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were examined by RT-PCR. The protein levels of iNOS, COX-2, nuclear factor kappa Bp65 (NF-κBp65) and phosphorylated nuclear factor κB inhibitor α (p-IκBα) were detected by Western blotting. Results The expressions of Notch1 and Hes1 mRNAs significantly increased in mouse RAW264.7 cells after stimulated with LPS. The levels of TNF-α, IL-1β, IL-6, NO and PGE 2 were significantly up-regulated in cell culture media after stimulated with LPS, but the levels of those inflammatory mediators were reduced by DAPT. The mRNA and protein levels of iNOS and COX-2 were significant raised in mouse RAW264.7 cells after stimulated with LPS, while they were inhibited by DAPT. Both IκBα-phosphorylation and NF-κBp65 translocation into nuclear in LPS-induced RAW264.7 cells were also inhibited by DAPT. Conclusion Notch1 signaling activates NF-κB to participate in LPS-induced inflammatory mediator release in macrophages.

  16. Control of a hybrid HVDC link to increase inter-regional power transfer

    DEFF Research Database (Denmark)

    Kotb, Omar; Ghandhari, Mehrdad; Eriksson, Robert

    2016-01-01

    This paper examines the application of a hybrid HVDC link in a two area power system with the purpose of increasing the inter-regional power transfer. A hybrid HVDC system combines both LCCs and VSCs, and hence it is capable of combining the benefits of both converter technologies, such as reduced...... cost and power losses due to the LCCs, and ability to connect to weak AC grids due to the VSCs. The mathematical model of the power system including the HVDC link is presented. The increase in inter-area power transfer is demonstrated and compared to the case when the hybrid HVDC link is not used....... Furthermore, the transient stability of the AC/DC power system was enhanced using auxiliary controllers for Power Oscillation Damping (POD). The results show the ability of the hybrid HVDC link to increase the unidirectional inter-area power transfer, while enhancing the transient stability of the power...

  17. Filling the Gap : Relationship Between the Serotonin-Transporter-Linked Polymorphic Region and Amygdala Activation

    NARCIS (Netherlands)

    Bastiaansen, Jojanneke A.; Servaas, Michelle N.; Marsman, Jan-Bernard; Ormel, Johan; Nolte, Ilja M.; Riese, Harriette; Aleman, Andre

    2014-01-01

    The alleged association between the serotonin-transporter-linked polymorphic region (5-HTTLPR) and amygdala activation forms a cornerstone of the common view that carrying the short allele of this polymorphism is a potential risk factor for affective disorders. The authors of a recent meta-analysis

  18. Filling the Gap : Relationship Between the Serotonin-Transporter-Linked Polymorphic Region and Amygdala Activation

    NARCIS (Netherlands)

    Bastiaansen, Jojanneke A.; Servaas, Michelle N.; Marsman, Jan-Bernard; Ormel, Johan; Nolte, Ilja M.; Riese, Harriette; Aleman, Andre

    The alleged association between the serotonin-transporter-linked polymorphic region (5-HTTLPR) and amygdala activation forms a cornerstone of the common view that carrying the short allele of this polymorphism is a potential risk factor for affective disorders. The authors of a recent meta-analysis

  19. Genomic regions associated with the sex-linked inhibitor of dermal melanin in Silkie chicken

    Directory of Open Access Journals (Sweden)

    Ming TIAN,Rui HAO,Suyun FANG,Yanqiang WANG,Xiaorong GU,Chungang FENG,Xiaoxiang HU,Ning LI

    2014-09-01

    Full Text Available A unique characteristic of the Silkie chicken is its fibromelanosis phenotype. The dermal layer of its skin, its connective tissue and shank dermis are hyperpigmented. This dermal hyperpigmentation phenotype is controlled by the sex-linked inhibitor of dermal melanin gene (ID and the dominant fibromelanosis allele. This study attempted to confirm the genomic region associated with ID. By genotyping, ID was found to be closely linked to the region between GGA_rs16127903 and GGA_rs14685542 (8406919 bp on chromosome Z, which contains ten functional genes. The expression of these genes was characterized in the embryo and 4 days after hatching and it was concluded that MTAP, encoding methylthioadenosinephosphorylase, would be the most likely candidate gene. Finally, target DNA capture and sequence analysis was performed, but no specific SNP(s was found in the targeted region of the Silkie genome. Further work is necessary to identify the causal ID mutation located on chromosome Z.

  20. Epidemiological link of a major cholera outbreak in Greater Accra region of Ghana, 2014.

    Science.gov (United States)

    Ohene-Adjei, Kennedy; Kenu, Ernest; Bandoh, Delia Akosua; Addo, Prince Nii Ossah; Noora, Charles Lwanga; Nortey, Priscillia; Afari, Edwin Andrew

    2017-10-11

    Cholera remains an important public health challenge globally. Several pandemics have occurred in different parts of the world and have been epidemiologically linked by different researchers to illustrate how the cases were spread and how they were related to index cases. Even though the risk factors associated with the 2014 cholera outbreak were investigated extensively, the link between index cases and the source of infection was not investigated to help break the transmission process. This study sought to show how the index cases from various districts of the Greater Accra Region may have been linked. We carried out a descriptive cross sectional study to investigate the epidemiological link of the 2014 cholera outbreak in the Greater Accra region of Ghana. An extensive review of all district records on cholera cases in the Greater Accra region was carried out. Index cases were identified with the help of line lists. Univariate analyses were expressed as frequency distributions, percentages, mean ± Standard Deviation, and rates (attack rates, case-fatality rates etc.) as appropriate. Maps were drawn using Arc GIS and Epi info software to describe the pattern of transmission. Up to 20,199 cholera cases were recorded. Sixty percent of the cases were between 20 and 40 years and about 58% (11,694) of the total cases were males. Almost 50% of the cases occurred in the Accra Metro district. Two-thirds of the index cases ate food prepared outside their home and had visited the Accra Metropolis. The 2014 cholera outbreak can be described as a propagated source outbreak linked to the Accra Metropolis. The link between index cases and the source of infection, if investigated earlier could have helped break the transmission process. Such investigations also inform decision-making about the appropriate interventions to be instituted to prevent subsequent outbreaks.

  1. Transport corridors and settlements in a region. Linking settlements to public transport

    Directory of Open Access Journals (Sweden)

    Mojca Šašek Divjak

    2004-01-01

    Full Text Available The focus of the article is conditioning settlement to public transport on the regional and urban level. Similar to occurrences in Western Europe even in Slovenia strong settlement pressures and issues tied to development of suburbanisation are emerging in wider hinterlands of larger cities. In regional centres, where strong transport flows with frequent congestion happen, public transport should be the backbone of the transport system. It is important for consolidation of larger gravitation areas, especially conurbations. We can nevertheless establish that parallel to increasing use of private cars, the use of public transport is decreasing. Thus the present condition demands improvements of transport systems and suitable settlement density in conjunction with development of public transport. This can be achieved only by synergetic linking of public transport development and physical planning in a sustainable settlement system. In the Ljubljana functional region we specifically dealt with links between settlement and the regional public transport system, above all the proposed regional light-railway and tram system in the strict urban area. The decentralised denser settlement model is presented. Based on the study concerning settlement development in the railway corridors we proposed potential possibilities for denser settlement in the immediate areas of suburban railway stations in the northern part of the region, from Črnuče to Kamnik.

  2. Increased levels of NOTCH1, NF-kappaB, and other interconnected transcription factors characterize primitive sets of hematopoietic stem cells.

    Science.gov (United States)

    Panepucci, Rodrigo Alexandre; Oliveira, Lucila Habib B; Zanette, Dalila Luciola; Viu Carrara, Rita de Cassia; Araujo, Amélia Goes; Orellana, Maristela Delgado; Bonini de Palma, Patrícia Vianna; Menezes, Camila C B O; Covas, Dimas Tadeu; Zago, Marco Antonio

    2010-03-01

    As previously shown, higher levels of NOTCH1 and increased NF-kappaB signaling is a distinctive feature of the more primitive umbilical cord blood (UCB) CD34+ hematopoietic stem cells (HSCs), as compared to bone marrow (BM). Differences between BM and UCB cell composition also account for this finding. The CD133 marker defines a more primitive cell subset among CD34+ HSC with a proposed hemangioblast potential. To further evaluate the molecular basis related to the more primitive characteristics of UCB and CD133+ HSC, immunomagnetically purified human CD34+ and CD133+ cells from BM and UCB were used on gene expression microarrays studies. UCB CD34+ cells contained a significantly higher proportion of CD133+ cells than BM (70% and 40%, respectively). Cluster analysis showed that BM CD133+ cells grouped with the UCB cells (CD133+ and CD34+) rather than to BM CD34+ cells. Compared with CD34+ cells, CD133+ had a higher expression of many transcription factors (TFs). Promoter analysis on all these TF genes revealed a significantly higher frequency (than expected by chance) of NF-kappaB-binding sites (BS), including potentially novel NF-kappaB targets such as RUNX1, GATA3, and USF1. Selected transcripts of TF related to primitive hematopoiesis and self-renewal, such as RUNX1, GATA3, USF1, TAL1, HOXA9, HOXB4, NOTCH1, RELB, and NFKB2 were evaluated by real-time PCR and were all significantly positively correlated. Taken together, our data indicate the existence of an interconnected transcriptional network characterized by higher levels of NOTCH1, NF-kappaB, and other important TFs on more primitive HSC sets.

  3. The neuro-glial properties of adipose-derived adult stromal (ADAS) cells are not regulated by Notch 1 and are not derived from neural crest lineage.

    Science.gov (United States)

    Wrage, Philip C; Tran, Thi; To, Khai; Keefer, Edward W; Ruhn, Kelly A; Hong, John; Hattangadi, Supriya; Treviño, Isaac; Tansey, Malú G

    2008-01-16

    We investigated whether adipose-derived adult stromal (ADAS) are of neural crest origin and the extent to which Notch 1 regulates their growth and differentiation. Mouse ADAS cells cultured in media formulated for neural stem cells (NSC) displayed limited capacity for self-renewal, clonogenicity, and neurosphere formation compared to NSC from the subventricular zone in the hippocampus. Although ADAS cells expressed Nestin, GFAP, NSE and Tuj1 in vitro, exposure to NSC differentiation supplements did not induce mature neuronal marker expression. In contrast, in mesenchymal stem cell (MSC) media, ADAS cells retained their ability to proliferate and differentiate beyond 20 passages and expressed high levels of Nestin. In neuritizing cocktails, ADAS cells extended processes, downregulated Nestin expression, and displayed depolarization-induced Ca(2+) transients but no spontaneous or evoked neural network activity on Multi-Electrode Arrays. Deletion of Notch 1 in ADAS cell cultures grown in NSC proliferation medium did not significantly alter their proliferative potential in vitro or the differentiation-induced downregulation of Nestin. Co-culture of ADAS cells with fibroblasts that stably expressed the Notch ligand Jagged 1 or overexpression of the Notch intracellular domain (NICD) did not alter ADAS cell growth, morphology, or cellular marker expression. ADAS cells did not display robust expression of neural crest transcription factors or genes (Sox, CRABP2, and TH); and lineage tracing analyses using Wnt1-Cre;Rosa26R-lacZ or -EYFP reporter mice confirmed that fewer than 2% of the ADAS cell population derived from a Wnt1-positive population during development. In summary, although media formulations optimized for MSCs or NSCs enable expansion of mouse ADAS cells in vitro, we find no evidence that these cells are of neural crest origin, that they can undergo robust terminal differentiation into functionally mature neurons, and that Notch 1 is likely to be a key

  4. 14q deletions are associated with trisomy 12, NOTCH1 mutations and unmutated IGHV genes in chronic lymphocytic leukemia and small lymphocytic lymphoma.

    Science.gov (United States)

    Cosson, Adrien; Chapiro, Elise; Belhouachi, Nabila; Cung, Hong-Anh; Keren, Boris; Damm, Frederik; Algrin, Caroline; Lefebvre, Christine; Fert-Ferrer, Sandra; Luquet, Isabelle; Gachard, Nathalie; Mugneret, Francine; Terre, Christine; Collonge-Rame, Marie-Agnes; Michaux, Lucienne; Rafdord-Weiss, Isabelle; Talmant, Pascaline; Veronese, Lauren; Nadal, Nathalie; Struski, Stephanie; Barin, Carole; Helias, Catherine; Lafage, Marina; Lippert, Eric; Auger, Nathalie; Eclache, Virginie; Roos-Weil, Damien; Leblond, Veronique; Settegrana, Catherine; Maloum, Karim; Davi, Frederic; Merle-Beral, Helene; Lesty, Claude; Nguyen-Khac, Florence

    2014-08-01

    Deletions of the long arm of chromosome 14 [del(14q)] are rare but recurrently observed in mature B-cell neoplasms, particularly in chronic lymphocytic leukemia (CLL). To further characterize this aberration, we studied 81 cases with del(14q): 54 of CLL and 27 of small lymphocytic lymphoma (SLL), the largest reported series to date. Using karyotype and fluorescence in situ hybridization (FISH), the most frequent additional abnormality was trisomy 12 (tri12), observed in 28/79 (35%) cases, followed by del13q14 (12/79, 15%), delTP53 (11/80, 14%) delATM (5/79, 6%), and del6q21 (3/76, 4%). IGHV genes were unmutated in 41/53 (77%) patients, with a high frequency of IGHV1-69 (21/52, 40%). NOTCH1 gene was mutated in 14/45 (31%) patients. There was no significant difference in cytogenetic and molecular abnormalities between CLL and SLL. Investigations using FISH and SNP-array demonstrated the heterogeneous size of the 14q deletions. However, a group with the same del(14)(q24.1q32.33) was identified in 48% of cases. In this group, tri12 (P = 0.004) and NOTCH1 mutations (P = 0.02) were significantly more frequent than in the other patients. In CLL patients with del(14q), median treatment-free survival (TFS) was 27 months. In conclusion, del(14q) is associated with tri12 and with pejorative prognostic factors: unmutated IGHV genes (with over-representation of the IGHV1-69 repertoire), NOTCH1 mutations, and a short TFS. © 2014 Wiley Periodicals, Inc.

  5. Relay Placement for FSO Multihop DF Systems With Link Obstacles and Infeasible Regions

    KAUST Repository

    Zhu, Bingcheng

    2015-05-19

    Optimal relay placement is studied for free-space optical multihop communication with link obstacles and infeasible regions. An optimal relay placement scheme is proposed to achieve the lowest outage probability, enable the links to bypass obstacles of various geometric shapes, and place the relay nodes in specified available regions. When the number of relay nodes is large, the searching space can grow exponentially, and thus, a grouping optimization technique is proposed to reduce the searching time. We numerically demonstrate that the grouping optimization can provide suboptimal solutions close to the optimal solutions, but the average searching time linearly grows with the number of relay nodes. Two useful theorems are presented to reveal insights into the optimal relay locations. Simulation results show that our proposed optimization framework can effectively provide desirable solution to the problem of optimal relay nodes placement. © 2015 IEEE.

  6. Comprehensive Regional Modeling for Long-Range Planning: Linking Integrated Urban Models and Geographic Information Systems

    OpenAIRE

    Johnston, Robert; de la Barra, Thomas

    2000-01-01

    This study demonstrates the sequential linking of two types of models to permit the comprehensive evaluation of regional transportation and land use policies. First, we operate an integrated urban model (TRANUS), which represents both land and travel markets with zones and networks. The travel and land use projections from TRANUS are outlined, to demonstrate the general reasonableness of the results, as this is the first application of a market-based urban model in the US. Second, the land us...

  7. A regionally-linked, dynamic material flow modelling tool for rolled, extruded and cast aluminium products

    DEFF Research Database (Denmark)

    Bertram, M.; Ramkumar, S.; Rechberger, H.

    2017-01-01

    A global aluminium flow modelling tool, comprising nine trade linked regions, namely China, Europe, Japan, Middle East, North America, Other Asia, Other Producing Countries, South America and Rest of World, has been developed. The purpose of the Microsoft Excel-based tool is the quantification...... of regional stocks and flows of rolled, extruded and casting alloys across space and over time, giving the industry the ability to evaluate the potential to recycle aluminium scrap most efficiently. The International Aluminium Institute will update the tool annually and publish a visualisation of results...

  8. Short telomere length is associated with NOTCH1/SF3B1/TP53 aberrations and poor outcome in newly diagnosed chronic lymphocytic leukemia patients

    DEFF Research Database (Denmark)

    Mansouri, Larry; Grabowski, Pawel; Degerman, Sofie

    2013-01-01

    Most previous studies on telomere length (TL) in chronic lymphocytic leukemia (CLL) are based on referral cohorts including a high proportion of aggressive cases. Here, the impact of TL was analyzed in a population-based cohort of newly diagnosed CLL (n = 265) and in relation to other prognostic ...... markers. Short telomeres were particularly associated with high-risk genetic markers, such as NOTCH1, SF3B1, or TP53 aberrations, and predicted a short time to treatment (TTT) and overall survival (OS) (both P...

  9. Hematopoietic stem cell-derived exosomes promote hematopoietic differentiation of mouse embryonic stem cells in vitro via inhibiting the miR126/Notch1 pathway.

    Science.gov (United States)

    Liao, Feng-Ling; Tan, Lin; Liu, Hua; Wang, Jin-Ju; Ma, Xiao-Tang; Zhao, Bin; Chen, Yanfang; Bihl, Ji; Yang, Yi; Chen, Ri-Ling

    2018-04-01

    Cell-derived exosomes (EXs) can modulate target cell differentiation via microRNAs (miRs) that they carried. Previous studies have shown that miR126 is highly expressed in hematopoietic stem cells (HSCs) and plays a role in hematopoiesis via modulating the Notch pathway that participates in progenitors' cell fate decisions. In this study we investigated whether HSC-derived EXs (HSC-EXs) could affect the differentiation of mouse embryonic stem cells (ESCs) into HSCs. We prepared HSC-EXs con , HSC-EXs sc and HSC-EXs miR126 from control HSCs and the HSCs transfected with scramble control or miR126 mimics, respectively. HSC-EXs were isolated by ultracentrifugation and analyzed using nanoparticle tracking analysis. We incubated the collected EXs with mouse ESCs over a 10-d differentiation induction period, during which HSC-EXs and a Notch pathway activator (Jagged1, 100 ng/mL) were added to the cultures every 3 d. After the 10-d differentiation period, the expression levels of miR126, SSEA1, CD117, Sca1, Notch1 and Hes1 in ESCs were assessed. The generated HSCs were validated by flow cytometry using antibodies against HSC markers (CD117, CD34 and Sca1). Our results revealed that: (1) transfection with miR126 mimics significantly increased miR126 levels in HSC-EXs miR126 . (2) HSC-EX co-culture promoted mouse ESCs differentiation into HSCs with the most prominent effect found in the HSC-EXs miR126 co-culture. (3) HSC differentiation was verified by reduced SSEA1 expression and increased CD117 and Sca1 expression. (4) All the effects caused by HSC-EXs were accompanied by significant reduction of Notch1 and Hes1 expression, thus inhibition of the Notch1/Hes1 pathway, whereas activation of Notch by Jagged1 abolished the effects of HSC-EXs miR126 . In conclusion, HSC-EXs promote hematopoietic differentiation of mouse ESCs in vitro by inhibiting the miR126/Notch1 pathway.

  10. Fixed Links and Vague Discourses About Culture and the Making of Cross-border Regions

    Directory of Open Access Journals (Sweden)

    Birgit Stöber

    2011-06-01

    Full Text Available It has been en vogue for official bodies to focus on ‘culture’ as a strategic factor for the development of spatial entities such as cross-border regions in the making. This focus places high expectations and a strong belief in the power of ‘culture’. In this paper I will argue that in region building processes the focus on ‘culture’ is often due to an overriding wish to develop an economic well-functioning region. Moreover, it seems like ‘culture’ is used as a tool to distract people from a critique of bigger infrastructure projects that such developments entail. In order to strengthen these arguments, the paper will focus on two examples from Northern Europe, the existing Danish-Swedish Øresund link as well as the planned link between Denmark and Germany across the Femernbelt. In the course of the paper, focus will be on central bodies or actors that are taking up the issue of culture within a regional context. Hence, the concept of governance, particularly that of networked governance structures as well co-governance will be briefly discussed. All in all, the paper shows the ‘fragmented complexity of agency and the multitude of actors related to region building’ (Paasi 2010:2300.

  11. Garcinol downregulates Notch1 signaling via modulating miR-200c and suppresses oncogenic properties of PANC-1 cancer stem-like cells.

    Science.gov (United States)

    Huang, Chi-Cheng; Lin, Chien-Min; Huang, Yan-Jiun; Wei, Li; Ting, Lei-Li; Kuo, Chia-Chun; Hsu, Cheyu; Chiou, Jeng-Fong; Wu, Alexander T H; Lee, Wei-Hwa

    2017-03-01

    Pancreatic cancer represents one of the most aggressive types of malignancy due to its high resistance toward most clinically available treatments. The presence of pancreatic cancer stem-like cells (CSCs) has been attributed to the intrinsically high resistance and highly metastatic potential of this disease. Here, we identified and isolated pancreatic CSCs using the side population (SP) method from human pancreatic cancer cell line, PANC-1. We then compared the SP and non-SP PANC-1 cells genetically. PANC-1 SP cells exhibited CSC properties including enhanced self-renewal ability, increased metastatic potential, and resistance toward gemcitabine treatment. These cancer stem-like phenotypes were supported by their enhanced expression of ABCG2, Oct4, and CD44. A traditional plant-derived antioxidant, garcinol, has been implicated for its anticancer properties. Here, we found that garcinol treatment to PANC-1 SP cells significantly suppressed the stem-like properties of PANC-1 SP cells and metastatic potential by downregulating the expression of Mcl-1, EZH2, ABCG2, Gli-1, and Notch1. More importantly, garcinol treatment led to the upregulation of several tumor suppressor microRNAs, and miR-200c increased by garcinol treatment was found to target and downregulate Notch1. Thus, PANC-1 SP cells may serve as a model for studying drug-resistant pancreatic CSCs, and garcinol has the potential as an antagonist against pancreatic CSCs. © 2015 International Union of Biochemistry and Molecular Biology, Inc.

  12. Notch 1 Receptor, Delta 1 Ligand and HES 1 Transcription Factor are Expressed in the Lining Epithelium of Periapical Cysts (Preliminary Study).

    Science.gov (United States)

    Meliou, E; Kerezoudis, Np; Tosios, Ki; Kiaris, H

    2010-07-27

    Periapical cyst is a chronic inflammatory disorder of periradicular tissues. The precise pathological mechanisms involved in periapical cyst enlargement remain unclear. Notch signaling is an evolutionarily conserved pathway with a regulatory role in cell fate decisions during development and in carcinogenesis. To date, there are no published data available on the expression of Notch signaling components in periapical cysts or any other jaw cyst. In this immunohistochemical study we have examined the expression of the receptor Notch 1, the ligand Delta 1 and the transcription factor HES 1 in the epithelium of well defined periapical cysts. Immunostaining reaction of Notch 1, Delta 1 and HES 1 was observed in the cytoplasm and/or the cytoplasmic membrane and occasionally in the nucleus in the majority of epithelial cells of all periapical cysts. The present observations indicate that Notch pathway is active in the epithelium of periapical cysts. It can be speculated that activation of epithelial cells of periapical cysts is associated with activation of Notch pathway and imply involvement of this pathway in periapical cyst growth and expansion.

  13. New insights into Notch1 regulation of the PI3K-AKT-mTOR1 signaling axis: targeted therapy of γ-secretase inhibitor resistant T-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Hales, Eric C; Taub, Jeffrey W; Matherly, Larry H

    2014-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) is characterized as a high-risk stratified disease associated with frequent relapse, chemotherapy resistance, and a poorer prognostic outlook than B-precursor ALL. Many of the challenges in treating T-ALL reflect the lack of prognostic cytogenetic or molecular abnormalities on which to base therapy, including targeted therapy. Notch1 activating mutations were identified in more than 50% of T-ALL cases and can be therapeutically targeted with γ-secretase inhibitors (GSIs). Mutant Notch1 can activate cMyc and PI3K-AKT-mTOR1 signaling in T-ALL. In T-ALLs with wild-type phosphatase and tensin homolog deleted on chromosome ten (PTEN), Notch1 transcriptionally represses PTEN, an effect reversible by GSIs. Notch1 also promotes growth factor receptor (IGF1R and IL7Rα) signaling to PI3K-AKT. Loss of PTEN is common in primary T-ALLs due to mutation or posttranslational inactivation and results in chronic activation of PI3K-AKT-mTOR1 signaling, GSI-resistance, and repression of p53-mediated apoptosis. Notch1 itself might regulate posttranslational inactivation of PTEN. PP2A is activated by Notch1 in PTEN-null T-ALL cells, and GSIs reduce PP2A activity and increase phosphorylation of AKT, AMPK, and p70S6K. This review focuses on the central role of the PI3K-AKT-mTOR1 signaling in T-ALL, including its regulation by Notch1 and potential therapeutic interventions, with emphasis on GSI-resistant T-ALL. © 2013.

  14. Fixed Links and Vague Discourses About Culture and the Making of Cross-Border Regions

    DEFF Research Database (Denmark)

    Stöber, Birgit

    2011-01-01

    these arguments, the paper will focus on two examples from Northern Europe, the existing Danish-Swedish Øresund link as well as the planned link between Denmark and Germany across the Femernbelt. In the course of the paper, focus will be on central bodies or actors that are taking up the issue of culture within......It has been en vogue for official bodies to focus on ‘culture’ as a strategic factor for the development of spatial entities such as cross-border regions in the making. This focus places high expectations and a strong belief in the power of ‘culture’. In this paper I will argue that in region...... building processes the focus on ‘culture’ is often due to an overriding wish to develop an economic well-functioning region. Moreover, it seems like ‘culture’ is used as a tool to distract people from a critique of bigger infrastructure projects that such developments entail. In order to strengthen...

  15. X-linked recessive panhypopituitarism associated with a regional duplication in Xq25-q26.

    Science.gov (United States)

    Lagerström-Fermér, M; Sundvall, M; Johnsen, E; Warne, G L; Forrest, S M; Zajac, J D; Rickards, A; Ravine, D; Landegren, U; Pettersson, U

    1997-01-01

    We present a linkage analysis and a clinical update on a previously reported family with X-linked recessive panhypopituitarism, now in its fourth generation. Affected members exhibit variable degrees of hypopituitarism and mental retardation. The markers DXS737 and DXS1187 in the q25-q26 region of the X chromosome showed evidence for linkage with a peak LOD score (Zmax) of 4.12 at zero recombination fraction (theta(max) = 0). An apparent extra copy of the marker DXS102, observed in the region of the disease gene in affected males and heterozygous carrier females, suggests that a segment including this marker is duplicated. The gene causing this disorder appears to code for a dosage-sensitive protein central to development of the pituitary. Images Figure 2 PMID:9106538

  16. Congenital olfactory impairment is linked to cortical changes in prefrontal and limbic brain regions

    DEFF Research Database (Denmark)

    Karstensen, Helena Gásdal; Vestergaard, Martin; Baaré, William F C

    2018-01-01

    differently in individuals who suffer from lifelong olfactory deprivation relative to healthy normosmic individuals. To address this question, we examined if regional variations in gray matter volume were associated with smell ability in seventeen individuals with isolated congenital olfactory impairment (COI...... in left middle frontal gyrus and right superior frontal sulcus (SFS). COI subjects with severe olfactory impairment (anosmia) had reduced grey matter volume in the left mOFC and increased volume in right piriform cortex and SFS. Within the COI group olfactory ability, measured with the "Sniffin' Sticks...... piriform cortex, while olfactory identification was negatively associated with right SFS volume. Our findings suggest that lifelong olfactory deprivation trigger changes in the cortical volume of prefrontal and limbic brain regions previously linked to olfactory memory....

  17. Linking intended visitation to regional economic impact models of bison and elk management

    Science.gov (United States)

    Loomis, J.; Caughlan, L.

    2004-01-01

    This article links intended National Park visitation estimates to regional economic models to calculate the employment impacts of alternative bison and elk management strategies. The survey described alternative National Elk Refuge (NER) management actions and the effects on elk and bison populations at the NER and adjacent Grand Teton National Park (GTNP). Park visitors were then asked if they would change their number of visits with each potential management action. Results indicate there would be a 10% decrease in visitation if bison populations were reduced from 600 to 400 animals and elk populations were reduced in GTNP and the NER. The related decrease in jobs in Teton counties of Wyoming and Idaho is estimated at 5.5%. Adopting a “no active management” option of never feeding elk and bison on the NER yields about one-third the current bison population (200 bison) and about half the elk population. Visitors surveyed about this management option would take about 20% fewer trips, resulting in an 11.3% decrease in employment. Linking intended visitation surveys and regional economic models represents a useful tool for natural resource planners who must present the consequences of potential actions in Environmental Impact Statements and plans to the public and decision makers prior to any action being implemented.

  18. Clonal analysis of Notch1-expressing cells reveals the existence of unipotent stem cells that retain long-term plasticity in the embryonic mammary gland.

    Science.gov (United States)

    Lilja, Anna M; Rodilla, Veronica; Huyghe, Mathilde; Hannezo, Edouard; Landragin, Camille; Renaud, Olivier; Leroy, Olivier; Rulands, Steffen; Simons, Benjamin D; Fre, Silvia

    2018-06-01

    Recent lineage tracing studies have revealed that mammary gland homeostasis relies on unipotent stem cells. However, whether and when lineage restriction occurs during embryonic mammary development, and which signals orchestrate cell fate specification, remain unknown. Using a combination of in vivo clonal analysis with whole mount immunofluorescence and mathematical modelling of clonal dynamics, we found that embryonic multipotent mammary cells become lineage-restricted surprisingly early in development, with evidence for unipotency as early as E12.5 and no statistically discernable bipotency after E15.5. To gain insights into the mechanisms governing the switch from multipotency to unipotency, we used gain-of-function Notch1 mice and demonstrated that Notch activation cell autonomously dictates luminal cell fate specification to both embryonic and basally committed mammary cells. These functional studies have important implications for understanding the signals underlying cell plasticity and serve to clarify how reactivation of embryonic programs in adult cells can lead to cancer.

  19. Mutations in noncoding regions of GJB1 are a major cause of X-linked CMT

    Science.gov (United States)

    Tomaselli, Pedro J.; Rossor, Alexander M.; Horga, Alejandro; Jaunmuktane, Zane; Carr, Aisling; Saveri, Paola; Piscosquito, Giuseppe; Pareyson, Davide; Laura, Matilde; Blake, Julian C.; Poh, Roy; Polke, James; Houlden, Henry

    2017-01-01

    Objective: To determine the prevalence and clinical and genetic characteristics of patients with X-linked Charcot-Marie-Tooth disease (CMT) due to mutations in noncoding regions of the gap junction β-1 gene (GJB1). Methods: Mutations were identified by bidirectional Sanger sequence analysis of the 595 bases of the upstream promoter region, and 25 bases of the 3′ untranslated region (UTR) sequence in patients in whom mutations in the coding region had been excluded. Clinical and neurophysiologic data were retrospectively collected. Results: Five mutations were detected in 25 individuals from 10 kindreds representing 11.4% of all cases of CMTX1 diagnosed in our neurogenetics laboratory between 1996 and 2016. Four pathogenic mutations, c.-17G>A, c.-17+1G>T, c.-103C>T, and c.-146-90_146-89insT were detected in the 5′UTR. A novel mutation, c.*15C>T, was detected in the 3′ UTR of GJB1 in 2 unrelated families with CMTX1 and is the first pathogenic mutation in the 3′UTR of any myelin-associated CMT gene. Mutations segregated with the phenotype, were at sites predicted to be pathogenic, and were not present in the normal population. Conclusions: Mutations in noncoding DNA are a major cause of CMTX1 and highlight the importance of mutations in noncoding DNA in human disease. Next-generation sequencing platforms for use in inherited neuropathy should therefore include coverage of these regions. PMID:28283593

  20. The NatCarb geoportal: Linking distributed data from the Carbon Sequestration Regional Partnerships

    Science.gov (United States)

    Carr, T.R.; Rich, P.M.; Bartley, J.D.

    2007-01-01

    The Department of Energy (DOE) Carbon Sequestration Regional Partnerships are generating the data for a "carbon atlas" of key geospatial data (carbon sources, potential sinks, etc.) required for rapid implementation of carbon sequestration on a broad scale. The NATional CARBon Sequestration Database and Geographic Information System (NatCarb) provides Web-based, nation-wide data access. Distributed computing solutions link partnerships and other publicly accessible repositories of geological, geophysical, natural resource, infrastructure, and environmental data. Data are maintained and enhanced locally, but assembled and accessed through a single geoportal. NatCarb, as a first attempt at a national carbon cyberinfrastructure (NCCI), assembles the data required to address technical and policy challenges of carbon capture and storage. We present a path forward to design and implement a comprehensive and successful NCCI. ?? 2007 The Haworth Press, Inc. All rights reserved.

  1. Association of the serotonin transporter-linked polymorphic region genotype with lower bone mineral density.

    Science.gov (United States)

    Lapid, M I; Kung, S; Frye, M A; Biernacka, J M; Geske, J R; Drake, M T; Jankowski, M D; Clarke, B L

    2017-08-22

    The serotonin transporter-linked polymorphic region (5-HTTLPR) of the serotonin transporter gene (SLC6A4) S allele is linked to pathogenesis of depression and slower response to selective serotonin reuptake inhibitors (SSRIs); depression and SSRIs are independently associated with bone loss. We aimed to determine whether 5-HTTLPR was associated with bone loss. This cross-sectional study included psychiatric patients with both 5-HTTLPR analysis and bone mineral density (BMD) assessment (hip and spine Z-scores if age <50 years and T-scores if ⩾50 years). BMD association with 5-HTTLPR was evaluated under models with additive allele effects and dominant S allele effects using linear regression models. Patients were stratified by age (<50 and ⩾50 years) and sex. Of 3016 patients with 5-HTTLPR genotyping, 239 had BMD assessments. Among the younger patients, the S allele was associated with lower Z-scores at the hip (P=0.002, dominant S allele effects; P=0.004, additive allele effects) and spine (P=0.0006, dominant S allele effects; P=0.01, additive allele effects). In sex-stratified analyses, the association of the S allele with lower BMD in the younger patients was also significant in the subset of women (P⩽0.003 for both hip and spine BMD under the additive allele effect model). In the small group of men younger than 50 years, the S allele was marginally associated with higher spine BMD (P=0.05). BMD T-scores were not associated with 5-HTTLPR genotypes in patients 50 years or older. The 5-HTTLPR variants may modify serotonin effects on bone with sex-specific effects.

  2. Illegitimate V(D)J recombination-mediated deletions in Notch1 and Bcl11b are not sufficient for extensive clonal expansion and show minimal age or sex bias in frequency or junctional processing

    Energy Technology Data Exchange (ETDEWEB)

    Champagne, Devin P., E-mail: devin.champagne@uvm.edu; Shockett, Penny E., E-mail: pshockett@selu.edu

    2014-03-15

    Highlights: • Examines illegitimate V(D)J deletion junctions in Notch1 and Bcl11b. • Suggests little influence of deletions alone on clonal outgrowth in wild-type mice. • No age or sex biases in frequency, clonality, or junctional processing observed. • Contrasts with previous results at TCRβ and HPRT1 loci. • Deletions in Bcl11b may be tolerated more easily than those in Notch1. - Abstract: Illegitimate V(D)J recombination at oncogenes and tumor suppressor genes is implicated in formation of several T cell malignancies. Notch1 and Bcl11b, genes involved in developing T cell specification, selection, proliferation, and survival, were previously shown to contain hotspots for deletional illegitimate V(D)J recombination associated with radiation-induced thymic lymphoma. Interestingly, these deletions were also observed in wild-type animals. In this study, we conducted frequency, clonality, and junctional processing analyses of Notch1 and Bcl11b deletions during mouse development and compared results to published analyses of authentic V(D)J rearrangements at the T cell receptor beta (TCRβ) locus and illegitimate V(D)J deletions observed at the human, nonimmune HPRT1 locus not involved in T cell malignancies. We detect deletions in Notch1 and Bcl11b in thymic and splenic T cell populations, consistent with cells bearing deletions in the circulating lymphocyte pool. Deletions in thymus can occur in utero, increase in frequency between fetal and postnatal stages, are detected at all ages examined between fetal and 7 months, exhibit only limited clonality (contrasting with previous results in radiation-sensitive mouse strains), and consistent with previous reports are more frequent in Bcl11b, partially explained by relatively high Recombination Signal Information Content (RIC) scores. Deletion junctions in Bcl11b exhibit greater germline nucleotide loss, while in Notch1 palindromic (P) nucleotides are more abundant, although average P nucleotide length is

  3. Neglected diseases and ethnic minorities in the Western Pacific Region exploring the links.

    Science.gov (United States)

    Schratz, Alexander; Pineda, Martha Fernanda; Reforma, Liberty G; Fox, Nicole M; Le Anh, Tuan; Tommaso Cavalli-Sforza, L; Henderson, Mackenzie K; Mendoza, Raymond; Utzinger, Jürg; Ehrenberg, John P; Tee, Ah Sian

    2010-01-01

    Ethnic minority groups (EMGs) are often subject to exclusion, marginalization and poverty. These characteristics render them particularly vulnerable to neglected diseases, a diverse group of diseases that comprise bacteria, ecto-parasites, fungi, helminths and viruses. Despite the health policy relevance, only little is known of the epidemiological profile of neglected diseases among EMGs. We reviewed country data from Australia, Cambodia, Lao People's Democratic Republic, Malaysia, the Philippines and Vietnam and found several overlaps between regions with high proportions of EMG population and high prevalence rates of neglected diseases (infections with soil-transmitted helminths, filarial worms, schistosomes, food-borne trematodes and cestodes). While the links are not always clearly evident and it is impossible to establish correlations among highly aggregated data without control variables-such as environmental factors-there appear indeed to be important linkages between EMGs, socio-economic status and prevalence of neglected diseases. Some determinants under consideration are lack of access to health care and general health status, poverty and social marginalization, as well as education and literacy. Further research is needed to deepen the understanding of these linkages and to determine their public health and socio-economic significance. In particular, there is a need for more data from all countries in the Western Pacific Region that is disaggregated below the provincial level. Selected case studies that incorporate other control variables-such as risk factors from the physical environment-might be useful to inform policy makers about the feasibility of prevention and control interventions that are targeted at high-risk EMGs.

  4. Perceived discrimination, serotonin transporter linked polymorphic region status, and the development of conduct problems.

    Science.gov (United States)

    Brody, Gene H; Beach, Steven R H; Chen, Yi-Fu; Obasi, Ezemenari; Philibert, Robert A; Kogan, Steven M; Simons, Ronald L

    2011-05-01

    This study examined the prospective relations of adolescents' perceptions of discrimination and their genetic status with increases in conduct problems. Participants were 461 African American youths residing in rural Georgia (Wave 1 mean age = 15.5 years) who provided three waves of data and a saliva sample from which a polymorphism in the SCL6A4 (serotonin transporter [5-HTT]) gene polymorphism known as the 5-HTT linked promoter region (5-HTTLPR) was genotyped. Data analyses using growth curve modeling indicated that perceived discrimination was significantly related to the slope of conduct problems. As hypothesized, interactions between perceived discrimination and genetic status emerged for male but not female youths. Compared with those carrying two copies of the long allele variant of 5-HTTLPR, male youths carrying one or two copies of its short allele variant evinced higher rates of conduct problems over time when they perceived high levels of racial discrimination. These findings are consistent with resilience and differential susceptibility propositions stating that genes can both foster sensitivity to adverse events and confer protection from those events.

  5. Expresión de los genes Serrate1 y Notch1 durante el desarrollo del tercio medio facial del embrión de pollo.

    Directory of Open Access Journals (Sweden)

    Daniel Mauricio Meza Lasso

    2016-01-01

    Full Text Available La vía de señalización Notch se caracteriza por mediar la comunicación célula-célula, regulando diferentes procesos celulares como proliferación, apoptosis y definición del destino celular. Esta vía ha sido implicada en el desarrollo de estructuras craneofaciales como paladar, diente y bóveda craneal. El objetivo de esta investigación fue identificar los patrones de expresión de los genes componentes de la vía Notch, Serrate1 y Notch1, durante el desarrollo del tercio medio facial. Se utilizaron embriones de pollo (Gallus gallus seleccionados de acuerdo a los criterios de Hamilton y Hamburger y sobre los cuales se realizó hibridación in situ con ribosondas marcadas con Digoxigenina (DIG, para luego ser detectadas con anticuerpos Anti-Dig. Los resultados mostraron expresión de los genes evaluados, en las prominencias maxilares (pmx y frontonasal (pfn durante el desarrollo del tercio medio facial. Estos resultados sugieren una probable participación de la vía Notch a través de estos genes, en los diferentes procesos celulares que determinan la morfogénesis y el desarrollo del tercio medio facial.

  6. The Arctic Marine Pulses Model: Linking Contiguous Domains in the Pacific Arctic Region

    Science.gov (United States)

    Moore, S. E.; Stabeno, P. J.

    2016-02-01

    The Pacific Arctic marine ecosystem extends from the northern Bering Sea, across the Chukchi and into the East Siberian and Beaufort seas. Food webs in this domain are short, a simplicity that belies the biophysical complexity underlying trophic linkages from primary production to humans. Existing biophysical models, such as pelagic-benthic coupling and advective processes, provide frameworks for connecting certain aspects of the marine food web, but do not offer a full accounting of events that occur seasonally across the Pacific Arctic. In the course of the Synthesis of Arctic Research (SOAR) project, a holistic Arctic Marine Pulses (AMP) model was developed that depicts seasonal biophysical `pulses' across a latitudinal gradient, and linking four previously-described contiguous domains, including the: (i) Pacific-Arctic domain = the focal region; (ii) seasonal ice zone domain; (iii) Pacific marginal domain; and (iv) riverine coastal domain. The AMP model provides a spatial-temporal framework to guide research on dynamic ecosystem processes during this period of rapid biophysical changes in the Pacific Arctic. Some of the processes included in the model, such as pelagic-benthic coupling in the Northern Bering and Chukchi seas, and advection and upwelling along the Beaufort shelf, are already the focus of sampling via the Distributed Biological Observatory (DBO) and other research programs. Other aspects such as biological processes associated with the seasonal ice zone and trophic responses to riverine outflow have received less attention. The AMP model could be enhanced by the application of visualization tools to provide a means to watch a season unfold in space and time. The capability to track sea ice dynamics and water masses and to move nutrients, prey and upper-trophic predators in space and time would provide a strong foundation for the development of predictive human-inclusive ecosystem models for the Pacific Arctic.

  7. Surface ozone concentrations in Europe: Links with the regional-scale atmospheric circulation

    Science.gov (United States)

    Davies, T. D.; Kelly, P. M.; Low, P. S.; Pierce, C. E.

    1992-06-01

    Daily surface ozone observations from 1978 (1976 for some analyses) to 1988 for Bottesford (United Kingdom), Cabauw, Kloosterburen (The Netherlands), Hohenpeissenberg, Neuglobsow, Hamburg, and Arkona (Germany) are used to analyze links between surface ozone variations and the atmospheric circulation. A daily Europe-wide synoptic classification highlights marked differences between surface ozone/meteorology relationships in summer and winter. These relationships are characterized by correlations between daily surface ozone concentrations at each station and a local subregional surface pressure gradient (a wind speed index). Although there are geographical variations, which are explicable in terms of regional climatology, there are distinct annual cycles. In summer, the surface ozone/wind speed relationship exhibits the expected negative sign; however, in winter, the relationship is, in the main, strongly positive, especially at those stations which are more influenced by the vigorous westerlies. Spring and autumn exhibit negative, positive, or transitional (between summer and winter) behavior, depending on geographical position. It is suggested that these relationships reflect the importance of vertical exchange from the free troposphere to the surface in the nonsummer months. Composite surface pressure patterns and surface pressure anomaly (from the long-term mean) patterns associated with high surface ozone concentrations on daily and seasonal time scales are consistent with the surface ozone/wind speed relationships. Moreover, they demonstrate that high surface ozone concentrations, in a climatological time frame, can be associated with mean surface pressure patterns which have a synoptic reality and are robust. Such an approach may be useful in interpreting past variations in surface ozone and may help to isolate the effect of human activity. It is also possible that assessments can be made of the effect of projected future changes in the atmospheric circulation

  8. Linking the Lusi mud eruption dynamics with regional and global seismic activity: a statistical analysis.

    Science.gov (United States)

    Collignon, Marine; Hammer, Øyvind; Fallahi, Mohammad J.; Lupi, Matteo; Schmid, Daniel W.; Alwi, Husein; Hadi, Soffian; Mazzini, Adriano

    2017-04-01

    The 29th May 2006, gas water and mud breccia started to erupt at several localities along the Watukosek fault system in the Sidoarjo Regency in East Java Indonesia. The most prominent eruption site, named Lusi, is still active and the emitted material now covers a surface of nearly 7 km2, resulting in the displacement of 60.000 people (up to date). Due to its social and economic impacts, as well as its spectacular dimensions, the Lusi eruption still attracts the attention of international media and scientists. In the framework of the Lusi Lab project (ERC grant n° 308126), many efforts were made to develop a quasi-constant monitoring of the site and the regional areas. Several studies attempted to predict the flow rate evolution or ground deformation, resulting in either overestimating or underestimating the longevity of the eruption. Models have failed because Lusi is not a mud volcano but a sedimentary hosted hydrothermal system that became apparent after the M6.3 Yogyakarta earthquake. Another reason is because such models usually assume that the flow will decrease pacing the overpressure reduction during the deflation of the chamber. These models typically consider a closed system with a unique chamber that is not being recharged. Overall the flow rate has decreased over the past ten years, although it has been largely fluctuating with monthly periods of higher mud breccia discharge. Monitoring of the eruption has revealed that numerous anomalous events are temporally linked to punctual events such as earthquakes or volcanic eruptions. Nevertheless, the quantification of these events has never been investigated in details. In this study, we present a compilation of anomalous events observed at the Lusi site during the last 10 years. Using Monte Carlo simulations, we then statistically compare the displacement, recorded at different seismic stations around Lusi, with the regional and global earthquakes catalogue to test the probability that an earthquake

  9. Differential behaviors of trastuzumab-sensitive and -resistant SKBR3 cells treated with menadione reveal the involvement of Notch1/Akt/FOXO1 signaling elements.

    Science.gov (United States)

    Sajadimajd, Soraya; Yazdanparast, Razieh

    2015-10-01

    Given that HER2 serves as a putative target for therapy in HER2-positive breast cancer, intrinsic and/or acquired resistance to trastuzumab (T) has been proposed to be the major obstacle in treatments. In addition, chemoresistance is commonly attributed to increased antioxidant capacity. In that regard, we evaluated the effect of menadione (M) alone and/or its combination with trastuzumab on proliferation, intracellular GSH and ROS contents as well as HER2 and Notch1 signaling pathways in both trastuzumab-resistant (SKBR3(R)) and -sensitive SKBR3 (SKBR3(S)) cells. In spite of increased level of ROS and reduced level of GSH in M-treated SKBR3(S) cells, M-treated SKBR3(R) cells showed a decreased content of ROS and GSH compared to untreated cells. However, M/T co-treatment of SKBR3 cells indicated no effect on ROS content, while decreased the level of GSH compared to untreated control cells. Based on the extent of apoptosis, colony formation and wound healing assays, M alone, and/or in combination with T had a stronger inhibitory effect on proliferation of SKBR3(R) cells relative to SKBR3(S) cells. These effects might be due to the stronger effects of M and/or M/T on downregulation of p-Akt, Hes1, NICD, and upregulation of FOXO1 among SKBR3(R) cells relative to the sensitive SKBR3 cells. These findings would certainly shed light on some of the signaling factors involved in induction of trastuzumab resistance and would be of value in designing more efficient chemosensitization strategies.

  10. Redundant Notch1 and Notch2 signaling is necessary for IFNγ secretion by T helper 1 cells during infection with Leishmania major.

    Directory of Open Access Journals (Sweden)

    Floriane Auderset

    Full Text Available The protective immune response to intracellular parasites involves in most cases the differentiation of IFNγ-secreting CD4(+ T helper (Th 1 cells. Notch receptors regulate cell differentiation during development but their implication in the polarization of peripheral CD4(+ T helper 1 cells is not well understood. Of the four Notch receptors, only Notch1 (N1 and Notch2 (N2 are expressed on activated CD4(+ T cells. To investigate the role of Notch in Th1 cell differentiation following parasite infection, mice with T cell-specific gene ablation of N1, N2 or both (N1N2(ΔCD4Cre were infected with the protozoan parasite Leishmania major. N1N2(ΔCD4Cre mice, on the C57BL/6 L. major-resistant genetic background, developed unhealing lesions and uncontrolled parasitemia. Susceptibility correlated with impaired secretion of IFNγ by draining lymph node CD4(+ T cells and increased secretion of the IL-5 and IL-13 Th2 cytokines. Mice with single inactivation of N1 or N2 in their T cells were resistant to infection and developed a protective Th1 immune response, showing that CD4(+ T cell expression of N1 or N2 is redundant in driving Th1 differentiation. Furthermore, we show that Notch signaling is required for the secretion of IFNγ by Th1 cells. This effect is independent of CSL/RBP-Jκ, the major effector of Notch receptors, since L. major-infected mice with a RBP-Jκ deletion in their T cells were able to develop IFNγ-secreting Th1 cells, kill parasites and heal their lesions. Collectively, we demonstrate here a crucial role for RBP-Jκ-independent Notch signaling in the differentiation of a functional Th1 immune response following L. major infection.

  11. Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing.

    Science.gov (United States)

    Neltner, Janna H; Abner, Erin L; Baker, Steven; Schmitt, Frederick A; Kryscio, Richard J; Jicha, Gregory A; Smith, Charles D; Hammack, Eleanor; Kukull, Walter A; Brenowitz, Willa D; Van Eldik, Linda J; Nelson, Peter T

    2014-01-01

    Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer's Disease Centre, Nun Study, and National Alzheimer's Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case-control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin-immunoreactive arterioles had thicker walls (P < 0.05), larger perimeters (P < 0

  12. Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing

    Science.gov (United States)

    Neltner, Janna H.; Abner, Erin L.; Baker, Steven; Schmitt, Frederick A.; Kryscio, Richard J.; Jicha, Gregory A.; Smith, Charles D.; Hammack, Eleanor; Kukull, Walter A.; Brenowitz, Willa D.; Van Eldik, Linda J.

    2014-01-01

    Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer’s Disease Centre, Nun Study, and National Alzheimer’s Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case–control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin

  13. Clinical impact of de-regulated Notch-1 and Notch-3 in the development and progression of HPV-associated different histological subtypes of precancerous and cancerous lesions of human uterine cervix.

    Science.gov (United States)

    Tripathi, Richa; Rath, Gayatri; Jawanjal, Poonam; Sharma, Shweta; Singhal, Pallavi; Bhambhani, Suresh; Hussain, Showket; Bharadwaj, Mausumi

    2014-01-01

    Cervical cancer is the leading cause of cancer related deaths among women in India. Limited reports are available for Notch-1 and Notch-3 protein in cervical carcinoma, which play crucial role in cell proliferation, differentiation, and apoptosis. This study was designed to evaluate the role of Notch-1 and Notch-3 with context to HPV infection in cervical carcinoma. A total of 168 tissue biopsy samples comprising of tumor specimens (n = 98), precancer (n = 30) and non-neoplastic cervical tissues (n = 40) were screened for HPV infection by PCR and expression of Notch-1 and Notch-3 protein by Immunohistochemistry and Immunoblotting. 80% (24/30) were found to be positive for HPV in precancer and 86.7% (85/98) in cancer patients. Notch-1 expression of precancer and cancer cases was found to be significantly down-regulated with severity of disease in nuclear (3.43±0.29; 2.04±0.19, p = 0.0001, p = 0.0001) and cytoplasm (3.07±0.29; 2.29±0.17, p = 0.0001, p = 0.0001) obtained from different stages as compared to normal cervix tissue (5.40±0.19, 4.97±0.15; pcervix tissue (0.95±0.20, 0.70±0.20; pcancer through the deregulation of Notch signalling. This study also shows the clinical utility of both proteins which may be used as predictable biomarkers in diagnosing different histological sub-types of HPV associated cervical cancer. Nevertheless, abnormal activation of this pathway may provide legitimate targets for cervical cancer therapy.

  14. Deubiquitinase inhibitor b-AP15 activates endoplasmic reticulum (ER) stress and inhibits Wnt/Notch1 signaling pathway leading to the reduction of cell survival in hepatocellular carcinoma cells.

    Science.gov (United States)

    Ding, Youming; Chen, Xiaoyan; Wang, Bin; Yu, Bin; Ge, Jianhui

    2018-04-15

    b-AP15, a potent and selective inhibitor of the ubiquitin-specific peptidase 14 (USP14), displays in vitro and in vivo antitumor abilities on some types of cancer cells. However, the mechanism underlying its action is not well elucidated. The purposes of the present study are to observe the potential impacts of b-AP15 on cell survival of hepatocellular carcinoma cells and to investigate whether and how this compound inhibits some survival-promoting signaling pathways. We found that b-AP15 significantly decreased cell viability and increased cell apoptosis in a dose-dependent manner in hepatocellular carcinoma cells, along with the perturbation of cell cycle and the decreased expressions of cell cycle-related proteins. We also demonstrated that the endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) were enhanced by b-AP15 supplementation. The inhibition of ER stress/UPR only partly attenuated the cytotoxicity of b-AP15 on hepatocellular carcinoma cells. In addition, b-AP15 treatment inhibited Wnt/β-catenin and Notch1 signaling pathways, and suppressed phosphorylation of STAT3, Akt, and Erk1/2, which were not restored by the inhibition of ER stress/UPR. Furthermore, the expression levels of signaling molecules in Notch1 were reduced by specific inhibitor of Wnt/β-catenin pathway. Notably, either Wnt or Notch1 signaling inhibitor mitigated phosphorylation of STAT3, Akt, and Erk1/2, and mimicked the cytotoxicity of b-AP15 on hepatocellular carcinoma cells. These results clearly indicate that b-AP15 induced cytotoxic response to hepatocellular carcinoma cells by augmenting ER stress/UPR and inhibiting Wnt/Notch1 signaling pathways. This new finding provides a novel mechanism by which b-AP15 produces its antitumor therapeutic effects. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Linking regional stakeholder scenarios and shared socioeconomic pathways: Quantified West African food and climate futures in a global context.

    Science.gov (United States)

    Palazzo, Amanda; Vervoort, Joost M; Mason-D'Croz, Daniel; Rutting, Lucas; Havlík, Petr; Islam, Shahnila; Bayala, Jules; Valin, Hugo; Kadi Kadi, Hamé Abdou; Thornton, Philip; Zougmore, Robert

    2017-07-01

    The climate change research community's shared socioeconomic pathways (SSPs) are a set of alternative global development scenarios focused on mitigation of and adaptation to climate change. To use these scenarios as a global context that is relevant for policy guidance at regional and national levels, they have to be connected to an exploration of drivers and challenges informed by regional expertise. In this paper, we present scenarios for West Africa developed by regional stakeholders and quantified using two global economic models, GLOBIOM and IMPACT, in interaction with stakeholder-generated narratives and scenario trends and SSP assumptions. We present this process as an example of linking comparable scenarios across levels to increase coherence with global contexts, while presenting insights about the future of agriculture and food security under a range of future drivers including climate change. In these scenarios, strong economic development increases food security and agricultural development. The latter increases crop and livestock productivity leading to an expansion of agricultural area within the region while reducing the land expansion burden elsewhere. In the context of a global economy, West Africa remains a large consumer and producer of a selection of commodities. However, the growth in population coupled with rising incomes leads to increases in the region's imports. For West Africa, climate change is projected to have negative effects on both crop yields and grassland productivity, and a lack of investment may exacerbate these effects. Linking multi-stakeholder regional scenarios to the global SSPs ensures scenarios that are regionally appropriate and useful for policy development as evidenced in the case study, while allowing for a critical link to global contexts.

  16. Clinical impact of de-regulated Notch-1 and Notch-3 in the development and progression of HPV-associated different histological subtypes of precancerous and cancerous lesions of human uterine cervix.

    Directory of Open Access Journals (Sweden)

    Richa Tripathi

    Full Text Available Cervical cancer is the leading cause of cancer related deaths among women in India. Limited reports are available for Notch-1 and Notch-3 protein in cervical carcinoma, which play crucial role in cell proliferation, differentiation, and apoptosis.This study was designed to evaluate the role of Notch-1 and Notch-3 with context to HPV infection in cervical carcinoma. A total of 168 tissue biopsy samples comprising of tumor specimens (n = 98, precancer (n = 30 and non-neoplastic cervical tissues (n = 40 were screened for HPV infection by PCR and expression of Notch-1 and Notch-3 protein by Immunohistochemistry and Immunoblotting.80% (24/30 were found to be positive for HPV in precancer and 86.7% (85/98 in cancer patients. Notch-1 expression of precancer and cancer cases was found to be significantly down-regulated with severity of disease in nuclear (3.43±0.29; 2.04±0.19, p = 0.0001, p = 0.0001 and cytoplasm (3.07±0.29; 2.29±0.17, p = 0.0001, p = 0.0001 obtained from different stages as compared to normal cervix tissue (5.40±0.19, 4.97±0.15; p<0.001; p<0.001. However, Notch-3 expression of above cases was significantly up-regulated with severity of disease and showed intense nuclear (4.17±0.39; 4.74±0.18, p = 0.0001, p = 0.0001 and cytoplasm (3.67±0.36; 4.48±0.18, p = 0.0001, p = 0.0001 of different stages as compared to normal cervix tissue (0.95±0.20, 0.70±0.20; p<0.001; p<0.001 respectively.These findings suggest that Notch-1 and Notch-3 may play an important role with synergistic effect of HPV in regulating development and proliferation of cervical cancer through the deregulation of Notch signalling. This study also shows the clinical utility of both proteins which may be used as predictable biomarkers in diagnosing different histological sub-types of HPV associated cervical cancer. Nevertheless, abnormal activation of this pathway may provide legitimate targets for cervical cancer therapy.

  17. Immunoglobulin Heavy Chain Variable Region and Major Histocompatibility Region Genes Are Linked to Induced Graves' Disease in Females From Two Very Large Families of Recombinant Inbred Mice

    Science.gov (United States)

    Aliesky, Holly; Banuelos, Bianca; Magana, Jessica; Williams, Robert W.; Rapoport, Basil

    2014-01-01

    Graves' hyperthyroidism is caused by antibodies to the TSH receptor (TSHR) that mimic thyroid stimulation by TSH. Stimulating TSHR antibodies and hyperthyroidism can be induced by immunizing mice with adenovirus expressing the human TSHR A-subunit. Prior analysis of induced Graves' disease in small families of recombinant inbred (RI) female mice demonstrated strong genetic control but did not resolve trait loci for TSHR antibodies or elevated serum T4. We investigated the genetic basis for induced Graves' disease in female mice of two large RI families and combined data with earlier findings to provide phenotypes for 178 genotypes. TSHR antibodies measured by inhibition of TSH binding to its receptor were highly significantly linked in the BXD set to the major histocompatibility region (chromosome 17), consistent with observations in 3 other RI families. In the LXS family, we detected linkage between T4 levels after TSHR-adenovirus immunization and the Ig heavy chain variable region (Igvh, chromosome 12). This observation is a key finding because components of the antigen binding region of Igs determine antibody specificity and have been previously linked to induced thyroid-stimulating antibodies. Data from the LXS family provide the first evidence in mice of a direct link between induced hyperthyroidism and Igvh genes. A role for major histocompatibility genes has now been established for genetic susceptibility to Graves' disease in both humans and mice. Future studies using arrays incorporating variation in the complex human Ig gene locus will be necessary to determine whether Igvh genes are also linked to Graves' disease in humans. PMID:25051451

  18. Promoting University and Industry Links at the Regional Level: Comparing China's Reform and International Experience

    Science.gov (United States)

    Po, Yang; Cai, Yuzhuo; Lyytinen, Anu; Hölttä, Seppo

    2016-01-01

    This paper intends to learn from international experiences in order to facilitating China's ongoing regional university transformation with an ultimate goal to enhance the role of university in regional economic development and innovation. In so doing, this paper compares major models of universities of applied sciences (UAS) around the world from…

  19. Linking the uncertainty of low frequency variability in tropical forcing in regional climate change

    Energy Technology Data Exchange (ETDEWEB)

    Forest, Chris E. [Pennsylvania State Univ., University Park, PA (United States). Dept. of Meteorology; Barsugli, Joseph J. [Univ. of Colorado, Boulder, CO (United States). CIRES; Li, Wei [Pennsylvania State Univ., University Park, PA (United States). Dept. of Meteorology

    2015-02-20

    The project utilizes multiple atmospheric general circulation models (AGCMs) to examine the regional climate sensitivity to tropical sea surface temperature forcing through a series of ensemble experiments. The overall goal for this work is to use the global teleconnection operator (GTO) as a metric to assess the impact of model structural differences on the uncertainties in regional climate variability.

  20. Links between circulation indices and precipitation in the Mediterranean in an ensemble of regional climate models

    Czech Academy of Sciences Publication Activity Database

    Beranová, Romana; Kyselý, Jan

    2016-01-01

    Roč. 123, č. 3 (2016), s. 693-701 ISSN 0177-798X R&D Projects: GA ČR GAP209/10/2265 EU Projects: European Commission(XE) 505539 - ENSEMBLES Program:FP6 Institutional support: RVO:68378289 Keywords : atmospheric sciences climatology * atmospheric protection * air quality control * air pollution * waste water technology * water pollution control * water management * aquatic pollution Subject RIV: DG - Athmosphere Sciences, Meteorology Impact factor: 2.640, year: 2016 http://link.springer.com/article/10.1007%2Fs00704-015-1381-6

  1. Making the Most of World Natural Heritage—Linking Conservation and Sustainable Regional Development?

    Directory of Open Access Journals (Sweden)

    Katharina Conradin

    2016-03-01

    Full Text Available Today, more than 1000 World Heritage (WH sites are inscribed on UNESCO’s list, 228 of which are natural and mixed heritage sites. Once focused primarily on conservation, World Natural Heritage (WNH sites are increasingly seen as promoters of sustainable regional development. Sustainability-oriented regions, it is assumed, are safeguards for conservation and positively influence local conservation goals. Within UNESCO, discussions regarding the integration of sustainable development in official policies have recently gained momentum. In this article, we investigate the extent to which WNH sites trigger sustainability-oriented approaches in surrounding regions, and how such approaches in turn influence the WNH site and its protection. The results of the study are on the one hand based on a global survey with more than 60% of the WNH sites listed in 2011, and on the other hand on a complementary literature research. Furthermore, we analyze the policy framework necessary to support WNH sites in this endeavor. We conclude that a regional approach to WNH management is necessary to ensure that WNH sites support sustainable regional development effectively, but that the core focus of WNH status must remain environmental conservation.

  2. Using phylogenomics to understand the link between biogeographic origins and regional diversification in ratsnakes.

    Science.gov (United States)

    Chen, Xin; Lemmon, Alan R; Lemmon, Emily Moriarty; Pyron, R Alexander; Burbrink, Frank T

    2017-06-01

    Globally distributed groups may show regionally distinct rates of diversification, where speciation is elevated given timing and sources of ecological opportunity. However, for most organisms, nearly complete sampling at genomic-data scales to reduce topological error in all regions is unattainable, thus hampering conclusions related to biogeographic origins and rates of diversification. We explore processes leading to the diversity of global ratsnakes and test several important hypotheses related to areas of origin and enhanced diversification upon colonizing new continents. We estimate species trees inferred from phylogenomic scale data (304 loci) while exploring several strategies that consider topological error from each individual gene tree. With a dated species tree, we examine taxonomy and test previous hypotheses that suggest the ratsnakes originated in the Old World (OW) and dispersed to New World (NW). Furthermore, we determine if dispersal to the NW represented a source of ecological opportunity, which should show elevated rates of species diversification. We show that ratsnakes originated in the OW during the mid-Oligocene and subsequently dispersed to the NW by the mid-Miocene; diversification was also elevated in a subclade of NW taxa. Finally, the optimal biogeographic region-dependent speciation model shows that the uptick in ratsnake diversification was associated with colonization of the NW. We consider several alternative explanations that account for regionally distinct diversification rates. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. New Regions of the Human Genome Linked to Skin Color Variation in Some African Populations

    Science.gov (United States)

    In the first study of its kind, an international team of genomics researchers has identified new regions of the human genome that are associated with skin color variation in some African populations, opening new avenues for research on skin diseases and cancer in all populations.

  4. Reduced regional cerebral blood flow in SPG4-linked hereditary spastic paraplegia

    DEFF Research Database (Denmark)

    Scheuer, Kristin H; Nielsen, Jørgen E; Krabbe, Katja

    2005-01-01

    flow (rCBF) as an indirect marker of regional neuronal activity. Eighteen SPG4 patients and 18 matched control subjects were studied. Resting state rCBF was measured using Positron Emission Tomography (PET) and the (15)O-labelled water bolus technique and relative group differences were explored using...

  5. Form Characteristics of Regional Security Organizations - The Missing Link in the Explanation of the Democratic Peace

    OpenAIRE

    Dembinski, Matthias; Freistein, Katja; Weiffen, Brigitte

    2006-01-01

    This paper contributes both to the debate on the effects of regional security organizations and to the debate on democratic peace. It argues that even if international organizations as such may not be able to influence the conflict behavior of their member states, the subgroup of interdemocratic institutions is well suited to do so. The form of interdemocratic institutions differs in two significant respects from the form of traditional institutions: they are more densely connected via transn...

  6. On the link between potential evaporation and regional evaporation from a CBL perspective

    Science.gov (United States)

    Lhomme, J. P.; Guilioni, L.

    2010-07-01

    The relationship between potential evaporation and actual evaporation was first examined by Bouchet (Proc Berkeley Calif Symp IAHS Publ, 62:134-142, 1963) who considered potential evaporation as the consequence of regional evaporation due to atmospheric feedbacks. Using a heuristic approach, he derived a complementary relationship which, despite no real theoretical background, has proven to be very useful in interpreting many experimental data under various climatic conditions. Here, the relationship between actual and potential evaporation is reinterpreted in the context of the development of the convective boundary layer (CBL): first, with a closed-box approach, where the CBL has an impermeable lid; and then with an open system, where air is exchanged between the CBL and its external environment. By applying steady forcing to these systems, it is shown that an equilibrium state is reached, where potential evaporation has a specific equilibrium formulation as a function of two parameters: one representing large-scale advection and the other the feedback effect of regional evaporation on potential evaporation, i.e. a kind of “medium-scale advection”. It is also shown that the original form of Bouchet’s complementary relationship is not verified in the equilibrium state. This analysis leads us to propose a new and more rational approach of the relationship between potential and actual evaporation through the effective surface resistance of the region.

  7. Atmospheric circulation in regional climate models over Central Europe: links to surface air temperature and the influence of driving data

    Czech Academy of Sciences Publication Activity Database

    Plavcová, Eva; Kyselý, Jan

    2012-01-01

    Roč. 39, 7-8 (2012), s. 1681-1695 ISSN 0930-7575 R&D Project s: GA ČR GAP209/10/2265 Grant - others:ENSEMBLES: EU-FP6(XE) 505539 Program:FP6 Institutional support: RVO:68378289 Keywords : Regional climate models * Global climate models * Atmospheric circulation * Surface air temperature * ENSEMBLES * Central Europe Subject RIV: DG - Athmosphere Sciences, Meteorology Impact factor: 4.231, year: 2012 http://link.springer.com/article/10.1007%2Fs00382-011-1278-8#

  8. Adaptive antibody diversification through N-linked glycosylation of the immunoglobulin variable region.

    Science.gov (United States)

    van de Bovenkamp, Fleur S; Derksen, Ninotska I L; Ooijevaar-de Heer, Pleuni; van Schie, Karin A; Kruithof, Simone; Berkowska, Magdalena A; van der Schoot, C Ellen; IJspeert, Hanna; van der Burg, Mirjam; Gils, Ann; Hafkenscheid, Lise; Toes, René E M; Rombouts, Yoann; Plomp, Rosina; Wuhrer, Manfred; van Ham, S Marieke; Vidarsson, Gestur; Rispens, Theo

    2018-02-20

    A hallmark of B-cell immunity is the generation of a diverse repertoire of antibodies from a limited set of germline V(D)J genes. This repertoire is usually defined in terms of amino acid composition. However, variable domains may also acquire N -linked glycans, a process conditional on the introduction of consensus amino acid motifs ( N -glycosylation sites) during somatic hypermutation. High levels of variable domain glycans have been associated with autoantibodies in rheumatoid arthritis, as well as certain follicular lymphomas. However, the role of these glycans in the humoral immune response remains poorly understood. Interestingly, studies have reported both positive and negative effects on antibody affinity. Our aim was to elucidate the role of variable domain glycans during antigen-specific antibody responses. By analyzing B-cell repertoires by next-generation sequencing, we demonstrate that N -glycosylation sites are introduced at positions in which glycans can affect antigen binding as a result of a specific clustering of progenitor glycosylation sites in the germline sequences of variable domain genes. By analyzing multiple human monoclonal and polyclonal (auto)antibody responses, we subsequently show that this process is subject to selection during antigen-specific antibody responses, skewed toward IgG4, and positively contributes to antigen binding. Together, these results highlight a physiological role for variable domain glycosylation as an additional layer of antibody diversification that modulates antigen binding.

  9. NEO-INSTITUTIONALISM AND ENDOGENOUS DEVELOPMENT AS REGIONAL ALTERNATIVE. MODERNITY AND SUBJECTIVITY, LINKING AND LOCAL DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    José Mateo Bastidas-Morales

    2015-01-01

    Full Text Available The reconstruction of subjectivity involves overcoming criticism of individualism, utilitarianism and immediacy as the basis of society and consumer markets. Elemental is, with the addition of the individual as a subject of social action, the principal actor-oriented definition of welfare, community and local development. Obviously, the formation of human capital development. While it is imperative the state-society relationship in the context of the current modernization must also recover the principles of the community before the stressed relationship between the market-state. We intend here to link opposite the dichotomous thinking of Western rationalism, constitute an important element of social sustantivación. Along with this, the neo-institutionalism and institutional economics that questions the current neoliberal approves the participation of the state and, with new rules, can better confront the neoconservative positions. It is revalued, in the present work, interest in the new dynamics of social change in post-national or cosmopolitan side.

  10. Hepatitis B virus X protein promotes interleukin-7 receptor expression via NF-κB and Notch1 pathway to facilitate proliferation and migration of hepatitis B virus-related hepatoma cells

    Directory of Open Access Journals (Sweden)

    Fanyun Kong

    2016-11-01

    Full Text Available Abstract Background Interleukin-7 receptor (IL-7R is involved in the abnormal function of solid tumors, but the role and regulatory mechanisms of IL-7R in HBV-related hepatocellular carcinoma (HCC are still unclear. Methods Gene and protein expression levels of IL-7R were examined in hepatoma cells transfected with hepatitis B virus (HBV plasmids and in hepatoma cells transfected with the multifunctional nonstructural protein X (HBX. The expression of HBX and IL-7R was measured by immunohistochemical analysis in HBV-related HCC tissues. The role of NF-κB and Notch1 pathways in HBX-mediated expression of IL-7R in hepatoma cells was examined. Activation of IL-7R downstream of intracellular signaling proteins AKT, JNK, STAT5, and the associated molecules CyclinD1 and matrix metalloproteinase-9 (MMP-9, was assessed in HBX-positive cells with or without treatment with IL-7R short hairpin RNA (shRNA. Additionally, the role of IL-7R in HBX-mediated proliferation and migration of hepatoma cells was investigated. Results The expression of IL-7R was increased in hepatoma cells transfected with HBV plasmids; HBX was responsible for the HBV-mediated upregulation of IL-7R. Compared to adjacent tissues, the expression of HBX and IL-7R was increased in HBV-related HCC tissues. Additionally, the relative expression levels of HBX were associated with IL-7R in HBV-related HCC tissues. The activation of NF-κB pathways and expression of Notch1 were increased in hepatoma cells transfected with HBX, and inhibition of NF-κB and Notch1 pathways significantly decreased HBX-mediated expression of IL-7R. The activation of AKT and JNK and the expression of CyclinD1 and MMP-9 were increased in HBX-positive cells. When cells were treated with IL-7R shRNA, the activation of AKT and JNK, as well as the expression of CyclinD1 and MMP-9, were significantly inhibited. Additionally, IL-7R was responsible for HBX-induced proliferation and migration ability of hepatoma cells

  11. Linking source region and ocean wave parameters with the observed primary microseismic noise

    Science.gov (United States)

    Juretzek, C.; Hadziioannou, C.

    2017-12-01

    In previous studies, the contribution of Love waves to the primary microseismic noise field was found to be comparable to those of Rayleigh waves. However, so far only few studies analysed both wave types present in this microseismic noise band, which is known to be generated in shallow water and the theoretical understanding has mainly evolved for Rayleigh waves only. Here, we study the relevance of different source region parameters on the observed primary microseismic noise levels of Love and Rayleigh waves simultaneously. By means of beamforming and correlation of seismic noise amplitudes with ocean wave heights in the period band between 12 and 15 s, we analysed how source areas of both wave types compare with each other around Europe. The generation effectivity in different source regions was compared to ocean wave heights, peak ocean gravity wave propagation direction and bathymetry. Observed Love wave noise amplitudes correlate comparably well with near coastal ocean wave parameters as Rayleigh waves. Some coastal regions serve as especially effective sources for one or the other wave type. These coincide not only with locations of high wave heights but also with complex bathymetry. Further, Rayleigh and Love wave noise amplitudes seem to depend equally on the local ocean wave heights, which is an indication for a coupled variation with swell height during the generation of both wave types. However, the wave-type ratio varies directionally. This observation likely hints towards a spatially varying importance of different source mechanisms or structural influences. Further, the wave-type ratio is modulated depending on peak ocean wave propagation directions which could indicate a variation of different source mechanism strengths but also hints towards an imprint of an effective source radiation pattern. This emphasizes that the inclusion of both wave types may provide more constraints for the understanding of acting generation mechanisms.

  12. On the link between column density distribution and density scaling relation in star formation regions

    Science.gov (United States)

    Veltchev, Todor; Donkov, Sava; Stanchev, Orlin

    2017-07-01

    We present a method to derive the density scaling relation ∝ L^{-α} in regions of star formation or in their turbulent vicinities from straightforward binning of the column-density distribution (N-pdf). The outcome of the method is studied for three types of N-pdf: power law (7/5≤α≤5/3), lognormal (0.7≲α≲1.4) and combination of lognormals. In the last case, the method of Stanchev et al. (2015) was also applied for comparison and a very weak (or close to zero) correlation was found. We conclude that the considered `binning approach' reflects rather the local morphology of the N-pdf with no reference to the physical conditions in a considered region. The rough consistency of the derived slopes with the widely adopted Larson's (1981) value α˜1.1 is suggested to support claims that the density-size relation in molecular clouds is indeed an artifact of the observed N-pdf.

  13. Sedimentation rates in eastern North America reveal strong links between regional climate, depositional environments, and sediment accumulation

    Science.gov (United States)

    Goring, S. J.; McLachlan, J. S.; Jackson, S. T.; Blaauw, M.; Christen, J.; Marlon, J.; Blois, J.; Williams, J. W.

    2011-12-01

    PalEON is a multidisciplinary project that combines paleo and modern ecological data with state-of-the-art statistical and modelling tools to examine the interactions between climate, fire and vegetation during the past two millennia in the northeastern United States. A fundamental challenge for PalEON (and paleo research more broadly) is to improve age modelling to yield more accurate sediment-core chronologies. To address this challenge, we assessed sedimentation rates and their controls for 218 lakes and mires in the northeastern U.S. Sedimentation rates (yr/cm) were calculated from age-depth models, which were obtained from the Neotoma database (www.neotomadb.org) and other contributed pollen records. The age models were recalibrated to IntCal09 and augmented in some cases using biostratigraphic markers (Picea decline, 16 kcal BP - 10.5 kcal BP; Quercus rise, 12 - 9.1 kcal BP; and Alnus decline, 11.5 - 10.6 kcal BP) as described in Blois et al. (2011). Relationships between sedimentation rates and sediment age, site longitude, and depositional environment (lacustrine or mire) are significant but weak. There are clear and significant links between variations in the NGRIP record of δ18O and sedimentation in mires across the PalEON region, but no links to lacustrine sedimentation rates. This result indicates that super-regional climatic control of primary productivity, and thus autochthonic sediment deposition, dominates in mires while deposition in lacustrine basins may be driven primarily by local and regional factors including watershed size, surficial materials,and regional vegetation. The shape of the gamma probability functions that best describe sedimentation rate distributions are calculated and presented here for use as priors in Bayesian age modelling applications such as BACON (Blaauw and Christen, in press). Future applications of this research are also discussed.

  14. Serotonin transporter linked polymorphic region (5-HTTLPR) genotype moderates the longitudinal impact of early caregiving on externalizing behavior.

    Science.gov (United States)

    Brett, Zoë H; Humphreys, Kathryn L; Smyke, Anna T; Gleason, Mary Margaret; Nelson, Charles A; Zeanah, Charles H; Fox, Nathan A; Drury, Stacy S

    2015-02-01

    We examined caregiver report of externalizing behavior from 12 to 54 months of age in 102 children randomized to care as usual in institutions or to newly created high-quality foster care. At baseline no differences by group or genotype in externalizing were found. However, changes in externalizing from baseline to 42 months of age were moderated by the serotonin transporter linked polymorphic region genotype and intervention group, where the slope for short-short (S/S) individuals differed as a function of intervention group. The slope for individuals carrying the long allele did not significantly differ between groups. At 54 months of age, S/S children in the foster care group had the lowest levels of externalizing behavior, while children with the S/S genotype in the care as usual group demonstrated the highest rates of externalizing behavior. No intervention group differences were found in externalizing behavior among children who carried the long allele. These findings, within a randomized controlled trial of foster care compared to continued care as usual, indicate that the serotonin transporter linked polymorphic region genotype moderates the relation between early caregiving environments to predict externalizing behavior in children exposed to early institutional care in a manner most consistent with differential susceptibility.

  15. Linking agricultural crop management and air quality models for regional to national-scale nitrogen assessments

    Science.gov (United States)

    Cooter, E. J.; Bash, J. O.; Benson, V.; Ran, L.

    2012-10-01

    While nitrogen (N) is an essential element for life, human population growth and demands for energy, transportation and food can lead to excess nitrogen in the environment. A modeling framework is described and implemented to promote a more integrated, process-based and system-level approach to the estimation of ammonia (NH3) emissions which result from the application of inorganic nitrogen fertilizers to agricultural soils in the United States. The United States Department of Agriculture (USDA) Environmental Policy Integrated Climate (EPIC) model is used to simulate plant demand-driven fertilizer applications to commercial cropland throughout the continental US. This information is coupled with a process-based air quality model to produce continental-scale NH3 emission estimates. Regional cropland NH3 emissions are driven by the timing and amount of inorganic NH3 fertilizer applied, soil processes, local meteorology, and ambient air concentrations. Initial fertilizer application often occurs when crops are planted. A state-level evaluation of EPIC-simulated, cumulative planted area compares well with similar USDA reported estimates. EPIC-annual, inorganic fertilizer application amounts also agree well with reported spatial patterns produced by others, but domain-wide the EPIC values are biased about 6% low. Preliminary application of the integrated fertilizer application and air quality modeling system produces a modified geospatial pattern of seasonal NH3 emissions that improves current simulations of observed atmospheric particle nitrate concentrations. This modeling framework provides a more dynamic, flexible, and spatially and temporally resolved estimate of NH3 emissions than previous factor-based NH3 inventories, and will facilitate evaluation of alternative nitrogen and air quality policy and adaptation strategies associated with future climate and land use changes.

  16. Atmospheric circulation in regional climate models over Central Europe: links to surface air temperature and the influence of driving data

    International Nuclear Information System (INIS)

    Plavcova, Eva; Kysely, Jan

    2012-01-01

    The study examines simulation of atmospheric circulation, represented by circulation indices (flow direction, strength and vorticity), and links between circulation and daily surface air temperatures in regional climate models (RCMs) over Central Europe. We explore control simulations of five high-resolution RCMs from the ENSEMBLES project driven by re-analysis (ERA-40) and the same global climate model (ECHAM5 GCM) plus of one RCM (RCA) driven by different GCMs. The aims are to (1) identify errors in RCM-simulated distributions of circulation indices in individual seasons, (2) identify errors in simulated temperatures under particular circulation indices, and (3) compare performance of individual RCMs with respect to the driving data. Although most of the RCMs qualitatively reflect observed distributions of the airflow indices, each produces distributions significantly different from the observations. General biases include overestimation of the frequency of strong flow days and of strong cyclonic vorticity. Some circulation biases obviously propagate from the driving data. ECHAM5 and all simulations driven by ECHAM5 underestimate frequency of easterly flow, mainly in summer. Except for HIRHAM, however, all RCMs driven by ECHAM5 improve on the driving GCM in simulating atmospheric circulation. The influence on circulation characteristics in the nested RCM differs between GCMs, as demonstrated in a set of RCA simulations with different driving data. The driving data control on circulation in RCA is particularly weak for the BCM GCM, in which case RCA substantially modifies (but does not improve) the circulation from the driving data in both winter and summer. Those RCMs with the most distorted atmospheric circulation are HIRHAM driven by ECHAM5 and RCA driven by BCM. Relatively strong relationships between circulation indices and surface air temperatures were found in the observed data for Central Europe. The links differ by season and are usually stronger for

  17. Atmospheric circulation in regional climate models over Central Europe: links to surface air temperature and the influence of driving data

    Energy Technology Data Exchange (ETDEWEB)

    Plavcova, Eva [Institute of Atmospheric Physics, Academy of Sciences of the Czech Republic, Prague 4 (Czech Republic); Technical University, Department of Applied Mathematics, Liberec (Czech Republic); Charles University, Faculty of Mathematics and Physics, Prague (Czech Republic); Kysely, Jan [Institute of Atmospheric Physics, Academy of Sciences of the Czech Republic, Prague 4 (Czech Republic); Technical University, Department of Applied Mathematics, Liberec (Czech Republic)

    2012-10-15

    The study examines simulation of atmospheric circulation, represented by circulation indices (flow direction, strength and vorticity), and links between circulation and daily surface air temperatures in regional climate models (RCMs) over Central Europe. We explore control simulations of five high-resolution RCMs from the ENSEMBLES project driven by re-analysis (ERA-40) and the same global climate model (ECHAM5 GCM) plus of one RCM (RCA) driven by different GCMs. The aims are to (1) identify errors in RCM-simulated distributions of circulation indices in individual seasons, (2) identify errors in simulated temperatures under particular circulation indices, and (3) compare performance of individual RCMs with respect to the driving data. Although most of the RCMs qualitatively reflect observed distributions of the airflow indices, each produces distributions significantly different from the observations. General biases include overestimation of the frequency of strong flow days and of strong cyclonic vorticity. Some circulation biases obviously propagate from the driving data. ECHAM5 and all simulations driven by ECHAM5 underestimate frequency of easterly flow, mainly in summer. Except for HIRHAM, however, all RCMs driven by ECHAM5 improve on the driving GCM in simulating atmospheric circulation. The influence on circulation characteristics in the nested RCM differs between GCMs, as demonstrated in a set of RCA simulations with different driving data. The driving data control on circulation in RCA is particularly weak for the BCM GCM, in which case RCA substantially modifies (but does not improve) the circulation from the driving data in both winter and summer. Those RCMs with the most distorted atmospheric circulation are HIRHAM driven by ECHAM5 and RCA driven by BCM. Relatively strong relationships between circulation indices and surface air temperatures were found in the observed data for Central Europe. The links differ by season and are usually stronger for

  18. Regional Approach for Linking Ecosystem Services and Livelihood Strategies Under Climate Change of Pastoral Communities in the Mongolian Steppe Ecosystem

    Science.gov (United States)

    Ojima, D. S.; Galvin, K.; Togtohyn, C.

    2012-12-01

    Dramatic changes due to climate and land use dynamics in the Mongolian Plateau affecting ecosystem services and agro-pastoral systems in Mongolia. Recently, market forces and development strategies are affecting land and water resources of the pastoral communities which are being further stressed due to climatic changes. Evaluation of pastoral systems, where humans depend on livestock and grassland ecosystem services, have demonstrated the vulnerability of the social-ecological system to climate change. Current social-ecological changes in ecosystem services are affecting land productivity and carrying capacity, land-atmosphere interactions, water resources, and livelihood strategies. The general trend involves greater intensification of resource exploitation at the expense of traditional patterns of extensive range utilization. Thus we expect climate-land use-land cover relationships to be crucially modified by the social-economic forces. The analysis incorporates information about the social-economic transitions taking place in the region which affect land-use, food security, and ecosystem dynamics. The region of study extends from the Mongolian plateau in Mongolia. Our research indicate that sustainability of pastoral systems in the region needs to integrate the impact of climate change on ecosystem services with socio-economic changes shaping the livelihood strategies of pastoral systems in the region. Adaptation strategies which incorporate integrated analysis of landscape management and livelihood strategies provides a framework which links ecosystem services to critical resource assets. Analysis of the available livelihood assets provides insights to the adaptive capacity of various agents in a region or in a community. Sustainable development pathways which enable the development of these adaptive capacity elements will lead to more effective adaptive management strategies for pastoral land use and herder's living standards. Pastoralists will have the

  19. Emerging European winter precipitation pattern linked to atmospheric circulation changes over the North Atlantic region in recent decades

    Science.gov (United States)

    Ummenhofer, Caroline C.; Seo, Hyodae; Kwon, Young-Oh; Parfitt, Rhys; Brands, Swen; Joyce, Terrence M.

    2017-08-01

    Dominant European winter precipitation patterns over the past century, along with their associated extratropical North Atlantic circulation changes, are evaluated using cluster analysis. Contrary to the four regimes traditionally identified based on daily wintertime atmospheric circulation patterns, five distinct seasonal precipitation regimes are detected here. Recurrent precipitation patterns in each regime are linked to changes in atmospheric blocking, storm track, and sea surface temperatures across the North Atlantic region. Multidecadal variability in the frequency of the precipitation patterns reveals more (fewer) winters with wet conditions in northern (southern) Europe in recent decades and an emerging distinct pattern of enhanced wintertime precipitation over the northern British Isles. This pattern has become unusually common since the 1980s and is associated with changes in moisture transport and more frequent atmospheric river events. The observed precipitation changes post-1950 coincide with changes in storm track activity over the central/eastern North Atlantic toward the northern British Isles.

  20. A tourism and cultural regional case study of the link between transportation and tourism: South of France

    Directory of Open Access Journals (Sweden)

    Jocelyne Napoli

    2017-05-01

    Full Text Available The article discusses the evolving role of transportation, and more especially air transport enabling tourism access to regions in the South of France. Historically, British citizens visited France by train, coach or car as the cost of air travel was restrictive and routes were only established in larger cities. ith the advent of the Channel Tunnel and Low Cost Carriers (LCCs in Europe, British tourism has increased within numerous destinations in France. These new means of transportation have filled the gap by providing easy access to smaller towns and allowing British tourists the French quality of life in the countryside. There is a shift in visitation numbers from the north of France to the south due to the wider range of travel choices. The South of France is becoming more attractive to British tourism because of the comparatively inexpensive cost of housing, the historical links between the two countries, and the cultural heritage of tradition. Other attractions include landscapes, the Mediterranean climate, restored medieval castles and villages, and the abundance of traditional French cuisine with regional wines. Due to the availability of LCCs some British tourists have chosen to settle and enjoy the historical links that are famous between the two countries. Many are now able to enjoy the tourist life for extended periods in the South of France by purchasing a second home. It’s also now possible to keep working in England as the LCCs make it affordable and possible to commute between their intercontinental homes. Through a review of issues and literature, the article will discuss the evolving air transportation heritage related to British tourism in the South of France. 

  1. Quantitative variation in obesity-related traits and insulin precursors linked to the OB gene region on human chromosome 7

    Energy Technology Data Exchange (ETDEWEB)

    Duggirala, R.; Stern, M.P.; Reinhart, L.J. [Univ. of Texas Health Science Center, San Antonio, TX (United States)] [and others

    1996-09-01

    Despite the evidence that human obesity has strong genetic determinants, efforts at identifying specific genes that influence human obesity have largely been unsuccessful. Using the sibship data obtained from 32 low-income Mexican American pedigrees ascertained on a type II diabetic proband and a multipoint variance-components method, we tested for linkage between various obesity-related traits plus associated metabolic traits and 15 markers on human chromosome 7. We found evidence for linkage between markers in the OB gene region and various traits, as follows: D7S514 and extremity skinfolds (LOD = 3.1), human carboxypeptidase A1 (HCPA1) and 32,33-split proinsulin level (LOD = 4.2), and HCPA1 and proinsulin level (LOD = 3.2). A putative susceptibility locus linked to the marker D7S514 explained 56% of the total phenotypic variation in extremity skinfolds. Variation at the HCPA1 locus explained 64% of phenotypic variation in proinsulin level and {approximately}73% of phenotypic variation in split proinsulin concentration, respectively. Weaker evidence for linkage to several other obesity-related traits (e.g., waist circumference, body-mass index, fat mass by bioimpedance, etc.) was observed for a genetic location, which is {approximately}15 cM telomeric to OB. In conclusion, our study reveals that the OB region plays a significant role in determining the phenotypic variation of both insulin precursors and obesity-related traits, at least in Mexican Americans. 66 refs., 3 figs., 4 tabs.

  2. Precipitation isotopes link regional climate patterns to water supply in a tropical mountain forest, eastern Puerto Rico

    Science.gov (United States)

    Scholl, Martha A.; Murphy, Sheila F.

    2014-05-01

    Like many mountainous areas in the tropics, watersheds in the Luquillo Mountains of eastern Puerto Rico have abundant rainfall and stream discharge and provide much of the water supply for the densely populated metropolitan areas nearby. Projected changes in regional temperature and atmospheric dynamics as a result of global warming suggest that water availability will be affected by changes in rainfall patterns. It is essential to understand the relative importance of different weather systems to water supply to determine how changes in rainfall patterns, interacting with geology and vegetation, will affect the water balance. To help determine the links between climate and water availability, stable isotope signatures of precipitation from different weather systems were established to identify those that are most important in maintaining streamflow and groundwater recharge. Precipitation stable isotope values in the Luquillo Mountains had a large range, from fog/cloud water with δ2H, δ18O values as high as +12 ‰, -0.73 ‰ to tropical storm rain with values as low as -127 ‰, -16.8 ‰. Temporal isotope values exhibit a reverse seasonality from those observed in higher latitude continental watersheds, with higher isotopic values in the winter and lower values in the summer. Despite the higher volume of convective and low-pressure system rainfall, stable isotope analyses indicated that under the current rainfall regime, frequent trade -wind orographic showers contribute much of the groundwater recharge and stream base flow. Analysis of rain events using 20 years of 15 -minute resolution data at a mountain station (643 m) showed an increasing trend in rainfall amount, in agreement with increased precipitable water in the atmosphere, but differing from climate model projections of drying in the region. The mean intensity of rain events also showed an increasing trend. The determination of recharge sources from stable isotope tracers indicates that water supply

  3. Greenland coastal air temperatures linked to Baffin Bay and Greenland Sea ice conditions during autumn through regional blocking patterns

    Science.gov (United States)

    Ballinger, Thomas J.; Hanna, Edward; Hall, Richard J.; Miller, Jeffrey; Ribergaard, Mads H.; Høyer, Jacob L.

    2018-01-01

    Variations in sea ice freeze onset and regional sea surface temperatures (SSTs) in Baffin Bay and Greenland Sea are linked to autumn surface air temperatures (SATs) around coastal Greenland through 500 hPa blocking patterns, 1979-2014. We find strong, statistically significant correlations between Baffin Bay freeze onset and SSTs and SATs across the western and southernmost coastal areas, while weaker and fewer significant correlations are found between eastern SATs, SSTs, and freeze periods observed in the neighboring Greenland Sea. Autumn Greenland Blocking Index values and the incidence of meridional circulation patterns have increased over the modern sea ice monitoring era. Increased anticyclonic blocking patterns promote poleward transport of warm air from lower latitudes and local warm air advection onshore from ocean-atmosphere sensible heat exchange through ice-free or thin ice-covered seas bordering the coastal stations. Temperature composites by years of extreme late freeze conditions, occurring since 2006 in Baffin Bay, reveal positive monthly SAT departures that often exceed 1 standard deviation from the 1981-2010 climate normal over coastal areas that exhibit a similar spatial pattern as the peak correlations.

  4. Characterization of the regions from E. coli 16 S RNA covalently linked to ribosomal proteins S4 and S20 after ultraviolet irradiation

    International Nuclear Information System (INIS)

    Ehresmann, B.; Backendorf, C.; Ehresmann, C.; Ebel, J.P.

    1977-01-01

    The use of ultraviolet irradiation to form photochemical covalent bonds between the 16 S RNA and a ribosomal protein is a reliable method to check RNA regions which are interacting with the protein. This technique was successfully used to covalently link RNA or DNA and specific proteins in several cases. In the case of ribosome, it has been shown that the irradiation of 30 S and 50 S subunits using high doses of ultraviolet light allowed the covalent binding of almost all of the ribosomal proteins to the 16 S or 23 S RNAs. Using mild conditions, only proteins S7 and L4 could be covalently linked to the 16 S and 23 S RNAs, respectively, and the 16 S RNA region linked to protein S7 has now been characterized. The specificity of the photoreaction was demonstrated earlier and the tryptic peptides from proteins S4 and S7, photochemically linked to the 16 S RNA complexes, were identified. A report is presented on the sequences of the RNA regions which can be photochemically linked to proteins S4 and S7 after ultraviolet irradiation of the specific S4-16 S RNA and 20 S-16 S RNA complexes

  5. The propeptide is required for in vivo formation of stable active yeast proteinase A and can function even when not covalently linked to the mature region

    DEFF Research Database (Denmark)

    van den Hazel, H B; Kielland-Brandt, Morten; Winther, Jakob R.

    1993-01-01

    The PEP4-encoded aspartate protease proteinase A from Saccharomyces cerevisiae is synthesized as a zymogen (Ammerer, G., Hunter, C. P., Rothman, J. H., Saari, G. C., Valls, L. A., and Stevens, T. H. (1986) Mol. Cell. Biol. 6, 2490-2499; Woolford, C. A., Daniels, L. B., Park, F. J., Jones, E. W., ...... folding of the mature region, even when the propeptide and the mature region are not covalently linked....

  6. Serotonin Transporter-Linked Polymorphic Region (5-HTTLPR) Genotype and Stressful Life Events Interact to Predict Preschool-Onset Depression: A Replication and Developmental Extension

    Science.gov (United States)

    Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S.; Tillman, Rebecca; Luby, Joan L.

    2014-01-01

    Background: Scientific enthusiasm about gene × environment interactions, spurred by the 5-HTTLPR (serotonin transporter-linked polymorphic region) × SLEs (stressful life events) interaction predicting depression, have recently been tempered by sober realizations of small effects and meta-analyses reaching opposing conclusions. These mixed findings…

  7. Bushmeat networks link the forest to urban areas in the trifrontier region between Brazil, Colombia, and Peru

    Directory of Open Access Journals (Sweden)

    Nathalie van Vliet

    2015-09-01

    Full Text Available Recent studies have intended to quantify urban consumption and trade in Amazonian towns. However, little is still known about the different ways in which bushmeat is made available in urban areas, including commercial and noncommercial flows, and how those flows contribute to link forests to urban livelihoods. In this study we qualitatively describe the structure and functioning of bushmeat flows in terms of species, catchment area, stakeholders involved, and the motivations for their activity in the main towns of the Amazon trifrontier region between Brazil, Colombia, and Peru. We show that bushmeat trade to urban areas exists under an organized but invisible commodity chain providing a source of income to about 195 persons. Bushmeat is made available either directly from the hunter to the urban consumer, at the main market place, or in food stalls and restaurants. On the Colombian border, the trade is totally invisible, whereas in Peru and Brazil, bushmeat is sold in open markets despite regulations. The catchment area comprises the main rivers: up to Caballococha along the Amazon River, along the Atacuary River in Peru, along the Javari River between Peru and Brazil, and along the Loretoyacu and Amacayacu rivers in Colombia and in periurban forests. Although the trade is rather localized (no commercial flows to larger towns, international transborder trade is commonplace, disregarding Convention on International Trade in Endangered Species of Wild Fauna and Flora regulations. Bushmeat clients in urban areas are mainly nonindigenous or mestizos who can afford bushmeat as a luxury meal. Instead, indigenous people in urban areas do not access bushmeat through the market but rather through their social networks with whom they maintain noncommercial flows including immediate exchange and long-term exchange mechanisms. Although bushmeat is no longer consumed as a daily meal among urban and periurban indigenous families, it constitutes what could be

  8. Narcissism and the Strategic Pursuit of Short-Term Mating: Universal Links across 11 World Regions of the International Sexuality Description Project-2

    OpenAIRE

    Schmitt, David P.; Alcalay, Lidia; Allik, Jüri; Alves, I. C. B.; Anderson, Craig A.; Angelini, A. L.; Asendorpf, Jens B.; Austers, Ivars; Balaguer, Isabel; Baptista, Américo; Bender, Sóley S.; Bennett, Kevin; Bianchi, Gabriel; Bianchi, Behrooz; Bleske-Rechek, April

    2017-01-01

    Previous studies have documented links between sub-clinical narcissism and the active pursuit of short-term mating strategies (e.g., unrestricted sociosexuality, marital infidelity, mate poaching). Nearly all of these investigations have relied solely on samples from Western cultures. In the current study, responses from a cross-cultural survey of 30,470 people across 53 nations spanning 11 world regions (North America, Central/South America, Northern Europe, Western Europe, Eastern Europe, S...

  9. Narcissism and the strategic pursuit of short-term mating : universal links across 11 world regions of the International Sexuality Description Project-2.

    OpenAIRE

    Schmitt, David; Alcalay, Lidia; Allik, Jüri; Alves, I.C.B.; Anderson, Craig; Angelini, A.L.; Asendorpf, Jens; Austers, Ivars; Balaguer, Isabel; Baptista, Américo; Bender, Sóley; Bennett, Kevin; Bianchi, Gabriel; Birashk, Behrooz; Bleske, April

    2017-01-01

    Previous studies have documented links between sub-clinical narcissism and the active pursuit of short-term mating strategies (e.g., unrestricted sociosexuality, marital infidelity, mate poaching). Nearly all of these investigations have relied solely on samples from Western cultures. In the current study, responses from a cross-cultural survey of 30,470 people across 53 nations spanning 11 world regions (North America, Central/South America, Northern Europe, Western Europe, Eastern Europe, S...

  10. Notch receptor expression in neurogenic regions of the adult zebrafish brain.

    Directory of Open Access Journals (Sweden)

    Vanessa de Oliveira-Carlos

    Full Text Available The adult zebrash brain has a remarkable constitutive neurogenic capacity. The regulation and maintenance of its adult neurogenic niches are poorly understood. In mammals, Notch signaling is involved in stem cell maintenance both in embryonic and adult CNS. To better understand how Notch signaling is involved in stem cell maintenance during adult neurogenesis in zebrafish we analysed Notch receptor expression in five neurogenic zones of the adult zebrafish brain. Combining proliferation and glial markers we identified several subsets of Notch receptor expressing cells. We found that 90 [Formula: see text] of proliferating radial glia express notch1a, notch1b and notch3. In contrast, the proliferating non-glial populations of the dorsal telencephalon and hypothalamus rarely express notch3 and about half express notch1a/1b. In the non-proliferating radial glia notch3 is the predominant receptor throughout the brain. In the ventral telencephalon and in the mitotic area of the optic tectum, where cells have neuroepithelial properties, notch1a/1b/3 are expressed in most proliferating cells. However, in the cerebellar niche, although progenitors also have neuroepithelial properties, only notch1a/1b are expressed in a high number of PCNA [Formula: see text] cells. In this region notch3 expression is mostly in Bergmann glia and at low levels in few PCNA [Formula: see text] cells. Additionally, we found that in the proliferation zone of the ventral telencephalon, Notch receptors display an apical high to basal low gradient of expression. Notch receptors are also expressed in subpopulations of oligodendrocytes, neurons and endothelial cells. We suggest that the partial regional heterogeneity observed for Notch expression in progenitor cells might be related to the cellular diversity present in each of these neurogenic niches.

  11. Transforming p21 ras protein: flexibility in the major variable region linking the catalytic and membrane-anchoring domains

    DEFF Research Database (Denmark)

    Willumsen, B M; Papageorge, A G; Hubbert, N

    1985-01-01

    or increasing it to 50 amino acids has relatively little effect on the capacity of the gene to induce morphological transformation of NIH 3T3 cells. Assays of GTP binding, GTPase and autophosphorylating activities of such mutant v-rasH-encoded proteins synthesized in bacteria indicated that the sequences...... that is required for post-translational processing, membrane localization and transforming activity of the proteins. We have now used the viral oncogene (v-rasH) of Harvey sarcoma virus to study the major variable region by deleting or duplicating parts of the gene. Reducing this region to five amino acids...... that encode these biochemical activities are located upstream from the major variable region. In the context of transformation, we propose that the region of sequence heterogeneity serves principally to connect the N-terminal catalytic domain with amino acids at the C terminus that are required to anchor...

  12. The Link between e-Waste and GDP—New Insights from Data from the Pan-European Region

    Directory of Open Access Journals (Sweden)

    Sigrid Kusch

    2017-03-01

    Full Text Available Waste electrical and electronic equipment (WEEE is difficult to sustainably manage. One key issue is the challenge of planning for WEEE flows as current and future quantities of waste are difficult to predict. To address this, WEEE generation and gross domestic product (GDP data from 50 countries of the pan-European region were assessed. A high economic elasticity was identified, indicating that WEEE and GDP are closely interlinked. More detailed analyses revealed that GDP at purchasing power parity (GDP PPP is a more meaningful measure when looking at WEEE flows, as a linear dependency between WEEE generation and GDP PPP was identified. This dependency applies to the whole region, regardless of the economic developmental stage of individual countries. In the pan-European region, an increase of 1000 international $ GDP PPP means an additional 0.5 kg WEEE is generated that requires management.

  13. No evidence for induction of key components of the Notch signaling pathway (Notch-1, Jagged-1) by treatment with UV-B, 1,25(OH)(2)D(3), and/or epigenetic drugs (TSA, 5-Aza) in human keratinocytes in vitro.

    Science.gov (United States)

    Reichrath, Sandra; Reichrath, Jörg

    2012-01-01

    Notch signaling is of high importance for growth and survival of various cell types. We now analyzed the protein expression of two key components of the Notch signaling pathway (Notch-1, Jagged-1) in spontaneously immortalized (HaCaT) and in malignant (SCL-1) human keratinocytes, using western analysis. We found that Notch-1 and its corresponding ligand Jagged-1 are expressed in both cell lines, with no marked change following UV-B treatment. Moreover, treatment of both cell lines before or after UV-B irradiation with 1,25-dihydroxyvitamin D(3), the biologically active form of vitamin D, and/or epigenetic modulating drugs (TSA; 5-Aza) did not result in a marked modulation of the protein expression of Notch-1 or Jagged-1. Under the experimental conditions of this study, treatment with 1,25(OH)(2)D(3) protected human keratinocytes in part against the antiproliferative effects of UV-B-radiation. In conclusion, our findings do not point at a differential expression of these two key components of Notch signaling in non-malignant as compared to malignant human keratinocytes, indicating that alterations in their expression are not of importance for the photocarcinogenesis of human squamous cell carcinomas. Moreover, our findings do not support the hypothesis that modulation of Notch signaling may be involved in the photoprotective effect of 1,25-dihydroxyvitamin D(3), that we and others reported previously. Additionally, we demonstrate that epigenetic modulating drugs (TSA, 5-Aza) do not markedly modulate the expression Notch-1 or Jagged-1 in UV-B-treated human keratinocytes in vitro.

  14. Current knowledge and future research directions to link soil health and water conservation in the Ogallala Aquifer region.

    Science.gov (United States)

    The Ogallala Aquifer is one of the largest freshwater aquifers in the world. It acts as a valuable resource in agriculture, animal production, and public water supplies across eight Great Plains states. However, with high irrigation demand, low recharge rates across most of the region, and extreme c...

  15. Linking regional stakeholder scenarios and shared socioeconomic pathways: Quantified West African food and climate futures in a global context

    NARCIS (Netherlands)

    Palazzo, Amanda; Vervoort, Joost M.; Mason-D’Croz, Daniel; Rutting, Lucas; Havlík, Petr; Islam, Shahnila; Bayala, Jules; Valin, Hugo; Kadi Kadi, Hamé Abdou; Thornton, Philip; Zougmore, Robert

    2017-01-01

    The climate change research community’s shared socioeconomic pathways (SSPs) are a set of alternative global development scenarios focused on mitigation of and adaptation to climate change. To use these scenarios as a global context that is relevant for policy guidance at regional and national

  16. Linking collaborative R&D strategies with the research and innovation performance of SMEs in peripheral regions

    DEFF Research Database (Denmark)

    Mitze, Timo; Alecke, Björn; Reinkowski, Janina

    2015-01-01

    We examine the empirical link between collaborative R&D strategies and the research and innovation performance of small- and medium-sized enterprises in peripheral locations. Using a survey of German firms combined with time series information on patent applications obtained from the European...... Patent Office, we apply a comparison-group approach and estimate different “treatment effect” models to assess the notion of causality underlying this relationship. Besides accounting for observed and unobserved firm-specific heterogeneity, we thereby also control for the likely endogeneity of R......&D collaboration as a strategic choice in the course of research and innovation activities. Our results for the period 2001–2007 indicate that engaging in R&D collaboration vis-á-vis a non-collaborative research strategy is related to higher outcome levels for a firm’s key research and innovation indicators...

  17. Sequencing and association analysis of the type 1 diabetes – linked region on chromosome 10p12-q11

    Directory of Open Access Journals (Sweden)

    Barratt Bryan J

    2007-05-01

    Full Text Available Abstract Background In an effort to locate susceptibility genes for type 1 diabetes (T1D several genome-wide linkage scans have been undertaken. A chromosomal region designated IDDM10 retained genome-wide significance in a combined analysis of the main linkage scans. Here, we studied sequence polymorphisms in 23 Mb on chromosome 10p12-q11, including the putative IDDM10 region, to identify genes associated with T1D. Results Initially, we resequenced the functional candidate genes, CREM and SDF1, located in this region, genotyped 13 tag single nucleotide polymorphisms (SNPs and found no association with T1D. We then undertook analysis of the whole 23 Mb region. We constructed and sequenced a contig tile path from two bacterial artificial clone libraries. By comparison with a clone library from an unrelated person used in the Human Genome Project, we identified 12,058 SNPs. We genotyped 303 SNPs and 25 polymorphic microsatellite markers in 765 multiplex T1D families and followed up 22 associated polymorphisms in up to 2,857 families. We found nominal evidence of association in six loci (P = 0.05 – 0.0026, located near the PAPD1 gene. Therefore, we resequenced 38.8 kb in this region, found 147 SNPs and genotyped 84 of them in the T1D families. We also tested 13 polymorphisms in the PAPD1 gene and in five other loci in 1,612 T1D patients and 1,828 controls from the UK. Overall, only the D10S193 microsatellite marker located 28 kb downstream of PAPD1 showed nominal evidence of association in both T1D families and in the case-control sample (P = 0.037 and 0.03, respectively. Conclusion We conclude that polymorphisms in the CREM and SDF1 genes have no major effect on T1D. The weak T1D association that we detected in the association scan near the PAPD1 gene may be either false or due to a small genuine effect, and cannot explain linkage at the IDDM10 region.

  18. Regional Brain Glucose Hypometabolism in Young Women with Polycystic Ovary Syndrome: Possible Link to Mild Insulin Resistance.

    Science.gov (United States)

    Castellano, Christian-Alexandre; Baillargeon, Jean-Patrice; Nugent, Scott; Tremblay, Sébastien; Fortier, Mélanie; Imbeault, Hélène; Duval, Julie; Cunnane, Stephen C

    2015-01-01

    To investigate whether cerebral metabolic rate of glucose (CMRglu) is altered in normal weight young women with polycystic ovary syndrome (PCOS) who exhibit mild insulin resistance. Seven women with PCOS were compared to eleven healthy female controls of similar age, education and body mass index. Regional brain glucose uptake was quantified using FDG with dynamic positron emission tomography and magnetic resonance imaging, and its potential relationship with insulin resistance assessed using the updated homeostasis model assessment (HOMA2-IR). A battery of cognitive tests was administered to evaluate working memory, attention and executive function. The PCOS group had 10% higher fasting glucose and 40% higher HOMA2-IR (p ≤ 0.035) compared to the Controls. The PCOS group had 9-14% lower CMRglu in specific regions of the frontal, parietal and temporal cortices (p ≤ 0.018). A significant negative relation was found between the CMRglu and HOMA2-IR mainly in the frontal, parietal and temporal cortices as well as in the hippocampus and the amygdala (p ≤ 0.05). Globally, cognitive performance was normal in both groups but scores on the PASAT test of working memory tended to be low in the PCOS group. The PCOS group exhibited a pattern of low regional CMRglu that correlated inversely with HOMA2-IR in several brain regions and which resembled the pattern seen in aging and early Alzheimer's disease. These results suggest that a direct association between mild insulin resistance and brain glucose hypometabolism independent of overweight or obesity can exist in young adults in their 20s. Further investigation of the influence of insulin resistance on brain glucose metabolism and cognition in younger and middle-aged adults is warranted.

  19. Regional Brain Glucose Hypometabolism in Young Women with Polycystic Ovary Syndrome: Possible Link to Mild Insulin Resistance.

    Directory of Open Access Journals (Sweden)

    Christian-Alexandre Castellano

    Full Text Available To investigate whether cerebral metabolic rate of glucose (CMRglu is altered in normal weight young women with polycystic ovary syndrome (PCOS who exhibit mild insulin resistance.Seven women with PCOS were compared to eleven healthy female controls of similar age, education and body mass index. Regional brain glucose uptake was quantified using FDG with dynamic positron emission tomography and magnetic resonance imaging, and its potential relationship with insulin resistance assessed using the updated homeostasis model assessment (HOMA2-IR. A battery of cognitive tests was administered to evaluate working memory, attention and executive function.The PCOS group had 10% higher fasting glucose and 40% higher HOMA2-IR (p ≤ 0.035 compared to the Controls. The PCOS group had 9-14% lower CMRglu in specific regions of the frontal, parietal and temporal cortices (p ≤ 0.018. A significant negative relation was found between the CMRglu and HOMA2-IR mainly in the frontal, parietal and temporal cortices as well as in the hippocampus and the amygdala (p ≤ 0.05. Globally, cognitive performance was normal in both groups but scores on the PASAT test of working memory tended to be low in the PCOS group.The PCOS group exhibited a pattern of low regional CMRglu that correlated inversely with HOMA2-IR in several brain regions and which resembled the pattern seen in aging and early Alzheimer's disease. These results suggest that a direct association between mild insulin resistance and brain glucose hypometabolism independent of overweight or obesity can exist in young adults in their 20s. Further investigation of the influence of insulin resistance on brain glucose metabolism and cognition in younger and middle-aged adults is warranted.

  20. Links between circulation types and precipitation in Central Europe in the observed data and regional climate model simulations

    Czech Academy of Sciences Publication Activity Database

    Plavcová, Eva; Kyselý, Jan; Štěpánek, P.

    2014-01-01

    Roč. 34, č. 9 (2014), s. 2885-2898 ISSN 0899-8418 R&D Projects: GA ČR GAP209/10/2265 Grant - others:FP6 ENSEMBLES(XE) 505539 Program:FP6 Institutional support: RVO:68378289 Keywords : precipitation * atmospheric circulation * regional climate models * ENSEMBLES * Central Europe Subject RIV: DG - Athmosphere Sciences, Meteorology; DG - Athmosphere Sciences, Meteorology (UEK-B) Impact factor: 3.157, year: 2014

  1. Primary syphilis cases in Guangdong Province 1995-2008: opportunities for linking syphilis control and regional development.

    Science.gov (United States)

    Yang, Li-Gang; Tucker, Joseph D; Yang, Bin; Shen, Song-Ying; Sun, Xi-Feng; Chen, Yong-Feng; Chen, Xiang-Sheng

    2010-12-30

    Syphilis cases have risen in many parts of China, with developed regions reporting the greatest share of cases. Since syphilis increases in these areas are likely driven by both increased screening and changes in sexual behaviours, distinguishing between these two factors is important. Examining municipal-level primary syphilis cases with spatial analysis allows a more direct understanding of changing sexual behaviours at a more policy-relevant level. In this study we examined all reported primary syphilis cases from Guangdong Province, a southern province in China, since the disease was first incorporated into the mandatory reporting system in 1995. Spatial autocorrelation statistics were used to correlate municipal-level clustering of reported primary syphilis cases and gross domestic product (GDP). A total of 52,036 primary syphilis cases were reported over the period 1995-2008, and the primary syphilis cases increased from 0.88 per 100,000 population in 1995 to 7.61 per 100,000 in 2008. The Pearl River Delta region has a disproportionate share (44.7%) of syphilis cases compared to other regions. Syphilis cases were spatially clustered (p = 0.01) and Moran's I analysis found that syphilis cases were clustered in municipalities with higher GDP (p = 0.004). Primary syphilis cases continue to increase in Guangdong Province, especially in the Pearl River Delta region. Considering the economic impact of syphilis and its tendency to spatially cluster, expanded syphilis testing in specific municipalities and further investigating the costs and benefits of syphilis screening are critical next steps.

  2. Linking Environmental Protection and Poverty Reduction in Africa: An Analysis of the Regional Legal Responses to Environmental Protection

    Directory of Open Access Journals (Sweden)

    Emeka Polycarp Amechi

    2010-09-01

    Full Text Available Poverty has been identified as the main cause and consequence of environmental degradation in Africa . It follows that if poverty is the main cause of environmental degradation in Africa , then policies, programmes and legal provisions designed to protect the environment in the region will be unsuccessful without a significant improvement in the living standards, wellbeing and livelihoods of the poor. In the same breath, since poverty is a consequence of environmental degradation, then the protection of the environment is critical to the achievement of poverty reduction initiatives such as the Millennium Development Goals in Africa . Hence, it can be argued that there is a mutual relationship between the achievement of environmental protection and reduction of poverty in Africa . This article therefore examines the extent to which the various regional legal instruments for the protection of the environment in Africa recognise this mutual linkage by providing for the promotion of poverty reduction and socio-economic development as integral aspect of their objective of ensuring the protection of the environment in the region.

  3. Novel procedure for genotyping of the human serotonin transporter gene-linked polymorphic region (5-HTTLPR)--a region with a high level of allele diversity

    DEFF Research Database (Denmark)

    Rasmussen, Henrik B; Werge, Thomas M

    2007-01-01

    determination. After having developed a 5-HTTLPR genotyping assay, we examined all samples of DNA in two separate rounds of analyses and found complete agreement between the results from these two rounds. CONCLUSION: On the basis of simultaneous analysis of tandem repeat size variation and variation of single......BACKGROUND: The serotonin transporter, the target of a group of antidepressant drugs, is involved in the regulation of the availability and reuptake of serotonin. A variable number of tandem repeats in the promoter region of the serotonin transporter gene, designated 5-HTTLPR, affects...... for detailed genotyping of 5-HTTLPR based upon simultaneous analysis of tandem repeat size variation and single nucleotide variations. METHODS: We elaborated a list of all known 5-HTTLPR alleles to provide an overview of the allele repertoire at this polymorphic locus. Fragments of 5-HTTLPR were PCR...

  4. Function and structure in social brain regions can link oxytocin-receptor genes with autistic social behavior.

    Science.gov (United States)

    Yamasue, Hidenori

    2013-02-01

    Difficulties in appropriate social and communicative behaviors are the most prevalent and core symptoms of autism spectrum disorders (ASDs). Although recent intensive research has focused on the neurobiological background of these difficulties, many aspects of them were not yet elucidated. Recent studies have employed multimodal magnetic resonance imaging (MRI) indices as intermediate phenotypes of this behavioral phenotype to link candidate genes with the autistic social difficulty. As MRI indices, functional MRI (fMRI), structural MRI, and MR-spectroscopy have been examined in subjects with autism spectrum disorders. As candidate genes, this mini-review has much interest in oxytocin-receptor genes (OXTR), since recent studies have repeatedly reported their associations with normal variations in social cognition and behavior as well as with their extremes, autistic social dysfunction. Through previous increasing studies, medial prefrontal cortex, hypothalamus and amygdala have repeatedly been revealed as neural correlates of autistic social behavior by MRI multimodalities and their relationship to OXTR. For further development of this research area, this mini-review integrates recent accumulating evidence about human behavioral and neural correlates of OXTR. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  5. More evidence for a planetary wave link with midlatitude E region coherent backscatter and sporadic E layers

    Directory of Open Access Journals (Sweden)

    K. Schlegel

    Full Text Available Measurements of midlatitude E region coherent backscatter obtained during four summers with SESCAT, a 50 MHz Doppler system operating in Crete, Greece, and concurrent ionosonde recordings from the same ionospheric volume obtained with a CADI for one of these summers, are used to analyse the long-term variability in echo and Es occurrence. Echo and Es layer occurrences, computed in percent of time over a 12-h nighttime interval, take the form of time sequences. Linear power spectrum analysis shows that there are dominant spectral peaks in the range of 2–9 days, the most commonly observed periods appearing in two preferential bands, of 2–3 days and 4–7 days. No connection with geomagnetic activity was found. The characteristics of these periodicities compare well with similar properties of planetary waves, which suggests the possibility that planetary waves are responsible for the observed long-term periodicities. These findings indicate also a likely close relation between planetary wave (PW activity and the well known but not well understood seasonal Es dependence. To test the PW postulation, we used simultaneous neutral wind data from the mesopause region around 95 km, measured from Collm, Germany. Direct comparison of the long-term periodicities in echo and Es layer occurrence with those in the neutral wind show some reasonable agreement. This new evidence, although not fully conclusive, is the first direct indication in favour of a planetary wave role on the unstable midlatitude E region ionosphere. Our results suggest that planetary waves observation is a viable option and a new element into the physics of midlatitude Es layers that needs to be considered and investigated.Key words: Ionosphere (ionosphere irregularities; mid-latitude ionosphere – Meteorology and atmospheric dynamics (waves and tides

  6. Linking Backbarrier Lacustrine Stratigraphy with Spatial Dynamics of Shoreline Retreat in a Rapidly Subsiding Region of the Mississippi River Delta

    Science.gov (United States)

    Dietz, M.; Liu, K. B.; Bianchette, T. A.; Yao, Q.

    2017-12-01

    The shoreline along the northern Gulf of Mexico is rapidly retreating as coastal features of abandoned Mississippi River delta complexes erode and subside. Bay Champagne is located in the Caminada-Moreau headland, a region of shoreline west of the currently active delta that has one of the highest rates of retreat and land loss. As a result, this site has transitioned from a stable, circular inland lake several kilometers from the shore to a frequently perturbed, semi-circular backbarrier lagoon, making it ideal to study the environmental effects of progressive land loss. Analyses of clastic layers in a series of sediment cores collected at this site over the past decade indicate the lake was less perturbed in the past and has become increasingly more sensitive to marine incursion events caused by tropical cyclones. Geochemical and pollen analyses of these cores also reveal profound changes in environmental and chemical conditions in Bay Champagne over the past century as the shoreline has retreated. Through relating stratigraphy to spatial changes observed from satellite imagery, this study attempts to identify the tipping point at which Bay Champagne began the transition from an inland lake to a backbarrier environment, and to determine the rate at which this transition occurred. Results will be used to develop a model of the environmental transition experienced by a rapidly retreating coastline and to predict how other regions of the Mississippi River deltaic system could respond to future shoreline retreat.

  7. Exploring the Links in Monthly to Decadal Variability of the Atmospheric Water Balance Over the Wettest Regions in ERA-20C

    Science.gov (United States)

    Nogueira, M.

    2017-10-01

    Monthly-to-decadal variability of the regional precipitation over Intertropical Convergence Zone and north-Atlantic and north-Pacific storm tracks was investigated using ERA-20C reanalysis. Satellite-based precipitation (P) and evaporation (E) climatological patterns were well reproduced by ERA-20C. Regional P and E monthly time series displayed 20% differences, but these decreased rapidly with time scale ( 10% at yearly time scales). Spectral analysis showed good scale-by-scale statistical agreement between ERA-20C and observations. Using ERA-Interim showed no improvement despite the much wider range of information assimilated (including satellites). Remarkably high Detrended Cross-Correlation Analysis coefficients (ρDCCA > 0.7 and often ρDCCA > 0.9) revealed tight links between the nonperiodic variability of P, moisture divergence (DIV), and pressure velocity (ω) at monthly-to-decadal time scales over all the wet regions. In contrast, ρDCCA was essentially nonsignificant between nonperiodic P and E or sea surface temperature (SST). Thus, the nonperiodic monthly-to-decadal variability of precipitation in these regions is almost fully controlled by dynamics and not by local E or SST (suggested by Clausius-Clapeyron relation). Analysis of regional nonperiodic standard deviations and power spectra (and respective spectral exponents, β) provided further robustness to this conclusion. Finally, clear transitions in β for P, DIV, and ω between tropical and storm track regions were found. The latter is dominated by transient storms, with energy accumulation at synoptic scales and β β values (0.2 to 0.4) were found in the tropics, implying longer-range autocorrelations and slower decreasing variability and information creation with time scale, consistent with the important forcing from internal modes of variability (e.g., El Niño-Southern Oscillation).

  8. Linking Regional Winter Sea Ice Thickness and Surface Roughness to Spring Melt Pond Fraction on Landfast Arctic Sea Ice

    Directory of Open Access Journals (Sweden)

    Sasha Nasonova

    2017-12-01

    Full Text Available The Arctic sea ice cover has decreased strongly in extent, thickness, volume and age in recent decades. The melt season presents a significant challenge for sea ice forecasting due to uncertainty associated with the role of surface melt ponds in ice decay at regional scales. This study quantifies the relationships of spring melt pond fraction (fp with both winter sea ice roughness and thickness, for landfast first-year sea ice (FYI and multiyear sea ice (MYI. In 2015, airborne measurements of winter sea ice thickness and roughness, as well as high-resolution optical data of melt pond covered sea ice, were collected along two ~5.2 km long profiles over FYI- and MYI-dominated regions in the Canadian Arctic. Statistics of winter sea ice thickness and roughness were compared to spring fp using three data aggregation approaches, termed object and hybrid-object (based on image segments, and regularly spaced grid-cells. The hybrid-based aggregation approach showed strongest associations because it considers the morphology of the ice as well as footprints of the sensors used to measure winter sea ice thickness and roughness. Using the hybrid-based data aggregation approach it was found that winter sea ice thickness and roughness are related to spring fp. A stronger negative correlation was observed between FYI thickness and fp (Spearman rs = −0.85 compared to FYI roughness and fp (rs = −0.52. The association between MYI thickness and fp was also negative (rs = −0.56, whereas there was no association between MYI roughness and fp. 47% of spring fp variation for FYI and MYI can be explained by mean thickness. Thin sea ice is characterized by low surface roughness allowing for widespread ponding in the spring (high fp whereas thick sea ice has undergone dynamic thickening and roughening with topographic features constraining melt water into deeper channels (low fp. This work provides an important contribution towards the parameterizations of fp in

  9. Trends in summer chemistry linked to productivity in lakes recovering from acid deposition in the Adirondack region of New York

    Science.gov (United States)

    Momen, B.; Lawrence, G.B.; Nierzwicki-Bauer, S. A.; Sutherland, J.W.; Eichler, L.W.; Harrison, J.P.; Boylen, C.W.

    2006-01-01

    The US Environmental Protection Agency established the Adirondack Effects Assessment Program (AEAP) to evaluate and monitor the status of biological communities in lakes in the Adirondack region of New York that have been adversely affected by acid deposition. This program includes chemical analysis of 30 lakes, sampled two to three times each summer. Results of trends analysis for lake chemistry and chlorophyll a (chlor a) are presented for 1994 to 2003, and a general comparison is made with recent results of the Adirondack Long-Term Monitoring (ALTM) Program, which included chemical analysis of all but two of these lakes (plus an additional 24 lakes) monthly, year-round for 1992-2004. Increases in pH were found in 25 of the 30 AEAP lakes (P level of P level of P level of P level of P level of P chemistry were similar to those of the ALTM Program, although decreases in SO 42- concentrations were more evident in the year-round ALTM record. Overall, the results suggest (a) a degree of chemical recovery from acidification during the summer, (b) an increase in phytoplankton productivity, and (c) a decreasing trend in NO 3- concentrations resulting from the increased productivity. ?? 2007 Springer Science+Business Media, Inc.

  10. Regional earthquakes followed by delayed ground uplifts at Campi Flegrei Caldera, Italy: Arguments for a causal link

    Science.gov (United States)

    Lupi, Matteo; Frehner, Marcel; Weis, Philipp; Skelton, Alasdair; Saenger, Erik H.; Tisato, Nicola; Geiger, Sebastian; Chiodini, Giovanni; Driesner, Thomas

    2017-09-01

    Earthquake-triggered volcanic activity promoted by dynamic and static stresses are considered rare and difficult-to-capture geological processes. Calderas are ideal natural laboratories to investigate earthquake-volcano interactions due to their sensitivity to incoming seismic energy. The Campi Flegrei caldera, Italy, is one of the most monitored volcanic systems worldwide. We compare ground elevation time series at Campi Flegrei with earthquake catalogues showing that uplift events at Campi Flegrei are associated with large regional earthquakes. Such association is supported by (yet non-definitive) binomial tests. Over a 70-year time window we identify 14 uplift events, 12 of them were preceded by an earthquake, and for 8 of them the earthquake-to-uplift timespan ranges from immediate responses to 1.2 yr. Such variability in the response delay may be due to the preparedness of the system with faster responses probably occurring in periods during which the Campi Flegrei system was already in a critical state. To investigate the process that may be responsible for the proposed association we simulate the propagation of elastic waves and show that passing body waves impose high dynamic strains at the roof of the magmatic reservoir of the Campi Flegrei at about 7 km depth. This may promote a short-lived embrittlement of the magma reservoir's carapace otherwise marked by a ductile behaviour. Such failure allows magma and exsolved volatiles to be released from the magmatic reservoir. The fluids, namely exsolved volatiles and/or melts, ascend through a nominally plastic zone above the magmatic reservoir. This mechanism and the associated inherent uncertainties require further investigations but the new concept already implies that geological processes triggered by passing seismic waves may become apparent several months after passage of the seismic waves.

  11. Linking satellite ICT application businesses with regional innovation centers and investors: The EC “INVESaT” project

    Science.gov (United States)

    Ghiron, Florence; Kreisel, Joerg

    2009-09-01

    In the sector of information and communication technologies (ICT), whether in the USA, Japan, or Europe, innovative services are already in use, based on large-scale space-based infrastructure investments. Such systems are e.g. earth observation, telecommunication, and navigation, timing and positioning satellites. In combination with the advent of powerful handheld terminals and the demand for ubiquitous services, it is expected that info-mobility applications will reveal new sources of business in the years ahead, using in particular the Earth observation and future GALILEO systems to position any feature or user anywhere in the world within a few meter accuracy. Hence, satellite-based capabilities provide new and unique opportunities for economic stimulation and development. Many incubators and innovation centers in Europe have already grasped this growth potential. Yet, for many European players business growth appears below expectations compared to developments in the USA following the launch of GPS (Global Positioning System). Europe still has to overcome intrinsic barriers to seize these new business opportunities faster and with more visible economic impact by leveraging on SMEs and regional innovation centers to expand the commercial utilization of satellite capabilities and mobilization of appropriate financial resources. The paper elaborates on the INVESat project (funded by the EuropeInnova—European Commission), which aims at bridging the gap between Innovative enterprises and financial In VEstors in the emerging markets of SaTellite applications. The critical success factors required to stimulate and support more efficiently investments in this bread of innovative services will also be highlighted.

  12. Post-harvest practices linked with ochratoxin A contamination of coffee in three provinces of Cordillera Administrative Region, Philippines.

    Science.gov (United States)

    Barcelo, Jonathan M; Barcelo, Racquel C

    2018-02-01

    One of the emerging concerns in the Cordillera Administrative Region, Philippines is ochratoxin A (OTA) contamination in coffee. During 2015 to 2016, a total of 51 Arabica (Coffea arabica) coffee samples from Benguet province and 71 Robusta (Coffea canephora var. Robusta) coffee samples from the provinces of Ifugao and Kalinga were analysed for OTA contamination. The OTA-producing fungal contaminants during drying and storage of Arabica and Robusta coffee were Aspergillus niger and Aspergillus ochraceus. Ochratoxin A was more commonly detected in Robusta coffee (36.6%) than in Arabica coffee (21.6%). Among the contaminated samples, Robusta coffee cherries in the drying yard had the highest mean OTA level (120.2 μg kg -1 , n = 10) while roasted Robusta coffee beans had the lowest mean level (4.8 μg kg -1 , n = 9). The onset of contamination of Arabica coffee occurred during storage, with a mean OTA level of 46.7 μg kg -1 (n = 9). Roasted coffee had lower OTA content although five samples had levels >5.0 μg kg -1 . Pearson Chi-square analysis (χ 2 ) and Fisher's exact test revealed that several post-harvest practices involving non-removal of the husk or hull and mixing of defective coffee were significantly associated with the occurrence of OTA during drying and storage (p coffee in all stages of post-harvest and rapid reduction of moisture content particularly during drying.

  13. Assessing the links among environmental contaminants, endocrinology, and parasites to understand amphibian declines in montane regions of Costa Rica.

    Science.gov (United States)

    Leary, Christopher J; Ralicki, Hannah F; Laurencio, David; Crocker-Buta, Sarah; Malone, John H

    2018-01-01

    Amphibians inhabiting montane riparian zones in the Neotropics are particularly vulnerable to decline, but the reasons are poorly understood. Because environmental contaminants, endocrine disruption, and pathogens often figure prominently in amphibian declines it is imperative that we understand how these factors are potentially interrelated to affect montane populations. One possibility is that increased precipitation associated with global warming promotes the deposition of contaminants in montane regions. Increased exposure to contaminants, in turn, potentially elicits chronic elevations in circulating stress hormones that could contribute to montane population declines by compromising resistance to pathogens and/or production of sex steroids regulating reproduction. Here, we test this hypothesis by examining contaminant levels, stress and sex steroid levels, and nematode abundances in male drab treefrogs, Smilisca sordida, from lowland and montane populations in Costa Rica. We found no evidence that montane populations were more likely to possess contaminants (i.e., organochlorine, organophosphate and carbamate pesticides or benzidine and chlorophenoxy herbicides) than lowland populations. We also found no evidence of elevational differences in circulating levels of the stress hormone corticosterone, estradiol or progesterone. However, montane populations possessed lower androgen levels, hosted more nematode species, and had higher nematode abundances than lowland populations. Although these results suggested that nematodes contributed to lower androgens in montane populations, we were unable to detect a significant inverse relationship between nematode abundance and androgen level. Our results suggest that montane populations of this species are not at greater risk of exposure to contaminants or chronic stress, but implicate nematodes and compromised sex steroid levels as potential threats to montane populations.

  14. Linking Bayesian and agent-based models to simulate complex social-ecological systems in semi-arid regions

    Directory of Open Access Journals (Sweden)

    Aloah J Pope

    2015-08-01

    Full Text Available Interdependencies of ecologic, hydrologic, and social systems challenge traditional approaches to natural resource management in semi-arid regions. As a complex social-ecological system, water demands in the Sonoran Desert from agricultural and urban users often conflicts with water needs for its ecologically-significant riparian corridors. To explore this system, we developed an agent-based model to simulate complex feedbacks between human decisions and environmental conditions in the Rio Sonora Watershed. Cognitive mapping in conjunction with stakeholder participation produced a Bayesian model of conditional probabilities of local human decision-making processes resulting to changes in water demand. Probabilities created in the Bayesian model were incorporated into the agent-based model, so that each agent had a unique probability to make a positive decision based on its perceived environment at each point in time and space. By using a Bayesian approach, uncertainty in the human decision-making process could be incorporated. The spatially-explicit agent-based model simulated changes in depth-to-groundwater by well pumping based on an agent’s water demand. Changes in depth-to-groundwater feedback to influence agent behavior, as well as determine unique vegetation classes within the riparian corridor. Each vegetation class then provides varying stakeholder-defined quality values of ecosystem services. Using this modeling approach allowed us to examine effects on both the ecological and social system of semi-arid riparian corridors under various scenarios. The insight provided by the model contributes to understanding how specific interventions may alter the complex social-ecological system in the future.

  15. Assessing the links among environmental contaminants, endocrinology, and parasites to understand amphibian declines in montane regions of Costa Rica.

    Directory of Open Access Journals (Sweden)

    Christopher J Leary

    Full Text Available Amphibians inhabiting montane riparian zones in the Neotropics are particularly vulnerable to decline, but the reasons are poorly understood. Because environmental contaminants, endocrine disruption, and pathogens often figure prominently in amphibian declines it is imperative that we understand how these factors are potentially interrelated to affect montane populations. One possibility is that increased precipitation associated with global warming promotes the deposition of contaminants in montane regions. Increased exposure to contaminants, in turn, potentially elicits chronic elevations in circulating stress hormones that could contribute to montane population declines by compromising resistance to pathogens and/or production of sex steroids regulating reproduction. Here, we test this hypothesis by examining contaminant levels, stress and sex steroid levels, and nematode abundances in male drab treefrogs, Smilisca sordida, from lowland and montane populations in Costa Rica. We found no evidence that montane populations were more likely to possess contaminants (i.e., organochlorine, organophosphate and carbamate pesticides or benzidine and chlorophenoxy herbicides than lowland populations. We also found no evidence of elevational differences in circulating levels of the stress hormone corticosterone, estradiol or progesterone. However, montane populations possessed lower androgen levels, hosted more nematode species, and had higher nematode abundances than lowland populations. Although these results suggested that nematodes contributed to lower androgens in montane populations, we were unable to detect a significant inverse relationship between nematode abundance and androgen level. Our results suggest that montane populations of this species are not at greater risk of exposure to contaminants or chronic stress, but implicate nematodes and compromised sex steroid levels as potential threats to montane populations.

  16. Regional Approach for Managing for Resilience Linking Ecosystem Services and Livelihood Strategies for Agro-Pastoral Communities in the Mongolian Steppe Ecosystem

    Science.gov (United States)

    Ojima, D. S.; Togtohyn, C.; Qi, J.; Galvin, K.

    2011-12-01

    Dramatic changes due to climate and land use dynamics in the Mongolian Plateau are affecting ecosystem services and agro-pastoral livelihoods in Mongolia and China. Recently, evaluation of pastoral systems, where humans depend on livestock and grassland ecosystem services, have demonstrated the vulnerability of the social-ecological system to climate change. Current social-ecological changes in ecosystem services are affecting land productivity and carrying capacity, land-atmosphere interactions, water resources, and livelihood strategies. Regional dust events, changes in hydrological cycle, and land use changes contribute to changing interactions between ecosystem and landscape processes which then affect social-ecological systems. The general trend involves greater intensification of resource exploitation at the expense of traditional patterns of extensive range utilization. Thus we expect climate-land use-land cover relationships to be crucially modified by the socio-economic forces. The analysis incorporates information of the socio-economic transitions taking place in the region which affect land-use, food security, and ecosystem dynamics. The region of study extends from the Mongolian plateau in Mongolia and China to the fertile northeast China plain. Sustainability of agro-pastoral systems in the region needs to integrate the impact of climate change on ecosystem services with socio-economic changes shaping the livelihood strategies of pastoral systems in the region. Adaptation strategies which incorporate landscape management provides a potential framework to link ecosystem services across space and time more effectively to meet the needs of agro-pastoral land use, herd quality, and herder's living standards. Under appropriate adaptation strategies agro-pastoralists will have the opportunity to utilize seasonal resources and enhance their ability to process and manufacture products from the available ecosystem services in these dynamic social

  17. Co-ordinate expression of glycine betaine synthesis genes linked by the FMDV 2A region in a single open reading frame in Pichia pastoris.

    Science.gov (United States)

    Wang, Sanhong; Yao, Quanhong; Tao, Jianmin; Qiao, Yushan; Zhang, Zhen

    2007-12-01

    The genes encoding the two enzymes choline monooxygenase (CMO) and betaine aldehyde dehydrogenase (BADH) of glycine betaine synthesis in Suaeda salsa were cloned and fused with the 2A region of foot-and-mouth disease virus in a single open reading frame. The fused genes were placed under the control of the alcohol oxidase (AOX1) promoter in pPIC3B and transformed into P. pastoris GS115. The expression of the fused genes in P. pastoris and the ability of recombinant yeasts to tolerate environmental stresses were studied. The results showed that induced with 0.5% methanol for 96 h, the maximal activities of CMO and BADH in the tested recombinant yeasts were 45- and 44-fold higher than those in the control yeast transformed empty vector only, respectively; the content of glycine betaine in the recombinant yeasts was 28- to 35-fold higher than that in the control. The fused genes linked by 2A region of foot-and-mouth disease virus were expressed in P. pastoris successfully and the polyprotein was 'cleaved' to each functional protein. The yeasts transformed the fused genes, which were more resistant to salt, methanol, and high temperature stresses than the control as result of glycine betaine synthesis genes introduced.

  18. Gains from trans-boundary water quality management in linked catchment and coastal socio-ecological systems: a case study for the Minho region

    Science.gov (United States)

    Roebeling, P. C.; Brito, A. G.; Rocha, J.; Alves, H.; Mamede, J.

    2012-04-01

    Worldwide, aquatic and coastal ecosystems are affected by point and diffuse source water pollution originating from rural, urban and industrial land uses in catchments, even though these ecosystems are of vital importance from an environmental and economic perspective. Integrated Catchment and Coastal Zone Management (ICCZM) specifically takes into account this inherent relationship between terrestrial land use, surface and ground water pollution, aquatic and coastal ecosystem state, and associated environmental values. To warrant sustainable regional economic development, we need to balance the marginal costs from terrestrial water pollution abatement and the associated marginal benefits from aquatic and coastal resource appreciation. In doing so, however, we need to differentiate between intra- and trans-boundary catchments because benefactors and beneficiaries from water quality improvement are not one and the same. In trans-boundary catchments, private (national) welfare maximizing rates of water quality improvement differ across nations as benefits from water quality improvement generally accrue to one nation while the costs are paid by multiple nations. While approaches for water quality management in linked catchment and coastal socio-ecological systems are fairly recent though existent, water quality management in trans-boundary catchments poses additional challenges. The objective of this paper is to develop and apply a deterministic optimal control approach that allows us to explore private and social welfare maximizing rates of water pollution abatement in linked catchment and coastal socio-ecological systems. For a case study of the Minho region in the Iberian Peninsula, we estimate nation-specific water pollution abatement cost (based on management practice adoption) and benefit (based on aquatic and coastal environmental values) functions, to determine as well as compare private (national) and social (trans-national) welfare maximizing rates of water

  19. Development of dominant sequence characterized amplified region (SCAR marker linked with plume moth (Exelastis atomosa Walsingham 1886 resistance in pigeon-pea

    Directory of Open Access Journals (Sweden)

    Ramya R Mishra

    2015-12-01

    Full Text Available The mode of gene action governing resistance to plume moth (Exelastis atomosa Walsingham 1886 derived from pigeon-pea (Cajanus scarabaeoides (L. Thouars accession ICPW-94 has been determined and the resistance alleles have been designated as PPM1. The progenies of F2 population and F3 families derived from an interspecific cross C. cajan (L. Huth ('ICP-26' x C. scarabaeoides (accession ICPW-94 revealed monogenic gene action for resistance to plume moth, and the dominant control by single locus or cluster of tightly linked alleles. Bulked segregant analysis (BSA of 116 F2 progenies by using 143 parental polymorphic RAPD primers could identify a fragment OPA09(910 associated with plume moth resistance in coupling phase of linkage. Further single plant analysis of the 116 F2 mapping population revealed OPA09(910 was linked to PPMi locus conferring host resistance to plume moth with recombination fraction (rf value of 0.125 (12.7 cM of Kosambi function. The resistance specific fragment OPA09(910 was cloned, sequenced and converted into a sequence characterized amplified region (SCAR marker, SCOPA09(942, which was also closely associated (10.3 cM with the locus PPMl with rf value 0.102. BLAST analysis with pigeon-pea genome sequence also confirmed its occurrence in CcLG02 (Scafseq.LG_V5.0fa and contig 01597 (AFSP01.fsa1. This SCAR marker showed reasonable screening efficiency in the F2, F3, and BC1F1 lines, thus it can be used as genetic handle in marker-assisted introgression of the genomic fragment conferring plume moth resistance and screening of breeding lines in pigeon-pea.

  20. Construction of a YAC contig and STS map spanning 2.5 Mbp in Xq25, the critical region for the X-linked lymphoproliferative (XLP) gene

    Energy Technology Data Exchange (ETDEWEB)

    Lanyi, A.; Li, B.F.; Li, S. [Univ. of Nebraska Medical Center, Omaha, NE (United States)] [and others

    1994-09-01

    X-linked lymphoproliferative disease (XLP) is characterized by a marked vulnerability in Epstein-Barr virus (EBV) infection. Infection of XLP patients with EBV invariably results in fatal mononucleosis, agammaglobulinemia or B-cell lymphoma. The XLP gene lies within a 10 cM region in Xq25 between DXS42 and DXS10. Initial chromosome studies revealed an interstitial, cytogenetically visible deletion in Xq25 in one XLP family (43-004). We estimated the size of the Xq25 deletion by dual laser flow karyotyping to involve 2% of the X chromosome, or approximately 3 Mbp of DNA sequences. To further delineate the deletion we performed a series of pulsed field gel electrophoresis (PFGE) analyses which showed that DXS6 and DXS100, two Xq25-specific markers, are missing from 45-004 DNA. Five yeast artificial chromosomes (YACs) from a chromosome X specific YAC library containing sequences deleted in patient`s 43-004 DNA were isolated. These five YACs did not overlap, and their end fragments were used to screen the CEPH MegaYAC library. Seven YACs were isolated from the CEPH MegaYAC library. They could be arranged into a contig which spans between DXS6 and DXS100. The contig contains a minimum of 2.5 Mbp of human DNA. A total of 12 YAC end clone, lambda subclones and STS probes have been used to order clones within the contig. These reagents were also used in Southern blot and patients showed interstitial deletions in Xq25. The size of these deletions range between 0.5 and 2.5 Mbp. The shortest deletion probably represents the critical region for the XLP gene.

  1. Does the Incredible Years reduce child externalizing problems through improved parenting? The role of child negative affectivity and serotonin transporter linked polymorphic region (5-HTTLPR) genotype.

    Science.gov (United States)

    Weeland, Joyce; Chhangur, Rabia R; Jaffee, Sara R; Van Der Giessen, Danielle; Matthys, Walter; Orobio De Castro, Bram; Overbeek, Geertjan

    2018-02-01

    In a randomized controlled trial, the Observational Randomized Controlled Trial of Childhood Differential Susceptibility (ORCHIDS study), we tested whether observed parental affect and observed and reported parenting behavior are mechanisms of change underlying the effects of the behavioral parent training program the Incredible Years (IY). Furthermore, we tested whether some children are more susceptible to these change mechanisms because of their temperamental negative affectivity and/or serotonin transporter linked polymorphic region (5-HTTLPR) genotype. Participants were 387 Dutch children between 4 and 8 years of age (M age = 6.31, SD = 1.33; 55.3% boys) and their parents. Results showed that although IY was successful in improving parenting behavior and increasing parental positive affect, these effects did not explain the significant decreases in child externalizing problems. We therefore found no evidence for changes in parenting behavior or parental affect being the putative mechanisms of IY effectiveness. Furthermore, intervention effects on child externalizing behavior were not moderated by child negative affectivity or 5-HTTLPR genotype. However, child 5-HTTLPR genotype did moderate intervention effects on negative parenting behavior. This suggests that in research on behavioral parent training programs, "what works for which parents" might also be an important question.

  2. A meta-analysis of the effects of the 5-hydroxytryptamine transporter gene-linked promoter region polymorphism on susceptibility to lifelong premature ejaculation.

    Directory of Open Access Journals (Sweden)

    Lijie Zhu

    Full Text Available OBJECTIVE: Premature ejaculation (PE has been reported as the most common male sexual dysfunction with global prevalence rates estimated at approximately 30%. The neurobiogenesis of ejaculation is very complex and involves the serotoninergic (5-hydroxytryptamine, 5-HT system. Recently, genetic polymorphisms located on SLC6A4 gene codifying for 5-HT transporter (5-HTT, the major regulator of serotonic neurotransmission, have been linked with the pathogenesis and risk of PE. Apparently studies of this type of polymorphism in PE have show conflicting results. METHODS: A meta-analysis was performed that are available in relation with 5-HTT gene-linked promoter region (5-HTTLPR polymorphism and the risk of lifelong PE (LPE in men to clarify this relationship. We searched Pubmed and Embase (last search updated on Aug 2012 using 'premature ejaculation', 'polymorphism or variant', 'genotype', 'ejaculatory function', and 'rapid ejaculation' as keywords and reference lists of studies corresponded to the inclusion criteria for meta-analysis. These studies involved the total number of 481 LPE men and 466 health control men subjects. Odds ratio (OR and 95% confidence intervals (CIs were used to evaluate this relationship. RESULTS: In the overall analysis, significant associations between LPE risk and 5-HTTLPR polymorphism were found (L-allele vs. S-allele OR = 0.86, 95% CI = 0.79-0.95, P = 0.002; LL vs. SS: OR = 0.80, 95% CI = 0.68-0.95, P = 0.009; LS vs. SS: OR = 0.85, 95% CI = 0.76-0.97, P = 0.012 and LL+LS vs. SS: OR = 0.88, 95% CI = 0.81-0.95, P = 0.002. Moreover, in subgroup analysis based on ethnicity, similar significant associations were detected. The Egger's test did not reveal presence of a publication bias. CONCLUSIONS: Our investigations demonstrate that 5-HTTLPR (L>S polymorphism might protect men against LPE risk. Further studies based on larger sample size and gene-environment interactions should

  3. Narcissism and the Strategic Pursuit of Short-Term Mating: Universal Links across 11 World Regions of the International Sexuality Description Project-2

    Directory of Open Access Journals (Sweden)

    David P. Schmitt et al.

    2017-05-01

    Full Text Available Previous studies have documented links between sub-clinical narcissism and the active pursuit of short-term mating strategies (e.g., unrestricted sociosexuality, marital infidelity, mate poaching. Nearly all of these investigations have relied solely on samples from Western cultures. In the current study, responses from a cross-cultural survey of 30,470 people across 53 nations spanning 11 world regions (North America, Central/South America, Northern Europe, Western Europe, Eastern Europe, Southern Europe, Middle East, Africa, Oceania, Southeast Asia, and East Asia were used to evaluate whether narcissism (as measured by the Narcissistic Personality Inventory; NPI was universally associated with short-term mating. Results revealed narcissism scores (including two broad factors and seven traditional facets as measured by the NPI were functionally equivalent across cultures, reliably associating with key sexual outcomes (e.g., more active pursuit of short-term mating, intimate partner violence, and sexual aggression and sex-related personality traits (e.g., higher extraversion and openness to experience. Whereas some features of personality (e.g., subjective well-being were universally associated with socially adaptive facets of Narcissism (e.g., self-sufficiency, most indicators of short-term mating (e.g., unrestricted sociosexuality and marital infidelity were universally associated with the socially maladaptive facets of narcissism (e.g., exploitativeness. Discussion addresses limitations of these cross-culturally universal findings and presents suggestions for future research into revealing the precise psychological features of narcissism that facilitate the strategic pursuit of short-term mating.

  4. Interaction effects between the 5-hydroxy tryptamine transporter-linked polymorphic region (5-HTTLPR) genotype and family conflict on adolescent alcohol use and misuse.

    Science.gov (United States)

    Kim, Jueun; Park, Aesoon; Glatt, Stephen J; Eckert, Tanya L; Vanable, Peter A; Scott-Sheldon, Lori A J; Carey, Kate B; Ewart, Craig K; Carey, Michael P

    2015-02-01

    To investigate whether the effects of family conflict on adolescent drinking differed as a function of 5-hydroxy tryptamine transporter-linked polymorphic region (5-HTTLPR) genotype cross-sectionally and prospectively in two independent samples of adolescents. Path analysis and multi-group analysis of two prospective datasets were conducted. United States and United Kingdom. Sample 1 was 175 adolescents in the United States (mean age = 15 at times 1 and 2 with a 6-month interval); Sample 2 was 4916 adolescents in the United Kingdon (mean age = 12 at time 1 and 15 at time 2). In both samples, demographics, tri-allelic 5-HTTLPR genotype and perceived family conflict were assessed at time 1. Alcohol use (frequency of drinking) and alcohol misuse (frequency of intoxication, frequency of drinking three or more drinks, maximum number of drinks) were assessed at times 1 and 2. A significant gene-environment interaction on alcohol misuse at time 1 was found in both sample 1 (β = 0.57, P = 0.001) and sample 2 (β = 0.19, P = 0.01), indicating that the 5-HTTLPR low-activity allele carriers exposed to higher levels of family conflict were more likely to engage in alcohol misuse than non-carriers. A significant gene-environment interaction effect on change in alcohol misuse over time was found only in sample 1 (β = 0.48, P = 0.04) but not in sample 2. Compared with non-carriers, adolescents carrying the 5-HTTLPR low-activity allele are more susceptible to the effects of family conflict on alcohol misuse. © 2014 Society for the Study of Addiction.

  5. Jagged1 is the pathological link between Wnt and Notch pathways in colorectal cancer.

    Science.gov (United States)

    Rodilla, Verónica; Villanueva, Alberto; Obrador-Hevia, Antonia; Robert-Moreno, Alex; Fernández-Majada, Vanessa; Grilli, Andrea; López-Bigas, Nuria; Bellora, Nicolás; Albà, M Mar; Torres, Ferran; Duñach, Mireia; Sanjuan, Xavier; Gonzalez, Sara; Gridley, Thomas; Capella, Gabriel; Bigas, Anna; Espinosa, Lluís

    2009-04-14

    Notch has been linked to beta-catenin-dependent tumorigenesis; however, the mechanisms leading to Notch activation and the contribution of the Notch pathway to colorectal cancer is not yet understood. By microarray analysis, we have identified a group of genes downstream of Wnt/beta-catenin (down-regulated when blocking Wnt/beta-catenin) that are directly regulated by Notch (repressed by gamma-secretase inhibitors and up-regulated by active Notch1 in the absence of beta-catenin signaling). We demonstrate that Notch is downstream of Wnt in colorectal cancer cells through beta-catenin-mediated transcriptional activation of the Notch-ligand Jagged1. Consistently, expression of activated Notch1 partially reverts the effects of blocking Wnt/beta-catenin pathway in tumors implanted s.c. in nude mice. Crossing APC(Min/+) with Jagged1(+/Delta) mice is sufficient to significantly reduce the size of the polyps arising in the APC mutant background indicating that Notch is an essential modulator of tumorigenesis induced by nuclear beta-catenin. We show that this mechanism is operating in human tumors from Familial Adenomatous Polyposis patients. We conclude that Notch activation, accomplished by beta-catenin-mediated up-regulation of Jagged1, is required for tumorigenesis in the intestine. The Notch-specific genetic signature is sufficient to block differentiation and promote vasculogenesis in tumors whereas proliferation depends on both pathways.

  6. Operative Links

    DEFF Research Database (Denmark)

    Wistoft, Karen; Højlund, Holger

    2012-01-01

    educational goals, learning content, or value clarification. Health pedagogy is often a matter of retrospective rationalization rather than the starting point of planning. Health and risk behaviour approaches override health educational approaches. Conclusions: Operational links between health education......, health professionalism, and management strategies pose the foremost challenge. Operational links indicates cooperative levels that facilitate a creative and innovative effort across traditional professional boundaries. It is proposed that such links are supported by network structures, shared semantics...

  7. Decrease in Adolescent Cannabis Use From 2002 to 2006 and Links to Evenings Out With Friends in 31 European and North American Countries and Regions

    NARCIS (Netherlands)

    Kuntsche, E.N.; Simons-Morton, B.; Fotiou, A.; Bogt, T.F.M. ter; Kokkevi, A.

    2009-01-01

    Objective: To compare adolescent cannabis use between 2002 and 2006 and to investigate links to the frequency of evenings spent out with friends. Design: The Health Behavior in School-Aged Children study, an international study carried out in collaboration with the World Health

  8. Localization of a novel X-linked congenital stationary night blindness locus: close linkage to the RP3 type retinitis pigmentosa gene region

    NARCIS (Netherlands)

    Bergen, A. A.; ten Brink, J. B.; Riemslag, F.; Schuurman, E. J.; Tijmes, N.

    1995-01-01

    X-linked congenital stationary night blindness (CSNBX) is a non-progressive retinal disorder characterized by decreased visual acuity and loss of night vision. CSNBX is clinically heterogeneous with respect to the involvement of retinal rods and/or cones in the disease. In this study, we localize a

  9. Narcissism and the Strategic Pursuit of Short-Term Mating : Pervasive Links across 11 World Regions of the International Sexuality Description Project-2

    NARCIS (Netherlands)

    Schmitt, David; Vanwesenbeeck, W.M.A.

    2017-01-01

    Previous studies have documented links between sub-clinical narcissism and the active pursuit of short-term mating strategies (e.g., unrestricted sociosexuality, marital infidelity, mate poaching). Nearly all of these investigations have relied solely on samples from Western cultures. In the current

  10. Decrease in adolescent cannabis use from 2002 to 2006 and links to evenings out with friends in 31 European and North American countries and regions

    DEFF Research Database (Denmark)

    Kuntsche, Emmanuel; Simons-Morton, Bruce; Fotiou, Anastasios

    2009-01-01

    OBJECTIVE: To compare adolescent cannabis use between 2002 and 2006 and to investigate links to the frequency of evenings spent out with friends. DESIGN: The Health Behavior in School-Aged Children study, an international study carried out in collaboration with the World Health Organization/Europ...

  11. Characterizing the transition region of an A508 cl3 steel using small specimens by the reference temperature and the weak-link distances

    International Nuclear Information System (INIS)

    Miranda, C.A.J.

    2001-01-01

    An experimental program was developed to characterize the transition region of an A508 cl3 steel. Some fracture mechanic specimens were tested in the transition region using three geometries with thickness B c values, the reference temperature values, To, associated with each geometry and test temperature, and the measured r wl distances and the theoretical ones. (author)

  12. Dynamic relationships between age, amyloid-β deposition, and glucose metabolism link to the regional vulnerability to Alzheimer’s disease

    Science.gov (United States)

    Madison, Cindee; Baker, Suzanne; Rabinovici, Gil; Jagust, William

    2016-01-01

    Abstract See Hansson and Gouras (doi:10.1093/aww146) for a scientific commentary on this article. Although some brain regions such as precuneus and lateral temporo-parietal cortex have been shown to be more vulnerable to Alzheimer’s disease than other areas, a mechanism underlying the differential regional vulnerability to Alzheimer’s disease remains to be elucidated. Using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography imaging glucose metabolism and amyloid-β deposition, we tested whether and how life-long changes in glucose metabolism relate to amyloid-β deposition and Alzheimer’s disease-related hypometabolism. Nine healthy young adults (age range: 20–30), 96 cognitively normal older adults (age range: 61–96), and 20 patients with Alzheimer’s disease (age range: 50–90) were scanned using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography. Among cognitively normal older subjects, 32 were further classified as amyloid-positive, with 64 as amyloid-negative. To assess the contribution of glucose metabolism to the regional vulnerability to amyloid-β deposition, we defined the highest and lowest metabolic regions in young adults and examined differences in amyloid deposition between these regions across groups. Two-way analyses of variance were conducted to assess regional differences in age and amyloid-β-related changes in glucose metabolism. Multiple regressions were applied to examine the association between amyloid-β deposition and regional glucose metabolism. Both region of interest and whole-brain voxelwise analyses were conducted to complement and confirm the results derived from the other approach. Regional differences in glucose metabolism between the highest and lowest metabolism regions defined in young adults (T = 12.85, P glucose metabolism regions defined in young adults (T = 2.05, P glucose metabolism were found such that frontal glucose metabolism was reduced with age, while glucose

  13. Groundwater Discharge of Legacy Nitrogen to River Networks: Linking Regional Groundwater Models to Streambed Groundwater-Surface Water Exchange and Nitrogen Processing

    Science.gov (United States)

    Barclay, J. R.; Helton, A. M.; Briggs, M. A.; Starn, J. J.; Hunt, A.

    2017-12-01

    Despite years of management, excess nitrogen (N) is a pervasive problem in many aquatic ecosystems. More than half of surface water in the United States is derived from groundwater, and widespread N contamination in aquifers from decades of watershed N inputs suggest legacy N discharging from groundwater may contribute to contemporary N pollution problems in surface waters. Legacy N loads to streams and rivers are controlled by both regional scale flow paths and fine-scale processes that drive N transformations, such as groundwater-surface water exchange across steep redox gradients that occur at stream bed interfaces. Adequately incorporating these disparate scales is a challenge, but it is essential to understanding legacy N transport and making informed management decisions. We developed a regional groundwater flow model for the Farmington River, a HUC-8 basin that drains to the Long Island Sound, a coastal estuary that suffers from elevated N loads despite decades of management, to understand broad patterns of regional transport. To evaluate and refine the regional model, we used thermal infrared imagery paired with vertical temperature profiling to estimate groundwater discharge at the streambed interface. We also analyzed discharging groundwater for multiple N species to quantify fine scale patterns of N loading and transformation via denitrification at the streambed interface. Integrating regional and local estimates of groundwater discharge of legacy N to river networks should improve our ability to predict spatiotemporal patterns of legacy N loading to and transformation within surface waters.

  14. Linking biochemical perturbations in tissues of the African catfish to the presence of polycyclic aromatic hydrocarbons in Ovia River, Niger Delta region.

    Science.gov (United States)

    Obinaju, Blessing E; Graf, Carola; Halsall, Crispin; Martin, Francis L

    2015-06-01

    Petroleum hydrocarbons including polycyclic aromatic hydrocarbons (PAHs) are a pollution issue in the Niger Delta region due to oil industry activities. PAHs were measured in the water column of the Ovia River with concentrations ranging from 0.1 to 1055.6 ng L(-1). Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy detected alterations in tissues of the African catfish (Heterobranchus bidorsalis) from the region showed varying degrees of statistically significant (Pinfrared spectroscopy in environmental studies and supports their potential application in biomonitoring. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Understanding and simulating the link between African easterly waves and Atlantic tropical cyclones using a regional climate model: the role of domain size and lateral boundary conditions

    Energy Technology Data Exchange (ETDEWEB)

    Caron, Louis-Philippe [MISU, Stockholm University, Stockholm (Sweden); Universite du Quebec a Montreal, CRCMD Network, Montreal, QC (Canada); Jones, Colin G. [Swedish Meterological and Hydrological Institute, Rossby Center, Norrkoeping (Sweden)

    2012-07-15

    Using a suite of lateral boundary conditions, we investigate the impact of domain size and boundary conditions on the Atlantic tropical cyclone and african easterly Wave activity simulated by a regional climate model. Irrespective of boundary conditions, simulations closest to observed climatology are obtained using a domain covering both the entire tropical Atlantic and northern African region. There is a clear degradation when the high-resolution model domain is diminished to cover only part of the African continent or only the tropical Atlantic. This is found to be the result of biases in the boundary data, which for the smaller domains, have a large impact on TC activity. In this series of simulations, the large-scale Atlantic atmospheric environment appears to be the primary control on simulated TC activity. Weaker wave activity is usually accompanied by a shift in cyclogenesis location, from the MDR to the subtropics. All ERA40-driven integrations manage to capture the observed interannual variability and to reproduce most of the upward trend in tropical cyclone activity observed during that period. When driven by low-resolution global climate model (GCM) integrations, the regional climate model captures interannual variability (albeit with lower correlation coefficients) only if tropical cyclones form in sufficient numbers in the main development region. However, all GCM-driven integrations fail to capture the upward trend in Atlantic tropical cyclone activity. In most integrations, variations in Atlantic tropical cyclone activity appear uncorrelated with variations in African easterly wave activity. (orig.)

  16. Evolution of a behavior-linked microsatellite-containing element in the 5' flanking region of the primate AVPR1A gene.

    Science.gov (United States)

    Donaldson, Zoe R; Kondrashov, Fyodor A; Putnam, Andrea; Bai, Yaohui; Stoinski, Tara L; Hammock, Elizabeth A D; Young, Larry J

    2008-06-23

    The arginine vasopressin V1a receptor (V1aR) modulates social cognition and behavior in a wide variety of species. Variation in a repetitive microsatellite element in the 5' flanking region of the V1aR gene (AVPR1A) in rodents has been associated with variation in brain V1aR expression and in social behavior. In humans, the 5' flanking region of AVPR1A contains a tandem duplication of two approximately 350 bp, microsatellite-containing elements located approximately 3.5 kb upstream of the transcription start site. The first block, referred to as DupA, contains a polymorphic (GT)25 microsatellite; the second block, DupB, has a complex (CT)4-(TT)-(CT)8-(GT)24 polymorphic motif, known as RS3. Polymorphisms in RS3 have been associated with variation in sociobehavioral traits in humans, including autism spectrum disorders. Thus, evolution of these regions may have contributed to variation in social behavior in primates. We examined the structure of these regions in six ape, six monkey, and one prosimian species. Both tandem repeat blocks are present upstream of the AVPR1A coding region in five of the ape species we investigated, while monkeys have only one copy of this region. As in humans, the microsatellites within DupA and DupB are polymorphic in many primate species. Furthermore, both single (lacking DupB) and duplicated alleles (containing both DupA and DupB) are present in chimpanzee (Pan troglodytes) populations with allele frequencies of 0.795 and 0.205 for the single and duplicated alleles, respectively, based on the analysis of 47 wild-caught individuals. Finally, a phylogenetic reconstruction suggests two alternate evolutionary histories for this locus. There is no obvious relationship between the presence of the RS3 duplication and social organization in primates. However, polymorphisms identified in some species may be useful in future genetic association studies. In particular, the presence of both single and duplicated alleles in chimpanzees provides a

  17. Evolution of a behavior-linked microsatellite-containing element in the 5' flanking region of the primate AVPR1A gene

    Directory of Open Access Journals (Sweden)

    Bai Yaohui

    2008-06-01

    Full Text Available Abstract Background The arginine vasopressin V1a receptor (V1aR modulates social cognition and behavior in a wide variety of species. Variation in a repetitive microsatellite element in the 5' flanking region of the V1aR gene (AVPR1A in rodents has been associated with variation in brain V1aR expression and in social behavior. In humans, the 5' flanking region of AVPR1A contains a tandem duplication of two ~350 bp, microsatellite-containing elements located approximately 3.5 kb upstream of the transcription start site. The first block, referred to as DupA, contains a polymorphic (GT25 microsatellite; the second block, DupB, has a complex (CT4-(TT-(CT8-(GT24 polymorphic motif, known as RS3. Polymorphisms in RS3 have been associated with variation in sociobehavioral traits in humans, including autism spectrum disorders. Thus, evolution of these regions may have contributed to variation in social behavior in primates. We examined the structure of these regions in six ape, six monkey, and one prosimian species. Results Both tandem repeat blocks are present upstream of the AVPR1A coding region in five of the ape species we investigated, while monkeys have only one copy of this region. As in humans, the microsatellites within DupA and DupB are polymorphic in many primate species. Furthermore, both single (lacking DupB and duplicated alleles (containing both DupA and DupB are present in chimpanzee (Pan troglodytes populations with allele frequencies of 0.795 and 0.205 for the single and duplicated alleles, respectively, based on the analysis of 47 wild-caught individuals. Finally, a phylogenetic reconstruction suggests two alternate evolutionary histories for this locus. Conclusion There is no obvious relationship between the presence of the RS3 duplication and social organization in primates. However, polymorphisms identified in some species may be useful in future genetic association studies. In particular, the presence of both single and duplicated

  18. Genetically based location from triploid populations and gene ontology of a 3.3-mb genome region linked to Alternaria brown spot resistance in citrus reveal clusters of resistance genes.

    Directory of Open Access Journals (Sweden)

    José Cuenca

    Full Text Available Genetic analysis of phenotypical traits and marker-trait association in polyploid species is generally considered as a challenge. In the present work, different approaches were combined taking advantage of the particular genetic structures of 2n gametes resulting from second division restitution (SDR to map a genome region linked to Alternaria brown spot (ABS resistance in triploid citrus progeny. ABS in citrus is a serious disease caused by the tangerine pathotype of the fungus Alternaria alternata. This pathogen produces ACT-toxin, which induces necrotic lesions on fruit and young leaves, defoliation and fruit drop in susceptible genotypes. It is a strong concern for triploid breeding programs aiming to produce seedless mandarin cultivars. The monolocus dominant inheritance of susceptibility, proposed on the basis of diploid population studies, was corroborated in triploid progeny. Bulk segregant analysis coupled with genome scan using a large set of genetically mapped SNP markers and targeted genetic mapping by half tetrad analysis, using SSR and SNP markers, allowed locating a 3.3 Mb genomic region linked to ABS resistance near the centromere of chromosome III. Clusters of resistance genes were identified by gene ontology analysis of this genomic region. Some of these genes are good candidates to control the dominant susceptibility to the ACT-toxin. SSR and SNP markers were developed for efficient early marker-assisted selection of ABS resistant hybrids.

  19. Genetically based location from triploid populations and gene ontology of a 3.3-mb genome region linked to Alternaria brown spot resistance in citrus reveal clusters of resistance genes.

    Science.gov (United States)

    Cuenca, José; Aleza, Pablo; Vicent, Antonio; Brunel, Dominique; Ollitrault, Patrick; Navarro, Luis

    2013-01-01

    Genetic analysis of phenotypical traits and marker-trait association in polyploid species is generally considered as a challenge. In the present work, different approaches were combined taking advantage of the particular genetic structures of 2n gametes resulting from second division restitution (SDR) to map a genome region linked to Alternaria brown spot (ABS) resistance in triploid citrus progeny. ABS in citrus is a serious disease caused by the tangerine pathotype of the fungus Alternaria alternata. This pathogen produces ACT-toxin, which induces necrotic lesions on fruit and young leaves, defoliation and fruit drop in susceptible genotypes. It is a strong concern for triploid breeding programs aiming to produce seedless mandarin cultivars. The monolocus dominant inheritance of susceptibility, proposed on the basis of diploid population studies, was corroborated in triploid progeny. Bulk segregant analysis coupled with genome scan using a large set of genetically mapped SNP markers and targeted genetic mapping by half tetrad analysis, using SSR and SNP markers, allowed locating a 3.3 Mb genomic region linked to ABS resistance near the centromere of chromosome III. Clusters of resistance genes were identified by gene ontology analysis of this genomic region. Some of these genes are good candidates to control the dominant susceptibility to the ACT-toxin. SSR and SNP markers were developed for efficient early marker-assisted selection of ABS resistant hybrids.

  20. Operative Links

    DEFF Research Database (Denmark)

    Wistoft, Karen; Højlund, Holger

    2012-01-01

    and have been the object of great expectations concerning the ability to incorporate health concerns into every welfare area through health promotion strategies. The paper draws on results and analyses of a collective research project funded by the Danish National Research Council and carried out...... links' that indicate cooperative levels which facilitate a creative and innovative effort in disease prevention and health promotion targeted at children and adolescents - across traditional professional boundaries. It is proposed that such links are supported by network structures, shared semantics...

  1. Projecting regional climate and cropland changes using a linked biogeophysical-socioeconomic modeling framework: 1. Model description and an equilibrium application over West Africa

    Science.gov (United States)

    Wang, Guiling; Ahmed, Kazi Farzan; You, Liangzhi; Yu, Miao; Pal, Jeremy; Ji, Zhenming

    2017-03-01

    Agricultural land use alters regional climate through modifying the surface mass, energy, and momentum fluxes; climate influences agricultural land use through their impact on crop yields. These interactions are not well understood and have not been adequately considered in climate projections. This study tackles the critical linkages within the coupled natural-human system of West Africa in a changing climate based on an equilibrium application of a modeling framework that asynchronously couples models of regional climate, crop yield, multimarket agricultural economics, and cropland expansion. Using this regional modeling framework driven with two global climate models, we assess the contributions of land use change (LUC) and greenhouse gas (GHGs) concentration changes to regional climate changes and assess the contribution of climate change and socioeconomic factors to agricultural land use changes. For future cropland expansion in West Africa, our results suggest that socioeconomic development would be the dominant driver in the east (where current cropland coverage is already high) and climate changes would be the primary driver in the west (where future yield drop is severe). For future climate, it is found that agricultural expansion would cause a dry signal in the west and a wet signal in the east downwind, with an east-west contrast similar to the GHG-induced changes. Over a substantial portion of West Africa, the strength of the LUC-induced climate signals is comparable to the GHG-induced changes. Uncertainties originating from the driving global models are small; human decision making related to land use and international trade is a major source of uncertainty.

  2. Exploring the links between social metabolism and biodiversity distribution across landscape gradients: A regional-scale contribution to the land-sharing versus land-sparing debate

    OpenAIRE

    Marull López, Joan; Tello, Enric; Bagaria Morató, Guillem; Font i Castell, Xavier; Cattaneo, Claudio; Pino i Vilalta, Joan

    2018-01-01

    The debate about the relative merits of the 'land-sparing' and 'land-sharing' approaches to biodiversity conservation is usually addressed at local scale. Here, however, we undertake a regional-scale approach to this issue by exploring the association between the Human Appropriation of Net Primary Production (HANPP) and biodiversity components (plants, amphibians, reptiles, birds and mammals) across a gradient of human-transformed landscapes in Catalonia, Spain. We propose an Intermediate Dis...

  3. The Region of Difference Four is a Robust Genetic Marker for Subtyping Mycobacterium caprae Isolates and is Linked to Spatial Distribution of Three Subtypes.

    Science.gov (United States)

    Rettinger, A; Broeckl, S; Fink, M; Prodinger, W M; Blum, H; Krebs, S; Domogalla, J; Just, F; Gellert, S; Straubinger, R K; Büttner, M

    2017-06-01

    Alpine Mycobacterium caprae isolates found in cattle and red deer display at least three genetic variations in the region of difference four (RD4) that can be used for further differentiation of the isolates into the subtypes 'Allgäu', 'Karwendel' and 'Lechtal'. Each genomic subtype is thereby characterized by a specific nucleotide deletion pattern in the 12.7-kb RD4 region. Even though M. caprae infections are frequently documented in cattle and red deer, little is known about the transmission routes. Hence, robust markers for M. caprae subtyping are needed to gain insight into the molecular epidemiology. For this reason, a rapid and robust multiplex PCR was developed for the simultaneous detection of three M. caprae RD4 subtypes and was used to subtype a total number of 241 M. caprae isolates from animals (145 cattle, 95 red deer and one fox) from Bavaria and Austria. All three subtypes occur spatially distributed and are found in cattle and in red deer suggesting transmission between the two species. As subtypes are genetically stable in both species it is hypothesized that the described genetic variations developed within the host due to 'within-host replication'. The results of this study recommend the genomic RD4 region as a reliable diagnostic marker for M. caprae subtype differentiation. © 2015 Blackwell Verlag GmbH.

  4. Source apportionment of PM2.5 at a regional background site in North China using PMF linked with radiocarbon analysis: insight into the contribution of biomass burning

    Directory of Open Access Journals (Sweden)

    Z. Zong

    2016-09-01

    Full Text Available Source apportionment of fine particles (PM2.5 at a background site in North China in the winter of 2014 was done using statistical analysis, radiocarbon (14C measurement and positive matrix factorization (PMF modeling. Results showed that the concentration of PM2.5 was 77.6 ± 59.3 µg m−3, of which sulfate (SO42− concentration was the highest, followed by nitrate (NO3−, organic carbon (OC, elemental carbon (EC and ammonium (NH4+. As demonstrated by backward trajectory, more than half of the air masses during the sampling period were from the Beijing–Tianjin–Hebei (BTH region, followed by Mongolia and the Shandong Peninsula. Cluster analysis of chemical species suggested an obvious signal of biomass burning in the PM2.5 from the Shandong Peninsula, while the PM2.5 from the BTH region showed a vehicle emission pattern. This finding was further confirmed by the 14C measurement of OC and EC in two merged samples. The 14C result indicated that biogenic and biomass burning emission contributed 59 ± 4 and 52 ± 2 % to OC and EC concentrations, respectively, when air masses originated from the Shandong Peninsula, while the contributions fell to 46 ± 4 and 38 ± 1 %, respectively, when the prevailing wind changed and came from the BTH region. The minimum deviation between source apportionment results from PMF and 14C measurement was adopted as the optimal choice of the model exercises. Here, two minor overestimates with the same range (3 % implied that the PMF result provided a reasonable source apportionment of the regional PM2.5 in this study. Based on the PMF modeling, eight sources were identified; of these, coal combustion, biomass burning and vehicle emission were the main contributors of PM2.5, accounting for 29.6, 19.3 and 15.9 %, respectively. Compared with overall source apportionment, the contributions of vehicle emission, mineral dust, coal combustion and biomass burning increased when air masses

  5. Scandinavian links

    DEFF Research Database (Denmark)

    Matthiessen, Christian Wichmann; Knowles, Richard D.

    2014-01-01

    are impressive mega structures spanning international waterways. These waterways between the Baltic Sea and the North Sea have played major roles in history. The length of each of the crossings are around 20 km. The fixed links closes gaps between the Scandinavian and European motorway and rail networks...

  6. Postpartum depressive symptoms moderate the link between mothers’ neural response to positive faces in reward and social regions and observed caregiving

    Science.gov (United States)

    Guo, Chaohui; Moses-Kolko, Eydie L; Phillips, Mary L; Stepp, Stephanie D; Hipwell, Alison E

    2017-01-01

    Abstract Postpartum depression may disrupt socio-affective neural circuitry and compromise provision of positive parenting. Although work has evaluated how parental response to negative stimuli is related to caregiving, research is needed to examine how depressive symptoms during the postpartum period may be related to neural response to positive stimuli, especially positive faces, given depression’s association with biased processing of positive faces. The current study examined the association between neural response to adult happy faces and observations of maternal caregiving and the moderating role of postpartum depression, in a sample of 18- to 22-year old mothers (n = 70) assessed at 17 weeks (s.d. = 4.7 weeks) postpartum. Positive caregiving was associated with greater precuneus and occipital response to positive faces among mothers with lower depressive symptoms, but not for those with higher symptoms. For mothers with higher depressive symptoms, greater ventral and dorsal striatal response to positive faces was associated with more positive caregiving, whereas the opposite pattern emerged for mothers with lower symptoms. There was no association between negative caregiving and neural response to positive faces or negative faces. Processing of positive stimuli may be an important prognostic target in mothers with depressive symptoms, given its link with healthy caregiving behaviors. PMID:29048603

  7. Soil organic matter dynamics and CO2 fluxes in relation to landscape scale processes: linking process understanding to regional scale carbon mass-balances

    Science.gov (United States)

    Van Oost, Kristof; Nadeu, Elisabet; Wiaux, François; Wang, Zhengang; Stevens, François; Vanclooster, Marnik; Tran, Anh; Bogaert, Patrick; Doetterl, Sebastian; Lambot, Sébastien; Van wesemael, Bas

    2014-05-01

    In this paper, we synthesize the main outcomes of a collaborative project (2009-2014) initiated at the UCL (Belgium). The main objective of the project was to increase our understanding of soil organic matter dynamics in complex landscapes and use this to improve predictions of regional scale soil carbon balances. In a first phase, the project characterized the emergent spatial variability in soil organic matter storage and key soil properties at the regional scale. Based on the integration of remote sensing, geomorphological and soil analysis techniques, we quantified the temporal and spatial variability of soil carbon stock and pool distribution at the local and regional scales. This work showed a linkage between lateral fluxes of C in relation with sediment transport and the spatial variation in carbon storage at multiple spatial scales. In a second phase, the project focused on characterizing key controlling factors and process interactions at the catena scale. In-situ experiments of soil CO2 respiration showed that the soil carbon response at the catena scale was spatially heterogeneous and was mainly controlled by the catenary variation of soil physical attributes (soil moisture, temperature, C quality). The hillslope scale characterization relied on advanced hydrogeophysical techniques such as GPR (Ground Penetrating Radar), EMI (Electromagnetic induction), ERT (Electrical Resistivity Tomography), and geophysical inversion and data mining tools. Finally, we report on the integration of these insights into a coupled and spatially explicit model and its application. Simulations showed that C stocks and redistribution of mass and energy fluxes are closely coupled, they induce structured spatial and temporal patterns with non negligible attached uncertainties. We discuss the main outcomes of these activities in relation to sink-source behavior and relevance of erosion processes for larger-scale C budgets.

  8. El Niño-Southern Oscillation and water resources in the headwaters region of the Yellow River: links and potential for forecasting

    Directory of Open Access Journals (Sweden)

    A. Lü

    2011-04-01

    Full Text Available This research explores the rainfall-El Niño-Southern Oscillation (ENSO and runoff-ENSO relationships and examines the potential for water resource forecasting using these relationships. The Southern Oscillation Index (SOI, Niño1.2, Niño3, Niño4, and Niño3.4 were selected as ENSO indicators for cross-correlation analyses of precipitation and runoff. There was a significant correlation (95% confidence level between precipitation and ENSO indicators during three periods: January, March, and from September to November. In addition, monthly streamflow and monthly ENSO indictors were significantly correlated during three periods: from January to March, June, and from October to December (OND, with lag periods between one and twelve months. Because ENSO events can be accurately predicted one to two years in advance using physical modeling of the coupled ocean-atmosphere system, the lead time for forecasting runoff using ENSO indicators in the Headwaters Region of the Yellow River could extend from one to 36 months. Therefore, ENSO may have potential as a powerful forecasting tool for water resources in the headwater regions of Yellow River.

  9. Linking biochemical perturbations in tissues of the African catfish to the presence of polycyclic aromatic hydrocarbons in Ovia River, Niger Delta region

    International Nuclear Information System (INIS)

    Obinaju, Blessing E.; Graf, Carola; Halsall, Crispin; Martin, Francis L.

    2015-01-01

    Petroleum hydrocarbons including polycyclic aromatic hydrocarbons (PAHs) are a pollution issue in the Niger Delta region due to oil industry activities. PAHs were measured in the water column of the Ovia River with concentrations ranging from 0.1 to 1055.6 ng L −1 . Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy detected alterations in tissues of the African catfish (Heterobranchus bidorsalis) from the region showed varying degrees of statistically significant (P < 0.0001, P < 0.001, P < 0.05) changes to absorption band areas and shifts in centroid positions of peaks. Alteration patterns were similar to those induced by benzo[a]pyrene in MCF-7 cells. These findings have potential health implications for resident local communities as H. bidorsalis constitutes a key nutritional source. The study provides supporting evidence for the sensitivity of infrared spectroscopy in environmental studies and supports their potential application in biomonitoring. - Highlights: • PAHs measured in the water column of the Ovia River (Nigeria). • ATR-FTIR spectroscopy detects alterations in tissues of the African catfish (Heterobranchus bidorsalis). • Spectral alteration similar to those induced by benzo[a]pyrene in MCF-7 cells. • Alterations in tissues of African catfish (H. bidorsalis) a function of exposure to waterborne PAHs. • Vibrational spectroscopy techniques detect minimal changes induced by environmental exposures. - Spatial and temporal analyses by biospectroscopy techniques of African catfish (Heterobranchus bidorsalis) tissues suggest that detected alterations can reflect fluctuating exposures to PAHs

  10. Proteolytic regulation of Notch1 receptor activity in cancer

    NARCIS (Netherlands)

    van Tetering, Geert

    2011-01-01

    The Notch receptor is part of a highly conserved signaling pathway essential in development and disease in embryos and adults. Notch proteins coordinate cell-cell communication through receptor-ligand interactions between adjacent cells. First Notch is cleaved in the Golgi by furin at Site-1 (S1)

  11. Plant endemism in the Sierras of Córdoba and San Luis (Argentina): understanding links between phylogeny and regional biogeographical patterns1

    Science.gov (United States)

    Chiapella, Jorge O.; Demaio, Pablo H.

    2015-01-01

    Abstract We compiled a checklist with all known endemic plants occurring in the Sierras of Córdoba and San Luis, an isolated mountainous range located in central Argentina. In order to obtain a better understanding of the evolutionary history, relationships and age of the regional flora, we gathered basic information on the biogeographical and floristic affinities of the endemics, and documented the inclusion of each taxon in molecular phylogenies. We listed 89 taxa (including 69 species and 20 infraspecific taxa) belonging to 53 genera and 29 families. The endemics are not distributed evenly, being more abundant in the lower than in the middle and upper vegetation belts. Thirty-two genera (60.3%) have been included in phylogenetic analyses, but only ten (18.8%) included local endemic taxa. A total of 28 endemic taxa of the Sierras CSL have a clear relationship with a widespread species of the same genus, or with one found close to the area. Available phylogenies for some taxa show divergence times between 7.0 – 1.8 Ma; all endemic taxa are most probably neoendemics sensu Stebbins and Major. Our analysis was specifically aimed at a particular geographic area, but the approach of analyzing phylogenetic patterns together with floristic or biogeographical relationships of the endemic taxa of an area, delimited by clear geomorphological features, could reveal evolutionary trends shaping the area. PMID:25878555

  12. Divergence in Forest-Type Response to Climate and Weather: Evidence for Regional Links Between Forest-Type Evenness and Net Primary Productivity

    Science.gov (United States)

    Bradford, J.B.

    2011-01-01

    Climate change is altering long-term climatic conditions and increasing the magnitude of weather fluctuations. Assessing the consequences of these changes for terrestrial ecosystems requires understanding how different vegetation types respond to climate and weather. This study examined 20 years of regional-scale remotely sensed net primary productivity (NPP) in forests of the northern Lake States to identify how the relationship between NPP and climate or weather differ among forest types, and if NPP patterns are influenced by landscape-scale evenness of forest-type abundance. These results underscore the positive relationship between temperature and NPP. Importantly, these results indicate significant differences among broadly defined forest types in response to both climate and weather. Essentially all weather variables that were strongly related to annual NPP displayed significant differences among forest types, suggesting complementarity in response to environmental fluctuations. In addition, this study found that forest-type evenness (within 8 ?? 8 km2 areas) is positively related to long-term NPP mean and negatively related to NPP variability, suggesting that NPP in pixels with greater forest-type evenness is both higher and more stable through time. This is landscape- to subcontinental-scale evidence of a relationship between primary productivity and one measure of biological diversity. These results imply that anthropogenic or natural processes that influence the proportional abundance of forest types within landscapes may influence long-term productivity patterns. ?? 2011 Springer Science+Business Media, LLC (outside the USA).

  13. Plant endemism in the Sierras of Córdoba and San Luis (Argentina): understanding links between phylogeny and regional biogeographical patterns.

    Science.gov (United States)

    Chiapella, Jorge O; Demaio, Pablo H

    2015-01-01

    We compiled a checklist with all known endemic plants occurring in the Sierras of Córdoba and San Luis, an isolated mountainous range located in central Argentina. In order to obtain a better understanding of the evolutionary history, relationships and age of the regional flora, we gathered basic information on the biogeographical and floristic affinities of the endemics, and documented the inclusion of each taxon in molecular phylogenies. We listed 89 taxa (including 69 species and 20 infraspecific taxa) belonging to 53 genera and 29 families. The endemics are not distributed evenly, being more abundant in the lower than in the middle and upper vegetation belts. Thirty-two genera (60.3%) have been included in phylogenetic analyses, but only ten (18.8%) included local endemic taxa. A total of 28 endemic taxa of the Sierras CSL have a clear relationship with a widespread species of the same genus, or with one found close to the area. Available phylogenies for some taxa show divergence times between 7.0 - 1.8 Ma; all endemic taxa are most probably neoendemics sensu Stebbins and Major. Our analysis was specifically aimed at a particular geographic area, but the approach of analyzing phylogenetic patterns together with floristic or biogeographical relationships of the endemic taxa of an area, delimited by clear geomorphological features, could reveal evolutionary trends shaping the area.

  14. Plasminogen activator inhibitor type 1 gene is located at region q21.3-q22 of chromosome 7 and genetically linked with cystic fibrosis

    International Nuclear Information System (INIS)

    Klinger, K.W.; Winqvist, R.; Riccio, A.

    1987-01-01

    The regional chromosomal location of the human gene for plasminogen activator inhibitor type 1 (PAI1) was determined by three independent methods of gene mapping. PAI1 was localized first to 7cen-q32 and then to 7q21.3-q22 by Southern blot hybridization analysis of a panel of human and mouse somatic cell hybrids with a PAI1 cDNA probe and in situ hybridization, respectively. The authors frequent HindIII restriction fragment length polymorphism (RFLP) of the PAI1 gene with an information content of 0.369. In family studies using this polymorphism, genetic linkage was found between PAI1 and the loci for erythropoietin (EPO), paraoxonase (PON), the met protooncogene (MET), and cystic fibrosis (CF), all previously assigned to the middle part of the long arm of chromosome 7. The linkage with EPO was closest with an estimated genetic distance of 3 centimorgans, whereas that to CF was 20 centimorgans. A three-point genetic linkage analysis and data from previous studies showed that the most likely order of these loci is EPO, PAI1, PON, (MET, CF), with PAI1 being located centromeric to CF. The PAI1 RFLP may prove to be valuable in ordering genetic markers in the CF-linkage group and may also be valuable in genetic analysis of plasminogen activation-related diseases, such as certain thromboembolic disorders and cancer

  15. Near N-S paleo-extension in the western Deccan region, India: Does it link strike-slip tectonics with India-Seychelles rifting?

    Science.gov (United States)

    Misra, Achyuta Ayan; Bhattacharya, Gourab; Mukherjee, Soumyajit; Bose, Narayan

    2014-09-01

    This is the first detailed report and analyses of deformation from the W part of the Deccan large igneous province (DLIP), Maharashtra, India. This deformation, related to the India-Seychelles rifting during Late Cretaceous-Early Paleocene, was studied, and the paleostress tensors were deduced. Near N-S trending shear zones, lineaments, and faults were already reported without significant detail. An E-W extension was envisaged by the previous workers to explain the India-Seychelles rift at ~64 Ma. The direction of extension, however, does not match with their N-S brittle shear zones and also those faults (sub-vertical, ~NE-SW/~NW-SE, and few ~N-S) we report and emphasize in this work. Slickenside-bearing fault planes, brittle shear zones, and extension fractures in meso-scale enabled us to estimate the paleostress tensors (directions and relative magnitudes). The field study was complemented by remote sensing lineament analyses to map dykes and shear zones. Dykes emplaced along pre-existing ~N-S to ~NE-SW/~NW-SE shears/fractures. This information was used to derive regional paleostress trends. A ~NW-SE/NE-SW minimum compressive stress in the oldest Kalsubai Subgroup and a ~N-S direction for the younger Lonavala, Wai, and Salsette Subgroups were deciphered. Thus, a ~NW/NE to ~N-S extension is put forward that refutes the popular view of E-W India-Seychelles extension. Paleostress analyses indicate that this is an oblique rifted margin. Field criteria suggest only ~NE-SW and ~NW-SE, with some ~N-S strike-slip faults/brittle shear zones. We refer this deformation zone as the "Western Deccan Strike-slip Zone" (WDSZ). The observed deformation was matched with offshore tectonics deciphered mainly from faults interpreted on seismic profiles and from magnetic seafloor spreading anomalies. These geophysical findings too indicate oblique rifting in this part of the W Indian passive margin. We argue that the Seychelles microcontinent separated from India only after much of

  16. Sex-linked dominant

    Science.gov (United States)

    Inheritance - sex-linked dominant; Genetics - sex-linked dominant; X-linked dominant; Y-linked dominant ... can be either an autosomal chromosome or a sex chromosome. It also depends on whether the trait ...

  17. Linking lab and field

    International Nuclear Information System (INIS)

    Cronje, P.B.

    1988-01-01

    The multitude of different supplements recommended for animals grazing natural pastures, which testifies to the need for a metabolic basis for supplementary feeding practices. The first approach to this problem was to simulate different feeding conditions in the laboratory, where the metabolic responses of body tissues to changes in the supply of purified nutrients could be studied using radioisotope techniques. The second step was to link these fundamental studies to field conditions. The results of these studies suggest that the efficiency of feed conversion and growth rates of ruminants grazing winter pastures in the highveld region of South Africa could be substantially improved by strategic supplementation with glucose precursors. Acetate clearance rate represents a valuable link in the process of applying information obtained from controlled laboratory experiments to field conditions. As this technique is inexpensive, quick and simple to carry out, it is ideally suited to application under field conditions where the use of isotopes is impractical. By providing a link with field conditions, it greatly extended the scope and practical application of isotope tracer techniques

  18. Regionalism, Regionalization and Regional Development

    Directory of Open Access Journals (Sweden)

    Liviu C. Andrei

    2016-03-01

    Full Text Available Sustained development is a concept associating other concepts, in its turn, in the EU practice, e.g. regionalism, regionalizing and afferent policies, here including structural policies. This below text, dedicated to integration concepts, will limit on the other hand to regionalizing, otherwise an aspect typical to Europe and to the EU. On the other hand, two aspects come up to strengthen this field of ideas, i.e. the region (al-regionalism-(regional development triplet has either its own history or precise individual outline of terms.

  19. Biallelic and Triallelic 5-Hydroxytyramine Transporter Gene-Linked Polymorphic Region (5-HTTLPR) Polymorphisms and Their Relationship with Lifelong Premature Ejaculation: A Case-Control Study in a Chinese Population

    Science.gov (United States)

    Huang, Yuanyuan; Zhang, Xiansheng; Gao, Jingjing; Tang, Dongdong; Gao, Pan; Li, Chao; Liu, Weiqun; Liang, Chaozhao

    2016-01-01

    Background This study aimed to explore the relationship between premature ejaculation (PE) and the serotonin transporter gene-linked polymorphic region (5-HTTLPR) with respect to the biallelic and triallelic classifications. Material/Methods A total of 115 outpatients who complained of ejaculating prematurely and who were diagnosed as having lifelong premature ejaculation (LPE) and 101 controls without PE complaint were recruited. All subjects completed a detailed questionnaire and were genotyped for 5-HTTLPR polymorphism using PCR-based technology. We evaluated the associations between 5-HTTLPR allelic and genotypic frequencies and their association with LPE, as well as the intravaginal ejaculation latency time (IELT) of different 5-HTTLPR genotypes among LPE patients. Results The patients and controls did not differ significantly in terms of any characteristic except age. The results showed no significant difference regarding biallelic 5-HTTLPR. According to the triallelic classification, no significant difference was found when comparing the genotypic distribution (P=0.091). However, the distribution of the S, LG, and LA alleles in the cases was significantly different from the controls (P=0.018). We found a significantly lower frequency of LA allele and higher frequency of LG allele in patients. Based on another classification by expression, we found a significantly lower frequency of the L’L’ genotype (OR=0.37; 95%CI=0.15–0.91, P=0.025) in patients with LPE. No significant association was detected between IELT of LPE and different genotypes. Conclusions Contrary to the general classification based on S/L alleles, triallelic 5-HTTLPR was associated with LPE. Triallelic 5-HTTLPR may be a promising field for genetic research in PE to avoid false-negative results in future studies. PMID:27311544

  20. Linked data management

    CERN Document Server

    Hose, Katja; Schenkel, Ralf

    2014-01-01

    Linked Data Management presents techniques for querying and managing Linked Data that is available on today’s Web. The book shows how the abundance of Linked Data can serve as fertile ground for research and commercial applications. The text focuses on aspects of managing large-scale collections of Linked Data. It offers a detailed introduction to Linked Data and related standards, including the main principles distinguishing Linked Data from standard database technology. Chapters also describe how to generate links between datasets and explain the overall architecture of data integration systems based on Linked Data. A large part of the text is devoted to query processing in different setups. After presenting methods to publish relational data as Linked Data and efficient centralized processing, the book explores lookup-based, distributed, and parallel solutions. It then addresses advanced topics, such as reasoning, and discusses work related to read-write Linked Data for system interoperation. Desp...

  1. EPA Region 3 Quality Management Plans

    Science.gov (United States)

    Has links to resources that describe the Region's Quality Assurance Program, which is a collection of the Region's ongoing quality assurance (QA) policies, procedures, responsibilities and management systems.

  2. Correction of the X-linked immunodeficiency phenotype by transgenic expression of human Bruton Tyrosine kinase under the control of the class II major histocompatibility complex Ea locus control region

    NARCIS (Netherlands)

    Drabek, D.; Raguz, S.; Wit, de T.P.M.; Dingjan, G.M.; Savelkoul, H.F.J.; Grosveld, F.; Hendriks, R.W.

    1997-01-01

    Bruton tyrosine kinase (Btk) is essential for the development of pre-B cells to mature B cell stages. Btk-deficient mice manifest an X-linked immunodeficiency (xid) defect characterized by a reduction of peripheral IgMlow IgDhigh B cells, a lack of peritoneal CD5 B cells, low serum levels of IgM and

  3. Dynamic link: user's manual

    International Nuclear Information System (INIS)

    Harada, Hiroo; Asai, Kiyoshi; Kihara, Kazuhisa.

    1981-09-01

    The purpose of dynamic link facility is to link a load module dynamically only when it is used in execution time. The facility is very useful for development, execution and maintenance of a large scale computer program which is too big to be saved as one load module in main memory, or it is poor economy to save it due to many unused subroutines depending on an input. It is also useful for standardization and common utilization of programs. Standard usage of dynamic link facility of FACOM M-200 computer system, a software tool which analyzes the effect of dynamic link facility and application of dynamic link to nuclear codes are described. (author)

  4. A subspecies of region crossing change, region freeze crossing change

    OpenAIRE

    Inoue, Ayumu; Shimizu, Ryo

    2016-01-01

    We introduce a local move on a link diagram named a region freeze crossing change which is close to a region crossing change, but not the same. We study similarity and difference between region crossing change and region freeze crossing change.

  5. Visualisierung von typisierten Links in Linked Data

    Directory of Open Access Journals (Sweden)

    Georg Neubauer

    2017-09-01

    Full Text Available Das Themengebiet der Arbeit behandelt Visualisierungen von typisierten Links in Linked Data. Die wissenschaftlichen Gebiete, die im Allgemeinen den Inhalt des Beitrags abgrenzen, sind das Semantic Web, das Web of Data und Informationsvisualisierung. Das Semantic Web, das von Tim Berners Lee 2001 erfunden wurde, stellt eine Erweiterung zum World Wide Web (Web 2.0 dar. Aktuelle Forschungen beziehen sich auf die Verknüpfbarkeit von Informationen im World Wide Web. Um es zu ermöglichen, solche Verbindungen wahrnehmen und verarbeiten zu können sind Visualisierungen die wichtigsten Anforderungen als Hauptteil der Datenverarbeitung. Im Zusammenhang mit dem Sematic Web werden Repräsentationen von zuhammenhängenden Informationen anhand von Graphen gehandhabt. Der Grund des Entstehens dieser Arbeit ist in erster Linie die Beschreibung der Gestaltung von Linked Data-Visualisierungskonzepten, deren Prinzipien im Rahmen einer theoretischen Annäherung eingeführt werden. Anhand des Kontexts führt eine schrittweise Erweiterung der Informationen mit dem Ziel, praktische Richtlinien anzubieten, zur Vernetzung dieser ausgearbeiteten Gestaltungsrichtlinien. Indem die Entwürfe zweier alternativer Visualisierungen einer standardisierten Webapplikation beschrieben werden, die Linked Data als Netzwerk visualisiert, konnte ein Test durchgeführt werden, der deren Kompatibilität zum Inhalt hatte. Der praktische Teil behandelt daher die Designphase, die Resultate, und zukünftige Anforderungen des Projektes, die durch die Testung ausgearbeitet wurden.

  6. Linking open vocabularies

    CERN Document Server

    Greifender, Elke; Seadle, Michael

    2013-01-01

    Linked Data (LD), Linked Open Data (LOD) and generating a web of data, present the new knowledge sharing frontier. In a philosophical context, LD is an evolving environment that reflects humankinds' desire to understand the world by drawing on the latest technologies and capabilities of the time. LD, while seemingly a new phenomenon did not emerge overnight; rather it represents the natural progression by which knowledge structures are developed, used, and shared. Linked Open Vocabularies is a significant trajectory of LD. Linked Open Vocabularies targets vocabularies that have traditionally b

  7. Let's "Downscale" Linked Data

    NARCIS (Netherlands)

    Gueret, C.D.M.; de Boer, V.; Schlobach, K.S.

    2014-01-01

    Open data policies and linked data publication are powerful tools for increasing transparency, participatory governance, and accountability. The linked data community proudly emphasizes the economic and societal impact such technology shows. But a closer look proves that the design and deployment of

  8. Let's "Downscale" Linked Data

    NARCIS (Netherlands)

    Gueret, Christophe; de Boer, Victor; Schlobach, Stefan

    2014-01-01

    Open data policies and linked data publication are powerful tools for increasing transparency, participatory governance, and accountability. A closer look at linked data technologies, however, proves that their design and deployment exclude the majority of the world’s population. It will take small

  9. Weierstrass polynomials for links

    DEFF Research Database (Denmark)

    Hansen, Vagn Lundsgaard

    1997-01-01

    There is a natural way of identifying links in3-space with polynomial covering spaces over thecircle. Thereby any link in 3-space can be definedby a Weierstrass polynomial over the circle. Theequivalence relation for covering spaces over thecircle is, however, completely different from...

  10. Intersatellite link application to commercial communications satellites

    Science.gov (United States)

    Lee, Young S.; Atia, Ali E.; Ponchak, Denise S.

    1988-01-01

    The fundamental characteristics of intersatellite link (ISL) systems, and their application to domestic, regional, and global satellite communications, are described. The quantitative advantages of using ISLs to improve orbit utilization, spectrum occupancy, transmission delay (compared to multi-hop links), coverage, and connectivity, and to reduce the number of earth station antennas, are also presented. Cost-effectiveness and other systems benefits of using ISLs are identified, and the technical and systems planning aspects of ISL systems implementation are addressed.

  11. A high space-time resolution dataset linking meteorological forcing and hydro-sedimentary response in a mesoscale Mediterranean catchment (Auzon) of the Ardèche region, France

    OpenAIRE

    Nord, Guillaume; Boudevillain, Brice; Berne, Alexis; Branger, Flora; Braud, Isabelle; Dramais, Guillaume; Gérard, Simon; Coz, Le, Jérôme; Legoût, Cédric; Molinié, Gilles; Teuling, Ryan

    2017-01-01

    A comprehensive hydrometeorological dataset is presented spanning the period 1 January 2011-31 December 2014 to improve the understanding of the hydrological processes leading to flash floods and the relation between rainfall, runoff, erosion and sediment transport in a mesoscale catchment (Auzon, 116km2) of the Mediterranean region. Badlands are present in the Auzon catchment and well connected to high-gradient channels of bedrock rivers which promotes the transfer of suspended solids downst...

  12. Use of link to mammography screening information and link sharing strategies

    DEFF Research Database (Denmark)

    Mukai, Thomas; Bro, Flemming; Olesen, Frede

    2011-01-01

    -43%) reported use of the link. The difference between the two strategies was 15% (95% CI: 8-22%) (Pused the link prior to the screening event, and 37% (95% CI: 30-43%) used the link afterwards. The difference was 9% (95% CI: 0-17%) (P=0.035). Among the GPs in group 1, 40% (95% CI......Introduction: The Internet is increasingly being used for disseminating knowledge in health care. Often this is done through a ‘Uniform Resource Locator’ (URL), better known as a link. There are three ways of sharing a link: verbally, in print or electronically. Furthermore, timing and exposure...... in Central Denmark Region, we constructed a website containing screening programme information for GPs. We inserted the link to this website in different media and divided the GPs into three groups: Group 1 received a letter prior to the screening event and an electronic test result after the screening...

  13. Localization of Daucus carota NMCP1 to the nuclear periphery: the role of the N-terminal region and an NLS-linked sequence motif, RYNLRR, in the tail domain

    Directory of Open Access Journals (Sweden)

    Yuta eKimura

    2014-02-01

    Full Text Available Recent ultrastructural studies revealed that a structure similar to the vertebrate nuclear lamina exists in the nuclei of higher plants. However, plant genomes lack genes for lamins and intermediate-type filament proteins, and this suggests that plant-specific nuclear coiled-coil proteins make up the lamina-like structure in plants. NMCP1 is a protein, first identified in Daucus carota cells, that localizes exclusively to the nuclear periphery in interphase cells. It has a tripartite structure comprised of head, rod, and tail domains, and includes putative nuclear localization signal (NLS motifs. We identified the functional NLS of DcNMCP1 (carrot NMCP1 and determined the protein regions required for localizing to the nuclear periphery using EGFP-fused constructs transiently expressed in Apium graveolens epidermal cells. Transcription was driven under a CaMV35S promoter, and the genes were introduced into the epidermal cells by a DNA-coated microprojectile delivery system. Of the NLS motifs, KRRRK and RRHK in the tail domain were highly functional for nuclear localization. Addition of the N-terminal 141 amino acids from DcNMCP1 shifted the localization of a region including these NLSs from the entire nucleus to the nuclear periphery. Using this same construct, the replacement of amino acids in RRHK or its preceding sequence, YNL, with alanine residues abolished localization to the nuclear periphery, while replacement of KRRRK did not affect localization. The sequence R/Q/HYNLRR/H, including YNL and the first part of the sequence of RRHK, is evolutionarily conserved in a subclass of NMCP1 sequences from many plant species. These results show that NMCP1 localizes to the nuclear periphery by a combined action of a sequence composed of R/Q/HYNLRR/H, NLS, and the N-terminal region including the head and a portion of the rod domain, suggesting that more than one binding site is implicated in localization of NMCP1.

  14. Arctic Risk Management (ARMNet) Network: Linking Risk Management Practitioners and Researchers Across the Arctic Regions of Canada and Alaska To Improve Risk, Emergency and Disaster Preparedness and Mitigation Through Comparative Analysis and Applied Research

    Science.gov (United States)

    Garland, A.

    2015-12-01

    The Arctic Risk Management Network (ARMNet) was conceived as a trans-disciplinary hub to encourage and facilitate greater cooperation, communication and exchange among American and Canadian academics and practitioners actively engaged in the research, management and mitigation of risks, emergencies and disasters in the Arctic regions. Its aim is to assist regional decision-makers through the sharing of applied research and best practices and to support greater inter-operability and bilateral collaboration through improved networking, joint exercises, workshops, teleconferences, radio programs, and virtual communications (eg. webinars). Most importantly, ARMNet is a clearinghouse for all information related to the management of the frequent hazards of Arctic climate and geography in North America, including new and emerging challenges arising from climate change, increased maritime polar traffic and expanding economic development in the region. ARMNet is an outcome of the Arctic Observing Network (AON) for Long Term Observations, Governance, and Management Discussions, www.arcus.org/search-program. The AON goals continue with CRIOS (www.ariesnonprofit.com/ARIESprojects.php) and coastal erosion research (www.ariesnonprofit.com/webinarCoastalErosion.php) led by the North Slope Borough Risk Management Office with assistance from ARIES (Applied Research in Environmental Sciences Nonprofit, Inc.). The constituency for ARMNet will include all northern academics and researchers, Arctic-based corporations, First Responders (FRs), Emergency Management Offices (EMOs) and Risk Management Offices (RMOs), military, Coast Guard, northern police forces, Search and Rescue (SAR) associations, boroughs, territories and communities throughout the Arctic. This presentation will be of interest to all those engaged in Arctic affairs, describe the genesis of ARMNet and present the results of stakeholder meetings and webinars designed to guide the next stages of the Project.

  15. Link to paper

    Data.gov (United States)

    U.S. Environmental Protection Agency — Link to the paper. This dataset is associated with the following publication: Naile, J., A.W. Garrison, J. Avants, and J. Washington. Isomers/enantiomers of...

  16. The Missing Link

    DEFF Research Database (Denmark)

    Schultz, Laura Luise

    2014-01-01

    Paper presented at A Valentine to Gertrude Stein. The Reception of Gertrude Stein in the Arts and Humanities, held at the University of Copenhagen 8. - 10. May 2014, in collaboration with the universities of Ghent and Linköping......Paper presented at A Valentine to Gertrude Stein. The Reception of Gertrude Stein in the Arts and Humanities, held at the University of Copenhagen 8. - 10. May 2014, in collaboration with the universities of Ghent and Linköping...

  17. A WIDE DISTRIBUTION OF A NEW VRN-B1c ALLELE OF WHEAT TRITICUM AESTIVUM L. IN RUSSIA, UKRAINE AND ADJACENT REGIONS: A LINK WITH THE HEADING TIME AND ADAPTIVE POTENTIAL

    Directory of Open Access Journals (Sweden)

    Shcherban A.

    2012-08-01

    Full Text Available The adaptation of common wheat (T. aestivum L. to diverse environmental conditions is greatly under the control of genes involved in determination of vernalization response (Vrn-1 genes. It was found that the variation in common wheat heading time is affected not only by combination of Vrn-1 homoeoalleles but also by multiple alleles at a separate Vrn-1 locus. Previously, we described the Vrn-B1c allele from T.aestivum cv. 'Saratovskaya 29' and found significant differences in the structure of the first (1st intron of this allele when compared to another highly abundant Vrn-B1a allele, specifically, the deletion of 0.8 kb coupled with the duplication of 0.4 kb. We suggested that the changes in the intron 1 of Vrn-B1c allele caused earlier ear emergence in the near-isogenic line and cultivars, carrying this allele. In this study we investigate the distribution of the Vrn-B1c allele in a wide set of spring wheat cultivars from Russia, Ukraine and adjacent regions. The analysis revealed that 40% of Russian and 53% of Ukranian spring wheat cultivars contain the Vrn-B1c allele. The high distribution of the Vrn-B1c allele can be explained by a frequent using of 'Saratovskaya 29' in the breeding process inside the studied area. From the other hand, the predominance of the Vrn-B1c allele among cultivars cultivated in West Siberia and Kazakhstan may be due to the selective advantage of this allele for the region where there is a high risk of early fall frosts.

  18. Linked Ocean Data

    Science.gov (United States)

    Leadbetter, Adam; Arko, Robert; Chandler, Cynthia; Shepherd, Adam

    2014-05-01

    "Linked Data" is a term used in Computer Science to encapsulate a methodology for publishing data and metadata in a structured format so that links may be created and exploited between objects. Berners-Lee (2006) outlines the following four design principles of a Linked Data system: Use Uniform Resource Identifiers (URIs) as names for things. Use HyperText Transfer Protocol (HTTP) URIs so that people can look up those names. When someone looks up a URI, provide useful information, using the standards (Resource Description Framework [RDF] and the RDF query language [SPARQL]). Include links to other URIs so that they can discover more things. In 2010, Berners-Lee revisited his original design plan for Linked Data to encourage data owners along a path to "good Linked Data". This revision involved the creation of a five star rating system for Linked Data outlined below. One star: Available on the web (in any format). Two stars: Available as machine-readable structured data (e.g. An Excel spreadsheet instead of an image scan of a table). Three stars: As two stars plus the use of a non-proprietary format (e.g. Comma Separated Values instead of Excel). Four stars: As three stars plus the use of open standards from the World Wide Web Commission (W3C) (i.e. RDF and SPARQL) to identify things, so that people can point to your data and metadata. Five stars: All the above plus link your data to other people's data to provide context Here we present work building on the SeaDataNet common vocabularies served by the NERC Vocabulary Server, connecting projects such as the Rolling Deck to Repository (R2R) and the Biological and Chemical Oceanography Data Management Office (BCO-DMO) and other vocabularies such as the Marine Metadata Interoperability Ontology Register and Repository and the NASA Global Change Master Directory to create a Linked Ocean Data cloud. Publishing the vocabularies and metadata in standard RDF XML and exposing SPARQL endpoints renders them five-star Linked

  19. A high space-time resolution dataset linking meteorological forcing and hydro-sedimentary response in a mesoscale Mediterranean catchment (Auzon) of the Ardèche region, France

    Science.gov (United States)

    Nord, Guillaume; Boudevillain, Brice; Berne, Alexis; Branger, Flora; Braud, Isabelle; Dramais, Guillaume; Gérard, Simon; Le Coz, Jérôme; Legoût, Cédric; Molinié, Gilles; Van Baelen, Joel; Vandervaere, Jean-Pierre; Andrieu, Julien; Aubert, Coralie; Calianno, Martin; Delrieu, Guy; Grazioli, Jacopo; Hachani, Sahar; Horner, Ivan; Huza, Jessica; Le Boursicaud, Raphaël; Raupach, Timothy H.; Teuling, Adriaan J.; Uber, Magdalena; Vincendon, Béatrice; Wijbrans, Annette

    2017-03-01

    A comprehensive hydrometeorological dataset is presented spanning the period 1 January 2011-31 December 2014 to improve the understanding of the hydrological processes leading to flash floods and the relation between rainfall, runoff, erosion and sediment transport in a mesoscale catchment (Auzon, 116 km2) of the Mediterranean region. Badlands are present in the Auzon catchment and well connected to high-gradient channels of bedrock rivers which promotes the transfer of suspended solids downstream. The number of observed variables, the various sensors involved (both in situ and remote) and the space-time resolution ( ˜ km2, ˜ min) of this comprehensive dataset make it a unique contribution to research communities focused on hydrometeorology, surface hydrology and erosion. Given that rainfall is highly variable in space and time in this region, the observation system enables assessment of the hydrological response to rainfall fields. Indeed, (i) rainfall data are provided by rain gauges (both a research network of 21 rain gauges with a 5 min time step and an operational network of 10 rain gauges with a 5 min or 1 h time step), S-band Doppler dual-polarization radars (1 km2, 5 min resolution), disdrometers (16 sensors working at 30 s or 1 min time step) and Micro Rain Radars (5 sensors, 100 m height resolution). Additionally, during the special observation period (SOP-1) of the HyMeX (Hydrological Cycle in the Mediterranean Experiment) project, two X-band radars provided precipitation measurements at very fine spatial and temporal scales (1 ha, 5 min). (ii) Other meteorological data are taken from the operational surface weather observation stations of Météo-France (including 2 m air temperature, atmospheric pressure, 2 m relative humidity, 10 m wind speed and direction, global radiation) at the hourly time resolution (six stations in the region of interest). (iii) The monitoring of surface hydrology and suspended sediment is multi-scale and based on nested

  20. Searching for climate-conflict links

    Science.gov (United States)

    Hendrix, Cullen S.

    2018-03-01

    Environmental scarcity caused by climate change has been implicated as a driver of violent conflict. Now, research shows significant bias in the regions analysed for climate-conflict links. This may limit understanding of the socioeconomic and political conditions in which such conflict occurs, and how these conflicts could be prevented.

  1. Characterization of a human X-linked gene from the DXS732E locus in the candidate region for the anhidrotic ectodermal dysplasia (EDA) gene (Xq13.1)

    Energy Technology Data Exchange (ETDEWEB)

    Gault, J.; Zonana, J. [Oregon Health Sciences Univ., Portland, OR (United States); Zeltinger, J. [Univ. of Washington, Seattle, WA (United States)] [and others

    1994-09-01

    A conserved mouse genomic clone was used to identify a homologous human genomic clone (the DXS732E locus), which was subsequently employed to isolate cDNAs from a human fetal brain library. Nine unique overlapping cDNAs were isolated, and sequences analysis of 3.9 kb identified a putative 1 kb ORF. GRAIL analysis of the sequence supported the hypothesis that the putative ORF was coding sequence, and Prosite analysis of the putative ORF identified potential glycosylation and phosphorylation sites. The 5{prime} end of the gene maps within a CpG island, and comparison of cDNA sequences indicate the gene is alternatively spliced at its 3{prime} end. Northern analysis and RT-PCR indicate that two different sized messages appear to be expressed with the gene expressed in human fetal kidney, intestine, brain, and muscle. The gene is expressed in 77 day human skin, a time when hair follicle formation occurs. Anhidrotic ectodermal dysplasia (EDA) results in the abnormal morphogenesis of hair, teeth and eccrine sweat glands. A positional cloning strategy towards cloning the EDA gene had been used, and deletion and X-autosome translocation patients have been useful in further delimiting the EDA region. The present gene at the DXS732E locus is partially deleted in one EDA patient who does not have other apparent abnormalities. No rearrangements of the gene have been detected in two female X-autosome translocation EDA patients, nor in four additional male patients with submicroscopic molecular deletions.

  2. Age differences in search of web pages: the effects of link size, link number, and clutter.

    Science.gov (United States)

    Grahame, Michael; Laberge, Jason; Scialfa, Charles T

    2004-01-01

    Reaction time, eye movements, and errors were measured during visual search of Web pages to determine age-related differences in performance as a function of link size, link number, link location, and clutter. Participants (15 young adults, M = 23 years; 14 older adults, M = 57 years) searched Web pages for target links that varied from trial to trial. During one half of the trials, links were enlarged from 10-point to 12-point font. Target location was distributed among the left, center, and bottom portions of the screen. Clutter was manipulated according to the percentage of used space, including graphics and text, and the number of potentially distracting nontarget links was varied. Increased link size improved performance, whereas increased clutter and links hampered search, especially for older adults. Results also showed that links located in the left region of the page were found most easily. Actual or potential applications of this research include Web site design to increase usability, particularly for older adults.

  3. Link til hjemmesider

    DEFF Research Database (Denmark)

    Bervild, Charlotte

    2015-01-01

    Link til læringsobjekter/undervisningsportalhttp://videoportal.ucc.dk/channel/10492641/charlotte-bervilds-undervisninghttp://videoportal.ucc.dk/video/8248508/3d-printer-v-lektor-charlotte-bervildFotoblog:http://charlottebervild.blogspot.dk/2008/10/fotocollager-af-charlotte-bervild.html......Link til læringsobjekter/undervisningsportalhttp://videoportal.ucc.dk/channel/10492641/charlotte-bervilds-undervisninghttp://videoportal.ucc.dk/video/8248508/3d-printer-v-lektor-charlotte-bervildFotoblog:http://charlottebervild.blogspot.dk/2008/10/fotocollager-af-charlotte-bervild.html...

  4. Aerosol optical properties relevant to regional remote sensing of CCN activity and links to their organic mass fraction: airborne observations over Central Mexico and the US West Coast during MILAGRO/INTEX-B

    Science.gov (United States)

    Shinozuka, Y.; Clarke, A. D.; Decarlo, P. F.; Jimenez, J. L.; Dunlea, E. J.; Roberts, G. C.; Tomlinson, J. M.; Collins, D. R.; Howell, S. G.; Kapustin, V. N.; McNaughton, C. S.; Zhou, J.

    2009-09-01

    Remote sensing of cloud condensation nuclei (CCN) would help evaluate the indirect effects of tropospheric aerosols on clouds and climate. To assess its feasibility, we examined relationships of submicron aerosol composition to CCN activity and optical properties observed during the MILAGRO/INTEX-B aircraft campaigns. An indicator of CCN activity, κ, was calculated from hygroscopicity measured under saturation. κ for dry 100 nm particles decreased with increasing organic fraction of non-refractory mass of submicron particles (OMF) as 0.34-0.20×OMF over Central Mexico and 0.47-0.43×OMF over the US West Coast. These fits represent the critical dry diameter, centered near 100 nm for 0.2% supersaturation but varied as κ(-1/3), within measurement uncertainty (~20%). The decreasing trends of CCN activity with the organic content, evident also in our direct CCN counts, were consistent with previous ground and laboratory observations of highly organic particles. The wider range of OMF, 0-0.8, for our research areas means that aerosol composition will be more critical for estimation of CCN concentration than at the fixed sites previously studied. Furthermore, the wavelength dependence of extinction was anti-correlated with OMF as -0.70×OMF+2.0 for Central Mexico's urban and industrial pollution air masses, for unclear reasons. The Angstrom exponent of absorption increased with OMF, more rapidly under higher single scattering albedo, as expected for the interplay between soot and colored weak absorbers (some organic species and dust). Because remote sensing products currently use the wavelength dependence of extinction albeit in the column integral form and may potentially include that of absorption, these regional spectral dependencies are expected to facilitate retrievals of aerosol bulk chemical composition and CCN activity over Central Mexico.

  5. Erosional and depositional contourite features at the transition between the western Scotia Sea and southern South Atlantic Ocean: links with regional water-mass circulation since the Middle Miocene

    Science.gov (United States)

    Pérez, Lara F.; Hernández-Molina, F. Javier; Esteban, Federico D.; Tassone, Alejandro; Piola, Alberto R.; Maldonado, Andrés; Preu, Benedict; Violante, Roberto A.; Lodolo, Emanuele

    2015-08-01

    The aim of the present study was to characterise the morpho-sedimentary features and main stratigraphic stacking pattern off the Tierra del Fuego continental margin, the north-western sector of the Scotia Sea abyssal plain (Yaghan Basin) and the Malvinas/Falkland depression, based on single- and multi-channel seismic profiles. Distinct contourite features were identified within the sedimentary record from the Middle Miocene onwards. Each major drift developed in a water depth range coincident with a particular water mass, contourite terraces on top of some of these drifts being associated with interfaces between water masses. Two major palaeoceanographic changes were identified. One took place in the Middle Miocene with the onset of Antarctic Intermediate Water flow and the enhancement of Circumpolar Deep Water (CDW) flow, coevally with the onset of Weddell Sea Deep Water flow in the Scotia Sea. Another palaeoceanographic change occurred on the abyssal plain of the Yaghan Basin in the Late Miocene as a consequence of the onset of Southeast Pacific Deep Water flow and its complex interaction with the lower branch of the CDW. Interestingly, these two periods of change in bottom currents are coincident with regional tectonic episodes, as well as climate and Antarctic ice sheet oscillations. The results convincingly demonstrate that the identification of contourite features on the present-day seafloor and within the sedimentary record is the key for decoding the circulation of water masses in the past. Nevertheless, further detailed studies, especially the recovery of drill cores, are necessary to establish a more robust chronology of the evolutionary stages at the transition between the western Scotia Sea and the southern South Atlantic Ocean.

  6. Helically linked mirror arrangement

    International Nuclear Information System (INIS)

    Ranjan, P.

    1986-08-01

    A scheme is described for helical linking of mirror sections, which endeavors to combine the better features of toroidal and mirror devices by eliminating the longitudinal loss of mirror machines, having moderately high average β and steady state operation. This scheme is aimed at a device, with closed magnetic surfaces having rotational transform for equilibrium, one or more axisymmetric straight sections for reduced radial loss, a simple geometrical axis for the links and an overall positive magnetic well depth for stability. We start by describing several other attempts at linking of mirror sections, made both in the past and the present. Then a description of our helically linked mirror scheme is given. This example has three identical straight sections connected by three sections having helical geometric axes. A theoretical analysis of the magnetic field and single-particle orbits in them leads to the conclusion that most of the passing particles would be confined in the device and they would have orbits independent of pitch angle under certain conditions. Numerical results are presented, which agree well with the theoretical results as far as passing particle orbits are concerned

  7. Website Policies / Important Links | DOepatents

    Science.gov (United States)

    Links Website Policies / Important Links Javascript Not Enabled OSTI Security Website Policies and first) Publication Date (oldest first) Close Clear All Find DOepatents Website Policies / Important Important Links Some links on this page may take you to non-federal websites. Their policies may differ from

  8. Linking world scan and image

    International Nuclear Information System (INIS)

    Timmer, H.; Alcamo, J.; Bollen, J.; Gielen, A.; Gerlach, R.; Den Ouden, A.; Zuidema, G.

    1995-01-01

    In march 1994 the Central Planning Bureau (CPB) in the Hague, the National Institute of Public Health and Environmental Protection (RIVM) in Bilthoven and the Institute of Environmental Studies (IES) in Amsterdam started the first phase of a joint research program aimed at creating integrated scenarios of the global economy, GHG emissions, and climate impacts. The goal of the first phase of this project was to design and test a linked version of the economic model WORLD SCAN of the former, and the climate model IMAGE 2 of the latter institute. This first phase has resulted in the planned test runs with an operational version of the linked models by May 1995. The experiences in the first year were encouraging, both in the scientific and the organizational sense. In a sense, a link was made between scientific disciplines: a coupling of disciplines concerning with global economic development and the global physical climate system is difficult and novel. The goal of the project was to integrate long-term economic developments and effects of climate change. Both the WORLD SCAN model and IMAGE 2 provide a consistent analysis of the global system, but from different perspectives. IMAGE 2 simulates climate change and its effects in a global context but treats the economic system as exogenous. WORLD SCAN covers the world economic system in a consistent manner but does not take into account the global environment. The links are constructed in the area of agriculture and energy. The basic idea is that WORLD SCAN determines demand and supply on economic principles, while IMAGE 2 provides information on changes of land area and average quality of productive land, and other damage costs based on its three sub-systems. The demand for energy is fed into IMAGE 2's Energy Industry subsystem (EIS), which in turn determines emissions of greenhouse gases. Furthermore, some additional output from WORLD SCAN on activity levels, prices and capital structure can be used to determine

  9. Bottom-linked innovation

    DEFF Research Database (Denmark)

    Kristensen, Catharina Juul

    2018-01-01

    hitherto been paid little explicit attention, namely collaboration between middle managers and employees in innovation processes. In contrast to most studies, middle managers and employees are here both subjects of explicit investigation. The collaboration processes explored in this article are termed...... ‘bottom-linked innovation’. The empirical analysis is based on an in-depth qualitative study of bottom-linked innovation in a public frontline institution in Denmark. By combining research on employee-driven innovation and middle management, the article offers new insights into such collaborative......Employee-driven innovation is gaining ground as a strategy for developing sustainable organisations in the public and private sector. This type of innovation is characterised by active employee participation, and the bottom-up perspective is often emphasised. This article explores an issue that has...

  10. O-linked-N-acetylglucosamine modification of mammalian Notch receptors by an atypical O-GlcNAc transferase Eogt1

    Energy Technology Data Exchange (ETDEWEB)

    Sakaidani, Yuta [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Ichiyanagi, Naoki [Department of Applied Molecular Biosciences, Nagoya University Graduate School of Bioagricultural Sciences, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan); Saito, Chika; Nomura, Tomoko [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Ito, Makiko [Department of Applied Molecular Biosciences, Nagoya University Graduate School of Bioagricultural Sciences, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan); Nishio, Yosuke [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Nadano, Daita; Matsuda, Tsukasa [Department of Applied Molecular Biosciences, Nagoya University Graduate School of Bioagricultural Sciences, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan); Furukawa, Koichi [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Okajima, Tetsuya, E-mail: tokajima@med.nagoya-u.ac.jp [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Department of Applied Molecular Biosciences, Nagoya University Graduate School of Bioagricultural Sciences, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan)

    2012-03-02

    Highlights: Black-Right-Pointing-Pointer We characterized A130022J15Rik (Eogt1)-a mouse gene homologous to Drosophila Eogt. Black-Right-Pointing-Pointer Eogt1 encodes EGF domain O-GlcNAc transferase. Black-Right-Pointing-Pointer Expression of Eogt1 in Drosophila rescued the cell-adhesion defect in the Eogt mutant. Black-Right-Pointing-Pointer O-GlcNAcylation reaction in the secretory pathway is conserved through evolution. -- Abstract: O-linked-{beta}-N-acetylglucosamine (O-GlcNAc) modification is a unique cytoplasmic and nuclear protein modification that is common in nearly all eukaryotes, including filamentous fungi, plants, and animals. We had recently reported that epidermal growth factor (EGF) repeats of Notch and Dumpy are O-GlcNAcylated by an atypical O-GlcNAc transferase, EOGT, in Drosophila. However, no study has yet shown whether O-GlcNAcylation of extracellular proteins is limited to insects such as Drosophila or whether it occurs in other organisms, including mammals. Here, we report the characterization of A130022J15Rik, a mouse gene homolog of Drosophila Eogt (Eogt 1). Enzymatic analysis revealed that Eogt1 has a substrate specificity similar to that of Drosophila EOGT, wherein the Thr residue located between the fifth and sixth conserved cysteines of the folded EGF-like domains is modified. This observation is supported by the fact that the expression of Eogt1 in Drosophila rescued the cell-adhesion defect caused by Eogt downregulation. In HEK293T cells, Eogt1 expression promoted modification of Notch1 EGF repeats by O-GlcNAc, which was further modified, at least in part, by galactose to generate a novel O-linked-N-acetyllactosamine structure. These results suggest that Eogt1 encodes EGF domain O-GlcNAc transferase and that O-GlcNAcylation reaction in the secretory pathway is a fundamental biochemical process conserved through evolution.

  11. O-linked-N-acetylglucosamine modification of mammalian Notch receptors by an atypical O-GlcNAc transferase Eogt1

    International Nuclear Information System (INIS)

    Sakaidani, Yuta; Ichiyanagi, Naoki; Saito, Chika; Nomura, Tomoko; Ito, Makiko; Nishio, Yosuke; Nadano, Daita; Matsuda, Tsukasa; Furukawa, Koichi; Okajima, Tetsuya

    2012-01-01

    Highlights: ► We characterized A130022J15Rik (Eogt1)—a mouse gene homologous to Drosophila Eogt. ► Eogt1 encodes EGF domain O-GlcNAc transferase. ► Expression of Eogt1 in Drosophila rescued the cell-adhesion defect in the Eogt mutant. ► O-GlcNAcylation reaction in the secretory pathway is conserved through evolution. -- Abstract: O-linked-β-N-acetylglucosamine (O-GlcNAc) modification is a unique cytoplasmic and nuclear protein modification that is common in nearly all eukaryotes, including filamentous fungi, plants, and animals. We had recently reported that epidermal growth factor (EGF) repeats of Notch and Dumpy are O-GlcNAcylated by an atypical O-GlcNAc transferase, EOGT, in Drosophila. However, no study has yet shown whether O-GlcNAcylation of extracellular proteins is limited to insects such as Drosophila or whether it occurs in other organisms, including mammals. Here, we report the characterization of A130022J15Rik, a mouse gene homolog of Drosophila Eogt (Eogt 1). Enzymatic analysis revealed that Eogt1 has a substrate specificity similar to that of Drosophila EOGT, wherein the Thr residue located between the fifth and sixth conserved cysteines of the folded EGF-like domains is modified. This observation is supported by the fact that the expression of Eogt1 in Drosophila rescued the cell-adhesion defect caused by Eogt downregulation. In HEK293T cells, Eogt1 expression promoted modification of Notch1 EGF repeats by O-GlcNAc, which was further modified, at least in part, by galactose to generate a novel O-linked-N-acetyllactosamine structure. These results suggest that Eogt1 encodes EGF domain O-GlcNAc transferase and that O-GlcNAcylation reaction in the secretory pathway is a fundamental biochemical process conserved through evolution.

  12. TraceLink: A model of amnesia and consolidation.

    NARCIS (Netherlands)

    Meeter, M.; Murre, J.M.J.

    2005-01-01

    A connectionist model is presented, the TraceLink model, that implements an autonomous "off-line" consolidation process. The model consists of three subsystems: (1) a trace system (neocortex), (2) a link system (hippocampus and adjacent regions), and (3) a modulatory system (basal forebrain and

  13. Strengthening health systems through linking research evidence to ...

    African Journals Online (AJOL)

    informed policies. Accordingly, a critical way of addressing these challenges facing health systems in the region is through the linking of health research findings to policy. Keywords: Evidence; Sub-Saharan Africa; Health Policy; Health Systems ...

  14. True Time API Link (real time arrival info)

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — This link will take you to the site where you can create an account to access Port Authority's real time arrival information. To request access to Port Authority's...

  15. N-linked glycosylation of the immunoglobulin variable region

    NARCIS (Netherlands)

    van de Bovenkamp, Fleur S.; Derksen, Ninotska I. L.; Ooijevaar-de Heer, Pleuni; van Schie, Karin A.; Kruithof, Simone; Berkowska, Magdalena A.; van der Schoot, C. Ellen; Ijspeert, Hanna; van der Burg, Mirjam; Gils, Ann; Hafkenscheid, Lise; Toes, René E. M.; Rombouts, Yoann; Plomp, Rosina; Wuhrer, Manfred; van Ham, S. Marieke; Vidarsson, Gestur; Rispens, Theo

    2018-01-01

    N-glycosylation sites are introduced at positions in which glycans can affect antigen binding as a result of a specific clustering of progenitor glycosylation sites in the germline sequences of variable domain genes. By analyzing multiple human monoclonal and polyclonal (auto)antibody responses, we

  16. The Regional Dimension

    DEFF Research Database (Denmark)

    Eskjær, Mikkel Fugl

    2013-01-01

    is largely dependent on regional media systems, yet the role this regional dimension plays has been largely overlooked. This article presents a comparative study of climate-change coverage in three geo-cultural regions, The Middle East, Scandinavia, and North America, and explores the link between global......Global perspectives and national approaches have dominated studies of climate-change communication, reflecting the global nature of climate change as well as the traditional research focus on national media systems. In the absence of a global public sphere, however, transnational issue attention...... climate-change communication and regional media systems. It finds that regional variations in climate-change communication carry important communicative implications concerning perceptions of climate change's relevance and urgency...

  17. Linking consumer experiences

    DEFF Research Database (Denmark)

    Smed, Karina Madsen

    become part of the individual self, worldview, and behaviour. This paper seeks to explore links between consumer experiences through the exploration of narrative sequences in travel blogs. Findings indicate that non-consumption is a central element to the bloggers and also indicative of a community......Consumers consume products in various ways serving a number of purposes. Much attention has been paid to experiences attached to consumption, sometimes very explicitly, e.g. in tourism, the essence of which is experiences of various sorts, but often also implicitly as internalised experiences...

  18. Knots and links

    CERN Document Server

    Rolfsen, Dale

    2003-01-01

    Rolfsen's beautiful book on knots and links can be read by anyone, from beginner to expert, who wants to learn about knot theory. Beginners with a basic background find an inviting introduction to the elements of topology, emphasizing the tools needed for understanding knots, the fundamental group and van Kampen's theorem, for example, which are then applied to concrete problems, such as computing knot groups. For experts, Rolfsen explains advanced topics, such as the connections between knot theory and surgery and how they are useful to understanding three-manifolds. Besides providing a guide

  19. Regional characteristics, opportunity perception and entrepreneurial activities

    DEFF Research Database (Denmark)

    Stuetzer, Michael; Obschonka, Martin; Brixy, Udo

    2014-01-01

    This article seeks to better understand the link between regional characteristics and individual entrepreneurship. We combine individual-level Global Entrepreneurship Monitor data for Western Germany with regional-level data, using multilevel analysis to test our hypotheses. We find no direct link...

  20. Down-regulation of Notch-1 by γ-secretase inhibitor suppress the ...

    African Journals Online (AJOL)

    ajl yemi

    2011-11-30

    Nov 30, 2011 ... *Corresponding author. E-mail: liminl-kt@hotmail.com. Tel: ... photographed at the indicated times with an inverted microscopy equipped with a digital ... density with Image J Analyst software (NIH). ChIP assay. PC3 and ...

  1. Notch1-Dll4 signaling and mechanical force regulate leader cell formation during collective cell migration

    OpenAIRE

    Riahi, Reza; Sun, Jian; Wang, Shue; Long, Min; Zhang, Donna D.; Wong, Pak Kin

    2015-01-01

    At the onset of collective cell migration, a subset of cells within an initially homogenous population acquires a distinct “leader” phenotype with characteristic morphology and motility. However, the factors driving leader cell formation as well as the mechanisms regulating leader cell density during the migration process remain to be determined. Here, we use single cell gene expression analysis and computational modeling to show that leader cell identity is dynamically regulated by Dll4 sign...

  2. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the Link - Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors ... GA: CDC, DHHS. Retrieved November 2017. How are Drug Misuse and HIV Related? Drug misuse and addiction ...

  3. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the link between drug misuse and HIV infection. It contains information for young people, parents and teachers, ... present time. The virus (HIV) and the disease it causes (AIDS) are often linked and referred to ...

  4. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... teens and young adults have never known a world without it. NIDA’s "Learn the Link" campaign continues ... for HIV infection through risky sexual behaviors. NIDA researchers have studied and continue to study the links ...

  5. The HANDSS-55 Linking Equipment

    International Nuclear Information System (INIS)

    Crosby, S.

    2001-01-01

    The Bucket Translation Unit (BTU) and the Drum Handler are two of the HANDSS-55 subsystems identified as linking components. Both subsystems link other modules together by moving material to or from another module

  6. Phosphorylation of human link proteins

    International Nuclear Information System (INIS)

    Oester, D.A.; Caterson, B.; Schwartz, E.R.

    1986-01-01

    Three link proteins of 48, 44 and 40 kDa were purified from human articular cartilage and identified with monoclonal anti-link protein antibody 8-A-4. Two sets of lower molecular weight proteins of 30-31 kDa and 24-26 kDa also contained link protein epitopes recognized by the monoclonal antibody and were most likely degradative products of the intact link proteins. The link proteins of 48 and 40 kDa were identified as phosphoproteins while the 44 kDa link protein did not contain 32 P. The phosphorylated 48 and 40 kDa link proteins contained approximately 2 moles PO 4 /mole link protein

  7. Regions Matter

    DEFF Research Database (Denmark)

    Laursen, Keld; Masciarelli, Francesca; Prencipe, Andrea

    2012-01-01

    capital at the regional level, with a large-scale data set of the innovative activities of a representative sample of 2,413 Italian manufacturing firms from 21 regions, and controlling for a large set of firm and regional characteristics, we find that being located in a region characterized by a high...

  8. ITK optical links backup document

    CERN Document Server

    Huffman, B T; The ATLAS collaboration; Flick, T; Ye, J

    2013-01-01

    This document describes the proposed optical links to be used for the ITK in the phase II upgrade. The current R&D for optical links pursued in the Versatile Link group is reviewed. In particular the results demonstrating the radiation tolerance of all the on-detector components are documented. The bandwidth requirements and the resulting numerology are given.

  9. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... for young people, parents and teachers, and the media with links to our latest research findings and news updates. Read on to Learn the Link between ... to this site at: http://www.drugabuse.gov/news-events/public-education-projects/learn-link-drugs-hiv . ... Social Media Send the message to young people and to ...

  10. Seismic link at plate boundary

    Indian Academy of Sciences (India)

    time series to determine the causality and related orientation. The resulting link ... Triggering causes changes in the Coulomb stress on a specified fault, which is ... work link shows that the alignment of the links is parallel to the Honshu Trench ...

  11. Fermions and link invariants

    International Nuclear Information System (INIS)

    Kauffman, L.; Saleur, H.

    1991-01-01

    Various aspects of knot theory are discussed when fermionic degrees of freedom are taken into account in the braid group representations and in the state models. It is discussed how the R matrix for the Alexander polynomial arises from the Fox differential calculus, and how it is related to the quantum group U q gl(1,1). New families of solutions of the Yang Baxter equation obtained from ''linear'' representations of the braid group and exterior algebra are investigated. State models associated with U q sl(n,m), and in the case n=m=1 a state model for the multivariable Alexander polynomial are studied. Invariants of links in solid handlebodies are considered and it is shown how the non trivial topology lifts the boson fermion degeneracy is present in S 3 . (author) 36 refs

  12. Multilevel DC link inverter

    Science.gov (United States)

    Su, Gui-Jia

    2003-06-10

    A multilevel DC link inverter and method for improving torque response and current regulation in permanent magnet motors and switched reluctance motors having a low inductance includes a plurality of voltage controlled cells connected in series for applying a resulting dc voltage comprised of one or more incremental dc voltages. The cells are provided with switches for increasing the resulting applied dc voltage as speed and back EMF increase, while limiting the voltage that is applied to the commutation switches to perform PWM or dc voltage stepping functions, so as to limit current ripple in the stator windings below an acceptable level, typically 5%. Several embodiments are disclosed including inverters using IGBT's, inverters using thyristors. All of the inverters are operable in both motoring and regenerating modes.

  13. Linking Wayfinding and Wayfaring

    DEFF Research Database (Denmark)

    Lanng, Ditte Bendix; Jensen, Ole B.

    2016-01-01

    In this chapter we propose to expand and enhance the understanding of wayfi nding beyond the strictly “instrumental” (i.e., getting from point A to point B), to include the qualities and multi-sensorial inputs that inform and shape people’s movement through space. We take as a point of departure...... of environmental information , which includes the embodied, multi-sensorial experience of moving through physical space. We base our examination in part on the classic positions of the wayfi nding literature—for example, Lynch’s seminal study, The Image of the City ( 1960 ). However, we also examine the so......-called mobilities turn in which mobility is viewed as a complex, multilayered process that entails much more than simply getting from point A to point B (see Cresswell 2006 ; Jensen 2013 ; Urry 2007 ).The structure of the chapter is simple: We fi rst introduce the concepts that are key to linking wayfi nding...

  14. LinkLights

    DEFF Research Database (Denmark)

    Grönvall, Erik; Kramp, Gunnar

    2011-01-01

    The project described in this paper aims to provide assistive tools to support elderly people affected by vestibular dysfunction (i.e. a form of balance disorder leading to dizziness and nausea) in their home-based rehabilitation activities. Challenges emerge as the rehabilitation moves from...... a supervised hospital setting to private homes. Our studies have shown that the elderly people are less motivated to perform the training at home. This paper presents a tangible, portable, two dimensional modular platform called LinkLights that has been developed to sustain the home-based rehabilitation......, giving clear guidelines what to do, adding motivational cues and elements of variation and surprise in the activity. Furthermore, a set of challenges for successful translocation of the therapeutic regimen from a supervised, hospital setting to an unsupervised home-based setting together with some early...

  15. Named Entity Linking Algorithm

    Directory of Open Access Journals (Sweden)

    M. F. Panteleev

    2017-01-01

    Full Text Available In the tasks of processing text in natural language, Named Entity Linking (NEL represents the task to define and link some entity, which is found in the text, with some entity in the knowledge base (for example, Dbpedia. Currently, there is a diversity of approaches to solve this problem, but two main classes can be identified: graph-based approaches and machine learning-based ones. Graph and Machine Learning approaches-based algorithm is proposed accordingly to the stated assumptions about the interrelations of named entities in a sentence and in general.In the case of graph-based approaches, it is necessary to solve the problem of identifying an optimal set of the related entities according to some metric that characterizes the distance between these entities in a graph built on some knowledge base. Due to limitations in processing power, to solve this task directly is impossible. Therefore, its modification is proposed. Based on the algorithms of machine learning, an independent solution cannot be built due to small volumes of training datasets relevant to NEL task. However, their use can contribute to improving the quality of the algorithm. The adaptation of the Latent Dirichlet Allocation model is proposed in order to obtain a measure of the compatibility of attributes of various entities encountered in one context.The efficiency of the proposed algorithm was experimentally tested. A test dataset was independently generated. On its basis the performance of the model was compared using the proposed algorithm with the open source product DBpedia Spotlight, which solves the NEL problem.The mockup, based on the proposed algorithm, showed a low speed as compared to DBpedia Spotlight. However, the fact that it has shown higher accuracy, stipulates the prospects for work in this direction.The main directions of development were proposed in order to increase the accuracy of the system and its productivity.

  16. Regional Competitive Intelligence: Benchmarking and Policymaking

    OpenAIRE

    Huggins , Robert

    2010-01-01

    Benchmarking exercises have become increasingly popular within the sphere of regional policymaking in recent years. The aim of this paper is to analyse the concept of regional benchmarking and its links with regional policymaking processes. It develops a typology of regional benchmarking exercises and regional benchmarkers, and critically reviews the literature, both academic and policy oriented. It is argued that critics who suggest regional benchmarking is a flawed concept and technique fai...

  17. Too Many Links in the Horizon; What is Next? Linked Views and Linked History

    NARCIS (Netherlands)

    E. Liarou (Erietta); S. Idreos (Stratos)

    2011-01-01

    textabstractThe trend for more online linked data becomes stronger. Foreseeing a future where ``everything" will be online and linked, we ask the critical question; what is next? We envision that managing, querying and storing large amounts of links and data is far from yet another query

  18. Regional development and regional policy

    OpenAIRE

    Šabić, Dejan; Vujadinović, Snežana

    2017-01-01

    Economic polarization is a process that is present at global, national and regional level. Economic activity is extremely spatially concentrated. Cities and developed regions use the agglomeration effect to attract labor and capital, thus achieving more favorable economic conditions than the agrarian region. Scientific research and European experiences over the past decades have contributed to the discrepancy among theorists about the causes and consequences of regional inequalities. Regional...

  19. Deploying Linked Open Vocabulary (LOV to Enhance Library Linked Data

    Directory of Open Access Journals (Sweden)

    Oh, Sam Gyun

    2015-06-01

    Full Text Available Since the advent of Linked Data (LD as a method for building webs of data, there have been many attempts to apply and implement LD in various settings. Efforts have been made to convert bibliographic data in libraries into Linked Data, thereby generating Library Linked Data (LLD. However, when memory institutions have tried to link their data with external sources based on principles suggested by Tim Berners-Lee, identifying appropriate vocabularies for use in describing their bibliographic data has proved challenging. The objective of this paper is to discuss the potential role of Linked Open Vocabularies (LOV in providing better access to various open datasets and facilitating effective linking. The paper will also examine the ways in which memory institutions can utilize LOV to enhance the quality of LLD and LLD-based ontology design.

  20. Urban rainfall estimation employing commercial microwave links

    Science.gov (United States)

    Overeem, Aart; Leijnse, Hidde; Uijlenhoet, Remko; ten Veldhuis, Marie-claire

    2015-04-01

    Urban areas often lack rainfall information. To increase the number of rainfall observations in cities, microwave links from operational cellular telecommunication networks may be employed. Although this new potential source of rainfall information has been shown to be promising, its quality needs to be demonstrated more extensively. In the Rain Sense kickstart project of the Amsterdam Institute for Advanced Metropolitan Solutions (AMS), sensors and citizens are preparing Amsterdam for future weather. Part of this project is rainfall estimation using new measurement techniques. Innovative sensing techniques will be utilized such as rainfall estimation from microwave links, umbrellas for weather sensing, low-cost sensors at lamp posts and in drainage pipes for water level observation. These will be combined with information provided by citizens in an active way through smartphone apps and in a passive way through social media posts (Twitter, Flickr etc.). Sensor information will be integrated, visualized and made accessible to citizens to help raise citizen awareness of urban water management challenges and promote resilience by providing information on how citizens can contribute in addressing these. Moreover, citizens and businesses can benefit from reliable weather information in planning their social and commercial activities. In the end city-wide high-resolution rainfall maps will be derived, blending rainfall information from microwave links and weather radars. This information will be used for urban water management. This presentation focuses on rainfall estimation from commercial microwave links. Received signal levels from tens of microwave links within the Amsterdam region (roughly 1 million inhabitants) in the Netherlands are utilized to estimate rainfall with high spatial and temporal resolution. Rainfall maps will be presented and compared to a gauge-adjusted radar rainfall data set. Rainfall time series from gauge(s), radars and links will be compared.

  1. Link for Injured Kids

    Science.gov (United States)

    Ramirez, Marizen; Toussaint, Maisha; Woods-Jaeger, Briana; Harland, Karisa; Wetjen, Kristel; Wilgenbusch, Tammy; Pitcher, Graeme; Jennissen, Charles

    2017-01-01

    Objective Injury, the most common type of pediatric trauma, can lead to a number of adverse psychosocial outcomes, including posttraumatic stress disorder. Currently, few evidence-based parent programs exist to support children hospitalized after a traumatic injury. Using methods in evaluation and intervention research, we completed a formative research study to develop a new program of psychological first aid, Link for Injured Kids, aimed to educate parents in supporting their children after a severe traumatic injury. Methods Using qualitative methods, we held focus groups with parents and pediatric trauma providers of children hospitalized at a Level I Children's Hospital because of an injury in 2012. We asked focus group participants to describe reactions to trauma and review drafts of our intervention materials. Results Health professionals and caregivers reported a broad spectrum of emotional responses by their children or patients; however, difficulties were experienced during recovery at home and upon returning to school. All parents and health professionals recommended that interventions be offered to parents either in the emergency department or close to discharge among admissions. Conclusions Results from this study strongly indicate a need for posttrauma interventions, particularly in rural settings, to support families of children to address the psychosocial outcomes in the aftermath of an injury. Findings presented here describe the process of intervention development that responds to the needs of an affected population. PMID:26428077

  2. The CMS link system

    International Nuclear Information System (INIS)

    Vila, I.

    1999-01-01

    The Compact Muon Solenoid (CMS) is a multi-purpose detector that is going to be installed in the future Large Hadron Collider (LHC) at CERN. Muons are one of the main physical signatures of the expected new physics. The muons are going to be detected by the Central Tracker (CT) and the Muon Spectrometer (MS). Both, the CT and MS can provide an independent muon momentum measurement, but for all η and momentum values the highest precision for muon momentum measurement is achieved when the muon tracks are reconstructed using both tracking detectors. The calorimeters and the solenoid volumes separate about three meters the CT and the MS. It has been shown that the alignment of the CT with respect to the MS can not be guaranteed by a software alignment in a reasonable time scale. Therefore, an opto-mechanical system (the multipoint link system) have been designed to monitor, on-line, the relative position of both sub-detectors providing a common reference frame for both of them. The local alignment of the muon barrel spectrometer determines the relative position of the muon chambers with respect to themselves and also with respect to a carbon fiber rigid structure called MAB (Module for the Alignment of the Barrel). There are a total of 36 MABs distributed in the boundary planes of each muon spectrometer sector. This paper describes all the equipment and presents the principle of measurement. (author)

  3. Diabetes and dementia links

    Directory of Open Access Journals (Sweden)

    Paula Jankowska

    2018-06-01

    Full Text Available Introduction The number of patients suffering from diabetes mellitus is growing globally. It is expected to observe 253.4 million sufferers in geriatric population in 2045. In this time, also 131.5 million of people is going to have dementia and other cognitive problems. In people aged over 65 these two diseases are concomitant quite often. What are the connections in the area of etiology and treatment? Aim The purpose of this study is to present links between dementia and diabetes are depicted in professional literature. Results Diabetes and dementia are associated on many levels. These conditions have common risk factors. Diabetes may contribute to cognitive impairment in many ways, promoting development of atherosclerosis, brain vessel damage and vascular dementia. Alzheimer disease may be promoted by hyperglycemia and hyperinsulinemia. On contrary also hypoglycaemia, often met in elderly diabetic patients has negative impact on cognitive function. Dementia seriously affects treatment of diabetes. The main problems are not satisfying adherence and diabetes self-management. Conclusions Prevention of diabetes and dementia risk factors can be performed simultaneously as the are common for both diseases. Enhancing physical activity, reducing saturated fats consumption, levels of cholesterol and body mass are considered to be beneficial in the context of described conditions. Furthermore, treatment of diabetes is strongly affected by cognitive dysfunction. Management of dementive diabetics requires individualization and using long-acting drugs. It is crucial to reduce risk of life-threatening hypoglycaemias and to create wide team to take care of these patients.

  4. Hierarchical Linked Views

    Energy Technology Data Exchange (ETDEWEB)

    Erbacher, Robert; Frincke, Deb

    2007-07-02

    Coordinated views have proven critical to the development of effective visualization environments. This results from the fact that a single view or representation of the data cannot show all of the intricacies of a given data set. Additionally, users will often need to correlate more data parameters than can effectively be integrated into a single visual display. Typically, development of multiple-linked views results in an adhoc configuration of views and associated interactions. The hierarchical model we are proposing is geared towards more effective organization of such environments and the views they encompass. At the same time, this model can effectively integrate much of the prior work on interactive and visual frameworks. Additionally, we expand the concept of views to incorporate perceptual views. This is related to the fact that visual displays can have information encoded at various levels of focus. Thus, a global view of the display provides overall trends of the data while focusing in on individual elements provides detailed specifics. By integrating interaction and perception into a single model, we show how one impacts the other. Typically, interaction and perception are considered separately, however, when interaction is being considered at a fundamental level and allowed to direct/modify the visualization directly we must consider them simultaneously and how they impact one another.

  5. Linking to the Future

    Science.gov (United States)

    Moore, John W.

    1999-09-01

    of JCE in the mail each month, and I expect you do too. I can glance at the cover to get an overview of an issue's content, and I usually am enticed inside by intriguing cover art. I can scan the table of contents to find articles I want to read, or I can just browse through the issue to see what looks interesting. Usually the editors have juxtaposed related articles so that I often find a small treasure trove. The printed Journal is quite portable and can be read in a car or airplane. It will last a long time, and until the paper deteriorates, I will never have a problem reading back issues. I have almost every issue from the first day I subscribed and have even added some older ones from collections of retired colleagues who no longer had shelf space for them. I certainly would not want to give up my printed copies, and I want to keep getting them. I find that JCE Online provides a different kind of resource that is equally valuable. It contains more information, and information that is more appropriate in electronic form. It links related ideas into a much more complex web of information than is possible in print. And it opens pathways to lots of information that is not part of JCE but resides elsewhere. Using this issue as an example, let's take a tour of what JCE Online can do. Point your Web browser to http://jchemed.chem.wisc.edu Click on Journal and then on Current Issue (unless September 1999 is no longer the current issue, in which case you will find it in Past Issues). In the table of contents, find the article "UV Catalysis, Cyanotype Photography, and Sunscreens". Click on the title. When the abstract appears, click on Full Text (PDF) to see the article, just as it appears on page 1199 in this issue. When you are prompted, enter the name and subscriber number from your address label. At the end of the article you will find that supplementary materials are available (including a procedure for testing sunscreens) and you can click on the link to view them

  6. Object linking in repositories

    Science.gov (United States)

    Eichmann, David (Editor); Beck, Jon; Atkins, John; Bailey, Bill

    1992-01-01

    This topic is covered in three sections. The first section explores some of the architectural ramifications of extending the Eichmann/Atkins lattice-based classification scheme to encompass the assets of the full life cycle of software development. A model is considered that provides explicit links between objects in addition to the edges connecting classification vertices in the standard lattice. The second section gives a description of the efforts to implement the repository architecture using a commercially available object-oriented database management system. Some of the features of this implementation are described, and some of the next steps to be taken to produce a working prototype of the repository are pointed out. In the final section, it is argued that design and instantiation of reusable components have competing criteria (design-for-reuse strives for generality, design-with-reuse strives for specificity) and that providing mechanisms for each can be complementary rather than antagonistic. In particular, it is demonstrated how program slicing techniques can be applied to customization of reusable components.

  7. Linking research to practice

    DEFF Research Database (Denmark)

    Pinto-Correia, T.; Kristensen, L.

    2013-01-01

    , questions on the changes affecting the rural, addressed by society to the scientific community, are of a, new character and require novel research approaches. This paper argues that landscape based, approaches can be useful basis for the required conceptual innovation. The paper presents and, discusses...... a set of examples of practice driven research developments, in contrasting regions of Europe. And it proposes a conceptual model which aims to contextualize empirical research driven by, problems set up in practice, and combining the ecological and structural dimensions with the socioeconomic...

  8. Structural region

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Structural region. The two groups had 4 substitutions similar to Yawat strain. The Yawat strain had 5 unique mutations. 3 in the E2 region and 2 in the E1 region. The mutation, I702V (E2), though different from all the recent Indian and Reunion sequences was similar ...

  9. Regional systems of innovation: an evolutionary perspective

    OpenAIRE

    P Cooke; M G Uranga; G Etxebarria

    1998-01-01

    The authors develop the concept of regional systems of innovation and relate it to preexisting research on national systems of innovation. They argue that work conducted in the 'new regional science' field is complementary to systems of innovation approaches. They seek to link new regional work to evolutionary economics, and argue for the development of evolutionary regional science. Common elements of interest to evolutionary innovation research and new regional science are important in unde...

  10. Impact on local air quality of the planned fixed link across Oresund

    DEFF Research Database (Denmark)

    Fenger, Jes; Vignati, Elisabetta; Berkowicz, Ruwim

    1996-01-01

    The planned combined bridge and tunnel link between Sweden and Denmark (the Oresund Link) is expected to be in operation around the turn of the century. So far the impacts of the Oresund Link on air pollution have been discussed mainly in terms of changes in emissions, taking into account...... implications of the link on traffic in the region. It appears that the influence on regional and global air pollution will be marginal. Concerning local effects however, the situation is different; the new link across the Oresund and the island Amager will result in significant changes in traffic pattern...

  11. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... link between drug misuse and HIV. http://1.usa.gov/1z20ww6 How many of us think about ... can’t ignore. Learn the Link: http://1.usa.gov/1uSUAI3 Think you’re not at risk? ...

  12. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... at: http://www.drugabuse.gov/news-events/public-education-projects/learn-link-drugs-hiv . 120x90 460x80 486x60 Social Media Send the message to young people and to parents, teachers, and the media about the link between drug misuse and HIV. Post on Facebook or Twitter ; add photos to your Flickr , ...

  13. Decouplink: Dynamic Links for Java

    DEFF Research Database (Denmark)

    Jensen, Martin Lykke Rytter; Jørgensen, Bo Nørregaard

    2011-01-01

    of dimensions of extension that can be exploited without performing modification of existing types. Thus, dynamic links make it possible to enforce the open/closed principle in situations where it would otherwise not be possible. We present Decouplink – a library-based implementation of dynamic links for Java...

  14. [Sex-linked juvenile retinoschisis].

    Science.gov (United States)

    François, P; Turut, P; Soltysik, C; Hache, J C

    1976-02-01

    About 13 observations of sexe linked juvenile retinoschisis, the authors describe the ophthalmoscopic, fluorographic and functional aspects of the disease whose caracteristics are:--its sexe linked recessive heredity; --its clinical characterestics associating: a microcystic macular degeneration, peripheral retinal lesions, vitreous body alterations, --an electroretinogram of the negative type.

  15. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Learn the Link campaign uses TV, print, and Web public service announcements (PSAs), as well as posters, e-cards, ... to misuse drugs. The Learn the Link public service campaign is just one ... site. Sincerely, Nora D. Volkow, M.D. Director ...

  16. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Link Need ideas for posts? We’ve provided sample Facebook status updates that you can easily copy ... LearntheLink. Need ideas for tweets? We’ve provided sample tweets that you can easily copy and paste ...

  17. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... projects/learn-link-drugs-hiv . 120x90 460x80 486x60 Social Media Send the message to young people and ... HIV/AIDS and the discovery of promising treatment interventions for breaking the harmful links between them, we ...

  18. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... at: http://www.drugabuse.gov/news-events/public-education-projects/learn-link-drugs-hiv . 120x90 460x80 486x60 Social Media Send the message to young people and to parents, teachers, and the media about the link between drug ...

  19. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Children & Teens Search Connect with NIDA : Facebook LinkedIn Twitter YouTube Flickr RSS Menu Home Drugs of Abuse ... Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors associated with drug misuse are ...

  20. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV. Post on Facebook About Learn the Link Need ideas for posts? We’ve provided sample Facebook ... HIV, be sure to use the hashtag #LearntheLink. Need ideas for tweets? We’ve provided sample tweets ...

  1. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... NIDA : Facebook LinkedIn Twitter YouTube Flickr RSS Menu Home Drugs of Abuse Commonly Abused Drugs Charts Emerging ... Badges Other Resources Strategic Plan Search Share Print Home » News & Events » Public Education Projects » Learn the Link - ...

  2. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... site. Please link these banners back to this site at: http://www.drugabuse.gov/news-events/public-education-projects/learn-link-drugs-hiv . 120x90 460x80 486x60 Social Media Send the message to young people and to ...

  3. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Parents & Educators Children & Teens Search Connect with NIDA : Facebook LinkedIn Twitter YouTube Flickr RSS Menu Home Drugs ... HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors associated with drug misuse ...

  4. LinkMind: Link Optimization in Swarming Mobile Sensor Networks

    DEFF Research Database (Denmark)

    Ngo, Trung Dung

    2012-01-01

    of the most advantageous properties of the swarming wireless sensor network is that mobile nodes can work cooperatively to organize an ad-hoc network and optimize the network link capacity to maximize the transmission of gathered data from a source to a target. This paper describes a new method of link...... optimization of swarming mobile sensor networks. The new method is based on combination of the artificial potential force guaranteeing connectivities of the mobile sensor nodes and the max-flow min-cut theorem of graph theory ensuring optimization of the network link capacity. The developed algorithm...

  5. Regional Externalities

    NARCIS (Netherlands)

    Heijman, W.J.M.

    2007-01-01

    The book offers practical and theoretical insights in regional externalities. Regional externalities are a specific subset of externalities that can be defined as externalities where space plays a dominant role. This class of externalities can be divided into three categories: (1) externalities

  6. VT Biodiversity Project - Biophysical Regions boundary lines

    Data.gov (United States)

    Vermont Center for Geographic Information — (Link to Metadata) This dataset divides Vermont into eight sub-regions on the basis of bedrock geology, gross physiography, climate, and broad-scale patterns of...

  7. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Notes Podcasts E-Newsletters Public Education Projects National Drug & Alcohol Facts Week NIDA TV PEERx Drugs & Health Blog ... Award for Addiction Science USA Science & Engineering Festival Drug & Alcohol Chat Day HBO Addiction Project Learn the Link ...

  8. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... she went to a party and under the influence of drugs and alcohol engaged in risky sexual ... the message to young people and to parents, teachers, and the media about the link between drug ...

  9. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors associated with ... Send the Message . Get the Facts What are HIV and AIDS? HIV (human immunodeficiency virus) is the ...

  10. Medicare and Medicaid Linked Files

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Medicare-Medicaid Linked Enrollee Analytic Data Source (MMLEADS) has been developed to allow for the examination of all Medicare and Medicaid enrollment and...

  11. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available Skip to main content En español Researchers Medical & Health Professionals Patients & Families Parents & Educators Children & Teens Search Connect with NIDA : Facebook LinkedIn Twitter YouTube Flickr RSS Menu ...

  12. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Link between drug use and HIV and to help us Send the Message . Get the Facts What ... and the public. Send the Message Overview Please help us send the message to young people and ...

  13. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... people on HAART (highly active antiretroviral therapy), for example, who continue to misuse drugs. The Learn the Link public service campaign is just one example of how NIDA continues to respond to the ...

  14. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV Learn the Link - Drugs and HIV ... Drugs can change the way the brain works, disrupting the parts of the brain that people use to weigh risks and benefits when making decisions. ...

  15. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV (human immunodeficiency virus) is the virus that causes AIDS (acquired immune deficiency syndrome). AIDS is a ... time. The virus (HIV) and the disease it causes (AIDS) are often linked and referred to as " ...

  16. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... It contains information for young people, parents and teachers, and the media with links to our latest ... greater injury to cells in the brain and cognitive impairment among people who use methamphetamine than among ...

  17. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... of many drugs, which can alter judgment and inhibition and lead people to engage in impulsive and ... easily copy and paste to help show your support for Learn the Link . Be sure to check ...

  18. Front end data link processor

    International Nuclear Information System (INIS)

    Wallace, J.J.

    1988-01-01

    It is possible to expand the data acquisition capabilities of an existing process computer to include other dedicated computer based systems, provided each system has at least minimal data link capabilities. The following paper discusses the addition of three computer based acquisition systems to a Honeywell 4500C (also designated the 45000) running the SEER system. Only one data link port was required to support the link. Each of the three specialized systems implemented data link protocols used by their suppliers in previous projects: none of the three were compatible with Honeywell's protocol. Part one of the following provides a generic overview of the project and would be relevent to the operator of any process system interested in expansion. Part two provides specific details of this project and may serve to provide performance benchmarks to those who wish to consider a similar project

  19. EPA Linked Open Data (Collection)

    Data.gov (United States)

    U.S. Environmental Protection Agency — This is a collection item referencing the following EPA Linked Data resources: - EPA Facility Registry Service (FRS) - EPA Substance Registry Service (SRS) -...

  20. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... NIDA Donating to NIDA Frequently Asked Questions Contact Us Sharing Tools and Badges Other Resources Strategic Plan Search Share Print Home » News & Events » Public Education Projects » Learn the Link - Drugs and HIV Learn ...

  1. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... contracting or transmitting HIV/AIDS or other infectious diseases. Research Reports: HIV/AIDS : Explores the link between drug misuse and HIV/AIDS, populations most at risk, trends in HIV/AIDS, and ...

  2. Protein Linked to Atopic Dermatitis

    Science.gov (United States)

    ... Research Matters NIH Research Matters January 14, 2013 Protein Linked to Atopic Dermatitis Normal skin from a ... in mice suggests that lack of a certain protein may trigger atopic dermatitis, the most common type ...

  3. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Process Funding Priorities Research Training News & Events News Nora's Blog NIDA in the News NIDA Notes Podcasts ... of the National Institute on Drug Abuse, Dr. Nora D. Volkow. Message from the Director The Link ...

  4. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... their lives , but now their night out always will be associated with HIV/AIDS. The “d’cisions” ... for breaking the harmful links between them, we will continue to update this Web site. Sincerely, Nora ...

  5. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Link" campaign continues to raise awareness among this generation of the real risks of drug use for ... Resource Center (NWHRC) Mujeres Unidas Contra el SIDA New Mexico AIDS Services African Advocates Against AIDS The ...

  6. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... link between non-injection drug use and HIV. Television Networks: MunDos Azteca America ... and Families The American Academy of Child & Adolescent Psychiatry (AACAP) The United Negro College Fund, ...

  7. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... of people infected with HIV, drug misuse can interfere with an individual's likelihood of adhering to the ... HIV/AIDS and the discovery of promising treatment interventions for breaking the harmful links between them, we ...

  8. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... other organizations in your tweets to spread the word even further. Tweet About Learn the Link To ... other organizations in your tweets to spread the word even further. Share with Flickr, Pinterest or Instagram ...

  9. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... can affect anyone. Watch the “d’cisions” Videos Campaign Materials After the Party Posters: We have developed ... share on your social media accounts. About the Campaign Overview The Learn the Link campaign uses TV, ...

  10. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the main factors in the spread of HIV infection in the United States. Drugs can change the ... about the link between drug misuse and HIV infection. It contains information for young people, parents and ...

  11. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Parents & Educators Children & Teens Search Connect with NIDA : Facebook LinkedIn Twitter YouTube Flickr RSS Menu Home Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts ...

  12. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... En español Researchers Medical & Health Professionals Patients & Families Parents & Educators Children & Teens Search Connect with NIDA : Facebook ... HIV infection. It contains information for young people, parents and teachers, and the media with links to ...

  13. Analytic invariants of boundary links

    OpenAIRE

    Garoufalidis, Stavros; Levine, Jerome

    2001-01-01

    Using basic topology and linear algebra, we define a plethora of invariants of boundary links whose values are power series with noncommuting variables. These turn out to be useful and elementary reformulations of an invariant originally defined by M. Farber.

  14. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... that use text messaging as a means of communication. The "Text Message" PSA features two young girls ... about the link between drug misuse and HIV. Post on Facebook or Twitter ; add photos to your ...

  15. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... NIDA’s "Learn the Link" campaign continues to raise awareness among this generation of the real risks of ... Collaborators Thanks to Those Who Have Helped Raise Awareness of Our Campaign! NIDA acknowledges the following television ...

  16. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... educational institutions, magazines, newspapers, companies, events, and radio stations for helping to raise awareness of the link ... Poets Sistahs Getting Real About HIV Conference Radio Stations: WTOP Radio WPFW Radio WOL Radio News & Events ...

  17. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Addiction Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and ... Link campaign. This campaign shows teens and young adults that non-injection drug use and alcohol use ...

  18. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... works, disrupting the parts of the brain that people use to weigh risks and benefits when making ... and HIV infection. It contains information for young people, parents and teachers, and the media with links ...

  19. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... causes (AIDS) are often linked and referred to as "HIV/AIDS." HIV can be transferred between people ... years, HIV is no longer a death sentence, as it was when the epidemic began. This is ...

  20. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Campaign Overview The Learn the Link campaign uses TV, print, and Web public service announcements (PSAs), as ... CW BET NBC ABC FOX LATV My Network TV Organizations: AIDS.gov AIDS Alliance for Children, Youth ...

  1. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... risky behavior. Drug misuse by any route (not just injection) can put a person at risk for ... The Learn the Link public service campaign is just one example of how NIDA continues to respond ...

  2. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... your Flickr, Pinterest, Instagram or other visually interesting page using pictures from NIDA ... Link campaign uses TV, print, and Web public service announcements (PSAs), as well as posters, ...

  3. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... of HIV infection in the United States. Drugs can change the way the brain works, disrupting the ... linked and referred to as "HIV/AIDS." HIV can be transferred between people if an infected person's ...

  4. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Researchers Medical & Health Professionals Patients & Families Parents & Educators Children & Teens Search Connect with NIDA : Facebook LinkedIn Twitter ... Network TV Organizations: AIDS.gov AIDS Alliance for Children, Youth and Families The American Academy of Child & ...

  5. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Link Videos NIDA and Scholastic - Heads Up NIDA Media Campaign Postcards Public Service Announcements Other Government Observances for Substance Abuse Education Contact the Press Office Meetings & Events Media Guide ...

  6. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... November 2017. How are Drug Misuse and HIV Related? Drug misuse and addiction have been linked with ... Campaign messages and materials were tested among various groups of young people, guiding the use of technology, ...

  7. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the Link campaign. This campaign shows teens and young adults that non-injection drug use and alcohol ... After the Party Posters: We have developed posters with our campaign ...

  8. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Learn the Link campaign uses TV, print, and Web public service announcements (PSAs), as well as posters, e-cards, and other tools to send the message to America's youth that ...

  9. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the Learn the Link message. Campaign messages and materials were tested among various groups of young people, guiding the use of technology, the discussion between friends, and the importance of family. For ...

  10. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Learn the Link with Videos We have numerous videos on our website that are available for your use to share on your social media accounts. About the Campaign Overview The Learn the ...

  11. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... increases brain viral load and activates natural killer cells in simian immunodeficiency ... out with friends? It’s a topic you can’t ignore. Learn the Link: http://1.usa.gov/ ...

  12. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... pictures from NIDA images. Visit the NIDA Flickr account for images. Share your favorite image! Check out ... your use to share on your social media accounts. About the Campaign Overview The Learn the Link ...

  13. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Prevention Recovery Substance Use and SUDs in LGBT Populations Treatment Trends & Statistics Women and Drugs Publications Search ... the link between drug misuse and HIV/AIDS, populations most at risk, trends in HIV/AIDS, and ...

  14. The D-region of the ionosphere

    International Nuclear Information System (INIS)

    Mitra, A.P.

    1978-01-01

    The D-region of the ionosphere, traditionally defined as the region of ionization below 100 km, is a link between the non-ionized stratosphere below and the dense plasma above. In it, minor neutral constituents play a dominant role and chemical reactions, both neutral and ionic, are dominant. It plays a very important role in the propagation of radiowaves at all frequencies below 30 MHz, and is particularly important in effecting communication over areas of the earth, such as polar regions, that are inaccessible to synchronous satellite links. Work which has been carried out on the neutral environment, D-region ionization, positive and negative ions found in the D-region, disturbances in the D-region (of solar origin and due to local dynamics or thermal changes), and the chemistry of the region, is considered. Possible future D-region studies are outlined. (UK)

  15. Linked data and user interaction

    CERN Document Server

    Cervone, H Frank

    2015-01-01

    This collection of research papers provides extensive information on deploying services, concepts, and approaches for using open linked data from libraries and other cultural heritage institutions. With a special emphasis on how libraries and other cultural heritage institutions can create effective end user interfaces using open, linked data or other datasets. These papers are essential reading for any one interesting in user interface design or the semantic web.

  16. Wireless data link for FBTR

    International Nuclear Information System (INIS)

    Sundararajan, M.K.; Prabhakara Rao, G.; Ilango Sambasivan, S.; Swaminathan, P.; Ramakrishna, P.V.

    2004-01-01

    This paper deals with the design and development of a wireless data link for transmission of block pile signals at the Fast Breeder Test Reactor (FBTR) of Indira Gandhi Center for Atomic Research (IGCAR). This link is to establish wireless connectivity, typically at RS232C rates, over distances of the order of 50 m, and is expected to operate under electrically hostile conditions. (author)

  17. Linking Ethics and Economic Growth

    DEFF Research Database (Denmark)

    Foss, Nicolai Juul

    2012-01-01

    Hunt (2012) builds on his work concerning ethics and resource-advantage theory to link personal ethical standards, societal norms, and economic growth but offers few details concerning the precise mechanisms that link ethics and growth. This comment suggests a number of such mechanisms – for exam...... – for example, the influence of prevailing ethical norms on the aggregate elasticity of substitution and, therefore, total factor productivity and growth....

  18. Manual de LinkedIn

    OpenAIRE

    Blázquez Sevilla, Alegría; Borrás Gené, Oriol

    2016-01-01

    Manual básico sobre la red profesional LinkedIn, donde se analiza la red y se explica a fondo cómo crear un perfil y gestionarlo. Incluye información sobre las diferentes secciones características de la red LinkedIn y ofrece consejos para la correcta gestión de un perfil, buscando su mejor rendimiento.

  19. Khovanov homology of graph-links

    Energy Technology Data Exchange (ETDEWEB)

    Nikonov, Igor M [M. V. Lomonosov Moscow State University, Faculty of Mechanics and Mathematics, Moscow (Russian Federation)

    2012-08-31

    Graph-links arise as the intersection graphs of turning chord diagrams of links. Speaking informally, graph-links provide a combinatorial description of links up to mutations. Many link invariants can be reformulated in the language of graph-links. Khovanov homology, a well-known and useful knot invariant, is defined for graph-links in this paper (in the case of the ground field of characteristic two). Bibliography: 14 titles.

  20. Genetic moderation of child maltreatment effects on depression and internalizing symptoms by serotonin transporter linked polymorphic region (5-HTTLPR), brain-derived neurotrophic factor (BDNF), norepinephrine transporter (NET), and corticotropin releasing hormone receptor 1 (CRHR1) genes in African American children.

    Science.gov (United States)

    Cicchetti, Dante; Rogosch, Fred A

    2014-11-01

    Genetic moderation of the effects of child maltreatment on depression and internalizing symptoms was investigated in a sample of low-income maltreated and nonmaltreated African American children (N = 1,096). Lifetime child maltreatment experiences were independently coded from Child Protective Services records and maternal report. Child depression and internalizing problems were assessed in the context of a summer research camp by self-report on the Children's Depression Inventory and adult counselor report on the Teacher Report Form. DNA was obtained from buccal cell or saliva samples and genotyped for polymorphisms of the following genes: serotonin transporter linked polymorphic region (5-HTTLPR), brain-derived neurotrophic factor (BDNF), norepinephrine transporter, and corticotropin releasing hormone receptor 1. Analyses of covariance with age and gender as covariates were conducted, with maltreatment status and respective polymorphism as main effects and their Gene × Environment (G × E) interactions. Maltreatment consistently was associated with higher Children's Depression Inventory and Teacher Report Form symptoms. The results for child self-report symptoms indicated a G × E interaction for BDNF and maltreatment. In addition, BDNF and triallelic 5-HTTLPR interacted with child maltreatment in a G × G × E interaction. Analyses for counselor report of child anxiety/depression symptoms on the Teacher Report Form indicated moderation of child maltreatment effects by triallelic 5-HTTLPR. These effects were elaborated based on variation in developmental timing of maltreatment experiences. Norepinephrine transporter was found to further moderate the G × E interaction of 5-HTTLPR and maltreatment status, revealing a G × G × E interaction. This G × G × E was extended by consideration of variation in maltreatment subtype experiences. Finally, G × G × E effects were observed for the co-action of BDNF and the corticotropin releasing hormone receptor 1

  1. LinkMind: link optimization in swarming mobile sensor networks.

    Science.gov (United States)

    Ngo, Trung Dung

    2011-01-01

    A swarming mobile sensor network is comprised of a swarm of wirelessly connected mobile robots equipped with various sensors. Such a network can be applied in an uncertain environment for services such as cooperative navigation and exploration, object identification and information gathering. One of the most advantageous properties of the swarming wireless sensor network is that mobile nodes can work cooperatively to organize an ad-hoc network and optimize the network link capacity to maximize the transmission of gathered data from a source to a target. This paper describes a new method of link optimization of swarming mobile sensor networks. The new method is based on combination of the artificial potential force guaranteeing connectivities of the mobile sensor nodes and the max-flow min-cut theorem of graph theory ensuring optimization of the network link capacity. The developed algorithm is demonstrated and evaluated in simulation.

  2. LinkMind: Link Optimization in Swarming Mobile Sensor Networks

    Directory of Open Access Journals (Sweden)

    Trung Dung Ngo

    2011-08-01

    Full Text Available A swarming mobile sensor network is comprised of a swarm of wirelessly connected mobile robots equipped with various sensors. Such a network can be applied in an uncertain environment for services such as cooperative navigation and exploration, object identification and information gathering. One of the most advantageous properties of the swarming wireless sensor network is that mobile nodes can work cooperatively to organize an ad-hoc network and optimize the network link capacity to maximize the transmission of gathered data from a source to a target. This paper describes a new method of link optimization of swarming mobile sensor networks. The new method is based on combination of the artificial potential force guaranteeing connectivities of the mobile sensor nodes and the max-flow min-cut theorem of graph theory ensuring optimization of the network link capacity. The developed algorithm is demonstrated and evaluated in simulation.

  3. Photoreactivities and thermal properties of psoralen cross-links

    International Nuclear Information System (INIS)

    Yeung, A.T.; Jones, B.K.; Chu, C.T.

    1988-01-01

    The authors have studied the photoreaction of 8-methoxypsoralen (8-MOP), 4,5',8-trimethylpsoralen (TMP), and 4'-(hydroxymethyl)-4,5',8-trimethylpsoralen (HMT) with a pair of 18-base-long oligonucleotides in which a 14-base region is complementary. Only one 5'TpA site, favored for both monoadduct and cross-link formation with psoralen, is present in this oligonucleotide pair. They have used this model system to demonstrate, for the first time, strand specificity in the photoreaction of psoralen with DNA. They found that the two types of cross-links which form at this site have large differences in thermal stabilities. In addition, the denaturation of each cross-links isomer duplex occurred in at least three stages, which can be visualized as three bands in thermal equilibrium under the conditions of a denaturing polyacrylamide gel. This novel observation suggests that there are several domains differing in thermal stability in a psoralen cross-link

  4. Links

    Directory of Open Access Journals (Sweden)

    Alessandra Russo

    2006-02-01

    Full Text Available La lista de enlaces ofrecida a continuación tiene como objetivo la creación de una base de datos sobre los principales sitios de interés para el estudio de la imagen (en America Latina y más allá. Se ha tratado de incluir una vasta gama de instituciones (museos, colecciones, institutos, representando sin embargo también a revistas, proyectos de investigación, y catálogos en línea. Sin tener la pretensión de ser exhaustiva, esta selección es evolutiva y se pone al día continuamente. MuseosI...

  5. Links

    OpenAIRE

    Alessandra Russo

    2006-01-01

    La lista de enlaces ofrecida a continuación tiene como objetivo la creación de una base de datos sobre los principales sitios de interés para el estudio de la imagen (en America Latina y más allá). Se ha tratado de incluir una vasta gama de instituciones (museos, colecciones, institutos), representando sin embargo también a revistas, proyectos de investigación, y catálogos en línea. Sin tener la pretensión de ser exhaustiva, esta selección es evolutiva y se pone al día continuamente. MuseosI...

  6. LINKS to NATIONAL WEATHER SERVICE MARINE FORECAST OFFICES

    Science.gov (United States)

    ; Organization Search Search Landlubber's forecast: "City, St" or zip code (Pan/Zoom for Marine) Search SERVICE MARINE FORECAST OFFICES (Click on the NWS Forecast Center/Office of interest to link to that Marine Forecasts in text form ) Coastal NWS Forecast Offices have regionally focused marine webpages

  7. The OceanLink Project

    Science.gov (United States)

    Narock, T.; Arko, R. A.; Carbotte, S. M.; Chandler, C. L.; Cheatham, M.; Finin, T.; Hitzler, P.; Krisnadhi, A.; Raymond, L. M.; Shepherd, A.; Wiebe, P. H.

    2014-12-01

    A wide spectrum of maturing methods and tools, collectively characterized as the Semantic Web, is helping to vastly improve the dissemination of scientific research. Creating semantic integration requires input from both domain and cyberinfrastructure scientists. OceanLink, an NSF EarthCube Building Block, is demonstrating semantic technologies through the integration of geoscience data repositories, library holdings, conference abstracts, and funded research awards. Meeting project objectives involves applying semantic technologies to support data representation, discovery, sharing and integration. Our semantic cyberinfrastructure components include ontology design patterns, Linked Data collections, semantic provenance, and associated services to enhance data and knowledge discovery, interoperation, and integration. We discuss how these components are integrated, the continued automated and semi-automated creation of semantic metadata, and techniques we have developed to integrate ontologies, link resources, and preserve provenance and attribution.

  8. The ALICE detector data link

    CERN Document Server

    Rubin, G; Csató, P; Dénes, E; Kiss, T; Meggyesi, Z; Sulyán, J; Vesztergombi, G; Eged, B; Gerencsér, I; Novák, I; Soós, C; Tarján, D; Telegdy, A; Tóth, N

    1999-01-01

    The ALICE detector data link has been designed to cover all the needs for data transfer between the detector and the data-acquisition system. It is a 1 Gbit/s, full-duplex, multi-purpose fibre optic link that can be used as a medium for the bi-directional transmission of data blocks between the front-end electronics and the data- acquisition system and also for the remote control and test of the front-end electronics, In this paper the concept, the protocol, the specific test tools, the prototypes of the detector data link and the read-out receiver card, their application in the ALICE-TPC test system and the integration with the DATE software are presented. The test results on the performance are also shown. (14 refs).

  9. AMHARA REGION

    African Journals Online (AJOL)

    This study investigates the contribution of school curriculum committee in facilitating and coordinating ... schools of Amhara Region' ln undertaking the study the descriptive survey method was used. .... pupil and the teacher are available. ... prepared for each level and grade has ..... the principals have the opinion that the.

  10. Atlantic Region

    NARCIS (Netherlands)

    Elands, B.H.M.; Bell, S.; Blok, J.

    2010-01-01

    Chapter 2 explores recreation and tourism practices in forest areas in the Atlantic region, which refers to the geographical area close to the North Sea and the Atlantic Ocean. The Atlantic countries described in this section are Belgium (Flanders and Wallonia), Denmark, Iceland, Ireland, the

  11. When He Said Linking, He Really Meant Linking

    Science.gov (United States)

    Chudnov, Daniel

    2009-01-01

    There are many reasons to improve web links, starting with their design. The author tends to think about "design" on the web in terms of two things: (1) graphic/industrial design; and (2) human usability. A nice, clean URI (uniform resource identifier) that does not change, is readable to humans, is amenable to common web behaviors such as…

  12. Versatile Link PLUS transceiver development

    International Nuclear Information System (INIS)

    Soós, C.; Détraz, S.; Olanterä, L.; Sigaud, C.; Troska, J.; Vasey, F.; Zeiler, M.

    2017-01-01

    The Versatile Link PLUS project targets the phase II upgrades of the ATLAS and CMS experiments. It will develop a radiation resistant optical link, operating at up to 10 Gb/s in the upstream and up to 5 Gb/s in the downstream directions with a smaller footprint and higher channel count than its predecessor. A low-profile package is being developed that allows volume production at reduced costs, but which nevertheless can be configured to suit the individual channel count needs of different detectors. This paper describes the development strategies and summarizes the status of the feasibility demonstration phase of the project.

  13. Value diversity and regional economic development

    NARCIS (Netherlands)

    Beugelsdijk, Sjoerd; Klasing, Mariko; Milionis, Petros

    2018-01-01

    We investigate the link between culture and regional economic development within European countries. Considering a variety of cultural values, we provide evidence that it is the degree of diversity in these values at the regional level that strongly correlates with economic performance rather than

  14. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... and what to do to counter these trends. Online Resources NIDA for Teens Web site : This Web ... projects/learn-link-drugs-hiv . 120x90 460x80 486x60 Social Media Send the message to young people and ...

  15. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... women can pass HIV to their babies during pregnancy, delivery, and breastfeeding. HIV destroys a certain kind ... at: http://www.drugabuse.gov/news-events/public-education-projects/learn-link-drugs-hiv . 120x90 460x80 486x60 ...

  16. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... projects/learn-link-drugs-hiv . 120x90 460x80 486x60 Social Media Send the message to young people and ... following television networks, organizations, educational institutions, magazines, newspapers, companies, events, and radio stations for helping to raise ...

  17. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... AIDS : This site provides information both for health care providers and for Veterans and the public. Send the Message Overview Please help us send the message to young people and to parents, teachers, and the media about the link between ...

  18. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Topics Addiction Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and ... the Link campaign. This campaign shows teens and young adults that non-injection drug use and alcohol use ...

  19. Linking Customer Interaction and Innovation

    DEFF Research Database (Denmark)

    Foss, Nicolai Juul; Laursen, Keld; Pedersen, Torben

    2011-01-01

    employees for sharing and acquiring knowledge, and high levels of delegation of decision rights. In this paper, six hypotheses were developed and tested on a data set of 169 Danish firms drawn from a 2001 survey of the 1,000 largest firms in Denmark. A key result is that the link from customer knowledge...

  20. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... News NIDA Notes Podcasts E-Newsletters Public Education Projects Contact the Press Office Meetings & Events Media Guide ... Search Share Print Home » News & Events » Public Education Projects » Learn the Link - Drugs and HIV Learn the ...

  1. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... once can have serious health consequences. We also work to reach parents and teachers—influential figures in the lives of young people—with the Learn the Link message. Campaign messages and materials were tested among various groups of young people, guiding the use of technology, ...

  2. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available Skip to main content En español Researchers Medical & Health Professionals Patients & Families Parents & Educators Children & Teens Search Connect with NIDA : Facebook LinkedIn Twitter YouTube Flickr RSS Menu Home Drugs of Abuse Commonly Abused Drugs Charts ...

  3. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... projects/learn-link-drugs-hiv . 120x90 460x80 486x60 Social Media Send the message to young people and ... gov/1kSfBiz ​ Mention your friends, colleagues, or other organizations in your tweets to spread the word even ...

  4. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... projects/learn-link-drugs-hiv . 120x90 460x80 486x60 Social Media Send the message to young people and ... available for your use to share on your social media accounts. About the Campaign Overview The Learn ...

  5. Linking to MedlinePlus

    Science.gov (United States)

    ... want to link patients or healthcare providers from electronic health record (EHR) systems to relevant MedlinePlus information, use MedlinePlus ... updates Subscribe to RSS Follow us Disclaimers Copyright Privacy Accessibility Quality Guidelines Viewers & Players MedlinePlus Connect for ...

  6. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Health Professionals Patients & Families Parents & Educators Children & Teens Search Connect with NIDA : Facebook LinkedIn Twitter YouTube Flickr ... Populations Treatment Trends & Statistics Women and Drugs Publications Search Publications Orderable DrugFacts Research Reports Mind Over Matter ...

  7. What Is Linked Historical Data?

    NARCIS (Netherlands)

    Meroño-Peñuela, Albert; Hoekstra, Rinke; Janowicz, Krzysztof; Schlobach, Stefan; Lambrix, Patrick; Hyvönen, Eero

    2014-01-01

    Datasets that represent historical sources are relative new- comers in the Linked Open Data (LOD) cloud. Following the standard LOD practices for publishing historical sources raises several questions: how can we distinguish between RDF graphs of primary and secondary sources? Should we treat

  8. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available Skip to main content En español Researchers Medical & Health Professionals Patients & Families Parents & Educators Children & Teens Search Connect with NIDA : Facebook LinkedIn Twitter YouTube Flickr RSS Menu Home Drugs of Abuse ...

  9. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Educators Children & Teens Search Connect with NIDA : Facebook LinkedIn Twitter YouTube Flickr RSS Menu Home Drugs of ... Director of the National Institute on Drug Abuse, Dr. Nora D. Volkow. Message from the Director The ...

  10. Simmondsia chinensis (Link) Schneid.: jojoba

    Science.gov (United States)

    Susan E. Meyer

    2008-01-01

    The Simmondsiaceae (jojoba family), has only 1 genus, Simmondsia, which consists of only 1 species, jojoba - S. chinensis (Link) Schneid. Once considered an isolated member of the box family (Buxaceae), jojoba is now regarded as sufficiently distinct to be placed in its own family. Jojoba is found from coastal and cis-montane southern California east to central Arizona...

  11. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... young people and to parents, teachers, and the media about the link between drug misuse and HIV. We have produced a set of multicultural public service announcements (PSAs) that use text messaging as a means of communication. The "Text Message" PSA features two young girls ...

  12. Is Wikipedia link structure different?

    NARCIS (Netherlands)

    Kamps, J.; Koolen, M.; Baeza-Yates, R.; Boldi, P.; Ribeiro-Neto, B.; Cambazoglu, B.B.

    2010-01-01

    In this paper, we investigate the difference between Wikipedia and Web link structure with respect to their value as indicators of the relevance of a page for a given topic of request. Our experimental evidence is from two IR test-collections: the .GOV collection used at the TREC Web tracks and the

  13. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... gov/1kSfBiz ​ Mention your friends, colleagues, or other organizations in your tweets to spread the word even ... 1kSfBiz #LearntheLink Mention your friends, colleagues, or other organizations in your tweets to spread the word even ...

  14. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the News NIDA Notes Podcasts E-Newsletters Public Education Projects Contact the Press Office Meetings & Events Media ... Plan Search Share Print Home » News & Events » Public Education Projects » Learn the Link - Drugs and HIV Learn ...

  15. Current Leads, Links and Buses

    CERN Document Server

    Ballarino, A

    2014-01-01

    Electrical transfer from a room temperature power source to a superconducting system is done via conventional or superconducting current leads and superconducting buses or links. The principles of optimization of these devices are presented, with emphasis on the cryogenic, electrical, and superconductor related aspects that drive choices for a system.

  16. New links in the family

    NARCIS (Netherlands)

    Marion Duimel; Jos de Haan

    2007-01-01

    Original title: Nieuwe links in het gezin. Virtually all families with teenagers have at least one computer with an Internet connection, often more. Teenagers spend much of their daily lives on the Internet. They use it to communicate with each other, to do their schoolwork, to meet new

  17. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... projects/learn-link-drugs-hiv . 120x90 460x80 486x60 Social Media Send the message to young people and ... the Party" "Text Message" NIDA Home Site Map Accessibility Privacy FOIA(NIH) Working at NIDA FAQs Contact ...

  18. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Educators Children & Teens Search Connect with NIDA : Facebook LinkedIn Twitter YouTube Flickr RSS Menu Home Drugs of ... In animal studies, methamphetamine has been shown to increase the amount of HIV in brain cells 1 . ...

  19. Linking numbers and variational method

    International Nuclear Information System (INIS)

    Oda, I.; Yahikozawa, S.

    1989-09-01

    The ordinary and generalized linking numbers for two surfaces of dimension p and n-p-1 in an n dimensional manifold are derived. We use a variational method based on the properties of topological quantum field theory in order to derive them. (author). 13 refs, 2 figs

  20. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... and Drugs Publications Search Publications Orderable DrugFacts Research Reports Mind Over Matter Science of Addiction Funding Funding ... transmitting HIV/AIDS or other infectious diseases. Research Reports: HIV/AIDS : Explores the link between drug misuse ...

  1. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV to their babies during pregnancy, delivery, and breastfeeding. HIV destroys a certain kind of white blood ... at: http://www.drugabuse.gov/news-events/public-education-projects/learn-link-drugs-hiv . 120x90 460x80 486x60 ...

  2. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... she went to a party and under the influence of drugs and alcohol engaged in risky sexual ... learn-link-drugs-hiv . 120x90 460x80 486x60 Social Media Send the message to young people and to ...

  3. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... projects/learn-link-drugs-hiv . 120x90 460x80 486x60 Social Media Send the message to young people and to ... available for your use to share on your social media accounts. About the Campaign Overview The Learn the ...

  4. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Send the Message . Get the Facts What are HIV and AIDS? HIV (human immunodeficiency virus) is the virus that ... AIDS) are often linked and referred to as "HIV/AIDS." HIV can be transferred between people if an ...

  5. Current Leads, Links and Buses

    Energy Technology Data Exchange (ETDEWEB)

    Ballarino, A [European Organization for Nuclear Research, Geneva (Switzerland)

    2014-07-01

    Electrical transfer from a room temperature power source to a superconducting system is done via conventional or superconducting current leads and superconducting buses or links. The principles of optimization of these devices are presented, with emphasis on the cryogenic, electrical, and superconductor related aspects that drive choices for a system.

  6. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV > Learn the Link campaign. This campaign shows teens and young adults that non-injection drug use and alcohol use can lead to poor decision making, which can result in risky sexual behaviors and HIV infection. Although the characters are fictional, ...

  7. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... at: http://www.drugabuse.gov/news-events/public-education-projects/learn-link-drugs-hiv . 120x90 460x80 486x60 Social Media Send the message to young people and to parents, teachers, and the media ...

  8. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... in the spread of HIV infection in the United States. Drugs can change the way the brain works, disrupting the parts of the brain that people use to weigh risks and benefits when making decisions. This page connects you to information about the link between drug misuse and HIV ...

  9. X-linked congenital panhypopituitarism.

    Science.gov (United States)

    Schimke, R N; Spaulding, J J; Hollowell, J G

    1971-05-01

    Two half brothers with panhypopituitary dwarfism are reported who have the same mother and different, unrelated fathers. The subject of hereditary panhypopituitarism is reviewed briefly. It is concluded that there are at least two forms of hereditary panhypopituitary dwarfism, one of which may be X-linked.

  10. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... and what to do to counter these trends. Online Resources NIDA for Teens Web site : This Web ... at: http://www.drugabuse.gov/news-events/public-education-projects/learn-link-drugs-hiv . 120x90 460x80 486x60 ...

  11. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain ... projects/learn-link-drugs-hiv . 120x90 460x80 486x60 Social Media Send the message to young people and ...

  12. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Tobacco/Nicotine and E-Cigs Other Drugs Related Topics Addiction Science Adolescent Brain Comorbidity College-Age & Young ... parties or hanging out with friends? It’s a topic you can’t ignore. Learn the Link: http:// ...

  13. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Bath Salts) Tobacco/Nicotine and E-Cigs Other Drugs Related Topics Addiction Science Adolescent Brain Comorbidity College-Age & Young Adults ... 2017. How are Drug Misuse and HIV Related? Drug misuse and addiction have been linked with HIV/AIDS since the ...

  14. Compulsive exercise: links, risks and challenges faced

    Directory of Open Access Journals (Sweden)

    Lichtenstein MB

    2017-03-01

    Full Text Available Mia Beck Lichtenstein,1 Cecilie Juul Hinze,2 Bolette Emborg,3 Freja Thomsen,2 Simone Daugaard Hemmingsen4 1Department of Psychology, Faculty of Health Sciences, University of Southern Denmark, 2Research Unit for Telepsychiatry and E-mental Health, Mental Health Services in the Region of Southern Denmark, Odense, 3Department of Public Health, Aarhus University, Aarhus, 4Research Unit, Child and Adolescent Psychiatry, Mental Health Services in the Region of Southern Denmark, Odense, Denmark Abstract: Compulsive exercise is a condition described since 1970s. It is characterized by a craving for physical training, resulting in uncontrollable excessive exercise behavior with harmful consequences, such as injuries and impaired social relations. It has not been accepted as a mental disorder in either International Classification of Diseases or Diagnostic and Statistical Manual of Mental Disorders. The aim of this literature review was to critically examine the research on links (comorbidity, risks (negative consequences, and challenges faced (problems in a treatment context. This review found that compulsive exercise is associated with eating disorder pathology, perfectionism, neuroticism, narcissism, and obsessive compulsive traits. The most prominent negative consequences were injuries, social impairment, and depression, but more research is needed to uncover the potential dysfunction resulting from compulsive exercise. As the condition is not recognized as a psychiatric disorder, studies on treatment interventions are sparse. Problems with compliance have been reported; therefore, motivational interviewing has been proposed as a treatment approach, in combination with cognitive behavioral therapy. This review summarizes and discusses findings on links/comorbidity, risks/negative consequences, and treatment challenges. We suggest that future studies should pay attention to both prevention and counseling in sports settings, where compulsive exercise

  15. Smart POI: Open and linked spatial data

    Science.gov (United States)

    Cerba, Otakar; Berzins, Raitis; Charvat, Karel; Mildorf, Tomas

    2016-04-01

    The Smart Point of Interest (SPOI) represents an unique seamless spatial data set based on standards recommended for Linked and open data, which are supported by scientist and researchers as well as by several government authorities and European Union. This data set developed in cooperation of partners of SDI4Apps project contains almost 24 millions points of interest focused mainly on tourism, natural features, transport or citizen services. The SPOI data covers almost all countries and territories over the world. It is created as a harmonized combination of global data resources (selected points from OpenStreetMap, Natural Earth and GeoNames.org) and several local data sets (for example data published by the Citadel on the Move project, data from Posumavi region in the Czech Republic or experimental ontologies developed in the University of West Bohemia including ski regions in Europe or historical sights in Rome). The added value of the SDI4Apps approach in comparison to other similar solutions consists in implementation of linked data approach (several objects are connected to DBpedia or GeoNames.org), using of universal RDF format, using of standardized and respected properties or vocabularies (for example FOAF or GeoSPARQL) and development of the completely harmonized data set with uniform data model and common classification (not only a copy of original resources). The SPOI data is published as SPARQL endpoint as well as in the map client. The SPOI dataset is a specific set of POIs which could be "a data fuel" for applications and services related to tourism, local business, statistics or landscape monitoring. It can be used also as a background data layer for thematic maps.

  16. Interaction region

    International Nuclear Information System (INIS)

    Anon.

    1982-01-01

    The Interaction Region Group addressed the basic questions of how to collide the SLC beams, how to maximize and monitor the luminosity, and how to minimize the detector backgrounds at the interaction region. In practice, five subgroups evolved to study these questions. The final focus group provided three alternative designs to acheive the 1 to 2 micron beam spot size required by the SLC, as well as studying other problems including: eta, eta' matching from the collider arcs, the implementation of soft bends near the interaction region, beam emittance growth, and magnet tolerances in the final focus. The beam position monitor group proposed two devices, a strip line monitor, and a beamstrahlung monitor, to bring the beams into collision. The luminosity monitor group reviewed the possible QED processes that would be insensitive to weak interaction (Z 0 ) effects. The beam dumping group proposed locations for kicker and septum magnets in the final focus that would achieve a high dumping efficiency and would meet the desired beam tolerances at the Moller scattering target in the beam dump line. Working with the Polarization Group, the Moller experiment was designed into the beam dump beam line. A beam dump was proposed that would maintain radiation backgrounds (penetrating muons) at acceptible levels. The detector backgrounds group proposed soft-bend and masking configurations to shield the detector from synchrotron radiation from the hard/soft bends and from the final focus quadrupoles and evaluated the effectiveness of these designs for the three final focus optics designs. Backgrounds were also estimated from: large angle synchrotron radiation, local and distant beam-gas interactions, 2-photon interactions, and from neutrons and backscattered photons from the beamstrahlung dump

  17. LinkED: A Novel Methodology for Publishing Linked Enterprise Data

    Directory of Open Access Journals (Sweden)

    Shreyas Suresh Rao

    2017-01-01

    Full Text Available Semantic Web technologies have redefined and strengthened the Enterprise-Web interoperability over the last decade. Linked Open Data (LOD refers to a set of best practices that empower enterprises to publish and interlink their data using existing ontologies on the World Wide Web. Current research in LOD focuses on expert search, the creation of unified information space and augmentation of core data from an enterprise context. However, existing approaches for publication of enterprise data as LOD are domain-specific, ad-hoc and suffer from lack of uniform representation across domains. The paper proposes a novel methodology called LinkED that contributes towards LOD literature in two ways: (a streamlines the publishing process through five stages of cleaning, triplification, interlinking, storage and visualization; (b addresses the latest challenges in LOD publication, namely: inadequate links, inconsistencies in the quality of the dataset and replicability of the LOD publication process. Further, the methodology is demonstrated via the publication of digital repository data as LOD in a university setting, which is evaluated based on two semantic standards: Five-Star model and data quality metrics. Overall, the paper provides a generic LOD publication process that is applicable across various domains such as healthcare, e-governance, banking, and tourism, to name a few.

  18. Transition region

    International Nuclear Information System (INIS)

    Jordan, C.

    1977-01-01

    The Glossary is designed to be a technical dictionary that will provide solar workers of various specialties, students, other astronomers and theoreticians with concise information on the nature and the properties of phenomena of solar and solar-terrestrial physics. Each term, or group of related terms, is given a concise phenomenological and quantitative description, including the relationship to other phenomena and an interpretation in terms of physical processes. The references are intended to lead the non-specialist reader into the literature. This section deals with: transition region; di-electronic recombination; intersystem or intercombination lines; satellite lines; grazing-incidence optics; and crystal spectrometers. (B.R.H.)

  19. The importance of link evidence in Wikipedia

    NARCIS (Netherlands)

    Kamps, J.; Koolen, M.

    2008-01-01

    Wikipedia is one of the most popular information sources on the Web. The free encyclopedia is densely linked. The link structure in Wikipedia differs from the Web at large: internal links in Wikipedia are typically based on words naturally occurring in a page, and link to another semantically

  20. Collagen cross linking: Current perspectives

    Directory of Open Access Journals (Sweden)

    Srinivas K Rao

    2013-01-01

    Full Text Available Keratoconus is a common ectatic disorder occurring in more than 1 in 1,000 individuals. The condition typically starts in adolescence and early adulthood. It is a disease with an uncertain cause and its progression is unpredictable, but in extreme cases, vision deteriorates and can require corneal transplant surgery. Corneal collagen cross-linking (CCL with riboflavin (C3R is a recent treatment option that can enhance the rigidity of the cornea and prevent disease progression. Since its inception, the procedure has evolved with newer instrumentation, surgical techniques, and is also now performed for expanded indications other than keratoconus. With increasing experience, newer guidelines regarding optimization of patient selection, the spectrum of complications and their management, and combination procedures are being described. This article in conjunction with the others in this issue, will try and explore the uses of collagen cross-linking (CXL in its current form.

  1. X-linked Alport syndrome

    DEFF Research Database (Denmark)

    Jais, Jean Philippe; Knebelmann, Bertrand; Giatras, Iannis

    2003-01-01

    Alport syndrome (AS) is a type IV collagen hereditary disease characterized by progressive hematuric nephritis, hearing loss, and ocular changes. Mutations in the COL4A5 collagen gene are responsible for the more common X-linked dominant form of the disease characterized by much less severe disease...... in girls and women. A "European Community Alport Syndrome Concerted Action" (ECASCA) group was established to delineate the Alport syndrome phenotype in each gender and to determine genotype-phenotype correlations in a large number of families. Data concerning 329 families, 250 of them with an X...... to increase after the age of 60 yr in women. Because of the absence of genotype-phenotype correlation and the large intrafamilial phenotypic heterogeneity, early prognosis of the disease in X-linked Alport syndrome carriers remains moot. Risk factors for developing renal failure have been identified...

  2. Using turbocodes on optical links

    Directory of Open Access Journals (Sweden)

    Glenn Claes

    2006-04-01

    Full Text Available The fast evolving telecommunication world is permanently in search for faster and better communication links. On one hand, turbo codes are like a dream come true. Due to their amazing performance, they have become the reference in the word of error detecting and correcting codes. On the other hand, broadband transmission channels like optical fibres can meet the need for higher transmission velocity. In this paper therefore we will bring these two elements together and thus the performance of turbocodes on optical links will be studied. First the turbocode will be optimised throughout an individual analysis of each of its design parameters. Moreover it wil be shown that turbocodes have much better performance than the well known Reed-Solomon codes. Finally we will show that the 8Bit/10Bit code, which is required to comply with the Gigabit Ethernet standard, becomes superfluous when working with turbocodes. All tests were carried out on multimode graded-index glass fibres.

  3. The Øresund Link

    DEFF Research Database (Denmark)

    Møller, Jacob Steen

    "Øresundsbron" is the combined bridge and tunnel connecting Denmark and Sweden adjacent to Copenhagen. Øresundsbron was built and is operated by a consortium owned jointly by the Danish and Swedish states. The Link was inaugurated 1 July 2000 by the Queen of Denmark and the King of Sweden. The 16......-km link across the Sound could potentially impact the water exchange between the Baltic Sea and the North Sea, and the dredging activities during construction were a threat to the local marine environment. The public interest in the environmental issues together with a pro-active environmental policy...... of hydrodynamic modelling, on line monitoring and access to all environmental information through a GIS based information system. The public attitude towards the project in general and the environmental impact in particular shifted from a very sceptical one at the beginning of the project to a very positive one...

  4. [Linking learning theory with practice].

    Science.gov (United States)

    Ávalos-Carranza, María Teresa; Amador-Olvera, Eric; Zerón-Gutiérrez, Lydia

    2016-01-01

    It is often said that it is easier to learn what is observed and practiced on a daily basis; to the need to effectively link theory with practice considered in the process of teaching and learning, many strategies have been developed to allow this process to be carried out in a more efficiently maner. It is, therefore, very important to recognize that an appropriate teacher/student relationship is essential for students to acquire the skills and abilities required.

  5. Managing Your Team's Weakest Link.

    Science.gov (United States)

    Hills, Laura

    2015-01-01

    Do you have a poor-performing employee on your medical practice team? If so, you're not alone. Unfortunately, this is a problem that many medical practice managers face. This article describes the best strategies for managing your team's weakest link. It explores common yet very difficult circumstances that cause low employee performance and that test the patience, heart, and skills of a practice manager. It guides readers through a process of self-discovery to determine whether their negative biases or grudges may be causing employees to perform poorly. It suggests several possible other reasons for weak employee performance, including problems with the job, practice, leadership, communication, and fit between the employee and the job. This article also suggests the best strategy for communicating concerns about performance to the weakest-link employee. It offers guidance to practice managers about protecting their time and energy when handling a poor performer. It provides a simple formula for calculating the cost of a low-performing employee, 10 possible personal reasons for the employee's poor work performance, specific questions to ask to uncover the reasons for poor performance, and an eight-rule strategy for confronting poor performance effectively. Finally, this article offers practice managers a practical strategy for handling resistance from their weakest link, illustrated with a sample dialogue.

  6. Linking DC together with TRSL

    DEFF Research Database (Denmark)

    Haxthausen, Anne; Yong, Xia

    1999-01-01

    In this talk we present a method for linking the Duration Calculus together with the Timed RAISE Specification Language. Duration Calculus (DC) [ZHR91] is an interval-based real time logic, which can be used naturally in capturing and eliciting users' real time requirements in the form of constra......In this talk we present a method for linking the Duration Calculus together with the Timed RAISE Specification Language. Duration Calculus (DC) [ZHR91] is an interval-based real time logic, which can be used naturally in capturing and eliciting users' real time requirements in the form.......TRSL is a real-time extension of the RAISE Specification Language (RSL) [Rlg92] which together with its associated method [Rmg95]and tools has shown to be very useful in the industrial development of software systems. Therefore, a promising approach for the development of real-time systemscould be to use DC...... for high-level specifications of real-time requirementsand TRSL for specifying real-time implementations in the form of timed communicating concurrent processes.In order to link DC and TRSL together in a well-founded way, we formally define what it means for a TRSL process to satisfy a DC requirement...

  7. Linking GHG Emission Trading Systems and Markets

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-07-01

    Several different types of links are possible between different GHG-mitigation systems. These include: Linking two or more emission trading schemes so that emissions trading can occur both within and between different schemes ('direct links'); and Linking emission trading systems to registries/mechanisms and systems that generate offsets from project based mechanisms or from direct purchases/transfers of AAUs ('indirect links').

  8. A new nonsyndromic X-linked sensorineural hearing impairment linked to Xp21.2

    Energy Technology Data Exchange (ETDEWEB)

    Lalwani, A.K.; Brister, J.R.; Fex, J.; Grundfast, K.M.; Pikus, A.T.; Ploplis, B.; San Agustin, T.; Skarka, H.; Wilcox, E.R. [National Institutes of Health, Bethesda, MD (United States)

    1994-10-01

    X-linked deafness is a rare cause of hereditary hearing impairment. We have identified a family with X-linked dominant sensorineural hearing impairment, characterized by incomplete penetrance and variable expressivity in carrier females, that is linked to the Xp21.2, which contains the Duchenne muscular dystrophy (DMD) locus. The auditory impairment in affected males was congenital, bilateral, profound, sensorineural, affecting all frequencies, and without evidence of radiographic abnormality of the temporal bone. Adult carrier females manifested bilateral, mild-to-moderate high-frequency sensorineural hearing impairment of delayed onset during adulthood. Eighteen commercially available polymorphic markers from the X chromosome, generating a 10-15-cM map, were initially used for identification of a candidate region. DXS997, located within the DMD gene, generated a two-point LOD score of 2.91 at {theta} = 0, with every carrier mother heterozygous at this locus. Recombination events at DXS992 (located within the DMD locus, 3{prime} to exon 50 of the dystrophin gene) and at DXS1068 (5{prime} to the brain promoter of the dystrophin gene) were observed. No recombination events were noted with the following markers within the DMD locus: 5{prime}DYS II, intron 44, DXS997, and intron 50. There was no clinical evidence of Duchenne or Becker muscular dystrophy in any family member. It is likely that this family represents a new locus on the X chromosome, which when mutated results in nonsyndromic sensorineural hearing loss and is distinct from the heterogeneous group of X-linked hearing losses that have been previously described. 57 refs., 6 figs., 1 tab.

  9. Refinement of the localization of the X-linked ocular albinism gene

    NARCIS (Netherlands)

    Bergen, A. A.; Zijp, P.; Schuurman, E. J.; Bleeker-Wagemakers, E. M.; Apkarian, P.; van Ommen, G. J.

    1993-01-01

    Although physical and genetic mapping studies assigned the X-linked ocular albinism gene to Xp22.3, the exact gene order in this region is still unclear. We present additional genetic mapping data concerning X-linked ocular albinism that suggests the consensus order Xpter-STS-DXS237-KAL-(OA1,

  10. Regional Renewable Energy Cooperatives

    Science.gov (United States)

    Hazendonk, P.; Brown, M. B.; Byrne, J. M.; Harrison, T.; Mueller, R.; Peacock, K.; Usher, J.; Yalamova, R.; Kroebel, R.; Larsen, J.; McNaughton, R.

    2014-12-01

    We are building a multidisciplinary research program linking researchers in agriculture, business, earth science, engineering, humanities and social science. Our goal is to match renewable energy supply and reformed energy demands. The program will be focused on (i) understanding and modifying energy demand, (ii) design and implementation of diverse renewable energy networks. Geomatics technology will be used to map existing energy and waste flows on a neighbourhood, municipal, and regional level. Optimal sites and combinations of sites for solar and wind electrical generation (ridges, rooftops, valley walls) will be identified. Geomatics based site and grid analyses will identify best locations for energy production based on efficient production and connectivity to regional grids and transportation. Design of networks for utilization of waste streams of heat, water, animal and human waste for energy production will be investigated. Agriculture, cities and industry produce many waste streams that are not well utilized. Therefore, establishing a renewable energy resource mapping and planning program for electrical generation, waste heat and energy recovery, biomass collection, and biochar, biodiesel and syngas production is critical to regional energy optimization. Electrical storage and demand management are two priorities that will be investigated. Regional scale cooperatives may use electric vehicle batteries and innovations such as pump storage and concentrated solar molten salt heat storage for steam turbine electrical generation. Energy demand management is poorly explored in Canada and elsewhere - our homes and businesses operate on an unrestricted demand. Simple monitoring and energy demand-ranking software can easily reduce peaks demands and move lower ranked uses to non-peak periods, thereby reducing the grid size needed to meet peak demands. Peak demand strains the current energy grid capacity and often requires demand balancing projects and

  11. Phase-modulated radio over fiber multimode links.

    Science.gov (United States)

    Gasulla, Ivana; Capmany, José

    2012-05-21

    We present the first experimental demonstration of a phase-modulated MMF link implementing high-frequency digital transmission in a cost-effective solution based on direct detection. Successful subcarrier transmission of QPSK, 16-QAM and 64-QAM data channels for bit rates up to 120 Mb/s through a 5 km MMF link is achieved over the microwave region comprised between 6 and 20 GHz. The overall capacity of the proposed approach can be further increased by properly accommodating more passband channels in the operative frequency range determined by the phase-to-intensity conversion process provided by the dispersive nature of the optical fiber. In this sense, our results show the possibility of achieving an aggregate bit rate per length product of 144 Gb/s · km and confirm, in consequence, the possibility of broadband phase-modulated radio over fiber transmission through MMF links suitable for multichannel SCM signal distribution.

  12. Linking DC together with TRSL

    DEFF Research Database (Denmark)

    Haxthausen, Anne Elisabeth; Yong, X.

    2000-01-01

    in a method for real-time developments. An operational semantics with behavior is specified for TRSL. It is defined what its means for a TRSL process to satisfy a DC requirement, and a method for verifying whether the satisfaction relation holds or not is provided. Our contribution also demonstrates a general......Duration Calculus (DC) is an interval-based real-time logic, which can be used in capturing and eliciting users' real-time requirements. The Timed RAISE Specification Language (TRSL) is an extension of the RAISE Specification Language with real-time features. This paper links DC and TRSL together...

  13. X-linked Alport syndrome

    DEFF Research Database (Denmark)

    Jais, J P; Knebelmann, B; Giatras, I

    2000-01-01

    Alport syndrome (AS) is a type IV collagen hereditary disease characterized by the association of progressive hematuric nephritis, hearing loss, and, frequently, ocular changes. Mutations in the COL4A5 collagen gene are responsible for the more common X-linked dominant form of the disease....... Considerable allelic heterogeneity has been observed. A "European Community Alport Syndrome Concerted Action" has been established to delineate accurately the AS phenotype and to determine genotype-phenotype correlations in a large number of families. Data concerning 329 families, 250 of them with an X...

  14. O-linked glycosylation of retroviral envelope gene products

    Energy Technology Data Exchange (ETDEWEB)

    Pinter, A.; Honnen, W.J. (Public Health Research Institute of the City of New York Inc., NY (USA))

    1988-03-01

    Treatment of ({sup 3}H)glucosamine-labeled Friend mink cell focus-forming virus (FrMCF) gp70 with excess peptide:N-glycanase F (PNGase F) resulted in removal of the expected seven N-linked oligosaccharide chains; however, approximately 10% of the glucosamine label was retained in the resulting 49,000-M{sub r} (49K) product. For ({sup 3}H)mannose-labeled gp70, similar treatment led to removal of all the carbohydrate label from the protein. Prior digestion of the PNGase F-treated gp70 with neuraminidase resulted in an addition size shift, and treatment with O-glycanase led to the removal of almost all of the PNGase F-resistant sugars. These results indicate that gp70 possesses sialic acid-containing O-linked oligosaccharides. Analysis of intracellular env precursors demonstrated that O-linked sugars were present in gPr90{sup env}, the polyprotein intermediate which contains complex sugars, but not in the primary translation product, gPr80{sup env}, and proteolytic digestion studies allowed localization of the O-linked carbohydrates to a 10K region near the center of the gp70 molecule. similar substituents were detected on the gp70s of ecotropic and xenotropic murine leukemia viruses and two subgroups of feline leukemia virus, indicting that O-linked glycosylation is a conserved feature of retroviral env proteins.

  15. O-linked glycosylation of retroviral envelope gene products

    International Nuclear Information System (INIS)

    Pinter, A.; Honnen, W.J.

    1988-01-01

    Treatment of [ 3 H]glucosamine-labeled Friend mink cell focus-forming virus (FrMCF) gp70 with excess peptide:N-glycanase F (PNGase F) resulted in removal of the expected seven N-linked oligosaccharide chains; however, approximately 10% of the glucosamine label was retained in the resulting 49,000-M r (49K) product. For [ 3 H]mannose-labeled gp70, similar treatment led to removal of all the carbohydrate label from the protein. Prior digestion of the PNGase F-treated gp70 with neuraminidase resulted in an addition size shift, and treatment with O-glycanase led to the removal of almost all of the PNGase F-resistant sugars. These results indicate that gp70 possesses sialic acid-containing O-linked oligosaccharides. Analysis of intracellular env precursors demonstrated that O-linked sugars were present in gPr90 env , the polyprotein intermediate which contains complex sugars, but not in the primary translation product, gPr80 env , and proteolytic digestion studies allowed localization of the O-linked carbohydrates to a 10K region near the center of the gp70 molecule. similar substituents were detected on the gp70s of ecotropic and xenotropic murine leukemia viruses and two subgroups of feline leukemia virus, indicting that O-linked glycosylation is a conserved feature of retroviral env proteins

  16. Microprocessor-controlled CAMAC data link module

    International Nuclear Information System (INIS)

    Potter, J.M.

    1978-05-01

    Communication between the central control computer and remote, satellite data-acquisition/control stations at the Clinton P. Anderson Meson Physics Facility (LAMPF) is presently accomplished through the use of CAMAC-based Data Link modules. With the advent of the microprocessor, a new philosophy for digital data communications has evolved. Data Link modules containing microprocessor controllers provide link management and communication network protocol through algorithms executed in the Data Link microprocessor. 13 figures

  17. Website Policies / Important Links | Data Explorer

    Science.gov (United States)

    Website Policies / Important Links Javascript Not Enabled OSTI Security Website Policies and Important ) Publication Date (oldest first) Close Clear All Find DOE Data Explorer Website Policies / Important Links Science | Office of Scientific and Technical Information Website Policies / Important Links * Site Map

  18. Propensity to Click on Suspicious Links

    DEFF Research Database (Denmark)

    Sudzina, Frantisek; Pavlicek, Antonin

    2017-01-01

    such behavior. Big Five Inventory traits (extraversion, agreeableness, conscientiousness, neuroticism, openness to experience) and narcissism were used. Impact of openness to experience was significant at 0.05 level, and of narcissism 0.1 level. Significance of remaining independent variables was above 0.......1. Openness to experience was linked positively linked to responsible behavior, narcissism was negatively linked....

  19. Impact of Packet Sampling on Link Dimensioning

    NARCIS (Netherlands)

    Schmidt, R.D.O.; Sadre, R.; Sperotto, A.; Berg, H. van den; Pras, A.

    2015-01-01

    Link dimensioning is used by network operators to properly provision the capacity of their network links. Proposed methods for link dimensioning often require statistics, such as traffic variance, that need to be calculated from packet-level measurements. In practice, due to increasing traffic

  20. Impact of packet sampling on link dimensioning

    NARCIS (Netherlands)

    de Oliveira Schmidt, R.; Stadler, R.; Sadre, R.; Sperotto, Anna; van den Berg, Hans Leo; Pras, Aiko

    Link dimensioning is used by network operators to properly provision the capacity of their network links. Proposed methods for link dimensioning often require statistics, such as traffic variance, that need to be calculated from packet-level measurements. In practice, due to increasing traffic

  1. Production and Consumption of University Linked Data

    Science.gov (United States)

    Zablith, Fouad; Fernandez, Miriam; Rowe, Matthew

    2015-01-01

    Linked Data increases the value of an organisation's data over the web by introducing explicit and machine processable links at the data level. We have adopted this new stream of data representation to produce and expose existing data within The Open University (OU) as Linked Data. We present in this paper our approach for producing the data,…

  2. Restricted linking of emissions trading systems

    NARCIS (Netherlands)

    Schneider, Lambert; Lazarus, Michael; Lee, Carrie; Asselt, van Harro

    2017-01-01

    With over 17 emissions trading systems (ETSs) now in place across four continents, interest in linking ETSs is growing. Linking ETSs offers economic, political, and administrative benefits. It also faces major challenges. Linking can affect overall ambition, financial flows, and the location and

  3. Link Anchors in Images: Is there Truth?

    NARCIS (Netherlands)

    Aly, Robin; McGuinness, Kevin; Kleppe, Martijn; Ordelman, Roeland J.F.; O'Connor, Noel; de Jong, Franciska M.G.

    2012-01-01

    While automatic linking in text collections is well understood, little is known about links in images. In this work, we investigate two aspects of anchors, the origin of a link, in images: 1) the requirements of users for such anchors, e.g. the things users would like more information on, and 2)

  4. Data links for the EOS TPC

    International Nuclear Information System (INIS)

    Bieser, F.; Jones, R.; McParland, C.

    1991-01-01

    This paper reports on the design and performance of high speed data links and slower configuration control links used between the EOS TPC detector and the data processing electronics. Data rates of 5 MBytes/link are maintained over 30m with optical isolation. Pedestal subtraction, hit detection, and data reordering are performed online

  5. Data links for the EOS TPC

    International Nuclear Information System (INIS)

    Bieser, F.; Jones, R.; McParland, C.

    1990-10-01

    We report on the design and performance of high speed data links and slower configuration control links used between the EOS TPC detector and the data processing electronics. Data rates of 5MBytes/s/link are maintained over 30m with optical isolation. Pedestal subtraction, hit detection, and data reordering are performed online. 3 refs., 1 fig

  6. Property Testing on Linked Lists

    DEFF Research Database (Denmark)

    Afshani, Peyman; Matulef, Kevin; Wilkinson, Bryan Thomas

    2013-01-01

    We define a new property testing model for algorithms that do not have arbitrary query access to the input, but must instead traverse it in a manner that respects the underlying data structure in which it is stored. In particular, we consider the case when the underlying data structure is a linked...... list, and the testing algorithm is allowed to either sample randomly from the list, or walk to nodes that are adjacent to those already visited. We study the well-known monotonicity testing problem in this model, and show that (n13) queries are both necessary and sufficient to distinguish whether...... a list is sorted (monotone increasing) versus a constant distance from sorted. Our bound is strictly greater than the (logn) queries required in the standard testing model, that allows element access indexed by rank, and strictly less than the (n12) queries required by a weak model that only allows...

  7. Linking brain, mind and behavior.

    Science.gov (United States)

    Makeig, Scott; Gramann, Klaus; Jung, Tzyy-Ping; Sejnowski, Terrence J; Poizner, Howard

    2009-08-01

    Cortical brain areas and dynamics evolved to organize motor behavior in our three-dimensional environment also support more general human cognitive processes. Yet traditional brain imaging paradigms typically allow and record only minimal participant behavior, then reduce the recorded data to single map features of averaged responses. To more fully investigate the complex links between distributed brain dynamics and motivated natural behavior, we propose the development of wearable mobile brain/body imaging (MoBI) systems that continuously capture the wearer's high-density electrical brain and muscle signals, three-dimensional body movements, audiovisual scene and point of regard, plus new data-driven analysis methods to model their interrelationships. The new imaging modality should allow new insights into how spatially distributed brain dynamics support natural human cognition and agency.

  8. Link between physics and biology

    International Nuclear Information System (INIS)

    Zaider, M.; Brenner, D.J.; Hall, E.J.; Kliauga, P.

    1988-01-01

    In the general causative chain: radiation physics-radiation chemistry - radiobiology - cancer treatment, physics, the initiating and therefore cardinal agent, continues to play the role of the poor relation. The main reason for this state of affairs rests with the fact that most models of radiation action - the actual link between physics and biology - make very little or no use of information concerning the radiation field: they are simply convenient vehicles for describing a large body of radiobiological data with analytical expressions containing a minimum number of parameters. In spite of their practical usefulness such models will not be further considered here. It is a reasonable assertion that the main goal of radiation biophysics is to elucidate the mechanisms of radiation action on biological entities

  9. Security Concepts for Satellite Links

    Science.gov (United States)

    Tobehn, C.; Penné, B.; Rathje, R.; Weigl, A.; Gorecki, Ch.; Michalik, H.

    2008-08-01

    The high costs to develop, launch and maintain a satellite network makes protecting the assets imperative. Attacks may be passive such as eavesdropping on the payload data. More serious threat are active attacks that try to gain control of the satellite, which may lead to the total lost of the satellite asset. To counter these threats, new satellite and ground systems are using cryptographic technologies to provide a range of services: confidentiality, entity & message authentication, and data integrity. Additionally, key management cryptographic services are required to support these services. This paper describes the key points of current satellite control and operations, that are authentication of the access to the satellite TMTC link and encryption of security relevant TM/TC data. For payload data management the key points are multi-user ground station access and high data rates both requiring frequent updates and uploads of keys with the corresponding key management methods. For secure satellite management authentication & key negotiation algorithms as HMAC-RIPEMD160, EC- DSA and EC-DH are used. Encryption of data uses algorithms as IDEA, AES, Triple-DES, or other. A channel coding and encryption unit for payload data provides download data rates up to Nx250 Mbps. The presented concepts are based on our experience and heritage of the security systems for all German MOD satellite projects (SATCOMBw2, SAR-Lupe multi- satellite system and German-French SAR-Lupe-Helios- II systems inter-operability) as well as for further international (KOMPSAT-II Payload data link system) and ESA activities (TMTC security and GMES).

  10. Track with overlapping links for dry coal extrusion pumps

    Science.gov (United States)

    Saunders, Timothy; Brady, John D

    2014-01-21

    A chain for a particulate material extrusion pump includes a plurality of links, each of the plurality of links having a link body and a link ledge, wherein each link ledge of the plurality of links at least partially overlaps the link body of an adjacent one of the plurality of links.

  11. Notch1 and 4 Signaling Responds to an Increasing Vascular Wall Shear Stress in a Rat Model of Arteriovenous Malformations

    Directory of Open Access Journals (Sweden)

    Jian Tu

    2014-01-01

    Full Text Available Notch signaling is suggested to promote the development and maintenance of cerebral arteriovenous malformations (AVMs, and an increasing wall shear stress (WSS contributes to AVM rupture. Little is known about whether WSS impacts Notch signaling, which is important for understanding the angiogenesis of AVMs. WSS was measured in arteriovenous fistulas (AVF surgically created in 96 rats at different time points over a period of 84 days. The expression of Notch receptors 1 and 4 and their ligands, Delta1 and 4, Jagged1, and Notch downstream gene target Hes1 was quantified in “nidus” vessels. The interaction events between Notch receptors and their ligands were quantified using proximity ligation assay. There was a positive correlation between WSS and time (r=0.97; P<0.001. The expression of Notch receptors and their ligands was upregulated following AVF formation. There was a positive correlation between time and the number of interactions between Notch receptors and their ligands aftre AVF formation (r=0.62, P<0.05 and a positive correlation between WSS and the number of interactions between Notch receptors and their ligands (r=0.87, P<0.005. In conclusion, an increasing WSS may contribute to the angiogenesis of AVMs by activation of Notch signaling.

  12. Social attitudes and regional inequalities

    Directory of Open Access Journals (Sweden)

    Vinko Muštra

    2014-03-01

    Full Text Available As the budgets of the European Union (EU become tighter, the questions about the effectiveness of EU’s expenditure, especially the most important parts such as Cohesion policy, are hotly debated. The aim of this paper is to examine whether the presence of social attitudes may influence the effectiveness of EU budget expenditure, measured by the level of regional inequalities. The analysis starts by focusing on individuals’ attitudes towards income from their own effort and income which is derived from other people’s effort, having in mind that individual actions depend on their attitudes. The next step establishes the link between the income from other people’s effort with the re-distributive dimension of the EU budget, considering that different attitudes among individuals in the EU could lead to significant differences in effectiveness of this redistributive policy among European regions and, consequently, diverse regional inequalities. Empirical research uses data for 27 EU countries observed over two waves of European Value Surveys: 1999-2000 (Wave 1 and 2008–2009 (Wave 2. The results indicate a significant role of social attitudes for regional inequalities, which raises the question of the appropriateness of simplification and uniform regional policy instruments in solving EU regional problems.

  13. Link prediction with node clustering coefficient

    Science.gov (United States)

    Wu, Zhihao; Lin, Youfang; Wang, Jing; Gregory, Steve

    2016-06-01

    Predicting missing links in incomplete complex networks efficiently and accurately is still a challenging problem. The recently proposed Cannistrai-Alanis-Ravai (CAR) index shows the power of local link/triangle information in improving link-prediction accuracy. Inspired by the idea of employing local link/triangle information, we propose a new similarity index with more local structure information. In our method, local link/triangle structure information can be conveyed by clustering coefficient of common-neighbors directly. The reason why clustering coefficient has good effectiveness in estimating the contribution of a common-neighbor is that it employs links existing between neighbors of a common-neighbor and these links have the same structural position with the candidate link to this common-neighbor. In our experiments, three estimators: precision, AUP and AUC are used to evaluate the accuracy of link prediction algorithms. Experimental results on ten tested networks drawn from various fields show that our new index is more effective in predicting missing links than CAR index, especially for networks with low correlation between number of common-neighbors and number of links between common-neighbors.

  14. Hacking 360 Link: A hybrid approach

    Directory of Open Access Journals (Sweden)

    John Durno

    2012-10-01

    Full Text Available When the University of Victoria Libraries switched from a locally-hosted link resolver (SFX to a vendor-hosted link resolver (360Link, new strategies were required to effectively integrate the vendor-hosted link resolver with the Libraries' other systems and services. Custom javascript is used to add links to the 360Link page; these links then point at local PHP code running on UVic servers, which can then redirect to appropriate local service or display a form directly. An open source PHP OpenURL parser class is announced. Consideration is given to the importance of maintaining open protocols and standards in the transition to vendor-hosted services.

  15. A Simple Forecasting Model Linking Macroeconomic Policy to Industrial Employment Demand.

    Science.gov (United States)

    Malley, James R.; Hady, Thomas F.

    A study detailed further a model linking monetary and fiscal policy to industrial employment in metropolitan and nonmetropolitan areas of four United States regions. The model was used to simulate the impacts on area and regional employment of three events in the economy: changing real gross national product (GNP) via monetary policy, holding the…

  16. Linking Diversity and Disparity Measures

    Directory of Open Access Journals (Sweden)

    Sahadeb Sarkar

    2012-07-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman","serif";} The purpose of this paper is to examine links between the diversity measures (Patil and Taillie 1982 and the disparity measures (Lindsay 1994, quantities apparently developed for somewhat different purposes. We demonstrate that numerous diversity measures satisfying all the desirable criteria mentioned by Patil and Taillie can be defined by the generating functions of certain disparities and the associated residual adjustment functions. This provides the statistician and the ecologist a wide class of flexible indices for the statistical measurement of diversity.

  17. Returning "Region" to World Regional Geography

    Science.gov (United States)

    Rees, Peter W.; Legates, Margaret

    2013-01-01

    World regional geography textbooks rarely focus on the process of region formation, despite frequent calls to reincorporate a regional approach to teaching global geography. An instructional strategy using problem-based learning in a small honors section of a large world regional geography course is described. Using a hypothetical scenario…

  18. Corrosion analysis in mooring chain links; Analise de corrosao em elos de amarras

    Energy Technology Data Exchange (ETDEWEB)

    Leal, Silvia N.; Pereira, Marcos V. [Pontificia Univ. Catolica do Rio de Janeiro, RJ (Brazil). Dept. de Ciencia dos Materiais e Metalurgia; Costa, Luis C. [PETROBRAS S.A., Rio de Janeiro, RJ (Brazil). Centro de Pesquisas; Motta, Sergio H. [Brasilamarras - Companhia Brasileira de Amarras, Niteroi, RJ (Brazil)

    2004-07-01

    The purpose of this work was to characterize the localized corrosion phenomenon in the weld region of offshore mooring chain links type ORQ. In this sense, a number of chain links were selected after finishing their projected life time without corrosion signs (chains without corrosion) as well as chain links which showed a reduced life time caused by localized corrosion (chains with corrosion). In the sequence, electrochemistry tests evaluated the corrosion susceptibility of the different regions of the weld joint. The results showed that the heat affected zone concerning the chains with corrosion was the anodic region, with high corrosion rate, while the same region on the not corroded chains was the cathodic one, with low corrosion rate. (author)

  19. The Femarnbelt Tunnel: Regional Development Perspectives

    DEFF Research Database (Denmark)

    Matthiessen, Christian Wichmann; Lundhus, Peter

    2011-01-01

    structures (bridges/ tunnels) spanning international waterways. They concentrate traffic flows and create strong transport corridors and are the basis of new regional development regimes. In early 2011, following almost two years of extensive work on different conceptual designs for the fixed link...

  20. Development of regional growth centres and impact on regional growth: A case study of Thailand’s Northeastern region

    Directory of Open Access Journals (Sweden)

    Nattapon Sang-arun

    2013-01-01

    Full Text Available This study investigates the spatial economic structure and inequality in Thailand at the national and regional levels, with a particular focus on the Northeastern region in the period from 1987 to 2007. The study has three main points: 1 examination of the economic structure and inequality at the national level and in the Northeastern region according to the Theil index, 2 determination of regional growth centres and satellite towns by using growth pole theory as a conceptual framework and incorporating spatial interaction analysis and 3 analysis of the relationship between regional growth centres and satellite towns with regard to the impact on growth and inequality. The results show that the Northeastern region is definitely the lagging region in the nation, by both gross domestic product (GDP and gross regional product (GRP per capita. It was therefore selected for a case study. Spatial analysis identified Nakhon Ratchasima, Khon Kaen, Udon Thani and Ubon Ratchathani as regional growth centres. Each of them has its own sphere of influence (or satellite towns, and the total area of regional growth centres and satellite towns are classified as sub-regions. The development of regional growth centres has a direct impact on sub-regional economic growth through economic and social relationships: urbanisation, industrial development, per capita growth, the number of higher educational institutes and so on. However, such growth negatively correlates with economic equality among the provinces in a sub-region. The inequality trend is obviously on an upswing. This study suggests that industrial links between regional growth centres and their satellite towns should be improved in order for regional growth centre development to have a consistently desirable effect on both economic growth and equality. Such a strong process means that the growth of regional growth centres will spread, leading to the development of their surrounding areas.

  1. Exploring the Link between Nucleosome Occupancy and DNA Methylation

    Directory of Open Access Journals (Sweden)

    Cecilia Lövkvist

    2018-01-01

    Full Text Available Near promoters, both nucleosomes and CpG sites form characteristic spatial patterns. Previously, nucleosome depleted regions were observed upstream of transcription start sites and nucleosome occupancy was reported to correlate both with CpG density and the level of CpG methylation. Several studies imply a causal link where CpG methylation might induce nucleosome formation, whereas others argue the opposite, i.e., that nucleosome occupancy might influence CpG methylation. Correlations are indeed evident between nucleosomes, CpG density and CpG methylation—at least near promoter sites. It is however less established whether there is an immediate causal relation between nucleosome occupancy and the presence of CpG sites—or if nucleosome occupancy could be influenced by other factors. In this work, we test for such causality in human genomes by analyzing the three quantities both near and away from promoter sites. For data from the human genome we compare promoter regions with given CpG densities with genomic regions without promoters but of similar CpG densities. We find the observed correlation between nucleosome occupancy and CpG density, respectively CpG methylation, to be specific to promoter regions. In other regions along the genome nucleosome occupancy is statistically independent of the positioning of CpGs or their methylation levels. Anti-correlation between CpG density and methylation level is however similarly strong in both regions. On promoters, nucleosome occupancy is more strongly affected by the level of gene expression than CpG density or CpG methylation—calling into question any direct causal relation between nucleosome occupancy and CpG organization. Rather, our results suggest that for organisms with cytosine methylation nucleosome occupancy might be primarily linked to gene expression, with no strong impact on methylation.

  2. Materializing the web of linked data

    CERN Document Server

    Konstantinou, Nikolaos

    2015-01-01

    This book explains the Linked Data domain by adopting a bottom-up approach: it introduces the fundamental Semantic Web technologies and building blocks, which are then combined into methodologies and end-to-end examples for publishing datasets as Linked Data, and use cases that harness scholarly information and sensor data. It presents how Linked Data is used for web-scale data integration, information management and search. Special emphasis is given to the publication of Linked Data from relational databases as well as from real-time sensor data streams. The authors also trace the transformation from the document-based World Wide Web into a Web of Data. Materializing the Web of Linked Data is addressed to researchers and professionals studying software technologies, tools and approaches that drive the Linked Data ecosystem, and the Web in general.

  3. Dynamic Link Inclusion in Online PDF Journals

    OpenAIRE

    Probets, Steve; Brailsford, David; Carr, Les; Hall, Wendy

    1998-01-01

    Two complementary de facto standards for the publication of electronic documents are HTML on theWorldWideWeb and Adobe s PDF (Portable Document Format) language for use with Acrobat viewers. Both these formats provide support for hypertext features to be embedded within documents. We present a method, which allows links and other hypertext material to be kept in an abstract form in separate link databases. The links can then be interpreted or compiled at any stage and applied, in the correct ...

  4. Cascade of links in complex networks

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Yeqian; Sun, Bihui [Department of Management Science, School of Government, Beijing Normal University, 100875 Beijing (China); Zeng, An, E-mail: anzeng@bnu.edu.cn [School of Systems Science, Beijing Normal University, 100875 Beijing (China)

    2017-01-30

    Cascading failure is an important process which has been widely used to model catastrophic events such as blackouts and financial crisis in real systems. However, so far most of the studies in the literature focus on the cascading process on nodes, leaving the possibility of link cascade overlooked. In many real cases, the catastrophic events are actually formed by the successive disappearance of links. Examples exist in the financial systems where the firms and banks (i.e. nodes) still exist but many financial trades (i.e. links) are gone during the crisis, and the air transportation systems where the airports (i.e. nodes) are still functional but many airlines (i.e. links) stop operating during bad weather. In this letter, we develop a link cascade model in complex networks. With this model, we find that both artificial and real networks tend to collapse even if a few links are initially attacked. However, the link cascading process can be effectively terminated by setting a few strong nodes in the network which do not respond to any link reduction. Finally, a simulated annealing algorithm is used to optimize the location of these strong nodes, which significantly improves the robustness of the networks against the link cascade. - Highlights: • We propose a link cascade model in complex networks. • Both artificial and real networks tend to collapse even if a few links are initially attacked. • The link cascading process can be effectively terminated by setting a few strong nodes. • A simulated annealing algorithm is used to optimize the location of these strong nodes.

  5. Cascade of links in complex networks

    International Nuclear Information System (INIS)

    Feng, Yeqian; Sun, Bihui; Zeng, An

    2017-01-01

    Cascading failure is an important process which has been widely used to model catastrophic events such as blackouts and financial crisis in real systems. However, so far most of the studies in the literature focus on the cascading process on nodes, leaving the possibility of link cascade overlooked. In many real cases, the catastrophic events are actually formed by the successive disappearance of links. Examples exist in the financial systems where the firms and banks (i.e. nodes) still exist but many financial trades (i.e. links) are gone during the crisis, and the air transportation systems where the airports (i.e. nodes) are still functional but many airlines (i.e. links) stop operating during bad weather. In this letter, we develop a link cascade model in complex networks. With this model, we find that both artificial and real networks tend to collapse even if a few links are initially attacked. However, the link cascading process can be effectively terminated by setting a few strong nodes in the network which do not respond to any link reduction. Finally, a simulated annealing algorithm is used to optimize the location of these strong nodes, which significantly improves the robustness of the networks against the link cascade. - Highlights: • We propose a link cascade model in complex networks. • Both artificial and real networks tend to collapse even if a few links are initially attacked. • The link cascading process can be effectively terminated by setting a few strong nodes. • A simulated annealing algorithm is used to optimize the location of these strong nodes.

  6. Estimating Rain Attenuation In Satellite Communication Links

    Science.gov (United States)

    Manning, R. M.

    1991-01-01

    Attenuation computed with help of statistical model and meteorological data. NASA Lewis Research Center Satellite Link Attenuation Model (SLAM) program QuickBASIC computer program evaluating static and dynamic statistical assessment of impact of rain attenuation on communication link established between Earth terminal and geosynchronous satellite. Application in specification, design, and assessment of satellite communication links for any terminal location in continental United States. Written in Microsoft QuickBASIC.

  7. The GDP-Energy Link

    International Nuclear Information System (INIS)

    Bourdaire, J.M.

    2000-01-01

    The analysis of primary or final energy consumptions as a function of total regional GDP, aggregated on the basis of purchasing power parities, does not bring significant results for the transition economies because of the poor quality of their data. Conversely, for the market economies, such an analysis highlights the regularity of the trends as long as final prices remain unchanged, the nature of energy shock impacts and the close relationship between the energy intensity and the level of final prices. French energy evolutions are similar and lead to question what the benefits brought by energy efficiency policies are. These benefits seem to be qualitative only, i.e. more comfort and well-being, with no indication of lesser energy consumption as long as the final prices remain unchanged. The conclusion is three-fold: importance of prices reflecting all costs, choice of supply policies which can shoulder energy shocks, and need to continue and deepen the energy debate. (authors)

  8. Fast Link Adaptation for MIMO-OFDM

    DEFF Research Database (Denmark)

    Jensen, Tobias Lindstrøm; Kant, Shashi; Wehinger, Joachim

    2010-01-01

    We investigate link-quality metrics (LQMs) based on raw bit-error-rate, effective signal-to-interference-plus-noise ratio, and mutual information (MI) for the purpose of fast link adaptation (LA) in communication systems employing orthogonal frequency-division multiplexing and multiple-input–mult......We investigate link-quality metrics (LQMs) based on raw bit-error-rate, effective signal-to-interference-plus-noise ratio, and mutual information (MI) for the purpose of fast link adaptation (LA) in communication systems employing orthogonal frequency-division multiplexing and multiple...

  9. LINKING STATE, UNIVERSITY AND BUSINESS IN NICARAGUA

    Directory of Open Access Journals (Sweden)

    Máximo Andrés Rodríguez Pérez

    2015-07-01

    Full Text Available In Nicaragua levels Linking state, university and business are low, Nicaraguan universities have initiated communication strategies with the state and the private sector. The idiosyncrasies of its citizens favor this link. The entailment policies formalize the communications and information networks. Universities have a key role in building models and organizations that provide alternatives to economic development. Linking the university with the environment, generating virtuous circles, where companies achieve greater competitiveness, the state, higher taxes and public stability, universities generate new knowledge. This article analyzes the strategies linking U-E- E that can be applied in Nicaragua, to strengthen and achieve positive developments in the country.

  10. Linking Orbital, Field, and Laboratory Analyses of Dolerites in the McMurdo Dry Valleys of Antarctica: Terrestrial Studies and Planetary Applications

    Science.gov (United States)

    Salvatore, M. R.; Mustard, J. F.; Head, J. W.; Marchant, D. R.; Wyatt, M. B.; Seeley, J.

    2012-03-01

    Primary igneous and secondary alteration signatures can be resolved using orbital spectroscopy over mafic regions of the McMurdo Dry Valleys. We assess the nature of these signatures and their link to surface stability and regional microclimates.

  11. An edge-centric perspective on the human connectome: link communities in the brain.

    Science.gov (United States)

    de Reus, Marcel A; Saenger, Victor M; Kahn, René S; van den Heuvel, Martijn P

    2014-10-05

    Brain function depends on efficient processing and integration of information within a complex network of neural interactions, known as the connectome. An important aspect of connectome architecture is the existence of community structure, providing an anatomical basis for the occurrence of functional specialization. Typically, communities are defined as groups of densely connected network nodes, representing clusters of brain regions. Looking at the connectome from a different perspective, instead focusing on the interconnecting links or edges, we find that the white matter pathways between brain regions also exhibit community structure. Eleven link communities were identified: five spanning through the midline fissure, three through the left hemisphere and three through the right hemisphere. We show that these link communities are consistently identifiable and investigate the network characteristics of their underlying white matter pathways. Furthermore, examination of the relationship between link communities and brain regions revealed that the majority of brain regions participate in multiple link communities. In particular, the highly connected and central hub regions showed a rich level of community participation, supporting the notion that these hubs play a pivotal role as confluence zones in which neural information from different domains merges. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  12. X linked exudative vitreoretinopathy: clinical features and genetic linkage analysis.

    Science.gov (United States)

    Fullwood, P; Jones, J; Bundey, S; Dudgeon, J; Fielder, A R; Kilpatrick, M W

    1993-03-01

    A four generation family in which familial exudative vitreoretinopathy is inherited as an X linked condition is described. Essentially the condition is one of abnormal vascularisation and signs at birth are those of a retinopathy superficially resembling retinopathy of prematurity, retinal folds, or, in advanced cases, enophthalmos or even phthisis. Prognosis depends on the progression of the retinal changes. The family members, including seven affected males and five obligate carrier females, have been types for 20 DNA markers, and linkage analysis suggests a gene locus either at Xq21.3 or at Xp11. As the latter region includes the locus for the gene for Norrie disease, it is possible that this and X linked vitreoretinopathy are allelic. We can further speculate that the differences in severity of the clinical manifestations are dependent only upon the timing of the insult.

  13. Regional alternative transportation evaluation report - Region 4

    Science.gov (United States)

    2013-08-15

    The U.S. Fish and Wildlife Service (FWS) and the U.S. Department of Transportation (DOT) Volpe Center (Volpe Center) conducted a regional alternative transportation evaluation (RATE) in Region 4, which is comprised of Alabama, Arkansas, Florida, Geor...

  14. Regional alternative transportation evaluation report - region 2

    Science.gov (United States)

    2012-03-01

    The U.S. Fish and Wildlife Service (FWS) and the U.S. Department of Transportation (DOT) Volpe : Center (Volpe Center) conducted a regional alternative transportation evaluation (RATE) in Region 2, : which is comprised of Arizona, Oklahoma, New Mexic...

  15. Regional alternative transportation evaluation report - region 5

    Science.gov (United States)

    2011-11-14

    The U.S. Fish and Wildlife Service (FWS) and the U.S. Department of Transportation (DOT) Volpe Center (Volpe Center) conducted a regional alternative transportation evaluation (RATE) in Region 3, which is comprised of Illinois, Indiana, Iowa, Michiga...

  16. Why transmission is still the critical link

    Energy Technology Data Exchange (ETDEWEB)

    Flynn, V. [ESBI Alberta Ltd., Calgary, AB (Canada)

    2002-07-01

    This paper describes the important role that transmission plays in the competitive electric power industry in North America and around the world. In the past several years the transmission sector has experienced a lack of investment, congestion on transmission networks, merchant transmission development, and the creation of Regional Transmission Organizations (RTOs). The transmission grid is central to the reliability of the entire electricity system. It also plays a vital role in promoting efficient markets in electricity. The author discusses the consequences of inadequate investment to this critical link within the power industry. He also discusses how much investment is needed, and the challenges and solutions to building an infrastructure. The integrated electric system and the electricity industry in Alberta is very different from those in the United Sates, but the issues facing the industry are the same. The challenge is the sharp increase in the number of system access requests by new generators combined with the difficulties in siting new transmission lines. There are 17,000 km of transmission lines in Alberta, at voltages ranging from 69 kV to 500 kV. There are also connections between neighbouring provinces. The transmission lines have a value of C$1.5 billion. Since there have been no major additions to the transmission grid since the mid-1980s, significant investments in the coming years will have a disproportionate impact on the cost of transmission. Two merchant transmission projects have been proposed. The first will enhance transfer of electricity between Alberta and Saskatchewan by 150 MW, and the second is proposed to be a 1,500 MW, 500 kV DC line from the Fort McMurray area to the Pacific Northwest. 5 figs.

  17. S-LINK, a data link interface specification for the LHC era

    International Nuclear Information System (INIS)

    Bij, H.C. van der; McLaren, R.A.; Boyle, O.

    1996-01-01

    In the Technical Proposals for ATLAS, CMS and ALICE there is a requirement for several thousand data links. Although there is an obvious need for standardization, this seems difficult to achieve as the links run at different speeds, over different distances and have various constraints of power consumption, size and radiation hardness. An additional complication is that today we cannot decide which will be the most cost effective technology for the implementation of the final links. Furthermore, we must allow designers of boards at each end of the link, for example readout electronics and input buffers, to work in parallel with the development of the links. The S-LINK is a new concept which should provide the benefits of standardization without the limitations. The S-LINK specification defines, at both ends of the link, a simple FIFO-like user interface which remains independent of the technology used to implement the physical link. The physical link provides transfer of event data and control words, error detection, optional flow control and test facilities. This paper describes the S-LINK specification and gives examples of the use of the S-LINK, the physical links being designed, and the test equipment that is being developed

  18. A cosmic ray-climate link and cloud observations

    Directory of Open Access Journals (Sweden)

    Dunne Eimear M.

    2012-11-01

    Full Text Available Despite over 35 years of constant satellite-based measurements of cloud, reliable evidence of a long-hypothesized link between changes in solar activity and Earth’s cloud cover remains elusive. This work examines evidence of a cosmic ray cloud link from a range of sources, including satellite-based cloud measurements and long-term ground-based climatological measurements. The satellite-based studies can be divided into two categories: (1 monthly to decadal timescale analysis and (2 daily timescale epoch-superpositional (composite analysis. The latter analyses frequently focus on sudden high-magnitude reductions in the cosmic ray flux known as Forbush decrease events. At present, two long-term independent global satellite cloud datasets are available (ISCCP and MODIS. Although the differences between them are considerable, neither shows evidence of a solar-cloud link at either long or short timescales. Furthermore, reports of observed correlations between solar activity and cloud over the 1983–1995 period are attributed to the chance agreement between solar changes and artificially induced cloud trends. It is possible that the satellite cloud datasets and analysis methods may simply be too insensitive to detect a small solar signal. Evidence from ground-based studies suggests that some weak but statistically significant cosmic ray-cloud relationships may exist at regional scales, involving mechanisms related to the global electric circuit. However, a poor understanding of these mechanisms and their effects on cloud makes the net impacts of such links uncertain. Regardless of this, it is clear that there is no robust evidence of a widespread link between the cosmic ray flux and clouds.

  19. Radiation-induced linking reactions in polyethylene

    International Nuclear Information System (INIS)

    Zoepfl, F.J.

    1983-01-01

    Three types of measurements are reported relating to chemical reactions in polyethylene induced by ionizing radiation: 1) viscometric and low-angle laser light scattering measurements to determine the effect of a radical scavenger on the yield of links; 2) calorimetric measurements to determine the effect of radiation-induced linking on the melting behavior of polyethylene; and 3) high-resolution solution carbon 13 nuclear magnetic resonance (NMR) spectrometry measurements to determine the nature of the links and the method of their formation. The NMR results present the first direct detection of radiation-induced long-chain branching (Y links) in polyethylene, and place an apparent upper limit on the yield of H-shaped crosslinks that are formed when polyethylene is irradiated to low absorbed doses. The effect of radiation-induced linking on the melting behavior of polyethylene was examined using differential scanning calorimetry (DSC). It was found that radiation-induced links do not change the heat of fusion of polythylene crystals, but decrease the melt entropy and increase the fold surface free energy per unit area of the crystals. The carbon 13 NMR results demonstrate that long-chain branches (Y links) are formed much more frequently than H-shaped crosslinks at low absorbed doses. The Y links are produced by reactions of alkyl free radicals with terminal vinyl groups in polyethylene

  20. Using linked data in Learning Analytics

    NARCIS (Netherlands)

    Mathieu, d'Aquin; Stefan, Dietze; Eelco, Herder; Drachsler, Hendrik; Davide, Taibi

    2014-01-01

    d’Aquin, M., Dietze, S., Herder, E., Drachsler, H., & Taibi, D. (2014). Using linked data in learning analytics. eLearning Papers. Nr. 36/2. ISSN: 1887-1542. http://www.openeducationeuropa.eu/en/article/Using-linked-data-in-Learning-Analytics?paper=134810