Sample records for nhp6-delta cells display

  1. Chromatin-mediated transcriptional regulation by the yeast architectural factors NHP6A and NHP6B

    DEFF Research Database (Denmark)

    Moreira, José Manuel Alfonso; Holmberg, S


    The Saccharomyces cerevisiae NHP6A and NHP6B proteins are chromatin architectural factors, functionally and structurally related to the mammalian high mobility group (HMG)-1 and -2 proteins, a family of non-sequence-specific DNA binding proteins. nhp6a nhp6b mutants have various morphological...

  2. Dopaminergic neurotoxicant 6-OHDA induces oxidative damage through proteolytic activation of PKC{delta} in cell culture and animal models of Parkinson's disease

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    Latchoumycandane, Calivarathan; Anantharam, Vellareddy; Jin, Huajun; Kanthasamy, Anumantha; Kanthasamy, Arthi, E-mail:


    The neurotoxicant 6-hydroxydopamine (6-OHDA) is used to investigate the cellular and molecular mechanisms underlying selective degeneration of dopaminergic neurons in Parkinson's disease (PD). Oxidative stress and caspase activation contribute to the 6-OHDA-induced apoptotic cell death of dopaminergic neurons. In the present study, we sought to systematically characterize the key downstream signaling molecule involved in 6-OHDA-induced dopaminergic degeneration in cell culture and animal models of PD. Treatment of mesencephalic dopaminergic neuronal N27 cells with 6-OHDA (100 {mu}M) for 24 h significantly reduced mitochondrial activity and increased cytosolic cytochrome c, followed by sequential activation of caspase-9 and caspase-3. Co-treatment with the free radical scavenger MnTBAP (10 {mu}M) significantly attenuated 6-OHDA-induced caspase activities. Interestingly, 6-OHDA induced proteolytic cleavage and activation of protein kinase C delta (PKC{delta}) was completely suppressed by treatment with a caspase-3-specific inhibitor, Z-DEVD-FMK (50 {mu}M). Furthermore, expression of caspase-3 cleavage site-resistant mutant PKC{delta}{sup D327A} and kinase dead PKC{delta}{sup K376R} or siRNA-mediated knockdown of PKC{delta} protected against 6-OHDA-induced neuronal cell death, suggesting that caspase-3-dependent PKC{delta} promotes oxidative stress-induced dopaminergic degeneration. Suppression of PKC{delta} expression by siRNA also effectively protected N27 cells from 6-OHDA-induced apoptotic cell death. PKC{delta} cleavage was also observed in the substantia nigra of 6-OHDA-injected C57 black mice but not in control animals. Viral-mediated delivery of PKC{delta}{sup D327A} protein protected against 6-OHDA-induced PKC{delta} activation in mouse substantia nigra. Collectively, these results strongly suggest that proteolytic activation of PKC{delta} is a key downstream event in dopaminergic degeneration, and these results may have important translational value for

  3. TAF6delta controls apoptosis and gene expression in the absence of p53.

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    Emmanuelle Wilhelm

    Full Text Available BACKGROUND: Life and death decisions of metazoan cells hinge on the balance between the expression of pro- versus anti-apoptotic gene products. The general RNA polymerase II transcription factor, TFIID, plays a central role in the regulation of gene expression through its core promoter recognition and co-activator functions. The core TFIID subunit TAF6 acts in vitro as an essential co-activator of transcription for the p53 tumor suppressor protein. We previously identified a splice variant of TAF6, termed TAF6delta that can be induced during apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: To elucidate the impact of TAF6delta on cell death and gene expression, we have employed modified antisense oligonucleotides to enforce expression of endogenous TAF6delta. The induction of endogenous TAF6delta triggered apoptosis in tumor cell lines, including cells devoid of p53. Microarray experiments revealed that TAF6delta activates gene expression independently of cellular p53 status. CONCLUSIONS: Our data define TAF6delta as a pivotal node in a signaling pathway that controls gene expression programs and apoptosis in the absence of p53.

  4. Plasticity of gamma delta T cells: impact on the anti-tumor response

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    Virginie eLafont


    Full Text Available The tumor immune microenvironment contributes to tumor initiation, progression and response to therapy. Among the immune cell subsets that play a role in the tumor microenvironment, innate-like T cells that express T cell receptors composed of gamma and delta chains (gamma delta T cells are of particular interest. gamma delta T cells can contribute to the immune response against many tumor types (lymphoma, myeloma, melanoma, breast, colon, lung, ovary and prostate cancer directly through their cytotoxic activity and indirectly by stimulating or regulating the biological functions of other cell types required for the initiation and establishment of the anti-tumor immune response, such as dendritic cells and cytotoxic CD8+ T cells. However, the notion that tumor-infiltrating gamma delta T cells are a good prognostic marker in cancer was recently challenged by studies showing that the presence of these cells in the tumor microenvironment was associated with poor prognosis in both breast and colon cancer. These findings suggest that gamma delta T cells may also display pro-tumor activities. Indeed, breast tumor-infiltrating gamma deltaT cells could exert an immunosuppressive activity by negatively regulating DC maturation. Furthermore, recent studies demonstrated that signals from the microenvironment, particularly cytokines, can confer some plasticity to gamma delta T cells and promote their differentiation into gamma delta T cells with regulatory functions. This review focuses on the current knowledge on the functional plasticity of gamma delta T cells and its effect on their anti-tumor activities. It also discusses the putative mechanisms underlying gamma delta T cell expansion, differentiation and recruitment in the tumor microenvironment.

  5. Clinical applications of gamma delta T cells with multivalent immunity

    Directory of Open Access Journals (Sweden)

    Drew C Deniger


    Full Text Available Gamma delta T cells hold promise for adoptive immunotherapy because of their reactivity to bacteria, viruses, and tumors. However, these cells represent a small fraction (1-5% of the peripheral T-cell pool and require activation and propagation to achieve clinical benefit. Aminobisphosphonates specifically expand the Vgamma9Vdelta2 subset of gamma delta T cells and have been used in clinical trials of cancer where objective responses were detected. The Vgamma9Vdelta2 TCR heterodimer binds multiple ligands and results in a multivalent attack by a monoclonal T cell population. Alternatively, populations of gamma delta T cells with oligoclonal or polyclonal TCR repertoire could be infused for broad-range specificity. However, this goal has been restricted by a lack of applicable expansion protocols for non-Vgamma9Vdelta2 cells. Recent advances using immobilized antigens, agonistic monoclonal antibodies (mAbs, tumor-derived artificial antigen presenting cells (aAPC, or combinations of activating mAbs and aAPC have been successful in expanding gamma delta T cells with oligoclonal or polyclonal TCR repertoires. Immobilized MHC Class-I chain-related A was a stimulus for gamma delta T cells expressing TCRdelta1 isotypes, and plate-bound activating antibodies have expanded Vdelta1 and Vdelta2 cells ex vivo. Clinically-sufficient quantities of TCRdelta1, TCRdelta2, and TCRdelta1negTCRdelta2neg have been produced following co-culture on aAPC, and these subsets displayed differences in memory phenotype and reactivity to tumors in vitro and in vivo. Gamma delta T cells are also amenable to genetic modification as evidenced by introduction of alpha beta TCRs, chimeric antigen receptors (CARs, and drug-resistance genes. This represents a promising future for the clinical application of oligoclonal or polyclonal gamma delta T cells in autologous and allogeneic settings that builds on current trials testing the safety and efficacy of Vgamma9Vdelta2 T cells.

  6. The Canadian Natural Health Products (NHP) regulations: industry compliance motivations. (United States)

    Laeeque, Hina; Boon, Heather; Kachan, Natasha; Cohen, Jillian Clare; D'Cruz, Joseph


    This qualitative study explores corporations' motivations to comply with new natural health products (NHP) Regulations in Canada. Interviews were conducted with representatives from 20 Canadian NHP companies. Findings show that the rationale for compliance differs for large compared to small and medium-sized enterprises (SMEs). Large firms are motivated to comply with the regulations because of the deterrent fear of negative media coverage, social motivations, ability to comply and maintaining a competitive market advantage. In contrast, SMEs are motivated to comply due to the deterrent fear of legal prosecution and a sense of duty.

  7. The Canadian Natural Health Products (NHP regulations: industry perceptions and compliance factors

    Directory of Open Access Journals (Sweden)

    Boon Heather


    Full Text Available Abstract Background The use of natural health products, such as vitamins, minerals, and herbs, by Canadians has been increasing with time. As a result of consumer concern about the quality of these products, the Canadian Department of Health created the Natural Health Products (NHP Regulations. The new Canadian regulations raise questions about whether and how the NHP industry will be able to comply and what impact they will have on market structure. The objectives of this study were to explore who in the interview sample is complying with Canada's new NHP Regulations (i.e., submitted product licensing applications on time; and explore the factors that affect regulatory compliance. Methods Twenty key informant interviews were conducted with employees of the NHP industry. The structured interviews focused on the level of satisfaction with the Regulations and perceptions of compliance and non-compliance. Interviews were tape recorded and then transcribed verbatim. Data were independently coded, using qualitative content analysis. Team meetings were held after every three to four interviews to discuss emerging themes. Results The major finding of this study is that most (17 out of 20 companies interviewed were beginning to comply with the new regulatory regime. The factors that contribute to likelihood of regulatory compliance were: perceptions and knowledge of the regulations and business size. Conclusion The Canadian case can be instructive for other countries seeking to implement regulatory standards for natural health products. An unintended consequence of the Canadian NHP regulations may be the exit of smaller firms, leading to industry consolidation.

  8. The low-temperature structures of Hgsub(3-delta)SbF6 and Hgsub(3-delta)TaF6

    International Nuclear Information System (INIS)

    Tun, Z.; Brown, I.D.


    The Hg chains in both Hgsub(3-delta)SbF 6 and Hgsub(3-delta)TaF 6 order below room temperature. Down to about 190 K the ordering results from the interaction between parallel chains. It is short range and is different for the two compounds. Below 190 K both compounds transform to an isostructural long-range-ordered phase which is driven by the interaction between perpendicular chains. The structure of this phase in both compounds has been determined. Hgsub(3-delta)SbF 6 at 173 K, delta=0.134(1), Msub(r)=810.6(2). It is monoclinic but pseudotetragonal with I4 1 /amd, a=7.655(1), c=12.558(1) A, V=735.9(2) A 3 , Z=4, Dsub(x)=7.314(3) Mg m -3 , graphite-monochromated Mo Kα radiation, lambda=0.71069 A, μ=64.8 mm -1 , F(000)=1337.1(3). Hgsub(3-delta)TaF 6 at 150 K is isostructural but has delta=0.142(1), Msub(r)=868.2(2), a=7.634(1), c=12.610(2) A, V=734.9(2) A, Dsub(x)=7.844(3) Mg m -3 , μ=76.4 mm -1 , F(000)=1422.6(3). Comparison of the low-temperature structures with those at room temperature shows that the thermal contraction results from the shortening of interatomic distances associated with the weak bonds, with the result that the MF 6 (M=Sb, Ta) host lattice shrinks more than the Hg chains. Variation of the atomic displacement parameters with temperature indicates that the large librational displacements of the MF 6 ion result from thermal motion rather than static disorder. (orig.)

  9. delta 6 Hexadecenoic acid is synthesized by the activity of a soluble delta 6 palmitoyl-acyl carrier protein desaturase in Thunbergia alata endosperm. (United States)

    Cahoon, E B; Cranmer, A M; Shanklin, J; Ohlrogge, J B


    delta 6 Hexadecenoic acid (16:1 delta 6) composes more than 80% of the seed oil of Thunbergia alata. Studies were conducted to determine the biosynthetic origin of the double bond of this unusual fatty acid. Assays of fractions of developing T. alata seed endosperm with [1-14C]palmitoyl (16:0)-acyl carrier protein (ACP) revealed the presence of a soluble delta 6 desaturase activity. This activity was greatest when 16:0-ACP was provided as a substrate, whereas no desaturation of the coenzyme A ester of this fatty acid was detected. In addition, delta 6 16:0-ACP desaturase activity in T. alata endosperm extracts was dependent on the presence of ferredoxin and molecular oxygen and was stimulated by catalase. To further characterize this enzyme, a cDNA encoding a diverged acyl-ACP desaturase was isolated from a T. alata endosperm cDNA library using polymerase chain reaction with degenerate oligonucleotides corresponding to conserved amino acid sequences in delta 9 stearoyl (18:0)- and delta 4 16:0-ACP desaturases. The primary structure of the mature peptide encoded by this cDNA shares 66% identity with the mature castor delta 9 18:0-ACP desaturase and 57% identity with the mature coriander delta 4 16:0-ACP desaturase. Extracts of Escherichia coli that express the T. alata cDNA catalyzed the delta 6 desaturation of 16:0-ACP. These results demonstrate that 16:1 delta 6 in T. alata endosperm is formed by the activity of a soluble delta 6 16:0-ACP desaturase that is structurally related to the delta 9 18:0- and delta 4 16:0-ACP desaturases. Implications of this work to an understanding of active site structures of acyl-ACP desaturases are discussed.

  10. CCL20, (gamma)(delta) T cells, and IL-22 in corneal epithelial healing (United States)

    After corneal epithelial abrasion, leukocytes and platelets rapidly enter the corneal stroma, and CCR6 (+) IL-17(+) gamma delta T cells migrate into the epithelium. Gamma delta T-cell-deficient (TCRd(-/-)) mice have significantly reduced inflammation and epithelial wound healing. Epithelial CCL20 mR...

  11. 78 FR 11521 - Control of Communicable Disease; Foreign-Requirements for Importers of Nonhuman Primates (NHP) (United States)


    ... Part 71 Control of Communicable Disease; Foreign--Requirements for Importers of Nonhuman Primates (NHP... Primates (NHP) AGENCY: Centers for Disease Control and Prevention (CDC), Department of Health and Human... live nonhuman primates (NHPs) by extending existing requirements for the importation of Macaca...

  12. Improved γ-linolenic acid production in Mucor circinelloides by homologous overexpressing of delta-12 and delta-6 desaturases. (United States)

    Zhang, Yao; Luan, Xiao; Zhang, Huaiyuan; Garre, Victoriano; Song, Yuanda; Ratledge, Colin


    γ-Linolenic acid (GLA) is important because of its nutritional value and medicinal applications. Although the biosynthetic pathways of some plant and microbial GLA have been deciphered, current understanding of the correlation between desaturases and GLA synthesis in oleaginous fungi is incomplete. In previous work, we found that a large amount of oleic acid (OA) had not been converted to linoleic acid (LA) or GLA in Mucor circinelloides CBS 277.49, which may be due to inadequate activities of the delta-12 or delta-6 desaturases, and thus leading to the accumulation of OA and LA. Thus, it is necessary to explore the main contributing factor during the process of GLA biosynthesis in M. circinelloides. To enhance GLA production in M. circinelloides, homologous overexpression of delta-12 and two delta-6 desaturases (named delta-6-1 and delta-6-2, respectively) were analyzed. When delta-6 desaturase were overexpressed in M. circinelloides, up to 43% GLA was produced in the total fatty acids, and the yield of GLA reached 180 mg/l, which were, respectively, 38 and 33% higher than the control strain. These findings revealed that delta-6 desaturase (especially for delta-6-1 desaturase) plays an important role in GLA synthesis by M. circinelloides. The strain overexpressing delta-6-1 desaturase may have potential application in microbial GLA production.

  13. Display of adenoregulin with a novel Pichia pastoris cell surface display system. (United States)

    Ren, Ren; Jiang, Zhengbing; Liu, Meiyun; Tao, Xinyi; Ma, Yushu; Wei, Dongzhi


    Two Pichia pastoris cell surface display vectors were constructed. The vectors consisted of the flocculation functional domain of Flo1p with its own secretion signal sequence or the alpha-factor secretion signal sequence, a polyhistidine (6xHis) tag for detection, an enterokinase recognition site, and the insertion sites for target proteins. Adenoregulin (ADR) is a 33-amino-acid antimicrobial peptide isolated from Phyllomedusa bicolor skin. The ADR was expressed and displayed on the Pichia pastoris KM71 cell surface with the system reported. The displayed recombinant ADR fusion protein was detected by fluorescence microscopy and confocal laser scanning microscopy (CLSM). The antimicrobial activity of the recombinant adenoregulin was detected after proteolytic cleavage of the fusion protein on cell surface. The validity of the Pichia pastoris cell surface display vectors was proved by the displayed ADR.

  14. Apoptosis of murine melanoma B16-BL6 cells induced by quercetin targeting mitochondria, inhibiting expression of PKC-alpha and translocating PKC-delta. (United States)

    Zhang, Xian-Ming; Chen, Jia; Xia, Yu-Gui; Xu, Qiang


    In our previous study, quercetin was found to induce apoptosis of murine melanoma B16-BL6 cells. The cellular and molecular mechanism of quercetin-induced apoptosis was investigated in the present study. Nuclear morphology was determined by fluorescence microscopy. DNA fragmentation was analyzed by electrophoresis and quantified by the diphenylamine method. The transmembrane potential of mitochondria was measured by flow cytometry. Bcl-2, Bcl-X(L), PKC-alpha, PKC-beta, and PKC-delta were detected by Western blotting. Caspase activity was determined spectrophotometrically. Quercetin induced the condensation of nuclei of B16-BL6 cells in a dose-dependent pattern as visualized by Hoechst 33258 and propidium iodide dying. Phorbol 12-myristate 13-acetate (PMA), a PKC activator, significantly enhanced apoptosis induced by quercetin, while doxorubicin, a PKC inhibitor, markedly decreased it. Both PMA and doxorubicin showed a consistent effect on the fragmentation of nuclear DNA caused by various dosages of quercetin. Quercetin dose-dependently led to loss of the mitochondrial membrane potential, which was also significantly reinforced or antagonized by PMA and doxorubicin, respectively. Moreover, PMA showed reinforcement, while doxorubicin showed significant antagonization, of the quercetin-mediated decrease in the expression of Bcl-2. Quercetin promoted caspase-3 activity in a dose-dependent manner, which was also regulated by PMA and doxorubicin with a pattern similar to that seen in their effect on apoptosis, mitochondrial membrane potential and Bcl-2 expression, but none of these were directly affected by PMA and doxorubicin. Free fatty acid and chlorpromazine, a PKC activator and inhibitor, respectively, did not interfere with these effects of quercetin. B16-BL6 cells expressed PKC-alpha, PKC-beta, and PKC-delta. Quercetin dose-dependently inhibited the expression of PKC-alpha but not that of PKC-beta and PKC-delta. Doxorubicin almost completely blocked the effect of

  15. Cell-to-cell communication and cellular environment alter the somatostatin status of delta cells

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    Kelly, Catriona, E-mail: [SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster, Coleraine (United Kingdom); Flatt, Peter R.; McClenaghan, Neville H. [SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster, Coleraine (United Kingdom)


    Research highlights: {yields} TGP52 cells display enhanced functionality in pseudoislet form. {yields} Somatostatin content was reduced, but secretion increased in high glucose conditions. {yields} Cellular interactions and environment alter the somatostatin status of TGP52 cells. -- Abstract: Introduction: Somatostatin, released from pancreatic delta cells, is a potent paracrine inhibitor of insulin and glucagon secretion. Islet cellular interactions and glucose homeostasis are essential to maintain normal patterns of insulin secretion. However, the importance of cell-to-cell communication and cellular environment in the regulation of somatostatin release remains unclear. Methods: This study employed the somatostatin-secreting TGP52 cell line maintained in DMEM:F12 (17.5 mM glucose) or DMEM (25 mM glucose) culture media. The effect of pseudoislet formation and culture medium on somatostatin content and release in response to a variety of stimuli was measured by somatostatin EIA. In addition, the effect of pseudoislet formation on cellular viability (MTT and LDH assays) and proliferation (BrdU ELISA) was determined. Results: TGP52 cells readily formed pseudoislets and showed enhanced functionality in three-dimensional form with increased E-cadherin expression irrespective of the culture environment used. However, culture in DMEM decreased cellular somatostatin content (P < 0.01) and increased somatostatin secretion in response to a variety of stimuli including arginine, calcium and PMA (P < 0.001) when compared with cells grown in DMEM:F12. Configuration of TGP52 cells as pseudoislets reduced the proliferative rate and increased cellular cytotoxicity irrespective of culture medium used. Conclusions: Somatostatin secretion is greatly facilitated by cell-to-cell interactions and E-cadherin expression. Cellular environment and extracellular glucose also significantly influence the function of delta cells.

  16. Cell-to-cell communication and cellular environment alter the somatostatin status of delta cells

    International Nuclear Information System (INIS)

    Kelly, Catriona; Flatt, Peter R.; McClenaghan, Neville H.


    Research highlights: → TGP52 cells display enhanced functionality in pseudoislet form. → Somatostatin content was reduced, but secretion increased in high glucose conditions. → Cellular interactions and environment alter the somatostatin status of TGP52 cells. -- Abstract: Introduction: Somatostatin, released from pancreatic delta cells, is a potent paracrine inhibitor of insulin and glucagon secretion. Islet cellular interactions and glucose homeostasis are essential to maintain normal patterns of insulin secretion. However, the importance of cell-to-cell communication and cellular environment in the regulation of somatostatin release remains unclear. Methods: This study employed the somatostatin-secreting TGP52 cell line maintained in DMEM:F12 (17.5 mM glucose) or DMEM (25 mM glucose) culture media. The effect of pseudoislet formation and culture medium on somatostatin content and release in response to a variety of stimuli was measured by somatostatin EIA. In addition, the effect of pseudoislet formation on cellular viability (MTT and LDH assays) and proliferation (BrdU ELISA) was determined. Results: TGP52 cells readily formed pseudoislets and showed enhanced functionality in three-dimensional form with increased E-cadherin expression irrespective of the culture environment used. However, culture in DMEM decreased cellular somatostatin content (P < 0.01) and increased somatostatin secretion in response to a variety of stimuli including arginine, calcium and PMA (P < 0.001) when compared with cells grown in DMEM:F12. Configuration of TGP52 cells as pseudoislets reduced the proliferative rate and increased cellular cytotoxicity irrespective of culture medium used. Conclusions: Somatostatin secretion is greatly facilitated by cell-to-cell interactions and E-cadherin expression. Cellular environment and extracellular glucose also significantly influence the function of delta cells.

  17. Transcriptomic profiling of pancreatic alpha, beta and delta cell populations identifies delta cells as a principal target for ghrelin in mouse islets

    DEFF Research Database (Denmark)

    Adriaenssens, Alice E; Svendsen, Berit; Lam, Brian Y H


    cytometry and analysed by RNA sequencing. The role of the ghrelin receptor was validated by imaging delta cell calcium concentrations using islets with delta cell restricted expression of the calcium reporter GCaMP3, and in perfused mouse pancreases. RESULTS: A database was constructed of all genes...... expressed in alpha, beta and delta cells. The gene encoding the ghrelin receptor, Ghsr, was highlighted as being highly expressed and enriched in delta cells. Activation of the ghrelin receptor raised cytosolic calcium levels in primary pancreatic delta cells and enhanced somatostatin secretion in perfused...... pancreases, correlating with a decrease in insulin and glucagon release. The inhibition of insulin secretion by ghrelin was prevented by somatostatin receptor antagonism. CONCLUSIONS/INTERPRETATION: Our transcriptomic database of genes expressed in the principal islet cell populations will facilitate...

  18. T-cell receptor gamma delta bearing cells in normal human skin

    NARCIS (Netherlands)

    Bos, J. D.; Teunissen, M. B.; Cairo, I.; Krieg, S. R.; Kapsenberg, M. L.; Das, P. K.; Borst, J.


    T-cell antigen receptors (TCR) are divided into common alpha beta and less common gamma delta types. In the murine skin, TCR gamma delta+ cells have been reported to form the great majority of epidermal T lymphocytes. We have examined the relative contribution of TCR alpha beta+ and TCR gamma delta+

  19. Experimental primates and non-human primate (NHP) models of human diseases in China: current status and progress. (United States)

    Zhang, Xiao-Liang; Pang, Wei; Hu, Xin-Tian; Li, Jia-Li; Yao, Yong-Gang; Zheng, Yong-Tang


    Non-human primates (NHPs) are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China's growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China's life sciences and pharmaceutical industry, and enhance China's position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective countermeasures to better utilize NHP resources and further foster NHP research in China.

  20. Casscf/ci Calculations for First Row Transition Metal Hydrides - the TIH(4-PHI), VH(5-DELTA), CRH(6-SIGMA-PLUS), MNH(7-SIGMA-PLUS), FEH(4,6-DELTA) and NIH(2-DELTA) States (United States)

    Walch, S. P.; Bauschlicher, C. W., Jr.


    Calculations are performed for the predicted ground states of TiH(4-phi), VH(5-delta), CrH(6-sigma-plus), MnH(7-sigma-plus), Fett(4,6-delta) and NiH(2-delta). For FeH both the 6-delta and 4-delta states are studied, since both are likely candidates for the ground state. The ground state symmetries are predicted based on a combination of atomic coupling arguments and coupling of 4s(2)3d(n) and 4s(1)3d(n+1) terms in the molecular system. Electron correlation is included by a CASSCF/CI (SD) treatment. The CASSCF includes near-degeneracy effects, while correlation of the 3d electrons in included at the CI level.

  1. Electrochemical performance of La-doped Sr{sub 2}MgMoO{sub 6-{delta}} in natural gas

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Yuan [Texas Materials Institute, ETC 9.102, The University of Texas at Austin, Austin, TX 78712 (United States); College of Physics, Jilin University, 2519 Jiefang Road, Changchun 130023, Jilin Province (China); Huang, Yun-Hui; Goodenough, John B. [Texas Materials Institute, ETC 9.102, The University of Texas at Austin, Austin, TX 78712 (United States); Ying, Jie-Rong [Texas Materials Institute, ETC 9.102, The University of Texas at Austin, Austin, TX 78712 (United States); Institute of Nuclear and New Energy Technology, Tsinghua University, P.O. Box 1021, Beijing 102201 (China)


    Modification of the double perovskite Sr{sub 2}MgMoO{sub 6-{delta}} by La substitution has shown that Sr{sub 2-x}La{sub x}MgMoO{sub 6-{delta}} with 0.6 {<=} x {<=} 0.8 has better performance as the anode of a solid oxide fuel cell. With a Sr{sub 1.2}La{sub 0.8}MgMoO{sub 6-{delta}} anode, LSGM electrolyte, SrCo{sub 0.8}Fe{sub 0.2}O{sub 3-{delta}} cathode, and a La{sub 0.5}Ce{sub 0.4}O{sub 1.7-{delta}} buffer layer between the anode and the electrolyte, a maximum power density of 550 mW/cm{sup 2} has been obtained for a SOFC operating on wet methane (3%H{sub 2}O) at 800 C. The performance of the SOFC using C{sub 2}H{sub 6} fuel, like that of CH{sub 4}, changes little on switching from dry C{sub 2}H{sub 6} to 3% H{sub 2}O/C{sub 2}H{sub 6}, but improvement with wet C{sub 3}H{sub 8} shows that some steam will need to be added to a moderately desulfurized natural-gas fuel. (author)

  2. Expansion of mycobacterium-reactive gamma delta T cells by a subset of memory helper T cells. (United States)

    Vila, L M; Haftel, H M; Park, H S; Lin, M S; Romzek, N C; Hanash, S M; Holoshitz, J


    Human gamma delta T cells expressing the V gamma 9/V delta 2 T-cell receptor have been previously found to proliferate in response to certain microorganisms and to expand throughout life, presumably because of extrathymic activation by foreign antigens. In vitro expansion of V gamma 9/V delta 2 cells by mycobacteria has been previously shown to be dependent on accessory cells. In order to gain an insight into the mechanisms involved in the expansion of these cells, we have undertaken to identify the peripheral blood subset of cells on which proliferation of V gamma 9/V delta 2 cells in response to mycobacteria is dependent. Contrary to their role in antigen presentation to alpha beta T cells, professional antigen-presenting cells, such as monocytes, B cells, and dendritic cells, were unable to provide the cellular support for the expansion of V gamma 9/V delta 2 cells. Selective depletion of T-cell subsets, as well as the use of highly purified T-cell populations, indicated that the only subset of peripheral blood cells that could expand V gamma 9/V delta 2 cells were CD4+ CD45RO+ CD7- alpha beta T cells. These cells underwent distinct intracellular signaling events after stimulation with the mycobacterial antigen. Expansion of V gamma 9/V delta 2 cells by alpha beta T cells was dependent on cell-cell contact. This is the first evidence that a small subset of the memory helper T-cell population is exclusively responsible for the peripheral expansion of V gamma 9/V delta 2 cells. These data illustrate a unique aspect of antigen recognition by gamma delta T cells and provide new means to study their immune defense role.

  3. Omega-6 polyunsaturated fatty acids, serum zinc, delta-5- and delta-6-desaturase activities and incident metabolic syndrome. (United States)

    Yary, T; Voutilainen, S; Tuomainen, T-P; Ruusunen, A; Nurmi, T; Virtanen, J K


    The associations of n-6 polyunsaturated fatty acids (PUFA) with metabolic syndrome have been poorly explored. We investigated the associations of the serum n-6 PUFA and the activities of enzymes involved in the PUFA metabolism, delta-5-desaturase (D5D) and delta-6-desaturase (D6D) with risk of incident metabolic syndrome. We also investigated whether zinc, a cofactor for these enzymes, modifies these associations. A prospective follow-up study was conducted on 661 men who were aged 42-60 years old at baseline in 1984-1989 and who were re-examined in 1998-2001. Men in the highest versus the lowest serum total omega-6 PUFA tertile had a 70% lower multivariate-adjusted risk of incident metabolic syndrome [odds ratio (OR) = 0.30; 95% confidence interval (CI) = 0.18-0.51, P trend metabolic syndrome components at the re-examinations. Most associations were attenuated after adjustment for body mass index. Finally, the associations of D6D and LA were stronger among those with a higher serum zinc concentration. Higher serum total n-6 PUFA, linoleic acid and arachidonic acid concentrations and D5D activity were associated with a lower risk of developing metabolic syndrome and higher D6D activity was associated with a higher risk. The role of zinc also needs to be investigated in other populations. © 2016 The British Dietetic Association Ltd.

  4. Identification and utilization of inter-species conserved (ISC probesets on Affymetrix human GeneChip® platforms for the optimization of the assessment of expression patterns in non human primate (NHP samples

    Directory of Open Access Journals (Sweden)

    Arnold Alma


    Full Text Available Abstract Background While researchers have utilized versions of the Affymetrix human GeneChip® for the assessment of expression patterns in non human primate (NHP samples, there has been no comprehensive sequence analysis study undertaken to demonstrate that the probe sequences designed to detect human transcripts are reliably hybridizing with their orthologs in NHP. By aligning probe sequences with expressed sequence tags (ESTs in NHP, inter-species conserved (ISC probesets, which have two or more probes complementary to ESTs in NHP, were identified on human GeneChip® platforms. The utility of human GeneChips® for the assessment of NHP expression patterns can be effectively evaluated by analyzing the hybridization behaviour of ISC probesets. Appropriate normalization methods were identified that further improve the reliability of human GeneChips® for interspecies (human vs NHP comparisons. Results ISC probesets in each of the seven Affymetrix GeneChip® platforms (U133Plus2.0, U133A, U133B, U95Av2, U95B, Focus and HuGeneFL were identified for both monkey and chimpanzee. Expression data was generated from peripheral blood mononuclear cells (PBMCs of 12 human and 8 monkey (Indian origin Rhesus macaque samples using the Focus GeneChip®. Analysis of both qualitative detection calls and quantitative signal intensities showed that intra-species reproducibility (human vs. human or monkey vs. monkey was much higher than interspecies reproducibility (human vs. monkey. ISC probesets exhibited higher interspecies reproducibility than the overall expressed probesets. Importantly, appropriate normalization methods could be leveraged to greatly improve interspecies correlations. The correlation coefficients between human (average of 12 samples and monkey (average of 8 Rhesus macaque samples are 0.725, 0.821 and 0.893 for MAS5.0 (Microarray Suite version 5.0, dChip and RMA (Robust Multi-chip Average normalization method, respectively. Conclusion It is

  5. 27 CFR 6.56 - Renting display space. (United States)


    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Renting display space. 6.56 Section 6.56 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... Distribution Service § 6.56 Renting display space. A promotion whereby an industry member rents display space...

  6. 27 CFR 6.55 - Display service. (United States)


    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Display service. 6.55 Section 6.55 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS âTIED-HOUSEâ Unlawful Inducements Paying for Advertising, Display Or...

  7. 27 CFR 6.35 - Renting display space. (United States)


    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Renting display space. 6.35 Section 6.35 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... Renting display space. The renting of display space by an industry member at a retail establishment...

  8. Alpha-, gamma- and delta-tocopherols reduce inflammatory angiogenesis in human microvascular endothelial cells. (United States)

    Wells, Shannon R; Jennings, Merilyn H; Rome, Courtney; Hadjivassiliou, Vicky; Papas, Konstantinos A; Alexander, Jonathon S


    Vitamin E, a micronutrient (comprising alpha-, beta-, gamma- and delta-tocopherols, alpha-, beta-, gamma- and delta-tocotrienols), has documented antioxidant and non-antioxidant effects, some of which inhibit inflammation and angiogenesis. We compared the abilities of alpha-, gamma- and delta-tocopherols to regulate human blood cytotoxicity (BEC) and lymphatic endothelial cytotoxicity (LEC), proliferation, invasiveness, permeability, capillary formation and suppression of TNF-alpha-induced VCAM-1 as in vitro models of inflammatory angiogenesis. alpha-, gamma- and delta-tocopherols were not toxic to either cell type up to 40 microM. In BEC, confluent cell density was decreased by all concentrations of delta- and gamma-tocopherol (10-40 microM) but not by alpha-tocopherol. LEC showed no change in cell density in response to tocopherols. delta-Tocopherol (40 microM), but not other isomers, decreased BEC invasiveness. In LEC, all doses of gamma-tocopherol, as well as the highest dose of alpha-tocopherol (40 microM), decreased cell invasiveness. delta-Tocopherol had no effect on LEC invasiveness at any molarity. delta-Tocopherol dose dependently increased cell permeability at 48 h in BEC and LEC; alpha- and gamma-tocopherols showed slight effects. Capillary tube formation was decreased by high dose (40 microM) concentrations of alpha-, gamma- and delta-tocopherol, but showed no effects with smaller doses (10-20 microM) in BEC. gamma-Tocopherol (10-20 microM) and alpha-tocopherol (10 microM), but not delta-tocopherol, increased LEC capillary tube formation. Lastly, in BEC, alpha-, gamma- and delta-tocopherol each dose-dependently reduced TNF-alpha-induced expression of VCAM-1. In LEC, there was no significant change to TNF-alpha-induced VCAM-1 expression with any concentration of alpha-, gamma- or delta-tocopherol. These data demonstrate that physiological levels (0-40 microM) of alpha-, gamma- and delta-tocopherols are nontoxic and dietary tocopherols, especially delta

  9. Study of nuclear proteins in normal and xeroderma pigmentosum lymphoblastoid cells

    International Nuclear Information System (INIS)

    Amari, N.M.B.


    Nuclear histone and nonhistone (NHP) proteins from normal human and xeroderma pigmentosum, complementation group A (XP-A) lymphoblastoid cells were compared both qualitatively, quantitatively and for binding affinity for DNA. Histones and four NHP fractions (NHP/sub 1-4/) were isolated from purified cell nuclei. Binding affinity to [ 3 H] melanoma DNA of histones and each NHP fraction was then determined using gradient dialysis followed by a filter assay. Histones and each NHP fraction were then sub-fractionated by polyacrylamide gel electrophoresis. Densitometric scans of the separation of these proteins on the gels were qualitatively, and quantitatively analyzed and compared between the two cell lines. No qualitative or quantitative differences were observed between histones from XP-A or normal cells

  10. Roles of POLD4, smallest subunit of DNA polymerase {delta}, in nuclear structures and genomic stability of human cells

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Qin Miao [Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya (Japan); Akashi, Tomohiro [Division of Molecular Mycology and Medicine, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya (Japan); Masuda, Yuji; Kamiya, Kenji [Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553 (Japan); Takahashi, Takashi [Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya (Japan); Suzuki, Motoshi, E-mail: [Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya (Japan)


    Mammalian DNA polymerase {delta} (pol {delta}) is essential for DNA replication, though the functions of this smallest subunit of POLD4 have been elusive. We investigated pol {delta} activities in vitro and found that it was less active in the absence of POLD4, irrespective of the presence of the accessory protein PCNA. shRNA-mediated reduction of POLD4 resulted in a marked decrease in colony formation activity by Calu6, ACC-LC-319, and PC-10 cells. We also found that POLD4 reduction was associated with an increased population of karyomere-like cells, which may be an indication of DNA replication stress and/or DNA damage. The karyomere-like cells retained an ability to progress through the cell cycle, suggesting that POLD4 reduction induces modest genomic instability, while allowing cells to grow until DNA damage reaches an intolerant level. Our results indicate that POLD4 is required for the in vitro pol {delta} activity, and that it functions in cell proliferation and maintenance of genomic stability of human cells.

  11. Dermal absorption of the insecticide lindane (1 delta, 2 delta, 3 beta, 4 delta, 5 delta, 6 beta-hexachlorocyclohexane) in rats and rhesus monkeys: Effect of anatomical site

    International Nuclear Information System (INIS)

    Moody, R.P.; Ritter, L.


    Dermal absorption of the insecticide lindane (1 delta, 2 delta, 3 beta, 4 delta, 5 delta, 6 beta-hexachlorocyclohexane) was determined in rats and rhesus monkeys. Lindane is in widespread use as a 1% cream or lotion scabicide formulation and as a 1% miticide shampoo for body lice control in humans. Results obtained following our in vivo dermal absorption procedure demonstrated that 18 +/- 4.1%, 34 +/- 5.2%, and 54 +/- 26.3% of the applied dose was absorbed following topical applications at a rate of 1.5 micrograms/cm2 (6.2 micrograms/100 microliters of acetone) of the 14C-labeled pesticide to 4.2-cm2 regions of the forearm (n = 8), forehead (n = 7), and palm (n = 4) of rhesus monkeys, respectively. Dose sites were washed with soapy water 24 h posttreatment. Comparative studies in rats (n = 5) dosed middorsally demonstrated 31 +/- 9.5% absorption. Statistical analysis of the 14C excretion kinetics demonstrated slower clearance of lindane from rats than monkey forearm, forehead, or palm. Intramuscular (im) injections of 14C-lindane gave 52 +/- 7.1% recovery in monkey (n = 8) and 64 +/- 5.9% in rats (n = 5), suggesting body storage of this lipophilic chemical

  12. Induced Pluripotent Stem Cells from Nonhuman Primates. (United States)

    Mishra, Anuja; Qiu, Zhifang; Farnsworth, Steven L; Hemmi, Jacob J; Li, Miao; Pickering, Alexander V; Hornsby, Peter J


    Induced pluripotent stem cells from nonhuman primates (NHPs) have unique roles in cell biology and regenerative medicine. Because of the relatedness of NHPs to humans, NHP iPS cells can serve as a source of differentiated derivatives that can be used to address important questions in the comparative biology of primates. Additionally, when used as a source of cells for regenerative medicine, NHP iPS cells serve an invaluable role in translational experiments in cell therapy. Reprogramming of NHP somatic cells requires the same conditions as previously established for human cells. However, throughout the process, a variety of modifications to the human cell protocols must be made to accommodate significant species differences.

  13. Nigerian Hospital Practice - Vol 7, No 5-6 (2011)

    African Journals Online (AJOL)

    Awareness of Sickle Cell Disease amongst Mothers of Under-Fives in Ekosodin community, Edo state, Nigeria. EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. BI Abhulimhen-Iyoba, ME Odunvbun, AA Okolo, 57-63. ...

  14. Polyvalent Display of Biomolecules on Live Cells. (United States)

    Shi, Peng; Zhao, Nan; Lai, Jinping; Coyne, James; Gaddes, Erin R; Wang, Yong


    Surface display of biomolecules on live cells offers new opportunities to treat human diseases and perform basic studies. Existing methods are primarily focused on monovalent functionalization, that is, the display of single biomolecules across the cell surface. Here we show that the surface of live cells can be functionalized to display polyvalent biomolecular structures through two-step reactions under physiological conditions. This polyvalent functionalization enables the cell surface to recognize the microenvironment one order of magnitude more effectively than with monovalent functionalization. Thus, polyvalent display of biomolecules on live cells holds great potential for various biological and biomedical applications. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. On approximation and energy estimates for delta 6-convex functions. (United States)

    Saleem, Muhammad Shoaib; Pečarić, Josip; Rehman, Nasir; Khan, Muhammad Wahab; Zahoor, Muhammad Sajid


    The smooth approximation and weighted energy estimates for delta 6-convex functions are derived in this research. Moreover, we conclude that if 6-convex functions are closed in uniform norm, then their third derivatives are closed in weighted [Formula: see text]-norm.

  16. Opioid receptors in human neuroblastoma SH-SY5Y cells: evidence for distinct morphine (. mu. ) and enkephalin (delta) binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Kazmi, S.M.I.; Mishra, R.K.


    Human neuroblastoma SH-SY5Y cells exhibited a heterogeneous population of and delta types of opioid binding sites. These specific binding sites displayed the characteristic saturability, stereospecificity and reversibility, expected of a receptor. Scatchard analysis of (/sup 3/H)-D-Ala/sup 2/-D-Leu/sup 5/-enkephalin (DADLE) in the presence of 10/sup -5/M D-Pro/sup 4/-morphiceptin (to block the receptors) and the competitive displacement by various highly selective ligands yielded the binding parameters of delta sites which closely resemble those of the delta receptors in brain and mouse neuroblastoma clones. Similarly, the high affinity binding of (/sup 3/H)-dihydromorphine, together with the higher potency of morphine analogues to displace (/sup 3/H)-naloxone binding established the presence of sites. Guanine nucleotides and NaCl significantly inhibited the association and increased the dissociation of (/sup 3/H)-DADLE binding.

  17. Serum-dependent effects of tamoxifen and cannabinoids upon C6 glioma cell viability. (United States)

    Jacobsson, S O; Rongård, E; Stridh, M; Tiger, G; Fowler, C J


    In the present study, the effects of the combination of tamoxifen ((Z)-2[p-(1,2-diphenyl-1-butenyl)phenoxy]-N,N-dimethylamine citrate) and three cannabinoids (Delta(9)-tetrahydrocannabinol [Delta(9)-THC], cannabidiol, and anandamide [AEA]) upon the viability of C6 rat glioma cells was assessed at different incubation times and using different culturing concentrations of foetal bovine serum (FBS). Consistent with previous data for human glioblastoma cells, the tamoxifen sensitivity of the cells was increased as the FBS content of the culture medium was reduced from 10 to 0.4 and 0%. The cells expressed protein kinase C alpha and calmodulin (the concentration of which did not change significantly as the FBS concentration was reduced), but did not express estrogen receptors. Delta(9)-THC and cannabidiol, but not AEA, produced a modest reduction in cell viability after 6 days of incubation in serum-free medium, whereas no effects were seen in 10% FBS-containing medium. There was no observed synergy between the effects of tamoxifen and the cannabinoids upon cell viability.

  18. Characterization of T cell receptor assembly and expression in a Ti gamma delta-positive cell line

    DEFF Research Database (Denmark)

    Kuhlmann, J; Caspar-Bauguil, S; Geisler, C


    - variants of the T cell Lyon were induced and found to produce all of the Ti/CD3 components, with the exception of Ti-delta. Biochemical analysis indicated that: (1) Ti-gamma/CD3 gamma, delta, epsilon complexes were formed in the endoplasmic reticulum in the absence of Ti-delta; (2) the CD3-zeta chain did...

  19. Novel primary thymic defect with T lymphocytes expressing gamma delta T cell receptor

    DEFF Research Database (Denmark)

    Geisler, C; Pallesen, G; Platz, P


    Flow cytometric analysis of the peripheral blood mononuclear cells in a six year old girl with a primary cellular immune deficiency showed a normal fraction of CD3 positive T cells. Most (70%) of the CD3 positive cells, however, expressed the gamma delta and not the alpha beta T cell receptor....... Immunoprecipitation and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that most of the gamma delta T cell receptors existed as disulphide-linked heterodimers. Proliferative responses to mitogens were severely reduced, but specific antibody responses after vaccination could be detected...... deficiency associated with a high proportion of T cells expressing the gamma delta T cell receptor has been described in nude mice, and it is suggested that the immune deficiency of this patient may represent a human analogue....

  20. On approximation and energy estimates for delta 6-convex functions

    Directory of Open Access Journals (Sweden)

    Muhammad Shoaib Saleem


    Full Text Available Abstract The smooth approximation and weighted energy estimates for delta 6-convex functions are derived in this research. Moreover, we conclude that if 6-convex functions are closed in uniform norm, then their third derivatives are closed in weighted L2 $L^{2}$-norm.

  1. DeltaFosB induces osteosclerosis and decreases adipogenesis by two independent cell-autonomous mechanisms

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Sabatakos, George; Chiusaroli, Riccardo


    establishes that the skeletal phenotype is cell autonomous to the osteoblast lineage and independent of adipocyte formation. It also strongly suggests that the decreased fat phenotype of NSE-DeltaFosB mice is independent of the changes in the osteoblast lineage. In vitro, overexpression of Delta......Osteoblasts and adipocytes may develop from common bone marrow mesenchymal precursors. Transgenic mice overexpressing DeltaFosB, an AP-1 transcription factor, under the control of the neuron-specific enolase (NSE) promoter show both markedly increased bone formation and decreased adipogenesis...... of DeltaFosB on adipocyte differentiation appears to occur at early stages of stem cell commitment, affecting C/EBPbeta functions. It is concluded that the changes in osteoblast and adipocyte differentiation in DeltaFosB transgenic mice result from independent cell-autonomous mechanisms....

  2. Regulation of Mammary Stem Cell Quiescence via Post-Translational Modification of DeltaNp63alpha (United States)


    This document is the Annual Summary Report on the training grant awarded to Andrew DeCastro entitled Regulation of Mammary Stem Cell Quiescence via...screen) mediated phosphorylation of deltaNPdelta3 on stem cell behavior and mitotic activity. Task 1 aims to determine the effects of wild-type, phospho...ablative and phospho-mimetic alleles of deltaNP63delta phosphorylation on stem cell behavior in vitro. Thus far, we demonstrate that stem cell enriched

  3. Measuring bovine gamma delta T cell function at the site of Mycobacterium bovis infection (United States)

    Bovine gamma delta T cells are amongst the first cells to accumulate at the site of Mycobacterium bovis infection; however, their role in the developing lesion remains unclear. We utilized transcriptomics analysis, in situ hybridization, and a macrophage/gamma delta T cell co-culture system to eluc...

  4. The HDAC Inhibitors Scriptaid and LBH589 Combined with the Oncolytic Virus Delta24-RGD Exert Enhanced Anti-Tumor Efficacy in Patient-Derived Glioblastoma Cells.

    Directory of Open Access Journals (Sweden)

    Lotte M E Berghauser Pont

    Full Text Available A phase I/II trial for glioblastoma with the oncolytic adenovirus Delta24-RGD was recently completed. Delta24-RGD conditionally replicates in cells with a disrupted retinoblastoma-pathway and enters cells via αvβ3/5 integrins. Glioblastomas are differentially sensitive to Delta24-RGD. HDAC inhibitors (HDACi affect integrins and share common cell death pathways with Delta24-RGD. We studied the combination treatment effects of HDACi and Delta24-RGD in patient-derived glioblastoma stem-like cells (GSC, and we determined the most effective HDACi.SAHA, Valproic Acid, Scriptaid, MS275 and LBH589 were combined with Delta24-RGD in fourteen distinct GSCs. Synergy was determined by Chou Talalay method. Viral infection and replication were assessed using luciferase and GFP encoding vectors and hexon-titration assays. Coxsackie adenovirus receptor and αvβ3 integrin levels were determined by flow cytometry. Oncolysis and mechanisms of cell death were studied by viability, caspase-3/7, LDH and LC3B/p62, phospho-p70S6K. Toxicity was studied on normal human astrocytes. MGMT promotor methylation status, TCGA classification, Rb-pathway and integrin gene expression levels were assessed as markers of responsiveness.Scriptaid and LBH589 acted synergistically with Delta24-RGD in approximately 50% of the GSCs. Both drugs moderately increased αvβ3 integrin levels and viral infection in responding but not in non-responding GSCs. LBH589 moderately increased late viral gene expression, however, virus titration revealed diminished viral progeny production by both HDACi, Scriptaid augmented caspase-3/7 activity, LC3B conversion, p62 and phospho-p70S6K consumption, as well as LDH levels. LBH589 increased LDH and phospho-p70S6K consumption. Responsiveness correlated with expression of various Rb-pathway genes and integrins. Combination treatments induced limited toxicity to human astrocytes.LBH589 and Scriptaid combined with Delta24-RGD revealed synergistic anti

  5. A novel approach for craniofacial symmetry evaluation: Using the midsagittal Reference line drawn from “Crista Gali” with NHP technique

    Directory of Open Access Journals (Sweden)

    Morteza Ordobazari


    Full Text Available Please cite this article as: Ordobazari M, Naqavi Al-Hosseini AA, Zafarmand H. A novel approach for craniofacial symmetry evaluation: Using the midsagittal Reference line drawn from “Crista Gali” with NHP technique. Novel Biomed 2013;1(2:48-53.Background and objective: The purpose of this study was the determination of midsagittal reference line (MSL for craniofacial asymmetry assessment by drawing a line from Crista gali parallel to the true vertical line in PA cephalometry, using Natural Head Position (NHP technique.Method and Materials: 60 Iranian subjects within the age range of 9-13 years old were selected for this prospective study. Patients referred for orthodontic treatment and ghad no supernumerary or missing teeth, no skeletal anomaly, or any history of orthodontic and jaw surgery with normal occlusion. Posteroanterior cephalometric radiographs (PA Ceph were taken of all subjects with NHP technique. The midsagittal line was also traced parallel to the hanging chain from Crista gali. True horizontal line (THL and true vertical line (TVL were also traced from Crista gali (Cg. Using Cartesian system based upon Cg point (0~0, the craniofacial symmetry was assessed with linear, angular and proportional measurements in PA cephalogam, related to TVL and THL lines, for 10 bilateral (R&L anatomical landmarks. The mean differences of the above measurements in left and right sides were analyzed by T- test.Results: The proportional ratios for all left and right measurements were not statistically significant. This was true for both vertical and horizontal distances. The significant level for MSL drawn from Cg as referred to ANS (0±0.255 and Me points (0.007±0.527 was 0.002 and 0.004, respectively.Conclusion: In posteroanterior cephalometry radiographs taken with NHP method, the MSL drawn from Crista gali is reproducible and reliable up to 96% of the times for facial symmetry diagnosis.

  6. Gulf-Wide Information System, Environmental Sensitivity Index National Heritage Program Database, Geographic NAD83, LDWF (2001) [esi_nhp_LDWF_2001 (United States)

    Louisiana Geographic Information Center — This data set contains sensitive biological resource data developed from the Louisiana National Heritage Program (NHP) database for coastal Louisiana. Vector...

  7. Yeast cell surface display for lipase whole cell catalyst and its applications

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yun; Zhang, Rui; Lian, Zhongshuai; Wang, Shihui; Wright, Aaron T.


    The cell surface display technique allows for the expression of target proteins or peptides on the microbial cell surface by fusing an appropriate protein as an anchoring motif. Yeast display systems, such as Pichia pastoris, Yarowia lipolytica and Saccharomyces cerevisiae, are ideal, alternative and extensive display systems with the advantage of simple genetic manipulation and post-translational modification of expressed heterologous proteins. Engineered yeasts show high performance characteristics and variant utilizations. Herein, we comprehensively summarize the variant factors affecting lipase whole cell catalyst activity and display efficiency, including the structure and size of target proteins, screening anchor proteins, type and chain length of linkers, and the appropriate matching rules among the above-mentioned display units. Furthermore, we also address novel approaches to enhance stability and activity of recombinant lipases, such as VHb gene co-expression, multi-enzyme co-display technique, and the micro-environmental interference and self-assembly techniques. Finally, we represent the variety of applications of whole cell surface displayed lipases on yeast cells in non-aqueous phases, including synthesis of esters, PUFA enrichment, resolution of chiral drugs, organic synthesis and biofuels. We demonstrate that the lipase surface display technique is a powerful tool for functionalizing yeasts to serve as whole cell catalysts, and increasing interest is providing an impetus for broad application of this technique.

  8. C-terminal cleavage of DeltaNp63alpha is associated with TSA-induced apoptosis in immortalized corneal epithelial cells. (United States)

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


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

  9. Derivation and characterization of novel nonhuman primate embryonic stem cell lines from in vitro-fertilized baboon preimplantation embryos. (United States)

    Chang, Tien-Cheng; Liu, Ya-Guang; Eddy, Carlton A; Jacoby, Ethan S; Binkley, Peter A; Brzyski, Robert G; Schenken, Robert S


    The development of nonhuman primate (NHP) embryonic stem cell (ESC) models holds great promise for cell-mediated treatment of debilitating diseases and to address numerous unanswered questions regarding the therapeutic efficacy of ESCs while supplanting ethical considerations involved with human studies. Here we report successful establishment and characterization of 3 novel baboon (Papio cynocephalus) ESC lines from the inner cell mass of intracytoplasmic sperm injection-derived blastocysts. Embryos were cultured in an improved baboon embryo in vitro culture protocol. The inner cell mass of blastocyst was laser-dissected and plated on mouse embryonic fibroblast feeder cell monolayer in the NHP ESC culture medium. Three cell lines with characteristic ESC morphology have been cultured through an extended period (>14 months), with 2 male cell lines (UT-1 and -2) and 1 female cell line (UT-3) displaying normal baboon karyotypes. Reverse transcription-polymerase chain reaction analysis confirmed that all 3 lines express primate ESC pluripotency markers, including OCT-4, NANOG, SOX-2, TERT, TDGF, LEFTYA, and REX-1. All 3 lines demonstrated positive immunocytochemical staining for OCT-4, stage-specific embryonic antigen-3, stage-specific embryonic antigen-4, TRA-1-60, and TRA-1-81. Baboon ESCs injected into NOD/SCID mice formed teratomas with all 3 germ layers. In addition, embryoid body-like spherical structures were derived and initial outgrowth was observed when embedded into extracellular matrix Matrigel. The ESC lines established in this NHP model have the potential to extend our knowledge in the fields of developmental biology, regenerative medicine, and future applications, including preclinical safety assessment of in vivo stem cell therapy.

  10. Gamma Delta T-Cells Regulate Inflammatory Cell Infiltration of the Lung after Trauma-Hemorrhage (United States)


    suggesting a role for this T- cell subset in both innate and acquired immunity (7, 8). Studies have shown that +% T cells are required for both controlled...increased infiltration of both lymphoid and myeloid cells in WT mice after TH-induced ALI. In parallel to +% T cells , myeloid cells (i.e., monocytes...GAMMA DELTA T CELLS REGULATE INFLAMMATORY CELL INFILTRATION OF THE LUNG AFTER TRAUMA-HEMORRHAGE Meenakshi Rani,* Qiong Zhang,* Richard F. Oppeltz

  11. P38 delta MAPK promotes breast cancer progression and lung metastasis by enhancing cell proliferation and cell detachment. (United States)

    Wada, M; Canals, D; Adada, M; Coant, N; Salama, M F; Helke, K L; Arthur, J S; Shroyer, K R; Kitatani, K; Obeid, L M; Hannun, Y A


    The protein p38 mitogen-activated protein kinase (MAPK) delta isoform (p38δ) is a poorly studied member of the MAPK family. Data analysis from The Cancer Genome Atlas database revealed that p38δ is highly expressed in all types of human breast cancers. Using a human breast cancer tissue array, we confirmed elevation in cancer tissue. The breast cancer mouse model, MMTV-PyMT (PyMT), developed breast tumors with lung metastasis; however, mice deleted in p38δ (PyMT/p38δ -/- ) exhibited delayed primary tumor formation and highly reduced lung metastatic burden. At the cellular level, we demonstrate that targeting of p38δ in breast cancer cells, MCF-7 and MDA-MB-231 resulted in a reduced rate of cell proliferation. In addition, cells lacking p38δ also displayed an increased cell-matrix adhesion and reduced cell detachment. This effect on cell adhesion was molecularly supported by the regulation of the focal adhesion kinase by p38δ in the human breast cell lines. These studies define a previously unappreciated role for p38δ in breast cancer development and evolution by regulating tumor growth and altering metastatic properties. This study proposes MAPK p38δ protein as a key factor in breast cancer. Lack of p38δ resulted in reduced primary tumor size and blocked the metastatic potential to the lungs.

  12. Deltas on the move. Making deltas cope with the effects of climate change

    International Nuclear Information System (INIS)

    Reker, J.; Van Winden, A.; Braakhekke, W.; Vermaat, J.; Eleveld, M.; Janssen, R.; De Reus, N.; Omzigt, N.


    -based context. Subsequently, a system was built to facilitate the handling of quality controlled data and results. This system has a web interface. Chapter 6 provides technical details, explains the use of the website and displays rankings of deltas with the DELTAS tool. Four examples of system-based measures in deltas are presented in Chapter 7. Finally, the conclusions of the study and recommendations for the next phase are presented in Chapter 8.

  13. Interleukin-1 beta induced synthesis of protein kinase C-delta and protein kinase C-epsilon in EL4 thymoma cells: possible involvement of phosphatidylinositol 3-kinase. (United States)

    Varley, C L; Royds, J A; Brown, B L; Dobson, P R


    We present evidence here that the proinflammatory cytokine, interleukin-1 beta (IL-1 beta) stimulates a significant increase in protein kinase C (PKC)-epsilon and PKC-delta protein levels and increases PKC-epsilon, but not PKC-delta, transcripts in EL4 thymoma cells. Incubation of EL4 cells with IL-1 beta induced protein synthesis of PKC-epsilon (6-fold increase) by 7 h and had a biphasic effect on PKC-delta levels with peaks at 4 h (2-fold increase) and 24 h (4-fold increase). At the level of mRNA, PKC-epsilon, but not PKC-delta levels, were induced after incubation of EL4 cells with IL-1 beta. The signalling mechanisms utilized by IL-1 beta to induce the synthesis of these PKC isoforms were investigated. Two phosphatidylinositol (PI) 3-kinase-specific inhibitors, wortmannin and LY294002, inhibited IL-1 beta-induced synthesis of PKC-epsilon. However, the PI 3-kinase inhibitors had little effect on the IL-1 beta-induced synthesis of PKC-delta in these cells. Our results indicate that IL-1 beta induced both PKC-delta and PKC-epsilon expression over different time periods. Furthermore, our evidence suggests that IL-1 beta induction of PKC-epsilon, but not PKC-delta, may occur via the PI 3-kinase pathway. Copyright 2001 S. Karger AG, Basel

  14. Alteration of RNA splicing by small molecule inhibitors of the interaction between NHP2L1 and U4 (United States)

    Diouf, Barthelemy; Lin, Wenwei; Goktug, Asli; Grace, Christy R. R.; Waddell, Michael Brett; Bao, Ju; Shao, Youming; Heath, Richard J.; Zheng, Jie J.; Shelat, Anang A.; Relling, Mary V.; Chen, Taosheng; Evans, William E.


    Splicing is an important eukaryotic mechanism for expanding the transcriptome and proteome, influencing a number of biological processes. Understanding its regulation and identifying small molecules that modulate this process remains a challenge. We developed an assay based on time-resolved FRET (TR-FRET) to detect the interaction between the protein NHP2L1 and U4 RNA, which are two key components of the spliceosome. We used this assay to identify small molecules that interfere with this interaction in a high-throughput screening (HTS) campaign. Topotecan and other camptothecin derivatives were among the top hits. We confirmed that topotecan disrupts the interaction between NHP2L1 and U4 by binding to U4 and inhibits RNA splicing. Our data reveal new functions of known drugs which could facilitate the development of therapeutic strategies to modify splicing and alter gene function. PMID:28985478

  15. Growth laws for sub-delta crevasses in the Mississippi River Delta (United States)

    Yocum, T. A.; Georgiou, I. Y.; Straub, K. M.


    River deltas are threatened by environmental change, including subsidence, global sea level rise, reduced sediment inputs and other local factors. In the Mississippi River Delta (MRD) these impacts are exemplified, and have led to proposed solutions to build land that include sediment diversions to reinitiate the delta cycle. Deltas were studied extensively using numerical models, theoretical and conceptual frameworks, empirical scaling relationships, laboratory models and field observations. But predicting the future of deltas relies on field observations where for most deltas data are still lacking. Moreover, empirical and theoretical scaling laws may be influenced by the data used to develop them, while laboratory deltas may be influenced by scaling issues. Anthropogenic crevasses in the MRD are large enough to overcome limitations of laboratory deltas, and small enough to allow for rapid channel and wetland development, providing an ideal setting to investigate delta development mechanics. Here we assessed growth laws of sub-delta crevasses (SDC) in the MRD, in two experimental laboratory deltas (LD - weakly and strongly cohesive) and compared them to river dominated deltas worldwide. Channel and delta geometry metrics for each system were obtained using geospatial tools, bathymetric datasets, sediment size, and hydrodynamic observations. Results show that SDC follow growth laws similar to large river dominated deltas, with the exception of some that exhibit anomalous behavior with respect to the frequency and distance to a bifurcation and the fraction of wetted delta shoreline (allometry metrics). Most SDC exhibit a systematic decrease of non-dimensional channel geometries with increased bifurcation order, indicating that channels are adjusting to decreased flow after bifurcations occur, and exhibit linear trends for land allometry and width-depth ratio, although geometries decrease more rapidly per bifurcation order. Measured distance to bifurcations in SDC

  16. Independence of protein kinase C-delta activity from activation loop phosphorylation: structural basis and altered functions in cells. (United States)

    Liu, Yin; Belkina, Natalya V; Graham, Caroline; Shaw, Stephen


    Activation loop phosphorylation plays critical regulatory roles for many kinases. Unlike other protein kinase Cs (PKC), PKC-delta does not require phosphorylation of its activation loop (Thr-507) for in vitro activity. We investigated the structural basis for this unusual capacity and its relevance to PKC-delta function in intact cells. Mutational analysis demonstrated that activity without Thr-507 phosphorylation depends on 20 residues N-terminal to the kinase domain and a pair of phenylalanines (Phe-500/Phe-527) unique to PKC-delta in/near the activation loop. Molecular modeling demonstrated that these elements stabilize the activation loop by forming a hydrophobic chain of interactions from the C-lobe to activation loop to N-terminal (helical) extension. In cells PKC-delta mediates both apoptosis and transcription regulation. We found that the T507A mutant of the PKC-delta kinase domain resembled the corresponding wild type in mediating apoptosis in transfected HEK293T cells. But the T507A mutant was completely defective in AP-1 and NF-kappaB reporter assays. A novel assay in which the kinase domain of PKC-delta and its substrate (a fusion protein of PKC substrate peptide with green fluorescent protein) were co-targeted to lipid rafts revealed a major substrate-selective defect of the T507A mutant in phosphorylating the substrate in cells. In vitro analysis showed strong product inhibition on the T507A mutant with particular substrates whose characteristics suggest it contributes to the substrate selective defect of the PKC-delta T507A mutant in cells. Thus, activation loop phosphorylation of PKC-delta may regulate its function in cells in a novel way.

  17. Carbon Nanotube Driver Circuit for 6 × 6 Organic Light Emitting Diode Display

    KAUST Repository

    Zou, Jianping; Zhang, Kang; Li, Jingqi; Zhao, Yongbiao; Wang, Yilei; Pillai, Suresh Kumar Raman; Volkan Demir, Hilmi; Sun, Xiaowei; Chan-Park, Mary B.; Zhang, Qing


    Single-walled carbon nanotube (SWNT) is expected to be a very promising material for flexible and transparent driver circuits for active matrix organic light emitting diode (AM OLED) displays due to its high field-effect mobility, excellent current carrying capacity, optical transparency and mechanical flexibility. Although there have been several publications about SWNT driver circuits, none of them have shown static and dynamic images with the AM OLED displays. Here we report on the first successful chemical vapor deposition (CVD)-grown SWNT network thin film transistor (TFT) driver circuits for static and dynamic AM OLED displays with 6 × 6 pixels. The high device mobility of ~45 cm2V−1s−1 and the high channel current on/off ratio of ~105 of the SWNT-TFTs fully guarantee the control capability to the OLED pixels. Our results suggest that SWNT-TFTs are promising backplane building blocks for future OLED displays.

  18. Carbon Nanotube Driver Circuit for 6 × 6 Organic Light Emitting Diode Display

    KAUST Repository

    Zou, Jianping


    Single-walled carbon nanotube (SWNT) is expected to be a very promising material for flexible and transparent driver circuits for active matrix organic light emitting diode (AM OLED) displays due to its high field-effect mobility, excellent current carrying capacity, optical transparency and mechanical flexibility. Although there have been several publications about SWNT driver circuits, none of them have shown static and dynamic images with the AM OLED displays. Here we report on the first successful chemical vapor deposition (CVD)-grown SWNT network thin film transistor (TFT) driver circuits for static and dynamic AM OLED displays with 6 × 6 pixels. The high device mobility of ~45 cm2V−1s−1 and the high channel current on/off ratio of ~105 of the SWNT-TFTs fully guarantee the control capability to the OLED pixels. Our results suggest that SWNT-TFTs are promising backplane building blocks for future OLED displays.

  19. Circulating gamma delta T cells are activated and depleted during progression of high-grade gliomas: Implications for gamma delta T cell therapy of GBM (United States)

    Glioblastoma multiforme (GBM) remains frustratingly impervious to any existing therapy. We have previously shown that GBM is sensitive to recognition and lysis by ex vivo activated gamma delta T cells, a minor subset of lymphocytes that innately recognize autologous stress-associated target antigens...

  20. Delta Scuti variables. Lecture 6

    International Nuclear Information System (INIS)

    Cox, A.N.


    The class of variables near or on the upper main sequence, the delta Scuti variables, are not only the usual ones about the masses, radii, and luminosities, but also the age, rotation, element diffusion to change the surface layer composition, the occurance of convection and the presence of radial and nonradial pulsation modes

  1. Complex rearrangements within the human J delta-C delta/J alpha-C alpha locus and aberrant recombination between J alpha segments

    NARCIS (Netherlands)

    Baer, R.; Boehm, T.; Yssel, H.; Spits, H.; Rabbitts, T. H.


    We have examined DNA rearrangements within a 120 kb cloned region of the human T cell receptor J delta-C delta/J alpha-C alpha locus. Three types of pattern emerge from an analysis of T cell lines and clones. Firstly, cells with two rearrangements within J delta-C delta; secondly, cells with one

  2. The roles of MCP-1 and protein kinase C delta activation in human eosinophilic leukemia EoL-1 cells. (United States)

    Lee, Ji-Sook; Yang, Eun Ju; Kim, In Sik


    Idiopathic hypereosinophilc syndrome is a disorder associated with clonally eosinophilic proliferation. The importance of FIP1-like-1-platelet-derived growth factor receptor-alpha (FIP1L1-PDGFRA) in the pathogenesis and classification of HES has been recently reported. In this study, we investigated the contribution of monocyte chemoattractant protein-1 (MCP-1)/CCL2 to chemotactic activity and protein kinase C delta (PKC delta in the human eosinophilic leukemia cell line EoL-1. These cells express CCR2 protein among the CC chemokine receptors (CCR1-5). MCP-1 induces strong migration of EoL-1 cells and the chemotaxis signal in response to MCP-1 involves a G(i)/G(o) protein, phospholipase C (PLC), PKC delta, p38 MAPK and NF-kappaB. MCP-1 activates p38 MAPK via G(i)/G(o) protein, PLC and PKC delta cascade. MCP-1 also induces NF-kappaB translocation and the activation is inhibited by PKC delta activation. The increase in the basal expression and activity of PKC delta in EoL-1 cells, compared to normal eosinophils, inhibits apoptosis in EoL-1 cells. Anti-apoptotic mechanism of PKC delta is related to inhibition of caspase 3 and caspase 9, but not to FIP1L1-PDGFRA. PKC delta functions as an anti-apoptotic molecule, and is involved in EoL-1 cell movement stimulated by MCP-1. This study contributes to an understanding of MCP-1 in eosinophil biology and pathogenic mechanism of eosinophilic disorders.

  3. Development of exosome surface display technology in living human cells

    International Nuclear Information System (INIS)

    Stickney, Zachary; Losacco, Joseph; McDevitt, Sophie; Zhang, Zhiwen; Lu, Biao


    Surface display technology is an emerging key player in presenting functional proteins for targeted drug delivery and therapy. Although a number of technologies exist, a desirable mammalian surface display system is lacking. Exosomes are extracellular vesicles that facilitate cell–cell communication and can be engineered as nano-shuttles for cell-specific delivery. In this study, we report the development of a novel exosome surface display technology by exploiting mammalian cell secreted nano-vesicles and their trans-membrane protein tetraspanins. By constructing a set of fluorescent reporters for both the inner and outer surface display on exosomes at two selected sites of tetraspanins, we demonstrated the successful exosomal display via gene transfection and monitoring fluorescence in vivo. We subsequently validated our system by demonstrating the expected intracellular partitioning of reporter protein into sub-cellular compartments and secretion of exosomes from human HEK293 cells. Lastly, we established the stable engineered cells to harness the ability of this robust system for continuous production, secretion, and uptake of displayed exosomes with minimal impact on human cell biology. In sum, our work paved the way for potential applications of exosome, including exosome tracking and imaging, targeted drug delivery, as well as exosome-mediated vaccine and therapy.

  4. Development of exosome surface display technology in living human cells

    Energy Technology Data Exchange (ETDEWEB)

    Stickney, Zachary, E-mail:; Losacco, Joseph, E-mail:; McDevitt, Sophie, E-mail:; Zhang, Zhiwen, E-mail:; Lu, Biao, E-mail:


    Surface display technology is an emerging key player in presenting functional proteins for targeted drug delivery and therapy. Although a number of technologies exist, a desirable mammalian surface display system is lacking. Exosomes are extracellular vesicles that facilitate cell–cell communication and can be engineered as nano-shuttles for cell-specific delivery. In this study, we report the development of a novel exosome surface display technology by exploiting mammalian cell secreted nano-vesicles and their trans-membrane protein tetraspanins. By constructing a set of fluorescent reporters for both the inner and outer surface display on exosomes at two selected sites of tetraspanins, we demonstrated the successful exosomal display via gene transfection and monitoring fluorescence in vivo. We subsequently validated our system by demonstrating the expected intracellular partitioning of reporter protein into sub-cellular compartments and secretion of exosomes from human HEK293 cells. Lastly, we established the stable engineered cells to harness the ability of this robust system for continuous production, secretion, and uptake of displayed exosomes with minimal impact on human cell biology. In sum, our work paved the way for potential applications of exosome, including exosome tracking and imaging, targeted drug delivery, as well as exosome-mediated vaccine and therapy.

  5. Changing T cell specificity by retroviral T cell receptor display

    NARCIS (Netherlands)

    Kessels, H. W.; van den Boom, M. D.; Spits, H.; Hooijberg, E.; Schumacher, T. N.


    The diversity of the T cell receptor (TCR) repertoire is limited, because of the processes of positive and negative T cell selection. To obtain T cells with specificities beyond the immune system's capacity, we have developed a strategy for retroviral TCR display. In this approach, a library of T

  6. Interspecies chimera between primate embryonic stem cells and mouse embryos: monkey ESCs engraft into mouse embryos, but not post-implantation fetuses. (United States)

    Simerly, Calvin; McFarland, Dave; Castro, Carlos; Lin, Chih-Cheng; Redinger, Carrie; Jacoby, Ethan; Mich-Basso, Jocelyn; Orwig, Kyle; Mills, Parker; Ahrens, Eric; Navara, Chris; Schatten, Gerald


    Unequivocal evidence for pluripotency in which embryonic stem cells contribute to chimeric offspring has yet to be demonstrated in human or nonhuman primates (NHPs). Here, rhesus and baboons ESCs were investigated in interspecific mouse chimera generated by aggregation or blastocyst injection. Aggregation chimera produced mouse blastocysts with GFP-nhpESCs at the inner cell mass (ICM), and embryo transfers (ETs) generated dimly-fluorescencing abnormal fetuses. Direct injection of GFP-nhpESCs into blastocysts produced normal non-GFP-fluorescencing fetuses. Injected chimera showed >70% loss of GFP-nhpESCs after 21 h culture. Outgrowths of all chimeric blastocysts established distinct but separate mouse- and NHP-ESC colonies. Extensive endogenous autofluorescence compromised anti-GFP detection and PCR analysis did not detect nhpESCs in fetuses. NhpESCs localize to the ICM in chimera and generate pregnancies. Because primate ESCs do not engraft post-implantation, and also because endogenous autofluorescence results in misleading positive signals, interspecific chimera assays for pluripotency with primate stem cells is unreliable with the currently available ESCs. Testing primate ESCs reprogrammed into even more naïve states in these inter-specific chimera assays will be an important future endeavor. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Detection of Staphylococcus aureus delta-toxin production by whole-cell MALDI-TOF mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Julie Gagnaire

    Full Text Available The aim of the present study was to detect the Staphylococcus aureus delta-toxin using Whole-Cell (WC Matrix Assisted Laser Desorption Ionization-Time-of-Flight (MALDI-TOF mass spectrometry (MS, correlate delta-toxin expression with accessory gene regulator (agr status, and assess the prevalence of agr deficiency in clinical isolates with and without resistance to methicillin and glycopeptides. The position of the delta-toxin peak in the mass spectrum was identified using purified delta-toxin and isogenic wild type and mutant strains for agr-rnaIII, which encodes delta-toxin. Correlation between delta-toxin production and agr RNAIII expression was assessed by northern blotting. A series of 168 consecutive clinical isolates and 23 unrelated glycopeptide-intermediate S. aureus strains (GISA/heterogeneous GISA were then tested by WC-MALDI-TOF MS. The delta-toxin peak was detected at 3005±5 Thomson, as expected for the naturally formylated delta toxin, or at 3035±5 Thomson for its G10S variant. Multivariate analysis showed that chronicity of S. aureus infection and glycopeptide resistance were significantly associated with delta-toxin deficiency (p = 0.048; CI 95%: 1.01-10.24; p = 0.023; CI 95%: 1.20-12.76, respectively. In conclusion, the S. aureus delta-toxin was identified in the WC-MALDI-TOF MS spectrum generated during routine identification procedures. Consequently, agr status can potentially predict infectious complications and rationalise application of novel virulence factor-based therapies.

  8. Study of LnBaCo{sub 2}O{sub 6-d}elta (Ln = Pr, Nd, Sm and Gd) double perovskites as new cathode material for IT-SOFC

    Energy Technology Data Exchange (ETDEWEB)

    Chavez, E; Mueller, M; Mogni, L; Caneiro, A, E-mail: [Centro Atomico Bariloche-CNEA, Instituto Balseiro. Av. Bustillo 9500, S. C. de Bariloche 8400 (Argentina)


    Oxides with double perovskites structures of general composition LnBaCo{sub 2}O{sub 6-d}elta (Ln = Pr, Nd, Sm and Gd) were synthesized by solid state reaction with the purpose to evaluate new materials to be used as cathodes in intermediate temperature solid oxide fuel cell (IT-SOFC). A preliminary study about electrochemical properties was performed by impedance spectroscopy between 500 and 800 deg. C under atmosphere of pure O{sub 2}. Symmetrical cells were obtained by spray deposition of LnBaCo{sub 2}O{sub 6-d}elta (Ln = Pr, Nd, Sm and Gd) at both sides of a dense ceramic electrolyte. The impedance spectroscopy measurements as a function of temperatures show a hysteresis loop which could be associated to a tetragonal/orthorhombic phase transition. The existence of this transition was corroborated by high temperature X-Ray diffraction and Differential Scanning Calorimetry measurements.

  9. CD271+ osteosarcoma cells display stem-like properties.

    Directory of Open Access Journals (Sweden)

    Jiguang Tian

    Full Text Available Cancer stem cell (CSC theory has been proposed and verified in many cancers. The existence of osteosarcoma CSCs has been confirmed for many years and multiple surface markers have been employed to identify them. In this study, we identified CD271(+ subpopulation of osteosarcoma displaying stem-like properties. CD271, known as the neural crest nerve growth factor receptor, is the marker of bone marrow mesenchymal stem cells (MSCs and human melanoma-initiating cells. We discovered that CD271 was expressed differentially in diverse types of human osteosarcoma and stabilized cell lines. CD271(+ osteosarcoma cells displayed most of the properties of CSC, such as self-renewal, differentiation, drug resistance and tumorigenicity in vivo. Nanog, Oct3/4, STAT3, DNA-PKcs, Bcl-2 and ABCG2 were more expressed in CD271(+ cells compared with CD271- cells. Our study supported the osteosarcoma CSC hypothesis and, to a certain extent, revealed one of the possible mechanisms involved in maintaining CSCs properties.

  10. A Novel Dual HDAC6 and Tubulin Inhibitor, MPT0B451, Displays Anti-tumor Ability in Human Cancer Cells in Vitro and in Vivo

    Directory of Open Access Journals (Sweden)

    Yi-Wen Wu


    Full Text Available The combination cancer therapy is a new strategy to circumvent drug resistance for the treatment of high metastasis and advanced malignancies. Herein, we developed a synthesized compound MPT0B451 that display inhibitory effect against histone deacetylase (HDAC 6 and tubulin assembly. Our data demonstrated that MPT0B451 significantly inhibited cancer cell growths in HL-60 and PC-3 cells due to inhibition of HDAC activity. MPT0B451 also markedly increased caspase-mediated apoptosis in these cells. The cell cycle analysis showed mitotic arrest induced by MPT0B451 with enhanced expression of G2/M transition proteins. Moreover, molecular docking analysis supported MPT0B451 as a dual HDAC6 and tubulin inhibitor. Finally, MPT0B451 led to tumor growth inhibition (TGI in HL-60 and PC-3 xenograft models. These findings indicated that MPT0B451 has dual inhibition effects for HDAC6 and tubulin, and also contributed to G2/M arrest followed by apoptotic induction. Together, our results suggested that MPT0B451 may serve as a potent anti-cancer treatment regimen in human prostate cancer and acute myeloid leukemia.

  11. Primate Cerebellar Granule Cells Exhibit a Tonic GABAAR Conductance that is not Affected by Alcohol: A Possible Cellular Substrate of the Low Level of Response Phenotype.

    Directory of Open Access Journals (Sweden)

    Claudia eMohr


    Full Text Available In many rodent brain regions, alcohol increases vesicular release of GABA, resulting in an increase in the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs and the magnitude of tonic GABAA receptor (GABAAR currents. A neglected issue in translating the rodent literature to humans is the possibility that phylogenetic differences alter the actions of alcohol. To address this issue we made voltage-clamp recordings from granule cells (GCs in cerebellar slices from the non-human primate, Macaca fascicularis. We found that similar to Sprague Dawley rats (SDRs, non-human primate (NHP GCs exhibit a tonic conductance generated by 6 subunit containing GABAARs, as evidenced by its blockade by the broad spectrum GABAAR antagonist, GABAzine (10M, inhibition by 6 selective antagonist, furosemide (100M, and enhancement by THDOC (10-20nM and THIP (500nM. In contrast to SDR GCs, in most NHP GCs (~60%, application of EtOH (25-105mM did not increase sIPSC frequency or the tonic GABAAR current. In a minority of cells (~40%, EtOH did increase sIPSC frequency and the tonic current. The relative lack of response to EtOH was associated with reduced expression of neuronal nitric oxide synthase (nNOS, which we recently reported mediates EtOH-induced enhancement of vesicular GABA release in rats. The EtOH-induced increase in tonic GABAAR current was significantly smaller in NHPs than in SDRs, presumably due to less GABA release, because there were no obvious differences in the density of GABAARs or GABA transporters between SDR and NHP GCs. Thus, EtOH does not directly modulate 6 subunit GABAARs in NHPs. Instead, EtOH enhanced GABAergic transmission is mediated by enhanced GABA release. Further, SDR GC responses to alcohol are only representative of a subpopulation of NHP GCs. This suggests that the impact of EtOH on NHP cerebellar physiology will be reduced compared to SDRs, and will likely have different computational and behavioral

  12. Cell-surface display of enzymes by the yeast Saccharomyces cerevisiae for synthetic biology. (United States)

    Tanaka, Tsutomu; Kondo, Akihiko


    In yeast cell-surface displays, functional proteins, such as cellulases, are genetically fused to an anchor protein and expressed on the cell surface. Saccharomyces cerevisiae, which is often utilized as a cell factory for the production of fuels, chemicals, and proteins, is the most commonly used yeast for cell-surface display. To construct yeast cells with a desired function, such as the ability to utilize cellulose as a substrate for bioethanol production, cell-surface display techniques for the efficient expression of enzymes on the cell membrane need to be combined with metabolic engineering approaches for manipulating target pathways within cells. In this Minireview, we summarize the recent progress of biorefinery fields in the development and application of yeast cell-surface displays from a synthetic biology perspective and discuss approaches for further enhancing cell-surface display efficiency. © FEMS 2015. All rights reserved. For permissions, please e-mail:

  13. Bioadsorption of cadmium ion by cell surface-engineered yeasts displaying metallothionein and hexa-His

    Energy Technology Data Exchange (ETDEWEB)

    Kuroda, K.; Ueda, M. [Lab. of Applied Biological Chemistry, Kyoto Univ., Yoshida, Kyoto (Japan)


    The Cd{sup 2+}-chelating abilities of yeast metallothionein (YMT) and hexa-His displayed on the yeast-cell surface were compared. Display of YMT and hexa-His by {alpha}-agglutinin-based cell-surface engineering was confirmed by immunofluorescent labeling. Surface-engineered yeast cells with YMT and hexa-His fused in tandem showed superior cell-surface adsorption and recovery of Cd{sup 2+} under EDTA treatment on the cell surface than hexa-His-displaying cells. YMT was demonstrated to be more effective than hexa-His for the adsorption of Cd{sup 2+}. Yeast cells displaying YMT and/or hexa-His exhibited a higher potential for the adsorption of Cd{sup 2+} than Escherichia coli cells displaying these molecules. In order to investigate the effect of the displayed YMT and hexa-His on sensitivity to toxic Cd{sup 2+}, growth in Cd{sup 2+}-containing liquid medium was monitored. Unlike hexa-His-displaying cells, cells displaying YMT and hexa-His fused in tandem induced resistance to Cd{sup 2+} through active and enhanced adsorption of toxic Cd{sup 2+}. These results indicate that YMT-displaying yeast cells are a unique bioadsorbent with a functional chelating ability superior to that of E. coli. (orig.)

  14. Perturbation and proinflammatory type activation of Vd1+ gamma delta T cells in African children with Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Hviid, L; Kurtzhals, J A; Adabayeri, V


    of Plasmodium falciparum malaria in Ghanaian children and they can constitute 30 to 50% of all T cells shortly after initiation of antimalarial chemotherapy. The bulk of the gamma delta T cells involved in this perturbation expressed V delta 1 and had a highly activated phenotype. Analysis of the T...

  15. The transcriptomes of novel marmoset monkey embryonic stem cell lines reflect distinct genomic features. (United States)

    Debowski, Katharina; Drummer, Charis; Lentes, Jana; Cors, Maren; Dressel, Ralf; Lingner, Thomas; Salinas-Riester, Gabriela; Fuchs, Sigrid; Sasaki, Erika; Behr, Rüdiger


    Embryonic stem cells (ESCs) are useful for the study of embryonic development. However, since research on naturally conceived human embryos is limited, non-human primate (NHP) embryos and NHP ESCs represent an excellent alternative to the corresponding human entities. Though, ESC lines derived from naturally conceived NHP embryos are still very rare. Here, we report the generation and characterization of four novel ESC lines derived from natural preimplantation embryos of the common marmoset monkey (Callithrix jacchus). For the first time we document derivation of NHP ESCs derived from morula stages. We show that quantitative chromosome-wise transcriptome analyses precisely reflect trisomies present in both morula-derived ESC lines. We also demonstrate that the female ESC lines exhibit different states of X-inactivation which is impressively reflected by the abundance of the lncRNA X inactive-specific transcript (XIST). The novel marmoset ESC lines will promote basic primate embryo and ESC studies as well as preclinical testing of ESC-based regenerative approaches in NHP.

  16. A novel mouse PKC{delta} splice variant, PKC{delta}IX, inhibits etoposide-induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung D. [School of Biological Sciences, University of Ulsan, Ulsan (Korea, Republic of); Seo, Kwang W. [Department of Internal Medicines, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan (Korea, Republic of); Lee, Eun A.; Quang, Nguyen N. [School of Biological Sciences, University of Ulsan, Ulsan (Korea, Republic of); Cho, Hong R. [Department of Surgery, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan (Korea, Republic of); Biomedical Research Center, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan (Korea, Republic of); Kwon, Byungsuk, E-mail: [School of Biological Sciences, University of Ulsan, Ulsan (Korea, Republic of); Biomedical Research Center, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan (Korea, Republic of)


    Highlights: {yields} A novel PKC{delta} isoform, named PKC{delta}IX, that lacks the C1 domain and the ATP-binding site is ubiquitously expressed. {yields} PKC{delta}IX inhibits etoposide-induced apoptosis. {yields} PKC{delta}IX may function as an endogenous dominant negative isoform for PKC{delta}. -- Abstract: Protein kinase C (PKC) {delta} plays an important role in cellular proliferation and apoptosis. The catalytic fragment of PKC{delta} generated by caspase-dependent cleavage is essential for the initiation of etoposide-induced apoptosis. In this study, we identified a novel mouse PKC{delta} isoform named PKC{delta}IX (Genebank Accession No. (HQ840432)). PKC{delta}IX is generated by alternative splicing and is ubiquitously expressed, as seen in its full-length PKC{delta}. PKC{delta}IX lacks the C1 domain, the caspase 3 cleavage site, and the ATP binding site but preserves an almost intact c-terminal catalytic domain and a nuclear localization signal (NLS). The structural characteristics of PKC{delta}IX provided a possibility that this PKC{delta} isozyme functions as a novel dominant-negative form for PKC{delta} due to its lack of the ATP-binding domain that is required for the kinase activity of PKC{delta}. Indeed, overexpression of PKC{delta}IX significantly inhibited etoposide-induced apoptosis in NIH3T3 cells. In addition, an in vitro kinase assay showed that recombinant PKC{delta}IX protein could competitively inhibit the kinase activity of PKC{delta}. We conclude that PKC{delta}IX can function as a natural dominant-negative inhibitor of PKC{delta}in vivo.

  17. Lentivirus display: stable expression of human antibodies on the surface of human cells and virus particles.

    Directory of Open Access Journals (Sweden)

    Ran Taube

    Full Text Available BACKGROUND: Isolation of human antibodies using current display technologies can be limited by constraints on protein expression, folding and post-translational modifications. Here we describe a discovery platform that utilizes self-inactivating (SIN lentiviral vectors for the surface display of high-affinity single-chain variable region (scFv antibody fragments on human cells and lentivirus particles. METHODOLOGY/PRINCIPAL FINDINGS: Bivalent scFvFc human antibodies were fused in frame with different transmembrane (TM anchoring moieties to allow efficient high-level expression on human cells and the optimal TM was identified. The addition of an eight amino acid HIV-1 gp41 envelope incorporation motif further increased scFvFc expression on human cells and incorporation into lentiviral particles. Both antibody-displaying human cells and virus particles bound antigen specifically. Sulfation of CDR tyrosine residues, a property recently shown to broaden antibody binding affinity and antigen recognition was also demonstrated. High level scFvFc expression and stable integration was achieved in human cells following transduction with IRES containing bicistronic SIN lentivectors encoding ZsGreen when scFvFc fusion proteins were expressed from the first cassette. Up to 10(6-fold enrichment of antibody expressing cells was achieved with one round of antigen coupled magnetic bead pre-selection followed by FACS sorting. Finally, the scFvFc displaying human cells could be used directly in functional biological screens with remarkable sensitivity. CONCLUSIONS/SIGNIFICANCE: This antibody display platform will complement existing technologies by virtue of providing properties unique to lentiviruses and antibody expression in human cells, which, in turn, may aid the discovery of novel therapeutic human mAbs.

  18. [mRNA expression of notch ligand-delta-like-1 and jagged-1 in mesenchymal stem cells of MDS patients]. (United States)

    Fei, Cheng-Ming; Gu, Shu-Cheng; Zhao, You-Shan; Guo, Juan; Li, Xiao; Chang, Chun-Kang


    This study was aimed to investigated the mRNA expression levels of Notch ligands- Delta-like-1 and Jagged-1 in bone marrow mesenchymal stem cells of patients with myelodysplastic syndrome (MDS), and to explore their relation with onset of MDS. Bone marrow mesenchymal stem cells of 38 patients with MDS and 16 normal subjects as control were collected to detect mRNA expression of Delta-like-1 and Jagged-1 by using real-time quantitative polymerase chain reaction. The results showed that the expression levels of Delta-like-1 and Jagged-1 in mesenchymal stem cells of MDS patients were significantly higher than that in normal controls (P MDS patients (r = 0.502, P MDS patients with abnormal karyotypes were significantly higher than those in MDS patients with normal karyotypes (P 0.05). It is concluded that the changes of Delta-like-1 and Jagged-1 expression level in MSC may play a role in the pathogenesis of myelodysplastic syndrome.

  19. Cell wall structure suitable for surface display of proteins in Saccharomyces cerevisiae. (United States)

    Matsuoka, Hiroyuki; Hashimoto, Kazuya; Saijo, Aki; Takada, Yuki; Kondo, Akihiko; Ueda, Mitsuyoshi; Ooshima, Hiroshi; Tachibana, Taro; Azuma, Masayuki


    A display system for adding new protein functions to the cell surfaces of microorganisms has been developed, and applications of the system to various fields have been proposed. With the aim of constructing a cell surface environment suitable for protein display in Saccharomyces cerevisiae, the cell surface structures of cell wall mutants were investigated. Four cell wall mutant strains were selected by analyses using a GFP display system via a GPI anchor. β-Glucosidase and endoglucanase II were displayed on the cell surface in the four mutants, and their activities were evaluated. mnn2 deletion strain exhibited the highest activity for both the enzymes. In particular, endoglucanase II activity using carboxymethylcellulose as a substrate in the mutant strain was 1.9-fold higher than that of the wild-type strain. In addition, the activity of endoglucanase II released from the mnn2 deletion strain by Zymolyase 20T treatment was higher than that from the wild-type strain. The results of green fluorescent protein (GFP) and endoglucanase displays suggest that the amounts of enzyme displayed on the cell surface were increased by the mnn2 deletion. The enzyme activity of the mnn2 deletion strain was compared with that of the wild-type strain. The relative value (mnn2 deletion mutant/wild-type strain) of endoglucanase II activity using carboxymethylcellulose as a substrate was higher than that of β-glucosidase activity using p-nitrophenyl-β-glucopyranoside as a substrate, suggesting that the cell surface environment of the mnn2 deletion strain facilitates the binding of high-molecular-weight substrates to the active sites of the displayed enzymes. Copyright © 2014 John Wiley & Sons, Ltd.

  20. Activation of PPAR{delta} up-regulates fatty acid oxidation and energy uncoupling genes of mitochondria and reduces palmitate-induced apoptosis in pancreatic {beta}-cells

    Energy Technology Data Exchange (ETDEWEB)

    Wan, Jun; Jiang, Li; Lue, Qingguo; Ke, Linqiu [Department of Endocrinology, West China Hospital of Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan 610041 (China); Li, Xiaoyu [State Key Laboratory of Oral Diseases, Sichuan University, No. 14, 3rd Section, Renmin South Road, Chengdu, Sichuan 610041 (China); Tong, Nanwei, E-mail: [Department of Endocrinology, West China Hospital of Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan 610041 (China)


    Recent evidence indicates that decreased oxidative capacity, lipotoxicity, and mitochondrial aberrations contribute to the development of insulin resistance and type 2 diabetes. The goal of this study was to investigate the effects of peroxisome proliferator-activated receptor {delta} (PPAR{delta}) activation on lipid oxidation, mitochondrial function, and insulin secretion in pancreatic {beta}-cells. After HIT-T15 cells (a {beta}-cell line) were exposed to high concentrations of palmitate and GW501516 (GW; a selective agonist of PPAR{delta}), we found that administration of GW increased the expression of PPAR{delta} mRNA. GW-induced activation of PPAR{delta} up-regulated carnitine palmitoyltransferase 1 (CPT1), long-chain acyl-CoA dehydrogenase (LCAD), pyruvate dehydrogenase kinase 4 (PDK4), and uncoupling protein 2 (UCP2); alleviated mitochondrial swelling; attenuated apoptosis; and reduced basal insulin secretion induced by increased palmitate in HIT cells. These results suggest that activation of PPAR{delta} plays an important role in protecting pancreatic {beta}-cells against aberrations caused by lipotoxicity in metabolic syndrome and diabetes.

  1. A Fluid Membrane-Based Soluble Ligand Display System for Live CellAssays

    Energy Technology Data Exchange (ETDEWEB)

    Nam, Jwa-Min; Nair, Pradeep N.; Neve, Richard M.; Gray, Joe W.; Groves, Jay T.


    Cell communication modulates numerous biological processes including proliferation, apoptosis, motility, invasion and differentiation. Correspondingly, there has been significant interest in the development of surface display strategies for the presentation of signaling molecules to living cells. This effort has primarily focused on naturally surface-bound ligands, such as extracellular matrix components and cell membranes. Soluble ligands (e.g. growth factors and cytokines) play an important role in intercellular communications, and their display in a surface-bound format would be of great utility in the design of array-based live cell assays. Recently, several cell microarray systems that display cDNA, RNAi, or small molecules in a surface array format were proven to be useful in accelerating high-throughput functional genetic studies and screening therapeutic agents. These surface display methods provide a flexible platform for the systematic, combinatorial investigation of genes and small molecules affecting cellular processes and phenotypes of interest. In an analogous sense, it would be an important advance if one could display soluble signaling ligands in a surface assay format that allows for systematic, patterned presentation of soluble ligands to live cells. Such a technique would make it possible to examine cellular phenotypes of interest in a parallel format with soluble signaling ligands as one of the display parameters. Herein we report a ligand-modified fluid supported lipid bilayer (SLB) assay system that can be used to functionally display soluble ligands to cells in situ (Figure 1A). By displaying soluble ligands on a SLB surface, both solution behavior (the ability to become locally enriched by reaction-diffusion processes) and solid behavior (the ability to control the spatial location of the ligands in an open system) could be combined. The method reported herein benefits from the naturally fluid state of the supported membrane, which allows

  2. COMMD1 regulates the delta epithelial sodium channel ({delta}ENaC) through trafficking and ubiquitination

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Tina; Ke, Ying; Ly, Kevin [Department of Physiology, University of Otago, P.O. Box 913, Dunedin 9054 (New Zealand); McDonald, Fiona J., E-mail: [Department of Physiology, University of Otago, P.O. Box 913, Dunedin 9054 (New Zealand)


    Highlights: {yields} The COMM domain of COMMD1 mediates binding to {delta}ENaC. {yields} COMMD1 reduces the cell surface population of {delta}ENaC. {yields} COMMD1 increases the population of {delta}ENaC-ubiquitin. {yields} Both endogenous and transfected {delta}ENaC localize with COMMD1 and transferrin suggesting they are located in early/recycling endosomes. -- Abstract: The delta subunit of the epithelial sodium channel ({delta}ENaC) is a member of the ENaC/degenerin family of ion channels. {delta}ENaC is distinct from the related {alpha}-, {beta}- and {gamma}ENaC subunits, known for their role in sodium homeostasis and blood pressure control, as {delta}ENaC is expressed in brain neurons and activated by external protons. COMMD1 (copper metabolism Murr1 domain 1) was previously found to associate with and downregulate {delta}ENaC activity. Here, we show that COMMD1 interacts with {delta}ENaC through its COMM domain. Co-expression of {delta}ENaC with COMMD1 significantly reduced {delta}ENaC surface expression, and led to an increase in {delta}ENaC ubiquitination. Immunocytochemical and confocal microscopy studies show that COMMD1 promoted localization of {delta}ENaC to the early/recycling endosomal pool where the two proteins were localized together. These results suggest that COMMD1 downregulates {delta}ENaC activity by reducing {delta}ENaC surface expression through promoting internalization of surface {delta}ENaC to an intracellular recycling pool, possibly via enhanced ubiquitination.

  3. Delta Cell Hyperplasia in Adult Goto-Kakizaki (GK/MolTac) Diabetic Rats

    Czech Academy of Sciences Publication Activity Database

    Alán, Lukáš; Olejár, Tomáš; Cahová, M.; Zelenka, Jaroslav; Berková, Z.; Smětáková, M.; Saudek, F.; Matěj, R.; Ježek, Petr


    Roč. 2015, č. 2015 (2015), s. 385395 ISSN 2314-6745 R&D Projects: GA ČR(CZ) GA13-06666S Institutional support: RVO:67985823 Keywords : Goto Kakizaki rats * diabetes * delta cell hyperplasia * somatostatin * pancreatic polypeptide deficiency Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 2.431, year: 2015

  4. Human SGT interacts with Bag-6/Bat-3/Scythe and cells with reduced levels of either protein display persistence of few misaligned chromosomes and mitotic arrest

    International Nuclear Information System (INIS)

    Winnefeld, Marc; Grewenig, Annabel; Schnoelzer, Martina; Spring, Herbert; Knoch, Tobias A.; Gan, Eugene C.; Rommelaere, Jean; Cziepluch, Celina


    The human small glutamine-rich TPR-containing protein (hSGT) is essential for cell division since RNA-interference-mediated strong reduction of hSGT protein levels causes mitotic arrest (M. Winnefeld, J. Rommelaere, and C. Cziepluch, The human small glutamine-rich TPR-containing protein is required for progress through cell division, Exp. Cell Res. 293 (2004), 43-57). Analysis of HeLa cells expressing a histone 2A-YFP fusion protein revealed the continuous presence of few mislocalized chromosomes close to the spindle poles as possible cause for hSGT depletion-dependent prometaphase arrest. Cells unable to rescue these mislocalized chromosomes into the metaphase plate died at this stage through apoptosis. In order to address hSGT function at the molecular level, mass spectrometry analysis of proteins which co-immunoprecipitated with Flag-tagged hSGT was performed. Thereby, Hsp70 and Bag-6/Bat-3/Scythe were identified as novel hSGT interaction partners while interaction with Hsc70 was confirmed. Results obtained with truncated versions of the hSGT protein revealed that Bag-6/Bat-3/Scythe and Hsp70 or Hsc70 were independently able to form complexes with hSGT. Interaction of hSGT with Hsc70, Hsp70 or Bag-6/Bat-3/Scythe was demonstrated in prometaphase, thereby suggesting a possible role for complexes containing hSGT and distinct (co)-chaperones during mitosis. Finally, cells from populations with reduced levels of Bag-6/Bat-3/Scythe also displayed persistence of mislocalized chromosomes and mitotic arrest, which strongly indicated that hSGT-Bag-6/Bat-3/Scythe complexes could be directly or indirectly required for complete chromosome congression

  5. Renal Allograft Survival in Nonhuman Primates Infused With Donor Antigen-Pulsed Autologous Regulatory Dendritic Cells. (United States)

    Ezzelarab, M B; Raich-Regue, D; Lu, L; Zahorchak, A F; Perez-Gutierrez, A; Humar, A; Wijkstrom, M; Minervini, M; Wiseman, R W; Cooper, D K C; Morelli, A E; Thomson, A W


    Systemic administration of autologous regulatory dendritic cells (DCreg; unpulsed or pulsed with donor antigen [Ag]), prolongs allograft survival and promotes transplant tolerance in rodents. Here, we demonstrate that nonhuman primate (NHP) monocyte-derived DCreg preloaded with cell membrane vesicles from allogeneic peripheral blood mononuclear cells induce T cell hyporesponsiveness to donor alloantigen (alloAg) in vitro. These donor alloAg-pulsed autologous DCreg (1.4-3.6 × 10 6 /kg) were administered intravenously, 1 day before MHC-mismatched renal transplantation to rhesus monkeys treated with costimulation blockade (cytotoxic T lymphocyte Ag 4 immunoglobulin [CTLA4] Ig) and tapered rapamycin. Prolongation of graft median survival time from 39.5 days (no DCreg infusion; n = 6 historical controls) and 29 days with control unpulsed DCreg (n = 2), to 56 days with donor Ag-pulsed DCreg (n = 5) was associated with evidence of modulated host CD4 + and CD8 + T cell responses to donor Ag and attenuation of systemic IL-17 production. Circulating anti-donor antibody (Ab) was not detected until CTLA4 Ig withdrawal. One monkey treated with donor Ag-pulsed DCreg rejected its graft in association with progressively elevated anti-donor Ab, 525 days posttransplant (160 days after withdrawal of immunosuppression). These findings indicate a modest but not statistically significant beneficial effect of donor Ag-pulsed autologous DCreg infusion on NHP graft survival when administered with a minimal immunosuppressive drug regimen. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  6. Reliable cloning of functional antibody variable domains from hybridomas and spleen cell repertoires employing a reengineered phage display system. (United States)

    Krebber, A; Bornhauser, S; Burmester, J; Honegger, A; Willuda, J; Bosshard, H R; Plückthun, A


    A prerequisite for the use of recombinant antibody technologies starting from hybridomas or immune repertoires is the reliable cloning of functional immunoglobulin genes. For this purpose, a standard phage display system was optimized for robustness, vector stability, tight control of scFv-delta geneIII expression, primer usage for PCR amplification of variable region genes, scFv assembly strategy and subsequent directional cloning using a single rare cutting restriction enzyme. This integrated cloning, screening and selection system allowed us to rapidly obtain antigen binding scFvs derived from spleen-cell repertoires of mice immunized with ampicillin as well as from all hybridoma cell lines tested to date. As representative examples, cloning of monoclonal antibodies against a his tag, leucine zippers, the tumor marker EGP-2 and the insecticide DDT is presented. Several hybridomas whose genes could not be cloned in previous experimental setups, but were successfully obtained with the present system, expressed high amounts of aberrant heavy and light chain mRNAs, which were amplified by PCR and greatly exceeded the amount of binding antibody sequences. These contaminating variable region genes were successfully eliminated by employing the optimized phage display system, thus avoiding time consuming sequencing of non-binding scFv genes. To maximize soluble expression of functional scFvs subsequent to cloning, a compatible vector series to simplify modification, detection, multimerization and rapid purification of recombinant antibody fragments was constructed.

  7. Somato-synaptic variation of GABA(A) receptors in cultured murine cerebellar granule cells: investigation of the role of the alpha6 subunit. (United States)

    Mellor, J R; Wisden, W; Randall, A D


    Electrophysiological investigation of cultured cerebellar murine granule cells revealed differences between the GABA(A) receptors at inhibitory synapses and those on the cell body. Specifically, mIPSCs decayed more rapidly than cell body receptors deactivated, the mean single channel conductance at the synapse (32 pS) was greater than that at cell body (21 pS) and only cell body receptors were sensitive to Zn(2+) (150 microM), which depressed response amplitude by 82+/-5% and almost doubled the rate of channel deactivation. The GABA(A) receptor alpha6 subunit is selectively expressed in cerebellar granule cells. Although concentrated at synapses, it is also found on extrasynaptic membranes. Using a mouse line (Deltaalpha6lacZ) lacking this subunit, we investigated its role in the somato-synaptic differences in GABA(A) receptor function. All differences between cell body and synaptic GABA(A) receptors observed in wild-type (WT) granule cells persisted in Deltaalpha6lacZ cells, thus demonstrating that they are not specifically due to the cellular distribution of the alpha6 subunit. However, mIPSCs from WT and Deltaalpha6lacZ cells differed in both their kinetics (faster decay in WT cells) and underlying single channel conductance (32 pS WT, 25 pS Deltaalpha6lacZ). This provides good evidence for a functional contribution of the alpha6 subunit to postsynaptic GABA(A) receptors in these cells. Despite this, deactivation kinetics of mIPSCs in WT and Deltaalpha6lacZ granule cells exhibited similar benzodiazepene (BDZ) sensitivity. This suggests that the enhanced BDZ-induced ataxia seen in Deltaalpha6lacZ mice may reflect physiological activity at extrasynaptic receptors which, unlike those at synapses, display differential BDZ-sensitivity in WT and Deltaalpha6lacZ granule cells (Jones, A.M., Korpi, E.R., McKernan, R.M., Nusser, Z., Pelz, R., Makela, R., Mellor, J.R., Pollard, S., Bahn, S., Stephenson, F.A., Randall, A.D., Sieghart, W., Somogyi, P., Smith, A.J.H., Wisden

  8. Enrichment of human embryonic stem cell-derived NKX6.1-expressing pancreatic progenitor cells accelerates the maturation of insulin-secreting cells in vivo. (United States)

    Rezania, Alireza; Bruin, Jennifer E; Xu, Jean; Narayan, Kavitha; Fox, Jessica K; O'Neil, John J; Kieffer, Timothy J


    Human embryonic stem cells (hESCs) are considered a potential alternative to cadaveric islets as a source of transplantable cells for treating patients with diabetes. We previously described a differentiation protocol to generate pancreatic progenitor cells from hESCs, composed of mainly pancreatic endoderm (PDX1/NKX6.1-positive), endocrine precursors (NKX2.2/synaptophysin-positive, hormone/NKX6.1-negative), and polyhormonal cells (insulin/glucagon-positive, NKX6.1-negative). However, the relative contributions of NKX6.1-negative versus NKX6.1-positive cell fractions to the maturation of functional β-cells remained unclear. To address this question, we generated two distinct pancreatic progenitor cell populations using modified differentiation protocols. Prior to transplant, both populations contained a high proportion of PDX1-expressing cells (~85%-90%) but were distinguished by their relatively high (~80%) or low (~25%) expression of NKX6.1. NKX6.1-high and NKX6.1-low progenitor populations were transplanted subcutaneously within macroencapsulation devices into diabetic mice. Mice transplanted with NKX6.1-low cells remained hyperglycemic throughout the 5-month post-transplant period whereas diabetes was reversed in NKX6.1-high recipients within 3 months. Fasting human C-peptide levels were similar between groups throughout the study, but only NKX6.1-high grafts displayed robust meal-, glucose- and arginine-responsive insulin secretion as early as 3 months post-transplant. NKX6.1-low recipients displayed elevated fasting glucagon levels. Theracyte devices from both groups contained almost exclusively pancreatic endocrine tissue, but NKX6.1-high grafts contained a greater proportion of insulin-positive and somatostatin-positive cells, whereas NKX6.1-low grafts contained mainly glucagon-expressing cells. Insulin-positive cells in NKX6.1-high, but not NKX6.1-low grafts expressed nuclear MAFA. Collectively, this study demonstrates that a pancreatic endoderm

  9. La(0.4)Ba(0.6)Fe(0.8)Zn(0.2)O(3-delta) as cathode in solid oxide fuel cells for simultaneous NO reduction and electricity generation. (United States)

    Zhou, Renjie; Bu, Yunfei; Xu, Dandan; Zhong, Qin


    A perovskite-type oxide La(0.4)Ba(0.6)Fe(0.8)Zn(0.2)O(3-delta) (LBFZ) was investigated as the cathode material for simultaneous NO reduction and electricity generation in solid oxide fuel cells (SOFCs). The microstructure of LBFZ was demonstrated by X-ray diffraction and scanning electron microscopy. The results showed that a single cubic perovskite LBFZ was formed after calcined at 1100 degrees C. Meanwhile, the solid-state reaction between LBFZ and Ce(0.8)Sm(0.2)O(1.9) (SDC) at 900 degrees C was negligible. To measure the electrochemical properties, SOFC units were constructed with Sm(0.9)Sr(0.1)Cr(0.5)Fe(0.5)O3 as the anode, SDC as the electrolyte and LBFZ as the cathode. The maximum power density increased with the increasing NO concentration and temperature. The cell resistance is mainly due to the cathodic polarization resistance.

  10. Changes in thymocytes due to local irradiation of a portion of the maxilla in mice. A study of NKT cells and {gamma}{delta}T cells

    Energy Technology Data Exchange (ETDEWEB)

    Satho, Taigo; Tamasawa, Ken; Yosue, Takashi [Nippon Dental Univ., Tokyo (Japan); Arai, Thiaki


    We have been investigating the changes of lymphocyte subsets in immune organs after head and neck irradiation. The aim of the present study was to determine the influence of local irradiation (10 Gy) of a portion of the maxilla on the thymocyte subsets, specifically NKT cells and {gamma}{delta}T cells in mice. The thymocyte subsets were analyzed following irradiation using a fluorometer (anti-CD4, CD8, TCR{alpha}{beta}, TCR{gamma}{delta} and NK1.1 monoclonal antibodies) and the outcome compared with that obtained from no-irradiation groups. The following results were obtained: The total number of thymocytes showed a significant decrease one day and three days after irradiation. The absolute number of DN (double negative; CD4{sup -} CD8{sup -}), CD4{sup +} SP (CD4{sup +} single positive; CD4{sup +} CD8{sup -}) and CD8{sup +} SP (CD8{sup +} single positive; CD4{sup -} CD8{sup +}) thymocytes showed a significant decrease one day after irradiation. The absolute number of DP (double positive; CD4{sup +} CD8{sup +}) thymocytes showed a significant decrease one day and three days after irradiation. The absolute number of NKT and {gamma}{delta}T cells showed a significant decrease one day after irradiation. In conclusion, the results suggest that NKT cells and {gamma}{delta}T cells exhibit behavior which is the same as main stream thymocytes, except DP thymocytes. (author)

  11. Yeast cell surface display: An efficient strategy for improvement of bioethanol fermentation performance. (United States)

    Chen, Xianzhong


    The cell surface serves as a functional interface between the inside and the outside of the cell. Within the past 20 y the ability of yeast (Saccharomyces cerevisiae) to display heterologous proteins on the cell surface has been demonstrated. Furthermore, S. cerevisiae has been both developed and applied in expression of various proteins on the cell surface. Using this novel and useful strategy, proteins and peptides of various kinds can be displayed on the yeast cell surface by fusing the protein of interest with the glycosylphosphatidylinositol (GPI)-anchoring system. Consolidated bioprocessing (CBP) using S. cerevisiae represents a promising technology for bioethanol production. However, further work is needed to improve the fermentation performance. There is some excellent previous research regarding construction of yeast biocatalyst using the surface display system to decrease cost, increase efficiency of ethanol production and directly utilize starch or biomass for fuel production. In this commentary, we reviewed the yeast surface display system and highlighted recent work. Additionally, the strategy for decrease of phytate phosphate content in dried distillers grains with solubles (DDGS) by display of phytase on the yeast cell surface is discussed.

  12. Nigerian Hospital Practice - Vol 5, No 6 (2010)

    African Journals Online (AJOL)

    child transmission of HIV in Rivers State, Nigeria · EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. C.I Tobin-West, M.M Mezie-Okoye. ...

  13. Autoradiographic localization of mu and delta opioid receptors in the mesocorticolimbic dopamine system

    Energy Technology Data Exchange (ETDEWEB)

    Dilts, R.P. Jr.


    In vitro autoradiographic techniques were coupled with selective chemical lesions of the A10 dopamine cells and intrinsic perikarya of the region to delineate the anatomical localization of mu and delta opioid receptors, as well as, neurotensin receptors. Mu opioid receptors were labeled with {sup 125}I-DAGO. Delta receptors were labeled with {sup 125}I-DPDPE. Neurotensin receptors were labeled with {sup 125}I-NT3. Unilateral lesions of the dopamine perikarya were produced by injections of 6-OHDA administered in the ventral mesencephalon. Unilateral lesions of intrinsic perikarya were induced by injections of quinolinic acid in to the A10 dopamine cell region. Unilateral lesions produced with 6-OHDA resulted in the loss of neurotensin receptors in the A10 region and within the terminal fields. Mu opioid receptors were unaffected by this treatment, but delta opioid receptors increased in the contralateral striatum and nucleus accumbens following 6-OHDA administration. Quinolinic acid produced a reduction of mu opioid receptors within the A10 region with a concomitant reduction in neurotensin receptors in both the cell body region and terminal fields. These results are consistent with a variety of biochemical and behavioral data which suggest the indirect modulation of dopamine transmission by the opioids. In contrast these results strongly indicate a direct modulation of the mesolimbic dopamine system by neurotensin.

  14. The dynamics of central Main Ethiopian Rift waters: Evidence from {delta}D, {delta}{sup 18}O and {sup 87}Sr/{sup 86}Sr ratios

    Energy Technology Data Exchange (ETDEWEB)

    Rango, Tewodros, E-mail: [Division of Earth and Ocean Sciences, Nicholas School of the Environment, Duke University, Durham, NC 27708 (United States)] [Addis Ababa University, Department of Earth Sciences, P.O. Box 1176, Addis Ababa (Ethiopia); Petrini, Riccardo; Stenni, Barbara [University of Trieste, Department of Geosciences, Via Weiss 1, I-34100 Trieste (Italy); Bianchini, Gianluca [Istituto di Geoscienze e Georisorse-CNR, Pisa (Italy)] [Department of Earth Sciences, University of Ferrara, Via Saragat 1, 44100 Ferrara (Italy); Slejko, Francesca [University of Trieste, Department of Geosciences, Via Weiss 1, I-34100 Trieste (Italy); Beccaluva, Luigi [Department of Earth Sciences, University of Ferrara, Via Saragat 1, 44100 Ferrara (Italy); Ayenew, Tenalem [Addis Ababa University, Department of Earth Sciences, P.O. Box 1176, Addis Ababa (Ethiopia)


    Research highlights: {yields} Chemical and isotope ({delta}D, {delta}{sup 18}O and {sup 87}Sr/{sup 86}Sr) techniques are applied to understand various hydrological processes in the Main Ethiopian Rift. {yields} Some of the studied groundwaters display a depleted {delta}D-{delta}{sup 18}O composition when compared to the present-day average precipitation, thus suggesting that the rift floor aquifers also contains paleo-meteoric waters recharge associated with deep flow system. {yields} The pristine waters coming from the highlands display isotopic compositions characterized by less radiogenic {sup 87}Sr/{sup 86}Sr (and more depleted {delta}D, {delta}{sup 18}O). This isotopic signature subsequently evolves towards higher {sup 87}Sr/{sup 86}Sr by an interaction with the more radiogenic rhyolites of the rift and their weathered and redeposited products. - Abstract: Water samples from cold and geothermal boreholes, hot springs, lakes and rivers were analyzed for {delta}D, {delta}{sup 18}O and {sup 87}Sr/{sup 86}Sr compositions in order to investigate lake water-groundwater mixing processes, water-rock interactions, and to evaluate groundwater flow paths in the central Main Ethiopian Rift (MER) of the Ziway-Shala basin. Different ranges of isotopic values were recorded for different water types: hot springs show {delta}{sup 18}O -3.36 to +3.69 and {delta}D -15.85 to +24.23, deep Aluto-Langano geothermal wells show {delta}{sup 18}O -4.65 to -1.24 and {delta}D -12.39 to -9.31, groundwater wells show {delta}{sup 18}O -3.99 to +5.14 and {delta}D -19.69 to +32.27, whereas the lakes show {delta}{sup 18}O and {delta}D in the range +3.98 to +7.92 and +26.19 to +45.71, respectively. The intersection of the Local Meteoric Water Line (LMWL: {delta}D = 7 {delta}{sup 18}O + 11.2, R{sup 2} = 0.94, n = 42) and the Local Evaporation Line (LEL: {delta}D = 5.63{delta}{sup 18}O + 8, n = 14, R{sup 2} = 0.82) was used to estimate the average isotopic composition of recharge water into the

  15. Nigerian Hospital Practice - Vol 6, No 1-2 (2010)

    African Journals Online (AJOL)

    Evaluation and Management of The Child with Failure to Thrive · EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. A.N Onyiriuka. ...

  16. Phospholipase C-{delta}{sub 1} regulates interleukin-1{beta} and tumor necrosis factor-{alpha} mRNA expression

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Eric; Jakinovich, Paul; Bae, Aekyung [Department of Anesthesiology, Health Sciences Center L4 Rm 081, Stony Brook University, Stony Brook, NY 11794 (United States); Rebecchi, Mario, E-mail: [Department of Anesthesiology, Health Sciences Center L4 Rm 081, Stony Brook University, Stony Brook, NY 11794 (United States)


    Phospholipase C-{delta}{sub 1} (PLC{delta}{sub 1}) is a widely expressed highly active PLC isoform, modulated by Ca{sup 2+} that appears to operate downstream from receptor signaling and has been linked to regulation of cytokine production. Here we investigated whether PLC{delta}{sub 1} modulated expression of the pro-inflammatory cytokines interleukin-1{beta} (IL-1{beta}), tumor necrosis factor-{alpha} (TNF-{alpha}) and interleukin-6 (IL-6) in rat C6 glioma cells. Expression of PLC{delta}{sub 1} was specifically suppressed by small interfering RNA (siRNA) and the effects on cytokine mRNA expression, stimulated by the Toll-like receptor (TLR) agonist, lipopolysaccharide (LPS), were examined. Real-time polymerase chain reaction (RT-PCR) results showed that PLC{delta}{sub 1} knockdown enhanced expression IL-1{beta} and tumor necrosis factor-{alpha} (TNF-{alpha}) mRNA by at least 100 fold after 4 h of LPS stimulation compared to control siRNA treatment. PLC{delta}{sub 1} knock down caused persistently high Nf{kappa}b levels at 4 h of LPS stimulation compared to control siRNA-treated cells. PLC{delta}{sub 1} knockdown was also associated with elevated nuclear levels of c-Jun after 30 min of LPS stimulation, but did not affect LPS-stimulated p38 or p42/44 MAPK phosphorylation, normally associated with TLR activation of cytokine gene expression; rather, enhanced protein kinase C (PKC) phosphorylation of cellular proteins was observed in the absence of LPS stimulation. An inhibitor of PKC, bisindolylmaleimide II (BIM), reversed phosphorylation, prevented elevation of nuclear c-Jun levels, and inhibited LPS-induced increases of IL-1{beta} and TNF-{alpha} mRNA's induced by PLC{delta}{sub 1} knockdown. Our results show that loss of PLC{delta}{sub 1} enhances PKC/c-Jun signaling and up-modulates pro-inflammatory cytokine gene transcription in concert with the TLR-stimulated p38MAPK/Nf{kappa}b pathway. Our findings are consistent with the idea that PLC{delta}{sub 1} is a

  17. Affinity crosslinking of /sup 125/I-human beta-endorphin to cell lines possessing either mu or delta type opioid binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Keren, O.; Gioannini, T.L.; Hiller, J.M.; Simon, E.J.


    Affinity crosslinking of human /sup 125/I-beta-Endorphin to cell lines possessing either mu or delta binding sites was carried out. Autoradiography of SDS-PAGE gels from these crosslinked cell lines revealed that these two sites contain major peptide subunits that differ in molecular size. This confirms our earlier finding in mammalian brain which demonstrated separate and distinct subunits for mu and delta opioid receptors.

  18. A Preclinical Population Pharmacokinetic Model for Anti-CD20/CD3 T-Cell-Dependent Bispecific Antibodies. (United States)

    Ferl, Gregory Z; Reyes, Arthur; Sun, Liping L; Cheu, Melissa; Oldendorp, Amy; Ramanujan, Saroja; Stefanich, Eric G


    CD20 is a cell-surface receptor expressed by healthy and neoplastic B cells and is a well-established target for biologics used to treat B-cell malignancies. Pharmacokinetic (PK) and pharmacodynamic (PD) data for the anti-CD20/CD3 T-cell-dependent bispecific antibody BTCT4465A were collected in transgenic mouse and nonhuman primate (NHP) studies. Pronounced nonlinearity in drug elimination was observed in the murine studies, and time-varying, nonlinear PK was observed in NHPs, where three empirical drug elimination terms were identified using a mixed-effects modeling approach: i) a constant nonsaturable linear clearance term (7 mL/day/kg); ii) a rapidly decaying time-varying, linear clearance term (t ½  = 1.6 h); and iii) a slowly decaying time-varying, nonlinear clearance term (t ½  = 4.8 days). The two time-varying drug elimination terms approximately track with time scales of B-cell depletion and T-cell migration/expansion within the central blood compartment. The mixed-effects NHP model was scaled to human and prospective clinical simulations were generated. © 2018 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  19. Association of papillomavirus E6 proteins with either MAML1 or E6AP clusters E6 proteins by structure, function, and evolutionary relatedness.

    Directory of Open Access Journals (Sweden)

    Nicole Brimer


    Full Text Available Papillomavirus E6 proteins bind to LXXLL peptide motifs displayed on targeted cellular proteins. Alpha genus HPV E6 proteins associate with the cellular ubiquitin ligase E6AP (UBE3A, by binding to an LXXLL peptide (ELTLQELLGEE displayed by E6AP, thereby stimulating E6AP ubiquitin ligase activity. Beta, Gamma, and Delta genera E6 proteins bind a similar LXXLL peptide (WMSDLDDLLGS on the cellular transcriptional co-activator MAML1 and thereby repress Notch signaling. We expressed 45 different animal and human E6 proteins from diverse papillomavirus genera to ascertain the overall preference of E6 proteins for E6AP or MAML1. E6 proteins from all HPV genera except Alpha preferentially interacted with MAML1 over E6AP. Among animal papillomaviruses, E6 proteins from certain ungulate (SsPV1 from pigs and cetacean (porpoises and dolphins hosts functionally resembled Alpha genus HPV by binding and targeting the degradation of E6AP. Beta genus HPV E6 proteins functionally clustered with Delta, Pi, Tau, Gamma, Chi, Mu, Lambda, Iota, Dyokappa, Rho, and Dyolambda E6 proteins to bind and repress MAML1. None of the tested E6 proteins physically and functionally interacted with both MAML1 and E6AP, indicating an evolutionary split. Further, interaction of an E6 protein was insufficient to activate degradation of E6AP, indicating that E6 proteins that target E6AP co-evolved to separately acquire both binding and triggering of ubiquitin ligase activation. E6 proteins with similar biological function clustered together in phylogenetic trees and shared structural features. This suggests that the divergence of E6 proteins from either MAML1 or E6AP binding preference is a major event in papillomavirus evolution.

  20. A Polymorphism within the Internal Fusion Loop of the Ebola Virus Glycoprotein Modulates Host Cell Entry. (United States)

    Hoffmann, Markus; Crone, Lisa; Dietzel, Erik; Paijo, Jennifer; González-Hernández, Mariana; Nehlmeier, Inga; Kalinke, Ulrich; Becker, Stephan; Pöhlmann, Stefan


    The large scale of the Ebola virus disease (EVD) outbreak in West Africa in 2013-2016 raised the question whether the host cell interactions of the responsible Ebola virus (EBOV) strain differed from those of other ebolaviruses. We previously reported that the glycoprotein (GP) of the virus circulating in West Africa in 2014 (EBOV2014) exhibited reduced ability to mediate entry into two nonhuman primate (NHP)-derived cell lines relative to the GP of EBOV1976. Here, we investigated the molecular determinants underlying the differential entry efficiency. We found that EBOV2014-GP-driven entry into diverse NHP-derived cell lines, as well as human monocyte-derived macrophages and dendritic cells, was reduced compared to EBOV1976-GP, although entry into most human- and all bat-derived cell lines tested was comparable. Moreover, EBOV2014 replication in NHP but not human cells was diminished relative to EBOV1976, suggesting that reduced cell entry translated into reduced viral spread. Mutagenic analysis of EBOV2014-GP and EBOV1976-GP revealed that an amino acid polymorphism in the receptor-binding domain, A82V, modulated entry efficiency in a cell line-independent manner and did not account for the reduced EBOV2014-GP-driven entry into NHP cells. In contrast, polymorphism T544I, located in the internal fusion loop in the GP2 subunit, was found to be responsible for the entry phenotype. These results suggest that position 544 is an important determinant of EBOV infectivity for both NHP and certain human target cells. IMPORTANCE The Ebola virus disease outbreak in West Africa in 2013 entailed more than 10,000 deaths. The scale of the outbreak and its dramatic impact on human health raised the question whether the responsible virus was particularly adept at infecting human cells. Our study shows that an amino acid exchange, A82V, that was acquired during the epidemic and that was not observed in previously circulating viruses, increases viral entry into diverse target cells

  1. Formation of conjugated delta8,delta10-double bonds by delta12-oleic-acid desaturase-related enzymes: biosynthetic origin of calendic acid. (United States)

    Cahoon, E B; Ripp, K G; Hall, S E; Kinney, A J


    Divergent forms of the plant Delta(12)-oleic-acid desaturase (FAD2) have previously been shown to catalyze the formation of acetylenic bonds, epoxy groups, and conjugated Delta(11),Delta(13)-double bonds by modification of an existing Delta(12)-double bond in C(18) fatty acids. Here, we report a class of FAD2-related enzymes that modifies a Delta(9)-double bond to produce the conjugated trans-Delta(8),trans-Delta(10)-double bonds found in calendic acid (18:3Delta(8trans,10trans,12cis)), the major component of the seed oil of Calendula officinalis. Using an expressed sequence tag approach, cDNAs for two closely related FAD2-like enzymes, designated CoFADX-1 and CoFADX-2, were identified from a C. officinalis developing seed cDNA library. The deduced amino acid sequences of these polypeptides share 40-50% identity with those of other FAD2 and FAD2-related enzymes. Expression of either CoFADX-1 or CoFADX-2 in somatic soybean embryos resulted in the production of calendic acid. In embryos expressing CoFADX-2, calendic acid accumulated to as high as 22% (w/w) of the total fatty acids. In addition, expression of CoFADX-1 and CoFADX-2 in Saccharomyces cerevisiae was accompanied by calendic acid accumulation when induced cells were supplied exogenous linoleic acid (18:2Delta(9cis,12cis)). These results are thus consistent with a route of calendic acid synthesis involving modification of the Delta(9)-double bond of linoleic acid. Regiospecificity for Delta(9)-double bonds is unprecedented among FAD2-related enzymes and further expands the functional diversity found in this family of enzymes.

  2. Bacterial whole-cell biocatalysts by surface display of enzymes: toward industrial application. (United States)

    Schüürmann, Jan; Quehl, Paul; Festel, Gunter; Jose, Joachim


    Despite the first report on the bacterial display of a recombinant peptide appeared almost 30 years ago, industrial application of cells with surface-displayed enzymes is still limited. To display an enzyme on the surface of a living cell bears several advantages. First of all, neither the substrate nor the product of the enzymatic reaction needs to cross a membrane barrier. Second, the enzyme being linked to the cell can be separated from the reaction mixture and hence the product by simple centrifugation. Transfer to a new substrate preparation results in multiple cycles of enzymatic conversion. Finally, the anchoring in a matrix, in this case, the cell envelope stabilizes the enzyme and makes it less accessible to proteolytic degradation and material adsorption resulting in continuous higher activities. These advantages in common need to balance some disadvantages before this application can be taken into account for industrial processes, e.g., the exclusion of the enzyme from the cellular metabolome and hence from redox factors or other co-factors that need to be supplied. Therefore, this digest describes the different systems in Gram-positive and Gram-negative bacteria that have been used for the surface display of enzymes so far and focuses on examples among these which are suitable for industrial purposes or for the production of valuable resources, not least in order to encourage a broader application of whole-cell biocatalysts with surface-displayed enzymes.

  3. α6 Integrin and CD44 enrich for a primary keratinocyte population that displays resistance to UV-induced apoptosis.

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    Helen Wray

    Full Text Available Epidermal human keratinocytes are exposed to a wide range of environmental genotoxic insults, including the UV component of solar radiation. Epidermal homeostasis in response to cellular or tissue damage is maintained by a population of keratinocyte stem cells (KSC that reside in the basal layer of the epithelium. Using cell sorting based on cell-surface markers, we have identified a novel α6 integrin(high+/CD44(+ sub-population of basal keratinocytes. These α6 integrin(high+/CD44(+ keratinocytes have both high proliferative potential, form colonies in culture that have characteristics of holoclones and have a unique pattern of resistance to apoptosis induced by UVB radiation or by agents that induce single- or double strand DNA breaks. Resistance to UVB induced apoptosis in the α6 integrin(high+/CD44(+ cells involved increased expression of TAp63 and was overcome by PI-3 kinase inhibition. In marked contrast, the α6 integrin(high+/CD44(+ cells were sensitive to apoptosis induced by the cross-linking agent cisplatin, and imatinib inhibition of c-Abl blocked the ability of cisplatin to kill α6 integrin(high+/CD44(+ cells. Our findings reveal a population of basal keratinocytes with long-term proliferative properties that display specific patterns of apoptotic resistance that is dependent upon the genotoxic stimulus, and provide insights into how these cells can be targeted with chemotherapeutic agents.

  4. Changes in Circulating B Cell Subsets Associated with Aging and Acute SIV Infection in Rhesus Macaques. (United States)

    Chang, W L William; Gonzalez, Denise F; Kieu, Hung T; Castillo, Luis D; Messaoudi, Ilhem; Shen, Xiaoying; Tomaras, Georgia D; Shacklett, Barbara L; Barry, Peter A; Sparger, Ellen E


    Aging and certain viral infections can negatively impact humoral responses in humans. To further develop the nonhuman primate (NHP) model for investigating B cell dynamics in human aging and infectious disease, a flow cytometric panel was developed to characterize circulating rhesus B cell subsets. Significant differences between human and macaque B cells included the proportions of cells within IgD+ and switched memory populations and a prominent CD21-CD27+ unswitched memory population detected only in macaques. We then utilized the expanded panel to analyze B cell alterations associated with aging and acute simian immunodeficiency virus (SIV) infection in the NHP model. In the aging study, distinct patterns of B cell subset frequencies were observed for macaques aged one to five years compared to those between ages 5 and 30 years. In the SIV infection study, B cell frequencies and absolute number were dramatically reduced following acute infection, but recovered within four weeks of infection. Thereafter, the frequencies of activated memory B cells progressively increased; these were significantly correlated with the magnitude of SIV-specific IgG responses, and coincided with impaired maturation of anti-SIV antibody avidity, as previously reported for HIV-1 infection. These observations further validate the NHP model for investigation of mechanisms responsible for B cells alterations associated with immunosenescence and infectious disease.

  5. Cell clusters overlying focally disrupted mammary myoepithelial cell layers and adjacent cells within the same duct display different immunohistochemical and genetic features: implications for tumor progression and invasion

    International Nuclear Information System (INIS)

    Man, Yan-gao; Vinh, Tuyethoa N; Strauss, Brian L; Tai, Lisa; Barner, Ross; Vang, Russell; Saenger, Jeffrey S; Shekitka, Kris M; Bratthauer, Gary L; Wheeler, Darren T; Liang, Chang Y


    Our previous studies detected focal disruptions in myoepithelial cell layers of several ducts with carcinoma in situ. The cell cluster overlying each of the myoepithelial disruptions showed a marked reduction in or a total loss of immunoreactivity for the estrogen receptor (ER). This is in contrast to the adjacent cells within the same duct, which were strongly immunoreactive for the ER. The current study attempts to confirm and expand previous observations on a larger scale. Paraffin sections from 220 patients with ER-positive intraductal breast tumors were double immunostained with the same protocol previously used. Cross-sections of ducts lined by ≥ 40 epithelial cells were examined for myoepithelial cell layer disruptions and for ER expression. In five selected cases, ER-negative cells overlying the disrupted myoepithelial cell layer and adjacent ER-positive cells within the same duct were separately microdissected and assessed for loss of heterozygosity and microsatellite instability. Of the 220 cases with 5698 duct cross-sections examined, 94 showed disrupted myoepithelial cell layers with 405 focal disruptions. Of the 94 cases, 79 (84%) contained only ER-negative cell clusters, nine (9.6%) contained both ER-negative and ER-positive cell clusters, and six (6.4%) contained only ER-positive cell clusters overlying disrupted myoepithelial cell layers. Of the 405 disruptions, 350 (86.4%) were overlain by ER-negative cell clusters and 55 (13.6%) were overlain by ER-positive cell clusters (P < 0.01). Microdissected ER-negative and ER-positive cells within the same duct from all five selected cases displayed a different frequency or pattern of loss of heterozygosity and/or microsatellite instability at 10 of the 15 DNA markers. Cells overlying focally disrupted myoepithelial layers and their adjacent counterparts within the same duct displayed different immunohistochemical and molecular features. These features potentially represent an early sign of the formation

  6. Identification of human embryonic progenitor cell targeting peptides using phage display.

    Directory of Open Access Journals (Sweden)

    Paola A Bignone

    Full Text Available Human pluripotent stem (hPS cells are capable of differentiation into derivatives of all three primary embryonic germ layers and can self-renew indefinitely. They therefore offer a potentially scalable source of replacement cells to treat a variety of degenerative diseases. The ability to reprogram adult cells to induced pluripotent stem (iPS cells has now enabled the possibility of patient-specific hPS cells as a source of cells for disease modeling, drug discovery, and potentially, cell replacement therapies. While reprogramming technology has dramatically increased the availability of normal and diseased hPS cell lines for basic research, a major bottleneck is the critical unmet need for more efficient methods of deriving well-defined cell populations from hPS cells. Phage display is a powerful method for selecting affinity ligands that could be used for identifying and potentially purifying a variety of cell types derived from hPS cells. However, identification of specific progenitor cell-binding peptides using phage display may be hindered by the large cellular heterogeneity present in differentiating hPS cell populations. We therefore tested the hypothesis that peptides selected for their ability to bind a clonal cell line derived from hPS cells would bind early progenitor cell types emerging from differentiating hPS cells. The human embryonic stem (hES cell-derived embryonic progenitor cell line, W10, was used and cell-targeting peptides were identified. Competition studies demonstrated specificity of peptide binding to the target cell surface. Efficient peptide targeted cell labeling was accomplished using multivalent peptide-quantum dot complexes as detected by fluorescence microscopy and flow cytometry. The cell-binding peptides were selective for differentiated hPS cells, had little or no binding on pluripotent cells, but preferential binding to certain embryonic progenitor cell lines and early endodermal hPS cell derivatives. Taken

  7. Role of Natural Killer and Gamma-Delta T cells in West Nile Virus Infection

    Directory of Open Access Journals (Sweden)

    Thomas Welte


    Full Text Available Natural Killer (NK cells and Gamma-delta T cells are both innate lymphocytes that respond rapidly and non-specifically to viral infection and other pathogens. They are also known to form a unique link between innate and adaptive immunity. Although they have similar immune features and effector functions, accumulating evidence in mice and humans suggest these two cell types have distinct roles in the control of infection by West Nile virus (WNV, a re-emerging pathogen that has caused fatal encephalitis in North America over the past decade. This review will discuss recent studies on these two cell types in protective immunity and viral pathogenesis during WNV infection.

  8. Display of a Maize cDNA library on baculovirus infected insect cells

    Directory of Open Access Journals (Sweden)

    Jones Ian M


    Full Text Available Abstract Background Maize is a good model system for cereal crop genetics and development because of its rich genetic heritage and well-characterized morphology. The sequencing of its genome is well advanced, and new technologies for efficient proteomic analysis are needed. Baculovirus expression systems have been used for the last twenty years to express in insect cells a wide variety of eukaryotic proteins that require complex folding or extensive posttranslational modification. More recently, baculovirus display technologies based on the expression of foreign sequences on the surface of Autographa californica (AcMNPV have been developed. We investigated the potential of a display methodology for a cDNA library of maize young seedlings. Results We constructed a full-length cDNA library of young maize etiolated seedlings in the transfer vector pAcTMVSVG. The library contained a total of 2.5 × 105 independent clones. Expression of two known maize proteins, calreticulin and auxin binding protein (ABP1, was shown by western blot analysis of protein extracts from insect cells infected with the cDNA library. Display of the two proteins in infected insect cells was shown by selective biopanning using magnetic cell sorting and demonstrated proof of concept that the baculovirus maize cDNA display library could be used to identify and isolate proteins. Conclusion The maize cDNA library constructed in this study relies on the novel technology of baculovirus display and is unique in currently published cDNA libraries. Produced to demonstrate proof of principle, it opens the way for the development of a eukaryotic in vivo display tool which would be ideally suited for rapid screening of the maize proteome for binding partners, such as proteins involved in hormone regulation or defence.

  9. Holocene evolution of a wave-dominated fan-delta: Godavari delta, India (United States)

    Saito, Y.; Nageswara Rao, K.; Nagakumar, K.; Demudu, G.; Rajawat, A.; Kubo, S.; Li, Z.


    The Godavari delta is one of the world's largest wave-dominated deltas. The Godavari River arises in the Western Ghats near the west coast of India and drains an area of about 3.1x10^5 km^2, flowing about 1465 km southeast across the Indian peninsula to the Bay of Bengal. The Godavari delta consists of a gentle seaward slope from its apex (12 m elevation) at Rajahmundry and a coastal beach-ridge plain over a distance of about 75 km and covers ~5200 km^2 as a delta plain. The river splits into two major distributary channels, the Gautami and the Vasishta, at a barrage constructed in the mid-1800s. The coastal environment of the deltaic coast is microtidal (~1 m mean tidal range) and wave-dominated (~1.5 m mean wave height in the June-September SW monsoon season, ~0.8 m in the NE monsoon season). Models of the Holocene evolution of the Godavari delta have changed from a zonal progradation model (e.g. Nageswara Rao & Sadakata, 1993) to a truncated cuspate delta model (Nageswara Rao et al., 2005, 2012). Twelve borehole cores (340 m total length), taken in the coastal delta plain during 2010-2013, yielded more than 100 C-14 dates. Sediment facies and C-14 dates from these and previous cores and remote-sensing data support a new delta evolution model. The Holocene coastal delta plain is divided into two parts by a set of linear beach ridges 12-14 km landward from the present shoreline in the central part of the delta. The location of the main depocenter (lobe) has shifted during the Holocene from 1) the center to 2) the west, 3) east, 4) center, 5) west, and 6) east. The linear beach ridges separate the first three from the last three stages. These lobe shifts are controlled by river channel shifts near the apex. Just as the current linear shoreline of the central part of the delta and the concave-up nearshore topography are the result of coastal erosion of a cuspate delta, the linear beach ridges indicate a former eroded shoreline. An unconformity within the deltaic

  10. An expanded Notch-Delta model exhibiting long-range patterning and incorporating MicroRNA regulation.

    Directory of Open Access Journals (Sweden)

    Jerry S Chen


    Full Text Available Notch-Delta signaling is a fundamental cell-cell communication mechanism that governs the differentiation of many cell types. Most existing mathematical models of Notch-Delta signaling are based on a feedback loop between Notch and Delta leading to lateral inhibition of neighboring cells. These models result in a checkerboard spatial pattern whereby adjacent cells express opposing levels of Notch and Delta, leading to alternate cell fates. However, a growing body of biological evidence suggests that Notch-Delta signaling produces other patterns that are not checkerboard, and therefore a new model is needed. Here, we present an expanded Notch-Delta model that builds upon previous models, adding a local Notch activity gradient, which affects long-range patterning, and the activity of a regulatory microRNA. This model is motivated by our experiments in the ascidian Ciona intestinalis showing that the peripheral sensory neurons, whose specification is in part regulated by the coordinate activity of Notch-Delta signaling and the microRNA miR-124, exhibit a sparse spatial pattern whereby consecutive neurons may be spaced over a dozen cells apart. We perform rigorous stability and bifurcation analyses, and demonstrate that our model is able to accurately explain and reproduce the neuronal pattern in Ciona. Using Monte Carlo simulations of our model along with miR-124 transgene over-expression assays, we demonstrate that the activity of miR-124 can be incorporated into the Notch decay rate parameter of our model. Finally, we motivate the general applicability of our model to Notch-Delta signaling in other animals by providing evidence that microRNAs regulate Notch-Delta signaling in analogous cell types in other organisms, and by discussing evidence in other organisms of sparse spatial patterns in tissues where Notch-Delta signaling is active.

  11. Differential regulation of. mu. , delta, kappa opioid receptors by Mn/sup + +/

    Energy Technology Data Exchange (ETDEWEB)

    Szuecs, M.; Oetting, G.M.; Coscia, C.J.


    Differential effects of Mn/sup + +/ on three opioid receptor subtypes of rat brain membranes were evaluated. Concentration dependency studies performed with 0.05-20 mM Mn/sup + +/ revealed that only the delta receptors are stimulated at any concentration. The binding of 1 nM /sup 3/H-DAGO was not stimulated by low concentrations (< 1mM) of Mn/sup + +/, and was significantly inhibited at higher concentrations (40% at 20 mM). 1 nM /sup 3/H-EKC (+100nM DAGO and 100nM DADLE) binding was inhibited by Mn/sup + +/ in the entire concentration range. While regulation of receptor binding did not change during postnatal development, delta and kappa binding displayed a pronounced developmental time-dependency. Kappa sites were hardly affected by Mn/sup + +/ at day 5, and adult levels of inhibition were reached only after the third week postnatal. In contrast, 1 nM /sup 3/H-DADLE (+10nM DAGO) binding was most sensitive to Mn/sup + +/ on day 5 after birth (100% stimulation with 5-20 mM). The ED/sub 50/ of Mn/sup + +/ stimulation was unchanged during maturation. These immature delta sites displayed a similar extent of Mn/sup + +/ reversal of Gpp(NH)p inhibition as seen in microsomes, which represent a good model of N/sub i/-uncoupled receptors. These data suggest that, delta and kappa receptors are differently coupled to N/sub i/. Moreover, a second divalent cation binding site, in addition to that on N/sub i/ might exist for delta receptors.

  12. In vitro Fab display: a cell-free system for IgG discovery (United States)

    Stafford, Ryan L.; Matsumoto, Marissa L.; Yin, Gang; Cai, Qi; Fung, Juan Jose; Stephenson, Heather; Gill, Avinash; You, Monica; Lin, Shwu-Hwa; Wang, Willie D.; Masikat, Mary Rose; Li, Xiaofan; Penta, Kalyani; Steiner, Alex R.; Baliga, Ramesh; Murray, Christopher J.; Thanos, Christopher D.; Hallam, Trevor J.; Sato, Aaron K.


    Selection technologies such as ribosome display enable the rapid discovery of novel antibody fragments entirely in vitro. It has been assumed that the open nature of the cell-free reactions used in these technologies limits selections to single-chain protein fragments. We present a simple approach for the selection of multi-chain proteins, such as antibody Fab fragments, using ribosome display. Specifically, we show that a two-chain trastuzumab (Herceptin) Fab domain can be displayed in a format which tethers either the heavy or light chain to the ribosome while retaining functional antigen binding. Then, we constructed synthetic Fab HC and LC libraries and performed test selections against carcinoembryonic antigen (CEA) and vascular endothelial growth factor (VEGF). The Fab selection output was reformatted into full-length immunoglobulin Gs (IgGs) and directly expressed at high levels in an optimized cell-free system for immediate screening, purification and characterization. Several novel IgGs were identified using this cell-free platform that bind to purified CEA, CEA positive cells and VEGF. PMID:24586053

  13. Antagonistic effect of disulfide-rich peptide aptamers selected by cDNA display on interleukin-6-dependent cell proliferation

    International Nuclear Information System (INIS)

    Nemoto, Naoto; Tsutsui, Chihiro; Yamaguchi, Junichi; Ueno, Shingo; Machida, Masayuki; Kobayashi, Toshikatsu; Sakai, Takafumi


    Highlights: ► Disulfide-rich peptide aptamer inhibits IL-6-dependent cell proliferation. ► Disulfide bond of peptide aptamer is essential for its affinity to IL-6R. ► Inhibitory effect of peptide depends on number and pattern of its disulfide bonds. -- Abstract: Several engineered protein scaffolds have been developed recently to circumvent particular disadvantages of antibodies such as their large size and complex composition, low stability, and high production costs. We previously identified peptide aptamers containing one or two disulfide-bonds as an alternative ligand to the interleukin-6 receptor (IL-6R). Peptide aptamers (32 amino acids in length) were screened from a random peptide library by in vitro peptide selection using the evolutionary molecular engineering method “cDNA display”. In this report, the antagonistic activity of the peptide aptamers were examined by an in vitro competition enzyme-linked immunosorbent assay (ELISA) and an IL-6-dependent cell proliferation assay. The results revealed that a disulfide-rich peptide aptamer inhibited IL-6-dependent cell proliferation with similar efficacy to an anti-IL-6R monoclonal antibody.

  14. WC1+ gamma delta T cells from cattle naturally infected with Mycobacterium avium subsp. paratuberculosis respond differentially to stimulation with PPD-J. (United States)

    A role for gamma delta T cells in protection against mycobacterial infections including Johne’s disease (JD) has been suggested. In neonatal calves where the risk to infection with Mycobacterium avium subsp. paratuberculosis (MAP) is high, the majority of circulating CD3+ lymphocytes are gamma delta...

  15. DELTAS: A new Global Delta Sustainability Initiative (Invited) (United States)

    Foufoula-Georgiou, E.


    Deltas are economic and environmental hotspots, food baskets for many nations, home to a large part of the world population, and hosts of exceptional biodiversity and rich ecosystems. Deltas, being at the land-water interface, are international, regional, and local transport hubs, thus providing the basis for intense economic activities. Yet, deltas are deteriorating at an alarming rate as 'victims' of human actions (e.g. water and sediment reduction due to upstream basin development), climatic impacts (e.g. sea level rise and flooding from rivers and intense tropical storms), and local exploration (e.g. sand or aggregates, groundwater and hydrocarbon extraction). Although many efforts exist on individual deltas around the world, a comprehensive global delta sustainability initiative that promotes awareness, science integration, data and knowledge sharing, and development of decision support tools for an effective dialogue between scientists, managers and policy makers is lacking. Recently, the international scientific community proposed to establish the International Year of Deltas (IYD) to serve as the beginning of such a Global Delta Sustainability Initiative. The IYD was proposed as a year to: (1) increase awareness and attention to the value and vulnerability of deltas worldwide; (2) promote and enhance international and regional cooperation at the scientific, policy, and stakeholder level; and (3) serve as a launching pad for a 10-year committed effort to understand deltas as complex socio-ecological systems and ensure preparedness in protecting and restoring them in a rapidly changing environment. In this talk, the vision for such an international coordinated effort on delta sustainability will be presented as developed by a large number of international experts and recently funded through the Belmont Forum International Opportunities Fund. Participating countries include: U.S., France, Germany, U.K., India, Japan, Netherlands, Norway, Brazil, Bangladesh

  16. Mechanistic and Treatment Implications of DeltaNp63 Expression in a Rare Case of Metastatic Hidradenocarcinoma. (United States)

    Driscoll, James J; Gauerke, Steven; Monahan, Brian C


    Hidradenocarcinomas are rare, aggressive adnexal tumors of sweat gland origin that demonstrate a high potential for local recurrence, metastasis and poor outcome. These neoplasms can derive from preexisting clear cell hidradenomas, but more commonly appear de novo with the molecular events responsible for the pathogenesis currently unknown. Molecular markers of pathogenesis as well as effective forms of adjuvant chemotherapy are missing due to the lack of accurate diagnosis, paucity of cases and confusion with other visceral solid tumors. Here, we report a 37-year-old man who presented with a rapidly growing, painful palpable mass located in the right inguinal area. The patient was a nonsmoker, did not consume alcohol and had a medical history remarkable only for a lower abdominal superficial skin lesion in the same area that had been excised 11 years earlier. Although initially slow growing, the lesion eventually expanded, was surgically excised and was diagnosed as a hidradenoma. There was no family history of malignancy and the patient had not experienced any constitutional symptoms. We probed the immunohistochemical status and detected negative staining for the estrogen, progesterone and Her2 receptors, while strong, diffuse nuclear staining was seen in the majority of cells consistent with p53 overexpression. Similarly, strong nuclear reactivity was seen with p63 and p73 antibodies. The p63 gene contains 2 separate promoters which express at least 6 major transcripts that lead to 2 fundamentally different classes of proteins; 3 isoforms (TAp63alpha, beta and gamma) encode proteins that induce apoptosis, whereas the other 3 isoforms (DeltaNp63alpha, beta and gamma) may exert inhibitory effects on p53. Interest in p63 stems from this 'two genes in one'-concept. Importantly, the nuclear presence of DeltaNp63 was detected widespread throughout the tumor. We have identified a subtype of hidradenocarcinomas that express DeltaNp63 and uncovered an unforeseen

  17. [Human herpesvirus-6 pneumonitis following autologous peripheral blood stem cell transplantation]. (United States)

    Saitoh, Yuu; Gotoh, Moritaka; Yoshizawa, Seiichiro; Akahane, Daigo; Fujimoto, Hiroaki; Ito, Yoshikazu; Ohyashiki, Kazuma


    A-46-year-old man was diagnosed with peripheral T cell lymphoma, not otherwise specified. He achieved a complete remission after pirarubicin, cyclophosphamide, vincristine, and prednisolone (THP-COP) therapy and successful autologous peripheral blood stem-cell transplantation (AutoSCT). However, 6 months post AutoSCT, he complained of fever. Chest computed tomography of the patient displayed bilateral interstitial pneumonitis. Human herpesvirus-6 (HHV-6) DNA was detected in his bronchoalveolar lavage fluid. Therefore, the patient was confirmed for HHV-6 pneumonitis. The treatment with foscarnet was effective, and no relapse was noticed in the patient. Besides, we have experienced pneumonitis of unknown origin in some patients after autologous or allogeneic stem-cell transplantations. Moreover, most of the above patients were clinically diagnosed using serum or plasma markers. Therefore, examining respiratory symptoms after AutoSCT would enable a more accurate diagnosis as well as treatment of patients with HHV-6 pneumonitis.

  18. Display of a β-mannanase and a chitosanase on the cell surface of Lactobacillus plantarum towards the development of whole-cell biocatalysts. (United States)

    Nguyen, Hoang-Minh; Mathiesen, Geir; Stelzer, Elena Maria; Pham, Mai Lan; Kuczkowska, Katarzyna; Mackenzie, Alasdair; Agger, Jane W; Eijsink, Vincent G H; Yamabhai, Montarop; Peterbauer, Clemens K; Haltrich, Dietmar; Nguyen, Thu-Ha


    Lactobacillus plantarum is considered as a potential cell factory because of its GRAS (generally recognized as safe) status and long history of use in food applications. Its possible applications include in situ delivery of proteins to a host, based on its ability to persist at mucosal surfaces of the human intestine, and the production of food-related enzymes. By displaying different enzymes on the surface of L. plantarum cells these could be used as whole-cell biocatalysts for the production of oligosaccharides. In this present study, we aimed to express and display a mannanase and a chitosanase on the cell surface of L. plantarum. ManB, a mannanase from Bacillus licheniformis DSM13, and CsnA, a chitosanase from Bacillus subtilis ATCC 23857 were fused to different anchoring motifs of L. plantarum for covalent attachment to the cell surface, either via an N-terminal lipoprotein anchor (Lp_1261) or a C-terminal cell wall anchor (Lp_2578), and the resulting fusion proteins were expressed in L. plantarum WCFS1. The localization of the recombinant proteins on the bacterial cell surface was confirmed by flow cytometry and immunofluorescence microscopy. The highest mannanase and chitosanase activities obtained for displaying L. plantarum cells were 890 U and 1360 U g dry cell weight, respectively. In reactions with chitosan and galactomannans, L. plantarum CsnA- and ManB-displaying cells produced chito- and manno-oligosaccharides, respectively, as analyzed by high performance anion exchange chromatography (HPAEC) and mass spectrometry (MS). Surface-displayed ManB is able to break down galactomannan (LBG) into smaller manno-oligosaccharides, which can support growth of L. plantarum. This study shows that mannanolytic and chitinolytic enzymes can be anchored to the cell surface of L. plantarum in active forms. L. plantarum chitosanase- and mannanase-displaying cells should be of interest for the production of potentially 'prebiotic' oligosaccharides. This approach

  19. Engineering the cell surface display of cohesins for assembly of cellulosome-inspired enzyme complexes on Lactococcus lactis

    Directory of Open Access Journals (Sweden)

    Wieczorek Andrew S


    Full Text Available Abstract Background The assembly and spatial organization of enzymes in naturally occurring multi-protein complexes is of paramount importance for the efficient degradation of complex polymers and biosynthesis of valuable products. The degradation of cellulose into fermentable sugars by Clostridium thermocellum is achieved by means of a multi-protein "cellulosome" complex. Assembled via dockerin-cohesin interactions, the cellulosome is associated with the cell surface during cellulose hydrolysis, forming ternary cellulose-enzyme-microbe complexes for enhanced activity and synergy. The assembly of recombinant cell surface displayed cellulosome-inspired complexes in surrogate microbes is highly desirable. The model organism Lactococcus lactis is of particular interest as it has been metabolically engineered to produce a variety of commodity chemicals including lactic acid and bioactive compounds, and can efficiently secrete an array of recombinant proteins and enzymes of varying sizes. Results Fragments of the scaffoldin protein CipA were functionally displayed on the cell surface of Lactococcus lactis. Scaffolds were engineered to contain a single cohesin module, two cohesin modules, one cohesin and a cellulose-binding module, or only a cellulose-binding module. Cell toxicity from over-expression of the proteins was circumvented by use of the nisA inducible promoter, and incorporation of the C-terminal anchor motif of the streptococcal M6 protein resulted in the successful surface-display of the scaffolds. The facilitated detection of successfully secreted scaffolds was achieved by fusion with the export-specific reporter staphylococcal nuclease (NucA. Scaffolds retained their ability to associate in vivo with an engineered hybrid reporter enzyme, E. coli β-glucuronidase fused to the type 1 dockerin motif of the cellulosomal enzyme CelS. Surface-anchored complexes exhibited dual enzyme activities (nuclease and β-glucuronidase, and were

  20. Recent advances in yeast cell-surface display technologies for waste biorefineries. (United States)

    Liu, Zhuo; Ho, Shih-Hsin; Hasunuma, Tomohisa; Chang, Jo-Shu; Ren, Nan-Qi; Kondo, Akihiko


    Waste biorefinery aims to maximize the output of value-added products from various artificial/agricultural wastes by using integrated bioprocesses. To make waste biorefinery economically feasible, it is thus necessary to develop a low-cost, environment-friendly technique to perform simultaneous biodegradation and bioconversion of waste materials. Cell-surface display engineering is a novel, cost-effective technique that can auto-immobilize proteins on the cell exterior of microorganisms, and has been applied for use with waste biofinery. Through tethering different enzymes (e.g., cellulase, lipase, and protease) or metal-binding peptides on cell surfaces, various yeast strains can effectively produce biofuels and biochemicals from sugar/protein-rich waste materials, catalyze waste oils into biodiesels, or retrieve heavy metals from wastewater. This review critically summarizes recent applications of yeast cell-surface display on various types of waste biorefineries, highlighting its potential and future challenges with regard to commercializing this technology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. La{sub 0.84}Sr{sub 0.16}MnO{sub 3-{delta}} cathodes impregnated with Bi{sub 1.4}Er{sub 0.6}O{sub 3} for intermediate-temperature solid oxide fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Junliang; Wang, Shaorong; Wang, Zhenrong; Liu, Renzhu; Wen, Tinglian; Wen, Zhaoyin [The Key Laboratory of Energy Conversion Materials, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai 200050 (China)


    La{sub 0.84}Sr{sub 0.16}MnO{sub 3-{delta}}-Bi{sub 1.4}Er{sub 0.6}O{sub 3} (LSM-ESB) composite cathodes are fabricated by impregnating LSM electronic conducting matrix with the ion-conducting ESB for intermediate-temperature solid oxide fuel cells (IT-SOFCs). The performance of LSM-ESB cathodes is investigated at temperatures below 750 C by AC impedance spectroscopy. The ion-impregnation of ESB significantly enhances the electrocatalytic activity of the LSM electrodes for the oxygen reduction reactions, and the ion-impregnated LSM-ESB composite cathodes show excellent performance. At 750 C, the value of the cathode polarization resistance (R{sub p}) is only 0.11 {omega} cm{sup 2} for an ion-impregnated LSM-ESB cathode, which also shows high stability during a period of 200 h. For the performance testing of single cells, the maximum power density is 0.74 W cm{sup -2} at 700 C for a cell with the LSM-ESB cathode. The results demonstrate the ion-impregnated LSM-ESB is one of the promising cathode materials for intermediate-temperature solid oxide fuel cells. (author)

  2. Head orientation prediction: delta quaternions versus quaternions. (United States)

    Himberg, Henry; Motai, Yuichi


    Display lag in simulation environments with helmet-mounted displays causes a loss of immersion that degrades the value of virtual/augmented reality training simulators. Simulators use predictive tracking to compensate for display lag, preparing display updates based on the anticipated head motion. This paper proposes a new method for predicting head orientation using a delta quaternion (DQ)-based extended Kalman filter (EKF) and compares the performance to a quaternion EKF. The proposed framework operates on the change in quaternion between consecutive data frames (the DQ), which avoids the heavy computational burden of the quaternion motion equation. Head velocity is estimated from the DQ by an EKF and then used to predict future head orientation. We have tested the new framework with captured head motion data and compared it with the computationally expensive quaternion filter. Experimental results indicate that the proposed DQ method provides the accuracy of the quaternion method without the heavy computational burden.

  3. Noggin and BMP4 co-modulate adult hippocampal neurogenesis in the APP{sub swe}/PS1{sub {Delta}E9} transgenic mouse model of Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Jun [Department of Medical Genetics, Third Military Medical University, Chongqing 400038 (China); Department of Physiology, Third Military Medical University, Chongqing 400038 (China); Song, Min; Wang, Yanyan [Department of Medical Genetics, Third Military Medical University, Chongqing 400038 (China); Fan, Xiaotang [Department of Histology and Embryology, Third Military Medical University, Chongqing 400038 (China); Xu, Haiwei, E-mail: [Department of Physiology, Third Military Medical University, Chongqing 400038 (China); Bai, Yun, E-mail: [Department of Medical Genetics, Third Military Medical University, Chongqing 400038 (China)


    In addition to the subventricular zone, the dentate gyrus of the hippocampus is one of the few brain regions in which neurogenesis continues into adulthood. Perturbation of neurogenesis can alter hippocampal function, and previous studies have shown that neurogenesis is dysregulated in Alzheimer disease (AD) brain. Bone morphogenetic protein-4 (BMP4) and its antagonist Noggin have been shown to play important roles both in embryonic development and in the adult nervous system, and may regulate hippocampal neurogenesis. Previous data indicated that increased expression of BMP4 mRNA within the dentate gyrus might contribute to decreased hippocampal cell proliferation in the APP{sub swe}/PS1{sub {Delta}E9} mouse AD model. However, it is not known whether the BMP antagonist Noggin contributes to the regulation of neurogenesis. We therefore studied the relative expression levels and localization of BMP4 and its antagonist Noggin in the dentate gyrus and whether these correlated with changes in neurogenesis in 6-12 mo old APP{sub swe}/PS1{sub {Delta}E9} transgenic mice. Bromodeoxyuridine (BrdU) was used to label proliferative cells. We report that decreased neurogenesis in the APP/PS1 transgenic mice was accompanied by increased expression of BMP4 and decreased expression of Noggin at both the mRNA and protein levels; statistical analysis showed that the number of proliferative cells at different ages correlated positively with Noggin expression and negatively with BMP4 expression. Intraventricular administration of a chimeric Noggin/Fc protein was used to block the action of endogenous BMP4; this resulted in a significant increase in the number of BrdU-labeled cells in dentate gyrus subgranular zone and hilus in APP/PS1 mice. These results suggest that BMP4 and Noggin co-modulate neurogenesis.

  4. The adhesion force of Notch with Delta and the rate of Notch signaling. (United States)

    Ahimou, Francois; Mok, Lee-Peng; Bardot, Boris; Wesley, Cedric


    Notch signaling is repeatedly used during animal development to specify cell fates. Using atomic force microscopy on live cells, chemical inhibitors, and conventional analyses, we show that the rate of Notch signaling is linked to the adhesion force between cells expressing Notch receptors and Delta ligand. Both the Notch extracellular and intracellular domains are required for the high adhesion force with Delta. This high adhesion force is lost within minutes, primarily due to the action of Presenilin on Notch. Reduced turnover or Delta pulling accelerate this loss. These data suggest that strong adhesion between Notch and Delta might serve as a booster for initiating Notch signaling at a high rate.

  5. Display of GPI-anchored anti-EGFR nanobodies on extracellular vesicles promotes tumour cell targeting

    Directory of Open Access Journals (Sweden)

    Sander A. A. Kooijmans


    Full Text Available Background: Extracellular vesicles (EVs are attractive candidate drug delivery systems due to their ability to functionally transport biological cargo to recipient cells. However, the apparent lack of target cell specificity of exogenously administered EVs limits their therapeutic applicability. In this study, we propose a novel method to equip EVs with targeting properties, in order to improve their interaction with tumour cells. Methods: EV producing cells were transfected with vectors encoding for anti-epidermal growth factor receptor (EGFR nanobodies, which served as targeting ligands for tumour cells, fused to glycosylphosphatidylinositol (GPI anchor signal peptides derived from decay-accelerating factor (DAF. EVs were isolated using ultrafiltration/size-exclusion liquid chromatography and characterized using western blotting, Nanoparticle Tracking Analysis, and electron microscopy. EV–tumour cell interactions were analyzed under static conditions using flow cytometry and under flow conditions using a live-cell fluorescence microscopy-coupled perfusion system. Results: V analysis showed that GPI-linked nanobodies were successfully displayed on EV surfaces and were highly enriched in EVs compared with parent cells. Display of GPI-linked nanobodies on EVs did not alter general EV characteristics (i.e. morphology, size distribution and protein marker expression, but greatly improved EV binding to tumour cells dependent on EGFR density under static conditions. Moreover, nanobody-displaying EVs showed a significantly improved cell association to EGFR-expressing tumour cells under flow conditions. Conclusions: We show that nanobodies can be anchored on the surface of EVs via GPI, which alters their cell targeting behaviour. Furthermore, this study highlights GPI-anchoring as a new tool in the EV toolbox, which may be applied for EV display of a variety of proteins, such as antibodies, reporter proteins and signaling molecules.

  6. Haematological and genetic features of delta beta-thalassaemia in Pakistan

    International Nuclear Information System (INIS)

    Ahmad, S.; Anwar, M.


    Objective: To describe the hematological and genetic features of delta beta-thalassaemia in Pakistani patients. Design: Descriptive case series. Place and Duration of Study: Department of Pathology, PNS Shifa, Karachi and Department of Hematology, Armed Forces Institute of Pathology, Rawalpindi, from January 1994 to April 2004. Patients and Methods: Thirteen individuals from six unrelated Pakistani families with a hematological diagnosis of delta beta-thalassaemia were studied. A brief clinical history, and the results of blood counts, absolute values, Hb-F, Hb-A/sub 2/, and hemoglobin electrophoresis were recorded. The DNA from each subject was first screened for the delta beta-thalassaemia mutations found in the Pakistani population. The samples were then screened for the Invl Del sup G/gamma(sup A/gamma delta beta). Results: The subjects included six heterozygote, six homozygotes and one compound heterozygote of delta beta and delta beta-thalassaemia. All heterozygote and 4/6 homozygotes were asymptomatic. One homo zygote had thalassaemia intermedia while another had transfusion dependent anemia. The mean Hb, TRBC, MCV, MCH, Hb-F and Hb-A/sub 2/ in delta beta-thalassaemia heterozygote were 11.6 g/dl, 5.37 x 1012/L, 70.9 fl, and 21.7 pg, 14% and 2.6% respectively. The same values in the four un transfused homo zygote were 10.6 g/dl, 5.34x1012/L, 69.211, and 20.8pg, 100% and 0% respectively. The mutation analysis revealed that all 13 individuals had the same Invl Del sup G/gamma(sup A/gamma delta beta). Conclusion: delta beta-thalassaemia is a rare disorder in Pakistan. Although the clinical picture is very mild its combination with delta beta-thalassaemia trait can produce a sever transfusion dependent thalassaemia. The DNA based diagnosis is possible in the prenatal as well as the postnatal period. (author)

  7. Magnetic cell sorting purification of differentiated embryonic stem cells stably expressing truncated human CD4 as surface marker. (United States)

    David, Robert; Groebner, Michael; Franz, Wolfgang-Michael


    Embryonic stem (ES) cells offer great potential in regenerative medicine and tissue engineering. Clinical applications are still hampered by the lack of protocols for gentle, high-yield isolation of specific cell types for transplantation expressing no immunogenic markers. We describe labeling of stably transfected ES cells expressing a human CD4 molecule lacking its intracellular domain (DeltaCD4) under control of the phosphoglycerate kinase promoter for magnetic cell sorting (MACS). To track the labeled ES cells, we fused DeltaCD4 to an intracellular enhanced green fluorescent protein domain (DeltaCD4EGFP). We showed functionality of the membrane-bound fluorescent fusion protein and its suitability for MACS leading to purities greater than 97%. Likewise, expression of DeltaCD4 yielded up to 98.5% positive cells independently of their differentiation state. Purities were not limited by the initial percentage of DeltaCD4(+) cells, ranging from 0.6%-16%. The viability of MACS-selected cells was demonstrated by reaggregation and de novo formation of embryoid bodies developing all three germ layers. Thus, expression of DeltaCD4 in differentiated ES cells may enable rapid, high-yield purification of a desired cell type for tissue engineering and transplantation studies.

  8. A Nonhuman Primate Transplantation Model to Evaluate Hematopoietic Stem Cell Gene Editing Strategies for β-Hemoglobinopathies

    Directory of Open Access Journals (Sweden)

    Olivier Humbert


    Full Text Available Reactivation of fetal hemoglobin (HbF is a promising approach for the treatment of β-hemoglobinopathies and the targeting of genes involved in HbF regulation is under intensive investigation. Here, we established a nonhuman primate (NHP transplantation model to evaluate hematopoietic stem cell (HSC-based gene editing strategies aimed at reactivating HbF. We first characterized the transient HbF induction to autologous HSC transplantation in pigtailed macaques, which was comparable in duration and amplitude to that of human patients. After validating function of the HbF repressor BCL11A in NHPs, we transplanted a pigtailed macaque with CD34+ cells electroporated with TALE nuclease mRNA targeting the BCL11A coding sequence. In vivo gene editing levels were low, but some BCL11A deletions were detected as late as 200 days post-transplantation. HbF production, as determined by F-cell staining and γ-globin expression, was slightly increased in this animal as compared to transplant controls. We also provided proof-of-concept results for the selection of edited NHP CD34+ cells in culture following integration of the P140K/MGMT cassette at the BCL11A locus. In summary, the NHP model described here will allow the testing of novel therapeutic approaches for hemoglobinopathies and should facilitate clinical translation.

  9. Halotolerance of Methanobacterium thermoautotrophicum delta H and Marburg.


    Ciulla, R; Clougherty, C; Belay, N; Krishnan, S; Zhou, C; Byrd, D; Roberts, M F


    Methanobacterium thermoautotrophicum delta H and Marburg were adapted to grow in medium containing up to 0.65 M NaCl. From 0.01 to 0.5 M NaCl, there was a lag before cell growth which increased with increasing external NaCl. The effect of NaCl on methane production was not significant once the cells began to grow. Intracellular solutes were monitored by nuclear magnetic resonance (NMR) spectroscopy as a function of osmotic stress. In the delta H strain, the major intracellular small organic s...

  10. Proinflammatory effect of sodium 4-phenylbutyrate in deltaF508-cystic fibrosis transmembrane conductance regulator lung epithelial cells: involvement of extracellular signal-regulated protein kinase 1/2 and c-Jun-NH2-terminal kinase signaling. (United States)

    Roque, Telma; Boncoeur, Emilie; Saint-Criq, Vinciane; Bonvin, Elise; Clement, Annick; Tabary, Olivier; Jacquot, Jacky


    Sodium 4-phenylbutyrate (4-PBA) has attracted a great deal of attention in cystic fibrosis (CF) pathology due to its capacity to traffic DeltaF508-cystic fibrosis transmembrane conductance regulator (CFTR) to the cell membrane and restore CFTR chloride function at the plasma membrane of CF lung cells in vitro and in vivo. Using two different DeltaF508-CFTR lung epithelial cell lines (CFBE41o- and IB3-1 cells, characterized with DeltaF508-homozygous and heterozygous genotype, respectively) in vitro, 4-PBA induced an increase of proinflammatory cytokine interleukin (IL)-8 production in a concentration-dependent manner. This 4-PBA-induced IL-8 production was associated with a strong reduction of proteasome and nuclear factor-kappaB transcriptional activities in the two DeltaF508-CFTR lung cells either in a resting state or after tumor necrosis factor-alpha stimulation. In contrast, a strong increase of activator protein-1 transcriptional activity was observed. The inhibition of extracellular signal-regulated protein kinase 1/2 (ERK1/2) by 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene (U0126) and 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD98059) and c-Jun-NH(2)-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) by anthra[1,9-cd] pyrazol-6 (2H)-one (SP600125), respectively, was associated with a reduction (2-3.5-fold) of IL-8 production in both DeltaF508-CFTR lung cell lines treated with 4-PBA. No significant change of IL-8 production was observed after an inhibition of p38 MAPK with 4-[4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazol-2-yl] phenol (SB202190). Therefore, we suggest that inhibition of both ERK1/2 and JNK signaling may be a means to strongly reduce 4-PBA-induced IL-8 production in combination with 4-PBA treatment to restore CFTR Cl(-) channel function in lung epithelial cells of patients with CF.

  11. Antiferromagnetic ordering in reduced Al doped YBa2Cu3-xAlxO6+#delta# single crystals

    DEFF Research Database (Denmark)

    Brecht, E.; Casalta, H.; Schleger, P.


    In YBa2Cu3-AlxO6+delta single crystals antiferromagnetic AFII ordering has been observed below 18 K by neutron diffraction. The transition temperature T-2 to the AFI ordering increases with x and delta.......In YBa2Cu3-AlxO6+delta single crystals antiferromagnetic AFII ordering has been observed below 18 K by neutron diffraction. The transition temperature T-2 to the AFI ordering increases with x and delta....

  12. Oxygen nonstoichiometry and ionic transport properties of La0.4Sr0.6CoO3-delta . (United States)

    Sitte, W; Bucher, E; Benisek, A; Preis, W


    Homogeneous samples of La0.4Sr0.6CoO3-delta were obtained by the glycine nitrate process. The oxygen nonstoichiometry was determined from oxygen exchange measurements as a function of oxygen partial pressure (10(-4) bar PO2 PO2-range between 10(-4) and 10(-2) bar to yield D and the ionic conductivity sigma(i) from the long time solution of the diffusion equation. Values for D from polarization measurements at T= 775 degrees C and from oxygen exchange measurements at T= 725 degrees C are in good agreement with each other. D and sigma(1) increase with increasing PO2 (10(-4) to 10(-2) bar). The ionic conductivity shows a maximum at 3-delta approximately 2.82 and decreases with decreasing oxygen content indicating the possible formation of vacancy ordered structures.

  13. Engineering the Substrate Specificity of the DhbE Adenylation Domain by Yeast Cell Surface Display


    Zhang, Keya; Nelson, Kathryn M.; Bhuripanyo, Karan; Grimes, Kimberly D.; Zhao, Bo; Aldrich, Courtney C.; Yin, Jun


    The adenylation (A) domains of nonribosomal peptide synthetases (NRPSs) activate aryl acids or amino acids to launch their transfer through the NRPS assembly line for the biosynthesis of many medicinally important natural products. In order to expand the substrate pool of NRPSs, we developed a method based on yeast cell surface display to engineer the substrate specificities of the A-domains. We acquired A-domain mutants of DhbE that have 11- and 6-fold increases in kcat/Km with nonnative sub...

  14. Multimode delta-E effect magnetic field sensors with adapted electrodes

    Energy Technology Data Exchange (ETDEWEB)

    Zabel, Sebastian; Fichtner, Simon; Kirchhof, Christine; Quandt, Eckhard; Faupel, Franz, E-mail: [Faculty of Engineering, Institute for Materials Science, Kiel University, Kaiserstraße 2, 24143 Kiel (Germany); Reermann, Jens; Schmidt, Gerhard [Faculty of Engineering, Institute for Electrical Engineering, Kiel University, Kaiserstraße 2, 24143 Kiel (Germany); Wagner, Bernhard [Fraunhofer Institute for Silicon Technology ISIT, Fraunhoferstraße 1, 25524 Itzehoe (Germany)


    We present an analytical and experimental study on low-noise piezoelectric thin film resonators that utilize the delta-E effect of a magnetostrictive layer to measure magnetic fields at low frequencies. Calculations from a physical model of the electromechanical resonator enable electrode designs to efficiently operate in the first and second transversal bending modes. As predicted by our calculations, the adapted electrode design improves the sensitivity by a factor of 6 and reduces the dynamic range of the sensor output by 16 dB, which significantly eases the requirements on readout electronics. Magnetic measurements show a bandwidth of 100 Hz at a noise level of about 100 pTHz{sup −0.5}.

  15. On Integrity of Flexible Displays (United States)

    Bouten, Piet C. P.

    Nowadays two display types are dominant in the display market: the bulky cathode ray tube (CRT) and liquid crystal displays (LCD). Both types use glass as substrate material. The LCD display is the dominant player for mobile applications, in for instance mobile phones and portable computers. In the development of displays and their applications a clear interest exists to replace the rigid rectangular display cells by free-shaped, curved or even roll-up cells. These types of applications require flexible displays.

  16. Late quaternary evolution of the Orinoco Delta, Venezuela (United States)

    Warne, A.G.; Guevara, E.H.; Aslan, A.


    The modern Orinoco Delta is the latest of a series of stacked deltas that have infilled the Eastern Venezuelan Basin (EVB) since the Oligocene. During the late Pleistocene sea-level lowstand (20,000 to 16,000 yrs BP), bedrock control points at the position of the present delta apex prevented the river channel from incising as deeply as many other major river systems. Shallow seismic data indicate that the late Pleistocene Orinoco incised into the present continental shelf, where it formed a braided-river complex that transported sediment to a series of shelf-edge deltas. As sea level rose from 16,000 to 9,500 yrs BP, the Orinoco shoreline shifted rapidly landward, causing shallow-marine waves and currents to form a widespread transgressive sand unit. Decelerating sea-level rise and a warmer, wetter climate during the early Holocene (9,500 to 6,000 yrs BP) induced delta development within the relatively quiet-water environment of the EVB embayment. Sea level approached its present stand in the middle Holocene (6,000 to 3,000 yrs BP), and the Orinoco coast prograded, broadening the delta plain and infilling the EVB embayment. Significant quantities of Amazon sediment began to be transported to the Orinoco coast by littoral currents. Continued progradation in the late Holocene caused the constriction at Boca de Serpientes to alter nearshore and shelf hydrodynamics and subdivide the submarine delta into two distinct areas: the Atlantic shelf and the Gulf of Paria. The increased influence of littoral currents along the coast promoted mudcape development. Because most of the water and sediment were transported across the delta plain through the Rio Grande distributary in the southern delta, much of the central and northwestern delta plain became sediment starved, promoting widespread accumulation of peat deposits. Human impacts on the delta are mostly associated with the Volca??n Dam on Can??o Manamo. However, human activities have had relatively little effect on the

  17. Membranes of activated CD4+ T cells expressing T cell receptor (TcR) alpha beta or TcR gamma delta induce IgE synthesis by human B cells in the presence of interleukin-4

    NARCIS (Netherlands)

    Gascan, H.; Aversa, G. G.; Gauchat, J. F.; van Vlasselaer, P.; Roncarolo, M. G.; Yssel, H.; Kehry, M.; Spits, H.; de Vries, J. E.


    In the present study it is demonstrated that human B cells can be induced to switch to IgE production following a contact-mediated signal provided by activated T cell receptor (TcR) gamma delta+, CD4+ and TcR alpha beta+, CD4+ T cell clones and interleukin (IL)-4. The signal provided by these T cell

  18. Stenotrophomonas maltophilia with histopathological features mimicking cutaneous gamma/delta T-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Natalie Kash


    Full Text Available We report a case of cutaneous Stenotrophomonas maltophilia infection which presented with clinical and histopathological findings that mimicked a gamma/delta (γδ T-cell lymphoma. In this case, tissue culture of the biopsy specimen was key to determining the diagnosis and allowing appropriate treatment with oral trimethoprim–sulfamethoxazole and topical silvadene. A prompt complete resolution of lesions was observed following antibiotic treatment, with no recurrence of disease over the last 5 years, supporting an infectious rather than malignant etiology. In our patient, radiation therapy was indicated based on the misdiagnosis of γδ T-cell lymphoma, which was supported both clinically and histopathologically. However, tissue culture in this case avoided unnecessary radiation exposure and highlights the role of tissue culture in the evaluation of the biopsy of an undiagnosed cutaneous lesion.

  19. Displacement waves in La2CuO(4-delta) and La(1.85)Sr(0.15)CuO(4-delta) (United States)

    Kajitani, Tsuyoshi; Onozuka, Takashi; Yamaguchi, Yasuo; Hirabayashi, Makoto; Syono, Yasuhiko


    Structural investigation of orthorhombic La2CuO(4-delta) and La(1.85)Sr(0.15)CuO(4-delta) was carried out by means of X-ray and neutron diffraction on the basis of the space group Cmmm. The periodic expansion/contraction type distortion of CuO6 octahedra was found in both orthorhombic compounds. The distortion is nearly one-dimensional in La2CuO(4-delta) but is two-dimensional in La(1.85)Sr(0.15)CuO(4-delta). The existence of a charge-density wave is highly possible in the structures.

  20. Control of communicable disease; foreign--requirements for importers of nonhuman primates (NHP). Final rule. (United States)


    The Centers for Disease Control and Prevention (CDC), located within the Department of Health and Human Services (HHS), is amending regulations for the importation of live nonhuman primates (NHPs) by extending existing requirements for the importation of Macaca fascicularis (cynomolgus), Chlorocebus aethiops (African green), and Macaca mulatta (rhesus) monkeys to all NHPs with the exception of the filovirus testing requirement. Filovirus testing will only be required for Old World NHPs in quarantine that have illness consistent with filovirus infection or that die for any reason other than trauma during quarantine. HHS/CDC is also finalizing a provision to reduce the frequency at which importers of cynomolgus, African green, and rhesus monkeys are required to renew their special permits (from every 180 days to every 2 years). HHS/CDC is incorporating existing guidelines into the regulations and adding new provisions to address the following: NHPs imported as part of an animal act; NHPs imported or transferred by zoological societies; the transfer of NHPs from approved laboratories; and non-live imported NHP products. Finally, HHS/CDC is also requiring that all NHPs be imported only through ports of entry where a HHS/CDC quarantine station is located.

  1. Reconfigurable Full-Page Braille Displays (United States)

    Garner, H. Douglas


    Electrically actuated braille display cells of proposed type arrayed together to form full-page braille displays. Like other braille display cells, these provide changeable patterns of bumps driven by digitally recorded text stored on magnetic tapes or in solid-state electronic memories. Proposed cells contain electrorheological fluid. Viscosity of such fluid increases in strong electrostatic field.

  2. Gamma delta T cells promote inflammation and insulin resistance during high fat diet-induced obesity in mice (United States)

    Gamma delta T cells are resident in adipose tissue and increase during diet-induced obesity. Their possible contribution to the inflammatory response that accompanies diet-induced obesity was investigated in mice after a 5-10 week high milk fat diet. The high milk fat diet resulted in significant in...

  3. Effects of out-of-plane disorder on the superconductivity of Bi{sub 2}Sr{sub 2-x}La{sub x}CuO{sub 6+{delta}}

    Energy Technology Data Exchange (ETDEWEB)

    Roehler, Juergen; Trabant, Christoph; Frielingsdorf, Johanna; Djemour, Rabia [Universitaet Koeln, 50937 Koeln (Germany); Martovitsky, Victor [Lebedev-Institute, 119991 Moscow (Russian Federation); Dudy, Lenart; Dwelk, Helmut; Krapf, Alica [Humboldt Universitaet Berlin, 12489 Berlin (Germany)


    The effects of out-of-plane substitutional order/disorder on cuprate superconductivity remains to a large extent an unresolved issue. We have investigated the connection between superconductivity and the lattice effects arising from the heterovalent doping of Bi{sub 2}Sr{sub 2-x}La{sub x}CuO{sub 6+{delta}}, x = 0.8-0.1. Decreasing lanthanum content tunes the compound through the entire underdoped and overdoped regimes. Cu-K and La- K EXAFS served as local structural probes, and single crystal X-ray diffraction for the determination of the basic unit cell, and the symmetry of the supercell. The oxygen atoms in the CuO{sub 2} planes were found significantly disordered, dependent on doping, and to exhibit minimum disorder around x{sub opt}=0.33. But the degree of substitutional disorder in the out-of-plane La environment turned out independent on the concentration of the La dopants, the superstructure symmetry, and the crystal growth parameters, whereas T{sub c} depends sensitively on them. No evidence was found for possible concentration dependent site changes of the La dopant from the nominal Sr to the Bi sites. We discuss the probably crucial role of the interstitial oxygen atoms for the superconducting properties of the Bi{sub 2}Sr{sub 2-x}La{sub x}CuO{sub 6+{delta}} system.

  4. Modeling Glaucoma: Retinal Ganglion Cells Generated from Induced Pluripotent Stem Cells of Patients with SIX6 Risk Allele Show Developmental Abnormalities. (United States)

    Teotia, Pooja; Van Hook, Matthew J; Wichman, Christopher S; Allingham, R Rand; Hauser, Michael A; Ahmad, Iqbal


    Glaucoma represents a group of multifactorial diseases with a unifying pathology of progressive retinal ganglion cell (RGC) degeneration, causing irreversible vision loss. To test the hypothesis that RGCs are intrinsically vulnerable in glaucoma, we have developed an in vitro model using the SIX6 risk allele carrying glaucoma patient-specific induced pluripotent stem cells (iPSCs) for generating functional RGCs. Here, we demonstrate that the efficiency of RGC generation by SIX6 risk allele iPSCs is significantly lower than iPSCs-derived from healthy, age- and sex-matched controls. The decrease in the number of RGC generation is accompanied by repressed developmental expression of RGC regulatory genes. The SIX6 risk allele RGCs display short and simple neurites, reduced expression of guidance molecules, and immature electrophysiological signature. In addition, these cells have higher expression of glaucoma-associated genes, CDKN2A and CDKN2B, suggesting an early onset of the disease phenotype. Consistent with the developmental abnormalities, the SIX6 risk allele RGCs display global dysregulation of genes which map on developmentally relevant biological processes for RGC differentiation and signaling pathways such as mammalian target of rapamycin that integrate diverse functions for differentiation, metabolism, and survival. The results suggest that SIX6 influences different stages of RGC differentiation and their survival; therefore, alteration in SIX6 function due to the risk allele may lead to cellular and molecular abnormalities. These abnormalities, if carried into adulthood, may make RGCs vulnerable in glaucoma. Stem Cells 2017;35:2239-2252. © 2017 AlphaMed Press.

  5. Delta opioid receptor on equine sperm cells: subcellular localization and involvement in sperm motility analyzed by computer assisted sperm analyzer (CASA

    Directory of Open Access Journals (Sweden)

    Lacalandra Giovanni M


    Full Text Available Abstract Background Opioid receptors and endogenous opioid peptides act not only in the control of nociceptive pathways, indeed several reports demonstrate the effects of opiates on sperm cell motility and morphology suggesting the importance of these receptors in the modulation of reproduction in mammals. In this study we investigated the expression of delta opioid receptors on equine spermatozoa by western blot/indirect immunofluorescence and its relationship with sperm cell physiology. Methods We analyzed viability, motility, capacitation, acrosome reaction and mitochondrial activity in the presence of naltrindole and DPDPE by means of a computer assisted sperm analyzer and a fluorescent confocal microscope. The evaluation of viability, capacitation and acrosome reaction was carried out by the double CTC/Hoechst staining, whereas mitochondrial activity was assessed by means of MitoTracker Orange dye. Results We showed that in equine sperm cells, delta opioid receptor is expressed as a doublet of 65 and 50 kDa molecular mass and is localized in the mid piece of tail; we also demonstrated that naltrindole, a delta opioid receptor antagonist, could be utilized in modulating several physiological parameters of the equine spermatozoon in a dose-dependent way. We also found that low concentrations of the antagonist increase sperm motility whereas high concentrations show the opposite effect. Moreover low concentrations hamper capacitation, acrosome reaction and viability even if the percentage of cells with active mitochondria seems to be increased; the opposite effect is exerted at high concentrations. We have also observed that the delta opioid receptor agonist DPDPE is scarcely involved in affecting the same parameters at the employed concentrations. Conclusions The results described in this paper add new important details in the comprehension of the mammalian sperm physiology and suggest new insights for improving reproduction and for

  6. Protein Kinase C-{delta} mediates down-regulation of heterogeneous nuclear ribonucleoprotein K protein: involvement in apoptosis induction

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Feng-Hou [NO.3 People' s Hospital affiliated to Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai 201900 (China); The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China); Wu, Ying-Li [The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China); Zhao, Meng [Institute of Health Science, SJTU-SM/Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai (China); Liu, Chuan-Xu; Wang, Li-Shun [The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China); Chen, Guo-Qiang, E-mail: [The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China); Institute of Health Science, SJTU-SM/Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai (China)


    We reported previously that NSC606985, a camptothecin analogue, induces apoptosis of acute myeloid leukemia (AML) cells through proteolytic activation of protein kinase C delta ({Delta}PKC-{delta}). By subcellular proteome analysis, heterogeneous nuclear ribonucleoprotein K (hnRNP K) was identified as being significantly down-regulated in NSC606985-treated leukemic NB4 cells. HnRNP K, a docking protein for DNA, RNA, and transcriptional or translational molecules, is implicated in a host of processes involving the regulation of gene expression. However, the molecular mechanisms of hnRNP K reduction and its roles during apoptosis are still not understood. In the present study, we found that, following the appearance of the {Delta}PKC-{delta}, hnRNP K protein was significantly down-regulated in NSC606985, doxorubicin, arsenic trioxide and ultraviolet-induced apoptosis. We further provided evidence that {Delta}PKC-{delta} mediated the down-regulation of hnRNP K protein during apoptosis: PKC-{delta} inhibitor could rescue the reduction of hnRNP K; hnRNP K failed to be decreased in PKC-{delta}-deficient apoptotic KG1a cells; conditional induction of {Delta}PKC-{delta} in U937T cells directly down-regulated hnRNP K protein. Moreover, the proteasome inhibitor also inhibited the down-regulation of hnRNP K protein by apoptosis inducer and the conditional expression of {Delta}PKC-{delta}. More intriguingly, the suppression of hnRNP K with siRNA transfection significantly induced apoptosis. To our knowledge, this is the first demonstration that proteolytically activated PKC-{delta} down-regulates hnRNP K protein in a proteasome-dependent manner, which plays an important role in apoptosis induction.

  7. Patient-specific induced pluripotent stem cells in neurological disease modeling: the importance of nonhuman primate models

    Directory of Open Access Journals (Sweden)

    Qiu Z


    Full Text Available Zhifang Qiu,1,2 Steven L Farnsworth,2 Anuja Mishra,1,2 Peter J Hornsby1,21Geriatric Research Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, TX, USA; 2Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX, USAAbstract: The development of the technology for derivation of induced pluripotent stem (iPS cells from human patients and animal models has opened up new pathways to the better understanding of many human diseases, and has created new opportunities for therapeutic approaches. Here, we consider one important neurological disease, Parkinson's, the development of relevant neural cell lines for studying this disease, and the animal models that are available for testing the survival and function of the cells, following transplantation into the central nervous system. Rapid progress has been made recently in the application of protocols for neuroectoderm differentiation and neural patterning of pluripotent stem cells. These developments have resulted in the ability to produce large numbers of dopaminergic neurons with midbrain characteristics for further study. These cells have been shown to be functional in both rodent and nonhuman primate (NHP models of Parkinson's disease. Patient-specific iPS cells and derived dopaminergic neurons have been developed, in particular from patients with genetic causes of Parkinson's disease. For complete modeling of the disease, it is proposed that the introduction of genetic changes into NHP iPS cells, followed by studying the phenotype of the genetic change in cells transplanted into the NHP as host animal, will yield new insights into disease processes not possible with rodent models alone.Keywords: Parkinson's disease, pluripotent cell differentiation, neural cell lines, dopaminergic neurons, cell transplantation, animal models

  8. Epoetin Delta Reduces Oxidative Stress in Primary Human Renal Tubular Cells

    Directory of Open Access Journals (Sweden)

    Annelies De Beuf


    Full Text Available Erythropoietin (EPO exerts (renal tissue protective effects. Since it is unclear whether this is a direct effect of EPO on the kidney or not, we investigated whether EPO is able to protect human renal tubular epithelial cells (hTECs from oxidative stress and if so which pathways are involved. EPO (epoetin delta could protect hTECs against oxidative stress by a dose-dependent inhibition of reactive oxygen species formation. This protective effect is possibly related to the membranous expression of the EPO receptor (EPOR since our data point to the membranous EPOR expression as a prerequisite for this protective effect. Oxidative stress reduction went along with the upregulation of renoprotective genes. Whilst three of these, heme oxygenase-1 (HO-1, aquaporin-1 (AQP-1, and B-cell CLL/lymphoma 2 (Bcl-2 have already been associated with EPO-induced renoprotection, this study for the first time suggests carboxypeptidase M (CPM, dipeptidyl peptidase IV (DPPIV, and cytoglobin (Cygb to play a role in this process.

  9. DNA repair synthesis in human fibroblasts requires DNA polymerase delta

    International Nuclear Information System (INIS)

    Nishida, C.; Reinhard, P.; Linn, S.


    When UV-irradiated cultured diploid human fibroblasts were permeabilized with Brij-58 then separated from soluble material by centrifugation, conservative DNA repair synthesis could be restored by a soluble factor obtained from the supernatant of similarly treated HeLa cells. Extensive purification of this factor yielded a 10.2 S, 220,000-dalton polypeptide with the DNA polymerase and 3'- to 5'-exonuclease activities reported for DNA polymerase delta II. Monoclonal antibody to KB cell DNA polymerase alpha, while binding to HeLa DNA polymerase alpha, did not bind to the HeLa DNA polymerase delta. Moreover, at micromolar concentrations N2-(p-n-butylphenyl)-2'-deoxyguanosine 5'-triphosphate (BuPdGTP) and 2-(p-n-butylanilino)-2'-deoxyadenosine 5'-triphosphate (BuAdATP) were potent inhibitors of DNA polymerase alpha, but did not inhibit the DNA polymerase delta. Neither purified DNA polymerase alpha nor beta could promote repair DNA synthesis in the permeabilized cells. Furthermore, under conditions which inhibited purified DNA polymerase alpha by greater than 90%, neither monoclonal antibodies to DNA polymerase alpha, BuPdGTP, nor BuAdATP was able to inhibit significantly the DNA repair synthesis mediated by the DNA polymerase delta. Thus, it appears that a major portion of DNA repair synthesis induced by UV irradiation might be catalyzed by DNA polymerase delta. When xeroderma pigmentosum human diploid fibroblasts were utilized, DNA repair synthesis dependent upon ultraviolet light could be restored by addition of both T4 endonuclease V and DNA polymerase delta, but not by addition of either one alone

  10. Diminished self-chaperoning activity of the DeltaF508 mutant of CFTR results in protein misfolding.

    Directory of Open Access Journals (Sweden)

    Adrian W R Serohijos


    Full Text Available The absence of a functional ATP Binding Cassette (ABC protein called the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR from apical membranes of epithelial cells is responsible for cystic fibrosis (CF. Over 90% of CF patients carry at least one mutant allele with deletion of phenylalanine at position 508 located in the N-terminal nucleotide binding domain (NBD1. Biochemical and cell biological studies show that the DeltaF508 mutant exhibits inefficient biosynthetic maturation and susceptibility to degradation probably due to misfolding of NBD1 and the resultant misassembly of other domains. However, little is known about the direct effect of the Phe508 deletion on the NBD1 folding, which is essential for rational design strategies of cystic fibrosis treatment. Here we show that the deletion of Phe508 alters the folding dynamics and kinetics of NBD1, thus possibly affecting the assembly of the complete CFTR. Using molecular dynamics simulations, we find that meta-stable intermediate states appearing on wild type and mutant folding pathways are populated differently and that their kinetic accessibilities are distinct. The structural basis of the increased misfolding propensity of the DeltaF508 NBD1 mutant is the perturbation of interactions in residue pairs Q493/P574 and F575/F578 found in loop S7-H6. As a proof-of-principle that the S7-H6 loop conformation can modulate the folding kinetics of NBD1, we virtually design rescue mutations in the identified critical interactions to force the S7-H6 loop into the wild type conformation. Two redesigned NBD1-DeltaF508 variants exhibited significantly higher folding probabilities than the original NBD1-DeltaF508, thereby partially rescuing folding ability of the NBD1-DeltaF508 mutant. We propose that these observed defects in folding kinetics of mutant NBD1 may also be modulated by structures separate from the 508 site. The identified structural determinants of increased misfolding propensity of

  11. Displacement waves in La/sub 2/CuO(4-delta) and La(1. 85)Sr(0. 15)CuO(4-delta)

    Energy Technology Data Exchange (ETDEWEB)

    Kajitani, T.; Onozuka, T.; Yamaguchi, Y.; Hirabayashi, M.; Syono, Y.


    Structural investigation of orthorhombic La/sub 2/CuO(4-delta) and La(1.85)Sr(0.15)CuO(4-delta) was carried out by means of X-ray and neutron diffraction on the basis of the space group Cmmm. The periodic expansion/contraction type distortion of CuO6 octahedra was found in both orthorhombic compounds. The distortion is nearly one-dimensional in La/sub 2/CuO(4-delta) but is two-dimensional in La(1.85)Sr(0.15)CuO(4-delta). The existence of a charge-density wave is highly possible in the structures. 20 references.

  12. Doubly truncated FosB isoform (Delta2DeltaFosB) induces osteosclerosis in transgenic mice and modulates expression and phosphorylation of Smads in osteoblasts independent of intrinsic AP-1 activity

    DEFF Research Database (Denmark)

    Sabatakos, George; Rowe, Glenn C; Kveiborg, Marie


    DeltaFosB and a further truncated isoform (Delta2DeltaFosB) that lacks known transactivation domains but, like DeltaFosB, induces increased expression of osteoblast marker genes. MATERIALS AND METHODS: To test Delta2DeltaFosB's ability to induce bone formation in vivo, we generated transgenic mice......6 expression. CONCLUSIONS: DeltaFosB's AP-1 transactivating function is not needed to induce increased bone formation, and Delta2DeltaFosB may act, at least in part, by increasing Smad1 expression, phosphorylation, and translocation to the nucleus....

  13. A nanobody:GFP bacterial platform that enables functional enzyme display and easy quantification of display capacity

    DEFF Research Database (Denmark)

    Wendel, Sofie; Christian Fischer, Emil; Martinez, Virginia


    Background: Bacterial surface display is an attractive technique for the production of cell-anchored, functional proteins and engineering of whole-cell catalysts. Although various outer membrane proteins have been used for surface display, an easy and versatile high-throughput-compatible assay...... to displaying the nanobody alone. We used flow cytometry to analyse display capability on single-cell versus population level and found that the signal peptide of the anchor has great effect on display efficiency.Conclusions: We have developed an inexpensive and easy read-out assay for surface display using...... nanobody: GFP interactions. The assay is compatible with the most common fluorescence detection methods, including multi-well plate whole-cell fluorescence detection, SDS-PAGE in-gel fluorescence, microscopy and flow cytometry. We anticipate that the platform will facilitate future in-depth studies...

  14. Influence of different organic fertilizers on quality parameters and the delta(15)N, delta(13)C, delta(2)H, delta(34)S, and delta(18)O values of orange fruit (Citrus sinensis L. Osbeck). (United States)

    Rapisarda, Paolo; Camin, Federica; Fabroni, Simona; Perini, Matteo; Torrisi, Biagio; Intrigliolo, Francesco


    To investigate the influence of different types of fertilizers on quality parameters, N-containing compounds, and the delta(15)N, delta(13)C, delta(2)H, delta (34)S, and delta(18)O values of citrus fruit, a study was performed on the orange fruit cv. 'Valencia late' (Citrus sinensis L. Osbeck), which was harvested in four plots (three organic and one conventional) located on the same farm. The results demonstrated that different types of organic fertilizers containing the same amount of nitrogen did not effect important changes in orange fruit quality parameters. The levels of total N and N-containing compounds such as synephrine in fruit juice were not statistically different among the different treatments. The delta(15)N values of orange fruit grown under fertilizer derived from animal origin as well as from vegetable compost were statistically higher than those grown with mineral fertilizer. Therefore, delta(15)N values can be used as an indicator of citrus fertilization management (organic or conventional), because even when applied organic fertilizers are of different origins, the natural abundance of (15)N in organic citrus fruit remains higher than in conventional ones. These treatments also did not effect differences in the delta(13)C, delta(2)H, delta(34)S, and delta(18)O values of fruit.

  15. Challenges, Approaches and Experiences from Asian Deltas and the Rhine-Meuse Delta : Regional Training Workshop on Delta Planning and Management

    NARCIS (Netherlands)

    Wosten, J.H.M.; Douven, W.; Long Phi, H.; Fida Abdullah Khan, M.


    River delta's, like the Mekong Delta (Vietnam), Ganges-Brahmaputra Delta (Bangladesh), Ayeyarwady Delta (Myanmar), Nile (Egypt) and Ciliwung Delta (Indonesia) are developing rapidly and are characterised by large-scale urbanisation and industrialization processes. They are facing serious planning

  16. Delta Plaza kohvik = Delta Plaza cafe

    Index Scriptorium Estoniae


    Tallinnas Pärnu mnt 141 asuva kohviku Delta Plaza sisekujundusest. Sisearhitektid Tiiu Truus ja Marja Viltrop (Stuudio Truus OÜ). Tiiu Truusi tähtsamate tööde loetelu. Büroohoone Delta Plaza arhitektid Marika Lõoke ja Jüri Okas (AB J. Okas & M. Lõoke)

  17. 78 FR 45592 - DeltaPoint Capital IV, LP; (United States)


    ..., Suite 160, Pittsford, NY 14534. The financing was contemplated for working capital. The financing is... SMALL BUSINESS ADMINISTRATION [License No. 02/02-0662] DeltaPoint Capital IV, LP; Notice Seeking... given that DeltaPoint Capital IV, L.P., 45 East Avenue, 6th Floor, Rochester, NY 14604, Federal...

  18. Large Area Thin Film Silicon: Synergy between Displays and Solar Cells

    NARCIS (Netherlands)

    Schropp, R.E.I.


    Thin-film silicon technology has changed our society, owing to the rapid advance of its two major application fields in communication (thin-film displays) and sustainable energy (thin-film solar cells). Throughout its development, advances in these application fields have always benefitted each

  19. Circular displays: control/display arrangements and stereotype strength with eight different display locations. (United States)

    Chan, Alan H S; Hoffmann, Errol R


    Two experiments are reported that were designed to investigate control/display arrangements having high stereotype strengths when using circular displays. Eight display locations relative to the operator and control were tested with rotational and translational controls situated on different planes according to the Frame of Reference Transformation Tool (FORT) model of Wickens et al. (2010). (Left. No, Right! Development of the Frame of Reference Transformation Tool (FORT), Proceedings of the Human Factors and Ergonomics Society 54th Annual Meeting, 54: 1022-1026). In many cases, there was little effect of display locations, indicating the importance of the Worringham and Beringer (1998. Directional stimulus-response compatibility: a test of three alternative principles. Ergonomics, 41(6), 864-880) Visual Field principle and an extension of this principle for rotary controls (Hoffmann and Chan (2013). The Worringham and Beringer 'visual field' principle for rotary controls. Ergonomics, 56(10), 1620-1624). The initial indicator position (12, 3, 6 and 9 o'clock) had a major effect on control/display stereotype strength for many of the six controls tested. Best display/control arrangements are listed for each of the different control types (rotational and translational) and for the planes on which they are mounted. Data have application where a circular display is used due to limited display panel space and applies to space-craft, robotics operators, hospital equipment and home appliances. Practitioner Summary: Circular displays are often used when there is limited space available on a control panel. Display/control arrangements having high stereotype strength are listed for four initial indicator positions. These arrangements are best for design purposes.

  20. Oxygen ordering in the high-T$_c$ superconductor HgBa$_2$CaCu$_2$O$_{6+\\delta}$ as revealed by perturbed angular correlation

    CERN Document Server

    Mendonca, Tania Melo; Haas, Heinz; Odier, Philippe; Tavares, Pedro; Silva, Manuel Ribeiro; Lopes, Armandina; Pereira, Andre; Goncalves, Joao Nuno; Amaral, Joao; Darie, Celine; Araujo, Joao Pedro


    Lattice sites and collective ordering of oxygen atoms in HgBa$_2$CaCu$_2$O$_{6+\\delta}$ were studied using the perturbed angular correlation (PAC) technique at ISOLDE/CERN. The electric field gradients (EFG) at $^{199m}$Hg nuclei have been measured as functions of oxygen doping on the Hg planes, above and below T$_c$. In comparison with the results obtained for oxygen and fluorine doping in Hg-1201, the analysis shows a different oxygen ordering exhibited by Hg-1212. Moreover, for all studied cases, the experimental results show that at a local scale there is non-uniform oxygen distribution. A series of ab initio EFG calculations allowed to infer that at low concentrations, regions without oxygen coexist with regions where O$_{2\\delta}$ dumbbell molecules are located at the center of the Hg mesh. On the other side, at high concentrations, O$_{2\\delta}$ dumbbell molecules coexist with single O$_\\delta$ atoms occupying the center of the Hg mesh. The present results suggest that oxygen sits on the Hg planes in t...

  1. PJA-BP expression and TCR delta deletion during human T cell differentiation

    NARCIS (Netherlands)

    M.C.M. Verschuren (Martie); B. Blom (Bianca); A.J.J.C. Bogers (Ad); H. Spits (Hergen); J.J.M. van Dongen (Jacques)


    textabstractRecombination of deltaRec to psiJalpha will delete the TCR delta gene, which is thought to play an important role in the bifurcation of the TCR alphabeta versus TCR gammadelta differentiation lineages. We recently detected a DNA-binding protein in human

  2. Human DNA polymerase delta double-mutant D316A;E318A interferes with DNA mismatch repair in vitro

    DEFF Research Database (Denmark)

    Liu, Dekang; Frederiksen, Jane H.; Liberti, Sascha Emilie


    DNA mismatch repair (MMR) is a highly-conserved DNA repair mechanism, whose primary role is to remove DNA replication errors preventing them from manifesting as mutations, thereby increasing the overall genome stability. Defects in MMR are associated with increased cancer risk in humans and other...... organisms. Here, we characterize the interaction between MMR and a proofreading-deficient allele of the human replicative DNA polymerase delta, PolδD316A;E318A, which has a higher capacity for strand displacement DNA synthesis than wild type Polδ. Human cell lines overexpressing PolδD316A;E318A display...

  3. Deformation characteristics of {delta} phase in the delta-processed Inconel 718 alloy

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, H.Y., E-mail: [Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Zhang, S.H., E-mail: [Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Cheng, M. [Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Li, Z.X. [Beijing Institute of Aeronautica1 Materials, Beijing 100095 (China)


    The hot working characteristics of {delta} phase in the delta-processed Inconel 718 alloy during isothermal compression deformation at temperature of 950 deg. C and strain rate of 0.005 s{sup -1}, were studied by using optical microscope, scanning electron microscope and quantitative X-ray diffraction technique. The results showed that the dissolution of plate-like {delta} phase and the precipitation of spherical {delta} phase particles coexisted during the deformation, and the content of {delta} phase decreased from 7.05 wt.% to 5.14 wt.%. As a result of deformation breakage and dissolution breakage, the plate-like {delta} phase was spheroidized and transferred to spherical {delta} phase particles. In the center with largest strain, the plate-like {delta} phase disappeared and spherical {delta} phase appeared in the interior of grains and grain boundaries.

  4. Correlation of infrared reflectance ratios at 2.3 microns/1.6 micron and 1.1 micron/1.6 micron with delta O-18 values delineating fossil hydrothermal systems in the Idaho batholith (United States)

    Gillespie, A. R.; Criss, R. E.


    Reflectance ratios from laboratory spectra and airborne multispectral images are found to be strongly correlated with delta O-18 values of granite rocks in the Idaho batholith. The correlation is largely a result of interactions between hot water and rock, which lowered the delta O-18 values of the rocks and produced secondary hydrous material. Maps of the ratio of reflectivities at 2.3 and 1.6 microns should delineate fossil hydrothermal systems and provide estimates of alteration intensity. However, hydrous minerals produced during deuteric alteration or weathering cannot be unambiguously distinguished in remotely sensed images from the products of propylitic alteration without the use of narrow-band scanners. The reflectivity at 1.6 micron is strongly correlated with rock density and may be useful in distinguishing rock types in granitic terranes.

  5. Dclk1+ small intestinal epithelial tuft cells display the hallmarks of quiescence and self-renewal (United States)

    Chandrakesan, Parthasarathy; May, Randal; Qu, Dongfeng; Weygant, Nathaniel; Taylor, Vivian E.; Li, James D.; Ali, Naushad; Sureban, Sripathi M.; Qante, Michael; Wang, Timothy C.; Bronze, Michael S.; Houchen, Courtney W.


    To date, no discrete genetic signature has been defined for isolated Dclk1+ tuft cells within the small intestine. Furthermore, recent reports on the functional significance of Dclk1+ cells in the small intestine have been inconsistent. These cells have been proposed to be fully differentiated cells, reserve stem cells, and tumor stem cells. In order to elucidate the potential function of Dclk1+ cells, we FACS-sorted Dclk1+ cells from mouse small intestinal epithelium using transgenic mice expressing YFP under the control of the Dclk1 promoter (Dclk1-CreER;Rosa26-YFP). Analysis of sorted YFP+ cells demonstrated marked enrichment (~6000 fold) for Dclk1 mRNA compared with YFP− cells. Dclk1+ population display ~6 fold enrichment for the putative quiescent stem cell marker Bmi1. We observed significantly greater expression of pluripotency genes, pro-survival genes, and quiescence markers in the Dclk1+ population. A significant increase in self-renewal capability (14-fold) was observed in in vitro isolated Dclk1+ cells. The unique genetic report presented in this manuscript suggests that Dclk1+ cells may maintain quiescence, pluripotency, and metabolic activity for survival/longevity. Functionally, these reserve characteristics manifest in vitro, with Dclk1+ cells exhibiting greater ability to self-renew. These findings indicate that quiescent stem-like functionality is a feature of Dclk1-expressing tuft cells. PMID:26362399

  6. In Situ Foaming of Porous (La 0.6 Sr 0.4 ) 0.98 (Co 0.2 Fe 0.8 ) O 3-δ (LSCF) Cathodes for Solid Oxide Fuel Cell Applications

    Energy Technology Data Exchange (ETDEWEB)

    Gandavarapu, Sodith [US DOE-National Energy Technology Laboratory, 3610 Collins Ferry Road P.O.Box.880 Morgantown West Virginia 26507; Department of Mechanical and Aerospace Engineering, West Virginia University, Morgantown West Virginia 26506; Sabolsky, Edward [US DOE-National Energy Technology Laboratory, 3610 Collins Ferry Road P.O.Box.880 Morgantown West Virginia 26507; Department of Mechanical and Aerospace Engineering, West Virginia University, Morgantown West Virginia 26506; Sabolsky, Katarzyna [Department of Mechanical and Aerospace Engineering, West Virginia University, Morgantown West Virginia 26506; Gerdes, Kirk [US DOE-National Energy Technology Laboratory, 3610 Collins Ferry Road P.O.Box.880 Morgantown West Virginia 26507


    A binder system containing polyurethane precursors was used to in situ foam (direct foam) a (La{sub 0.6}Sr{sub 0.4}){sub 0.98} (Co{sub 0.2} Fe{sub 0.8}) O{sub 3-{ delta}} (LSCF) composition for solid oxide fuel cell (SOFC) cathode applications. The relation between in situ foaming parameters on the final microstructure and electrochemical properties was characterized by microscopy and electrochemical impedance spectroscopy (EIS), respectively. The optimal porous cathode architecture was formed with a 70 vol% solids loading within a polymer precursor composition with a volume ratio of 8:4:1 (isocyanate: PEG: surfactant) in a terpineol-based ink vehicle. The resultant microstructure displayed a broad pore size distribution with highly elongated pore structure.

  7. Engineering the substrate specificity of the DhbE adenylation domain by yeast cell surface display. (United States)

    Zhang, Keya; Nelson, Kathryn M; Bhuripanyo, Karan; Grimes, Kimberly D; Zhao, Bo; Aldrich, Courtney C; Yin, Jun


    The adenylation (A) domains of nonribosomal peptide synthetases (NRPSs) activate aryl acids or amino acids to launch their transfer through the NRPS assembly line for the biosynthesis of many medicinally important natural products. In order to expand the substrate pool of NRPSs, we developed a method based on yeast cell surface display to engineer the substrate specificities of the A-domains. We acquired A-domain mutants of DhbE that have 11- and 6-fold increases in k(cat)/K(m) with nonnative substrates 3-hydroxybenzoic acid and 2-aminobenzoic acid, respectively and corresponding 3- and 33-fold decreases in k(cat)/K(m) values with the native substrate 2,3-dihydroxybenzoic acid, resulting in a dramatic switch in substrate specificity of up to 200-fold. Our study demonstrates that yeast display can be used as a high throughput selection platform to reprogram the "nonribosomal code" of A-domains. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. The Niger Delta Amnesty Program

    Directory of Open Access Journals (Sweden)

    Benjamin A. Okonofua


    Full Text Available The armed conflict between militias and government forces in Nigeria’s Niger Delta region has spanned for more than two decades, defying all solutions. A disarmament, demobilization, and reintegration (DDR program was established in August 2015 in effort to end the violence and has remained in place. It is a radically different approach from past approaches that displayed zero tolerance to all political challenges to oil production or the allocation of oil profits. The approach appeared to be immediately successful in that it forced a ceasefire, engaged militants in planned programs to rehabilitate and reintegrate them into civilian society, and opened up the oil wells (many of which had been shut due to the crisis with the effect of increasing government revenue, which depends 85% on oil exports. Yet, few studies have attempted to understand the dynamics within the country that are responsible for the design and implementation of this broad policy shift or to understand whether and how the current initiative is able to end the conflict and institute peace beyond the short term. This study, therefore, is important because it provides a critical perspective that anticipates and explains emerging issues with the Niger Delta Amnesty Program, which have implications for DDR adaptation and implementation all over the world. Ultimately, the research demonstrates how the DDR program both transforms the Niger Delta conflict and becomes embroiled in intense contestations not only about the mechanism for transforming the targeted population but also whether and how the program incorporates women who are being deprioritized by the program.

  9. Delta antibody radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Kselikova, M; Urbankova, J


    The principle and procedure are described of the radioimmunoassay of delta antibody (delta-Ab) using the ABBOTT ANTI-DELTA kit by Abbott Co. A description is given of the kit, the working procedure and the method of evaluation. The results are reported of the incidence of delta-Ab in sera of patients with viral hepatitis B, in haemophiliacs, carriers of the hepatitis B virus surface antigen (HBsAg) and blood donors. The presence was detected of delta-Ab in one HBsAg carrier. The necessity is emphasized of delta-Ab determinations in the blood of donors in view of the antibody transfer with blood and blood preparations.

  10. Liquid crystal displays with plastic substrates (United States)

    Lueder, Ernst H.


    Plastic substrates for the cells of displays exhibit only 1/6 of the weight of glass substrates; they are virtually unbreakable; their flexibility allows the designer to give them a shape suppressing reflections, to realize a display board on a curved surface or meeting the requirements for an appealing styling; displays with plastics are thinner which provides a wider viewing angle. These features render them attractive for displays in portable systems such as mobile phones, pagers, smart cards, personal digital assistants (PDAs) and portable computers. Reflective displays are especially attractive as they don't need a back light. The most important requirements are the protection of plastics against gas permeation and chemical agents, the prevention of layers on plastics to crack or peel off when the plastic is bent and the development of low temperature thin film processes because the plastics, as a rule, only tolerate temperatures below 150 degrees Celsius. Bistable reflective FLC- and PSCT-displays with plastic substrates will be introduced. Special sputtered SiO2-orientation layers preserve the displayed information even if pressure or torsion is applied. MIM-addressed PDLC-displays require additional Al- or Ti-layers which provide the necessary ductility. Sputtered or PECVD-generated TFTs can be fabricated on plastics at temperatures below 150 degrees Celsius.

  11. Production of erythrocytes from directly isolated or Delta1 Notch ligand expanded CD34+ hematopoietic progenitor cells: process characterization, monitoring and implications for manufacture. (United States)

    Glen, Katie E; Workman, Victoria L; Ahmed, Forhad; Ratcliffe, Elizabeth; Stacey, Adrian J; Thomas, Robert J


    Economic ex vivo manufacture of erythrocytes at 10(12) cell doses requires an efficiently controlled bio-process capable of extensive proliferation and high terminal density. High-resolution characterization of the process would identify production strategies for increased efficiency, monitoring and control. CD34(+) cord blood cells or equivalent cells that had been pre-expanded for 7 days with Delta1 Notch ligand were placed in erythroid expansion and differentiation conditions in a micro-scale ambr suspension bioreactor. Multiple culture parameters were varied, and phenotype markers and metabolites measured to identify conserved trends and robust monitoring markers. The cells exhibited a bi-modal erythroid differentiation pattern with an erythroid marker peak after 2 weeks and 3 weeks of culture; differentiation was comparatively weighted toward the second peak in Delta1 pre-expanded cells. Both differentiation events were strengthened by omission of stem cell factor and dexamethasone. The cumulative cell proliferation and death, or directly measured CD45 expression, enabled monitoring of proliferative rate of the cells. The metabolic activities of the cultures (glucose, glutamine and ammonia consumption or production) were highly variable but exhibited systematic change synchronized with the change in differentiation state. Erythroid differentiation chronology is partly determined by the heterogeneous CD34(+) progenitor compartment with implications for input control; Delta1 ligand-mediated progenitor culture can alter differentiation profile with control benefits for engineering production strategy. Differentiation correlated changes in cytokine response, markers and metabolic state will enable scientifically designed monitoring and timing of manufacturing process steps. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  12. 27 CFR 6.83 - Product displays. (United States)


    ... industry member of giving or selling product displays to a retailer does not constitute a means to induce... (c) of this section are met. (b) Definition. “Product display” means any wine racks, bins, barrels... industry member under paragraph (a) of this section may not exceed $300 per brand at any one time in any...

  13. Sr{sub 2}CoMoO{sub 6} anode for solid oxide fuel cell running on H{sub 2} and CH{sub 4} fuels

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ping [Engineering Research Center of Nano-GEO Materials of Education Ministry, China University of Geosciences, Wuhan 430074 (China); Texas Materials Institute, ETC 9.102, The University of Texas at Austin, Austin, TX 78712 (United States); Huang, Yun-Hui [Texas Materials Institute, ETC 9.102, The University of Texas at Austin, Austin, TX 78712 (United States); State Key Laboratory of Materials Processing and Die and Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074 (China); Cheng, Jin-Guang; Goodenough, John B. [Texas Materials Institute, ETC 9.102, The University of Texas at Austin, Austin, TX 78712 (United States); Mao, Zong-Qiang [Institute of Nuclear and New Energy Technology, Tsinghua University, Beijing 100084 (China)


    The double perovskite Sr{sub 2}CoMoO{sub 6-{delta}} was investigated as a candidate anode for a solid oxide fuel cell (SOFC). Thermogravimetric analysis (TGA) and powder X-ray diffraction (XRD) showed that the cation array is retained to 800 C in H{sub 2} atmosphere with the introduction of a limited concentration of oxide-ion vacancies. Stoichiometric Sr{sub 2}CoMoO{sub 6} has an antiferromagnetic Neel temperature T{sub N} {approx} 37 K, but after reduction in H{sub 2} at 800 C for 10 h, long-range magnetic order appears to set in above 300 K. In H{sub 2}, the electronic conductivity increases sharply with temperature in the interval 400 C < T < 500 C due to the onset of a loss of oxygen to make Sr{sub 2}CoMoO{sub 6-{delta}} a good mixed oxide-ion/electronic conductor (MIEC). With a 300-{mu}m-thick La{sub 0.8}Sr{sub 0.12}Ga{sub 0.83}Mg{sub 0.17}O{sub 2.815} (LSGM) as oxide-ion electrolyte and SrCo{sub 0.8}Fe{sub 0.2}O{sub 3-{delta}} as the cathode, the Sr{sub 2}CoMoO{sub 6-{delta}} anode gave a maximum power density of 1017 mW cm{sup -2} in H{sub 2} and 634 mW cm{sup -2} in wet CH{sub 4}. A degradation of power in CH{sub 4} was observed, which could be attributed to coke build up observed by energy dispersive spectroscopy (EDS). (author)

  14. A nanobody:GFP bacterial platform that enables functional enzyme display and easy quantification of display capacity. (United States)

    Wendel, Sofie; Fischer, Emil C; Martínez, Virginia; Seppälä, Susanna; Nørholm, Morten H H


    Bacterial surface display is an attractive technique for the production of cell-anchored, functional proteins and engineering of whole-cell catalysts. Although various outer membrane proteins have been used for surface display, an easy and versatile high-throughput-compatible assay for evaluating and developing surface display systems is missing. Using a single domain antibody (also called nanobody) with high affinity for green fluorescent protein (GFP), we constructed a system that allows for fast, fluorescence-based detection of displayed proteins. The outer membrane hybrid protein LppOmpA and the autotransporter C-IgAP exposed the nanobody on the surface of Escherichia coli with very different efficiency. Both anchors were capable of functionally displaying the enzyme Chitinase A as a fusion with the nanobody, and this considerably increased expression levels compared to displaying the nanobody alone. We used flow cytometry to analyse display capability on single-cell versus population level and found that the signal peptide of the anchor has great effect on display efficiency. We have developed an inexpensive and easy read-out assay for surface display using nanobody:GFP interactions. The assay is compatible with the most common fluorescence detection methods, including multi-well plate whole-cell fluorescence detection, SDS-PAGE in-gel fluorescence, microscopy and flow cytometry. We anticipate that the platform will facilitate future in-depth studies on the mechanism of protein transport to the surface of living cells, as well as the optimisation of applications in industrial biotech.

  15. Ribosome display: next-generation display technologies for production of antibodies in vitro. (United States)

    He, Mingyue; Khan, Farid


    Antibodies represent an important and growing class of biologic research reagents and biopharmaceutical products. They can be used as therapeutics in a variety of diseases. With the rapid expansion of proteomic studies and biomarker discovery, there is a need for the generation of highly specific binding reagents to study the vast number of proteins encoded by the genome. Display technologies provide powerful tools for obtaining antibodies. Aside from the preservation of natural antibody repertoires, they are capable of exploiting diversity by DNA recombination to create very large libraries for selection of novel molecules. In contrast to in vivo immunization processes, display technologies allow selection of antibodies under in vitro-defined selection condition(s), resulting in enrichment of antibodies with desired properties from large populations. In addition, in vitro selection enables the isolation of antibodies against difficult antigens including self-antigens, and this can be applied to the generation of human antibodies against human targets. Display technologies can also be combined with DNA mutagenesis for antibody evolution in vitro. Some methods are amenable to automation, permitting high-throughput generation of antibodies. Ribosome display is considered as representative of the next generation of display technologies since it overcomes the limitations of cell-based display methods by using a cell-free system, offering advantages of screening larger libraries and continuously expanding new diversity during selection. Production of display-derived antibodies can be achieved by choosing one of a variety of prokaryotic and eukaryotic cell-based expression systems. In the near future, cell-free protein synthesis may be developed as an alternative for large-scale generation of antibodies.

  16. Effects of biodegradable Mg–6Zn alloy extracts on apoptosis of intestinal epithelial cells

    International Nuclear Information System (INIS)

    Wang Zhanhui; Yan Jun; Li Jianan; Zheng Qi; Wang Zhigang; Zhang Xiaonong; Zhang Shaoxiang


    Highlights: ► We evaluated the effects of Mg–6Zn alloys on apoptosis of IEC-6 cells. ► The apoptosis was evaluated by investigating the expression of caspase-1 and Bcl-2. ► The IEC-6 cells displayed better cell functions in 60% or 20% extract. ► The conspicuous alkaline environment is disadvantageous to apoptosis of IEC cells. ► The excessive Mg concentration is disadvantageous to apoptosis of IEC-6 cells. - Abstract: In this study, intestinal epithelial cells (IEC)-6 were cultured in different concentration extracts of Mg–6Zn alloys for different time periods. To achieve a total of three concentrations (100%, 60% and 20% concentration), the extracts were serially diluted with Dulbecco's modified Eagle medium High Glucose to observe a dose–response relationship. We studied the indirect effects of Mg–6Zn alloys on IEC-6 cells apoptosis. The apoptosis of IEC-6 cells was measured using flow cytometry. And the apoptosis of IEC-6 cells was evaluated by investigating the expression of caspase-1and Bcl-2 using real-time polymerase chain reaction (PCR) and Western blotting tests. It was found that the levels of apoptosis in IEC-6 cells cultured in 100% Mg–6Zn alloy extracts were significantly higher than those in 60% and 20% extracts; the 100% extract can down-regulate expression of Bcl-2 after culture. The in vitro results indicated that the conspicuous alkaline environment and excessive Mg concentration, even Zn concentration caused by rapid corrosion of Mg–6Zn alloys promote IEC-6 cells apoptosis, although further experiments will be necessary to formally prove our conclusions. Therefore, the adjustment of the degradation rate is needed for using Mg–Zn alloy as a surgical suture material.

  17. Inhibition of NMDARs in the nucleus reticularis of the thalamus produces delta frequency bursting

    Directory of Open Access Journals (Sweden)

    Yuchun Zhang


    Full Text Available Injection of NMDAR antagonist into the thalamus can produce delta frequency EEG oscillations in the thalamocortical system. It is surprising that an antagonist of an excitatory neurotransmitter should trigger such activity, and the mechanism is unknown. One hypothesis is that the antagonist blocks excitation of GABAergic cells, thus producing disinhibition. To test this hypothesis, we investigated the effect of NMDAR antagonist (APV on cells of the nucleus reticularis (nRT in rat brain slices, a thalamic nucleus that can serve as a pacemaker for thalamocortical delta oscillations and that is composed entirely of GABAergic neurons. We found, unexpectedly, that nRT cells are hyperpolarized by APV. This occurs because these cells have an unusual form of NMDAR (probably NR2C that contributes inward current at resting potential in response to ambient glutamate. The hyperpolarization produced by APV is sufficient to deinactivate T-type calcium channels, and these trigger rhythmic bursting at delta frequency. The APV-induced delta frequency bursting is abolished by dopamine D2 receptor antagonist, indicating that dopamine and NMDAR antagonist work synergistically to stimulate delta frequency bursting. Our results have significant implications concerning the electrophysiological basis of schizophrenia and bring together the NMDAR hypofunction, dopamine, and GABA theories of the disease. Our results suggest that NMDAR hypofunction and dopamine work synergistically on the GABAergic cells of the nRT to generate the delta frequency EEG oscillations, a thalamocortical dysrhythmia (TCD in the awake state that is an established abnormality in schizophrenia.

  18. Identification of di- and tri-substituted hydroxy and ketone metabolites of delta1-tetrahydrocannabinol in mouse liver. (United States)

    Harvey, D J; Martin, B R; Paton, W D


    In vivo liver metabolites of delta1-tetrahydrocannabinol (delta1-THC) were examined with a gas chromatograph--mass spectrometer--computer system as trimethylsilyl (TMS), [2H9]TMS and methyloxime-TMS derivatives. In addition to the reported monohydroxy, acid, and hydroxyacid metabolites, the following multiply substituted metabolites were identified: 2'',7-, 3'', 7-, and 6beta,7-dihydroxy-delta1-THC; 2'',6alpha,7-, and 3'',6alpha,7-trihydroxy-delta1-THC; 2''-, 3''-, and 7-hydroxy-6-oxo-delta1-THC, and 2'',7- and 3'',7-dihydroxy-6-oxo-delta1-THC. The ketones and hydroxyacids were reduced to common alcohols with lithium aluminium deuteride and the number of deuterium atoms in the product was used to distinguish the metabolic alcohols from those produced by reduction.

  19. Dichroic Liquid Crystal Displays (United States)

    Bahadur, Birendra

    The following sections are included: * INTRODUCTION * DICHROIC DYES * Chemical Structure * Chemical and Photochemical Stability * THEORETICAL MODELLING * DEFECTS CAUSED BY PROLONGED LIGHT IRRADIATION * CHEMICAL STRUCTURE AND PHOTOSTABILITY * OTHER PARAMETERS AFFECTING PHOTOSTABILITY * CELL PREPARATION * DICHROIC PARAMETERS AND THEIR MEASUREMENTS * Order Parameter and Dichroic Ratio Of Dyes * Absorbance, Order Parameter and Dichroic Ratio Measurements * IMPACT OF DYE STRUCTURE AND LIQUID CRYSTAL HOST ON PHYSICAL PROPERTIES OF A DICHROIC MIXTURE * Order Parameter and Dichroic Ratio * EFFECT OF LENGTH OF DICHROIC DYES ON THE ORDER PARAMETER * EFFECT OF THE BREADTH OF DYE ON THE ORDER PARAMETER * EFFECT OF THE HOST ON THE ORDER PARAMETER * TEMPERATURE VARIATION OF THE ORDER PARAMETER OF DYES IN A LIQUID CRYSTAL HOST * IMPACT OF DYE CONCENTRATION ON THE ORDER PARAMETER * Temperature Range * Viscosity * Dielectric Constant and Anisotropy * Refractive Indices and Birefringence * solubility43,153-156 * Absorption Wavelength and Auxochromic Groups * Molecular Engineering of Dichroic Dyes * OPTICAL, ELECTRO-OPTICAL AND LIFE PARAMETERS * Colour And CIE Colour space120,160-166 * CIE 1931 COLOUR SPACE * CIE 1976 CHROMATICITY DIAGRAM * CIE UNIFORM COLOUR SPACES & COLOUR DIFFERENCE FORMULAE120,160-166 * Electro-Optical Parameters120 * LUMINANCE * CONTRAST AND CONTRAST RATIO * SWITCHING SPEED * Life Parameters and Failure Modes * DICHROIC MIXTURE FORMULATION * Monochrome Mixture * Black Mixture * ACHROMATIC BLACK MIXTURE FOR HEILMEIER DISPLAYS * Effect of Illuminant on Display Colour * Colour of the Field-On State * Effect of Dye Linewidth * Optimum Centroid Wavelengths * Effect of Dye Concentration * Mixture Formulation Using More Than Three Dyes * ACHROMATIC MIXTURE FOR WHITE-TAYLOR TYPE DISPLAYS * HEILMEIER DISPLAYS * Theoretical Modelling * Threshold Characteristic * Effects of Dye Concentration on Electro-optical Parameters * Effect of Cholesteric Doping * Effect of Alignment

  20. Genomic organization of the mouse peroxisome proliferator-activated receptor beta/delta gene

    DEFF Research Database (Denmark)

    Larsen, Leif K; Amri, Ez-Zoubir; Mandrup, Susanne


    Peroxisome proliferator-activated receptor (PPAR) beta/delta is ubiquitously expressed, but the level of expression differs markedly between different cell types. In order to determine the molecular mechanisms governing PPARbeta/delta gene expression, we have isolated and characterized the mouse...

  1. Plasmids and packaging cell lines for use in phage display (United States)

    Bradbury, Andrew M.


    The invention relates to a novel phagemid display system for packaging phagemid DNA into phagemid particles which completely avoids the use of helper phage. The system of the invention incorporates the use of bacterial packaging cell lines which have been transformed with helper plasmids containing all required phage proteins but not the packaging signals. The absence of packaging signals in these helper plasmids prevents their DNA from being packaged in the bacterial cell, which provides a number of significant advantages over the use of both standard and modified helper phage. Packaged phagemids expressing a protein or peptide of interest, in fusion with a phage coat protein such as g3p, are generated simply by transfecting phagemid into the packaging cell line.

  2. Characterization of bovine gamma delta T cells phenotype during post-natal development and following Mycobacterium bovis vaccination or virulent infection (United States)

    Bovine tuberculosis caused by Mycobacterium bovis is a globally significant veterinary health problem. Gamma delta T cells are known to participate in the immune control of mycobacterial infections. Data in human and non-human primates suggest that mycobacterial infection regulates memory/effector p...

  3. Delta Dynamics

    DEFF Research Database (Denmark)

    Bendixen, Mette

    . The warming air temperature affects the soil temperature and permafrost thaws and destabilizes the material in the coastal zone. In Greenland, the warming temperature lowers the surface mass balance of the Greenland Ice Sheet and more material is transported to the coastal zone. The sea ice extent is thinning...... of a fjord and the second type is a wider fan-shaped open delta. Most deltas are directly coupled to the Greenland Ice Sheet or local icecaps and are highly influenced by the dynamics in the catchments. It is demonstrated how a modern changing climate directly affects delta dynamics, and that Greenlandic...... deltas are prograding, contrary to the global trend showing eroding Arctic coasts. Moreover, it is revealed that the increasing proglacial freshwater runoff, caused by a lowering of the surface mass balance of the Greenland Ice Sheet is the main determining agent in delta progradation. The final part...

  4. Solitary expression of CD7 among T-cell antigens in acute myeloid leukemia: identification of a group of patients with similar T-cell receptor beta and delta rearrangements and course of disease suggestive of poor prognosis

    DEFF Research Database (Denmark)

    Jensen, A W; Hokland, M; Jørgensen, H


    rearrangements in Ig- or T-cell receptor (TCR) genes, such genetic alterations were demonstrated in four of five patients for the TCR delta gene and in all patients for the TCR beta gene. Interestingly, DNA fragments of similar size were demonstrated in three of five patients for both the beta and delta genes...

  5. ABI domain-containing proteins contribute to surface protein display and cell division in Staphylococcus aureus. (United States)

    Frankel, Matthew B; Wojcik, Brandon M; DeDent, Andrea C; Missiakas, Dominique M; Schneewind, Olaf


    The human pathogen Staphylococcus aureus requires cell wall anchored surface proteins to cause disease. During cell division, surface proteins with YSIRK signal peptides are secreted into the cross-wall, a layer of newly synthesized peptidoglycan between separating daughter cells. The molecular determinants for the trafficking of surface proteins are, however, still unknown. We screened mutants with non-redundant transposon insertions by fluorescence-activated cell sorting for reduced deposition of protein A (SpA) into the staphylococcal envelope. Three mutants, each of which harboured transposon insertions in genes for transmembrane proteins, displayed greatly reduced envelope abundance of SpA and surface proteins with YSIRK signal peptides. Characterization of the corresponding mutations identified three transmembrane proteins with abortive infectivity (ABI) domains, elements first described in lactococci for their role in phage exclusion. Mutations in genes for ABI domain proteins, designated spdA, spdB and spdC (surface protein display), diminish the expression of surface proteins with YSIRK signal peptides, but not of precursor proteins with conventional signal peptides. spdA, spdB and spdC mutants display an increase in the thickness of cross-walls and in the relative abundance of staphylococci with cross-walls, suggesting that spd mutations may represent a possible link between staphylococcal cell division and protein secretion. © 2010 Blackwell Publishing Ltd.

  6. Delta(9)-tetrahydrocannabinol inhibits 17beta-estradiol-induced proliferation and fails to activate androgen and estrogen receptors in MCF7 human breast cancer cells. (United States)

    von Bueren, A O; Schlumpf, M; Lichtensteiger, W


    Delta(9)-tetrahydrocannabinol (THC) exerts palliative effects in cancer patients, but produces adverse effects on the endocrine and reproductive systems. Experimental evidence concerning such effects is controversial. Whether THC exhibits estrogenic or androgenic activity in vitro was investigated. Estrogenic effects of THC were analyzed in vitro by measuring the proliferation of estrogen-sensitive MCF7 cells. Androgenic activity was investigated by the A-Screen assay that measures androgen-dependent inhibition of proliferation of the androgen receptor (AR)-positive human mammary carcinoma cell line, MCF7-AR1. In contrast to 17beta-estradiol, included as positive control with an EC50 value (concentration required for 50% of maximal 17beta-estradiol-induced proliferation) of 1.00 x 10(-12) M, THC failed to induce cell proliferation in the MCF7 cell line at concentrations between 10(-13) and 10(-4) M. THC inhibited 17beta-estradiol-induced proliferation in wild-type MCF7 and MCF7-AR1 cells, with an IC50 value of 2.6 x 10(-5) M and 9 x 10(-6) M, respectively. THC failed to act as an estrogen, but antagonized 17beta-estradiol-induced proliferation. This effect was independent of the AR expression level.

  7. Mu and delta opioid receptors oppositely regulate motor impulsivity in the signaled nose poke task.

    Directory of Open Access Journals (Sweden)

    Mary C Olmstead

    Full Text Available Impulsivity is a primary feature of many psychiatric disorders, most notably attention deficit hyperactivity disorder and drug addiction. Impulsivity includes a number of processes such as the inability to delay gratification, the inability to withhold a motor response, or acting before all of the relevant information is available. These processes are mediated by neural systems that include dopamine, serotonin, norepinephrine, glutamate and cannabinoids. We examine, for the first time, the role of opioid systems in impulsivity by testing whether inactivation of the mu- (Oprm1 or delta- (Oprd1 opioid receptor gene alters motor impulsivity in mice. Wild-type and knockout mice were examined on either a pure C57BL6/J (BL6 or a hybrid 50% C57Bl/6J-50% 129Sv/pas (HYB background. Mice were trained to respond for sucrose in a signaled nose poke task that provides independent measures of associative learning (responses to the reward-paired cue and motor impulsivity (premature responses. Oprm1 knockout mice displayed a remarkable decrease in motor impulsivity. This was observed on the two genetic backgrounds and did not result from impaired associative learning, as responses to the cue signaling reward did not differ across genotypes. Furthermore, mutant mice were insensitive to the effects of ethanol, which increased disinhibition and decreased conditioned responding in wild-type mice. In sharp contrast, mice lacking the Oprd1 gene were more impulsive than controls. Again, mutant animals showed no deficit in associative learning. Ethanol completely disrupted performance in these animals. Together, our results suggest that mu-opioid receptors enhance, whereas delta-opioid receptors inhibit, motor impulsivity. This reveals an unanticipated contribution of endogenous opioid receptor activity to disinhibition. In a broader context, these data suggest that alterations in mu- or delta-opioid receptor function may contribute to impulse control disorders.

  8. The adhesion force of Notch with Delta and the rate of Notch signaling


    Ahimou, Francois; Mok, Lee-Peng; Bardot, Boris; Wesley, Cedric


    Notch signaling is repeatedly used during animal development to specify cell fates. Using atomic force microscopy on live cells, chemical inhibitors, and conventional analyses, we show that the rate of Notch signaling is linked to the adhesion force between cells expressing Notch receptors and Delta ligand. Both the Notch extracellular and intracellular domains are required for the high adhesion force with Delta. This high adhesion force is lost within minutes, primarily due to the action of ...

  9. Preclinical Testing of Antihuman CD28 Fab' Antibody in a Novel Nonhuman Primate Small Animal Rodent Model of Xenogenic Graft-Versus-Host Disease. (United States)

    Hippen, Keli L; Watkins, Benjamin; Tkachev, Victor; Lemire, Amanda M; Lehnen, Charles; Riddle, Megan J; Singh, Karnail; Panoskaltsis-Mortari, Angela; Vanhove, Bernard; Tolar, Jakub; Kean, Leslie S; Blazar, Bruce R


    Graft-versus-host disease (GVHD) is a severe complication of hematopoietic stem cell transplantation. Current therapies to prevent alloreactive T cell activation largely cause generalized immunosuppression and may result in adverse drug, antileukemia and antipathogen responses. Recently, several immunomodulatory therapeutics have been developed that show efficacy in maintaining antileukemia responses while inhibiting GVHD in murine models. To analyze efficacy and better understand immunological tolerance, escape mechanisms, and side effects of clinical reagents, testing of species cross-reactive human agents in large animal GVHD models is critical. We have previously developed and refined a nonhuman primate (NHP) large animal GVHD model. However, this model is not readily amenable to semi-high throughput screening of candidate clinical reagents. Here, we report a novel, optimized NHP xenogeneic GVHD (xeno-GVHD) small animal model that recapitulates many aspects of NHP and human GVHD. This model was validated using a clinically available blocking, monovalent anti-CD28 antibody (FR104) whose effects in a human xeno-GVHD rodent model are known. Because human-reactive reagents may not be fully cross-reactive or effective in vivo on NHP immune cells, this NHP xeno-GVHD model provides immunological insights and direct testing on NHP-induced GVHD before committing to the intensive NHP studies that are being increasingly used for detailed evaluation of new immune therapeutic strategies before human trials.

  10. Unexpected {delta}{sup 18}O and {delta}{sup 2}H Variability of Groundwater in the Eastern Paris Basin

    Energy Technology Data Exchange (ETDEWEB)

    Gourcy, L.; Petelet-Giraud, E. [BRGM Service EAU, Orleans (France)


    The Paris Basin covers about one-third of the total surface area of France. In 2009, two campaigns sampling 25 boreholes tapping Tertiary aquifers were carried out in the Basin. These aquifers are recharged at a similar altitude and the groundwater age is too young to have registered climate change. In the past, regional studies included the use of isotopes to understand groundwater origin and dynamics. Both {delta}{sup 18}O and {delta}{sup 2}H as well as ages (CFC/SF{sub 6)} and chemical components were determined in all collected samples. A noticeable stable isotope 'anomaly' appears in the south-western part of the Basin, where the average {delta}{sup 18}O and {delta}{sup 2}H values are more depleted and do not fit the pattern given by the continental effect in this area. A regional particularity of the spatial distribution of such isotopes in precipitation may be possible, but should be confirmed by additional work. (author)

  11. Prazosin Displays Anticancer Activity against Human Prostate Cancers: Targeting DNA, Cell Cycle

    Directory of Open Access Journals (Sweden)

    Ssu-Chia Lin


    Full Text Available Quinazoline-based α1,-adrenoceptor antagonists, in particular doxazosin, terazosin, are suggested to display antineoplastic activity against prostate cancers. However, there are few studies elucidating the effect of prazosin. In this study, prazosin displayed antiproliferative activity superior to that of other α1-blockers, including doxazosin, terazosin, tamsulosin, phentolamine. Prazosin induced G2 checkpoint arrest, subsequent apoptosis in prostate cancer PC-3, DU-145, LNCaP cells. In p53-null PC-3 cells, prazosin induced an increase in DNA str, breaks, ATM/ATR checkpoint pathways, leading to the activation of downstream signaling cascades, including Cdc25c phosphorylation at Ser216, nuclear export of Cdc25c, cyclin-dependent kinase (Cdk 1 phosphorylation at Tyr15. The data, together with sustained elevated cyclin A levels (other than cyclin B1 levels, suggested that Cdki activity was inactivated by prazosin. Moreover, prazosin triggered mitochondria-mediated, caspaseexecuted apoptotic pathways in PC-3 cells. The oral administration of prazosin significantly reduced tumor mass in PC-3-derived cancer xenografts in nude mice. In summary, we suggest that prazosin is a potential antitumor agent that induces cell apoptosis through the induction of DNA damage stress, leading to Cdki inactivation, G2 checkpoint arrest. Subsequently, mitochondriamediated caspase cascades are triggered to induce apoptosis in PC-3 cells.

  12. Stimulation of accumbal GABAA receptors inhibits delta2-, but not delta1-, opioid receptor-mediated dopamine efflux in the nucleus accumbens of freely moving rats. (United States)

    Aono, Yuri; Kiguchi, Yuri; Watanabe, Yuriko; Waddington, John L; Saigusa, Tadashi


    The nucleus accumbens contains delta-opioid receptors that may reduce inhibitory neurotransmission. Reduction in GABA A receptor-mediated inhibition of accumbal dopamine release due to delta-opioid receptor activation should be suppressed by stimulating accumbal GABA A receptors. As delta-opioid receptors are divided into delta2- and delta1-opioid receptors, we analysed the effects of the GABA A receptor agonist muscimol on delta2- and delta1-opioid receptor-mediated accumbal dopamine efflux in freely moving rats using in vivo microdialysis. Drugs were administered intracerebrally through the dialysis probe. Doses of compounds indicate total amount administered (mol) during 25-50min infusions. The delta2-opioid receptor agonist deltorphin II (25.0nmol)- and delta1-opioid receptor agonist DPDPE (5.0nmol)-induced increases in dopamine efflux were inhibited by the delta2-opioid receptor antagonist naltriben (1.5nmol) and the delta1-opioid receptor antagonist BNTX (150.0pmol), respectively. Muscimol (250.0pmol) inhibited deltorphin II (25.0nmol)-induced dopamine efflux. The GABA A receptor antagonist bicuculline (50.0pmol), which failed to affect deltorphin II (25.0nmol)-induced dopamine efflux, counteracted the inhibitory effect of muscimol on deltorphin II-induced dopamine efflux. Neither muscimol (250.0pmol) nor bicuculline (50.0 and 500.0pmol) altered DPDPE (5.0nmol)-induced dopamine efflux. The present results show that reduction in accumbal GABA A receptor-mediated inhibition of dopaminergic activity is necessary to produce delta2-opioid receptor-induced increase in accumbal dopamine efflux. This study indicates that activation of delta2- but not delta1-opioid receptors on the cell bodies and/or terminals of accumbal GABAergic interneurons inhibits GABA release and, accordingly, decreases GABA A receptor-mediated inhibition of dopaminergic terminals, resulting in enhanced accumbal dopamine efflux. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Process connectivity in a naturally prograding river delta (United States)

    Sendrowski, Alicia; Passalacqua, Paola


    River deltas are lowland systems that can display high hydrological connectivity. This connectivity can be structural (morphological connections), functional (control of fluxes), and process connectivity (information flow from system drivers to sinks). In this work, we quantify hydrological process connectivity in Wax Lake Delta, coastal Louisiana, by analyzing couplings among external drivers (discharge, tides, and wind) and water levels recorded at five islands and one channel over summer 2014. We quantify process connections with information theory, a branch of mathematics concerned with the communication of information. We represent process connections as a network; variables serve as network nodes and couplings as network links describing the strength, direction, and time scale of information flow. Comparing process connections at long (105 days) and short (10 days) time scales, we show that tides exhibit daily synchronization with water level, with decreasing strength from downstream to upstream, and that tides transfer information as tides transition from spring to neap. Discharge synchronizes with water level and the time scale of its information transfer compares well to physical travel times through the system, computed with a hydrodynamic model. Information transfer and physical transport show similar spatial patterns, although information transfer time scales are larger than physical travel times. Wind events associated with water level setup lead to increased process connectivity with highly variable information transfer time scales. We discuss the information theory results in the context of the hydrologic behavior of the delta, the role of vegetation as a connector/disconnector on islands, and the applicability of process networks as tools for delta modeling results.

  14. Anaerobic Transformation of Furfural by Methanococcus deltae (Delta)LH (United States)

    Belay, N.; Boopathy, R.; Voskuilen, G.


    Methanococcus deltae (Delta)LH was grown on H(inf2)-CO(inf2) in the presence of various concentrations of furfural. Furfural at higher concentrations, namely, 20 and 25 mM, inhibited growth of this organism. At concentration of 5 and 10 mM, no inhibition of growth was observed. The other methanogens in this study were not inhibited by 10 mM furfural. Among the methanogens tested, M. deltae was capable of transforming furfural, whereas Methanobacterium thermoautotrophicum Marburg, Methanosarcina barkeri 227, Methanococcus thermolithotrophicus, and Methanobrevibacter ruminantium lacked this capability. One hundred percent removal of furfural was observed within 48 h of incubation in M. deltae cultures. The end product observed during furfural metabolism was furfuryl alcohol. An almost stoichiometric amount of furfuryl alcohol was produced by M. deltae. This transformation is likely to be of value in the detoxification of furfural and in its ultimate conversion to methane and CO(inf2) by anaerobic digestion. PMID:16535618

  15. Identification of three subgroups of B cell chronic lymphocytic leukemia based upon mutations of BCL-6 and IgV genes. (United States)

    Capello, D; Fais, F; Vivenza, D; Migliaretti, G; Chiorazzi, N; Gaidano, G; Ferrarini, M


    Although B cell chronic lymphocytic leukemia (B-CLL) has been traditionally viewed as a tumor of virgin B cells, this notion has been recently questioned by data suggesting that a fraction of B-CLL derives from antigen experienced B cells. In order to further clarify the histogenetic derivation of this lymphoproliferation, we have analyzed the DNA sequences of the 5' non-coding region of BCL-6 proto-oncogene in 28 cases of B-CLL. Mutations of BCL-6 proto-oncogene, a zinc finger transcription factor implicated in lymphoma development, represent a histogenetic marker of B cell transit through the germinal center (GC) and occur frequently in B cell malignancies derived from GC or post-GC B cells. For comparison, the same tumor panel was analyzed for somatic mutations of the rearranged immunoglobulin variable (IgV) genes, which are known to be acquired at the time of B cell transit through the GC. Sequence analyses of BCL-6 and IgV genes allowed the definition of three groups of B-CLL. Group I B-CLL displayed mutations of both BCL-6 and IgV genes (10/28; 36%). Group II B-CLL displayed mutated IgV genes, but a germline BCL-6 gene (5/28; 18%). Finally, group III B-CLL included the remaining cases (13/28; 46%) that were characterized by the absence of somatic mutations of both BCL-6 and IgV genes. Overall, the distribution of BCL-6 and IgV mutations in B-CLL reinforce the notion that this leukemia is histogenetically heterogeneous and that a substantial subgroup of these lymphoproliferations derives from post-germinal center B cells.

  16. The Drosophila T-box transcription factor Midline functions within the Notch–Delta signaling pathway to specify sensory organ precursor cell fates and regulates cell survival within the eye imaginal disc (United States)

    Das, Sudeshna; Chen, Q. Brent; Saucier, Joseph D.; Drescher, Brandon; Zong, Yan; Morgan, Sarah; Forstall, John; Meriwether, Andrew; Toranzo, Randy; Leal, Sandra M.


    We report that the T-box transcription factor Midline (Mid), an evolutionary conserved homolog of the vertebrate Tbx20 protein, functions within the Notch–Delta signaling pathway essential for specifying the fates of sensory organ precursor cells. This complements an established history of research showing that Mid regulates the cell-fate specification of diverse cell types within the developing heart, epidermis and central nervous system. Tbx20 has been detected in diverse neuronal and epithelial cells of embryonic eye tissues in both mice and humans. However, the mechanisms by which either Mid or Tbx20 function to regulate cell-fate specification or other critical aspects of eye development including cell survival have not yet been elucidated. We have also gathered preliminary evidence suggesting that Mid may play an indirect, but vital role in selecting SOP cells within the third-instar larval eye disc by regulating the expression of the proneural gene atonal. During subsequent pupal stages, Mid specifies SOP cell fates as a member of the Notch–Delta signaling hierarchy and is essential for maintaining cell viability within by inhibiting apoptotic pathways. We present several new hypotheses that seek to understand the role of Mid in regulating developmental processes downstream of the Notch receptor that are critical for specifying unique cell fates, patterning the adult eye and maintaining cellular homeostasis during eye disc morphogenesis. PMID:23962751

  17. Catalytic surface promotion of highly active La0.85Sr0.15Cr0.8Ni0.2O3-δ anodes for La5.6WO11.4-δ based proton conducting fuel cells

    DEFF Research Database (Denmark)

    Solis, C.; Balaguer, M.; Bozza, Francesco


    La0.85Sr0.15CrO3-delta (LSC), La0.85Sr0.15Cr0.8Ni0.2O3-delta (LSCN) and LSCN infiltrated with Ni nanoparticles were tested as anodes for symmetrical cells based on La5.6WO11.4-delta (LWO) protonic electrolyte. These chromite-based electrode materials are compatible with LWO material, in contrast ...

  18. Suppressor T-cell factor(s) display an altered pattern of Igh (immunoglobulin heavy chain locus) genetic restriction when developed in an Igh-congeneic host

    International Nuclear Information System (INIS)

    HayGlass, K.T.; Naides, S.J.; Benacerraf, B.; Sy, M.S.


    Suppressor T cell factor(s) (TsF 1 ) inhibit the in vivo priming of azobenzenearsonate-specific cytotoxic T-cell responses. The activity of TsF 1 is restricted by genes linked to Igh-1 allotypic markers. TsF 1 obtained from B6.Igh-1/sup n/ mice was unable to suppress the immune response in B6.Igh-1/sup b/ mice and vice versa. However, TsF 1 prepared from B6.Igh-1/sup n/ T cells parked in an Igh-congeneic B6.Igh-1/sup b/ environment displays an additional restriction specificity of the host. Thus, TsF 1 prepared from these Igh-chimeric mice suppressed immune responses in both B6.Igh-1/sup n/ (donor) and B6.Igh-1/sup b/ (recipient) mice but not in mice of the unrelated strain BALB/c.Igh-1/sup a/. The results indicate that the establishment of the suppressor T-cell repertoire is dependent not only upon the genetic background of the individual T cell but also upon the influence of Igh-linked determinants present when T-cell clones are selected during the response

  19. delta-vision (United States)

    California Natural Resource Agency — Delta Vision is intended to identify a strategy for managing the Sacramento-San Joaquin Delta as a sustainable ecosystem that would continue to support environmental...

  20. High frequency of the CCR5delta32 variant among individuals from an admixed Brazilian population with sickle cell anemia

    Directory of Open Access Journals (Sweden)

    J.A.B. Chies


    Full Text Available Homozygous sickle cell disease (SCD has a wide spectrum of clinical manifestations. In Brazil, the main cause of death of individuals with SCD is recurrent infection. The CCR5delta32 allele, which confers relative resistance to macrophage-tropic HIV virus infection, probably has reached its frequency and world distribution due to other pathogens that target macrophage in European populations. In the present investigation a relatively higher prevalence (5.1% of the CCR5delta32 allele was identified, by PCR amplification using specific primers, in 79 SCD patients when compared to healthy controls (1.3% with the same ethnic background (Afro-Brazilians. Based on a hypothesis that considers SCD as a chronic inflammatory condition, and since the CCR5 chemokine receptor is involved in directing a Th1-type immune response, we suggest that a Th1/Th2 balance can influence the morbidity of SCD. If the presence of the null CCR5delta32 allele results in a reduction of the chronic inflammation state present in SCD patients, this could lead to differential survival of SCD individuals who are carriers of the CCR5delta32 allele. This differential survival could be due to the development of less severe infections and consequently reduced or less severe vaso-occlusive crises.

  1. The effect of the CCR5-delta32 deletion on global gene expression considering immune response and inflammation

    Directory of Open Access Journals (Sweden)

    Hütter Gero


    Full Text Available Abstract Background The natural function of the C-C chemokine receptor type 5 (CCR5 is poorly understood. A 32 base pair deletion in the CCR5 gene (CCR5-delta32 located on chromosome 3 results in a non-functional protein. It is supposed that this deletion causes an alteration in T-cell response to inflammation. For example, the presence of the CCR5-delta32 allele in recipients of allografts constitutes as an independent and protective factor associated with a decreased risk of graft-versus-host disease (GVHD and graft rejection. However, the mechanism of this beneficial effect of the deletion regarding GVHD is unknown. In this survey we searched for a CCR5-delta32 associated regulation of critical genes involved in the immune response and the development of GVHD. Methods We examined CD34+ hematopoietic progenitor cells derived from bone marrow samples from 19 healthy volunteers for the CCR5-delta32 deletion with a genomic PCR using primers flanking the site of the deletion. Results 12 individuals were found to be homozygous for CCR5 WT and 7 carried the CCR5-delta32 deletion heterozygously. Global gene expression analysis led to the identification of 11 differentially regulated genes. Six of them are connected with mechanisms of immune response and control: LRG1, CXCR2, CCRL2, CD6, CD7, WD repeat domain, and CD30L. Conclusions Our data indicate that the CCR5-delta32 mutation may be associated with differential gene expression. Some of these genes are critical for immune response, in the case of CD30L probably protective in terms of GVHD.

  2. Perspectives on Bay–Delta Science and Policy

    Directory of Open Access Journals (Sweden)

    Michael Healey


    Full Text Available doi: State of Bay–Delta Science 2008 highlighted seven emerging perspectives on science and management of the Delta. These perspectives had important effects on policy and legislation concerning management of the Delta ecosystem and water exports. From the collection of papers that make up the State of Bay–Delta Science 2016, we derive another seven perspectives that augment those published in 2008. The new perspectives address nutrient and contaminant concentrations in Delta waters, the failure of the Delta food web to support native species, the role of multiple stressors in driving species toward extinction, and the emerging importance of extreme events in driving change in the ecosystem and the water supply. The scientific advances that underpin these new perspectives were made possible by new measurement and analytic tools. We briefly discuss some of these, including miniaturized acoustic fish tags, sensors for monitoring of water quality, analytic techniques for disaggregating complex contaminant mixtures, remote sensing to assess levee vulnerability, and multidimensional hydrodynamic modeling. Despite these new tools and scientific insights, species conservation objectives for the Delta are not being met. We believe that this lack of progress stems in part from the fact that science and policy do not incorporate sufficiently long-term perspectives. Looking forward half a century was central to the Delta Visioning process, but science and policy have not embraced this conceptual breadth. We are also concerned that protection and enhancement of the unique cultural, recreational, natural resource, and agricultural values of the Delta as an evolving place, as required by the Delta Reform Act, has received no critical study and analysis. Adopting wider and longer science and policy perspectives immediately encourages recognition of the need for evaluation, analysis, and public discourse on

  3. From mannan to bioethanol: cell surface co-display of β-mannanase and β-mannosidase on yeast Saccharomyces cerevisiae. (United States)

    Ishii, Jun; Okazaki, Fumiyoshi; Djohan, Apridah Cameliawati; Hara, Kiyotaka Y; Asai-Nakashima, Nanami; Teramura, Hiroshi; Andriani, Ade; Tominaga, Masahiro; Wakai, Satoshi; Kahar, Prihardi; Yopi; Prasetya, Bambang; Ogino, Chiaki; Kondo, Akihiko


    Mannans represent the largest hemicellulosic fraction in softwoods and also serve as carbohydrate stores in various plants. However, the utilization of mannans as sustainable resources has been less advanced in sustainable biofuel development. Based on a yeast cell surface-display technology that enables the immobilization of multiple enzymes on the yeast cell walls, we constructed a recombinant Saccharomyces cerevisiae strain that co-displays β-mannanase and β-mannosidase; this strain is expected to facilitate ethanol fermentation using mannan as a biomass source. Parental yeast S. cerevisiae assimilated mannose and glucose as monomeric sugars, producing ethanol from mannose. We constructed yeast strains that express tethered β-mannanase and β-mannosidase; co-display of the two enzymes on the cell surface was confirmed by immunofluorescence staining and enzyme activity assays. The constructed yeast cells successfully hydrolyzed 1,4-β-d-mannan and produced ethanol by assimilating the resulting mannose without external addition of enzymes. Furthermore, the constructed strain produced ethanol from 1,4-β-d-mannan continually during the third batch of repeated fermentation. Additionally, the constructed strain produced ethanol from ivory nut mannan; ethanol yield was improved by NaOH pretreatment of the substrate. We successfully displayed β-mannanase and β-mannosidase on the yeast cell surface. Our results clearly demonstrate the utility of the strain co-displaying β-mannanase and β-mannosidase for ethanol fermentation from mannan biomass. Thus, co-tethering β-mannanase and β-mannosidase on the yeast cell surface provides a powerful platform technology for yeast fermentation toward the production of bioethanol and other biochemicals from lignocellulosic materials containing mannan components.

  4. Growth laws for delta crevasses in the Mississippi River Delta: observations and modeling (United States)

    Yocum, T. A.; Georgiou, I. Y.


    River deltas are accumulations of sedimentary deposits delivered by rivers via a network of distributary channels. Worldwide they are threatened by environmental changes, including subsidence, global sea level rise and a suite of other local factors. In the Mississippi River Delta (MRD) these impacts are exemplified, and have led to proposed solutions to build land that include sediment diversions, thereby reinitiating the delta cycle. While economically efficient, there are too few analogs of small deltas aside from laboratory studies, numerical modeling studies, theoretical approaches, and limited field driven observations. Anthropogenic crevasses in the modern delta are large enough to overcome limitations of laboratory deltas, and small enough to allow for "rapid" channel and wetland development, providing an ideal setting to investigate delta development mechanics. Crevasse metrics were obtained using a combination of geospatial tools, extracting key parameters (bifurcation length and width, channel order and depth) that were non-dimensionalized and compared to river-dominated delta networks previously studied. Analysis showed that most crevasses in the MRD appear to obey delta growth laws and delta allometry relationships, suggesting that crevasses do exhibit similar planform metrics to larger Deltas; the distance to mouth bar versus bifurcation order demonstrated to be a very reasonable first order estimate of delta-top footprint. However, some crevasses exhibited different growth metrics. To better understand the hydrodynamic and geomorphic controls governing crevasse evolution in the MRD, we assess delta dynamics via a suite of field observations and numerical modeling in both well-established and newly constructed crevasses. Our analysis suggests that delta development is affected by the relative influence of external (upstream and downstream) and internal controls on the hydrodynamic and sediment transport patterns in these systems.

  5. Neuroprotective effect of peroxiredoxin 6 against hypoxia-induced retinal ganglion cell damage

    Directory of Open Access Journals (Sweden)

    Kumar Anil


    Full Text Available Abstract Background The ability to respond to changes in the extra-intracellular environment is prerequisite for cell survival. Cellular responses to the environment include elevating defense systems, such as the antioxidant defense system. Hypoxia-evoked reactive oxygen species (ROS-driven oxidative stress is an underlying mechanism of retinal ganglion cell (RGC death that leads to blinding disorders. The protein peroxiredoxin 6 (PRDX6 plays a pleiotropic role in negatively regulating death signaling in response to stressors, and thereby stabilizes cellular homeostasis. Results We have shown that RGCs exposed to hypoxia (1% or hypoxia mimetic cobalt chloride display reduced expression of PRDX6 with higher ROS expression and activation of NF-κB. These cells undergo apoptosis, while cells with over-expression of PRDX6 demonstrate resistance against hypoxia-driven RGC death. The RGCs exposed to hypoxia either with 1% oxygen or cobalt chloride (0-400 μM, revealed ~30%-70% apoptotic cell death after 48 and 72 h of exposure. Western analysis and real-time PCR showed elevated expression of PRDX6 during hypoxia at 24 h, while PRDX6 protein and mRNA expression declined from 48 h onwards following hypoxia exposure. Concomitant with this, RGCs showed increased ROS expression and activation of NF-κB with IkB phosphorylation/degradation, as examined with H2DCF-DA and transactivation assays. These hypoxia-induced adverse reactions could be reversed by over-expression of PRDX6. Conclusion Because an abundance of PRDX6 in cells was able to attenuate hypoxia-induced RGC death, the protein could possibly be developed as a novel therapeutic agent acting to postpone RGC injury and delay the progression of glaucoma and other disorders caused by the increased-ROS-generated death signaling related to hypoxia.

  6. Characterization and comparison of fatty acyl Delta6 desaturase cDNAs from freshwater and marine teleost fish species. (United States)

    Zheng, X; Seiliez, I; Hastings, N; Tocher, D R; Panserat, S; Dickson, C A; Bergot, P; Teale, A J


    Fish are the most important dietary source of the n-3 highly unsaturated fatty acids (HUFA), eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), that have particularly important roles in human nutrition reflecting their roles in critical physiological processes. The objective of the study described here was to clone, functionally characterize and compare expressed fatty acid desaturase genes involved in the production of EPA and DHA in freshwater and marine teleost fish species. Putative fatty acid desaturase cDNAs were isolated and cloned from common carp (Cyprinus carpio) and turbot (Psetta maximus). The enzymic activities of the products of these cDNAs, together with those of cDNAs previously cloned from rainbow trout (Oncorhynchus mykiss) and gilthead sea bream (Sparus aurata), were determined by heterologous expression in the yeast Saccharomyces cerevisiae. The carp and turbot desaturase cDNAs included open reading frames (ORFs) of 1335 and 1338 base pairs, respectively, specifying proteins of 444 and 445 amino acids. The protein sequences possessed all the characteristic features of microsomal fatty acid desaturases, including three histidine boxes, two transmembrane regions, and N-terminal cytochrome b(5) domains containing the haem-binding motif, HPGG. Functional expression showed all four fish cDNAs encode basically unifunctional Delta6 fatty acid desaturase enzymes responsible for the first and rate-limiting step in the biosynthesis of HUFA from 18:3n-3 and 18:2n-6. All the fish desaturases were more active towards the n-3 substrate with 59.5%, 31.5%, 23.1% and 7.0% of 18:3n-3 being converted to 18:4n-3 in the case of turbot, trout, sea bream and carp, respectively. The enzymes also showed very low, probably physiologically insignificant, levels of Delta5 desaturase activity, but none of the products showed Delta4 desaturase activity. The cloning and characterization of desaturases from these fish is an important advance, as they are species in which

  7. Fgf signaling controls pharyngeal taste bud formation through miR-200 and Delta-Notch activity. (United States)

    Kapsimali, Marika; Kaushik, Anna-Lila; Gibon, Guillaume; Dirian, Lara; Ernest, Sylvain; Rosa, Frederic M


    Taste buds, the taste sensory organs, are conserved in vertebrates and composed of distinct cell types, including taste receptor, basal/presynaptic and support cells. Here, we characterize zebrafish taste bud development and show that compromised Fgf signaling in the larva results in taste bud reduction and disorganization. We determine that Fgf activity is required within pharyngeal endoderm for formation of Calb2b(+) cells and reveal miR-200 and Delta-Notch signaling as key factors in this process. miR-200 knock down shows that miR-200 activity is required for taste bud formation and in particular for Calb2b(+) cell formation. Compromised delta activity in mib(-/-) dramatically reduces the number of Calb2b(+) cells and increases the number of 5HT(+) cells. Conversely, larvae with increased Notch activity and ascl1a(-/-) mutants are devoid of 5HT(+) cells, but have maintained and increased Calb2b(+) cells, respectively. These results show that Delta-Notch signaling is required for intact taste bud organ formation. Consistent with this, Notch activity restores Calb2b(+) cell formation in pharyngeal endoderm with compromised Fgf signaling, but fails to restore the formation of these cells after miR-200 knock down. Altogether, this study provides genetic evidence that supports a novel model where Fgf regulates Delta-Notch signaling, and subsequently miR-200 activity, in order to promote taste bud cell type differentiation.

  8. Redundant role of protein kinase C delta and epsilon during mouse embryonic development.

    Directory of Open Access Journals (Sweden)

    Sergio Carracedo

    Full Text Available Protein Kinase C delta and epsilon are mediators of important cellular events, such as cell proliferation, migration or apoptosis. The formation of blood vessels, i.e., vasculo- and angiogenesis, is a process where these isoforms have also been shown to participate. However, mice deficient in either Protein Kinase C delta or epsilon are viable and therefore their individual contribution to the formation of the vasculature appeared so far dispensable. In this study, we show that double null mutation of Protein Kinase C delta and epsilon causes embryonic lethality at approximately E9.5. At this stage, whole mount staining of the endothelial marker CD31 in double null embryos revealed defective blood vessel formation. Moreover, culture of double deficient mouse allantois showed impaired endothelial cell organization, and analyses of double deficient embryo sections showed dilated vessels, decreased endothelial-specific adherent junctions, and decreased contact of endothelial cells with mural cells. Protein kinase C delta and epsilon also appeared essential for vascular smooth muscle cell differentiation, since α-smooth muscle actin, a classical marker for vascular smooth muscle cells, was almost undetectable in double deficient embryonic aorta at E9.5. Subsequent qPCR analyses showed decreased VE-cadherin, Vegfr2, Cd31, Cdh2, Ets1, and Fli-1, among other angiogenesis related transcripts in double deficient embryos. Taken together, these data suggest for the first time an in vivo redundant role between members of the novel Protein Kinase C subfamily that allows for mutual compensation during mouse embryonic development, with vasculogenesis/angiogenesis as an obvious common function of these two Protein Kinase Cs. Protein Kinase C delta and epsilon might therefore be useful targets for inhibiting vasculo- and/or angiogenesis.

  9. Future Deltas Utrecht University research focus area: towards sustainable management of sinking deltas (United States)

    Stouthamer, E.; van Asselen, S.


    Deltas are increasingly under pressure from human impact and climate change. To deal with these pressures that threat future delta functioning, we need to understand interactions between physical, biological, chemical and social processes in deltas. This requires an integrated approach, in which knowledge on natural system functioning is combined with knowledge on spatial planning, land and water governance and legislative frameworks. In the research focus area Future Deltas of Utrecht University an interdisciplinary team from different research groups therefore works together. This allows developing integrated sustainable and resilient delta management strategies, which is urgently needed to prevent loss of vital delta services.

  10. Rapid agonist-induced loss of sup 125 I-. beta. -endorphin opioid receptor sites in NG108-15, but not SK-N-SH neuroblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Cone, R.I.; Lameh, J.; Sadee, W. (Univ. of California, San Francisco (United States))


    The authors have measured {mu} and {delta} opioid receptor sites on intact SK-N-SH and NG108-15 neuroblastoma cells, respectively, in culture. Use of {sup 125}I-{beta}-endorphin ({beta}E) as a tracer, together with {beta}E(6-31) to block high-affinity non-opioid binding in both cell lines, permitted the measurement of cell surface {mu} and {delta} opioid receptor sites. Labeling was at {delta} sites in NG108-15 cells and predominantly at {mu} sites in SK-N-SH cells. Pretreatment with the {mu} and {delta} agonist, DADLE, caused a rapid loss of cell surface {delta} receptor sites in NG108-15 cells, but failed to reduce significantly {mu} receptor density in SK-N-SH cells.

  11. Limited protective effect of the CCR5Delta32/CCR5Delta32 genotype on human immunodeficiency virus infection incidence in a cohort of patients with hemophilia and selection for genotypic X4 virus

    DEFF Research Database (Denmark)

    Iversen, Astrid K N; Christiansen, Claus Bohn; Attermann, Jørn


    The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)-infected patients with hemophilia. One patient (0.6%) had the CCR5Delta32/CCR5Delta32 genotype (which occurs in approximately 2% of the Scand......The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)-infected patients with hemophilia. One patient (0.6%) had the CCR5Delta32/CCR5Delta32 genotype (which occurs in approximately 2...

  12. Inhibition of cortiocosteroidogenesis by delta-9-tetrahydrocannabinol. (United States)

    Warner, W; Harris, L S; Carchman, R A


    ACTH, cholera toxin, cyclic AMP but not pregnenolone-induced steroidogenesis in Y-1 functional mouse adrenal tumor cells was significantly inhibited by delta-9-tetrahydrocannabinol, cannabidiol, and cannabinol. The inhibition of steroidogenesis could not be correlated with a general depression in cell function or viability. The data suggest that cannabinoids inhibit corticosteroidogenesis at a site between the synthesis of cAMP and of pregnenolone.

  13. Individually programmable cell stretching microwell arrays actuated by a Braille display. (United States)

    Kamotani, Yoko; Bersano-Begey, Tommaso; Kato, Nobuhiro; Tung, Yi-Chung; Huh, Dongeun; Song, Jonathan W; Takayama, Shuichi


    Cell culture systems are often static and are therefore nonphysiological. In vivo, many cells are exposed to dynamic surroundings that stimulate cellular responses in a process known as mechanotransduction. To recreate this environment, stretchable cell culture substrate systems have been developed, however, these systems are limited by being macroscopic and low throughput. We have developed a device consisting of 24 miniature cell stretching chambers with flexible bottom membranes that are deformed using the computer-controlled, piezoelectrically actuated pins of a Braille display. We have also developed efficient image capture and analysis protocols to quantify morphological responses of the cells to applied strain. Human dermal microvascular endothelial cells (HDMECs) were found to show increasing degrees of alignment and elongation perpendicular to the radial strain in response to cyclic stretch at increasing frequencies of 0.2, 1, and 5 Hz, after 2, 4, and 12h. Mouse myogenic C2C12 cells were also found to align in response to the stretch, while A549 human lung adenocarcinoma epithelial cells did not respond to stretch.

  14. Functional and phenotypical analysis of IL-6-secreting CD4+ T cells in human adipose tissue. (United States)

    de Jong, Anja J; Pollastro, Sabrina; Kwekkeboom, Joanneke C; Andersen, Stefan N; Dorjée, Annemarie L; Bakker, Aleida M; Alzaid, Fawaz; Soprani, Antoine; Nelissen, Rob G H H; Mullers, Jan B; Venteclef, Nicolas; de Vries, Niek; Kloppenburg, Margreet; Toes, René E M; Ioan-Facsinay, Andreea


    Emerging evidence indicates that a dynamic interplay between the immune system and adipocytes contributes to the disturbed homeostasis in adipose tissue of obese subjects. Recently, we observed IL-6-secretion by CD4 + T cells from the stromal vascular fraction (SVF) of the infrapatellar fat pad (IFP) of knee osteoarthritis patients directly ex vivo. Here we show that human IL-6 + CD4 + T cells from SVF display a more activated phenotype than the IL-6 - T cells, as evidenced by the expression of the activation marker CD69. Analysis of cytokines secretion, as well as expression of chemokine receptors and transcription factors associated with different Th subsets (Treg, Th1, Th2, Th17 and Tfh) revealed that IL-6-secreting CD4 + T cells cannot be assigned to a conventional Th subset. TCRβ gene analysis revealed that IL-6 + and IL-6 - CD4 + T cells appear clonally unrelated to each other, suggesting a different specificity of these cells. In line with these observations, adipocytes are capable of enhancing IL-6 production by CD4 + T cells. Thus, IL-6 + CD4 + T cells are TCRαβ T cells expressing an activated phenotype potentially resulting from an interplay with adipocytes that could be involved in the inflammatory processes in the OA joint. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. New strategy for enhancement of microbial viability in simulated gastric conditions based on display of starch-binding domain on cell surface. (United States)

    Tarahomjoo, Shirin; Katakura, Yoshio; Shioya, Suteaki


    The C-terminal region of the peptidoglycan hydrolase (CPH) of Lactococcus lactis IL1403 fused to the linker region and the starch-binding domain (SBD) of the *-amylase of Streptococcus bovis 148 was produced intracellularly in Escherichia coli. The fusion protein (CPH-SBD) was able to bind to the cell surface of Lactobacillus casei NRRL B-441 and to corn starch. Therefore, adhesion of cells to corn starch was mediated by the fusion protein. At a cell density of 10(9) cfu/ml and a starch concentration of 5 mg/ml, CPH-SBD-displaying L. casei cells aggregated with corn starch, whereas the free cells of L. casei did not form any aggregates with corn starch. After incubation in simulated gastric juice (pH 3.0, 1 h), the survival percentages of free cells, amylose-coated free cells, and free cells mixed with corn starch were 0.074%, 7.2%, and 3.1% respectively. When CPH-SBD-displaying bacteria aggregated with corn starch, their survival percentage was 8% higher than that of free cells mixed with corn starch. The survival of the amylose-coated CPH-SBD-displaying L. casei cells was comparable to that of amylose-coated free cells, whereas the survival percentage of amylose-coated aggregates of CPH-SBD-displaying bacteria with corn starch was 28% higher than that of amylose-coated mixture of free cells with corn starch. These results demonstrate the potential usefulness of the cell-surface display technique for enhancement of the delivery of viable microorganisms to the intestinal tract.

  16. Frequency of CCR5 Delta-32 Mutation in Human Immunodeficiency Virus (HIV-seropositive and HIV-exposed Seronegative Individuals and in General Population of Medellin, Colombia

    Directory of Open Access Journals (Sweden)

    Francisco J Díaz


    Full Text Available Repeated exposure to human immunodeficiency virus (HIV does not always result in seroconversion. Modifications in coreceptors for HIV entrance to target cells are one of the factors that block the infection. We studied the frequency of Delta-32 mutation in ccr5 gene in Medellin, Colombia. Two hundred and eighteen individuals distributed in three different groups were analyzed for Delta-32 mutation in ccr5 gene by polymerase chain reaction (PCR: 29 HIV seropositive (SP, 39 exposed seronegative (ESN and 150 individuals as a general population sample (GPS. The frequency of the Delta-32 mutant allele was 3.8% for ESN, 2.7% for GPS and 1.7% for SP. Only one homozygous mutant genotype (Delta-32/Delta-32 was found among the ESN (2.6%. The heterozygous genotype (ccr5/Delta-32 was found in eight GPS (5.3%, in one SP (3.4% and in one ESN (2.6%. The differences in the allelic and genotypic frequencies among the three groups were not statistically significant. A comparison between the expected and the observed genotypic frequencies showed that these frequencies were significantly different for the ESN group, which indirectly suggests a protective effect of the mutant genotype (Delta-32/Delta-32. Since this mutant genotype explained the resistance of infection in only one of our ESN persons, different mechanisms of protection must be playing a more important role in this population.

  17. Epithelial cell specific properties and genetic complementation in a delta F508 cystic fibrosis nasal polyp cell line. (United States)

    Kunzelmann, K; Lei, D C; Eng, K; Escobar, L C; Koslowsky, T; Gruenert, D C


    Analysis of vectorial ion transport and protein trafficking in transformed cystic fibrosis (CF) epithelial cells has been limited because the cells tend to lose their tight junctions with multiple subcultures. To elucidate ion transport and protein trafficking in CF epithelial cells, a polar cell line with apical and basolateral compartments will facilitate analysis of the efficacy of different gene therapy strategies in a "tight epithelium" in vitro. This study investigates the genotypic and phenotypic properties of a CF nasal polyp epithelial, delta F508 homozygote, cell line that has tight junctions pre-crisis. The cells (sigma CFNPE14o-) were transformed with an origin-of-replication defective SV40 plasmid. They develop transepithelial resistance in Ussing chambers and are defective in cAMP-dependent Cl- transport as measured by efflux of radioactive Cl-, short circuit current (Isc), or whole-cell patch clamp. Stimulation of the cells by bradykinin, histamine, or ATP seems to activate both K(+)- and Ca(+2)-dependent Cl- transport. Measurement of 36Cl- efflux following stimulation with A23187 and ionomycin indicate a Ca(+2)-dependent Cl- transport. Volume regulatory capacity of the cells is indicated by cell swelling conductance. Expression of the CF transmembrane conductance regulator mRNA was indicated by RT-PCR amplification. When cells are grown at 26 degrees C for 48 h there is no indication of cAMP-dependent Cl- as has been previously indicated in heterologous expression systems. Antibodies specific for secretory cell antigens indicate the presence of antigens found in goblet, serous, and mucous cells; in goblet and serous cells; or in goblet and mucous cells; but not antigens found exclusively in mucous or serous cells.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Superantigen-Induced Cytokine Release from Whole-Blood Cell Culture as a Functional Measure of Drug Efficacy after Oral Dosing in Nonhuman Primates

    National Research Council Canada - National Science Library

    Krakauer, Teresa; Stephens, Julie; Buckley, Marilyn; Tate, Mallory


    ...) closely resemble humans. We examined the ex vivo cytokine response of superantigen-stimulated whole-blood cells as a first step to therapeutic efficacy testing for bacterial superantigen-induced shock in NHP after oral dosing of pentoxifylline...

  19. The Drosophila T-box transcription factor Midline functions within the Notch-Delta signaling pathway to specify sensory organ precursor cell fates and regulates cell survival within the eye imaginal disc. (United States)

    Das, Sudeshna; Chen, Q Brent; Saucier, Joseph D; Drescher, Brandon; Zong, Yan; Morgan, Sarah; Forstall, John; Meriwether, Andrew; Toranzo, Randy; Leal, Sandra M


    We report that the T-box transcription factor Midline (Mid), an evolutionary conserved homolog of the vertebrate Tbx20 protein, functions within the Notch-Delta signaling pathway essential for specifying the fates of sensory organ precursor (SOP) cells. These findings complement an established history of research showing that Mid regulates the cell-fate specification of diverse cell types within the developing heart, epidermis and central nervous system. Tbx20 has been detected in unique neuronal and epithelial cells of embryonic eye tissues in both mice and humans. However, the mechanisms by which either Mid or Tbx20 function to regulate cell-fate specification or other critical aspects of eye development including cell survival have not yet been elucidated. We have also gathered preliminary evidence suggesting that Mid may play an indirect, but vital role in selecting SOP cells within the third-instar larval eye disc by regulating the expression of the proneural gene atonal. During subsequent pupal stages, Mid specifies SOP cell fates as a member of the Notch-Delta signaling hierarchy and is essential for maintaining cell viability by inhibiting apoptotic pathways. We present several new hypotheses that seek to understand the role of Mid in regulating developmental processes downstream of the Notch receptor that are critical for specifying unique cell fates, patterning the adult eye and maintaining cellular homeostasis during eye disc morphogenesis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. Cytolytic T lymphocyte precursor cells in congenitally athymic C57BL/6 nu/nu mice: Quantitation, enrichment, and specificity

    Energy Technology Data Exchange (ETDEWEB)

    Maryanski, J.L. (Ludwig Inst. for Cancer Research, Epalinges, Switzerland); MacDonald, H.R.; Sordat, B.; Cerottini, J.C.


    A sensitive limiting dilution microculture system was used to obtain minimal estimates of the frequency of CTL precursor cells (CTL-P) in spleens from 5- to 14-mo-old C57BL/6 nu/nu mice. Frequency determinations of CTL-P directed against H-2delta alloantigens ranged from 1/159,000 to 1/12,400. The relatively low frequency of CTL-P was enriched nearly 10-fold (to 1/2300) by passage of nude spleen cells over a column of nylon wool. After priming nude spleen cells for 7 days in conventional MLC, 1 to 3% of the MLC cells could be operationally identified as CTL-P. Furthermore, the progeny of MLC-primed nude CTL-P were specifically cytolytic for target cells of the strain used for priming. Such a system may be useful for analyzing the specificity repertoires of cells of the T cell lineage that have not undergone thymic influence.

  1. Plant delta 15N correlates with the transpiration efficiency of nitrogen acquisition in tropical trees. (United States)

    Cernusak, Lucas A; Winter, Klaus; Turner, Benjamin L


    Based upon considerations of a theoretical model of (15)N/(14)N fractionation during steady-state nitrate uptake from soil, we hypothesized that, for plants grown in a common soil environment, whole-plant delta(15)N (deltaP) should vary as a function of the transpiration efficiency of nitrogen acquisition (F(N)/v) and the difference between deltaP and root delta(15)N (deltaP - deltaR). We tested these hypotheses with measurements of several tropical tree and liana species. Consistent with theoretical expectations, both F(N)/v and deltaP - deltaR were significant sources of variation in deltaP, and the relationship between deltaP and F(N)/v differed between non-N(2)-fixing and N(2)-fixing species. We interpret the correlation between deltaP and F(N)/v as resulting from variation in mineral nitrogen efflux-to-influx ratios across plasma membranes of root cells. These results provide a simple explanation of variation in delta(15)N of terrestrial plants and have implications for understanding nitrogen cycling in ecosystems.

  2. A novel cobalt-free layered GdBaFe{sub 2}O{sub 5+{delta}} cathode for proton conducting solid oxide fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Hanping; Xue, Xingjian [Department of Mechanical Engineering, University of South Carolina, Columbia, SC 29208 (United States)


    While cobalt-containing perovskite-type cathode materials facilitate the activation of oxygen reduction, they also suffer from problems like poor chemical stability in CO{sub 2} and high thermal expansion coefficients. In this research, a cobalt-free layered GdBaFe{sub 2}O{sub 5+{delta}} (GBF) perovskite was developed as a cathode material for protonic ceramic membrane fuel cells (PCMFCs) based on proton conducting electrolyte of stable BaZr{sub 0.1}Ce{sub 0.7}Y{sub 0.2}O{sub 3-{delta}} (BZCY7). The button cells of Ni-BZCY7 vertical stroke BZCY7 vertical stroke GBF were fabricated and characterized using complex impedance technique from 600 to 700 C. An open-circuit potential of 1.007 V, maximum power density of 417 mW cm{sup -2}, and a low electrode polarization resistance of 0.18 {omega} cm{sup 2} were achieved at 700 C. The results indicate that layered GBF perovskite is a good candidate for cobalt-free cathode material, while the developed Ni-BZCY7 vertical stroke BZCY7 vertical stroke GBF cell is a promising functional material system for solid oxide fuel cells. (author)

  3. Osteoblast Cell Response on the Ti6Al4V Alloy Heat-Treated

    Directory of Open Access Journals (Sweden)

    Mercedes Paulina Chávez-Díaz


    Full Text Available In an effort to examine the effect of the microstructural changes of the Ti6Al4V alloy, two heat treatments were carried out below (Ti6Al4V800 and above (Ti6Al4V1050 its β-phase transformation temperature. After each treatment, globular and lamellar microstructures were obtained. Saos-2 pre-osteoblast human osteosarcoma cells were seeded onto Ti6Al4V alloy disks and immersed in cell culture for 7 days. Electrochemical assays in situ were performed using OCP and EIS measurements. Impedance data show a passive behavior for the three Ti6Al4V alloys; additionally, enhanced impedance values were recorded for Ti6Al4V800 and Ti6Al4V1050 alloys. This passive behavior in culture medium is mostly due to the formation of TiO2 during their sterilization. Biocompatibility and cell adhesion were characterized using the SEM technique; Ti6Al4V as received and Ti6Al4V800 alloys exhibited polygonal and elongated morphology, whereas Ti6Al4V1050 alloy displayed a spherical morphology. Ti and O elements were identified by EDX analysis due to the TiO2 and signals of C, N and O, related to the formation of organic compounds from extracellular matrix. These results suggest that cell adhesion is more likely to occur on TiO2 formed in discrete α-phase regions (hcp depending on its microstructure (grains.

  4. Flipped SU(5) predicts {delta}T/T

    Energy Technology Data Exchange (ETDEWEB)

    Kyae, Bumseok [School of Physics, Korea Institute for Advanced Study, 207-43, Cheongnyangni-Dong, Dongdaemun-Gu, Seoul 130-722 (Korea, Republic of)]. E-mail:; Shafi, Qaisar [Bartol Research Institute, Department of Physics and Astronomy, University of Delaware, Newark, DE 19716 (United States)]. E-mail:


    We discuss hybrid inflation in supersymmetric flipped SU(5) model such that the cosmic microwave anisotropy {delta}T/T is essentially proportional to (M/M{sub P}){sup 2}, where M denotes the symmetry breaking scale and M{sub P} (=2.4x10{sup 18} GeV) is the reduced Planck mass. The magnitude of M determined from {delta}T/T measurements can be consistent with the value inferred from the evolution of SU(3) and SU(2) gauge couplings. In other words, one could state that flipped SU(5) predicts (more precisely 'postdicts') {delta}T/T. The scalar spectral index n{sub s}=0.993+/-0.007, the scalar to tensor ratio satisfies r-bar 10{sup -6}, while dn{sub s}/dlnk-bar 4x10{sup -4}.

  5. Display of wasp venom allergens on the cell surface of Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Borodina, Irina; Jensen, B. M.; Søndergaard, Ib


    Background: Yeast surface display is a technique, where the proteins of interest are expressed as fusions with yeast surface proteins and thus remain attached to the yeast cell wall after expression. Our purpose was to study whether allergens expressed on the cell surface of baker's yeast...... were expressed on the surface as fusions with a-agglutinin complex protein AGA2. The expression was confirmed by fluorescent cytometry (FACS) after staining the cells with antibody against a C-tag attached to the C-terminal end of the allergens. Phospholipase A1 and hyaluronidase retained...... their enzymatic activities. Phospholipase A1 severely inhibited the growth of the yeast cells. Antigen 5 - expressing yeast cells bound IgE antibodies from wasp venom allergic patient sera but not from control sera as demonstrated by FACS. Moreover, antigen 5 - expressing yeast cells were capable of mediating...

  6. Epitope selection from an uncensored peptide library displayed on avian leukosis virus

    International Nuclear Information System (INIS)

    Khare, Pranay D.; Rosales, Ana G.; Bailey, Kent R.; Russell, Stephen J.; Federspiel, Mark J.


    Phage display libraries have provided an extraordinarily versatile technology to facilitate the isolation of peptides, growth factors, single chain antibodies, and enzymes with desired binding specificities or enzymatic activities. The overall diversity of peptides in phage display libraries can be significantly limited by Escherichia coli protein folding and processing machinery, which result in sequence censorship. To achieve an optimal diversity of displayed eukaryotic peptides, the library should be produced in the endoplasmic reticulum of eukaryotic cells using a eukaryotic display platform. In the accompanying article, we presented experiments that demonstrate that polypeptides of various sizes could be efficiently displayed on the envelope glycoproteins of a eukaryotic virus, avian leukosis virus (ALV), and the displayed polypeptides could efficiently attach to cognate receptors without interfering with viral attachment and entry into susceptible cells. In this study, methods were developed to construct a model library of randomized eight amino acid peptides using the ALV eukaryotic display platform and screen the library for specific epitopes using immobilized antibodies. A virus library with approximately 2 x 10 6 different members was generated from a plasmid library of approximately 5 x 10 6 diversity. The sequences of the randomized 24 nucleotide/eight amino acid regions of representatives of the plasmid and virus libraries were analyzed. No significant sequence censorship was observed in producing the virus display library from the plasmid library. Different populations of peptide epitopes were selected from the virus library when different monoclonal antibodies were used as the target. The results of these two studies clearly demonstrate the potential of ALV as a eukaryotic platform for the display and selection of eukaryotic polypeptides libraries

  7. Vulnerability and Resilience of the Niger Delta Coastal Communities to Pollution and Environmental Degradation (United States)

    Ndimele, P. E.; Whenu, O. O.; Anwan, H. R.; Anetekhai, M. A.


    The Niger Delta is Africa's largest delta consisting of the third largest mangrove forest in the world and covering 70,000km2 of Nigeria land mass. This delta is the largest wetland in Africa and among the ten most important wetland and marine ecosystems in the world. The delta is home to all of Nigeria's endemic or near-endemic mammal species and to six IUCN Red List mammals. The Niger Delta harbours globally outstanding fish fauna and displays exceptional evolutionary phenomena with its higher taxonomic endemism and distinct species assemblages. The Niger delta is blessed with abundance of natural and human resources, including the majority of Nigeria's oil and gas deposits, good agricultural land, extensive forests, excellent fisheries as well as a well-developed industrial base, a large labour force and a vibrant private sector. However, this fragile but rich ecosystem is seriously threatened by increased industrial pollution, resource over-exploitation and environmental degradation caused by over six decades of oil exploitation. Aquatic life has been destroyed with the pollution of traditional fishing grounds, exacerbating hunger and poverty in fishing communities. The multifarious use of the delta has led to human-induced changes in biota, habitats and landscapes necessitating the development of a holistic policy that considers all the interacting factors in the ecosystem. Taking a systems approach incorporating an understanding of The Ecosystem Approach, vulnerability, resilience, the DPSIR framework, ecosystem services and societal benefits are integrated in order to evolve a management tool that will result in sustainable resource exploitation, improvement in living standards of locals and restoration of the ecosystem.

  8. Expression of the Ly-6 family proteins Lynx1 and Ly6H in the rat brain is compartmentalized, cell-type specific, and developmentally regulated

    DEFF Research Database (Denmark)

    Thomsen, Morten Skøtt; Cinar, Betül; Jensen, Majbrit Myrup


    regarding the distribution and developmental regulation of these proteins in the brain. We use protein cross-linking and synaptosomal fractions to demonstrate that the Ly-6 proteins Lynx1 and Ly6H are membrane-bound proteins in the brain, which are present on the cell surface and localize to synaptic...... demonstrate that Lynx1 and Ly6H are expressed in cultured neurons, but not cultured micro- or astroglial cultures. In addition, Lynx1, but not Ly6H was detected in the CSF. Finally, we show that the Ly-6 proteins Lynx1, Lynx2, Ly6H, and PSCA, display distinct expression patterns during postnatal development...

  9. Connectivity in river deltas (United States)

    Passalacqua, P.; Hiatt, M. R.; Sendrowski, A.


    Deltas host approximately half a billion people and are rich in ecosystem diversity and economic resources. However, human-induced activities and climatic shifts are significantly impacting deltas around the world; anthropogenic disturbance, natural subsidence, and eustatic sea-level rise are major causes of threat to deltas and in many cases have compromised their safety and sustainability, putting at risk the people that live on them. In this presentation, I will introduce a framework called Delta Connectome for studying connectivity in river deltas based on different representations of a delta as a network. Here connectivity indicates both physical connectivity (how different portions of the system interact with each other) as well as conceptual (pathways of process coupling). I will explore several network representations and show how quantifying connectivity can advance our understanding of system functioning and can be used to inform coastal management and restoration. From connectivity considerations, the delta emerges as a leaky network that evolves over time and is characterized by continuous exchanges of fluxes of matter, energy, and information. I will discuss the implications of connectivity on delta functioning, land growth, and potential for nutrient removal.

  10. Microgravity and bone cell mechanosensitivity: FLOW experiment during the DELTA mission (United States)

    Bacabac, Rommel G.; Van Loon, Jack J. W. A.; de Blieck-Hogervorst, Jolanda M. A.; Semeins, Cor M.; Zandieh-Doulabi, Behrouz; Helder, Marco N.; Smit, Theo H.; Klein-Nulend, Jenneke


    The catabolic effects of microgravity on mineral metabolism in bone organ cultures might be explained as resulting from an exceptional form of disuse. It is possible that the mechanosensitivity of bone cells is altered under near weightlessness conditions, which likely contributes to disturbed bone metabolism observed in astronauts. In the experiment "FLOW", we tested whether the production of early signaling molecules that are involved in the mechanical load-induced osteogenic response by bone cells is changed under microgravity conditions. FLOW was one of the Biological experiment entries to the Dutch Soyuz Mission "DELTA" (Dutch Expedition for Life Science, Technology and Atmospheric Research). FLOW was flown by the Soyuz craft, launched on April 19, 2004, on its way to the International Space Station. Primary osteocytes, osteoblasts, and periosteal fibroblasts were incubated in plunger boxes, developed by Centre for Concepts in Mechatronics, using plunger activation events for single pulse fluid shear stress stimulations. Due to unforeseen hardware complications, results from in-flight cultures are considered lost. Ground control experiments showed an accumulative increase of NO in medium for osteocytes (as well as for osteoblasts and periosteal fibroblasts). Data from the online-NO sensor showed that the NO produced in medium by osteocytes increased sharply after pulse shear stress stimulations. COX-2 mRNA expression revealed high levels in osteoblasts compared to the other cell types tested. In conclusion, preparations for the FLOW experiment and preliminary ground results indicate that the FLOW setup is viable for a future flight opportunity.

  11. The Stationary-Phase Cells of Saccharomyces cerevisiae Display Dynamic Actin Filaments Required for Processes Extending Chronological Life Span. (United States)

    Vasicova, Pavla; Lejskova, Renata; Malcova, Ivana; Hasek, Jiri


    Stationary-growth-phase Saccharomyces cerevisiae yeast cultures consist of nondividing cells that undergo chronological aging. For their successful survival, the turnover of proteins and organelles, ensured by autophagy and the activation of mitochondria, is performed. Some of these processes are engaged in by the actin cytoskeleton. In S. cerevisiae stationary-phase cells, F actin has been shown to form static aggregates named actin bodies, subsequently cited to be markers of quiescence. Our in vivo analyses revealed that stationary-phase cultures contain cells with dynamic actin filaments, besides the cells with static actin bodies. The cells with dynamic actin displayed active endocytosis and autophagy and well-developed mitochondrial networks. Even more, stationary-phase cell cultures grown under calorie restriction predominantly contained cells with actin cables, confirming that the presence of actin cables is linked to successful adaptation to stationary phase. Cells with actin bodies were inactive in endocytosis and autophagy and displayed aberrations in mitochondrial networks. Notably, cells of the respiratory activity-deficient cox4Δ strain displayed the same mitochondrial aberrations and actin bodies only. Additionally, our results indicate that mitochondrial dysfunction precedes the formation of actin bodies and the appearance of actin bodies corresponds to decreased cell fitness. We conclude that the F-actin status reflects the extent of damage that arises from exponential growth. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  12. Delta 2.0

    DEFF Research Database (Denmark)

    Skott, Jeppe; Skott, Charlotte Krog; Jess, Kristine

    DELTA 2.0 er en ny og helt opdateret udgave af Delta, der i ti år været brugt i matematiklærernes grund-, efter- og videreuddannelse. DELTA 2.0 er seriens almene fagdidaktik. Der er også fagdidaktiske overvejelser i de øvrige bøger i serien, men de er knyttet til specifikt matematisk indhold. DELTA...... 2.0 behandler mere generelle matematikdidaktiske problemstillinger såsom læringsteoretiske overvejelser i forbindelse med matematik, centrale aspekter af det at undervise i matematik og digitale teknologier som værktøj til at støtte elevers faglige læring af matematik....

  13. Microbial surface displayed enzymes based biofuel cell utilizing degradation products of lignocellulosic biomass for direct electrical energy. (United States)

    Fan, Shuqin; Hou, Chuantao; Liang, Bo; Feng, Ruirui; Liu, Aihua


    In this work, a bacterial surface displaying enzyme based two-compartment biofuel cell for the direct electrical energy conversion from degradation products of lignocellulosic biomass is reported. Considering that the main degradation products of the lignocellulose are glucose and xylose, xylose dehydrogenase (XDH) displayed bacteria (XDH-bacteria) and glucose dehydrogenase (GDH) displayed bacteria (GDH-bacteria) were used as anode catalysts in anode chamber with methylene blue as electron transfer mediator. While the cathode chamber was constructed with laccase/multi-walled-carbon nanotube/glassy-carbon-electrode. XDH-bacteria exhibited 1.75 times higher catalytic efficiency than GDH-bacteria. This assembled enzymatic fuel cell exhibited a high open-circuit potential of 0.80 V, acceptable stability and energy conversion efficiency. Moreover, the maximum power density of the cell could reach 53 μW cm(-2) when fueled with degradation products of corn stalk. Thus, this finding holds great potential to directly convert degradation products of biomass into electrical energy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Intermediate-to-low temperature protonic ceramic membrane fuel cells with Ba{sub 0.5}Sr{sub 0.5}Co{sub 0.8}Fe{sub 0.2}O{sub 3-{delta}}-BaZr{sub 0.1}Ce{sub 0.7}Y{sub 0.2}O{sub 3-{delta}} composite cathode

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Bin; Ding, Hanping; Dong, Yingchao; Wang, Songlin; Zhang, Xiaozhen; Fang, Daru; Meng, Guangyao [Department of Materials Science and Engineering, University of Science and Technology of China (USTC), Hefei, Anhui 230026 (China)


    The perovskite-type Ba{sub 0.5}Sr{sub 0.5}Co{sub 0.8}Fe{sub 0.2}O{sub 3-{delta}}-BaZr{sub 0.1}Ce{sub 0.7}Y{sub 0.2}O{sub 3-{delta}} (BSCF-BZCY) composite oxides were synthesized by a modified Pechini method and examined as a novel composite cathode for intermediate-to-low temperature protonic ceramic membrane fuel cells (ILT-PCMFCs). Thin proton-conducting BaZr{sub 0.1}Ce{sub 0.7}Y{sub 0.2}O{sub 3-{delta}} (BZCY) electrolyte and NiO-BaZr{sub 0.1}Ce{sub 0.7}Y{sub 0.2}O{sub 3-{delta}} (NiO-BZCY) anode functional layer were prepared over porous anode substrates composed of NiO-BaZr{sub 0.1}Ce{sub 0.7}Y{sub 0.2}O{sub 3-{delta}} by a one-step dry-pressing/co-firing process. A laboratory-sized quad-layer cell of NiO-BZCY/NiO-BZCY({proportional_to}50 {mu}m)/BZCY({proportional_to}20 {mu}m)/BSCF-BZCY({proportional_to}50 {mu}m) was operated from 550 to 700 C with humidified hydrogen ({proportional_to}3% H{sub 2}O) as fuel and the static air as oxidant. A high open-circuit potential of 1.009 V, a maximum power density of 418 mW cm{sup -2}, and a low polarization resistance of the electrodes of 0.10 {omega} cm{sup 2} was achieved at 700 C. These investigations have indicated that proton-conducting BZCY electrolyte with BSCF perovskite cathode is a promising material system for the next generation solid oxide fuel cells (SOFCs). (author)

  15. 3-D electromagnetic plasma particle simulations on the Intel Delta parallel computer

    International Nuclear Information System (INIS)

    Wang, J.; Liewer, P.C.


    A three-dimensional electromagnetic PIC code has been developed on the 512 node Intel Touchstone Delta MIMD parallel computer. This code is based on the General Concurrent PIC algorithm which uses a domain decomposition to divide the computation among the processors. The 3D simulation domain can be partitioned into 1-, 2-, or 3-dimensional sub-domains. Particles must be exchanged between processors as they move among the subdomains. The Intel Delta allows one to use this code for very-large-scale simulations (i.e. over 10 8 particles and 10 6 grid cells). The parallel efficiency of this code is measured, and the overall code performance on the Delta is compared with that on Cray supercomputers. It is shown that their code runs with a high parallel efficiency of ≥ 95% for large size problems. The particle push time achieved is 115 nsecs/particle/time step for 162 million particles on 512 nodes. Comparing with the performance on a single processor Cray C90, this represents a factor of 58 speedup. The code uses a finite-difference leap frog method for field solve which is significantly more efficient than fast fourier transforms on parallel computers. The performance of this code on the 128 node Cray T3D will also be discussed

  16. Morita-Baylis-Hillman Adducts Display Anti-Inflammatory Effects by Modulating Inflammatory Mediator Expression in RAW264.7 Cells

    Directory of Open Access Journals (Sweden)

    Glaucia V. Faheina-Martins


    Full Text Available Inflammatory response plays an important role not only in the normal physiology but also in pathologies such as cancers. The Morita-Baylis-Hillman adducts (MBHA are a novel group of synthetic molecules that have demonstrated many biological activities against some parasitic cells such as Plasmodium falciparum, Leishmania amazonensis, and Leishmania chagasi, and antimitotic activity against sea urchin embryonic cells was also related. However, little is known about the mechanisms induced by MBHA in inflammatory process and its relation with anticancer activity. The present work investigated the cytotoxicity of three MBHA derivatives (A2CN, A3CN, and A4CN, on human colorectal adenocarcinoma, HT-29 cells, and their anti-inflammatory activities were examined in lipopolysaccharide- (LPS- stimulated RAW264.7 macrophage cells, being these derivatives potentially cytotoxic to HT-29 cells. Coincubation with A2CN, A3CN, or A4CN and LPS in RAW264.7 cells inhibited NO production, as well as the production of reactive oxygen species (ROS was also repressed. The mRNA expressions of IL-1β and IL-6 were significantly downregulated by such MBHA compounds in RAW264.7 cells, but only A2CN was able to inhibit the COX-2 gene expression. We also showed that MBHA compounds decreased almost to zero the production of IL-1β and IL-6. These findings display that such MBHA compounds exhibit anticancer and anti-inflammatory activities.

  17. Tumour cells expressing single VEGF isoforms display distinct growth, survival and migration characteristics.

    Directory of Open Access Journals (Sweden)

    Chryso Kanthou

    Full Text Available Vascular endothelial growth factor-A (VEGF is produced by most cancer cells as multiple isoforms, which display distinct biological activities. VEGF plays an undisputed role in tumour growth, vascularisation and metastasis; nevertheless the functions of individual isoforms in these processes remain poorly understood. We investigated the effects of three main murine isoforms (VEGF188, 164 and 120 on tumour cell behaviour, using a panel of fibrosarcoma cells we developed that express them individually under endogenous promoter control. Fibrosarcomas expressing only VEGF188 (fs188 or wild type controls (fswt were typically mesenchymal, formed ruffles and displayed strong matrix-binding activity. VEGF164- and VEGF120-producing cells (fs164 and fs120 respectively were less typically mesenchymal, lacked ruffles but formed abundant cell-cell contacts. On 3D collagen, fs188 cells remained mesenchymal while fs164 and fs120 cells adopted rounded/amoeboid and a mix of rounded and elongated morphologies respectively. Consistent with their mesenchymal characteristics, fs188 cells migrated significantly faster than fs164 or fs120 cells on 2D surfaces while contractility inhibitors accelerated fs164 and fs120 cell migration. VEGF164/VEGF120 expression correlated with faster proliferation rates and lower levels of spontaneous apoptosis than VEGF188 expression. Nevertheless, VEGF188 was associated with constitutively active/phosphorylated AKT, ERK1/2 and Stat3 proteins. Differences in proliferation rates and apoptosis could be explained by defective signalling downstream of pAKT to FOXO and GSK3 in fs188 and fswt cells, which also correlated with p27/p21 cyclin-dependent kinase inhibitor over-expression. All cells expressed tyrosine kinase VEGF receptors, but these were not active/activatable suggesting that inherent differences between the cell lines are governed by endogenous VEGF isoform expression through complex interactions that are independent of tyrosine

  18. Peat compaction in deltas : implications for Holocene delta evolution

    NARCIS (Netherlands)

    van Asselen, S.


    Many deltas contain substantial amounts of peat, which is the most compressible soil type. Therefore, peat compaction potentially leads to high amounts of subsidence in deltas. The main objective of this research was to quantify subsidence due to peat compaction in Holocene fluvial-deltaic settings

  19. The impact of human activities in the Wulan Delta Estuary, Indonesia (United States)

    Fadlillah, L. N.; Sunarto; Widyastuti, M.; Marfai, M. A.


    The increasing of human population in the watershed and the coastal area and the need of life exert pressure in the delta that provides various resources. Wulan Delta is one of active Delta in Central Java, Indonesia. It has been experienced multiple pressures because of natural factors and human factors. In order to provide the scientific solution and to analyze the impact of human intervention in delta, we collected several pieces of evidence based on secondary data and primary data. The secondary data is water quality data on sites 6 and 7, meanwhile the secondary data is the water quality data in site 1 to 5. This paper present a review and problems identification in Wulan Delta, based on hydrological condition, land use, and human activities in the delta. Meanwhile, the human intervention in the land which is land use exchange leads to several problems such as the land use changes, high sediment load, and water degradation. Almost 80% of Delta has been transformed into the fish pond by local communities.

  20. Turbidity and salinity affect feeding performance and physiological stress in the endangered delta smelt. (United States)

    Hasenbein, Matthias; Komoroske, Lisa M; Connon, Richard E; Geist, Juergen; Fangue, Nann A


    Coastal estuaries are among the most heavily impacted ecosystems worldwide with many keystone fauna critically endangered. The delta smelt (Hypomesus transpacificus) is an endangered pelagic fish species endemic to the Sacramento-San Joaquin Estuary in northern California, and is considered as an indicator species for ecosystem health. This ecosystem is characterized by tidal and seasonal gradients in water parameters (e.g., salinity, temperature, and turbidity), but is also subject to altered water-flow regimes due to water extraction. In this study, we evaluated the effects of turbidity and salinity on feeding performance and the stress response of delta smelt because both of these parameters are influenced by water flows through the San Francisco Bay Delta (SFBD) and are known to be of critical importance to the completion of the delta smelt's life cycle. Juvenile delta smelt were exposed to a matrix of turbidities and salinities ranging from 5 to 250 nephelometric turbidity units (NTUs) and 0.2 to 15 parts per thousand (ppt), respectively, for 2 h. Best statistical models using Akaike's Information Criterion supported that increasing turbidities resulted in reduced feeding rates, especially at 250 NTU. In contrast, best explanatory models for gene transcription of sodium-potassium-ATPase (Na/K-ATPase)-an indicator of osmoregulatory stress, hypothalamic pro-opiomelanocortin-a precursor protein to adrenocorticotropic hormone (expressed in response to biological stress), and whole-body cortisol were affected by salinity alone. Only transcription of glutathione-S-transferase, a phase II detoxification enzyme that protects cells against reactive oxygen species, was affected by both salinity and turbidity. Taken together, these data suggest that turbidity is an important determinant of feeding, whereas salinity is an important abiotic factor influencing the cellular stress response in delta smelt. Our data support habitat association studies that have shown greater

  1. The in vivo therapeutic efficacy of the oncolytic adenovirus Delta24-RGD is mediated by tumor-specific immunity.

    Directory of Open Access Journals (Sweden)

    Anne Kleijn

    Full Text Available The oncolytic adenovirus Delta24-RGD represents a new promising therapeutic agent for patients with a malignant glioma and is currently under investigation in clinical phase I/II trials. Earlier preclinical studies showed that Delta24-RGD is able to effectively lyse tumor cells, yielding promising results in various immune-deficient glioma models. However, the role of the immune response in oncolytic adenovirus therapy for glioma has never been explored. To this end, we assessed Delta24-RGD treatment in an immune-competent orthotopic mouse model for glioma and evaluated immune responses against tumor and virus. Delta24-RGD treatment led to long-term survival in 50% of mice and this effect was completely lost upon administration of the immunosuppressive agent dexamethasone. Delta24-RGD enhanced intra-tumoral infiltration of F4/80+ macrophages, CD4+ and CD8+ T-cells, and increased the local production of pro-inflammatory cytokines and chemokines. In treated mice, T cell responses were directed to the virus as well as to the tumor cells, which was reflected in the presence of protective immunological memory in mice that underwent tumor rechallenge. Together, these data provide evidence that the immune system plays a vital role in the therapeutic efficacy of oncolytic adenovirus therapy of glioma, and may provide angles to future improvements on Delta24-RGD therapy.

  2. A novel lentiviral scFv display library for rapid optimization and selection of high affinity antibodies. (United States)

    Qudsia, Sehar; Merugu, Siva B; Mangukiya, Hitesh B; Hema, Negi; Wu, Zhenghua; Li, Dawei


    Antibody display libraries have become a popular technique to screen monoclonal antibodies for therapeutic purposes. An important aspect of display technology is to generate an optimization library by changing antibody affinity to antigen through mutagenesis and screening the high affinity antibody. In this study, we report a novel lentivirus display based optimization library antibody in which Agtuzumab scFv is displayed on cell membrane of HEK-293T cells. To generate an optimization library, hotspot mutagenesis was performed to achieve diverse antibody library. Based on sequence analysis of randomly selected clones, library size was estimated approximately to be 1.6 × 10 6 . Lentivirus display vector was used to display scFv antibody on cell surface and flow cytometery was performed to check the antibody affinity to antigen. Membrane bound scFv antibodies were then converted to secreted antibody through cre/loxP recombination. One of the mutant clones, M8 showed higher affinity to antigen in flow cytometery analysis. Further characterization of cellular and secreted scFv through western blot showed that antibody affinity was increased by three fold after mutagenesis. This study shows successful construction of a novel antibody library and suggests that hotspot mutagenesis could prove a useful and rapid optimization tool to generate similar libraries with various degree of antigen affinity. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Giant T{sub c} shift in HgBa{sub 2}CaCu{sub 2}O{sub 6+{delta}} and TlBa{sub 2}CaCu{sub 2}O{sub 7{minus}{delta}} superconductors due to Hg-Tl exchange

    Energy Technology Data Exchange (ETDEWEB)

    Gapud, A.A.; Wu, J.Z.; Kang, B.W.; Yan, S.L.; Xie, Y.Y. [Department of Physics and Astronomy, University of Kansas, Lawrence, Kansas 66045-2151 (United States); Siegal, M.P. [Sandia National Laboratories, Albuquerque, New Mexico 87185 (United States)


    The irreversibility lines of epitaxial thin films of HgBa{sub 2}CaCu{sub 2}O{sub 6+{delta}} and TlBa{sub 2}CaCu{sub 2}O{sub 7{minus}{delta}}, whether deduced from field-induced magnetoresistive broadening or onset of nonhysteretic magnetization, were found to coincide when plotted against reduced temperature, showing the same exponential-decay temperature behavior for T/T{sub c}{lt}0.8 and power-law behavior for T/T{sub c}{gt}0.8 (where T{sub c} is zero-field, zero-resistivity critical temperature). These results indicate that replacing Tl with Hg has no noticeable effect on the anisotropy and suggests that T{sub c} is not determined by anisotropy. {copyright} {ital 1999} {ital The American Physical Society}

  4. Geochronology of priority pollutants in sedimentation zones of the Volga and Danube delta in comparison with the Rhine delta

    International Nuclear Information System (INIS)

    Winkels, H.J.; Kroonenberg, S.B.; Lychagin, M.Y.; Marin, G.; Rusakov, G.V.; Kasimov, N.S.


    Six sediment cores were taken in sedimentation zones of the Volga river (located in the southern part of the Russian Federation) and, additionally, 6 sediment cores were taken in several lakes (sedimentation zones) in the central and western part of the Danube delta in Romania. Priority pollutants (8 metals, 7 polychlorinated biphenyls and 10 polycyclic aromatic hydrocarbons) were determined in all samples of all cores. Present-day and historical levels of pollutants since the late 1930s were established through the use of radionuclide time tracers ( 137 Cs, 134 Cs). For the persistent metals and polycyclic aromatic hydrocarbons, trends in the concentration profiles during the last 5 decades are described. Low and hardly changing concentrations of As, Cu, Zn and all studied PAHs were observed during the last five decades in the sediments of the Volga river. Recently deposited sediments show slightly increasing levels for the heavy metals Zn and Cr and As in the Volga delta. For the studied metals and PAHs, maximum concentrations were found around 1987 in the sediments of the Danube delta. Sediments deposited around 1940 and recently deposited sediments in the Danube delta showed lower pollutant levels. If the contents of heavy metals, PAHs and PCBs in the aquatic sediments in the deltas of the rivers Rhine, Danube and Volga are compared, it is clear that the Volga delta is and was the cleanest delta during the last 5 decades. Nowadays the contents of heavy metals (except Cu and Ni), PAHs and PCBs in the aquatic sediments of the river Rhine are still highest compared to the other two rivers. The recent load of heavy metals (except Cd and Zn) in the sediments of the river Danube is the highest compared to the other two rivers. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  5. Multiple myeloma in Niger Delta, Nigeria: complications and the outcome of palliative interventions

    Directory of Open Access Journals (Sweden)

    Nwabuko OC


    prednisone (MP double regimen, while 19% and 8% patients were on MP–thalidomide and MP–bortezomib triple regimens, respectively. A total of 3.8% of patients at DS stage IIIB disease had autologous stem-cell transplantation (ASCT. Only 7.6% of the myeloma patients survived up to 5 years post diagnosis. The overall mean survival interval was 39.7 months (95% CI, 32.1–47.2.Conclusion: Late diagnosis and inadequate palliative care account for major complications encountered by MM patients in the Niger-Delta region of Nigeria. This could be responsible for the poor prognostic outcome and low survival interval of MM individuals in this region. There is, therefore, a need to improve the quality of palliative care received by myeloma patients in this region. This is achievable via provision of relevant and affordable health care facilities for diagnosis and treatment of the disease. Keywords: multiple myeloma, palliative care, melphalan-prednisone, bone marrow plasma cells, autologous stem-cell transplantation, Niger Delta

  6. Shift in the Equilibrium between On and Off States of the Allosteric Switch in Ras-GppNHp Affected by Small Molecules and Bulk Solvent Composition

    Energy Technology Data Exchange (ETDEWEB)

    Holzapfel, Genevieve; Buhrman, Greg; Mattos, Carla (NCSU)


    Ras GTPase cycles between its active GTP-bound form promoted by GEFs and its inactive GDP-bound form promoted by GAPs to affect the control of various cellular functions. It is becoming increasingly apparent that subtle regulation of the GTP-bound active state may occur through promotion of substates mediated by an allosteric switch mechanism that induces a disorder to order transition in switch II upon ligand binding at an allosteric site. We show with high-resolution structures that calcium acetate and either dithioerythritol (DTE) or dithiothreitol (DTT) soaked into H-Ras-GppNHp crystals in the presence of a moderate amount of poly(ethylene glycol) (PEG) can selectively shift the equilibrium to the 'on' state, where the active site appears to be poised for catalysis (calcium acetate), or to what we call the 'ordered off' state, which is associated with an anticatalytic conformation (DTE or DTT). We also show that the equilibrium is reversible in our crystals and dependent on the nature of the small molecule present. Calcium acetate binding in the allosteric site stabilizes the conformation observed in the H-Ras-GppNHp/NOR1A complex, and PEG, DTE, and DTT stabilize the anticatalytic conformation observed in the complex between the Ras homologue Ran and Importin-{beta}. The small molecules are therefore selecting biologically relevant conformations in the crystal that are sampled by the disordered switch II in the uncomplexed GTP-bound form of H-Ras. In the presence of a large amount of PEG, the ordered off conformation predominates, whereas in solution, in the absence of PEG, switch regions appear to remain disordered in what we call the off state, unable to bind DTE.

  7. Mesenchymal Stem Cells from Patients with Rheumatoid Arthritis Display Impaired Function in Inhibiting Th17 Cells

    Directory of Open Access Journals (Sweden)

    Yue Sun


    Full Text Available Mesenchymal stem cells (MSCs possess multipotent and immunomodulatory properties and are suggested to be involved in the pathogenesis of immune-related diseases. This study explored the function of bone marrow MSCs from rheumatoid arthritis (RA patients, focusing on immunomodulatory effects. RA MSCs showed decreased proliferative activity and aberrant migration capacity. No significant differences were observed in cytokine profiles between RA and control MSCs. The effects of RA MSCs on proliferation of peripheral blood mononuclear cells (PBMCs and distribution of specific CD4+ T cell subtypes (Th17, Treg, and Tfh cells were investigated. RA MSCs appeared to be indistinguishable from controls in suppressing PBMC proliferation, decreasing the proportion of Tfh cells, and inducing the polarization of Treg cells. However, the capacity to inhibit Th17 cell polarization was impaired in RA MSCs, which was related to the low expression of CCL2 in RA MSCs after coculture with CD4+ T cells. These findings indicated that RA MSCs display defects in several important biological activities, especially the capacity to inhibit Th17 cell polarization. These functionally impaired MSCs may contribute to the development of RA disease.

  8. Delta count-rate monitoring system

    International Nuclear Information System (INIS)

    Van Etten, D.; Olsen, W.A.


    A need for a more effective way to rapidly search for gamma-ray contamination over large areas led to the design and construction of a very sensitive gamma detection system. The delta count-rate monitoring system was installed in a four-wheel-drive van instrumented for environmental surveillance and accident response. The system consists of four main sections: (1) two scintillation detectors, (2) high-voltage power supply amplifier and single-channel analyzer, (3) delta count-rate monitor, and (4) count-rate meter and recorder. The van's 6.5-kW generator powers the standard nuclear instrument modular design system. The two detectors are mounted in the rear corners of the van and can be run singly or jointly. A solid-state bar-graph count-rate meter mounted on the dashboard can be read easily by both the driver and passenger. A solid-state strip chart recorder shows trends and provides a permanent record of the data. An audible alarm is sounded at the delta monitor and at the dashboard count-rate meter if a detected radiation level exceeds the set background level by a predetermined amount

  9. Lack of genetic variation in tree ring delta13C suggests a uniform, stomatally-driven response to drought stress across Pinus radiata genotypes. (United States)

    Rowell, Douglas M; Ades, Peter K; Tausz, Michael; Arndt, Stefan K; Adams, Mark A


    We assessed the variation in delta(13)C signatures of Pinus radiata D. Don stemwood taken from three genetic trials in southern Australia. We sought to determine the potential of using delta(13)C signatures as selection criteria for drought tolerance. Increment cores were taken from P. radiata and were used to determine the basal area increment and the delta(13)C signature of extracted cellulose. Both growth increment and cellulose delta(13)C were affected by water availability. Growth increment and delta(13)C were negatively correlated suggesting that growth was water-limited. While there was significant genetic variation in growth, there was no significant genetic variation in cellulose delta(13)C of tree rings. This suggests that different genotypes of P. radiata display significant differences in growth and yet respond similarly to drought stress. The delta(13)C response to drought stress was more due to changes in stomatal conductance than to the variation in photosynthetic capacity, and this may explain the lack of genetic variation in delta(13)C. The lack of genetic variation in cellulose delta(13)C of tree rings precludes its use as a selection criterion for drought tolerance among P. radiata genotypes.

  10. Medicago truncatula Zinc-Iron Permease6 provides zinc to rhizobia-infected nodule cells. (United States)

    Abreu, Isidro; Saéz, Ángela; Castro-Rodríguez, Rosario; Escudero, Viviana; Rodríguez-Haas, Benjamín; Senovilla, Marta; Larue, Camille; Grolimund, Daniel; Tejada-Jiménez, Manuel; Imperial, Juan; González-Guerrero, Manuel


    Zinc is a micronutrient required for symbiotic nitrogen fixation. It has been proposed that in model legume Medicago truncatula, zinc is delivered by the root vasculature into the nodule and released in the infection/differentiation zone. There, transporters must introduce this element into rhizobia-infected cells to metallate the apoproteins that use zinc as a cofactor. MtZIP6 (Medtr4g083570) is an M. truncatula Zinc-Iron Permease (ZIP) that is expressed only in roots and nodules, with the highest expression levels in the infection/differentiation zone. Immunolocalization studies indicate that it is located in the plasma membrane of nodule rhizobia-infected cells. Down-regulating MtZIP6 expression levels with RNAi does not result in any strong phenotype when plants are fed mineral nitrogen. However, these plants displayed severe growth defects when they depended on nitrogen fixed by their nodules, losing of 80% of their nitrogenase activity. The reduction of this activity was likely an indirect effect of zinc being retained in the infection/differentiation zone and not reaching the cytosol of rhizobia-infected cells. These data are consistent with a model in which MtZIP6 would be responsible for zinc uptake by rhizobia-infected nodule cells in the infection/differentiation zone. © 2017 John Wiley & Sons Ltd.

  11. Experience on tangent delta norms adopted for repaired generator

    International Nuclear Information System (INIS)

    Misra, N.N.; Sood, D.K.


    The repair techniques of the generators are very crucial for avoiding prolonged forced outages. The crucial decisions based on sound knowledge and judgement becomes essential in many cases. The unit under discussions had failed on account of flash over in the Exciter end overhang windings. The failure resulted in damaged to the stator bars as well as generator core. The damaged end packets of the stator core were replaced at site. The total winding bars were removed from stator core and damaged bars were replaced with new bars. The rest of the bars were tested for tangent delta tests for reuse. Acceptance norms of 0.6% tip up from 0.2pu to 0.6pu of rated stator voltage were adopted. Some of the bars outside the acceptable limits of tangent delta were shifted close to neutral so that the standard norms of tan delta are met. This was felt necessary because lead-time for procurement of new bars was more than six months. The above-adopted norms for tangent delta will be of much use for the operating utilities. The unit under discussions was of 67.5 MW operating at 50 Hz, 0.85 pf lag and had logged 66160.46 operating hours before failure. (author)

  12. Cell surface expression system for the display of heterologous gene products using chimeric flagellin fusions of bacillus halodurans isolate

    CSIR Research Space (South Africa)

    Du Plessis, A


    Full Text Available system for the display of heterologous gene products using chimeric flagellin fusions of a Bacillus halodurans isolate Slide 2 © CSIR 2006 Bacillus halodurans Alk 36 xrhombus Ability to over-produce cell... for functionality of the His-tag for metal binding. Slide 13 © CSIR 2006 PAGE gel showing over-production of chimeric poly-His flagellin proteins 66.2 kDa 45.0 kDa 31.0 kDa 1. LMW ladder 2. NC3 3. NHisC3 4. NC6 5...

  13. Pharmacological characterisation of α6β4* nicotinic acetylcholine receptors assembled from three different α6/α3 subunit chimeras in tsA201 cells

    DEFF Research Database (Denmark)

    Jensen, Anne Bjørnskov; Hoestgaard-Jensen, Kirsten; Jensen, Anders A.


    by their inefficient functional expression in vitro. In the present study we have characterized and compared the pharmacological properties displayed by α6β4 and α6β4β3 nicotinic acetylcholine receptors assembled in tsA201 cells from the classical α6/α3 chimera (C1) and two novel α6/α3 chimeras (C6F223L and C16F223L...... should be made keeping the molecular modifications in the α6 surrogate subunits in mind, this study sheds light on the pharmacological properties of α6β4⁎ nicotinic acetylcholine receptors and demonstrates the applicability of the C6F223L and C16F223L chimeras for studies of these receptors....

  14. $\\delta$-Expansion at Finite Temperature


    Ramos, Rudnei O.


    We apply the $\\delta$-expansion perturbation scheme to the $\\lambda \\phi^{4}$ self-interacting scalar field theory in 3+1 D at finite temperature. In the $\\delta$-expansion the interaction term is written as $\\lambda (\\phi^{2})^{ 1 + \\delta}$ and $\\delta$ is considered as the perturbation parameter. We compute within this perturbative approach the renormalized mass at finite temperature at a finite order in $\\delta$. The results are compared with the usual loop-expansion at finite temperature.


    Directory of Open Access Journals (Sweden)

    Daniel Souza LIMA

    Full Text Available ABSTRACT BACKGROUND: The Amazon region is one of the main endemic areas of hepatitis delta in the world and the only one related to the presence of genotype 3 of the delta virus. OBJECTIVE: To analyze the profile, mortality and survival of cirrhotic patients submitted to liver transplantation for chronic hepatitis delta virus and compare with those transplanted by hepatitis B virus monoinfection. METHODS: Retrospective, observational and descriptive study. From May 2002 to December 2011, 629 liver transplants were performed at the Walter Cantídio University Hospital, of which 29 patients were transplanted due to cirrhosis caused by chronic delta virus infection and 40 by hepatitis B chronic monoinfection. The variables analyzed were: age, sex, MELD score, Child-Pugh score, upper gastrointestinal bleeding and hepatocellular carcinoma occurrence before the transplantation, perioperative platelet count, mortality and survival. RESULTS: The Delta Group was younger and all came from the Brazilian Amazon Region. Group B presented a higher proportion of male patients (92.5% compared to Group D (58.6%. The occurrence of upper gastrointestinal bleeding before transplantation, MELD score, and Child-Pugh score did not show statistical differences between groups. The occurrence of hepatocellular carcinoma and mortality were higher in the hepatitis B Group. The survival in 4 years was 95% in the Delta Group and 75% in the B Group, with a statistically significant difference (P=0.034. Patients with hepatitis delta presented more evident thrombocytopenia in the pre-transplantation and in the immediate postoperative period. CONCLUSION: The hepatitis by delta virus patients who underwent liver transplantation were predominantly male, coming from the Brazilian Amazon region and with similar liver function to the hepatitis B virus patients. They had a lower incidence of hepatocellular carcinoma, more marked perioperative thrombocytopenia levels and frequent

  16. Variation in leaf water delta D and delta 18O values during the evapotranspiration process

    International Nuclear Information System (INIS)

    Leopoldo, P.R.; Foloni, L.L.


    A theoretical model was developed to evaluate leaf water delta D and delta 18 O variation in relation to: leaf temperature, relative humidity converted to leaf temperature and delta D and delta 18 O values of atmospheric water vapour and soil water. (M.A.C.) [pt

  17. Rise and Fall of one of World's largest deltas; the Mekong delta in Vietnam (United States)

    Minderhoud, P. S. J.; Eslami Arab, S.; Pham, H. V.; Erkens, G.; van der Vegt, M.; Oude Essink, G.; Stouthamer, E.; Hoekstra, P.


    The Mekong delta is the third's largest delta in the world. It is home to almost 20 million people and an important region for the food security in South East Asia. As most deltas, the Mekong delta is the dynamic result of a balance of sediment supply, sea level rise and subsidence, hosting a system of fresh and salt water dynamics. Ongoing urbanization, industrialization and intensification of agricultural practices in the delta, during the past decades, resulted in growing domestic, agricultural and industrial demands, and have led to a dramatic increase of fresh water use. Since the year 2000, the amount of fresh groundwater extracted from the subsurface increased by 500%. This accelerated delta subsidence as the groundwater system compacts, with current sinking rates exceeding global sea level rise up to an order of magnitude. These high sinking rates have greatly altered the sediment budget of the delta and, with over 50% of the Mekong delta surface elevated less than 1 meter above sea level, greatly increase vulnerability to flooding and storm surges and ultimately, permanent inundation. Furthermore, as the increasingly larger extractions rapidly reduce the fresh groundwater reserves, groundwater salinization subsequently increases. On top of that, dry season low-flows by the Mekong river cause record salt water intrusion in the delta's estuarine system, creating major problems for rice irrigation. We present the work of three years research by the Dutch-Vietnamese `Rise and Fall' project on land subsidence and salinization in both groundwater and surface water in the Vietnamese Mekong delta.

  18. Losing ground in mega-deltas: basin-scale response to existential threats to the Mekong Delta (United States)

    Arias, M. E.; Kondolf, G. M.; Schmitt, R. J. P.; Carling, P. A.; Darby, S. E.; Bizzi, S.; Castelletti, A.; Cochrane, T. A.; Gibson, S.; Kummu, M.; Oeurng, C.; Rubin, Z.; Wild, T. B.


    The Mekong Delta is, in terms of the number of livelihoods it supports, its economic importance, and in its vulnerability to climate change and sinking lands, one of the world's critically threatened mega-deltas. Livelihoods depend on the mere existence of the delta, but also on ecosystem services provided by the delta's drainage basin spanning 795,000 km2 in six abutting countries. These ecosystem services include delivery of sand required to build delta land in the face of rising sea-levels and sediment bound nutrients, provision of spawning habitat for fish that are ultimately harvested in the delta, and hydrologic regulation driving the delta's unique flood-pulse regime. However, while the delta is mainly located in Vietnam, the basin of the Mekong River is shared among China, Myanmar, Laos, Thailand, Cambodia, and Vietnam. In the context of the region's dynamic growth, individual countries are pushing their own development agendas, which include extensive dam building, in-channel sand mining, construction of dykes and canals, and groundwater pumping, all of which contribute to subsidence and erosion of the Delta. Our synthesis of recent research indicates that most of the Mekong's delta land will likely fall below sea-level by 2100 as result of these drivers, exacerbating the impacts of global climatic changes. In this context, local infrastructural projects and changes in land- and water-management may temporarily mitigate some negative effects, but do not address the existential threat to the delta as a whole. To prevent, or at least substantially postpone, the drowning of the Mekong Delta requires identification of the key drivers and immediate concerted management actions on the basin-scale to change the trajectory of subsidence and sediment deficit. A specific challenge is to find the institutional arrangements in this transnational context that could support the needed management changes and equitably distribute costs and impacts. The Mekong Delta is

  19. Involvement of triacylglycerol in the metabolism of fatty acids by cultured neuroblastoma and glioma cells

    International Nuclear Information System (INIS)

    Cook, H.W.; Clarke, J.T.; Spence, M.W.


    The metabolism (chain elongation, desaturation, and incorporation into complex lipids) of thirteen different radiolabeled fatty acids and acetate was examined in N1E-115 neuroblastoma and C-6 glioma cell lines in culture. During 6-hr incubations, all fatty acids were extensively (14-80%) esterified to complex lipids, mainly choline phosphoglycerides and triacylglycerol. With trienoic and tetraenoic substrates, inositol and ethanolamine phosphoglycerides also contained up to 30% of the labeled fatty acids; plasmalogen contained up to half of the label in the ethanolamine phosphoglyceride fraction of neuroblastoma cells. Chain elongation and delta 9, delta 6, and delta 5 desaturation occurred in both cell lines; delta 4 desaturation was not observed. Seemingly anomalous utilization of arachidic acid and some selectivity based on the geometric configuration of double bonds was observed. These studies indicate that these cell lines are capable of modulating cellular membrane composition by a combination of selective exclusion and removal of inappropriate acyl chains and of modification of other acyl chains by desaturation and chain elongation. The time courses and patterns of modification and incorporation of exogenous substrates into phospholipids and triacylglycerol suggest that exogenous unsaturated fatty acid may be incorporated into triacylglycerol and later released for further metabolism and incorporation into phospholipids. This supports a role for triacylglycerol in the synthesis of membrane complex lipids in cell lines derived from neural tissue

  20. Hepatitis delta genotypes in chronic delta infection in the northeast of Spain (Catalonia). (United States)

    Cotrina, M; Buti, M; Jardi, R; Quer, J; Rodriguez, F; Pascual, C; Esteban, R; Guardia, J


    Based on genetic analysis of variants obtained around the world, three genotypes of the hepatitis delta virus have been defined. Hepatitis delta virus variants have been associated with different disease patterns and geographic distributions. To determine the prevalence of hepatitis delta virus genotypes in the northeast of Spain (Catalonia) and the correlation with transmission routes and clinical disease, we studied the nucleotide divergence of the consensus sequence of HDV RNA obtained from 33 patients with chronic delta hepatitis (24 were intravenous drug users and nine had no risk factors), and four patients with acute self-limited delta infection. Serum HDV RNA was amplified by the polymerase chain reaction technique and a fragment of 350 nucleotides (nt 910 to 1259) was directly sequenced. Genetic analysis of the nucleotide consensus sequence obtained showed a high degree of conservation among sequences (93% of mean). Comparison of these sequences with those derived from different geographic areas and pertaining to genotypes I, II and III, showed a mean sequence identity of 92% with genotype I, 73% with genotype II and 61% with genotype III. At the amino acid level (aa 115 to 214), the mean identity was 87% with genotype I, 63% with genotype II and 56% with genotype III. Conserved regions included the RNA editing domain, the carboxyl terminal 19 amino acids of the hepatitis delta antigen and the polyadenylation signal of the viral mRNA. Hepatitis delta virus isolates in the northeast of Spain are exclusively genotype I, independently of the transmission route and the type of infection. No hepatitis delta virus subgenotypes were found, suggesting that the origin of hepatitis delta virus infection in our geographical area is homogeneous.

  1. The Neurotropic Properties of AAV-PHP.B Are Limited to C57BL/6J Mice. (United States)

    Hordeaux, Juliette; Wang, Qiang; Katz, Nathan; Buza, Elizabeth L; Bell, Peter; Wilson, James M


    Improved delivery of adeno-associated virus (AAV) vectors to the CNS will greatly enhance their clinical utility. Selection of AAV9 variants in a mouse model led to the isolation of a capsid called PHP.B, which resulted in remarkable transduction of the CNS following intravenous infusion. However, we now show here that this enhanced CNS tropism is restricted to the model in which it was selected, i.e., a Cre transgenic mouse in a C57BL/6J background, and was not found in nonhuman primates or the other commonly used mouse strain BALB/cJ. We also report the potential for serious acute toxicity in NHP after systemic administration of high dose of AAV. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  2. Novel urinary metabolite of d-delta-tocopherol in rats

    International Nuclear Information System (INIS)

    Chiku, S.; Hamamura, K.; Nakamura, T.


    A novel metabolite of d-delta-tocopherol was isolated from the urine of rats given d-3,4-[ 3 H 2 ]-delta-tocopherol intravenously. The metabolite was collected from the urine of rats given d-delta-tocopherol in the same manner as that of the labeled compound. It was found that the metabolites consisted of sulfate conjugates. The portion of the major metabolite released with sulfatase was determined to be 2,8-dimethyl-2-(2'-carboxyethyl)-6-chromanol by infrared spectra, nuclear magnetic resonance spectra, and mass spectra. The proposed structure was confirmed by comparing the analytical results with those of a synthetically derived compound. As a result of the structural elucidation of this novel metabolite, a pathway for the biological transformation of delta-tocopherol is proposed which is different from that of alpha-tocopherol. A characteristic feature of the pathway is the absence of any opening of the chroman ring throughout the sequence

  3. Adulteration of honey : relation between microscopic analysis and delta C-13 measurements

    NARCIS (Netherlands)

    Kerkvliet, JD; Meijer, HAJ


    Upon routine microscopic analysis of some honey samples, parenchyma cells, single rings of ring vessels and epidermal cells are found. These cells originate from the sugar cane stem. We investigated whether there was a relation between these plant fragments and the delta C-13 value of honey. 17

  4. Display of phytase on the cell surface of Saccharomyces cerevisiae to degrade phytate phosphorus and improve bioethanol production. (United States)

    Chen, Xianzhong; Xiao, Yan; Shen, Wei; Govender, Algasan; Zhang, Liang; Fan, You; Wang, Zhengxiang


    Currently, development of biofuels as an alternative fuel has gained much attention due to resource and environmental challenges. Bioethanol is one of most important and dominant biofuels, and production using corn or cassava as raw materials has become a prominent technology. However, phytate contained in the raw material not only decreases the efficiency of ethanol production, but also leads to an increase in the discharge of phosphorus, thus impacting on the environment. In this study, to decrease phytate and its phosphorus content in an ethanol fermentation process, Saccharomyces cerevisiae was engineered through a surface-displaying system utilizing the C-terminal half of the yeast α-agglutinin protein. The recombinant yeast strain, PHY, was constructed by successfully displaying phytase on the surface of cells, and enzyme activity reached 6.4 U/g wet biomass weight. Ethanol productions using various strains were compared, and the results demonstrated that the specific growth rate and average fermentation rate of the PHY strain were higher 20 and 18 %, respectively, compared to the control strain S. cerevisiae CICIMY0086, in a 5-L bioreactor process by simultaneous saccharification and fermentation. More importantly, the phytate phosphorus concentration decreased by 89.8 % and free phosphorus concentration increased by 142.9 % in dry vinasse compared to the control in a 5-L bioreactor. In summary, we constructed a recombinant S. cerevisiae strain displaying phytase on the cell surface, which could improve ethanol production performance and effectively reduce the discharge of phosphorus. The strain reported here represents a useful novel engineering platform for developing an environment-friendly system for bioethanol production from a corn substrate.

  5. Tides Stabilize Deltas until Humans Interfere (United States)

    Hoitink, T.; Zheng Bing, W.; Vermeulen, B.; Huismans, Y.; Kastner, K.


    Despite global concerns about river delta degradation caused by extraction of natural resources, sediment retention by reservoirs and sea-level rise, human activity in the world's largest deltas intensifies. In this review, we argue that tides tend to stabilize deltas until humans interfere. Under natural circumstances, delta channels subject to tides are more stable than their fluvial-dominated counterparts. The oscillatory tidal flow counteracts the processes responsible for bank erosion, which explains why unprotected tidal channels migrate only slowly. Peak river discharges attenuate the tides, which creates storage space to accommodate the extra river discharge during extreme events and as a consequence, reduce flood risk. With stronger tides, the river discharge is being distributed more evenly over the various branches in a delta, preventing silting up of smaller channels. Human interference in deltas is massive. Storm surge barriers are constructed, new land is being reclaimed and large-scale sand excavation takes place, to collect building material. Evidence from deltas around the globe shows that in human-controlled deltas the tidal motion often plays a destabilizing role. In channels of the Rhine-Meuse Delta, some 100 scour holes are identified, which relates to the altered tidal motion after completion of a storm surge barrier. Sand mining has led to widespread river bank failures in the tidally-influenced Mekong Delta. The catastrophic flood event in the Gauges-Brahmaputra Delta by Cyclone Aila, which caused the inundation of an embanked polder area for over two years, was preceded by river bank erosion at the mouths of formal tidal channels that were blocked by the embankment. Efforts to predict the developments of degrading deltas are few. Existing delta models are capable of reproducing expanding deltas, which is essentially a matter of simulating the transport of sediment from source in a catchment to the sink in a delta. Processes of soil

  6. Structure and mechanical properties of swift heavy ion irradiated tungsten-bearing delta-phase oxides Y{sub 6}W{sub 1}O{sub 12} and Yb{sub 6}W{sub 1}O{sub 12}

    Energy Technology Data Exchange (ETDEWEB)

    Tang, M., E-mail: [Materials Science and Technology Division, Mail-Stop G755, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Wynn, T.A. [Materials Physics and Application Division, Mail-Stop K771, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Patel, M.K.; Won, J. [Materials Science and Technology Division, Mail-Stop G755, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Monnet, I. [CIMAP, CEA-CNRS-ENSICAEN-Universite de Caen Normandie, Bd Henri Becquerel, BP 5133, F-14070, Caen Cedex 5 (France); Pivin, J.C. [Centre de Spectrometrie Nucleaire et de Spectrometrie de Masse, CNRS-IN2P3-Universite Paris Sud, UMR 8609, Bat. 108, 91405 Orsay (France); Mara, N.A. [Materials Physics and Application Division, Mail-Stop K771, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Sickafus, K.E. [Materials Science and Technology Division, Mail-Stop G755, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States)


    We report on the relationship between structure and mechanical properties of complex oxides whose structures are derivatives of fluorite, following irradiation with swift heavy ion (92 MeV Xe) which approximately simulates fission product irradiation, where the electronic energy loss dominates. The two compounds of interest in this paper are Y{sub 6}W{sub 1}O{sub 12} and Yb{sub 6}W{sub 1}O{sub 12}. These compounds possess an ordered, fluorite derivative crystal structure known as the delta ({delta}) phase, a rhombohedral structure belonging to space group R3{sup Macron}. Structural changes induced by irradiation were examined using X-ray diffraction (XRD) and transmission electron microscopy (TEM). XRD investigations indicated an irradiation-induced amorphization in these compounds. This result is consistent with our previous study on Y{sub 6}W{sub 1}O{sub 12} under displacive radiation environment in which the nuclear energy loss is dominant. High resolution TEM also revealed that individual ion tracks was amorphized. The mechanical properties of both irradiated compounds, were determined by cross-sectional nano-indentation measurements as a function of ion penetration depth. The decreases in Young's modulus, E, and hardness, H (both by about 40% at the irradiated surface) suggest amorphization beyond simple defect accumulation occurs under this irradiation condition.

  7. Surface Immobilization of Human Arginase-1 with an Engineered Ice Nucleation Protein Display System in E. coli.

    Directory of Open Access Journals (Sweden)

    Zhen Zhang

    Full Text Available Ice nucleation protein (INP is frequently used as a surface anchor for protein display in gram-negative bacteria. Here, MalE and TorA signal peptides, and three charged polypeptides, 6×Lys, 6×Glu and 6×Asp, were anchored to the N-terminus of truncated INP (InaK-N to improve its surface display efficiency for human Arginase1 (ARG1. Our results indicated that the TorA signal peptide increased the surface translocation of non-protein fused InaK-N and human ARG1 fused InaK-N (InaK-N/ARG1 by 80.7% and 122.4%, respectively. Comparably, the MalE signal peptide decreased the display efficiencies of both the non-protein fused InaK-N and InaK-N/ARG1. Our results also suggested that the 6×Lys polypeptide significantly increased the surface display efficiency of K6-InaK-N/ARG1 by almost 2-fold, while also practically abolishing the surface translocation of non-protein fused InaK-N, indicating the interesting roles of charged polypeptides in bacteria surface display systems. Cell surface-immobilized K6-InaK-N/ARG1 presented an arginase activity of 10.7 U/OD600 under the optimized conditions of 40°C, pH 10.0 and 1 mM Mn2+, which could convert more than 95% of L-Arginine (L-Arg to L-Ornithine (L-Orn in 16 hours. The engineered InaK-Ns expanded the INP surface display system, which aided in the surface immobilization of human ARG1 in E. coli cells.

  8. Dopaminergic neurotoxicant 6-OHDA induces oxidative damage through proteolytic activation of PKCδ in cell culture and animal models of Parkinson's disease

    International Nuclear Information System (INIS)

    Latchoumycandane, Calivarathan; Anantharam, Vellareddy; Jin, Huajun; Kanthasamy, Anumantha; Kanthasamy, Arthi


    The neurotoxicant 6-hydroxydopamine (6-OHDA) is used to investigate the cellular and molecular mechanisms underlying selective degeneration of dopaminergic neurons in Parkinson's disease (PD). Oxidative stress and caspase activation contribute to the 6-OHDA-induced apoptotic cell death of dopaminergic neurons. In the present study, we sought to systematically characterize the key downstream signaling molecule involved in 6-OHDA-induced dopaminergic degeneration in cell culture and animal models of PD. Treatment of mesencephalic dopaminergic neuronal N27 cells with 6-OHDA (100 μM) for 24 h significantly reduced mitochondrial activity and increased cytosolic cytochrome c, followed by sequential activation of caspase-9 and caspase-3. Co-treatment with the free radical scavenger MnTBAP (10 μM) significantly attenuated 6-OHDA-induced caspase activities. Interestingly, 6-OHDA induced proteolytic cleavage and activation of protein kinase C delta (PKCδ) was completely suppressed by treatment with a caspase-3-specific inhibitor, Z-DEVD-FMK (50 μM). Furthermore, expression of caspase-3 cleavage site-resistant mutant PKCδ D327A and kinase dead PKCδ K376R or siRNA-mediated knockdown of PKCδ protected against 6-OHDA-induced neuronal cell death, suggesting that caspase-3-dependent PKCδ promotes oxidative stress-induced dopaminergic degeneration. Suppression of PKCδ expression by siRNA also effectively protected N27 cells from 6-OHDA-induced apoptotic cell death. PKCδ cleavage was also observed in the substantia nigra of 6-OHDA-injected C57 black mice but not in control animals. Viral-mediated delivery of PKCδ D327A protein protected against 6-OHDA-induced PKCδ activation in mouse substantia nigra. Collectively, these results strongly suggest that proteolytic activation of PKCδ is a key downstream event in dopaminergic degeneration, and these results may have important translational value for development of novel treatment strategies for PD.

  9. In vivo metabolism of the methyl homologues of delta-8-tetrahydrocannabinol, delta-9-tetrahydrocannabinol and abn-delta-8-tetrahydrocannabinol in the mouse. (United States)

    Brown, N K; Harvey, D J


    Methyl-delta-8-tetrahydrocannabinol (methyl-delta-8-THC), methyl-delta-9-THC and abn-methyl-delta-8-THC were synthesized by condensation of orcinol and (1S)-cis-verbenol and were administered to male Charles River CD-1 mice. Extracted hepatic metabolites were isolated by chromatography on Sephadex LH-20 and examined by gas chromatography/mass spectrometry as trimethylsilyl (TMS), (2H9)TMS and methyl ester/TMS derivatives. In addition, metabolic fractions were reduced with lithium aluminium deuteride to convert carboxylic acids to alcohols for structural correlation. Metabolites from methyl-delta-8-THC were similar with respect to the positions substituted to those produced by higher homologues; the major metabolite was methyl-delta-8-THC-11-oic acid. abn-Methyl-delta-8-THC was metabolized in a different manner. The location of the aromatic methyl group at the position adjacent to ring fusion appeared to inhibit metabolism at C(11) to a considerable extent and also to reduce the amount of the resulting alcohol from being oxidized to a carboxylic acid. This caused other metabolic pathways to become dominant, with the result that a compound containing a hydroxy group at the gem-methyl position was the major metabolite. Hydroxylation at this position has not been confirmed with any other cannabinoid, although it is thought to result in trace concentrations of hydroxy metabolites from some compounds. Metabolism of methyl-delta-9-THC was also similar to that of the higher homologues, with the exception that less metabolism occurred at C(8) and a higher percentage of the total metabolic fraction was accounted for by the 11-oic acid metabolite. Minor metabolites were mainly dihydroxy compounds and hydroxylated derivatives of delta-9-THC-11-oic acid.

  10. Phenotypic expressions of CCR5-Delta 32/Delta 32 homozygosity

    NARCIS (Netherlands)

    Nguyen, GT; Carrington, M; Beeler, JA; Dean, M; Aledort, LM; Blatt, PM; Cohen, AR; DiMichele, D; Eyster, ME; Kessler, CM; Konkle, B; Leissinger, C; Luban, N; O'Brien, SJ; Goedert, JJ; O'Brien, TR


    Objective: As blockade of CC-chemokine receptor 5 (CCR5) has been proposed as therapy for HIV-1, we examined whether the CCR5-Delta 32/Delta 32 homozygous genotype has phenotypic expressions other than those related to HIV-1. Design: Study subjects were white homosexual men or men with hemophilia

  11. Novel layered perovskite GdBaCoFeO{sub 5+{delta}} as a potential cathode for proton-conducting solid oxide fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Hanping; Xue, Xingjian [Department of Mechanical Engineering, University of South Carolina, Columbia, SC 29208 (United States)


    While cobalt-containing perovskite-type cathode materials facilitate the activation of oxygen reduction, they also suffer from problems like poor chemical stability in CO{sub 2}, high thermal expansion coefficients, etc. Partial B site substitution with Fe element is expected to be able to mitigate these problems while keeping high catalyst performance. In this paper, a layered perovskite GdBaCoFeO{sub 5+{delta}} (GBCF) was developed as a cathode material for protonic ceramic membrane fuel cells (PCMFCs) based on proton-conducting electrolyte of stable BaZr{sub 0.1}Ce{sub 0.7}Y{sub 0.2}O{sub 3-{delta}} (BZCY7). The button cells of Ni-BZCY7 vertical stroke BZCY7 vertical stroke GBCF were fabricated and tested from 600 to 700 C with humidified H{sub 2} ({proportional_to}3% H{sub 2}O) as a fuel and ambient oxygen as oxidant. An open-circuit potential of 1.002 V, maximum power density of 482 mW cm{sup -2}, and a low electrode polarization resistance of 0.11 {omega}cm{sup 2} were achieved at 700 C. The experimental results indicated that the layered perovskite GBCF is a good candidate for cathode material, while the developed Ni-BZCY7 vertical stroke BZCY7 vertical stroke GBCF cell is a promising functional material system for intermediate temperature solid oxide fuel cells. (author)

  12. ( sup 3 H)(D-PEN sup 2 , D-PEN sup 5 ) enkephalin binding to delta opioid receptors on intact neuroblastoma-glioma (NG 108-15) hybrid cells

    Energy Technology Data Exchange (ETDEWEB)

    Knapp, R.J.; Yamamura, H.I. (Univ. of Arizona College of Medicine, Tucson (USA))


    ({sup 3}H)(D-Pen{sup 2}, D-Pen{sup 5})enkephalin binding to intact NG 108-15 cells has been measured under physiological conditions of temperature and medium. The dissociation constant, receptor density, and Hill slope values measured under these conditions are consistent with values obtained by others using membranes prepared from these cells. Kinetic analysis of the radioligand binding to these cells show biphasic association and monophasic dissociation processes suggesting the presence of different receptor affinity states for the agonist. The data show that the binding affinity of ({sup 3}H)(D-Pen{sup 2}, D-Pen{sup 5})enkephalin under physiological conditions is not substantially different to that measured in 50 mM Tris buffer using cell membrane fractions. Unlike DPDPE, the {mu} opioid agonists morphine, normorphine, PL-17, and DAMGO, have much lower affinity for the {delta} receptor measured under these conditions than is observed by studies using 50 mM Tris buffer. The results described here suggest that this assay may serve as a useful model of {delta} opioid receptor binding in vivo.

  13. Computerized microfluidic cell culture using elastomeric channels and Braille displays. (United States)

    Gu, Wei; Zhu, Xiaoyue; Futai, Nobuyuki; Cho, Brenda S; Takayama, Shuichi


    Computer-controlled microfluidics would advance many types of cellular assays and microscale tissue engineering studies wherever spatiotemporal changes in fluidics need to be defined. However, this goal has been elusive because of the limited availability of integrated, programmable pumps and valves. This paper demonstrates how a refreshable Braille display, with its grid of 320 vertically moving pins, can power integrated pumps and valves through localized deformations of channel networks within elastic silicone rubber. The resulting computerized fluidic control is able to switch among: (i) rapid and efficient mixing between streams, (ii) multiple laminar flows with minimal mixing between streams, and (iii) segmented plug-flow of immiscible fluids within the same channel architecture. The same control method is used to precisely seed cells, compartmentalize them into distinct subpopulations through channel reconfiguration, and culture each cell subpopulation for up to 3 weeks under perfusion. These reliable microscale cell cultures showed gradients of cellular behavior from C2C12 myoblasts along channel lengths, as well as differences in cell density of undifferentiated myoblasts and differentiation patterns, both programmable through different flow rates of serum-containing media. This technology will allow future microscale tissue or cell studies to be more accessible, especially for high-throughput, complex, and long-term experiments. The microfluidic actuation method described is versatile and computer programmable, yet simple, well packaged, and portable enough for personal use.

  14. Levels of soluble delta-like ligand 1 in the serum and cerebrospinal fluid of tuberculous meningitis patients

    Institute of Scientific and Technical Information of China (English)

    Jinghong Li; Jinyi Li; Yanjie Jia


    In this study, the levels of soluble delta-like ligand 1 in cerebrospinal fluid and serum of 50 patients with tuberculous meningitis, 30 patients with viral meningitis, 20 patients with purulent meningitis and 40 subjects without central nervous system disease were determined using an enzyme-linked immunosorbent assay. The mean levels of soluble delta-like ligand 1 in both cerebrospinal fluid and serum from patients with tuberculous meningitis were significantly higher compared with those from patients with viral meningitis or purulent meningitis or from subjects without central nervous system disease. Meanwhile, the level of soluble delta-like ligand 1 gradually decreased as tuberculous meningitis patients recovered. If patients deteriorated after treatment, the level of soluble delta-like ligand 1 in cerebrospinal fluid gradually increased. There was no correlation between the level of soluble delta-like ligand 1 and the protein level/cell number in cerebrospinal fluid. Our findings in-dicate that the levels of soluble delta-like ligand 1 in cerebrospinal fluid and serum are reliable markers for the diagnosis of tuberculous meningitis and for monitoring treatment progress. At the same time, this index is not influenced by protein levels or cell numbers in cerebrospinal fluid.

  15. Experimental investigation of channel avulsion frequency on river deltas under rising sea levels (United States)

    Silvestre, J.; Chadwick, A. J.; Steele, S.; Lamb, M. P.


    River deltas are low-relief landscapes that are socioeconomically important; they are home to over half a billion people worldwide. Many deltas are built by cycles of lobe growth punctuated by abrupt channel shifts, or avulsions, which often reoccur at a similar location and with a regular frequency. Previous experimental work has investigated the effect of hydrodynamic backwater in controlling channel avulsion location and timing on deltas under constant sea level conditions, but it is unclear how sea-level rise impacts avulsion dynamics. We present results from a flume experiment designed to isolate the role of relative sea-level rise on the evolution of a backwater-influenced delta. The experiment was conducted in the river-ocean facility at Caltech, where a 7m long, 14cm wide alluvial river drains into a 6m by 3m "ocean" basin. The experimental delta grew under subcritical flow, a persistent backwater zone, and a range of sea level rise rates. Without sea level rise, lobe progradation produced in-channel aggradation and periodic avulsions every 3.6 ± 0.9 hours, which corresponded to when channels aggraded to approximately one-half of their flow depth. With a modest rate of sea-level rise (0.25 mm/hr), we observed enhanced aggradation in the backwater zone, causing channels to aggrade more quickly and avulse more frequently (every 2.1 ± 0.6 hours). In future work, we expect further increases in the rate of relative sea-level rise to cause avulsion frequency to decrease as the delta drowns and the backwater zone retreats upstream. Experimental results can serve as tests of numerical models that are needed for hazard mitigation and coastal sustainability efforts on drowning deltas.

  16. Yeast surface displaying glucose oxidase as whole-cell biocatalyst: construction, characterization, and its electrochemical glucose sensing application. (United States)

    Wang, Hongwei; Lang, Qiaolin; Li, Liang; Liang, Bo; Tang, Xiangjiang; Kong, Lingrang; Mascini, Marco; Liu, Aihua


    The display of glucose oxidase (GOx) on yeast cell surface using a-agglutinin as an anchor motif was successfully developed. Both the immunochemical analysis and enzymatic assay showed that active GOx was efficiently expressed and translocated on the cell surface. Compared with conventional GOx, the yeast cell surface that displayed GOx (GOx-yeast) demonstrated excellent enzyme properties, such as good stability within a wide pH range (pH 3.5-11.5), good thermostability (retaining over 94.8% enzyme activity at 52 °C and 84.2% enzyme activity at 56 °C), and high d-glucose specificity. In addition, direct electrochemistry was achieved at a GOx-yeast/multiwalled-carbon-nanotube modified electrode, suggesting that the host cell of yeast did not have any adverse effect on the electrocatalytic property of the recombinant GOx. Thus, a novel electrochemical glucose biosensor based on this GOx-yeast was developed. The as-prepared biosensor was linear with the concentration of d-glucose within the range of 0.1-14 mM and a low detection limit of 0.05 mM (signal-to-noise ratio of S/N = 3). Moreover, the as-prepared biosensor is stable, specific, reproducible, simple, and cost-effective, which can be applicable for real sample detection. The proposed strategy to construct robust GOx-yeast may be applied to explore other oxidase-displaying-system-based whole-cell biocatalysts, which can find broad potential application in biosensors, bioenergy, and industrial catalysis.

  17. Migration in Deltas: An Integrated Analysis (United States)

    Nicholls, Robert J.; Hutton, Craig W.; Lazar, Attila; Adger, W. Neil; Allan, Andrew; Arto, Inaki; Vincent, Katharine; Rahman, Munsur; Salehin, Mashfiqus; Sugata, Hazra; Ghosh, Tuhin; Codjoe, Sam; Appeaning-Addo, Kwasi


    Deltas and low-lying coastal regions have long been perceived as vulnerable to global sea-level rise, with the potential for mass displacement of exposed populations. The assumption of mass displacement of populations in deltas requires a comprehensive reassessment in the light of present and future migration in deltas, including the potential role of adaptation to influence these decisions. At present, deltas are subject to multiple drivers of environmental change and often have high population densities as they are accessible and productive ecosystems. Climate change, catchment management, subsidence and land cover change drive environmental change across all deltas. Populations in deltas are also highly mobile, with significant urbanization trends and the growth of large cities and mega-cities within or adjacent to deltas across Asia and Africa. Such migration is driven primarily by economic opportunity, yet environmental change in general, and climate change in particular, are likely to play an increasing direct and indirect role in future migration trends. The policy challenges centre on the role of migration within regional adaptation strategies to climate change; the protection of vulnerable populations; and the future of urban settlements within deltas. This paper reviews current knowledge on migration and adaptation to environmental change to discern specific issues pertinent to delta regions. It develops a new integrated methodology to assess present and future migration in deltas using the Volta delta in Ghana, Mahanadi delta in India and Ganges-Brahmaputra-Meghna delta across India and Bangladesh. The integrated method focuses on: biophysical changes and spatial distribution of vulnerability; demographic changes and migration decision-making using multiple methods and data; macro-economic trends and scenarios in the deltas; and the policies and governance structures that constrain and enable adaptation. The analysis is facilitated by a range of

  18. Autostereoscopic display technology for mobile 3DTV applications (United States)

    Harrold, Jonathan; Woodgate, Graham J.


    Mobile TV is now a commercial reality, and an opportunity exists for the first mass market 3DTV products based on cell phone platforms with switchable 2D/3D autostereoscopic displays. Compared to conventional cell phones, TV phones need to operate for extended periods of time with the display running at full brightness, so the efficiency of the 3D optical system is key. The desire for increased viewing freedom to provide greater viewing comfort can be met by increasing the number of views presented. A four view lenticular display will have a brightness five times greater than the equivalent parallax barrier display. Therefore, lenticular displays are very strong candidates for cell phone 3DTV. Selection of Polarisation Activated Microlens TM architectures for LCD, OLED and reflective display applications is described. The technology delivers significant advantages especially for high pixel density panels and optimises device ruggedness while maintaining display brightness. A significant manufacturing breakthrough is described, enabling switchable microlenses to be fabricated using a simple coating process, which is also readily scalable to large TV panels. The 3D image performance of candidate 3DTV panels will also be compared using autostereoscopic display optical output simulations.

  19. Oxygen Reduction Kinetics of La2-xSrxNiO 4+delta Electrodes for Solid Oxide Fuel Cells (United States)

    Guan, Bo

    In the development of intermediate temperature solid oxide fuel cell (IT-SOFC), mixed ionic-electronic conductors (MIEC) have drawn big interests due to their both ionic and electronic species transport which can enlarge the 3-dimension of the cathode network. This thesis presents an investigation of MIEC of Ruddlesden-popper (RP) phases like K2NiF4 type La2NiO4+delta (LNO)-based oxides which have interesting transport, catalytic properties and suitable thermal expansion coefficients. The motivation of this present work is to further understand the fundamental of the effect of Sr doing on the oxygen reduction reaction (ORR) kinetics of LNO cathode. Porous symmetrical cells of La2-xSrxNiO4+delta (0≤x≤0.4) were fabricated and characterized by electrochemical impedance spectroscopy (EIS) in different PO2 from temperature range of 600˜800°C. The spectra were analyzed based on the impedance model introduced by Adler et al. The rate determining steps (RDS) for ORR were proposed and the responsible reasons were discussed. The overall polarization resistances of doped samples increase with Sr level. Surface oxygen exchange and bulk ionic diffusion co-control the ORR kinetics. With high Sr content (x=0.3, 0.4), oxygen ion transfer resistance between nickelate/electrolyte is observed. However for porous symmetrical cells it is hard to associate the resistance from EIS directly to each ORR elementary processes because of the difficulty in describing the microstructure of the porous electrode. The dense electrode configuration was adopted in this thesis. By using the dense electrode, the surface area, the thickness of electrode, the interface between electrode and electrolyte and lastly the 3PB are theoretically well-defined. Through this method, there is a good chance to distinguish the contribution of surface exchange from other processes. Dense and thin electrode layers in thickness of ˜40 mum are fabricated by using a novel spray modified pressing method. Negligible

  20. 9 CFR 101.6 - Cell cultures. (United States)


    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Cell cultures. 101.6 Section 101.6..., SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS DEFINITIONS § 101.6 Cell cultures. When used in conjunction with or in reference to cell cultures, which may be referred to as tissue cultures...

  1. Endothelial progenitor cells display clonal restriction in multiple myeloma

    International Nuclear Information System (INIS)

    Braunstein, Marc; Özçelik, Tayfun; Bağişlar, Sevgi; Vakil, Varsha; Smith, Eric LP; Dai, Kezhi; Akyerli, Cemaliye B; Batuman, Olcay A


    In multiple myeloma (MM), increased neoangiogenesis contributes to tumor growth and disease progression. Increased levels of endothelial progenitor cells (EPCs) contribute to neoangiogenesis in MM, and, importantly, covary with disease activity and response to treatment. In order to understand the mechanisms responsible for increased EPC levels and neoangiogenic function in MM, we investigated whether these cells were clonal by determining X-chromosome inactivation (XCI) patterns in female patients by a human androgen receptor assay (HUMARA). In addition, EPCs and bone marrow cells were studied for the presence of clonotypic immunoglobulin heavy-chain (IGH) gene rearrangement, which indicates clonality in B cells; thus, its presence in EPCs would indicate a close genetic link between tumor cells in MM and endothelial cells that provide tumor neovascularization. A total of twenty-three consecutive patients who had not received chemotherapy were studied. Screening in 18 patients found that 11 displayed allelic AR in peripheral blood mononuclear cells, and these patients were further studied for XCI patterns in EPCs and hair root cells by HUMARA. In 2 patients whose EPCs were clonal by HUMARA, and in an additional 5 new patients, EPCs were studied for IGH gene rearrangement using PCR with family-specific primers for IGH variable genes (V H ). In 11 patients, analysis of EPCs by HUMARA revealed significant skewing (≥ 77% expression of a single allele) in 64% (n = 7). In 4 of these patients, XCI skewing was extreme (≥ 90% expression of a single allele). In contrast, XCI in hair root cells was random. Furthermore, PCR amplification with V H primers resulted in amplification of the same product in EPCs and bone marrow cells in 71% (n = 5) of 7 patients, while no IGH rearrangement was found in EPCs from healthy controls. In addition, in patients with XCI skewing in EPCs, advanced age was associated with poorer clinical status, unlike patients whose EPCs had random XCI

  2. The geographic spread of the CCR5 Delta32 HIV-resistance allele.

    Directory of Open Access Journals (Sweden)

    John Novembre


    Full Text Available The Delta32 mutation at the CCR5 locus is a well-studied example of natural selection acting in humans. The mutation is found principally in Europe and western Asia, with higher frequencies generally in the north. Homozygous carriers of the Delta32 mutation are resistant to HIV-1 infection because the mutation prevents functional expression of the CCR5 chemokine receptor normally used by HIV-1 to enter CD4+ T cells. HIV has emerged only recently, but population genetic data strongly suggest Delta32 has been under intense selection for much of its evolutionary history. To understand how selection and dispersal have interacted during the history of the Delta32 allele, we implemented a spatially explicit model of the spread of Delta32. The model includes the effects of sampling, which we show can give rise to local peaks in observed allele frequencies. In addition, we show that with modest gradients in selection intensity, the origin of the Delta32 allele may be relatively far from the current areas of highest allele frequency. The geographic distribution of the Delta32 allele is consistent with previous reports of a strong selective advantage (>10% for Delta32 carriers and of dispersal over relatively long distances (>100 km/generation. When selection is assumed to be uniform across Europe and western Asia, we find support for a northern European origin and long-range dispersal consistent with the Viking-mediated dispersal of Delta32 proposed by G. Lucotte and G. Mercier. However, when we allow for gradients in selection intensity, we estimate the origin to be outside of northern Europe and selection intensities to be strongest in the northwest. Our results describe the evolutionary history of the Delta32 allele and establish a general methodology for studying the geographic distribution of selected alleles.

  3. CCR6+ Th cell distribution differentiates systemic lupus erythematosus patients based on anti-dsDNA antibody status. (United States)

    Zhong, Wei; Jiang, Zhenyu; Wu, Jiang; Jiang, Yanfang; Zhao, Ling


    Systemic lupus erythematosus (SLE) disease has been shown to be associated with the generation of multiple auto-antibodies. Among these, anti-dsDNA antibodies (anti-DNAs) are specific and play a pathogenic role in SLE. Indeed, anti-DNA + SLE patients display a worse disease course. The generation of these pathogenic anti-DNAs has been attributed to the interaction between aberrant T helper (Th) cells and autoimmune B cells. Thus, in this study we have investigated whether CCR6 + Th cells have the ability to differentiate SLE patients based on anti-DNA status, and if their distribution has any correlation with disease activity. We recruited 25 anti-DNA + and 25 anti-DNA - treatment-naive onset SLE patients, matched for various clinical characteristics in our nested matched case-control study. CCR6 + Th cells and their additional subsets were analyzed in each patient by flow cytometry. Anti-DNA + SLE patients specifically had a higher percentage of Th cells expressing CCR6 and CXCR3. Further analysis of CCR6 + Th cell subsets showed that anti-DNA + SLE patients had elevated proportions of Th9, Th17, Th17.1 and CCR4/CXCR3 double-negative (DN) cells. However, the proportions of CCR6 - Th subsets, including Th1 and Th2 cells, did not show any association with anti-DNA status. Finally, we identified a correlation between CCR6 + Th subsets and clinical indicators, specifically in anti-DNA + SLE patients. Our data indicated that CCR6 + Th cells and their subsets were elevated and correlated with disease activity in anti-DNA + SLE patients. We speculated that CCR6 + Th cells may contribute to distinct disease severity in anti-DNA + SLE patients.

  4. Mystery of the delta(980)

    International Nuclear Information System (INIS)

    Cahn, R.N.; Landshoff, P.V.


    The apparent conflict between the dominance of the decay delta->etaπ in D->deltaπ and its absence in iota->deltaπ is analyzed. Explicit models are presented in which the nearby Kanti K threshold plays an important role in resolving the conflict. (orig.)

  5. Effects of recharge and discharge on delta2H and delta18O composition and chloride concentration of high arsenic/fluoride groundwater from the Datong Basin, northern China. (United States)

    Xie, Xianjun; Wang, Yanxin; Su, Chunli; Duan, Mengyu


    To better understand the effects of recharge and discharge on the hydrogeochemistry of high levels of arsenic (As) and fluoride (F) in groundwater, environmental isotopic composition (delta2H and delta18O) and chloride (Cl) concentrations were analyzed in 29 groundwater samples collected from the Datong Basin. High arsenic groundwater samples (As > 50 micog/L) were found to be enriched in lighter isotopic composition that ranged from -92 to -78 per thousand for deuterium (delta2H) and from -12.5 to -9.9 per thousand for oxygen-18 (delta18O). High F-containing groundwater (F > 1 mg/L) was relatively enriched in heavier isotopic composition and varied from -90 to -57 per thousand and from -12.2 to -6.7 per thousand for delta2H and delta18O, respectively. High chloride concentrations and delta18O values were primarily measured in groundwater samples from the northern and southwestern portions of the study area, indicating the effect of evaporation on groundwater. The observation of relatively homogenized and low delta18O values and chloride concentrations in groundwater samples from central part of the Datong Basin might be a result of fast recharge by irrigation returns, which suggests that irrigation using arsenic-contaminated groundwater affected the occurrence of high arsenic-containing groundwater in the basin.

  6. Maternal Adaptive Immune Cells in Decidua Parietalis Display a More Activated and Coinhibitory Phenotype Compared to Decidua Basalis

    Directory of Open Access Journals (Sweden)

    Martin Solders


    Full Text Available The maternal part of the placenta, the decidua, consists of maternal immune cells, decidual stromal cells, and extravillous fetal trophoblasts. In a successful pregnancy, these cell compartments interact to provide an intricate balance between fetal tolerance and antimicrobial defense. These processes are still poorly characterized in the two anatomically different decidual tissues, basalis and parietalis. We examined immune cells from decidua basalis and parietalis from term placentas (n=15 with flow cytometry. By using multivariate discriminant analysis, we found a clear separation between the two decidual compartments based on the 81 investigated parameters. Decidua parietalis lymphocytes displayed a more activated phenotype with a higher expression of coinhibitory markers than those isolated from basalis and contained higher frequencies of T regulatory cells. Decidua basalis contained higher proportions of monocytes, B cells, and mucosal-associated invariant T (MAIT cells. The basalis B cells were more immature, and parietalis MAIT cells showed a more activated phenotype. Conventional T cells, NK cells, and MAIT cells from both compartments potently responded with the production of interferon-γ and/or cytotoxic molecules in response to stimulation. To conclude, leukocytes in decidua basalis and parietalis displayed remarkable phenotypic disparities, indicating that the corresponding stromal microenvironments provide different immunoregulatory signals.

  7. RGD peptide-displaying M13 bacteriophage/PLGA nanofibers as cell-adhesive matrices for smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Yong Cheol; Lee, Jong Ho; Jin, Oh Seong; Lee, Eun Ji; Jin, Lin Hua; Kim, Chang Seok; Hong, Suck Won; Han, Dong Wook; Kim, Chun Tae; Oh, Jin Woo [Pusan National University, Busan (Korea, Republic of)


    Extracellular matrices (ECMs) are network structures that play an essential role in regulating cellular growth and differentiation. In this study, novel nanofibrous matrices were fabricated by electrospinning M13 bacteriophage and poly(lactic-co-glycolic acid) (PLGA) and were shown to be structurally and functionally similar to natural ECMs. A genetically-engineered M13 bacteriophage was constructed to display Arg-Gly-Asp (RGD) peptides on its surface. The physicochemical properties of RGD peptide-displaying M13 bacteriophage (RGD-M13 phage)/PLGA nanofibers were characterized by using scanning electron microscopy and Fourier-transform infrared spectroscopy. We used immunofluorescence staining to confirm that M13 bacteriophages were homogenously distributed in RGD-M13 phage/PLGA matrices. Furthermore, RGD-M13 phage/PLGA nanofibrous matrices, having excellent biocompatibility, can enhance the behaviors of vascular smooth muscle cells. This result suggests that RGD-M13 phage/PLGA nanofibrous matrices have potentials to serve as tissue engineering scaffolds.

  8. Versatile microbial surface-display for environmental remediation and biofuels production

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Cindy H.; Mulchandani, Ashok; Chen, wilfred


    Surface display is a powerful technique that utilizes natural microbial functional components to express proteins or peptides on the cell exterior. Since the reporting of the first surface-display system in the mid-1980s, a variety of new systems have been reported for yeast, Gram-positive and Gram-negative bacteria. Non-conventional display methods are emerging, eliminating the generation of genetically modified microorganisms. Cells with surface display are used as biocatalysts, biosorbents and biostimulants. Microbial cell-surface display has proven to be extremely important for numerous applications ranging from combinatorial library screening and protein engineering to bioremediation and biofuels production.

  9. Niger Delta Development Commission and Sustainable ...

    African Journals Online (AJOL)

    Niger Delta Development Commission and Sustainable Development of Niger Delta Region of Nigeria: The Case of Rivers State. Goddey Wilson. Abstract. The study is on Niger Delta Development Commission and sustainable development of Niger Delta region of Nigeria, the case of Rivers State. The main objective of the ...

  10. Murine FATP alleviates growth and biochemical deficiencies of yeast fat1Delta strains

    DEFF Research Database (Denmark)

    Dirusso, C C; Connell, E J; Færgeman, Nils J.


    following incubation of the cells with exogenous oleate. Expression of either Fat1p or murine FATP from a plasmid in a fat1Delta strain restored these phenotypic and biochemical deficiencies. Fat1p and FATP restored growth of fat1Delta cells in the presence of cerulenin and under hypoxic conditions....... Furthermore, fatty-acid transport was restored and was found to be chain length specific: octanoate, a medium-chain fatty acid was transported in a Fat1p- and FATP-independent manner while the long-chain fatty acids myristate, palmitate, and oleate required either Fat1p or FATP for maximal levels of transport....... Lignoceryl CoA synthetase activities were restored to wild-type levels in fat1Delta strains expressing either Fat1p or FATP. Fat1p or FATP also restored wild-type levels of beta-oxidation of exogenous long-chain fatty acids. These data show that Fat1p and FATP are functionally equivalent when expressed...

  11. Large old trees influence patterns of delta13C and delta15N in forests. (United States)

    Weber, Pascale; Bol, Roland; Dixon, Liz; Bardgett, Richard D


    Large old trees are the dominant primary producers of native pine forest, but their influence on spatial patterns of soil properties and potential feedback to tree regeneration in their neighbourhood is poorly understood. We measured stable isotopes of carbon (delta(13)C) and nitrogen (delta(15)N) in soil and litter taken from three zones of influence (inner, middle and outer zone) around the trunk of freestanding old Scots pine (Pinus sylvestris L.) trees, to determine the trees' influence on below-ground properties. We also measured delta(15)N and delta(13)C in wood cores extracted from the old trees and from regenerating trees growing within their three zones of influence. We found a significant and positive gradient in soil delta(15)N from the inner zone, nearest to the tree centre, to the outer zone beyond the tree crown. This was probably caused by the higher input of (15)N-depleted litter below the tree crown. In contrast, the soil delta(13)C did not change along the gradient of tree influence. Distance-related trends, although weak, were visible in the wood delta(15)N and delta(13)C of regenerating trees. Moreover, the wood delta(15)N of small trees showed a weak negative relationship with soil N content in the relevant zone of influence. Our results indicate that large old trees control below-ground conditions in their immediate surroundings, and that stable isotopes might act as markers for the spatial and temporal extent of these below-ground effects. John Wiley & Sons, Ltd

  12. Biogas Production from Local Biomass Feedstock in the Mekong Delta and Its Utilization for a Direct Internal Reforming Solid Oxide Fuel Cell

    Directory of Open Access Journals (Sweden)

    Yusuke Shiratori


    Full Text Available Fuel-flexible solid oxide fuel cell (SOFC technologies are presently under study in a Vietnam-Japan international joint research project. The purpose of this project is to develop and demonstrate an SOFC-incorporated energy circulation system for the sustainable development of the Mekong Delta region. Lab-scale methane fermentation experiments in this study with a mixture of biomass feedstock collected in the Mekong Delta (shrimp pond sludge, bagasse, and molasses from sugar production recorded biogas production yield over 400 L kgVS−1 with H2S concentration below 50 ppm level. This real biogas was directly supplied to an SOFC without any fuel processing such as desulfurization, methane enrichment and pre-reforming, and stable power generation was achieved by applying paper-structured catalyst (PSC technology.

  13. An analytical framework for strategic delta planning : negotiating consent for long-term sustainable delta development

    NARCIS (Netherlands)

    Seijger, C.; Douven, W; Hermans, L.M.; Evers, J.; Phi, H. L.; Brunner, J.; Pols, L.; Ligtvoet, W.; Koole, S.; Slager, K.; Vermoolen, M.S.; Hasan, S.; Hoang, V. T M; van Halsema, G


    Sectoral planning on water, agriculture and urban development has not been able to prevent increased flood risks and environmental degradation in many deltas. Governments conceive strategic delta planning as a promising planning approach and develop strategic delta plans. Such plans are linked to

  14. delta-EF1 is a negative regulator of Ihh in the developing growth plate. (United States)

    Bellon, Ellen; Luyten, Frank P; Tylzanowski, Przemko


    Indian hedgehog (Ihh) regulates proliferation and differentiation of chondrocytes in the growth plate. Although the biology of Ihh is currently well documented, its transcriptional regulation is poorly understood. delta-EF1 is a two-handed zinc finger/homeodomain transcriptional repressor. Targeted inactivation of mouse delta-EF1 leads to skeletal abnormalities including disorganized growth plates, shortening of long bones, and joint fusions, which are reminiscent of defects associated with deregulation of Ihh signaling. Here, we show that the absence of delta-EF1 results in delayed hypertrophic differentiation of chondrocytes and increased cell proliferation in the growth plate. Further, we demonstrate that delta-EF1 binds to the putative regulatory elements in intron 1 of Ihh in vitro and in vivo, resulting in down-regulation of Ihh expression. Finally, we show that delta-EF1 haploinsufficiency leads to a postnatal increase in trabecular bone mass associated with enhanced Ihh expression. In summary, we have identified delta-EF1 as an in vivo negative regulator of Ihh expression in the growth plate.

  15. ETV6/RUNX1 Induces Reactive Oxygen Species and Drives the Accumulation of DNA Damage in B Cells

    Directory of Open Access Journals (Sweden)

    Hans-Peter Kantner


    Full Text Available The t(12;21(p13;q22 chromosomal translocation is the most frequent translocation in childhood B cell precursor-acute lymphoblastic leukemia and results in the expression of an ETV6/RUNX1 fusion protein. The frequency of ETV6/RUNX1 fusions in newborns clearly exceeds the leukemia rate revealing that additional events occur in ETV6/RUNX1-positive cells for leukemic transformation. Hitherto, the mechanisms triggering these second hits remain largely elusive. Thus, we generated a novel ETV6/RUNX1 transgenic mouse model where the expression of the fusion protein is restricted to CD19+ B cells. These animals harbor regular B cell development and lack gross abnormalities. We established stable pro-B cell lines carrying the ETV6/RUNX1 transgene that allowed us to investigate whether ETV6/RUNX1 itself favors the acquisition of second hits. Remarkably, these pro-B cell lines as well as primary bone marrow cells derived from ETV6/RUNX1 transgenic animals display elevated levels of reactive oxygen species (ROS as tested with ETV6/RUNX1 transgenic dihydroethidium staining. In line, intracellular phospho-histone H2AX flow cytometry and comet assay revealed increased DNA damage indicating that ETV6/RUNX1 expression enhances ROS. On the basis of our data, we propose the following model: the expression of ETV6/RUNX1 creates a preleukemic clone and leads to increased ROS levels. These elevated ROS favor the accumulation of secondary hits by increasing genetic instability and doublestrand breaks, thus allowing preleukemic clones to develop into fully transformed leukemic cells.

  16. Generation and characterization of Dyt1 DeltaGAG knock-in mouse as a model for early-onset dystonia. (United States)

    Dang, Mai T; Yokoi, Fumiaki; McNaught, Kevin St P; Jengelley, Toni-Ann; Jackson, Tehone; Li, Jianyong; Li, Yuqing


    A trinucleotide deletion of GAG in the DYT1 gene that encodes torsinA protein is implicated in the neurological movement disorder of Oppenheim's early-onset dystonia. The mutation removes a glutamic acid in the carboxy region of torsinA, a member of the Clp protease/heat shock protein family. The function of torsinA and the role of the mutation in causing dystonia are largely unknown. To gain insight into these unknowns, we made a gene-targeted mouse model of Dyt1 DeltaGAG to mimic the mutation found in DYT1 dystonic patients. The mutated heterozygous mice had deficient performance on the beam-walking test, a measure of fine motor coordination and balance. In addition, they exhibited hyperactivity in the open-field test. Mutant mice also showed a gait abnormality of increased overlap. Mice at 3 months of age did not display deficits in beam-walking and gait, while 6-month mutant mice did, indicating an age factor in phenotypic expression as well. While striatal dopamine and 4-dihydroxyphenylacetic acid (DOPAC) levels in Dyt1 DeltaGAG mice were similar to that of wild-type mice, a 27% decrease in 4-hydroxy, 3-methoxyphenacetic acid (homovanillic acid) was detected in mutant mice. Dyt1 DeltaGAG tissues also have ubiquitin- and torsinA-containing aggregates in neurons of the pontine nuclei. A sex difference was noticed in the mutant mice with female mutant mice exhibiting fewer alterations in behavioral, neurochemical, and cellular changes. Our results show that knocking in a Dyt1 DeltaGAG allele in mouse alters their motor behavior and recapitulates the production of protein aggregates that are seen in dystonic patients. Our data further support alterations in the dopaminergic system as a part of dystonia's neuropathology.

  17. Oral administration of human papillomavirus type 16 E7 displayed on Lactobacillus casei induces E7-specific antitumor effects in C57/BL6 mice. (United States)

    Poo, Haryoung; Pyo, Hyun-Mi; Lee, Tae-Young; Yoon, Sun-Woo; Lee, Jong-Soo; Kim, Chul-Joong; Sung, Moon-Hee; Lee, Seung-Hoon


    The mounting of a specific immune response against the human papillomavirus type 16 E7 protein (HPV16 E7) is important for eradication of HPV16 E7-expressing cancer cells from the cervical mucosa. To induce a mucosal immune response by oral delivery of the E7 antigen, we expressed the HPV16 E7 antigen on the surface of Lactobacillus casei by employing a novel display system in which the poly-gamma-glutamic acid (gamma-PGA) synthetase complex A (PgsA) from Bacillus subtilis (chungkookjang) was used as an anchoring motif. After surface expression of the HPV16 E7 protein was confirmed by Western blot, flow cytometry and immunofluorescence microscopy, mice were orally inoculated with L. casei-PgsA-E7. E7-specific serum IgG and mucosal IgA productions were enhanced after oral administration and significantly enhanced after boosting. Systemic and local cellular immunities were significantly increased after boosting, as shown by increased counts of lymphocytes (SI = 9.7 +/- 1.8) and IFN-gamma secreting cells [510 +/- 86 spot-forming cells/10(6)cells] among splenocytes and increased IFN-gamma in supernatants of vaginal lymphocytes. Furthermore, in an E7-based mouse tumor model, animals receiving orally administered L. casei-PgsA-E7 showed reduced tumor size and increased survival rate versus mice receiving control (L. casei-PgsA) immunization. These results collectively indicate that the oral administration of E7 displayed on lactobacillus induces cellular immunity and antitumor effects in mice. Copyright 2006 Wiley-Liss, Inc.

  18. Catalyzing action towards the sustainability of deltas: deltas as integrated socio-ecological systems and sentinels of regional and global change (United States)

    Foufoula-Georgiou, E.; Tessler, Z. D.; Brondizio, E.; Overeem, I.; Renaud, F.; Sebesvari, Z.; Nicholls, R. J.; Anthony, E.


    Deltas are highly dynamic and productive environments: they are food baskets of the world, home to biodiverse and rich ecosystems, and they play a central role in food and water security. However, they are becoming increasingly vulnerable to risks arising from human activities, land subsidence, regional water management, global sea-level rise, and climate extremes. Our Belmont Forum DELTAS project (BF-DELTAS: Catalyzing actions towards delta sustainability) encompasses an international network of interdisciplinary research collaborators with focal areas in the Mekong, Ganges Brahmaputra, and the Amazon deltas. The project is organized around five main modules: (1) developing an analytical framework for assessing delta vulnerability and scenarios of change (Delta-SRES), (2) developing an open-acess, science-based integrative modeling framework for risk assessment and decision support (Delta-RADS), (3) developing tools to support quantitative mapping of the bio-physical and socio-economic environments of deltas and consolidate bio-physical and social data within shared data repositories (Delta-DAT), (4) developing Global Delta Vulnerability Indices (Delta-GDVI) that capture current and projected scenarios for major deltas around the world , and (5) collaborating with regional stakeholders to put the science, modeling, and data into action (Delta-ACT). In this talk, a research summary will be presented on three research domains around which significant collaborative work was developed: advancing biophysical classification of deltas, understanding deltas as coupled socio-ecological systems, and analyzing and informing social and environmental vulnerabilities in delta regions.

  19. X-ray diffraction study of delta-stabilized plutonium alloys under pressure

    Energy Technology Data Exchange (ETDEWEB)

    Faure, Ph, E-mail: philippe.faure@cea.f [CEA, Valduc, F-21120 Is-sur-Tille (France); Genestier, C. [CEA, Valduc, F-21120 Is-sur-Tille (France)


    Previous extensive studies of the delta -> alpha'-phase transformation induced by temperature and/or by pressure in delta-stabilized plutonium alloys indicate strong dependence on parameters such as solute type, solute distribution, chemical impurities, kinetics, thermodynamic path.... The present paper reports results obtained on two Pu-2.3at.%Ga binary alloys differing by solute homogenization treatment and studied under pressure by in situ by X-ray diffraction in diamond anvil cells. The gamma'-phase appears as an intermediate phase during the delta -> alpha'-phase transformation. In cored samples, unexpanded alpha'-phase is formed at the beginning of the transformation, from domains with low solute content, and expanded alpha'-phase subsequently forms (from domains with higher solute content) as the transformation progresses with the pressure increase.

  20. Role of T cell receptor delta gene in susceptibility to celiac disease. (United States)

    Roschmann, E; Wienker, T F; Volk, B A


    There is a strong genetic influence on the susceptibility to celiac disease. Although in the vast majority of patients with celiac disease, the HLA-DQ(alpha1*0501, beta1*0201) heterodimer encoded by the alleles HLA-DQA1*0501 and HLA-DQB1*0201 seems to confer the primary disease susceptibility, it cannot be excluded that other genes contribute to disease susceptibility, as indicated by the difference in concordance rates between monozygotic twins and HLA identical siblings (70% vs. 30%). Obviously other genes involved in the genetic control of T cell mediated immune response could potentially influence susceptibility to celiac disease. The density of T cells using the gammadelta T cell receptor (TCR) is considerably increased in the jejunal epithelium of patients with celiac disease, an abnormality considered to be specific for celiac disease. This suggests an involvement of gammadelta T cells in the pathogenesis of the disease. To ascertain whether the TCR delta (TCRD) gene contributes to celiac disease susceptibility we carried out an association study and genetic linkage analysis using a highly polymorphic microsatellite marker at the TCRD locus on chromosome 14q11.2. The association study demonstrated no significant difference in allele frequencies of the TCRD gene marker between celiac disease patients and controls; accordingly, the relative risk estimates did not reach the level of statistical significance. In the linkage analysis, performed in 23 families, the logarithm of the odds (LOD) scores calculated for celiac disease versus the TCRD gene marker excluded linkage, suggesting that there is no determinant contributing to celiac disease status at or 5 cM distant to the analyzed TCRD gene marker. In conclusion, the results of the present study provide no evidence that the analyzed TCRD gene contributes substantially to celiac disease susceptibility.

  1. BaZr{sub 0.1}Ce{sub 0.7}Y{sub 0.1}Yb{sub 0.1}O{sub 3-{delta}} electrolyte-based solid oxide fuel cells with cobalt-free PrBaFe{sub 2}O{sub 5+{delta}} layered perovskite cathode

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Hanping; Xue, Xingjian [Department of Mechanical Engineering, University of South Carolina, Columbia, SC 29208 (United States)


    A new anode-supported SOFC material system Ni-BZCYYb vertical stroke BZCYYb vertical stroke PBFO is investigated, in which a cobalt-free layered perovskite oxide, PrBaFe{sub 2}O{sub 5+{delta}} (PBFO), is synthesized and employed as a novel cathode while the synthesized BZCYYb is used as an electrolyte. The cell is fabricated by a simple dry-pressing/co-sintering process. The cell is tested and characterized under intermediate temperature range from 600 to 700 C with humified H{sub 2} ({proportional_to}3% H{sub 2}O) as fuel, ambient air as oxidant. The results show that the open-circuit potential of 1.006 V and maximal power density of 452 mW cm{sup -2} are achieved at 700 C. The polarization resistance of the electrodes is 0.18 {omega} cm{sup 2} at 700 C. Compared to BaZr{sub 0.1}Ce{sub 0.7}Y{sub 0.1}O{sub 3-{delta}}, the conductivity of co-doped barium zirconate-cerate BZCYYb is significantly improved. The ohmic resistance of single cell is 0.37 {omega} cm{sup 2} at 700 C. The results indicate that the developed Ni-BZCYYb vertical stroke BZCYYb vertical stroke PBFO cell is a promising functional material system for SOFCs. (author)

  2. WE-D-9A-03: CSDF: A Color Extension of the Grayscale Standard Display Function

    International Nuclear Information System (INIS)

    Kimpe, T; Marchessoux, C; Rostang, J; Piepers, B; Avanaki, A; Espig, K; Xthona, A


    Purpose: Use of color images in medical imaging has increased significantly the last few years. As of today there is no agreed standard on how color information needs to be visualized on medical color displays, resulting into large variability of color appearance and it making consistency and quality assurance a challenge. This paper presents a proposal for an extension of DICOM GSDF towards color. Methods: Visualization needs for several color modalities (multimodality imaging, nuclear medicine, digital pathology, quantitative imaging applications…) have been studied. On this basis a proposal was made for desired color behavior of color medical display systems and its behavior and effect on color medical images was analyzed. Results: Several medical color modalities could benefit from perceptually linear color visualization for similar reasons as why GSDF was put in place for greyscale medical images. An extension of the GSDF (Greyscale Standard Display Function) to color is proposed: CSDF (color standard display function). CSDF is based on deltaE2000 and offers a perceptually linear color behavior. CSDF uses GSDF as its neutral grey behavior. A comparison between sRGB/GSDF and CSDF confirms that CSDF significantly improves perceptual color linearity. Furthermore, results also indicate that because of the improved perceptual linearity, CSDF has the potential to increase perceived contrast of clinically relevant color features. Conclusion: There is a need for an extension of GSDF towards color visualization in order to guarantee consistency and quality. A first proposal (CSDF) for such extension has been made. Behavior of a CSDF calibrated display has been characterized and compared with sRGB/GSDF behavior. First results indicate that CSDF could have a positive influence on perceived contrast of clinically relevant color features and could offer benefits for quantitative imaging applications. Authors are employees of Barco Healthcare

  3. Heavy metals in system «Delta of Volga - Northern Caspian Sea

    Directory of Open Access Journals (Sweden)

    E. V. Ostrovscaya


    Full Text Available It is displayed that the composition of heavy metals compounds in water and suspensions in the area of marine and riverine waters mixing undergo natural changes due to sedimentation and transformation. The system “Volga Delta – North Caspian” as a geochemical barrier hampers the transfer of toxic heavy metals forms from the sea to the river, although the content of toxic iron and manganese forms at the marine border of coastal waters can reach up to 30% of total concentration.

  4. Whole-genome analysis of genetic recombination of hepatitis delta virus: molecular domain in delta antigen determining trans-activating efficiency. (United States)

    Chao, Mei; Lin, Chia-Chi; Lin, Feng-Ming; Li, Hsin-Pai; Iang, Shan-Bei


    Hepatitis delta virus (HDV) is the only animal RNA virus that has an unbranched rod-like genome with ribozyme activity and is replicated by host RNA polymerase. HDV RNA recombination was previously demonstrated in patients and in cultured cells by analysis of a region corresponding to the C terminus of the delta antigen (HDAg), the only viral-encoded protein. Here, a whole-genome recombination map of HDV was constructed using an experimental system in which two HDV-1 sequences were co-transfected into cultured cells and the recombinants were analysed by sequencing of cloned reverse transcription-PCR products. Fifty homologous recombinants with 60 crossovers mapping to 22 junctions were identified from 200 analysed clones. Small HDAg chimeras harbouring a junction newly detected in the recombination map were then constructed. The results further indicated that the genome-replication level of HDV was sensitive to the sixth amino acid within the N-terminal 22 aa of HDAg. Therefore, the recombination map established in this study provided a tool for not only understanding HDV RNA recombination, but also elucidating the related mechanisms, such as molecular elements responsible for the trans-activation levels of the small HDAg.

  5. Proton conducting solid oxide fuel cells with layered PrBa{sub 0.5}Sr{sub 0.5}Co{sub 2}O{sub 5+{delta}} perovskite cathode

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Hanping; Xue, Xingjian [Department of Mechanical Engineering, University of South Carolina, Columbia, SC 29208 (United States)


    BaZr{sub 0.1}Ce{sub 0.7}Y{sub 0.2}O{sub 3-{delta}} (BZCY7) exhibits adequate protonic conductivity as well as sufficient chemical and thermal stability over a wide range of SOFC operating conditions, while layered perovskite PrBa{sub 0.5}Sr{sub 0.5}Co{sub 2}O{sub 5+{delta}} (PBSC) has advanced electrochemical properties. This research fully takes advantage of these advanced properties and develops a novel protonic ceramic membrane fuel cell (PCMFC) of Ni-BZCY7 vertical stroke BZCY7 vertical stroke PBSC. Experimental results show that the cell may achieve the open-circuit potential of 1.005 V, the maximal power density of 520 mW cm{sup -2}, and a low electrode polarization resistance of 0.12 {omega}cm{sup 2} at 700 C. Increasing operating temperature leads to the decrease of total cell resistance, among which electrolyte resistance becomes increasingly dominant over polarization resistance. The results also indicate that PBSC perovskite cathode is a good candidate for intermediate temperature PCMFC development, while the developed Ni-BZCY7 vertical stroke BZCY7 vertical stroke PBSC cell is a promising functional material system for SOFCs. (author)


    Energy Technology Data Exchange (ETDEWEB)

    Hakim, Nabil Balnaves, Mike


    DELTA Diesel Engine Light Truck Application End of Contract Report DE-FC05-97-OR22606 EXECUTIVE SUMMARY This report is the final technical report of the Diesel Engine Light Truck Application (DELTA) program under contract DE-FC05-97-OR22606. During the course of this contract, Detroit Diesel Corporation analyzed, designed, tooled, developed and applied the ''Proof of Concept'' (Generation 0) 4.0L V-6 DELTA engine and designed the successor ''Production Technology Demonstration'' (Generation 1) 4.0L V-6 DELTA engine. The objectives of DELTA Program contract DE-FC05-97-OR22606 were to: Demonstrate production-viable diesel engine technologies, specifically intended for the North American LDT and SUV markets; Demonstrate emissions compliance with significant fuel economy advantages. With a clean sheet design, DDC produced the DELTA engine concept promising the following attributes: 30-50% improved fuel economy; Low cost; Good durability and reliability; Acceptable noise, vibration and harshness (NVH); State-of-the-art features; Even firing, 4 valves per cylinder; High pressure common rail fuel system; Electronically controlled; Turbocharged, intercooled, cooled EGR; Extremely low emissions via CLEAN Combustion{copyright} technology. To demonstrate the engine technology in the SUV market, DDC repowered a 1999 Dodge Durango with the DELTA Generation 0 engine. Fuel economy improvements were approximately 50% better than the gasoline engine replaced in the vehicle.

  7. Delta Morphodynamics Matters! Ecosystem Services, Poverty and Morphodynamic Change in the Ganges-Brahmaputra Mega-Delta (United States)

    Nicholls, R. J.; Adger, N.; Allan, A.; Darby, S. E.; Hutton, C.; Matthews, Z.; Rahman, M.; Whitehead, P. G.; Wolf, J.


    The world's deltas are probably the most vulnerable type of coastal environment, and they face multiple stresses in the coming decades. These stresses include, amongst others, local drivers due to land subsidence, population growth and urbanisation within the deltas, regional drivers due to changes in catchment management (e.g. upstream land use and dam construction), as well as global climate change impacts such as sea-level rise. At the same time, the ecosystem services of river deltas support high population densities, with around 14% of the global population inhabiting deltas. A large proportion of these people experience extremes of poverty and they are therefore severely exposed to vulnerability from environmental and ecological stress and degradation. In areas close to or below the poverty boundary, both subsistence and cash elements of the economy tend to rely disproportionately heavily on ecosystem services which underpin livelihoods. Therefore, to sustainably manage delta environments they must be viewed as complex social-environmental systems where change is only partially driven by physical drivers such as sea level rise and climate change, and human-induced development activities are also critical. Here we outline a new conceptual framework for the development of methods to understand and characterise the key drivers of change in ecosystem services that affect the environment and economic status of populous deltas, focusing specifically on the Ganges-Brahmaputra-Meghna (GBM) mega-delta. The GBM delta is characterised by densely populated coastal lowlands with significant poverty, with livelihoods supported to a large extent by natural ecosystems such as the Sunderbahns (the largest mangrove forest in the world). However, the GBM delta is under severe development pressure due to many growing cities. At present the importance of ecosystems services to poverty and livelihoods is poorly understood. This is due to due to the complexity of interactions

  8. (La{sub 0.74}Bi{sub 0.10}Sr{sub 0.16})MnO{sub 3-{delta}}-Ce{sub 0.8}Gd{sub 0.2}O{sub 2-{delta}} cathodes fabricated by ion-impregnating method for intermediate-temperature solid oxide fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Junliang; Wang, Shaorong; Wang, Zhenrong; Liu, Renzhu; Ye, Xiaofeng; Sun, Xiufu; Wen, Tinglian; Wen, Zhaoyin [Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai 200050 (China)


    Porous composite cathodes were fabricated by impregnating (La{sub 0.74}Bi{sub 0.10}Sr{sub 0.16})MnO{sub 3-{delta}} (LBSM) electronic conducting structure with the ionic conducting Ce{sub 0.8}Gd{sub 0.2}O{sub 2-{delta}} (GDC) phase. The ion impregnation of the GDC phase significantly enhanced the electrocatalytic activity of the LBSM electrodes for the O{sub 2} reduction reactions, and the ion-impregnated LBSM-GDC composite cathodes showed excellent performance. At 700 C, the value of the cathode polarization resistance (Rc) was only 0.097 {omega} cm{sup 2} for an ion-impregnated LBSM-GDC cathode, and the performance was gradually improved by increasing the loading of the impregnated GDC. For the performance testing of single cells, the maximum power density was 1036 mW cm{sup -2} at 700 C for a cell with the LBSM-GDC cathode. The results demonstrated the unique combination of the LBSM electronic conducting structure with high ionic conducting GDC phase was a valid method to improve the electrode performance, and the ion-impregnated LBSM-GDC was a promising composite cathode material for the intermediate-temperature solid oxide fuel cells. (author)

  9. Iodinated chlorin p6 copper complex induces anti-proliferative effect in oral cancer cells through elevation of intracellular reactive oxygen species. (United States)

    Sarbadhikary, Paromita; Dube, Alok


    We investigated the anticancer chemotoxicity of previously reported iodinated chlorin p 6 copper complex (ICp 6 -Cu), a novel chlorophyll derivative in which copper is attached to the side chain carboxylate groups via coordination. Human oral carcinoma cells NT8e, 4451 and the non-cancerous keratinocyte HaCaT cells were treated with ICp 6 -Cu for 48 h in dark and cell viability, proliferation and morphological alterations were examined. ICp 6 -Cu showed pronounced cytotoxicity in cancer cells with IC 50 ∼40 μM, whereas, the viability of HaCaT cells was not affected. Cell proliferation assay revealed that ICp 6 -Cu at IC 50 concentration led to complete inhibition of cell proliferation in both the cell lines. Cell morphology studied by confocal microscopy showed absence of cell death via necrosis or apoptosis. Instead, the treated cells displayed distinct features of non-apoptotic death such as highly vacuolated cytoplasm, lysosomal membrane permeabilization and damage to cytoskeleton F-actin filaments. In addition, ICp 6 -Cu treatment led to time dependent increase in the intracellular level of reactive oxygen species (ROS) and the cytotoxicity of ICp 6 -Cu was significantly inhibited by pre-treatment of cells with antioxidants (glutathione and trolox). These findings revealed that ICp 6 -Cu is a potent chemotoxic agent which can induce cytotoxic effect in cancer cells through elevation of intracellular ROS. It is suggested that ICp 6 -Cu may provide tumor selective chemotoxicity by exploiting difference of redox environment in normal and cancer cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Dynamic controls on shallow clinoform geometry: Mekong Delta, Vietnam (United States)

    Eidam, E. F.; Nittrouer, C. A.; Ogston, A. S.; DeMaster, D. J.; Liu, J. P.; Nguyen, T. T.; Nguyen, T. N.


    Compound deltas, composed of a subaerial delta plain and subaqueous clinoform, are common termini of large rivers. The transition between clinoform topset and foreset, or subaqueous rollover point, is located at 25-40-m water depth for many large tide-dominated deltas; this depth is controlled by removal of sediment from the topset by waves, currents, and gravity flows. However, the Mekong Delta, which has been classified as a mixed-energy system, has a relatively shallow subaqueous rollover at 4-6-m depth. This study evaluates dynamical measurements and seabed cores collected in Sep 2014 and Mar 2015 to understand processes of sediment transfer across the subaqueous delta, and evaluate possible linkages to geometry. During the southwest rainy monsoon (Sep 2014), high river discharge, landward return flow under the river plume, and regional circulation patterns facilitated limited sediment flux to the topset and foreset, and promoted alongshore flux to the northeast. Net observed sediment fluxes in Sep 2014 were landward, however, consistent with hypotheses about seasonal storage on the topset. During the northeast rainy monsoon, low river discharge and wind-driven currents facilitated intense landward and southwestward fluxes of sediment. In both seasons, bed shear velocities frequently exceeded the 0.01-0.02 m/s threshold of motion for sand, even in the absence of strong wave energy. Most sediment transport occurred at water depths 4 cm/yr at energy-limited, and thus rollover depths cannot be predicted solely by bed-stress distributions. In systems like the subaqueous Mekong Delta, direction of transport may have a key impact on morphology.

  11. 6′-Hydroxy Justicidin B Triggers a Critical Imbalance in Ca2+ Homeostasis and Mitochondrion-Dependent Cell Death in Human Leukemia K562 Cells

    Directory of Open Access Journals (Sweden)

    Jiaoyang Luo


    Full Text Available Justicia procumbens (J. procumbens is a traditional Chinese herbal medicine which was used for the treatment of fever, pain, and cancer. A compound 6′-hydroxy justicidin B (HJB isolated from J. procumbens exhibits promising biological properties. However, the mechanism of action and the in vivo behavior of HJB remain to be elucidated. In this study, we investigated the mechanism of action of HJB on human leukemia K562 cells and its pharmacokinetic properties in rats. The results demonstrated that HJB significantly inhibited the proliferation of K562 cells and promoted apoptosis. Besides, HJB resulted in decreased mitochondrial membrane potential deltaPSIm, increased the level of the calcium homeostasis regulator protein TRPC6 and cytosolic calcium. The activity of caspase-8, caspase-9 and the expression of p53 were significantly increased after treatment with HJB. Additionally, HJB has rapid absorption rate and relative long elimination t1/2, indicating a longer residence time in vivo. The results indicate that HJB inhibited the proliferation of K562 cells and induced apoptosis by affecting the function of mitochondria and calcium homeostasis to activate the p53 signaling pathway. The pharmacokinetic study of HJB suggested it is absorbed well and has moderate metabolism in vivo. These results present HJB as a potential novel alternative to standard human leukemia therapies.

  12. Refreshing Refreshable Braille Displays. (United States)

    Russomanno, Alexander; O'Modhrain, Sile; Gillespie, R Brent; Rodger, Matthew W M


    The increased access to books afforded to blind people via e-publishing has given them long-sought independence for both recreational and educational reading. In most cases, blind readers access materials using speech output. For some content such as highly technical texts, music, and graphics, speech is not an appropriate access modality as it does not promote deep understanding. Therefore blind braille readers often prefer electronic braille displays. But, these are prohibitively expensive. The search is on, therefore, for a low-cost refreshable display that would go beyond current technologies and deliver graphical content as well as text. And many solutions have been proposed, some of which reduce costs by restricting the number of characters that can be displayed, even down to a single braille cell. In this paper, we demonstrate that restricting tactile cues during braille reading leads to poorer performance in a letter recognition task. In particular, we show that lack of sliding contact between the fingertip and the braille reading surface results in more errors and that the number of errors increases as a function of presentation speed. These findings suggest that single cell displays which do not incorporate sliding contact are likely to be less effective for braille reading.

  13. Future Change to Tide-Influenced Deltas (United States)

    Nienhuis, Jaap H.; Hoitink, A. J. F. (Ton); Törnqvist, Torbjörn E.


    Tides tend to widen deltaic channels and shape delta morphology. Here we present a predictive approach to assess a priori the effect of fluvial discharge and tides on deltaic channels. We show that downstream channel widening can be quantified by the ratio of the tide-driven discharge and the fluvial discharge, along with a second metric representing flow velocities. A test of our new theory on a selection of 72 deltas globally shows good correspondence to a wide range of environments, including wave-dominated deltas, river-dominated deltas, and alluvial estuaries. By quantitatively relating tides and fluvial discharge to delta morphology, we offer a first-order prediction of deltaic change that may be expected from altered delta hydrology. For example, we expect that reduced fluvial discharge in response to dam construction will lead to increased tidal intrusion followed by enhanced tide-driven sediment import into deltas, with implications for navigation and other human needs.

  14. From Natural to Design River Deltas (United States)

    Giosan, Liviu


    Productive and biologically diverse, deltaic lowlands attracted humans since prehistory and may have spurred the emergence of the first urban civilizations. Deltas continued to be an important nexus for economic development across the world and are currently home for over half a billion people. But recently, under the double whammy of sea level rise and inland sediment capture behind dams, they have become the most threatened coastal landscape. Here I will address several deceptively simple questions to sketch some unexpected answers using example deltas from across the world from the Arctic to the Tropics, from the Danube to the Indus, Mississippi to Godavari and Krishna, Mackenzie to Yukon. What is a river delta? What is natural and what is not in a river delta? Are the geological and human histories of a delta important for its current management? Is maintaining a delta the same to building a new one? Can we design better deltas than Nature? These answers help us see clearly that survival of deltas in the next century depends on human intervention and is neither assured nor simple to address or universally applicable. Empirical observations on the hydrology, geology, biology and biochemistry of deltas are significantly lagging behind modeling capabilities endangering the applicability of numerical-based reconstruction solutions and need to be ramped up significantly and rapidly across the world.

  15. CARbodies: Human Antibodies Against Cell Surface Tumor Antigens Selected From Repertoires Displayed on T Cell Chimeric Antigen Receptors

    Directory of Open Access Journals (Sweden)

    Vanesa Alonso-Camino


    Full Text Available A human single-chain variable fragment (scFv antibody library was expressed on the surface of human T cells after transduction with lentiviral vectors (LVs. The repertoire was fused to a first-generation T cell receptor ζ (TCRζ-based chimeric antigen receptor (CAR. We used this library to isolate antibodies termed CARbodies that recognize antigens expressed on the tumor cell surface in a proof-of-principle system. After three rounds of activation-selection there was a clear repertoire restriction, with the emergence dominant clones. The CARbodies were purified from bacterial cultures as soluble and active proteins. Furthermore, to validate its potential application for adoptive cell therapy, human T cells were transduced with a LV encoding a second-generation costimulatory CAR (CARv2 bearing the selected CARbodies. Transduced human primary T cells expressed significant levels of the CARbodies-based CARv2 fusion protein on the cell surface, and importantly could be specifically activated, after stimulation with tumor cells. This approach is a promising tool for the generation of antibodies fully adapted to the display format (CAR and the selection context (cell synapse, which could extend the scope of current adoptive cell therapy strategies with CAR-redirected T cells.

  16. The Potential of Tiger Prawn Fry from Delta Mahakam, East Kalimantan Indonesia

    Directory of Open Access Journals (Sweden)

    Bob Suroso


    Full Text Available Normal 0 false false false IN X-NONE X-NONE Most of the life cycle of tiger prawns were estuarine (Delta Mahakam. In the juvenile stage life in estuarine and the adult stage in marine. The research objective is to assess the potential of the tiger prawn fry catches in the Mahakam Delta, as a source of tiger prawn fry in the Mahakam Delta area farms. Research using interviews and descriptive analysis through monitoring with fishermen. The results showed that the fry tiger prawn from the Delta Mahakam there on the beaches or the edge of the sea where the water is shallow and slightly brackish, as in the Delta Mahakam. Fry can be captured by using rumpon. Tiger prawns fry from Delta Mahakam durability is relatively higher than fry from the hatchery. However, the number and continuity of fry very limited because it depends on the season. Abundance of fry is determined by the number of larvae produced in the wild and their survival is greatly influenced by the availability of food. /* 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-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} Doi: 10.12777/ijse.6.1.43-46 [How to cite this article: Suroso, B., Hutabarat, J., and Afiati, N. (2013. The Potential of Tiger Prawn Fry from Delta Mahakam, East Kalimantan Indonesia, International Journal of Science and Engineering, 6(1,43-46. Doi: 10.12777/ijse.6.1.43-46

  17. Flexible Bistable Cholesteric Reflective Displays (United States)

    Yang, Deng-Ke


    Cholesteric liquid crystals (ChLCs) exhibit two stable states at zero field condition-the reflecting planar state and the nonreflecting focal conic state. ChLCs are an excellent candidate for inexpensive and rugged electronic books and papers. This paper will review the display cell structure,materials and drive schemes for flexible bistable cholesteric (Ch) reflective displays.

  18. Delta isobars in neutron stars

    Directory of Open Access Journals (Sweden)

    Pagliara Giuseppe


    Full Text Available The appearance of delta isobars in beta-stable matter is regulated by the behavior of the symmetry energy at densities larger than saturation density. We show that by taking into account recent constraints on the density derivative of the symmetry energy and the theoretical and experimental results on the excitations of delta isobars in nuclei, delta isobars are necessary ingredients for the equations of state used for studying neutron stars. We analyze the effect of the appearance of deltas on the structure of neutron stars: as in the case of hyperons, matter containing delta is too soft for allowing the existence of 2M⊙ neutron stars. Quark stars on the other hand, could reach very massive configurations and they could form from a process of conversion of hadronic stars in which an initial seed of strangeness appears through hyperons.

  19. High-yield production of a stable Vero cell-based vaccine candidate against the highly pathogenic avian influenza virus H5N1

    International Nuclear Information System (INIS)

    Zhou, Fangye; Zhou, Jian; Ma, Lei; Song, Shaohui; Zhang, Xinwen; Li, Weidong; Jiang, Shude; Wang, Yue; Liao, Guoyang


    Highlights: ► Vero cell-based HPAI H5N1 vaccine with stable high yield. ► Stable high yield derived from the YNVa H3N2 backbone. ► H5N1/YNVa has a similar safety and immunogenicity to H5N1delta. -- Abstract: Highly pathogenic avian influenza (HPAI) viruses pose a global pandemic threat, for which rapid large-scale vaccine production technology is critical for prevention and control. Because chickens are highly susceptible to HPAI viruses, the supply of chicken embryos for vaccine production might be depleted during a virus outbreak. Therefore, developing HPAI virus vaccines using other technologies is critical. Meeting vaccine demand using the Vero cell-based fermentation process has been hindered by low stability and yield. In this study, a Vero cell-based HPAI H5N1 vaccine candidate (H5N1/YNVa) with stable high yield was achieved by reassortment of the Vero-adapted (Va) high growth A/Yunnan/1/2005(H3N2) (YNVa) virus with the A/Anhui/1/2005(H5N1) attenuated influenza vaccine strain (H5N1delta) using the 6/2 method. The reassorted H5N1/YNVa vaccine maintained a high hemagglutination (HA) titer of 1024. Furthermore, H5N1/YNVa displayed low pathogenicity and uniform immunogenicity compared to that of the parent virus.

  20. Effect of pretreatment of hydrothermally processed rice straw with laccase-displaying yeast on ethanol fermentation

    Energy Technology Data Exchange (ETDEWEB)

    Nakanishi, Akihito; Bae, Jun Gu; Fukai, Kotaro; Tokumoto, Naoki; Kuroda, Kouichi; Ogawa, Jun; Shimizu, Sakayu; Ueda, Mitsuyoshi [Kyoto Univ. (Japan). Div. of Applied Life Sciences; Nakatani, Masato [Daiwa Kasei, Shiga (Japan)


    A gene encoding laccase I was identified and cloned from the white-rot fungus Trametes sp. Ha1. Laccase I contained 10 introns and an original secretion signal sequence. After laccase I without introns was prepared by overlapping polymerase chain reaction, it was inserted into expression vector pULD1 for yeast cell surface display. The oxidation activity of a laccase-I-displaying yeast as a whole-cell biocatalyst was examined with 2,2{sup '}-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS), and the constructed yeast showed a high oxidation activity. After the pretreatment of hydrothermally processed rice straw (HPRS) with laccase-I-displaying yeast with ABTS, fermentation was conducted with yeast codisplaying endoglucanase, cellobiohydrolase, and {beta}-glucosidase with HPRS. Fermentation of HPRS treated with laccase-I-displaying yeast was performed with 1.21-fold higher activities than those of HPRS treated with control yeast. The results indicated that pretreatment with laccase-I-displaying yeast with ABTS was effective for direct fermentation of cellulosic materials by yeast codisplaying endoglucanase, cellobiohydrolase, and {beta}-glucosidase. (orig.)

  1. Fabrication of an integrated {Delta}E-E-silicon detector by wafer bonding using cobalt disilicide

    Energy Technology Data Exchange (ETDEWEB)

    Thungstroem, G. [Mid-Sweden Univ., Sundsvall (Sweden). Dept. of Inf. Technol.]|[Royal Institute of Technology, Department of Electronics, Electrum 229, S-164 40 Kista (Sweden); Veldhuizen, E.J. van [Uppsala University, Department of Radiation Science, Box 535, S-751 21 Uppsala (Sweden); Westerberg, L. [Uppsala University, The Svedberg Laboratory, Box 533, S-751 21 Uppsala (Sweden); Norlin, L.-O. [Royal Institute of Technology, Department of Physics, Frescativaegen 24, S-104 05 Stockholm (Sweden); Petersson, C.S. [Royal Institute of Technology, Department of Electronics, Electrum 229, S-164 40 Kista (Sweden)


    The problem concerning mechanical stability of thin self-supporting {Delta}E detector in a {Delta}E-E semiconductor detector telescope, has been solved by integrating both detectors into one unit. We show here a low-cost method to integrate the detectors by wafer bonding using cobalt disilicide. The {Delta}E-detector has a thickness of 6.5 {mu}m and the E detector 290 {mu}m with an area of 24.8 mm{sup 2}. The system was characterized with secondary ion mass spectroscopy (SIMS), scanning electron microscopy (SEM), electrical measurement, particle measurement and two-dimensional electrical simulation. (orig.).

  2. Entropy and optimality in river deltas (United States)

    Tejedor, Alejandro; Longjas, Anthony; Edmonds, Douglas A.; Zaliapin, Ilya; Georgiou, Tryphon T.; Rinaldo, Andrea; Foufoula-Georgiou, Efi


    The form and function of river deltas is intricately linked to the evolving structure of their channel networks, which controls how effectively deltas are nourished with sediments and nutrients. Understanding the coevolution of deltaic channels and their flux organization is crucial for guiding maintenance strategies of these highly stressed systems from a range of anthropogenic activities. To date, however, a unified theory explaining how deltas self-organize to distribute water and sediment up to the shoreline remains elusive. Here, we provide evidence for an optimality principle underlying the self-organized partition of fluxes in delta channel networks. By introducing a suitable nonlocal entropy rate (nER) and by analyzing field and simulated deltas, we suggest that delta networks achieve configurations that maximize the diversity of water and sediment flux delivery to the shoreline. We thus suggest that prograding deltas attain dynamically accessible optima of flux distributions on their channel network topologies, thus effectively decoupling evolutionary time scales of geomorphology and hydrology. When interpreted in terms of delta resilience, high nER configurations reflect an increased ability to withstand perturbations. However, the distributive mechanism responsible for both diversifying flux delivery to the shoreline and dampening possible perturbations might lead to catastrophic events when those perturbations exceed certain intensity thresholds.

  3. [Peptide phage display in biotechnology and biomedicine]. (United States)

    Kuzmicheva, G A; Belyavskaya, V A


    To date peptide phage display is one of the most common combinatorial methods used for identifying specific peptide ligands. Phage display peptide libraries containing billions different clones successfully used for selection of ligands with high affinity and selectivity toward wide range of targets including individual proteins, bacteria, viruses, spores, different kind of cancer cells and variety of nonorganic targets (metals, alloys, semiconductors etc.) Success of using filamentous phage in phage display technologies relays on the robustness of phage particles and a possibility to genetically modify its DNA to construct new phage variants with novel properties. In this review we are discussing characteristics of the most known non-commercial peptide phage display libraries of different formats (landscape libraries in particular) and their successful applications in several fields of biotechnology and biomedicine: discovery of peptides with diagnostic values against different pathogens, discovery and using of peptides recognizing cancer cells, trends in using of phage display technologies in human interactome studies, application of phage display technologies in construction of novel nano materials.

  4. High performance protonic ceramic membrane fuel cells (PCMFCs) with Sm{sub 0.5}Sr{sub 0.5}CoO{sub 3-{delta}} perovskite cathode

    Energy Technology Data Exchange (ETDEWEB)

    Ding Hanping [Department of Mechanical Engineering, University of South Carolina, Columbia, SC 29208 (United States); Department of Materials Science and Engineering, University of Science and Technology of China (USTC), Hefei 230026 (China); Xue Xingjian, E-mail: [Department of Mechanical Engineering, University of South Carolina, Columbia, SC 29208 (United States); Liu Xingqin; Meng Guangyao [Department of Materials Science and Engineering, University of Science and Technology of China (USTC), Hefei 230026 (China)


    Protonic ceramic membrane fuel cells (PCMFCs) based on proton-conducting electrolytes have attracted much attention because of many advantages, such as low activation energy and high energy efficiency. A stable, easily sintered perovskite oxide BaCe{sub 0.5}Zr{sub 0.3}Y{sub 0.16}Zn{sub 0.04}O{sub 3-{delta}} (BCZYZ) as electrolyte for proton-conducting solid oxide fuel cells (SOFCs) with Sm{sub 0.5}Sr{sub 0.5}CoO{sub 3-{delta}} (SSC) composite cathode is investigated. By fabricating thin membrane BCZYZ electrolyte ({approx}20 {mu}m) synthesized by a modified Pechini method on NiO-BCZYZ anode support, PCMFCs are assembled and tested by selecting SSC perovskite cathode with high mixed ionic and electronic conductivities. An open-circuit potential of 1.015 V, a maximal power density of 528 mW cm{sup -2}, and a low polarization resistance of the electrodes of 0.15 {Omega} cm{sup 2} is achieved at 700 {sup o}C. The results indicate that BCZYZ proton-conducting electrolyte with SSC cathode is a promising material system for SOFCs.

  5. The evolution of a subaqueous delta in the Anthropocene: A stratigraphic investigation of the Brazos River delta, TX USA (United States)

    Carlin, Joseph A.; Dellapenna, Timothy M.


    Globally, deltas are increasingly threatened by anthropogenic activities. As a result, deltas now evolve through the combined effects of natural and human-induced processes occurring throughout the fluvial-deltaic system. The Brazos River delta, located along the Texas coast in the northwestern Gulf of Mexico, and its watershed have been impacted by direct and indirect human activities since the late 19th century. This provides an opportunity to investigate how such alterations have shaped the evolution of a delta in the Anthropocene, a time when humans are drivers of geological change. Historic alteration to the delta and watershed include extensive agricultural activity, jetty construction at the mouth in the late 1890s, mouth diversion ~10 km to the southwest in 1929, and reservoir construction throughout the early and mid 20th Century. Three subaerial deltaic geometries provided the framework to connect subaerial deltaic responses, to the anthropogenic alterations, to the resulting stratigraphic characteristics observed in the subaqueous delta. This study utilized high-resolution geophysical data (swath bathymetry, side scan sonar, CHIRP subbottom profiling) on the subaqueous delta to investigate the subaqueous delta stratigraphy and infer the processes that shaped the deltaic record over time. The results showed distinct areas across the subaqueous delta that were dominated by erosion and deposition. Erosional areas corresponded to earlier growth phase depocenters being exposed at the surface, while the depositional areas corresponded to areas with the most recent growth phase depocenter overlying the earlier depocenters. These results highlight that the subaqueous depocenter has migrated westward over time, consistent with the observed changes to the subaerial delta. Additionally, the data showed that evidence for these past growth phases and depocenters may be preserved within the subaqueous delta, even after subaerial portions of the delta returned to pre

  6. IL-6-induced Bcl6 variant 2 supports IL-6-dependent myeloma cell proliferation and survival through STAT3

    International Nuclear Information System (INIS)

    Tsuyama, Naohiro; Danjoh, Inaho; Otsuyama, Ken-ichiro; Obata, Masanori; Tahara, Hidetoshi; Ohta, Tsutomu; Ishikawa, Hideaki


    IL-6 is a growth and survival factor for myeloma cells, although the mechanism by which it induces myeloma cell proliferation through gene expression is largely unknown. Microarray analysis showed that some B-cell lymphoma-associated oncogenes such as Bcl6, which is absent in normal plasma cells, were upregulated by IL-6 in IL-6-dependent myeloma cell lines. We found that Bcl6 variant 2 was upregulated by STAT3. ChIP assay and EMSA showed that STAT3 bound to the upstream region of variant 2 DNA. Expression of p53, a direct target gene of Bcl6, was downregulated in the IL-6-stimulated cells, and this process was impaired by an HDAC inhibitor. Bcl6 was knocked down by introducing small hairpin RNA, resulting in decreased proliferation and increased sensitivity to a DNA damaging agent. Thus, STAT3-inducible Bcl6 variant 2 appears to generate an important IL-6 signal that supports proliferation and survival of IL-6-dependent myeloma cells

  7. Induction of CD3 delta epsilon omega by phorbol 12-myristate 13-acetate

    DEFF Research Database (Denmark)

    Vangsted, A; Neisig, A; Wallin, H


    The effect of phorbol 12-myristate 13-acetate (PMA) on the synthesis, assembly and processing of the components of the T cell receptor (TcR) was studied with special focus on the CD3 omega chain. Treatment of the human leukemic T cell line Jurkat with PMA increased the synthesis of the Ti alpha, CD......3 gamma and CG3 zeta chains two- to threefold and the synthesis of Ti beta and CD3 delta epsilon omega complexes five- to sevenfold as assessed by metabolic labeling, immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by scanning densitometry. The amount...... of TcR complexes expressed on the cell surface was decreased after 16 h of PMA treatment. Based on these results we propose a role of CD3 omega in retention of TcR complexes. From PMA-treated CEM cells more than 50-fold the amount of CD3 delta epsilon omega complexes was immunoprecipitated as compared...

  8. Cross-diagnostic validity of the Nottingham health profile index of distress (NHPD

    Directory of Open Access Journals (Sweden)

    Klevsgård Rosemarie


    Full Text Available Abstract Background The Nottingham Health Profile index of Distress (NHPD has been proposed as a generic undimensional 24-item measure of illness-related distress that is embedded in the Nottingham Health Profile (NHP. Data indicate that the NHPD may have psychometric advantages to the 6-dimensional NHP profile scores. Detailed psychometric evaluations are, however, lacking. Furthermore, to support the validity of the generic property of outcome measures evidence that scores can be interpreted in the same manner in different diagnostic groups are needed. It is currently unknown if NHPD scores have the same meaning across patient populations. This study evaluated the measurement properties and cross-diagnostic validity of the NHPD as a survey instrument among people with Parkinson's disease (PD and peripheral arterial disease (PAD. Methods Data from 215 (PD and 258 (PAD people were Rasch analyzed regarding model fit, reliability, differential item functioning (DIF, unidimensionality and targeting. In cases of cross-diagnostic DIF this was adjusted for and the impact of DIF on the total score and person measures was assessed. Results The NHPD was found to have good overall and individual item fit in both disorders as well as in the pooled sample, but seven items displayed signs of cross-diagnostic DIF. Following adjustment for DIF some aspects of model fit were slightly compromised, whereas others improved somewhat. DIF did not impact total NHPD scores or resulting person measures, but the unadjusted scale displayed minor signs of multidimensionality. Reliability was > 0.8 in all within- and cross-diagnostic analyses. Items tended to represent more distress (mean, 0 logits than that experienced by the sample (mean, -1.6 logits. Conclusion This study supports the within- and cross-diagnostic validity of the NHPD as a survey tool among people with PD and PAD. We encourage others to reassess available NHP data within the NHPD framework to further

  9. Three-dimensional display improves observer speed and accuracy

    International Nuclear Information System (INIS)

    Nelson, J.A.; Rowberg, A.H.; Kuyper, S.; Choi, H.S.


    In an effort to evaluate the potential cost-effectiveness of three-dimensional (3D) display equipment, we compared the speed and accuracy of experienced radiologists identifying in sliced uppercase letters from CT scans with 2D and pseudo-3D display. CT scans of six capital letters were obtained and printed as a 2D display or as a synthesized pseudo-3D display (Pixar). Six observes performed a timed identification task. Radiologists read the 3D display an average of 16 times faster than the 2D, and the average error rate of 2/6 (± 0.6/6) for 2D interpretations was totally eliminated. This degree of improvement in speed and accuracy suggests that the expense of 3D display may be cost-effective in a defined clinical setting

  10. Study on the visibility of an electroluminescent display for automobiles; Jidoshayo EL display no shininsei

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, N; Harada, M; Idogaki, T [Denso Corp., Aichi (Japan)


    This report explores the visibility of an Electroluminescent (EL) display for automotive use. Displays for automobiles are exposed to the direct rays of the sun and forced to operate in wide temperature range. Therefore, luminous flux density by the lighting on EL display panel and operating environment temperature must be considered for the visibility evaluation. Sensory evaluation on the visibility and physical measurements such as contrast, chromaticity difference in accordance with the viewing angle change indicate that the visibility of the EL display for automobiles is advantageous over other displays. 6 refs., 11 figs., 1 tab.

  11. deltaPlotR: An R Package for Di?erential Item Functioning Analysis with Ango? s Delta Plot


    David Magis; Bruno Facon


    Angoff's delta plot is a straightforward and not computationally intensive method to identify differential item functioning (DIF) among dichotomously scored items. This approach was recently improved by proposing an optimal threshold selection and by considering several item purification processes. Moreover, to support practical DIF analyses with the delta plot and these improvements, the R package deltaPlotR was also developed. The purpose of this paper is twofold: to outline the delta plot ...

  12. Differential display technique of RNA from tumorigenic and non-tumorigenic variants of hamster cells transformed with avian sarcoma virus

    International Nuclear Information System (INIS)

    Leksa, V.; Altaner, C.


    Differential display technique was applied to study expression of RNA in tumorigenic and non-tumorigenic cell variants of avian sarcoma virus transformed hamster cells. Methodical conditions were worked out, which allowed identifying a cDNA fragment of an unknown gene expressed in non-tumorigenic cell variant only. Its role in tumor suppression remains to be determined. (author)

  13. Delta hedging strategies comparison

    DEFF Research Database (Denmark)

    De Giovanni, Domenico; Ortobelli, S.; Rachev, S.T.


    In this paper we implement dynamic delta hedging strategies based on several option pricing models. We analyze different subordinated option pricing models and we examine delta hedging costs using ex-post daily prices of S&P 500. Furthermore, we compare the performance of each subordinated model...

  14. Cell lineage of timed cohorts of Tbx6-expressing cells in wild-type and Tbx6 mutant embryos

    Directory of Open Access Journals (Sweden)

    Daniel Concepcion


    Full Text Available Tbx6 is a T-box transcription factor with multiple roles in embryonic development as evidenced by dramatic effects on mesoderm cell fate determination, left/right axis determination, and somite segmentation in mutant mice. The expression of Tbx6 is restricted to the primitive streak and presomitic mesoderm, but some of the phenotypic features of mutants are not easily explained by this expression pattern. We have used genetically-inducible fate mapping to trace the fate of Tbx6-expressing cells in wild-type and mutant embryos to explain some of the puzzling features of the mutant phenotype. We created an inducible Tbx6-creERT2 transgenic mouse in which cre expression closely recapitulates endogenous Tbx6 expression both temporally and spatially. Using a lacZ-based Cre reporter and timed tamoxifen injections, we followed temporally overlapping cohorts of cells that had expressed Tbx6 and found contributions to virtually all mesodermally-derived embryonic structures as well as the extraembryonic allantois. Contribution to the endothelium of major blood vessels may account for the embryonic death of homozygous mutant embryos. In mutant embryos, Tbx6-creERT2-traced cells contributed to the abnormally segmented anterior somites and formed the characteristic ectopic neural tubes. Retention of cells in the mutant tail bud indicates a deficiency in migratory behavior of the mutant cells and the presence of Tbx6-creERT2-traced cells in the notochord, a node derivative provides a possible explanation for the heterotaxia seen in mutant embryos.

  15. The Enabling Delta Life Initiative - Global Programme of Action on Deltas - Programme description

    NARCIS (Netherlands)

    Driel, van W.F.; Skyllerstedt, S.; Wosten, J.H.M.


    Being ‘hotspots’ of human activity with generally high population densities, deltas are vulnerable to changes induced by a range of driving forces, both natural and anthropogenic. In addition to already existing challenges, uncertainty of the possible impacts of climate change, low lying deltas

  16. Involvement of the yeast DNA polymerase delta in DNA repair in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Giot, L. [State University of New York at Stony Brook, Stony Brook, NY. (United States); Chanet, R.; Simon, M.; Facca, C.; Faye, G.


    The POL3 encoded catalytic subunit of DNA polymerase delta possesses a highly conserved C-terminal cysteine-rich domain in Saccharomyces cerevisiae. Mutations in some of its cysteine codons display a lethal phenotype, which demonstrates an essential function of this domain. The thermosensitive mutant pol3-13, in which a serine replaces a cysteine of this domain, exhibits a range of defects in DNA repair, such as hypersensitivity to different DNA-damaging agents and deficiency for induced mutagenesis and for recombination. These phenotypes are observed at 24 degrees, a temperature at which DNA replication is almost normal; this differentiates the functions of POL3 in DNA repair and DNA replication. Since spontaneous mutagenesis and spontaneous recombination are efficient in pol3-13, we propose that POL3 plays an important role in DNA repair after irradiation, particularly in the error-prone and recombinational pathways. Extragenic suppressors of pol3-13 are allelic to sdp5-1, previously identified as an extragenic suppressor of pol3-11. SDP5, which is identical to HYS2, encodes a protein homologous to the p50 subunit of bovine and human DNA polymerase delta. SDP5 is most probably the p55 subunit of Pol delta of S. cerevisiae and seems to be associated with the catalytic subunit for both DNA replication and DNA repair. (author)

  17. Nicotinamide riboside kinases display redundancy in mediating nicotinamide mononucleotide and nicotinamide riboside metabolism in skeletal muscle cells

    Directory of Open Access Journals (Sweden)

    Rachel S. Fletcher


    Conclusions: These results identify skeletal muscle cells as requiring NAMPT to maintain NAD+ availability and reveal that NRK1 and 2 display overlapping function in salvage of exogenous NR and NMN to augment intracellular NAD+ availability.

  18. 15-00544_SI.doc

    Indian Academy of Sciences (India)

    31P{1H} NMR spectrum [C5H4N(BH3)-CH2NHP(BH3)Ph2] of (1a). S3. 11B{1H} NMR spectrum of [C5H4N(BH3)-CH2NHP(BH3)Ph2] of (1a). S4. 13C{1H} NMR spectrum of [C5H4N(BH3)-CH2NHP(BH3)Ph2] (1a). S5. 1H{1H} NMR spectrum of [C5H4N(BH3)-CH2NHP(Se)Ph2] (2a). S6. 31P{1H} NMR spectrum of ...

  19. The effect of delta-like 1 homologue on the proliferation and odontoblastic differentiation in human dental pulp stem cells. (United States)

    Qi, Shengcai; Yan, Yanhong; Wen, Yue; Li, Jialiang; Wang, Jing; Chen, Fubo; Tang, Xiaoshan; Shang, Guangwei; Xu, Yuanzhi; Wang, Raorao


    This study aimed to investigate the functions of delta-like homologue 1 (DLK1) in the proliferation and differentiation of human dental pulp stem cells (hDPSCs). Immunohistochemical analysis was used to determine the expression of alkaline phosphatase (ALP), dentin sialophosphoprotein (DSPP), DLK1, NOTCH1 and p-ERK1/2 in the mouse first maxillary molar. Recombinant lentivirus was constructed to overexpress DLK1 stably in hDPSCs. The cell viability and proliferation of hDPSCs were examined by CCK8 and EdU incorporation assay respectively. The odontoblastic differentiation of hDPSCs was determined by detection of ALPase activity assay, ALP and alizarin red staining and the expression of mineralization-related genes including ALP, DSPP and dental matrix protein. The mRNA and protein levels of DLK1 and p-ERK1/2 protein expression were detected. ERK inhibitor was used to test the differentiation effect of DLK1 on hDPSCs. Delta-like homologue 1 was highly expressed on the odontoblasts and dental pulp cells on the first maxillary molar; the expression of p-ERK1/2 is similar with the DLK1 in the same process. The expression level of DLK1 increased significantly after the odontoblastic induction of hDPSCs. DLK1 overexpression increased the proliferation ability of hDPSCs and inhibited odontoblastic differentiation of hDPSCs. The protein level of p-ERK1/2 significantly increased in hDPSCs/dlk1-oe group. ERK signalling pathway inhibitor reversed the odontoblastic differentiation effects of DLK1 on hDPSCs. The proliferation of hDPSCs was promoted after DLK1 overexpression. DLK1 inhibited the odontoblastic differentiation of hDPSCs, which maybe through ERK signalling pathway. © 2017 John Wiley & Sons Ltd.

  20. The A-cation deficient perovskite series La2-xCoTiO6-δ (0 ≤ x ≤ 0.20): new components for potential SOFC composite cathodes

    DEFF Research Database (Denmark)

    Gomez-Perez, Alejandro; Teresa Azcondo, M.; Yuste, Mercedes


    La2-xCoTiO6-delta/Ce0.9Gd0.1O2-delta composites are presented as promising new cathodes for solid oxide fuel cells. The B-site ordering characteristic of double perovskites is present in the whole series. Additionally, increasing amounts of La-vacancies give rise to ordering of alternating La...

  1. Antibody response is required for protection from Theiler's virus-induced encephalitis in C57BL/6 mice in the absence of CD8+ T cells

    International Nuclear Information System (INIS)

    Kang, B.-S.; Palma, Joann P.; Lyman, Michael A.; Dal Canto, Mauro; Kim, Byung S.


    Intracerebral infection of susceptible mice with Theiler's murine encephalomyelitis virus (TMEV) induces immune-mediated demyelinating disease and this system serves as a relevant infectious model for human multiple sclerosis. It was previously shown that β 2 M-deficient C57BL/6 mice lacking functional CD8 + T cells display increased viral persistence and enhanced susceptibility to TMEV-induced demyelination, and yet the majority of mice are free of clinical signs. To understand the mechanisms involved in this general resistance of C57BL/6 mice in the absence of CTL responses, mice (μMT) deficient in the B-cell compartment lacking membrane IgM molecules were treated with anti-CD8 antibody and then infected with TMEV. Although little difference in the proliferative responses of peripheral T cells to UV-inactivated TMEV and the resistance to demyelinating disease was observed between virus-infected μMT and control B6 mice, the levels of CD4 + T cells were higher in the CNS of μMT mice. However, after treatment with anti-CD8 antibody, 100% of the mice displayed clinical gray matter disease and prolonged viral persistence in μMT mice, while only 10% of B6 mice showed clinical symptoms and very low viral persistence. Transfusion of sera from TMEV-infected B6 mice into anti-CD8 antibody-treated μMT mice partially restored resistance to virus-induced encephalitis. These results indicate that the early anti-viral antibody response is also important in the protection from TMEV-induced encephalitis particularly in the absence of CD8 + T cells

  2. Effects of Out-of-Plane Disorder on the Nodal Quasiparticle and Superconducting Gap in Single-Layer Bi_2Sr_1.6Ln_0.4CuO_6 delta (Ln = La, Nd, Gd)

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, M.


    How out-of-plane disorder affects the electronic structure has been investigated for the single-layer cuprates Bi{sub 2}Sr{sub 1.6}Ln{sub 0.4}CuO{sub 6+{delta}} (Ln = La, Nd, Gd) by angle-resolved photoemission spectroscopy. We have observed that, with increasing disorder, while the Fermi surface shape and band dispersions are not affected, the quasi-particle width increases, the anti-nodal gap is enhanced and the superconducting gap in the nodal region is depressed. The results indicate that the superconductivity is significantly depressed by out-of-plane disorder through the enhancement of the anti-nodal gap and the depression of the superconducting gap in the nodal region.

  3. QCD in the {delta}-regime

    Energy Technology Data Exchange (ETDEWEB)

    Bietenholz, W. [Universidad Nacional Autonoma de Mexico, Mexico City (Mexico). Inst. de Ciencias Nucleares; Cundy, N. [Seoul National Univ. (Korea, Republic of). Lattice Gauge Theory Research Center; Goeckeler, M. [Regensburg Univ. (Germany). Inst. fuer Theoretische Physik; Horsley, R.; Zanotti, J.M. [Edinburgh Univ. (United Kingdom). School of Physics; Nakamura, Y. [Tsukuba Univ., Ibaraki (Japan). Center for Computational Sciences; Pleiter, D. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Rakow, P.E.L. [Liverpool Univ. (United Kingdom). Theoretical Physics Div.; Schierholz, G. [Regensburg Univ. (Germany). Inst. fuer Theoretische Physik; Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)


    The {delta}-regime of QCD is characterised by light quarks in a small spatial box, but a large extent in (Euclidean) time. In this setting a specific variant of chiral perturbation theory - the {delta}-expansion - applies, based on a quantum mechanical treatment of the quasi onedimensional system. In particular, for vanishing quark masses one obtains a residual pion mass M{sup R}{sub {pi}}, which has been computed to the third order in the {delta}-expansion. A comparison with numerical measurements of this residual mass allows for a new determination of some Low Energy Constants, which appear in the chiral Lagrangian. We first review the attempts to simulate 2-flavour QCD directly in the {delta}-regime. This is very tedious, but results compatible with the predictions for M{sup R}{sub {pi}} have been obtained. Then we show that an extrapolation of pion masses measured in a larger volume towards the {delta}-regime leads to good agreement with the theoretical predictions. From those results, we also extract a value for the (controversial) sub-leading Low Energy Constant anti l{sub 3}. (orig.)

  4. Low-temperature protonic ceramic membrane fuel cells (PCMFCs) with SrCo{sub 0.9}Sb{sub 0.1}O{sub 3-{delta}} cubic perovskite cathode

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Hanping; Lin, Bin; Wang, Songlin; Fang, Daru; Dong, Yingchao; Peng, Ranran; Liu, Xingqiu; Meng, Guangyao [Department of Materials Science and Engineering, University of Science and Technology of China (USTC), Hefei 230026 (China); Jiang, Yinzhu; Tao, Shanwen [Department of Chemistry, School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh EH14 4AS (United Kingdom)


    The SrCo{sub 0.9}Sb{sub 0.1}O{sub 3-{delta}} (SCS) composite oxide with cubic perovskite structure was synthesized by a modified Pechini method and examined as a novel cathode for protonic ceramic membrane fuel cells (PCMFCs). At 700 C and under open-circuit condition, symmetrical SCS cathode on BaZr{sub 0.1}Ce{sub 0.7}Y{sub 0.2}O{sub 3-{delta}} (BZCY7) electrolyte showed low polarization resistances (R{sub p}) of 0.22 {omega}cm{sup 2} in air. A laboratory-sized tri-layer cell of NiO-BZCY7/BZCY7/SCS was operated from 500 to 700 C with humidified hydrogen ({proportional_to}3% H{sub 2}O) as fuel and the static air as oxidant. A high open-circuit potential of 1.004 V, a maximum power density of 259 mW cm{sup -2}, and a low polarization resistance of the electrodes of 0.14 {omega}cm{sup 2} was achieved at 700 C. (author)

  5. Chlorin e6 Conjugated Interleukin-6 Receptor Aptamers Selectively Kill Target Cells Upon Irradiation

    Directory of Open Access Journals (Sweden)

    Sven Kruspe


    Full Text Available Photodynamic therapy (PDT uses the therapeutic properties of light in combination with certain chemicals, called photosensitizers, to successfully treat brain, breast, prostate, and skin cancers. To improve PDT, current research focuses on the development of photosensitizers to specifically target cancer cells. In the past few years, aptamers have been developed to directly deliver cargo molecules into target cells. We conjugated the photosensitizer chlorin e6 (ce6 with a human interleukin-6 receptor (IL-6R binding RNA aptamer, AIR-3A yielding AIR-3A-ce6 for application in high efficient PDT. AIR-3A-ce6 was rapidly and specifically internalized by IL-6R presenting (IL-6R+ cells. Upon light irradiation, targeted cells were selectively killed, while free ce6 did not show any toxic effect. Cells lacking the IL-6R were also not affected by AIR-3A-ce6. With this approach, we improved the target specificity of ce6-mediated PDT. In the future, other tumor-specific aptamers might be used to selectively localize photosensitizers into cells of interest and improve the efficacy and specificity of PDT in cancer and other diseases.

  6. Tidal controls on river delta morphology (United States)

    Hoitink, A. J. F.; Wang, Z. B.; Vermeulen, B.; Huismans, Y.; Kästner, K.


    River delta degradation has been caused by extraction of natural resources, sediment retention by reservoirs, and sea-level rise. Despite global concerns about these issues, human activity in the world’s largest deltas intensifies. Harbour development, construction of flood defences, sand mining and land reclamation emerge as key contemporary factors that exert an impact on delta morphology. Tides interacting with river discharge can play a crucial role in the morphodynamic development of deltas under pressure. Emerging insights into tidal controls on river delta morphology suggest that--despite the active morphodynamics in tidal channels and mouth bar regions--tidal motion acts to stabilize delta morphology at the landscape scale under the condition that sediment import during low flows largely balances sediment export during high flows. Distributary channels subject to tides show lower migration rates and are less easily flooded by the river because of opposing non-linear interactions between river discharge and the tide. These interactions lead to flow changes within channels, and a more uniform distribution of discharge across channels. Sediment depletion and rigorous human interventions in deltas, including storm surge defence works, disrupt the dynamic morphological equilibrium and can lead to erosion and severe scour at the channel bed, even decades after an intervention.

  7. Delta Semantics Defined By Petri Nets

    DEFF Research Database (Denmark)

    Jensen, Kurt; Kyng, Morten; Madsen, Ole Lehrmann

    and the possibility of using predicates to specify state changes. In this paper a formal semantics for Delta is defined and analysed using Petri nets. Petri nets was chosen because the ideas behind Petri nets and Delta concide on several points. A number of proposals for changes in Delta, which resulted from...

  8. Investigation of the biodistribution, breakdown and excretion of delta inulin adjuvant. (United States)

    Wang, Lixin; Barclay, Thomas; Song, Yunmei; Joyce, Paul; Sakala, Isaac G; Petrovsky, Nikolai; Garg, Sanjay


    Insoluble, nanostructured delta inulin particles enhance the immunogenicity of co-administered protein antigens and consequently are used as a vaccine adjuvant (Advax™). To better understand their immunomodulatory properties, the in vitro hydrolysis and in vivo distribution of delta inulin particles were investigated. Delta inulin particle hydrolysis under bio-relevant acidic conditions resulted in no observable change to the bulk morphology using SEM, and HPLC results showed that only 6.1% of the inulin was hydrolysed over 21days. However, 65% of the terminal glucose groups were released, showing that acid hydrolysis relatively rapidly releases surface bound chemistries. This was used to explain in vivo biodistribution results in which delta inulin particles surface-labelled with fluorescein-5-thiosemicabizide were administered to mice using intramuscular (I.M.) or subcutaneous (S.C.) routes. Comparison analysis of the fluorescence of soluble inulin in the supernatants of homogenised tissues maintained at room temperature or heated to 100°C to solubilise particulate inulin was used to distinguish between fluorescent probe on soluble inulin and probe bound to inulin within particles. Following both I.M. and S.C. injection delta inulin exhibited a depot behaviour with local injection site residence for several weeks. Over this time, as injection site inulin reduced, there was measurable transport of intact delta inulin particles by macrophages to secondary lymphoid organs and the liver. Ultimately, the injected delta inulin became solubilised resulting in its detection in the plasma and in the urine. Thus injected delta inulin particles are initially taken up by macrophages at the site of injection, trafficked to secondary lymphoid tissue and the liver, and hydrolysed resulting in their becoming soluble and diffusing into the blood stream, from whence they are glomerularly filtered and excreted into the urine. These results provide important insights into the

  9. Immunohistochemical observations of methionine-enkephalin and delta opioid receptor in the digestive system of Octopus ocellatus. (United States)

    Sha, Ailong; Sun, Hushan; Wang, Yiyan


    The study was designed to determine whether methionine-enkephalin (met-Enk) or delta opioid receptor was present in the digestive system of Octopus ocellatus. The results showed that they were both in the bulbus oris, esophagus, crop, stomach, gastric cecum, intestine, posterior salivary glands of O. ocellatus, one of them, met-Enk in the rectum, anterior salivary glands, digestive gland. And the distributions were extensive in the digestive system. Strong or general met-Enk immunoreactivity was observed in the inner epithelial cells of the bulbus oris, esophagus, stomach, gastric cecum, intestine, anterior salivary glands and the adventitia of the intestine and rectum, and so was the delta opioid receptor immunoreactivity in the inner epithelial cells of the bulbus oris, esophagus, and crop, however, they were weak in other parts. Combining with delta opioid receptor, met-Enk may be involved in the regulations of food intake, absorption, movement of gastrointestinal smooth muscle and secretion of digestive gland. The different densities of met-Enk and delta opioid receptor may be related to the different functions in the digestive system of O. ocellatus. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Novel β-lactamase-random peptide fusion libraries for phage display selection of cancer cell-targeting agents suitable for enzyme prodrug therapy (United States)

    Shukla, Girja S.; Krag, David N.


    Novel phage-displayed random linear dodecapeptide (X12) and cysteine-constrained decapeptide (CX10C) libraries constructed in fusion to the amino-terminus of P99 β-lactamase molecules were used for identifying β-lactamase-linked cancer cell-specific ligands. The size and quality of both libraries were comparable to the standards of other reported phage display systems. Using the single-round panning method based on phage DNA recovery, we identified severalβ-lactamase fusion peptides that specifically bind to live human breast cancer MDA-MB-361 cells. The β-lactamase fusion to the peptides helped in conducting the enzyme activity-based clone normalization and cell-binding screening in a very time- and cost-efficient manner. The methods were suitable for 96-well readout as well as microscopic imaging. The success of the biopanning was indicated by the presence of ~40% cancer cell-specific clones among recovered phages. One of the binding clones appeared multiple times. The cancer cell-binding fusion peptides also shared several significant motifs. This opens a new way of preparing and selecting phage display libraries. The cancer cell-specific β-lactamase-linked affinity reagents selected from these libraries can be used for any application that requires a reporter for tracking the ligand molecules. Furthermore, these affinity reagents have also a potential for their direct use in the targeted enzyme prodrug therapy of cancer. PMID:19751096

  11. Post-dam vegetation changes and small mammal populations in the Peace-Athabasca delta

    International Nuclear Information System (INIS)

    Pfister, O.


    Research aimed at monitoring wildlife populations is a useful way to estimate the impact and consequences of hydroelectric projects on northern deltas. Such studies could provide valuable insights on the potential effect of the drying of deltas in the context of global climate change. The Peace-Athabasca River Delta, one of the most extensive northern inland deltas in the western hemisphere, represents a unique site to study such effects. Construction of the Bennett Dam in 1968 has had serious effects on the delta's ecological integrity; the resulting lower water levels and colonization of grass meadow communities by willows and the movement of shorelines has affected wildlife distribution and population levels. A study was conducted to estimate the impact of the invasion of grass meadows by willows on small rodent populations in the delta. Live trapping grids were established at three sites. Population estimates were obtained by the minimum number known method and used to calculate biomass of small mammals in willow and meadow grids. Mean trapping estimates (MTEs) of adult meadow voles ranged from under 1 per hectare on willow grids to 28 per hectare on meadow grids. On willow grids only, MTEs for adult populations of deer mice, red-backed voles, and meadow jumping mice reached 6, 6, and less than 1 per hectare respectively. It is estimated that the development of grass meadows into willow shrublands over the next 20-40 y could result in a loss of over 50% of the biomass of small rodents present in 1976. This should have a negative effect on the foraging efficiency and productivity of secondary consumers such as weasel and owl. 109 refs., 16 figs., 29 tabs

  12. B-cell lymphoma 6 protein stimulates oncogenicity of human breast cancer cells

    International Nuclear Information System (INIS)

    Wu, Qiang; Kong, Xiang-jun; Xu, Xiao-chun; Lobie, Peter E; Zhu, Tao; Wu, Zheng-sheng; Liu, Xue; Yan, Hong; He, Yin-huan; Ye, Shan; Cheng, Xing-wang; Zhu, Gui-lu; Wu, Wen-yong; Wang, Xiao-nan


    B-cell lymphoma 6 (BCL6) protein, an evolutionarily conserved zinc finger transcription factor, showed to be highly expressed in various human cancers in addition to malignancies in the lymphoid system. This study investigated the role of BCL6 expression in breast cancer and its clinical significance in breast cancer patients. Expression of BCL6 protein was assessed using in situ hybridization and immunohistochemistry in 127 breast cancer patients and 50 patients with breast benign disease as well as in breast cell lines. Expression of BCL6 was restored or knocked down in two breast cancer cell lines (MCF-7 and T47D) using BCL6 cDNA and siRNA, respectively. The phenotypic change of these breast cancer cell lines was assessed using cell viability MTT, Transwell invasion, colony formation, and flow cytometry assays and in a xenograft mice model. Luciferase reporter gene, immunoblot, and qRT-PCR were used to investigate the molecular events after manipulated BCL6 expression in breast cancer cells. BCL6 protein was highly expressed in breast cancer cell lines and tissue specimens and expression of BCL6 protein was associated with disease progression and poor survival of breast cancer patients. In vitro, the forced expression of BCL6 results in increased proliferation, anchorage-independent growth, migration, invasion and survival of breast cancer cell lines, whereas knockdown of BCL6 expression reduced these oncogenic properties of breast cancer cells. Moreover, forced expression of BCL6 increased tumor growth and invasiveness in a nude mouse xenograft model. At the gene level, BCL6 was a target gene of miR-339-5p. Expression of BCL6 induced expression of CXCR4 and cyclinD1 proteins. The current study demonstrated the oncogenic property of BCL6 in breast cancer and further study could target BCL6 as a novel potential therapeutic strategy for breast cancer

  13. X-Windows Widget for Image Display (United States)

    Deen, Robert G.


    XvicImage is a high-performance XWindows (Motif-compliant) user interface widget for displaying images. It handles all aspects of low-level image display. The fully Motif-compliant image display widget handles the following tasks: (1) Image display, including dithering as needed (2) Zoom (3) Pan (4) Stretch (contrast enhancement, via lookup table) (5) Display of single-band or color data (6) Display of non-byte data (ints, floats) (7) Pseudocolor display (8) Full overlay support (drawing graphics on image) (9) Mouse-based panning (10) Cursor handling, shaping, and planting (disconnecting cursor from mouse) (11) Support for all user interaction events (passed to application) (12) Background loading and display of images (doesn't freeze the GUI) (13) Tiling of images.

  14. Comparative pharmacology of a new recombinant FSH expressed by a human cell line

    DEFF Research Database (Denmark)

    Koechling, Wolfgang; Plaksin, Daniel; Croston, Glenn E.


    Recombinant FSH proteins are important therapeutic agents for the treatment of infertility, including follitropin alfa expressed in Chinese Hamster Ovary (CHO) cells and, more recently, follitropin delta expressed in the human cell line PER.C6. These recombinant FSH proteins have distinct glycosy...

  15. Omega-3 fatty acid deficiency selectively up-regulates delta6-desaturase expression and activity indices in rat liver: prevention by normalization of omega-3 fatty acid status. (United States)

    Hofacer, Rylon; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Magrisso, I Jack; Benoit, Stephen C; McNamara, Robert K


    This study investigated the effects of perinatal dietary omega-3 (n-3) fatty acid depletion and subsequent repletion on the expression of genes that regulate long-chain (LC) polyunsaturated fatty acid biosynthesis in rat liver and brain. It was hypothesized that chronic n-3 fatty acid deficiency would increase liver Fads1 and Fads2 messenger RNA (mRNA) expression/activity and that n-3 fatty acid repletion would normalize this response. Adult rats fed the n-3-free diet during perinatal development exhibited significantly lower erythrocyte, liver, and frontal cortex LCn-3 fatty acid composition and reciprocal elevations in LC omega-6 (n-6) fatty acid composition compared with controls (CONs) and repleted rats. Liver Fads2, but not Fads1, Elovl2, or Elovl5, mRNA expression was significantly greater in n-3-deficient (DEF) rats compared with CONs and was partially normalized in repleted rats. The liver 18:3n-6/18:2n-6 ratio, an index of delta6-desturase activity, was significantly greater in DEF rats compared with CON and repleted rats and was positively correlated with Fads2 mRNA expression among all rats. The liver 18:3n-6/18:2n-6 ratio, but not Fads2 mRNA expression, was also positively correlated with erythrocyte and frontal cortex LCn-6 fatty acid compositions. Neither Fads1 or Fads2 mRNA expression was altered in brain cortex of DEF rats. These results confirm previous findings that liver, but not brain, delta6-desaturase expression and activity indices are negatively regulated by dietary n-3 fatty acids. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Holocene evolution of the Liaohe Delta, a tide-dominated delta formed by multiple rivers in Northeast China (United States)

    He, Lei; Xue, Chunting; Ye, Siyuan; Laws, Edward Allen; Yuan, Hongming; Yang, Shixiong; Du, Xiaolei


    The Liaohe Delta in Northeast China is one of the ecologically important estuarine deltas in China. It has been formed via the accumulation of sediment discharged by four rivers in the Liaohe Plain that enter Liaodong Bay. Twenty-seven 30-40 m long cores recovered from the Liaohe Plain and Liaodong Bay were analyzed for sedimentary characteristics, grain size, foraminifera species, and ages determined by accelerator mass spectrometry (AMS) 14C to document the stratigraphical sequence and the spatio-temporal evolution of the Liaohe Delta. Our results revealed that the sedimentary environments have evolved from fluvial, tidal flat/estuarine, to neritic and finally to a deltaic environment since the Late Pleistocene. The Holocene transgression arrived at the present coastline at ∼8500 cal a BP and flooded the maximum area of land at ∼7000 cal a BP. A deltaic environment prevailed in this area after 7000 cal a BP. Bounded by the modern Liaohe River mouth, the present deltaic sedimentary system can be divided into the eastern and western components. The rate of seaward progradation of the eastern paleocoastline was estimated to be ∼8.6 m/a since 7000 cal a BP; the eastern cores in the present coastline began receiving the deltaic sediments at ∼5000 cal a BP. The rate of seaward progradation of the western paleocoastline was estimated to be only ∼2.8 m/a since 7000 cal a BP. The coastline on the western side began accumulating deltaic sediments about 2000 years later than the eastern coastline. Depocenter shifting was hypothesized to be the reason for the spatial differences in the sedimentary processes. However, the change of sediment fluxes of the western rivers due to climate changes and ancient human impacts might be the reason for the differences of the temporal evolution of the eastern and western sedimentary systems in the Liaohe Delta.

  17. Neutron diffraction and NQR study of the intermediate turn angle phase formed during AFI to AFII recording in YBa2Cu3-xAlxO6+#delta#

    DEFF Research Database (Denmark)

    Brecht, E.; Schmahl, W.W.; Fuess, H.


    The reordering mechanism from the antiferromagnetic phase AFI to the antiferromagnetic phase AFII in an oxygen-deficient YBa2Cu2.94Al0.06O6+delta single crystal with an oxygen content delta=0.18 in the Cu(1) layer has been studied by neutron diffraction and nuclear quadrupole resonance (NQR......). The crystal orders magnetically from the paramagnetic state to the antiferromagnetic AFI state at the Neel temperature T-N=403 K with an empirical critical exponent of beta = 0.26. Reordering to the antiferromagnetic AFII state sets in at T-2 = 12 K. In both the AFI and AFII phases the ordered magnetic...... as a function of temperature. This result indicates unequivocally that the AFIAFII reordering takes place via a noncollinear intermediate turn angle phase AFI+II....

  18. Quantitative evaluation of Candia antarctica lipase B displayed on the cell surface of a Pichia pastoris based on an FS anchor system. (United States)

    Liang, Xing-xiang; Wang, Bei-bei; Sun, Yu-fei; Lin, Ying; Han, Shuang-yan; Zheng, Sui-ping; Cui, Tang-bing


    A new approach is described to quantify the number of enzyme molecules, such as Candia antarctica lipase B, that are displayed on the cell surface of Pichia pastoris. Enhanced green fluorescent protein (EGFP) and Candida antarctica lipase B (CALB) were fused and displayed on the surface of P. pastoris by linking to the anchor flocculation functional domain of FLO1p from Saccharomyces cerevisiae. Confocal laser scanning microscopy, flow cytometry, and fluorescence spectrophotometry were used to monitor the fluorescence intensity of fused EGFP. Combined with the corresponding protein concentration detected in the medium, a standard curve describing the relationship between the fusion protein concentration and fluorescence intensity were obtained and could be used to number CALB displayed on the cell surface. The results showed that approx. 10(4) molecules of CALB molecules were immobilized on the single P. pastoris cell wall based on FS anchor system.

  19. Optimality and self-organization in river deltas (United States)

    Tejedor, A.; Longjas, A.; Edmonds, D. A.; Zaliapin, I. V.; Georgiou, T. T.; Rinaldo, A.; Foufoula-Georgiou, E.


    Deltas are nourished by channel networks, whose connectivity constrains, if not drives, the evolution, functionality and resilience of these systems. Understanding the coevolution of deltaic channels and their flux organization is crucial for guiding maintenance strategies of these highly stressed systems from a range of anthropogenic activities. However, in contrast to tributary channel networks, to date, no theory has been proposed to explain how deltas self-organize to distribute water and sediment to the delta top and the shoreline. Here, we hypothesize the existence of an optimality principle underlying the self-organized partition of fluxes in delta channel networks. Specifically, we hypothesize that deltas distribute water and sediment fluxes on a given delta topology such as to maximize the diversity of flux delivery to the shoreline. By introducing the concept of nonlocal Entropy Rate (nER) and analyzing ten field deltas in diverse environments, we present evidence that supports our hypothesis, suggesting that delta networks achieve dynamically accessible maxima of their nER. Furthermore, by analyzing six simulated deltas using the Delf3D model and following their topologic and flux re-organization before and after major avulsions, we further study the evolution of nER and confirm our hypothesis. We discuss how optimal flux distributions in terms of nER, when interpreted in terms of resilience, are configurations that reflect an increased ability to withstand perturbations.

  20. Holocene Flexural Deformation over the Nile Delta: Evidence from Radar Interferometry (United States)

    Gebremichael, E.; Sultan, M.; Becker, R.


    deformation pattern is interrupted (replaced by subsidence) in some areas due to local deformation caused by high groundwater extraction rates in western (6 mm/yr) and gas extraction in north central delta (9 mm/yr).

  1. Houtman Abrolhos Isotope (delta 18O, delta 13C) Data for 1795 to 1994 (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — DESCRIPTION: VARIABLES AND UNITS: Column #1: core depth in mm Column #2: delta C-13 vs V-PDB Column #3: delta O-18 vs V-PDB Column #4: assigned date in years A.D....

  2. Scaling Robotic Displays: Displays and Techniques for Dismounted Movement with Robots (United States)


    you are performing the low crawl 4.25 5.00 Drive the robot while you are negotiating the hill 6.00 5.00 Drive the robot while you are climbing the... stairs 4.67 5.00 Drive the robot while you are walking 5.70 5.27 HMD It was fairly doable. 1 When you’re looking through the lens, it’s not...Scaling Robotic Displays: Displays and Techniques for Dismounted Movement with Robots by Elizabeth S. Redden, Rodger A. Pettitt

  3. Three dimensional [delta]f simulations of beams in the SSC

    Energy Technology Data Exchange (ETDEWEB)

    Koga, J.; Tajima, T. (Texas Univ., Austin, TX (United States). Inst. for Fusion Studies); Machida, S. (Superconducting Super Collider Lab., Dallas, TX (United States))


    A three dimensional [delta]f strong-strong algorithm has been developed to apply to the study of such effects as space charge and beam-beam interaction phenomena in the Superconducting Super Collider (SSC). The algorithm is obtained from the merging of the particle tracking code Simpsons used for 3-dimensional space charge effects and a [delta]f code. The [delta]f method is used to follow the evolution of the non-gaussian part of the beam distribution. The advantages of this method are twofold. First, the Simpsons code utilizes a realistic accelerator model including synchrotron oscillations and energy ramping in 6-dimensional phase space with electromagnetic fields of the beams calculated using a realistic 3-dimensional field solver. Second, the beams are evolving in the fully self-consistent strong-strong sense where finite particle fluctuation noise is greatly reduced as opposed to the weak-strong models where one beam is fixed.

  4. Three dimensional {delta}f simulations of beams in the SSC

    Energy Technology Data Exchange (ETDEWEB)

    Koga, J.; Tajima, T. [Texas Univ., Austin, TX (United States). Inst. for Fusion Studies; Machida, S. [Superconducting Super Collider Lab., Dallas, TX (United States)


    A three dimensional {delta}f strong-strong algorithm has been developed to apply to the study of such effects as space charge and beam-beam interaction phenomena in the Superconducting Super Collider (SSC). The algorithm is obtained from the merging of the particle tracking code Simpsons used for 3-dimensional space charge effects and a {delta}f code. The {delta}f method is used to follow the evolution of the non-gaussian part of the beam distribution. The advantages of this method are twofold. First, the Simpsons code utilizes a realistic accelerator model including synchrotron oscillations and energy ramping in 6-dimensional phase space with electromagnetic fields of the beams calculated using a realistic 3-dimensional field solver. Second, the beams are evolving in the fully self-consistent strong-strong sense where finite particle fluctuation noise is greatly reduced as opposed to the weak-strong models where one beam is fixed.

  5. Canthin-6-one induces cell death, cell cycle arrest and differentiation in human myeloid leukemia cells. (United States)

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


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

  6. Antioxidant Properties and PC12 Cell Protective Effects of a Novel Curcumin Analogue (2E,6E-2,6-Bis(3,5- dimethoxybenzylidenecyclohexanone (MCH

    Directory of Open Access Journals (Sweden)

    Gui-Zhen Ao


    Full Text Available The antioxidative properties of a novel curcumin analogue (2E,6E-2,6-bis(3,5-dimethoxybenzylidenecyclohexanone (MCH were assessed by several in vitro models, including superoxide anion, hydroxyl radical and 1,1-diphenyl-2-picrylhydrazyl (DPPH radical scavenging and PC12 cell protection from H2O2 damage. MCH displayed superior O2•− quenching abilities compared to curcumin and vitamin C. In vitro stability of MCH was also improved compared with curcumin. Exposure of PC12 cells to 150 µM H2O2 caused a decrease of antioxidant enzyme activities, glutathione (GSH loss, an increase in malondialdehyde (MDA level, and leakage of lactate dehydrogenase (LDH, cell apoptosis and reduction in cell viability. Pretreatment of the cells with MCH at 0.63–5.00 µM before H2O2 exposure significantly attenuated those changes in a dose-dependent manner. MCH enhanced cellular expression of transcription factor NF-E2-related factor 2 (Nrf2 at the transcriptional level. Moreover, MCH could mitigate intracellular accumulation of reactive oxygen species (ROS, the loss of mitochondrial membrane potential (MMP, and the increase of cleaved caspase-3 activity induced by H2O2. These results show that MCH protects PC12 cells from H2O2 injury by modulating endogenous antioxidant enzymes, scavenging ROS, activating the Nrf2 cytoprotective pathway and prevention of apoptosis.

  7. B cell, CD8 + T cell and gamma delta T cell infiltration alters alveolar immune cell homeostasis in HIV-infected Malawian adults [version 2; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Andrew Mwale


    Full Text Available Background: HIV infection is associated with increased risk to lower respiratory tract infections (LRTI. However, the impact of HIV infection on immune cell populations in the lung is not well defined. We sought to comprehensively characterise the impact of HIV infection on immune cell populations in the lung. Methods: Twenty HIV-uninfected controls and 17 HIV-1 infected ART-naïve adults were recruited from Queen Elizabeth Central Hospital, Malawi. Immunophenotyping of lymphocyte and myeloid cell populations was done on bronchoalveolar lavage fluid and peripheral blood cells. Results: We found that the numbers of CD8 + T cells, B cells and gamma delta T cells were higher in BAL fluid of HIV-infected adults compared to HIV-uninfected controls (all p<0.05. In contrast, there was no difference in the numbers of alveolar CD4 + T cells in HIV-infected adults compared to HIV-uninfected controls (p=0.7065. Intermediate monocytes were the predominant monocyte subset in BAL fluid (HIV-, 63%; HIV+ 81%, while the numbers of classical monocytes was lower in HIV-infected individuals compared to HIV-uninfected adults (1 × 10 5 vs. 2.8 × 10 5 cells/100ml of BAL fluid, p=0.0001. The proportions of alveolar macrophages and myeloid dendritic cells was lower in HIV-infected adults compared to HIV-uninfected controls (all p<0.05. Conclusions: Chronic HIV infection is associated with broad alteration of immune cell populations in the lung, but does not lead to massive depletion of alveolar CD4 + T cells. Disruption of alveolar immune cell homeostasis likely explains in part the susceptibility for LRTIs in HIV-infected adults.

  8. Delta infection evidenced by radioimmunoanalysis in selected collectives

    Energy Technology Data Exchange (ETDEWEB)

    Kselikova, M; Horejsi, J; Urbankova, J


    The presence of the Delta agent within the population was tested by means of the Delta-antibody radioimmunoassay using competitive kits of the firms ABBOTT (ABBOTT-ANTI-DELTA) and SORIN (AB-DELTAK). The Delta-antibody was found in 3.2% HBV patients, 5% HBsAg carriers, and in 20.8% of specific anti-Hbs-immunoglobulin. In hemophiliacs and blood donors no Delta-antibody was seen.

  9. Delta infection evidenced by radioimmunoanalysis in selected collectives

    International Nuclear Information System (INIS)

    Kselikova, M.; Horejsi, J.; Urbankova, J.


    The presence of the Delta agent within the population was tested by means of the Delta-antibody radioimmunoassay using competitive kits of the firms ABBOTT (ABBOTT-ANTI-DELTA) and SORIN (AB-DELTAK). The Delta-antibody was found in 3.2% HBV patients, 5% HBsAg carriers, and in 20.8% of specific anti-Hbs-immunoglobulin. In hemophiliacs and blood donors no Delta-antibody was seen. (author)

  10. Performance of NCAP projection displays (United States)

    Jones, Philip J.; Tomita, Akira; Wartenberg, Mark


    Prototypes of projection displays based on dispersions of liquid crystal in polymer matrices are beginning to appear. The principle of operation depends on electrically switchable light scattering. They are potentially much brighter than current cathode ray tube (CRT) or twisted nematic liquid crystal (TN LC) cell based displays. Comparisons of efficacy and efficiency show this. The contrast and brightness of such displays depend on a combination of the f- number of the projection system and the scattering characteristics of the light valve. Simplified equations can be derived to show these effects. The degree of scattering of current NCAP formulations is sufficient to produce good contrast projection displays, at convenient voltages, that are around three times brighter than TN LC projectors because of the lack of polarizers in the former.

  11. Generation of H1 PAX6WT/EGFP reporter cells to purify PAX6 positive neural stem/progenitor cells. (United States)

    Wu, Wei; Liu, Juli; Su, Zhenghui; Li, Zhonghao; Ma, Ning; Huang, Ke; Zhou, Tiancheng; Wang, Linli


    Neural conversion from human pluripotent cells (hPSCs) is a potential therapy to neurological disease in the future. However, this is still limited by efficiency and stability of existed protocols used for neural induction from hPSCs. To overcome this obstacle, we developed a reporter system to screen PAX6 + neural progenitor/stem cells using transcription activator like effector nuclease (TALEN). We found that knock-in 2 A-EGFP cassette into PAX6 exon of human embryonic stem cells H1 with TALEN-based homology recombination could establish PAX6 WT/EGFP H1 reporter cell line fast and efficiently. This reporter cell line could differentiate into PAX6 and EGFP double positive neural progenitor/stem cells (NPCs/NSCs) after neural induction. Those PAX6 WT/EGFP NPCs could be purified, expanded and specified to post-mitotic neurons in vitro efficiently. With this reporter cell line, we also screened out 1 NPC-specific microRNA, hsa-miR-99a-5p, and 3 ESCs-enriched miRNAs, hsa-miR-302c-5p, hsa-miR-512-3p and hsa-miR-518 b. In conclusion, the TALEN-based neural stem cell screening system is safe and efficient and could help researcher to acquire adequate and pure neural progenitor cells for further application. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Novel cell parameter determination of a twisted-nematic liquid crystal display

    International Nuclear Information System (INIS)

    Huang Xia; Jing Hai; Fu Guozhu


    In this paper a novel method is proposed to determine the cell parameters including the twist angle, optic retardation and rubbing direction of twisted-nematic liquid crystal displays (TNLCD) by rotating the TNLCD. It is a single-wavelength method. Because using subtraction equation of transmittance as curve fitting equation, the influence of the light from environment and the absorption by polarizer, the sample of TNLCD and analyser on the transmittance is eliminated. Accurate results can also be obtained in imperfect darkness. By large numbers of experiments, we found that not only the experimental setup is quite simple and can be easily adopted to be carried out, but also the results are accurate

  13. Reactivity, structure and physical properties of SrCo{sub 2.5+{delta}} and La{sub 2}CoO{sub 4.0+{delta}}. In situ X-ray diffraction and neutrons study; Reactivite, structure et proprietes physiques de SrCoO{sub 2.5+{delta}} et La{sub 2}CoO{sub 4.0+{delta}}. Etude par diffraction des rayons X et des neutrons in situ

    Energy Technology Data Exchange (ETDEWEB)

    Le Toquin, R.


    This work was devoted to the study of the reactivity and more specifically the influence of the intercalated oxygen amount {delta} on the structure and physical properties of SrCoO{sub 2.5+{delta}} et La{sub 2}CoO{sub 4.0+{delta}} We controlled the oxidation level by means of reversible electrochemical red ox reaction at room temperature. Structural modifications, especially disorder, and electronic properties were studied for the first time on large orientated single crystal. In the SrCoO{sub 2.5+{delta}} system, after structural and electronic characterisation of the end phases, we studied the real structure of the brownmillerite SrCoO{sub 2.5} phase using single crystal. Moreover, we investigated structural and magnetic evolution upon red ox cycle using X-ray diffraction on 6 times twinned single crystal and in situ neutron powder diffraction. Two intermediate SrCoO{sub 2.75} and SrCoO{sub 2.82} phases have been observed. The reaction on single crystal has evidenced the evolution of domain structure. For the La{sub 2}CoO{sub 4+{delta}} system, we synthesised a large variety of single crystal with stoichiometry {delta} 0.0, 0.09, 0.12, 0.16, 0.20 and 0.25. Using single crystal X-ray and neutron diffraction, we showed a disorder-order transition of the apical and interstitial oxygen for the higher {delta} values. (author)

  14. Determination of the positions and residues of the. delta. /sup + +/ and. delta. /sup 0/ poles. [Phase shifts,coulomb corrections

    Energy Technology Data Exchange (ETDEWEB)

    Vasan, S S [Carnegie-Mellon Univ., Pittsburgh, Pa. (USA). Dept. of Physics


    The poles and the associated residues in the ..pi..N P/sub 33/ amplitude corresponding to the resonances + +/ and 0/ are determined by fitting the ..pi../sup +/p and ..pi../sup -/p hadronic phase shifts from the Carter 73 analysis. The + +/ and 0/ pole positions are determined also from the nuclear phase shifts, these being the phase shifts made up of the hadronic phase shifts plus the Coulomb corrections. The pole positions obtained from the two sets of phase shifts are different, the differences being larger in the case of the + +/.

  15. [Simultaneous determination of delta13C values of glycerol and ethanol in wine by liquid chromatography coupled with isotope ratio mass spectrometry]. (United States)

    Li, Xuemin; Jia, Guangqun; Cao, Yanzhong; Zhang, Jinjie; Wang, Lei; Sun, Huiyuan


    A novel procedure was established for the characterization of delta13C values of glycerol and ethanol in wine by liquid chromatography-isotope ratio mass spectrometry (LC-IRMS). Several parameters influencing the separation of glycerol and ethanol from wine matrix were optimized. The precision and accuracy of the proposed method were 0.15 per thousand to 0.26 per thousand and 0.11 per thousand to 0.28 per thousand, respectively. The results obtained for 40 wine samples displayed that the delta13C value of glycerol ranged from--26.87 per thousand to--32.96 per thousand and that of ethanol ranged from--24.06 per thousand to--28.29 per thousand. Close correlations (R = 0.82) were obtained between the delta13C values of glycerol and ethanol. The proposed method didn't need complex sample treatment, and the delta13C values of glycerol and ethanol in wine can be simultaneously determined, thus improving the method in terms of simplicity and speed compared with traditional methods.

  16. Curcumin abates hypoxia-induced oxidative stress based-ER stress-mediated cell death in mouse hippocampal cells (HT22) by controlling Prdx6 and NF-κB regulation (United States)

    Chhunchha, Bhavana; Fatma, Nigar; Kubo, Eri; Rai, Prerana; Singh, Sanjay P.


    Oxidative stress and endoplasmic reticulum (ER) stress are emerging as crucial events in the etiopathology of many neurodegenerative diseases. While the neuroprotective contributions of the dietary compound curcumin has been recognized, the molecular mechanisms underlying curcumin's neuroprotection under oxidative and ER stresses remains elusive. Herein, we show that curcumin protects HT22 from oxidative and ER stresses evoked by the hypoxia (1% O2 or CoCl2 treatment) by enhancing peroxiredoxin 6 (Prdx6) expression. Cells exposed to CoCl2 displayed reduced expression of Prdx6 with higher reactive oxygen species (ROS) expression and activation of NF-κB with IκB phosphorylation. When NF-κB activity was blocked by using SN50, an inhibitor of NF-κB, or cells treated with curcumin, the repression of Prdx6 expression was restored, suggesting the involvement of NF-κB in modulating Prdx6 expression. These cells were enriched with an accumulation of ER stress proteins, C/EBP homologous protein (CHOP), GRP/78, and calreticulin, and had activated states of caspases 12, 9, and 3. Reinforced expression of Prdx6 in HT22 cells by curcumin reestablished survival signaling by reducing propagation of ROS and blunting ER stress signaling. Intriguingly, knockdown of Prdx6 by antisense revealed that loss of Prdx6 contributed to cell death by sustaining enhanced levels of ER stress-responsive proapoptotic proteins, which was due to elevated ROS production, suggesting that Prdx6 deficiency is a cause of initiation of ROS-mediated ER stress-induced apoptosis. We propose that using curcumin to reinforce the naturally occurring Prdx6 expression and attenuate ROS-based ER stress and NF-κB-mediated aberrant signaling improves cell survival and may provide an avenue to treat and/or postpone diseases associated with ROS or ER stress. PMID:23364261

  17. Aerodynamic improvement of a delta wing in combination with leading edge flaps

    Directory of Open Access Journals (Sweden)

    Tadateru Ishide


    Full Text Available Recently, various studies of micro air vehicle (MAV and unmanned air vehicle (UAV have been reported from wide range points of view. The aim of this study is to research the aerodynamic improvement of delta wing in low Reynold’s number region to develop an applicative these air vehicle. As an attractive tool in delta wing, leading edge flap (LEF is employed to directly modify the strength and structure of vortices originating from the separation point along the leading edge. Various configurations of LEF such as drooping apex flap and upward deflected flap are used in combination to enhance the aerodynamic characteristics in the delta wing. The fluid force measurement by six component load cell and particle image velocimetry (PIV analysis are performed as the experimental method. The relations between the aerodynamic superiority and the vortex behavior around the models are demonstrated.

  18. The Concentration Dependence of the (Delta)s Term in the Gibbs Free Energy Function: Application to Reversible Reactions in Biochemistry (United States)

    Gary, Ronald K.


    The concentration dependence of (delta)S term in the Gibbs free energy function is described in relation to its application to reversible reactions in biochemistry. An intuitive and non-mathematical argument for the concentration dependence of the (delta)S term in the Gibbs free energy equation is derived and the applicability of the equation to…

  19. 78 FR 21491 - DeltaPoint Capital IV, L.P., DeltaPoint Capital IV (New York), L.P.; Notice Seeking Exemption... (United States)


    ... SMALL BUSINESS ADMINISTRATION [License No. 02/02-0662, 02/02-0661] DeltaPoint Capital IV, L.P., DeltaPoint Capital IV (New York), L.P.; Notice Seeking Exemption Under Section 312 of the Small Business Investment Act, Conflicts of Interest Notice is hereby given that DeltaPoint Capital IV, L.P. and DeltaPoint...

  20. Mida pakub Delta? / Teele Kurm

    Index Scriptorium Estoniae

    Kurm, Teele


    Politsei- ja Piirivalveamet võtab kasutusele ühise Siseministeeriumi infotehnoloogia- ja arenduskeskuse ning Webmedia AS koostööna loodud dokumendihaldussüsteemi Delta. Kust sai Delta oma nime? Projekti "Dokumendihaldussüsteemi juurutamine Siseministeeriumi haldusalas" eesmärgid

  1. Microstructural analysis of the {delta} to {alpha}' phase transformation in plutonium alloys using X-ray diffraction

    Energy Technology Data Exchange (ETDEWEB)

    Platteau, C; Ravat, B; Texier, G; Oudot, B; Delaunay, F, E-mail: [CEA Valduc 21120 Is sur Tille (France)


    The partial martensitic {delta}{yields}{alpha}' transformation in plutonium alloys is sensitive to chemical composition, sample thermal history, as well as crystalline defects. The present work investigates the {delta}-Pu phase microstructure before and after the martensitic transformation {delta}{yields}{delta}+{alpha}'. More precisely, microstructural modifications of the host {delta}-phase, resulting from the stress induced by a cell volume difference of 19% between the {delta} and {alpha}'-phases, were analysed. Microstructural information about crystallite size and microstrain of a highly homogenized Pu-Ga alloy was extracted from x-ray diffraction patterns using a three dimension crystallite size and microstrain model. This is available in Rietveld refinement software and consists in anisotropic broadening analysis of diffraction peaks. Crystallite size doesn't significantly change with the phase transformation contrary to microstrain that is multiplied, on average, by five. Furthermore, internal normal and shear microstress are multiplied, respectively, by 2 and 13 when {alpha}'-phase appears. Last, dislocation densities, calculated from crystallite size and microstrain, are compared to TEM results available in the literature.

  2. Triterpenoid Saponins from Anemone rivularis var. Flore-Minore and Their Anti-Proliferative Activity on HSC-T6 Cells. (United States)

    Wang, Xiao-Yang; Gao, Hui; Xie, Xiao-Jie; Jurhiin, Jirimubatu; Zhang, Mu-Zi-He; Zhou, Yan-Ping; Liu, Rui; Ning, Meng; Han, Jin; Tang, Hai-Feng


    Five previously undescribed triterpenoid saponins ( 1 - 5 ), along with eight known ones ( 6 - 13 ), were isolated from the whole plants of Anemone rivularis var. flore-minore . Their structures were clarified by extensive spectroscopic data and chemical evidence. For the first time, the lupane-type saponins ( 3 and 12 ) were reported from the Anemone genus. The anti-proliferative activity of all isolated saponins was evaluated on hepatic stellate cells (HSC-T6). Saponins 12 and 13 , which possess more monosaccharides than the others, displayed potent anti-proliferative activity, with IC 50 values of 18.21 and 15.56 μM, respectively.

  3. Post-storage cell wall metabolism in two sweet cherry (Prunus avium L.) cultivars displaying different postharvest performance


    Belge, Burcu; Comabella, Eva; Graell i Sarle, Jordi; Lara Ayala, Isabel


    The biochemical processes underlying firmness loss of sweet cherry (Prunus avium L.) fruit are poorly understood.Studies on cell wall metabolism of sweet cherry have been generally undertaken during on-tree development or at harvest maturity, while published reports on postharvest changes are scarce and fragmentary. In this work, cell wall modifications after storage at 0 ºC were studied in two cherry cultivars ('Celeste' and 'Somerset') displaying different postharvest potential. Firmness wa...

  4. Delta-sleep inducing peptide entrapment in the charged macroporous matrices

    International Nuclear Information System (INIS)

    Sukhanova, Tatiana V.; Artyukhov, Alexander A.; Gurevich, Yakov M.; Semenikhina, Marina A.; Prudchenko, Igor A.; Shtilman, Mikhail I.; Markvicheva, Elena A.


    Various biomolecules, for example proteins, peptides etc., entrapped in polymer matrices, impact interactions between matrix and cells, including stimulation of cell adhesion and proliferation. Delta-sleep inducing peptide (DSIP) possesses numerous beneficial properties, including its abilities in burn treatment and neuronal protection. DSIP entrapment in two macroporous polymer matrices based on copolymer of dimethylaminoethyl methacrylate and methylen-bis-acrylamide (Co-DMAEMA-MBAA) and copolymer of acrylic acid and methylen-bis-acrylamide (Co-AA-MBAA) has been studied. Quite 100% of DSIP has been entrapped into positively charged Co-DMAEMA-MBAA matrix, while the quantity of DSIP adsorbed on negatively charged Co-AA-MBAA was only 2–6%. DSIP release from Co-DMAEMA-MBAA was observed in saline solutions (0.9% NaCl and PBS) while there was no DSIP release in water or 25% ethanol, thus ionic strength was a reason of this process. - Graphical abstract: Delta-sleep inducing peptide possessing neuroprotective and wound healing properties was adsorbed on positively charged polymer matrix Co-DMAEMA-MBAA for tissue engineering. The peptide released from Co-DMAEMA-MBAA matrix in function of ionic strength of solution, pH decreasing stimulated peptide release from Co-DMAEMA-MBAA matrix for 3 h. This construction could be a base of new bioactive implants. - Highlights: • Macroporous positively charged Co-DMAEMA-MBAA matrix pore size was 20–35 μm. • DSIP was adsorbed on Co-DMAEMA-MBAA totally in 16 h. • Its release depends on ionic strength of solution (no release in 25% ethanol or water). • Co-DMAEMA-MBAA matrix swelling depends on pH and ionic strength of solution. • DSIP is destroyed in PBS and 0.9% NaCl in 5 days, but in water it was more stable

  5. Delta-sleep inducing peptide entrapment in the charged macroporous matrices

    Energy Technology Data Exchange (ETDEWEB)

    Sukhanova, Tatiana V., E-mail: [Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Laboratory of Cell Interactions, Miklukho-Maklaya st., 16/10 Moscow (Russian Federation); Artyukhov, Alexander A.; Gurevich, Yakov M.; Semenikhina, Marina A. [Mendeleyev University of Chemical Technology of Russia, Research and Teaching Center “Biomaterials”, Miusskaya sq., 9 Moscow (Russian Federation); Prudchenko, Igor A. [Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Laboratory of Peptide Chemistry, Miklukho-Maklaya st., 16/10 Moscow (Russian Federation); Shtilman, Mikhail I. [Mendeleyev University of Chemical Technology of Russia, Research and Teaching Center “Biomaterials”, Miusskaya sq., 9 Moscow (Russian Federation); Markvicheva, Elena A. [Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Laboratory Polymers for Biology, Miklukho-Maklaya st., 16/10 Moscow (Russian Federation)


    Various biomolecules, for example proteins, peptides etc., entrapped in polymer matrices, impact interactions between matrix and cells, including stimulation of cell adhesion and proliferation. Delta-sleep inducing peptide (DSIP) possesses numerous beneficial properties, including its abilities in burn treatment and neuronal protection. DSIP entrapment in two macroporous polymer matrices based on copolymer of dimethylaminoethyl methacrylate and methylen-bis-acrylamide (Co-DMAEMA-MBAA) and copolymer of acrylic acid and methylen-bis-acrylamide (Co-AA-MBAA) has been studied. Quite 100% of DSIP has been entrapped into positively charged Co-DMAEMA-MBAA matrix, while the quantity of DSIP adsorbed on negatively charged Co-AA-MBAA was only 2–6%. DSIP release from Co-DMAEMA-MBAA was observed in saline solutions (0.9% NaCl and PBS) while there was no DSIP release in water or 25% ethanol, thus ionic strength was a reason of this process. - Graphical abstract: Delta-sleep inducing peptide possessing neuroprotective and wound healing properties was adsorbed on positively charged polymer matrix Co-DMAEMA-MBAA for tissue engineering. The peptide released from Co-DMAEMA-MBAA matrix in function of ionic strength of solution, pH decreasing stimulated peptide release from Co-DMAEMA-MBAA matrix for 3 h. This construction could be a base of new bioactive implants. - Highlights: • Macroporous positively charged Co-DMAEMA-MBAA matrix pore size was 20–35 μm. • DSIP was adsorbed on Co-DMAEMA-MBAA totally in 16 h. • Its release depends on ionic strength of solution (no release in 25% ethanol or water). • Co-DMAEMA-MBAA matrix swelling depends on pH and ionic strength of solution. • DSIP is destroyed in PBS and 0.9% NaCl in 5 days, but in water it was more stable.

  6. Six-six (6-6) cell used in X-ray and neutron diffraction experiments under high pressure

    International Nuclear Information System (INIS)

    Nishiyama, Norimasa; Yamada, Akihiro


    At synchrotron radiation facilities and neutron experimental facilities, X-ray diffraction experiments and neutron diffraction experiments under high-pressure for large-capacity of samples are conducted using DIA type device and 6-axis pressure device that add pressure on cubic space. As the anvil assembly capable of mounting on the above two devices, MA6-6 cell has come to be used. This paper introduces the advantages of using MA6-6 cell, pressure region where experiment is possible with MA6-6 cell, and large-capacity high-pressure press beamline P61.2 that simulates MA-6-6 cell. At MA6-6 cell, 6 pieces of the first-stage anvils of DIA type device or 6-axis pressure device pressurize 6 pieces of the second-stage anvils. These second-stage anvils are included in MA6-6 anvil assembly. The greatest feature of MA6-6 cell is the adoption of the frame for taking alignment of the second stage anvils. By combining MA6-6 cell with DIA-type device or 6-axis pressure device, the degree of freedom of experiment increases, which can simplify the experimental setup. (A.O.)

  7. Neolignans from Nectandra megapotamica (Lauraceae Display in vitro Cytotoxic Activity and Induce Apoptosis in Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Vitor Ponci


    Full Text Available Nectandra megapotamica (Spreng. Mez. (Lauraceae is a well-known Brazilian medicinal plant that has been used in folk medicine to treat several diseases. In continuation of our ongoing efforts to discover new bioactive natural products from the Brazilian flora, this study describes the identification of cytotoxic compounds from the MeOH extract of N. megapotamica (Lauraceae leaves using bioactivity-guided fractionation. This approach resulted in the isolation and characterization of eight tetrahydrofuran neolignans: calopeptin (1, machilin-G (2, machilin-I (3, aristolignin (4, nectandrin A (5, veraguensin (6, ganschisandrin (7, and galgravin (8. Different assays were conducted to evaluate their cytotoxic activities and to determine the possible mechanism(s related to the activity displayed against human leukemia cells. The most active compounds 4, 5 and 8 gave IC50 values of 14.2 ± 0.7, 16.9 ± 0.8 and 16.5 ± 0.8 µg/mL, respectively, against human leukemia (HL-60 tumor cells. Moreover, these compounds induced specific apoptotic hallmarks, such as plasma membrane bleb formation, nuclear DNA condensation, specific chromatin fragmentation, phosphatidyl-serine exposure on the external leaflet of the plasma membrane, cleavage of PARP as well as mitochondrial damage, which as a whole could be related to the intrinsic apoptotic pathway.

  8. High-yield production of a stable Vero cell-based vaccine candidate against the highly pathogenic avian influenza virus H5N1

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Fangye; Zhou, Jian; Ma, Lei; Song, Shaohui; Zhang, Xinwen; Li, Weidong; Jiang, Shude [No. 5, Department of Bioproducts, Institute of Medical Biology, Chinese Academy of Medical Science and Pecking Union Medical College, Jiaoling Avenue 935, Kunming, Yunnan Province 650102, People' s Republic of China (China); Wang, Yue [National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Yingxin Lane 100, Xicheng District, Beijing 100052, People' s Republic of China (China); Liao, Guoyang [No. 5, Department of Bioproducts, Institute of Medical Biology, Chinese Academy of Medical Science and Pecking Union Medical College, Jiaoling Avenue 935, Kunming, Yunnan Province 650102, People' s Republic of China (China)


    Highlights: Black-Right-Pointing-Pointer Vero cell-based HPAI H5N1 vaccine with stable high yield. Black-Right-Pointing-Pointer Stable high yield derived from the YNVa H3N2 backbone. Black-Right-Pointing-Pointer H5N1/YNVa has a similar safety and immunogenicity to H5N1delta. -- Abstract: Highly pathogenic avian influenza (HPAI) viruses pose a global pandemic threat, for which rapid large-scale vaccine production technology is critical for prevention and control. Because chickens are highly susceptible to HPAI viruses, the supply of chicken embryos for vaccine production might be depleted during a virus outbreak. Therefore, developing HPAI virus vaccines using other technologies is critical. Meeting vaccine demand using the Vero cell-based fermentation process has been hindered by low stability and yield. In this study, a Vero cell-based HPAI H5N1 vaccine candidate (H5N1/YNVa) with stable high yield was achieved by reassortment of the Vero-adapted (Va) high growth A/Yunnan/1/2005(H3N2) (YNVa) virus with the A/Anhui/1/2005(H5N1) attenuated influenza vaccine strain (H5N1delta) using the 6/2 method. The reassorted H5N1/YNVa vaccine maintained a high hemagglutination (HA) titer of 1024. Furthermore, H5N1/YNVa displayed low pathogenicity and uniform immunogenicity compared to that of the parent virus.

  9. Coulomb-Gas scaling law for a superconducting Bi(2+y)Sr(2-x-y)La(x)CuO(6+delta) thin films in magnetic fields (United States)

    Zhang; Deltour; Zhao


    The electrical transport properties of epitaxial superconducting Bi(2+y)Sr(2-x-y)La(x)CuO(6+delta) thin films have been studied in magnetic fields. Using a modified Coulomb-gas scaling law, we can fit all the magnetic field dependent low resistance data with a universal scaling curve, which allows us to determine a relation between the activation energy of the thermally activated flux flow resistance and the characteristic temperature scaling parameters.

  10. Changes in the areal extents of the Athabasca River, Birch River, and Cree Creek Deltas, 1950-2014, Peace-Athabasca Delta, Canada (United States)

    Timoney, Kevin; Lee, Peter


    Deltas form where riverborne sediment accumulates at the interface of river mouths and their receiving water bodies. Their areal extent is determined by the net effect of processes that increase their extent, such as sediment accumulation, and processes that decrease their extent, such as erosion and subsidence. Through sequential mapping and construction of river discharge and sediment histories, this study examined changes in the subaerial extents of the Cree Creek and Athabasca River Deltas (both on the Athabasca River system) and the Birch River Delta in northern Canada over the period 1950-2014. The purpose of the study was to determine how, when, and why the deltas changed in areal extent. Temporal growth patterns were similar across the Athabasca and Birch River systems indicative of a climatic signal. Little or no areal growth occurred from 1950 to 1968; moderate growth occurred between 1968 and the early to mid-1980s; and rapid growth occurred between 1992 and 2012. Factors that affected delta progradation included dredging, sediment supply, isostatic drowning, delta front bathymetry, sediment capture efficiency, and storms. In relation to sediment delivered, areal growth rates were lowest in the Athabasca Delta, intermediate in the Birch Delta, and highest in the Cree Creek Delta. Annual sediment delivery is increasing in the Cree Creek Delta; there were no significant trends in annual sediment delivery in the Birch and Athabasca Deltas. There was a lag of up to several years between sediment delivery events and progradation. Periods of delta progradation were associated with low water levels of the receiving basins. Predicted climate-change driven declines in river discharge and lake levels may accelerate delta progradation in the region. In the changing ecosystems of northeastern Alberta, inadequate monitoring of vegetation, landforms, and sediment regimes hampers the elucidation of the nature, rate, and causality of ecosystem changes.

  11. An analytical framework for strategic delta planning

    NARCIS (Netherlands)

    Seijger, C.; Douven, W.; Halsema, van G.; Hermans, L.; Evers, J.; Phi, H.L.; Khan, M.F.; Brunner, J.; Pols, L.; Ligtvoet, W.; Koole, S.; Slager, K.; Vermoolen, M.S.; Hasan, S.; Thi Minh Hoang, Vo


    Sectoral planning on water, agriculture and urban development has not been able to prevent increased flood risks and environmental degradation in many deltas. Governments conceive strategic delta planning as a promising planning approach and develop strategic delta plans. Such plans are linked to

  12. Whole thorax irradiation of non-human primates induces persistent nuclear damage and gene expression changes in peripheral blood cells.

    Directory of Open Access Journals (Sweden)

    Shanaz A Ghandhi

    Full Text Available We investigated the cytogenetic and gene expression responses of peripheral blood cells of non-human primates (NHP, Macaca mulatta that were whole-thorax irradiated with a single dose of 10 Gy. In this model, partial irradiation of NHPs in the thoracic region (Whole Thorax Lung Irradiation, WTLI allows the study of late radiation-induced lung injury, while avoiding acute radiation syndromes related to hematopoietic and gastrointestinal injury. A transient drop in circulating lymphocytes and platelets was seen by 9 days, followed by elevations in respiratory rate, circulating neutrophils, lymphocytes, and monocytes at 60-100 days, corresponding to computed tomography (CT and histologic evidence of pneumonitis, and elective euthanasia of four animals. To evaluate long-term DNA damage in NHP peripheral blood lymphocytes after 10 Gy WTLI, we used the cytokinesis-block micronucleus (CBMN assay to measure chromosomal aberrations as post-mitotic micronuclei in blood samples collected up to 8 months after irradiation. Regression analysis showed significant induction of micronuclei in NHP blood cells that persisted with a gradual decline over the 8-month study period, suggesting long-term DNA damage in blood lymphocytes after WTLI. We also report transcriptomic changes in blood up to 30 days after WTLI. We isolated total RNA from peripheral blood at 3 days before and then at 2, 5 and 30 days after irradiation. We identified 1187 transcripts that were significantly changed across the 30-day time course. From changes in gene expression, we identified biological processes related to immune responses, which persisted across the 30-day study. Response to oxygen-containing compounds and bacteria were implicated by gene-expression changes at the earliest day 2 and latest, day 30 time-points. Gene expression changes suggest a persistent altered state of the immune system, specifically response to infection, for at least a month after WTLI.

  13. Whole thorax irradiation of non-human primates induces persistent nuclear damage and gene expression changes in peripheral blood cells. (United States)

    Ghandhi, Shanaz A; Turner, Helen C; Shuryak, Igor; Dugan, Gregory O; Bourland, J Daniel; Olson, John D; Tooze, Janet A; Morton, Shad R; Batinic-Haberle, Ines; Cline, J Mark; Amundson, Sally A


    We investigated the cytogenetic and gene expression responses of peripheral blood cells of non-human primates (NHP, Macaca mulatta) that were whole-thorax irradiated with a single dose of 10 Gy. In this model, partial irradiation of NHPs in the thoracic region (Whole Thorax Lung Irradiation, WTLI) allows the study of late radiation-induced lung injury, while avoiding acute radiation syndromes related to hematopoietic and gastrointestinal injury. A transient drop in circulating lymphocytes and platelets was seen by 9 days, followed by elevations in respiratory rate, circulating neutrophils, lymphocytes, and monocytes at 60-100 days, corresponding to computed tomography (CT) and histologic evidence of pneumonitis, and elective euthanasia of four animals. To evaluate long-term DNA damage in NHP peripheral blood lymphocytes after 10 Gy WTLI, we used the cytokinesis-block micronucleus (CBMN) assay to measure chromosomal aberrations as post-mitotic micronuclei in blood samples collected up to 8 months after irradiation. Regression analysis showed significant induction of micronuclei in NHP blood cells that persisted with a gradual decline over the 8-month study period, suggesting long-term DNA damage in blood lymphocytes after WTLI. We also report transcriptomic changes in blood up to 30 days after WTLI. We isolated total RNA from peripheral blood at 3 days before and then at 2, 5 and 30 days after irradiation. We identified 1187 transcripts that were significantly changed across the 30-day time course. From changes in gene expression, we identified biological processes related to immune responses, which persisted across the 30-day study. Response to oxygen-containing compounds and bacteria were implicated by gene-expression changes at the earliest day 2 and latest, day 30 time-points. Gene expression changes suggest a persistent altered state of the immune system, specifically response to infection, for at least a month after WTLI.

  14. Inhibitor of DNA binding 1 (Id1) induces differentiation and proliferation of mouse embryonic carcinoma P19CL6 cells

    International Nuclear Information System (INIS)

    Meng, Qingzhen; Jia, Zhuqing; Wang, Weiping; Li, Binhong; Ma, Kangtao; Zhou, Chunyan


    Highlights: → Id1 was upregulated during the cardiac differentiation process of P19CL6 cells. → Id1 upregulated expression of cardiac specific genes Gata4, α-MHC and ISL1. → Id1 promoted proliferation of P19CL6 cells. → Overexpression of Id1 increased activity of TOP flash. → Wnt3a or LiCl treatment promoted Id1 expression in P19CL6 cells. -- Abstract: The inhibitor of DNA binding (Id) family of genes encodes negative regulators of basic helix-loop-helix transcription factors and has been implicated in such diverse cellular processes as differentiation, proliferation, apoptosis and migration. Id knockout mouse embryos display multiple cardiac defects but the specific role of Id1 in cardiac differentiation is unclear. In the present study, we investigated the function of Id1 in DMSO-induced P19CL6 cells, a widely-accepted cell model of cardiac differentiation. We found that Id1 was upregulated during the cardiac differentiation of P19CL6 cells. The expression of cardiac specific marker genes, Gata4, α-MHC and ISL1, was upregulated in P19CL6 cells stably transfected with Id1 (P19CL6-Id1) during cardiac differentiation. The overexpression of Id1 reduced the number of cells in G1 phase and increased the cell population in G2, M and S phases, while knockdown of Id1 increased the number of cells in G1 phase from 48.6 ± 2.51% to 62.2 ± 1.52% at day 0 of cardiac induction, and from 52.5 ± 3.41% to 63.7 ± 1.02% at day 3 after cardiac induction, indicating that Id1 promoted proliferation of P19CL6 cells. Luciferase assays showed that the activity of TOP flash was higher in P19CL6-Id1 cells than wildtype P19CL6 cells, while Id1 expression was also upregulated in P19CL6 cells treated with Wnt3a or LiCl. This indicates that there may be positive feedback between Id1 and Wnt signaling which plays an important role in cardiac differentiation.

  15. The GPRC6A Receptor displays Constitutive Internalization and Sorting to the Slow Recycling Pathway

    DEFF Research Database (Denmark)

    Jacobsen, Stine Engesgaard; Ammendrup-Johnsen, Ina; Jansen, Anna Mai


    The class C G protein-coupled receptor GPRC6A is a putative nutrient sensing receptor and represents a possible new drug target in metabolic disorders. However, the specific physiological role of this receptor has yet to be identified, and the mechanisms regulating its activity and cell surface...... availability also remain enigmatic. In the present study, we investigated the trafficking properties of GPRC6A by use of both a classical antibody feeding internalization assay in which cells were visualized using confocal microscopy and a novel internalization assay that is based on real-time measurements...... slow recycling pathway, which may be responsible for ensuring a persistent pool of GPRC6A receptors at the cell surface despite chronic agonist exposure. Distinct trafficking pathways have been reported for several of the class C receptors, and our results thus substantiate that non...

  16. Heterologous surface display on lactic acid bacteria: non-GMO alternative? (United States)

    Zadravec, Petra; Štrukelj, Borut; Berlec, Aleš


    Lactic acid bacteria (LAB) are food-grade hosts for surface display with potential applications in food and therapy. Alternative approaches to surface display on LAB would avoid the use of recombinant DNA technology and genetically-modified organism (GMO)-related regulatory requirements. Non-covalent surface display of proteins can be achieved by fusing them to various cell-wall binding domains, of which the Lysine motif domain (LysM) is particularly well studied. Fusion proteins have been isolated from recombinant bacteria or from their growth medium and displayed on unmodified bacteria, enabling heterologous surface display. This was demonstrated on non-viable cells devoid of protein content, termed bacteria-like particles, and on various species of genus Lactobacillus. Of the latter, Lactobacillus salivarius ATCC 11741 was recently shown to be particularly amenable for LysM-mediated display. Possible regulatory implications of heterologous surface display are discussed, particularly those relevant for the European Union.

  17. Tracks, spurs, blobs and delta-rays

    International Nuclear Information System (INIS)

    Magee, J.L.; Chatterjee, A.


    The track of a high-energy particle is the collection of all transient species created by the particle in the total degradation of its energy. Visible electron tracks are called delta rays. A microscopic description of the track with all its knocked-out electrons leads to spurs, blobs, and short tracks. Energy deposition criteria for these three track entities are 6 to 100 eV, 100 to 500 eV, and 500 eV to 5 keV, respectively

  18. Spatio-temporal distributions of delta18O, delta D and salinity in the Arabian Sea: Identifying processes and controls

    Digital Repository Service at National Institute of Oceanography (India)

    Deshpande, R.D; Muraleedharan, P.M.; Singh, R.L.; Kumar, B.; Rao, M.S.; Dave, M.; Sivakumar, K.U.; Gupta, S.K.

    the geographic distributions of the delta18O and S; (2) in spite of a large scatter, a statistically significant delta18O–S relationship can be identified in much of the investigated part of the AS; (3) the delta18Odelta...

  19. The Sur7 protein regulates plasma membrane organization and prevents intracellular cell wall growth in Candida albicans. (United States)

    Alvarez, Francisco J; Douglas, Lois M; Rosebrock, Adam; Konopka, James B


    The Candida albicans plasma membrane plays important roles in cell growth and as a target for antifungal drugs. Analysis of Ca-Sur7 showed that this four transmembrane domain protein localized to stable punctate patches, similar to the plasma membrane subdomains known as eisosomes or MCC that were discovered in S. cerevisiae. The localization of Ca-Sur7 depended on sphingolipid synthesis. In contrast to S. cerevisiae, a C. albicans sur7Delta mutant displayed defects in endocytosis and morphogenesis. Septins and actin were mislocalized, and cell wall synthesis was very abnormal, including long projections of cell wall into the cytoplasm. Several phenotypes of the sur7Delta mutant are similar to the effects of inhibiting beta-glucan synthase, suggesting that the abnormal cell wall synthesis is related to activation of chitin synthase activity seen under stress conditions. These results expand the roles of eisosomes by demonstrating that Sur7 is needed for proper plasma membrane organization and cell wall synthesis. A conserved Cys motif in the first extracellular loop of fungal Sur7 proteins is similar to a characteristic motif of the claudin proteins that form tight junctions in animal cells, suggesting a common role for these tetraspanning membrane proteins in forming specialized plasma membrane domains.

  20. GdBa{sub 0.5}Sr{sub 0.5}Co{sub 2}O{sub 5+{delta}} layered perovskite as promising cathode for proton conducting solid oxide fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Hanping [Department of Mechanical Engineering, University of South Carolina, Columbia, SC 29208 (United States); Xue, Xingjian, E-mail: [Department of Mechanical Engineering, University of South Carolina, Columbia, SC 29208 (United States)


    BaZr{sub 0.1}Ce{sub 0.7}Y{sub 0.2}O{sub 3-{delta}} (BZCY7) exhibits adequate proton conductivity as well as sufficient chemical and thermal stability over a wide range of SOFC operating conditions, while layered GdBa{sub 0.5}Sr{sub 0.5}Co{sub 2}O{sub 5+{delta}} (GBSC) perovskite deposited on a doped ceria electrolyte demonstrates advanced electrochemical properties. This research fully takes advantage of these advanced properties and develops novel protonic ceramic membrane fuel cells (PCMFCs) of Ni-BZCY7|BZCY7|GBSC. The results show that the open-circuit potential of 1.003 V, maximum power density of 430 mW cm{sup -2}, and a low polarization resistance of the electrodes of 0.08 {Omega} cm{sup 2} are achieved at 700 {sup o}C. With temperature increases, the total cell resistance decreases, among which electrolyte resistance becomes increasingly dominant over polarization resistance. The results also indicate that GBSC perovskite cathode is a good candidate for intermediate temperature PCMFC development, while the developed Ni-BZCY7|BZCY7|GBSC cell is a promising functional material system for next generation SOFCs.

  1. Adaptive Delta Management: cultural aspects of dealing with uncertainty (United States)

    Timmermans, Jos; Haasnoot, Marjolijn; Hermans, Leon; Kwakkel, Jan


    Deltas are generally recognized as vulnerable to climate change and therefore a salient topic in adaptation science. Deltas are also highly dynamic systems viewed from physical (erosion, sedimentation, subsidence), social (demographic), economic (trade), infrastructures (transport, energy, metropolization) and cultural (multi-ethnic) perspectives. This multi-faceted dynamic character of delta areas warrants the emergence of a branch of applied adaptation science, Adaptive Delta Management, which explicitly focuses on climate adaptation of such highly dynamic and deeply uncertain systems. The application of Adaptive Delta Management in the Dutch Delta Program and its active international dissemination by Dutch professionals results in the rapid dissemination of Adaptive Delta Management to deltas worldwide. This global dissemination raises concerns among professionals in delta management on its applicability in deltas with cultural conditions and historical developments quite different from those found in the Netherlands and the United Kingdom where the practices now labelled as Adaptive Delta Management first emerged. This research develops an approach and gives a first analysis of the interaction between the characteristics of different approaches in Adaptive Delta Management and their alignment with the cultural conditions encountered in various delta's globally. In this analysis, first different management theories underlying approaches to Adaptive Delta Management as encountered in both scientific and professional publications are identified and characterized on three dimensions: The characteristics dimensions used are: orientation on today, orientation on the future, and decision making (Timmermans, 2015). The different underlying management theories encountered are policy analysis, strategic management, transition management, and adaptive management. These four management theories underlying different approaches in Adaptive Delta Management are connected to

  2. Development of a middle cerebral artery occlusion model in the nonhuman primate and a safety study of i.v. infusion of human mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    Masanori Sasaki

    Full Text Available Most experimental stroke research is carried out in rodents, but given differences between rodents and human, nonhuman primate (NHP models may provide a valuable tool to study therapeutic interventions. The authors developed a surgical method for transient occlusion of the M1 branch of middle cerebral artery (MCA in the African green monkey to evaluate safety aspects of intravenous infusion of mesenchymal stem cells (hMSCs derived from human bone marrow.The left Sylvian fissure was exposed by a small fronto-temporal craniotomy. The M1 branch of the MCA was exposed by microsurgical dissection and clipped for 2 to 4 hours. Neurological examinations and magnetic resonance imaging (MRI were carried out at regular post-operative course. hMSCs were infused 1 hour after reperfusion (clip release in the 3-hour occlusion model.During M1 occlusion, two patterns of changes were observed in the lateral hemisphere surface. One pattern (Pattern 1 was darkening of venous blood, small vessel collapse, and blood pooling with no venous return in cortical veins. Animals with these three features had severe and lasting hemiplegia and MRI demonstrated extensive MCA territory infarction. Animals in the second pattern (Pattern 2 displayed darkening of venous blood, small vessel collapse, and reduced but incompletely occluded venous flow and the functional deficit was much less severe and MRI indicated smaller infarction areas in brain. The severe group (Pattern 1 likely had less extensive collateral circulation than the less severe group (Pattern 2 where venous pooling of blood was not observed. The hMSC infused animals showed a trend for greater functional improvement that was not statistically significant in the acute phase and no additive negative effects.These results indicate inter-animal variability of collateral circulation after complete M1 occlusion and that hMSC infusion is safe in the developed NHP stroke model.

  3. Time-Sequential Working Wavelength-Selective Filter for Flat Autostereoscopic Displays

    Directory of Open Access Journals (Sweden)

    René de la Barré


    Full Text Available A time-sequential working, spatially-multiplexed autostereoscopic 3D display design consisting of a fast switchable RGB-color filter array and a fast color display is presented. The newly-introduced 3D display design is usable as a multi-user display, as well as a single-user system. The wavelength-selective filter barrier emits the light from a larger aperture than common autostereoscopic barrier displays with similar barrier pitch and ascent. Measurements on a demonstrator with commercial display components, simulations and computational evaluations have been carried out to describe the proposed wavelength-selective display design in static states and to show the weak spots of display filters in commercial displays. An optical modelling of wavelength-selective barriers has been used for instance to calculate the light ray distribution properties of that arrangement. In the time-sequential implementation, it is important to avoid that quick eye or eyelid movement leads to visible color artifacts. Therefore, color filter cells, switching faster than conventional LC display cells, must distribute directed light from different primaries at the same time, to create a 3D presentation. For that, electric tunable liquid crystal Fabry–Pérot color filters are presented. They switch on-off the colors red, green and blue in the millisecond regime. Their active areas consist of a sub-micrometer-thick nematic layer sandwiched between dielectric mirrors and indium tin oxide (ITO-electrodes. These cells shall switch narrowband light of red, green or blue. A barrier filter array for a high resolution, glasses-free 3D display has to be equipped with several thousand switchable filter elements having different color apertures.

  4. Possible options to slow down the advancement rate of Tarbela delta. (United States)

    Habib-Ur-Rehman; Rehman, Mirza Abdul; Naeem, Usman Ali; Hashmi, Hashim Nisar; Shakir, Abdul Sattar


    The pivot point of delta in Tarbela dam has reached at about 10.6 km from the dam face which may result in blocking of tunnels. Tarbela delta was modeled from 1979 to 2060 using hec-6 model. Initially, the model was calibrated for year 1999 and validated for years 2000, 2001, 2002, and 2006 by involving the data of sediment concentration, reservoir cross sections (73 range lines), elevation-area capacity curves, and inflows and outflows from the reservoir. Then, the model was used to generate future scenarios, i.e., run-1, run-2, and run-3 with pool levels; 428, 442, and 457 m, respectively, till 2060. Results of run-1 and run-2 showed advancement to choke the tunnels by 2010 and 2030, respectively. Finally, in run-3, the advancement was further delayed showing that tunnels 1 and 2 will be choked by year 2050 and pivot point will reach at 6.4 km from the dam face.

  5. Baculovirus display of single chain antibody (scFv using a novel signal peptide

    Directory of Open Access Journals (Sweden)

    Gonzalez Gaëlle


    Full Text Available Abstract Background Cells permissive to virus can become refractory to viral replication upon intracellular expression of single chain fragment variable (scFv antibodies directed towards viral structural or regulatory proteins, or virus-coded enzymes. For example, an intrabody derived from MH-SVM33, a monoclonal antibody against a conserved C-terminal epitope of the HIV-1 matrix protein (MAp17, was found to exert an inhibitory effect on HIV-1 replication. Results Two versions of MH-SVM33-derived scFv were constructed in recombinant baculoviruses (BVs and expressed in BV-infected Sf9 cells, N-myristoylation-competent scFvG2/p17 and N-myristoylation-incompetent scFvE2/p17 protein, both carrying a C-terminal HA tag. ScFvG2/p17 expression resulted in an insoluble, membrane-associated protein, whereas scFvE2/p17 was recovered in both soluble and membrane-incorporated forms. When coexpressed with the HIV-1 Pr55Gag precursor, scFvG2/p17 and scFvE2/p17 did not show any detectable negative effect on virus-like particle (VLP assembly and egress, and both failed to be encapsidated in VLP. However, soluble scFvE2/p17 isolated from Sf9 cell lysates was capable of binding to its specific antigen, in the form of a synthetic p17 peptide or as Gag polyprotein-embedded epitope. Significant amounts of scFvE2/p17 were released in the extracellular medium of BV-infected cells in high-molecular weight, pelletable form. This particulate form corresponded to BV particles displaying scFvE2/p17 molecules, inserted into the BV envelope via the scFv N-terminal region. The BV-displayed scFvE2/p17 molecules were found to be immunologically functional, as they reacted with the C-terminal epitope of MAp17. Fusion of the N-terminal 18 amino acid residues from the scFvE2/p17 sequence (N18E2 to another scFv recognizing CD147 (scFv-M6-1B9 conferred the property of BV-display to the resulting chimeric scFv-N18E2/M6. Conclusion Expression of scFvE2/p17 in insect cells using a BV

  6. Plasticity in intact A delta- and C-fibers contributes to cold hypersensitivity in neuropathic rats. (United States)

    Ji, G; Zhou, S; Kochukov, M Y; Westlund, K N; Carlton, S M


    Cold hypersensitivity is a common sensory abnormality accompanying peripheral neuropathies and is difficult to treat. Progress has been made in understanding peripheral mechanisms underlying neuropathic pain but little is known concerning peripheral mechanisms of cold hypersensitivity. The aim of this study was to analyze the contribution of uninjured primary afferents to the cold hypersensitivity that develops in neuropathic rats. Rats with a lumbar 5 (L5) and L6 spinal nerve ligation (SNL, Chung model) but not sham, developed mechanical allodynia, evidenced by decreased paw withdrawal thresholds and increased magnitude of response to von Frey stimulation. Cold hypersensitivity also developed in SNL but not sham rats, evidenced by enhanced nociceptive behaviors induced by placement on a cold plate (6 degrees C) or application of icilin (a transient receptor potential M8 (TRPM8)/transient receptor potential A1 (TRPA1) receptor agonist) to nerve-injured hind paws. Single fiber recordings demonstrated that the mean conduction velocities of intact L4 cutaneous A delta- and C-fibers were not different between naive and SNL rats; however, mechanical thresholds of the A delta- but not the C-fibers were significantly decreased in SNL compared with naive. There was a higher prevalence of C-mechanoheat-cold (CMHC) fibers in SNL compared with naive, but the overall percentage of cold-sensitive C-fibers was not significantly increased compared with naive. This was in contrast to the numerous changes in A delta-fibers: the percentage of L4 cold sensitive A delta-, but not C-fibers, was significantly increased, the percentage of L4 icilin-sensitive A delta-, but not C-fibers, was significantly increased, the icilin-induced activity of L4 A delta-, but not C-fibers, was significantly increased. Icilin-induced activity was blocked by the TRPA1 antagonist Ruthenium Red. The results indicate plasticity in both A delta- and C-uninjured fibers, but A delta fibers appear to provide a

  7. Sediment and Vegetation Controls on Delta Channel Networks (United States)

    Lauzon, R.; Murray, A. B.; Piliouras, A.; Kim, W.


    Numerous factors control the patterns of distributary channels formed on a delta, including water and sediment discharge, grain size, sea level rise rates, and vegetation type. In turn, these channel networks influence the shape and evolution of a delta, including what types of plant and animal life - such as humans - it can support. Previous fluvial modeling and flume experiments, outside of the delta context, have addressed how interactions between sediment and vegetation, through their influence on lateral transport of sediment, determine what type of channel networks develops. Similar interactions likely also shape delta flow patterns. Vegetation introduces cohesion, tending to reduce channel migration rates and strengthen existing channel banks, reinforcing existing channels and resulting in localized, relatively stable flow patterns. On the other hand, sediment transport processes can result in lateral migration and frequent switching of active channels, resulting in flow resembling that of a braided stream. While previous studies of deltas have indirectly explored the effects of vegetation through the introduction of cohesive sediment, we directly incorporate key effects of vegetation on flow and sediment transport into the delta-building model DeltaRCM to explore how these effects influence delta channel network formation. Model development is informed by laboratory flume experiments at UT Austin. Here we present initial results of experiments exploring the effects of sea level rise rate, sediment grain size, vegetation type, and vegetation growth rate on delta channel network morphology. These results support the hypothesis that the ability for lateral transport of sediment to occur plays a key role in determining the evolution of delta channel networks and delta morphology.

  8. Cyclopentenone prostaglandins as potential inducers of phase II detoxification enzymes. 15-deoxy-delta(12,14)-prostaglandin j2-induced expression of glutathione S-transferases. (United States)

    Kawamoto, Y; Nakamura, Y; Naito, Y; Torii, Y; Kumagai, T; Osawa, T; Ohigashi, H; Satoh, K; Imagawa, M; Uchida, K


    Exposure of cells to a wide variety of chemoprotective compounds confers resistance to a broad set of carcinogens. For a subset of the chemoprotective compounds, protection is generated by an increase in the abundance of protective enzymes, such as glutathione S-transferases (GSTs). In the present study, we developed a cell culture system that potently responds to phenolic antioxidants and found that antitumor prostaglandins (PGs) are potential inducers of GSTs. We screened primary hepatocytes and multiple cell lines for inducing GST activity upon incubation with the phenolic antioxidant (tert-butylhydroquinone) and found that rat liver epithelial RL34 cells most potently responded. Based on an extensive screening of diverse chemical agents on the induction of GST activity in RL34 cells, the J2 series of PGs, 15-deoxy-Delta(12,14)-prostaglandin J2 (15-deoxy-Delta(12,14)-PGJ2) in particular, were found to be potential inducers of GST. Enhanced gene expression of Class pi GST isozyme (GSTP1) by 15-deoxy-Delta(12,14)-PGJ2 was evident as a drastic elevation of the mRNA level. Hence, we examined the molecular mechanism underlying the 15-deoxy-Delta(12, 14)-PGJ2-induced GSTP1 gene expression. From functional analysis of various deletion mutant genes, we found that the 15-deoxy-Delta(12, 14)-PGJ2 reponse element was localized in a region containing a GSTP1 enhancer I (GPEI) that consists of two imperfect phorbol 12-O-tetradecanoylphorbol-13-acetate response elements. When the GPEI was combined with the minimum GSTP1 promoter, the element indeed showed an enhancer activity in response to 15-deoxy-Delta(12, 14)-PGJ2. Point mutations of either of the two imperfect 12-O-tetradecanoylphorbol-13-acetate response elements in GPEI completely abolished the enhancer activity. Gel mobility shift assays demonstrated that 15-deoxy-Delta(12,14)-PGJ2 specifically stimulated the binding of nuclear proteins including the transcription factor c-Jun, but not Nrf2, to GPEI. These results

  9. A dynamic soil chamber system coupled with a tunable diode laser for online measurements of delta-13C, delta-18O, and efflux rate of soil respired CO2

    Energy Technology Data Exchange (ETDEWEB)

    Powers, Heath H [Los Alamos National Laboratory; Mcdowell, Nate [Los Alamos National Laboratory; Hanson, David [UNM; Hunt, John [LANDCARE RESEARCH


    High frequency observations of the stable isotopic composition of CO(2) effluxes from soil have been sparse due in part to measurement challenges. We have developed an open-system method that utilizes a flow-through chamber coupled to a tunable diode laser (TDL) to quantify the rate of soil CO(2) efflux and its delta(13)C and delta(18)O values (delta(13)C(R) and delta(18)O(R), respectively). We tested the method first in the laboratory using an artificial soil test column and then in a semi-arid woodland. We found that the CO(2) efflux rates of 1.2 to 7.3 micromol m(-2) s(-1) measured by the chamber-TDL system were similar to measurements made using the chamber and an infrared gas analyzer (IRGA) (R(2) = 0.99) and compared well with efflux rates generated from the soil test column (R(2) = 0.94). Measured delta(13)C and delta(18)O values of CO(2) efflux using the chamber-TDL system at 2 min intervals were not significantly different from source air values across all efflux rates after accounting for diffusive enrichment. Field measurements during drought demonstrated a strong dependency of CO(2) efflux and isotopic composition on soil water content. Addition of water to the soil beneath the chamber resulted in average changes of +6.9 micromol m(-2) s(-1), -5.0 per thousand, and -55.0 per thousand for soil CO(2) efflux, delta(13)C(R) and delta(18)O(R), respectively. All three variables initiated responses within 2 min of water addition, with peak responses observed within 10 min for isotopes and 20 min for efflux. The observed delta(18)O(R) was more enriched than predicted from temperature-dependent H(2)O-CO(2) equilibration theory, similar to other recent observations of delta(18)O(R) from dry soils (Wingate L, Seibt U, Maseyk K, Ogee J, Almeida P, Yakir D, Pereira JS, Mencuccini M. Global Change Biol. 2008; 14: 2178). The soil chamber coupled with the TDL was found to be an effective method for capturing soil CO(2) efflux and its stable isotope composition at high

  10. The Undiscovered Country: How Many Low-Delta-V Near-Earth Objects Remain to be Found? (United States)

    Elvis, Martin; Ranjan, Sukrit; Galache, Jose Luis


    Low delta-v near-Earth objects (NEOs) are of great interest as targets for science and human missions, for possible retrieval to cis-lunar space and as potential resource targets for both exploration and commercial uses. This interest stems from the exponential nature of the rocket equation that imposes a harsh mass penalty on any mission to a higher delta-v. We have compared the known NEO population from the IAU Minor Planet Center (MPC) with the NEOSSat-1 model residence times for the NEO population (Greenstreet & Gladman, 2012) to assess how many undiscovered NEOs there are as a function of H magnitude and delta-v. We find that the median of known NEOs is at lower delta-v (7.3 km/s) than the model population (9.8 km/s), suggesting a bias toward detecting lower delta-v NEOs. To the precision of our data, which is as low as 40% for the 300-500 m diameter (D) objects, the bulk of the larger D>300 m NEOs have been found from delta-v<10.3 km/s. However in the 50 < D < 300 m range there are tens of thousands of delta-v < 10.3 km/s to be found. We examine the total number of undiscovered NEOs as a function of delta-v and find that to find at least 100 now unknown NEOs requires a threshold delta-v of 5.7 km/s, while to find at least 1000 of them requires a threshold delta-v of 6.2 km/s. These numbers can be used to determine mission delta-v requirements for a given number of suitable targets, that will likely be restricted by other criteria (size, composition, spin state) to a few percent of the total population.

  11. Interaction of 3,8-diazabicyclo (3.2.1) octanes with mu and delta opioid receptors. (United States)

    Cignarella, G; Barlocco, D; Tranquillini, M E; Volterra, A; Brunello, N; Racagni, G


    A series of 3,8-diazabicyclo (3.2.1) octanes (DBO) (1) substituted at the nitrogen atoms by acyl and aralkenyl groups, were tested in in vitro binding assays towards mu and delta opioid receptors. The most representative terms (1a, 1d, 1g, 1j,) were also evaluated for the analgesic potency in vivo by the hot plate method. Among the compounds tested the most potent was the p.nitrocinnamyl DBO (1d) which displayed a mu/delta selectivity and an analgesic activity respectively 25 and 17 fold those of morphine. On the contrary, the m.hydroxycinnamyl DBO (1g) was markedly less active as agonist than the parent 1a, thus suggesting that structure 1 interacts with opioid receptors in a different fashion than morphine. Compound 1j isomer of 1a which is provided with high mu affinity, but lower analgesic potency, was found to possess a mixed agonist-antagonist activity.

  12. Perspectives on bay-delta science and policy (United States)

    Healey, Michael; Dettinger, Michael; Norgaard, Richard


    The State of Bay–Delta Science 2008 highlighted seven emerging perspectives on science and management of the Delta. These perspectives had important effects on policy and legislation concerning management of the Delta ecosystem and water exports. From the collection of papers that make up the State of Bay–Delta Science 2016, we derive another seven perspectives that augment those published in 2008. The new perspectives address nutrient and contaminant concentrations in Delta waters, the failure of the Delta food web to support native species, the role of multiple stressors in driving species toward extinction, and the emerging importance of extreme events in driving change in the ecosystem and the water supply. The scientific advances that underpin these new perspectives were made possible by new measurement and analytic tools. We briefly discuss some of these, including miniaturized acoustic fish tags, sensors for monitoring of water quality, analytic techniques for disaggregating complex contaminant mixtures, remote sensing to assess levee vulnerability, and multidimensional hydrodynamic modeling. Despite these new tools and scientific insights, species conservation objectives for the Delta are not being met. We believe that this lack of progress stems in part from the fact that science and policy do not incorporate sufficiently long-term perspectives. Looking forward half a century was central to the Delta Visioning process, but science and policy have not embraced this conceptual breadth. We are also concerned that protection and enhancement of the unique cultural, recreational, natural resource, and agricultural values of the Delta as an evolving place, as required by the Delta Reform Act, has received no critical study and analysis. Adopting wider and longer science and policy perspectives immediately encourages recognition of the need for evaluation, analysis, and public discourse on novel conservation approaches. These longer and wider perspectives

  13. Electronic Structure of TlBa2CaCu2O(7-Delta) (United States)

    Vasquez, R. P.; Novikov, D. L.; Freeman, A. J.; Siegal, M. P.


    The core levels of TlBa2CaCu2O(7-delta) (Tl-1212) epitaxial films have been measured with X-ray photoelectron spectroscopy (XPS). The valence electronic structure has been determined using the full-potential linear muffin-tin-orbital band-structure method and measured with XPS. The calculations show that a van Hove singularity (VHS) lies above the Fermi level (E(sub F)) for the stoichiometric compound (delta = 0.5), while for 50% oxygen vacancies in the Tl-O layer (delta = 0.5) E(sub F) is in close proximity to the VHS. Samples annealed in nitrogen (to reduce the hole overdoping by the removal of oxygen) exhibit higher core-level binding energies and a higher T(sub c), consistent with a shift of E(sub F) closer to the VHS. Comparisons are made to the core levels and valence bands of Tl2Ba2CaCu2O(8 + delta)(Tl-2212) and HgBa2CaCu2O)6 + delta) (Hg- 1212). The similarity of the Cu 2p(sub 3/2) spectra for Tl-1212 and Tl-2212 indicates that the number of Tl-O layers has little effect on the Cu-O bonding. However, the Tl-1212 and Hg-1212 Cu 2p(sub 3/2) signals exhibit differences which suggest that the replacement of T(sup 3+) with Hg(sup 2+) results in a decrease in the O 2p right arrow Cu 3d charge-transfer energy and differences in the probabilities of planar vs apical oxygen charge transfer and/or Zhang-Rice singlet-state formation. Differences between the Tl-1212 and the Tl-2212 and Hg-1212 measured valence bands are consistent with the calculated Cu 3d and (Tl,Hg) 6s/5d partial densities of states.

  14. Multiple myeloma in Niger Delta, Nigeria: complications and the outcome of palliative interventions (United States)

    Nwabuko, Ogbonna Collins; Igbigbi, Elizabeth Eneikido; Chukwuonye, Innocent Ijezie; Nnoli, Martin Anazodo


    Background Multiple myeloma (MM) is one of the hematological malignancies that require palliative care. This is because of the life-threatening nature and the suffering associated with the illness. The aim of this study is to bring to the fore the complications experienced by people living with MM in the Niger-Delta region of Nigeria and the outcome of various palliative interventions. Methods This was a 10-year multi-center retrospective study of 26 patients diagnosed and managed in three major centers in the Niger-Delta region of Nigeria from January 2003 to December 2012. Information on the clinical, laboratory, radiological data, and palliative treatment was obtained at presentation and subsequently at intervals of 3 months until the patient was lost to follow-up. Result The mean duration from onset of symptoms to diagnosis was 13.12 months (95% CI, 6.65–19.58). A total of 16 (61.5%), eight (30.8%), and two subjects (7.7%) presented in Durie–Salmon (DS) stages III, II, and I, respectively. The complications presented by patients at diagnoses included bone pain (84.6%), anemia (61.5%), nephropathy (23.1%), and hemiplegia (35%). All the patients received analgesics, while 50.0% received blood transfusion, 56.7% had surgery performed, 19% had hemodialysis, and 3.8% received radiotherapy. A total of 10 (38%) patients benefited from bisphosphonates (BPs). A total of 57.6% of patients were on melphalan–prednisone (MP) double regimen, while 19% and 8% patients were on MP–thalidomide and MP–bortezomib triple regimens, respectively. A total of 3.8% of patients at DS stage IIIB disease had autologous stem-cell transplantation (ASCT). Only 7.6% of the myeloma patients survived up to 5 years post diagnosis. The overall mean survival interval was 39.7 months (95% CI, 32.1–47.2). Conclusion Late diagnosis and inadequate palliative care account for major complications encountered by MM patients in the Niger-Delta region of Nigeria. This could be responsible for

  15. Characterization of middle Eocene tide-influenced delta: a study ...

    Indian Academy of Sciences (India)


    Running Title: Eocene tide-influenced delta in South Cambay Basin. Manuscript. Click here to view linked References. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10 .... systematic documentation of the facies types to establish the depositional environment of the .... Hazad Member consists of a number of sandstone units separated by intervening ...

  16. Speculations about the upper Miocene change in abyssal Pacific dissolved bicarbonate delta13C

    International Nuclear Information System (INIS)

    Bender, M.L.; Keigwin, L.D. Jr


    New data from three Tasman Sea cores support Kleigwin's observation that the delta 13 C of Pacific benthic foraminifera (and by inference bottom-water TCO 2 ) decreased by 0.7 per thousand at about 6.5 Myr B.P. Simple box models are developed and used to test several hypotheses about the cause of the delta 13 C decrease. The authors favor the idea that the delta 13 C shift was due to a rapid change in TCO 2 cycling within the oceans (such as would result from either a decrease in upwelling rate, or an increase in the fraction of PO 4 3- reaching the deep oceans in particulate organic matter and a corresponding drop in the performed PO 4 3- concentration). The delta 13 C decrease across the shift might reflect either a global decrease in upwelling rate, or a different abyssal circulation pattern before the shift. (Auth.)

  17. Water and nitrogen conditions affect the relationships of Delta13C and Delta18O to gas exchange and growth in durum wheat. (United States)

    Cabrera-Bosquet, Llorenç; Molero, Gemma; Nogués, Salvador; Araus, José Luis


    Whereas the effects of water and nitrogen (N) on plant Delta(13)C have been reported previously, these factors have scarcely been studied for Delta(18)O. Here the combined effect of different water and N regimes on Delta(13)C, Delta(18)O, gas exchange, water-use efficiency (WUE), and growth of four genotypes of durum wheat [Triticum turgidum L. ssp. durum (Desf.) Husn.] cultured in pots was studied. Water and N supply significantly increased plant growth. However, a reduction in water supply did not lead to a significant decrease in gas exchange parameters, and consequently Delta(13)C was only slightly modified by water input. Conversely, N fertilizer significantly decreased Delta(13)C. On the other hand, water supply decreased Delta(18)O values, whereas N did not affect this parameter. Delta(18)O variation was mainly determined by the amount of transpired water throughout plant growth (T(cum)), whereas Delta(13)C variation was explained in part by a combination of leaf N and stomatal conductance (g(s)). Even though the four genotypes showed significant differences in cumulative transpiration rates and biomass, this was not translated into significant differences in Delta(18)O(s). However, genotypic differences in Delta(13)C were observed. Moreover, approximately 80% of the variation in biomass across growing conditions and genotypes was explained by a combination of both isotopes, with Delta(18)O alone accounting for approximately 50%. This illustrates the usefulness of combining Delta(18)O and Delta(13)C in order to assess differences in plant growth and total transpiration, and also to provide a time-integrated record of the photosynthetic and evaporative performance of the plant during the course of crop growth.

  18. Autoradiographic analysis of mu1, mu2, and delta opioid binding in the central nervous system of C57BL/6BY and CXBK (opioid receptor-deficient) mice

    International Nuclear Information System (INIS)

    Moskowitz, A.S.


    In this study the authors used semi-quantitative in vitro autoradiography to compare the levels of binding to central mu 1 , mu 2 , and delta opioid sites in two strains of mice, C57BL/6BY and CXBK. The CXBK strain is known to be deficient in whole brain opioid binding sites and to be less sensitive than the C57 strain to the analgesic and locomotor stimulatory effects of opiates and opioids. Delta sites were visualized using [ 3 H][D-Ala 2 -D-Leu 5 ]-enkephalin (DADL) plus a low concentration of morphine, total mu sites (mu 1 and mu 2 ) were visualized using [ 3 H]dihydromorphine (DHM), and mu 2 sites were visualized using [ 3 H]DHM plus a low concentration of DADL. Binding to mu 1 sites was determined by subtracting mu 2 binding from total mu binding. The authors found that the two strains did not consistently differ in the levels of delta sites. The CXBK strain, however, either had less or the same amount of mu binding as the C57 strain in all areas studied. The CXBK strain was especially deficient in mu 1 binding, particularly in areas involved in pain processing. (Auth.)

  19. Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis. (United States)

    Schmitt, Sarah E; Pargeon, Kimberly; Frechette, Eric S; Hirsch, Lawrence J; Dalmau, Josep; Friedman, Daniel


    To determine continuous EEG (cEEG) patterns that may be unique to anti-NMDA receptor (NMDAR) encephalitis in a series of adult patients with this disorder. We evaluated the clinical and EEG data of 23 hospitalized adult patients with anti-NMDAR encephalitis who underwent cEEG monitoring between January 2005 and February 2011 at 2 large academic medical centers. Twenty-three patients with anti-NMDAR encephalitis underwent a median of 7 (range 1-123) days of cEEG monitoring. The median length of hospitalization was 44 (range 2-200) days. Personality or behavioral changes (100%), movement disorders (82.6%), and seizures (78.3%) were the most common symptoms. Seven of 23 patients (30.4%) had a unique electrographic pattern, which we named "extreme delta brush" because of its resemblance to waveforms seen in premature infants. The presence of extreme delta brush was associated with a more prolonged hospitalization (mean 128.3 ± 47.5 vs 43.2 ± 39.0 days, p = 0.008) and increased days of cEEG monitoring (mean 27.6 ± 42.3 vs 6.2 ± 5.6 days, p = 0.012). The modified Rankin Scale score showed a trend toward worse scores in patients with the extreme delta brush pattern (mean 4.0 ± 0.8 vs 3.1 ± 1.1, p = 0.089). Extreme delta brush is a novel EEG finding seen in many patients with anti-NMDAR encephalitis. The presence of this pattern is associated with a more prolonged illness. Although the specificity of this pattern is unclear, its presence should raise consideration of this syndrome.

  20. Initial isotopic geochemistry ({delta} 18 O, {delta} D) of fluids from wells of the Los Humeros, Pue., geothermal field; Geoquimica isotopica ({delta} 18 O, {delta} D) inicial de fluidos de pozos del campo geotermico de Los Humeros, Pue.

    Energy Technology Data Exchange (ETDEWEB)

    Barragan Reyes, Rosa Maria; Arellano Gomez, Victor Manuel [Instituto de Investigaciones Electricas, Gerencia de Geotermia, Cuernavaca, Morelos (Mexico)]. E-mail:; Ramirez Montes, Miguel; Tovar Aguado, Rigoberto [Comision Federal de Electricidad, Gerencia de Proyectos Geotermoelectricos, Morelia, Michoacan (Mexico)


    Isotopic data ({delta} 18 O, {delta} D) from fluids from production wells at the Los Humeros, Pue., geothermal field were analyzed to investigate the possible origin of these fluids and the dominant processes of the reservoir at its initial state. According to pre-exploitation data, it is suggested the Los Humeros reservoir fluids are made of a mixture of meteoric water of very light isotopic composition (paleo-fluids) and andesitic water. The relationship {delta} D vs {delta} 18 O from pre-exploitation data indicates the produced fluids are composed of a mixture of (at least) two fluids with distinct isotopic compositions. At the more enriched end of the mixing relationship are the isotopic compositions of the wells H-23 and H-18 (located in the southern area of the field), while the lighter fluids were found in well H-16 (originally) and then in well H-16 (repaired). It was found that the liquid phases of deep wells are more enriched in {delta} 18 O while the shallow wells present lower values, suggesting a convection process at the initial state. Based on this isotopic profile, it is considered that even the production depths of the wells H-1, H-12 and H-16 (repaired) are just about the same, but their respective isotopic compositions are quite different. The {delta} 18 O value for well H-16 (repaired) seems to be that of condensate steam, while the corresponding values for wells H-1 and H-12 fall within the value interval of the deep wells (H-23). This suggests wells H-1 and H-12 are collecting very deep fluids enriched in {delta} 18 O. These results could be useful in creating a conceptual model of the reservoir. [Spanish] Se analizaron datos isotopicos ({delta}18 O, {delta}D) de los fluidos de pozos productores del campo geotermico de Los Humeros, Pue., para investigar el posible origen de los fluidos asi como los procesos dominantes del yacimiento en su estado inicial. De acuerdo con datos previos a la explotacion, se plantea que los fluidos del yacimiento

  1. Opiate-induced seizures: a study of mu and delta specific mechanisms. (United States)

    Snead, O C


    Two groups of experiments were conducted to determine if morphine- and enkephalin-induced seizures are specifically mediated by the mu and delta receptor, respectively. In the first experiments, designed to assess the ontogeny of mu- or delta-seizures, rats from 6 h to 85 days of age received implanted cortical and depth electrodes as well as an indwelling cannula in the lateral ventricle. Various amounts of the mu-receptor agonists, morphine and morphiceptin, and the delta agonists, D-Ala2-D-Leu5-enkephalin (DADL) and Tyr-D-Ser-Gly-Phe-Leu-Thr (DSLET), were then administered intracerebroventricularly (icv) with continuous EEG monitoring. The second experiments entailed use of the nonspecific opiate antagonist, naloxone, as well as the specific delta antagonist, ICI 154,129, against seizures induced by icv-administered morphine, morphiceptin, DADL, or DSLET. Both morphine and morphiceptin produced electrical seizure activity in rats as young as 5 days after birth. The drugs produced similar seizure activity in terms of electrical morphology, observed behavior, ontogeny, threshold dose, and reversibility with small doses of naloxone. In the pharmacologic experiments, icv naloxone blocked all opiate-induced seizures. ICI 154,129 blocked DSLET seizure, had little effect on enkephalin or DADL seizures, and no effect on morphine or morphiceptin seizures. These data indicate that DSLET seizures are delta-specific but that all other opiate-induced seizures studied may involve multiple opiate receptor-mediated mechanisms.

  2. Conceptualizing delta forms and processes in Arctic coastal environments

    DEFF Research Database (Denmark)

    Bendixen, Mette; Kroon, Aart


    Climate warming in the Arctic directly causes two opposite changes in Arctic coastal systems: increased melt-water discharge through rivers induces extra influx of sediments and extended open water season increases wave impact which reworks and erodes the shores. A shoreline change analysis along...... and popped up as hotspots. The Tuapaat delta and Skansen delta showed large progradation rates (1.5 and 7m/yr) and migration of the adjacent barriers and spits. The dynamic behavior at the delta mouths was mainly caused by classic delta channel lobe switching at one delta (Tuapaat), and by a breach...... of the fringing spit at the other delta (Skansen). The longshore and cross-shore transports are responsible for reworking the sediment with a result of migrating delta mouths and adjacent subaqueous mouth bars. Seaward progradation of the deltas is limited due to the steep nature of the bathymetry in Disko Bay...

  3. Delta-ray spectroscopy of quasi-atoms

    International Nuclear Information System (INIS)

    Kozhuharov, C.


    The spectroscopy of high energy delta-rays, emitted in collisions of very heavy ions, is studied. The ''orange''-type beta-spectrometer and the achromatic electron channel are the experimental setups. Delta ray production probabilities are studied as a function of the distance of closest approach R /SUB min/ or the impact parameter b. Coulomb ionization, ion trajectory, scaling laws, double differential cross sections, and K-X-rays information is extracted from the experiment. The dependence of delta-ray emission on the united charge number Z /SUB u/ is discussed. Asymmetric collision systems with Z x alpha approx. = 1 (delta ray spectrum from Pb→Sn collisions) are studied. Finally, very heavy collisions, such as 208 Pb + 208 Pb collisions at bombarding energy fas below the Coulomb barrier are touched upon

  4. SNS online display technologies for EPICS

    International Nuclear Information System (INIS)

    Kasemir, K.U.; Chen, X.; Purcell, J.; Danilova, E.


    The ubiquitousness of web clients from personal computers to cell phones results in a growing demand for web-based access to control system data. At the Oak Ridge National Laboratory Spallation Neutron Source (SNS) we have investigated different technical approaches to provide read access to data in the Experimental Physics and Industrial Control System (EPICS) for a wide variety of web client devices. The core web technology, HTTP, is less than ideal for online control system displays. Appropriate use of Ajax, especially the Long Poll paradigm, can alleviate fundamental HTTP limitations. The SNS Status web uses basic Ajax technology to generate generic displays for a wide audience. The Dashboard uses Long Poll and more client-side Java-Script to offer more customization and faster updates for users that need specialized displays. The Web OPI uses RAP for web access to any BOY display, offering utmost flexibility because users can create their own BOY displays in CSS. These three approaches complement each other. Users can access generic status displays with zero effort, invest time in creating their fully customized displays for the Web OPI, or use the Dashboard as an intermediate solution

  5. Differential L1 regulation in pluripotent stem cells of humans and apes. (United States)

    Marchetto, Maria C N; Narvaiza, Iñigo; Denli, Ahmet M; Benner, Christopher; Lazzarini, Thomas A; Nathanson, Jason L; Paquola, Apuã C M; Desai, Keval N; Herai, Roberto H; Weitzman, Matthew D; Yeo, Gene W; Muotri, Alysson R; Gage, Fred H


    Identifying cellular and molecular differences between human and non-human primates (NHPs) is essential to the basic understanding of the evolution and diversity of our own species. Until now, preserved tissues have been the main source for most comparative studies between humans, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus). However, these tissue samples do not fairly represent the distinctive traits of live cell behaviour and are not amenable to genetic manipulation. We propose that induced pluripotent stem (iPS) cells could be a unique biological resource to determine relevant phenotypical differences between human and NHPs, and that those differences could have potential adaptation and speciation value. Here we describe the generation and initial characterization of iPS cells from chimpanzees and bonobos as new tools to explore factors that may have contributed to great ape evolution. Comparative gene expression analysis of human and NHP iPS cells revealed differences in the regulation of long interspersed element-1 (L1, also known as LINE-1) transposons. A force of change in mammalian evolution, L1 elements are retrotransposons that have remained active during primate evolution. Decreased levels of L1-restricting factors APOBEC3B (also known as A3B) and PIWIL2 (ref. 7) in NHP iPS cells correlated with increased L1 mobility and endogenous L1 messenger RNA levels. Moreover, results from the manipulation of A3B and PIWIL2 levels in iPS cells supported a causal inverse relationship between levels of these proteins and L1 retrotransposition. Finally, we found increased copy numbers of species-specific L1 elements in the genome of chimpanzees compared to humans, supporting the idea that increased L1 mobility in NHPs is not limited to iPS cells in culture and may have also occurred in the germ line or embryonic cells developmentally upstream to germline specification during primate evolution. We propose that differences in L1 mobility may have

  6. Generation and Characterisation of Cisplatin-Resistant Non-Small Cell Lung Cancer Cell Lines Displaying a Stem-Like Signature (United States)

    Barr, Martin P.; Gray, Steven G.; Hoffmann, Andreas C.; Hilger, Ralf A.; Thomale, Juergen; O’Flaherty, John D.; Fennell, Dean A.; Richard, Derek; O’Leary, John J.; O’Byrne, Kenneth J.


    Introduction Inherent and acquired cisplatin resistance reduces the effectiveness of this agent in the management of non-small cell lung cancer (NSCLC). Understanding the molecular mechanisms underlying this process may result in the development of novel agents to enhance the sensitivity of cisplatin. Methods An isogenic model of cisplatin resistance was generated in a panel of NSCLC cell lines (A549, SKMES-1, MOR, H460). Over a period of twelve months, cisplatin resistant (CisR) cell lines were derived from original, age-matched parent cells (PT) and subsequently characterized. Proliferation (MTT) and clonogenic survival assays (crystal violet) were carried out between PT and CisR cells. Cellular response to cisplatin-induced apoptosis and cell cycle distribution were examined by FACS analysis. A panel of cancer stem cell and pluripotent markers was examined in addition to the EMT proteins, c-Met and β-catenin. Cisplatin-DNA adduct formation, DNA damage (γH2AX) and cellular platinum uptake (ICP-MS) was also assessed. Results Characterisation studies demonstrated a decreased proliferative capacity of lung tumour cells in response to cisplatin, increased resistance to cisplatin-induced cell death, accumulation of resistant cells in the G0/G1 phase of the cell cycle and enhanced clonogenic survival ability. Moreover, resistant cells displayed a putative stem-like signature with increased expression of CD133+/CD44+cells and increased ALDH activity relative to their corresponding parental cells. The stem cell markers, Nanog, Oct-4 and SOX-2, were significantly upregulated as were the EMT markers, c-Met and β-catenin. While resistant sublines demonstrated decreased uptake of cisplatin in response to treatment, reduced cisplatin-GpG DNA adduct formation and significantly decreased γH2AX foci were observed compared to parental cell lines. Conclusion Our results identified cisplatin resistant subpopulations of NSCLC cells with a putative stem-like signature, providing

  7. Generation and characterisation of cisplatin-resistant non-small cell lung cancer cell lines displaying a stem-like signature.

    Directory of Open Access Journals (Sweden)

    Martin P Barr

    Full Text Available Inherent and acquired cisplatin resistance reduces the effectiveness of this agent in the management of non-small cell lung cancer (NSCLC. Understanding the molecular mechanisms underlying this process may result in the development of novel agents to enhance the sensitivity of cisplatin.An isogenic model of cisplatin resistance was generated in a panel of NSCLC cell lines (A549, SKMES-1, MOR, H460. Over a period of twelve months, cisplatin resistant (CisR cell lines were derived from original, age-matched parent cells (PT and subsequently characterized. Proliferation (MTT and clonogenic survival assays (crystal violet were carried out between PT and CisR cells. Cellular response to cisplatin-induced apoptosis and cell cycle distribution were examined by FACS analysis. A panel of cancer stem cell and pluripotent markers was examined in addition to the EMT proteins, c-Met and β-catenin. Cisplatin-DNA adduct formation, DNA damage (γH2AX and cellular platinum uptake (ICP-MS was also assessed.Characterisation studies demonstrated a decreased proliferative capacity of lung tumour cells in response to cisplatin, increased resistance to cisplatin-induced cell death, accumulation of resistant cells in the G0/G1 phase of the cell cycle and enhanced clonogenic survival ability. Moreover, resistant cells displayed a putative stem-like signature with increased expression of CD133+/CD44+cells and increased ALDH activity relative to their corresponding parental cells. The stem cell markers, Nanog, Oct-4 and SOX-2, were significantly upregulated as were the EMT markers, c-Met and β-catenin. While resistant sublines demonstrated decreased uptake of cisplatin in response to treatment, reduced cisplatin-GpG DNA adduct formation and significantly decreased γH2AX foci were observed compared to parental cell lines.Our results identified cisplatin resistant subpopulations of NSCLC cells with a putative stem-like signature, providing a further understanding of the

  8. Adaptive delta management : Roots and branches

    NARCIS (Netherlands)

    Timmermans, J.S.; Haasnoot, M.; Hermans, L.M.; Kwakkel, J.H.; Rutten, M.M.; Thissen, W.A.H.


    Deltas are generally recognized as vulnerable to climate change and therefore a salient topic in adaptation science. Deltas are also highly dynamic systems viewed from physical (erosion, sedimentation, subsidence), social (demographic), economic (trade), infrastructures (transport, energy,

  9. Adaptive Delta Management : Roots and Branches

    NARCIS (Netherlands)

    Timmermans, Jos; Haasnoot, Marjolijn; Hermans, Leon; Kwakkel, Jan H.; Rutten, Maarten; Thissen, Wil A.H.; Mynett, Arthur


    Deltas are generally recognized as vulnerable to climate change and therefore a salient topic in adaptation science. Deltas are also highly dynamic systems viewed from physical (erosion, sedimentation, subsidence), social (demographic), economic (trade), infrastructures (transport, energy,

  10. Perturbed angular correlations studies in the HgBa$_2$CaCu$_2$O$_{6+\\delta}$ high-T$_c$ superconductor

    CERN Document Server

    Mendonca, Tania Melo; Haas, Heinz; Odier, Philippe; Tavares, Pedro; SIlva, Manuel Ribeiro; Lopes, Armandina; Darie, Celine; Araujo, Joao Pedro


    The electric field gradients at $^{199m}$Hg nuclei have been measured via the perturbed angular correlation (PAC) technique, allowing a full characterization of the Hg neighborhood charge distribution at high oxygen doping on the Hg planes. The PAC technique has been applied to investigate the effect of high oxygen pressure during the measurement. Polycrystalline HgBa$_2$CaCu$_2$O$_{6+\\delta}$ (Hg-1212) samples have been annealed at 152 bar pressurized oxygen. The influence of oxygen pressure during the experiment was then investigated by measuring the samples at atmospheric pressure and under 152 bar oxygen pressure. The present set of PAC experiments shows that at high oxygen concentrations there is a non-uniform oxygen distribution. Moreover, the Hg environment is not free from oxygen and the results hint to a new type of ordering.

  11. Frequency of CCR5delta32 in Brazilian populations

    Directory of Open Access Journals (Sweden)

    A.E. Vargas


    Full Text Available A sample of 103 randomly chosen healthy individuals from Alegrete, RS, Brazil, was tested for the CCR5delta32 allele, which is known to influence susceptibility to HIV-1 infection. The CCR5delta32 allele was identified by PCR amplification using specific primers flanking the region of deletion, followed by electrophoresis on a 3% agarose gel. The data obtained were compared to those reported for other populations and interpreted in terms of Brazilian history. The individuals studied came from a highly admixed population. Most of them were identified as white (N = 59, while blacks and browns (mulattoes were N = 13 and N = 31, respectively. The observed frequencies, considering the white, black and brown samples (6.8, 3.8, and 6.4%, respectively, suggest an important European parental contribution, even in populations identified as black and brown. However, in Brazil as a whole, this allele shows gradients indicating a relatively good correlation with the classification based on skin color and other physical traits, used here to define major Brazilian population groups.

  12. Three dimensional [delta][ital f] simulations of beams in the SSC

    Energy Technology Data Exchange (ETDEWEB)

    Koga, J.; Tajima, T. (Institute for Fusion Studies, The University of Texas at Austin, Austin, Texas 78712-1060 (United States)); Machida, S. (SSC Laboratory, 2550 Beckleymeade Avenue, Dallas, Texas 75237 (United States))


    A three dimensional [delta][ital f] strong-strong algorithm has been developed to apply to the study of such effects as space charge and beam-beam interaction phenomena in the Superconducting Super Collider (SSC). The algorithm is obtained from the merging of the particle tracking code Simpsons used for 3 dimensional space charge effects and a [delta][ital f] code. The [delta][ital f] method is used to follow the evolution of the non-gaussian part of the beam distribution. The advantages of this method are twofold. First, the Simpsons code utilizes a realistic accelerator model including synchrotron oscillations and energy ramping in 6 dimensional phase space with electromagnetic fields of the beams calculated using a realistic 3 dimensional field solver. Second, the beams are evolving in the fully self-consistent strong-strong sense with finite particle fluctuation noise is greatly reduced as opposed to the weak-strong models where one beam is fixed.

  13. A preliminary disease survey in the wild Nile crocodile (Crocodylus niloticus population in the Okavango Delta, Botswana

    Directory of Open Access Journals (Sweden)

    A. J. Leslie


    Full Text Available The objective of this study was to conduct a preliminary survey of diseases that might be present in the wild Nile crocodile population in the Okavango Delta, Botswana. Blood samples were collected from crocodiles ranging in size from 34.0cmto 463.0cmtotal length. Samples were examined for blood parasites and underwent a haematological analysis. Before release the crocodiles were examined for various clinical abnormalities. Of the 144 crocodiles examined, none were visibly sick or displayed any signs of disease. No antibodies to Mycoplasma crocodyli were detected. Hepatozoon pettiti was present in 55.3 % of blood smears examined, but there was no significant difference in any of the haematological values between the infected and uninfected crocodiles, and a high prevalence of Hepatozoon infection is not uncommon in other species. Only 7.6 % of the examined crocodiles were infested with leeches. Further research is required for several of the crocodilian diseases, in particular to elucidate the role of wild crocodilians as reservoirs of infection.

  14. Shape Memory Polymers Containing Higher Acrylate Content Display Increased Endothelial Cell Attachment (United States)

    Govindarajan, Tina; Shandas, Robin


    Shape Memory Polymers (SMPs) are smart materials that can recall their shape upon the application of a stimulus, which makes them appealing materials for a variety of applications, especially in biomedical devices. Most prior SMP research has focused on tuning bulk properties; studying surface effects of SMPs may extend the use of these materials to blood-contacting applications, such as cardiovascular stents, where surfaces that support rapid endothelialization have been correlated to stent success. Here, we evaluate endothelial attachment onto the surfaces of a family of SMPs previously developed in our group that have shown promise for biomedical devices. Nine SMP formulations containing varying amounts of tert-Butyl acrylate (tBA) and Poly(ethylene glycol) dimethacrylate (PEGDMA) were analyzed for endothelial cell attachment. Dynamic mechanical analysis (DMA), contact angle studies, and atomic force microscopy (AFM) were used to verify bulk and surface properties of the SMPs. Human umbilical vein endothelial cell (HUVEC) attachment and viability was verified using fluorescent methods. Endothelial cells preferentially attached to SMPs with higher tBA content, which have rougher, more hydrophobic surfaces. HUVECs also displayed an increased metabolic activity on these high tBA SMPs over the course of the study. This class of SMPs may be promising candidates for next generation blood-contacting devices. PMID:29707382

  15. Shape Memory Polymers Containing Higher Acrylate Content Display Increased Endothelial Cell Attachment

    Directory of Open Access Journals (Sweden)

    Tina Govindarajan


    Full Text Available Shape Memory Polymers (SMPs are smart materials that can recall their shape upon the application of a stimulus, which makes them appealing materials for a variety of applications, especially in biomedical devices. Most prior SMP research has focused on tuning bulk properties; studying surface effects of SMPs may extend the use of these materials to blood-contacting applications, such as cardiovascular stents, where surfaces that support rapid endothelialization have been correlated to stent success. Here, we evaluate endothelial attachment onto the surfaces of a family of SMPs previously developed in our group that have shown promise for biomedical devices. Nine SMP formulations containing varying amounts of tert-Butyl acrylate (tBA and Poly(ethylene glycol dimethacrylate (PEGDMA were analyzed for endothelial cell attachment. Dynamic mechanical analysis (DMA, contact angle studies, and atomic force microscopy (AFM were used to verify bulk and surface properties of the SMPs. Human umbilical vein endothelial cell (HUVEC attachment and viability was verified using fluorescent methods. Endothelial cells preferentially attached to SMPs with higher tBA content, which have rougher, more hydrophobic surfaces. HUVECs also displayed an increased metabolic activity on these high tBA SMPs over the course of the study. This class of SMPs may be promising candidates for next generation blood-contacting devices.

  16. Projection display industry market and technology trends (United States)

    Castellano, Joseph A.; Mentley, David E.


    The projection display industry is diverse, embracing a variety of technologies and applications. In recent years, there has been a high level of interest in projection displays, particularly those using LCD panels or light valves because of the difficulty in making large screen, direct view displays. Many developers feel that projection displays will be the wave of the future for large screen HDTV (high-definition television), penetrating the huge existing market for direct view CRT-based televisions. Projection displays can have the images projected onto a screen either from the rear or the front; the main characteristic is their ability to be viewed by more than one person. In addition to large screen home television receivers, there are numerous other uses for projection displays including conference room presentations, video conferences, closed circuit programming, computer-aided design, and military command/control. For any given application, the user can usually choose from several alternative technologies. These include CRT front or rear projectors, LCD front or rear projectors, LCD overhead projector plate monitors, various liquid or solid-state light valve projectors, or laser-addressed systems. The overall worldwide market for projection information displays of all types and for all applications, including home television, will top DOL4.6 billion in 1995 and DOL6.45 billion in 2001.

  17. Programmable display of DNA-protein chimeras for controlling cell-hydrogel interactions via reversible intermolecular hybridization. (United States)

    Zhang, Zhaoyang; Li, Shihui; Chen, Niancao; Yang, Cheng; Wang, Yong


    Extensive studies have been recently carried out to achieve dynamic control of cell-material interactions primarily through physicochemical stimulation. The purpose of this study was to apply reversible intermolecular hybridization to program cell-hydrogel interactions in physiological conditions based on DNA-antibody chimeras and complementary oligonucleotides. The results showed that DNA oligonucleotides could be captured to and released from the immobilizing DNA-functionalized hydrogels with high specificity via DNA hybridization. Accordingly, DNA-antibody chimeras were captured to the hydrogels, successfully inducing specific cell attachment. The cell attachment to the hydrogels reached the plateau at approximately half an hour after the functionalized hydrogels and the cells were incubated together. The attached cells were rapidly released from the bound hydrogels when triggering complementary oligonucleotides were introduced to the system. However, the capability of the triggering complementary oligonucleotides in releasing cells was affected by the length of intermolecular hybridization. The length needed to be at least more than 20 base pairs in the current experimental setting. Notably, because the procedure of intermolecular hybridization did not involve any harsh condition, the released cells maintained the same viability as that of the cultured cells. The functionalized hydrogels also exhibited the potential to catch and release cells repeatedly. Therefore, this study demonstrates that it is promising to regulate cell-material interactions dynamically through the DNA-programmed display of DNA-protein chimeras.

  18. Standardization of the PCR technique for the detection of delta toxin in Staphylococcus spp.

    Directory of Open Access Journals (Sweden)

    C. Marconi


    Full Text Available Coagulase-negative staphylococci (CNS, components of the normal flora of neonates, have emerged as important opportunistic pathogens of nosocomial infections that occur in neonatal intensive care units. Some authors have reported the ability of some CNS strains, particularly Staphylococcus epidermidis, to produce a toxin similar to S. aureus delta toxin. This toxin is an exoprotein that has a detergent action on the membranes of various cell types resulting in rapid cell lysis. The objectives of the present study were to standardize the Polymerase Chain Reaction (PCR technique for the detection of the gene responsible for the production of delta toxin (hld gene in staphylococcal species isolated from catheters and blood cultures obtained from neonates, and to compare the results to those obtained with the phenotypic synergistic hemolysis method. Detection of delta toxin by the phenotypic and genotypic method yielded similar results for the S. aureus isolates. However, in S. epidermidis, a higher positivity was observed for PCR (97.4% compared to the synergistic hemolysis method (86.8%. Among CNS, S. epidermidis was the most frequent isolate and was a delta toxin producer. Staphylococcus simulans and S. warneri tested positive by the phenotypic method, but their positivity was not confirmed by PCR for the hld gene detection. These results indicate that different genes might be responsible for the production of this toxin in different CNS species, requiring highly specific primers for their detection. PCR was found to be a rapid and reliable method for the detection of the hld gene in S. aureus and S. epidermidis.

  19. Enhancing the understanding of earthworm feeding behaviour via the use of fatty acid delta13C values determined by gas chromatography-combustion-isotope ratio mass spectrometry. (United States)

    Dungait, Jennifer A J; Briones, Maria J I; Bol, Roland; Evershed, Richard P


    Litter-dwelling (epigeic) Lumbricus rubellus and soil-dwelling (endogeic) Allolobophora chlorotica earthworms were observed aggregating under C(3) (delta(13)C = -31.3 per thousand; delta(15)N = 10.7 per thousand) and C(4) (delta(13)C = -12.6 per thousand; delta(15)N = 7.5 per thousand) synthetic dung pats applied to a temperate grassland (delta(13)C = -30.3 per thousand; delta(15)N = 5.7 per thousand) in an experiment carried out for 372 days. Bulk delta(13)C values of earthworms collected from beneath either C(3) or C(4) dung after 28, 56, 112 and 372 days demonstrated that (i) L. rubellus beneath C(4) dung were significantly (13)C-enriched after 56 days (delta(13)C = -23.8 per thousand) and 112 days (delta(13)C = -22.4 per thousand) compared with those from C(3) dung treatments (56 days, delta(13)C = -26.5 per thousand; 112 days, delta(13)C = -27.0 per thousand), and (ii) A. chlorotica were 2.1 per thousand (13)C-enriched (delta(13)C = -24.2 per thousand) relative to those from C(3) dung (delta(13)C = -26.3 per thousand) treatments after 372 days. Bulk delta(15)N values did not suggest significant uptake of dung N by either species beneath C(3) or C(4) dung, but showed that the endogeic species (total mean delta(15)N = 3.3 per thousand) had higher delta(15)N values than the epigeic species (total mean delta(15)N = 5.4 per thousand). Although the two species exhibited similar fatty acid profiles, individual fatty acid delta(13)C values revealed extensive routing of dietary C into body tissue of L. rubellus, but minor incorporation into A. chlorotica. In particular, the direct incorporation of microbial biomarker fatty acids (iC(17:0), aC(17:0)) from (13)C-labelled dung in situ, the routing of dung C into de novo synthesised compounds (iC(20:4)(omega)(6),C(20:5)(omega)(3), and the assimilation of essential fatty acids ((C(18:1)(omega)(9), C(18:1)(omega(7), C(18:2)(omega(6), C(18:3)(omega)(3)) derived from dung, were determined. John Wiley & Sons, Ltd

  20. Migration in Vulnerable Deltas: A Research Strategy (United States)

    Hutton, C.; Nicholls, R. J.; Allan, A.


    C. Hutton1, & R. J. Nicholls1, , 1 University of Southampton, University Road, Southampton, Hampshire, United Kingdom, SO17 1BJ. cwh@geodata., deltas contain 500 million people and with rising sea levels often linked to large number of forced migrants are expected in the coming century. However, migration is already a major process in deltas, such as the growth of major cities such as Dhaka and Kolkata. Climate and environmental change interacts with a range of catchment and delta level drivers, which encompass a nexus of sea-level rise, storms, freshwater and sediment supply from the catchment, land degradation, subsidence, agricultural loss and socio-economic stresses. DECCMA (Deltas, Vulnerability and Climate Change: Migration and Adaptation/CARRIA) is investigating migration in the Ganges-Brahmaputra-Meghna (GBM), Mahanadi and Volta Deltas, including the influence of climate change. The research will explore migration from a range of perspectives including governance and stakeholder analysis, demographic analysis, household surveys of sending and receiving areas, macro-economic analysis, and hazards and hotspot analysis both historically and into the future. Migration under climate change will depend on other adaptation in the deltas and this will be examined. Collectively, integrated analysis will be developed to examine migration, other adaptation and development pathways with a particular focus on the implications for the poorest. This will require the development of input scenarios, including expert-derived exogenous scenarios (e.g., climate change) and endogenous scenarios of the delta developed in a participatory manner. This applied research will facilitate decision support methods for the development of deltas under climate change, with a focus on migration and other adaptation strategies.

  1. Upper-division student difficulties with the Dirac delta function

    Directory of Open Access Journals (Sweden)

    Bethany R. Wilcox


    Full Text Available The Dirac delta function is a standard mathematical tool that appears repeatedly in the undergraduate physics curriculum in multiple topical areas including electrostatics, and quantum mechanics. While Dirac delta functions are often introduced in order to simplify a problem mathematically, students still struggle to manipulate and interpret them. To characterize student difficulties with the delta function at the upper-division level, we examined students’ responses to traditional exam questions and a standardized conceptual assessment, and conducted think-aloud interviews. Our analysis was guided by an analytical framework that focuses on how students activate, construct, execute, and reflect on the Dirac delta function in the context of problem solving in physics. Here, we focus on student difficulties using the delta function to express charge distributions in the context of junior-level electrostatics. Common challenges included invoking the delta function spontaneously, translating a description of a charge distribution into a mathematical expression using delta functions, integrating 3D or non-Cartesian delta function expressions, and recognizing that the delta function can have units. We also briefly discuss implications of these difficulties for instruction.

  2. Ligand- and cell-dependent determinants of internalization and cAMP modulation by delta opioid receptor (DOR) agonists (United States)

    Charfi, Iness; Nagi, Karim; Mnie-Filali, Ouissame; Thibault, Dominic; Balboni, Gianfranco; Schiller, Peter W.; Trudeau, Louis-Eric


    Signaling bias refers to G protein-coupled receptor ligand ability to preferentially activate one type of signal over another. Bias to evoke signaling as opposed to sequestration has been proposed as a predictor of opioid ligand potential for generating tolerance. Here we measured whether delta opioid receptor agonists preferentially inhibited cyclase activity over internalization in HEK cells. Efficacy (τ) and affinity (KA) values were estimated from functional data and bias was calculated from efficiency coefficients (log τ/KA). This approach better represented the data as compared to alternative methods that estimate bias exclusively from τ values. Log (τ/KA) coefficients indicated that SNC-80 and UFP-512 promoted cyclase inhibition more efficiently than DOR internalization as compared to DPDPE (bias factor for SNC-80: 50 and for UFP-512: 132). Molecular determinants of internalization were different in HEK293 cells and neurons with βarrs contributing to internalization in both cell types, while PKC and GRK2 activities were only involved in neurons. Rank orders of ligand ability to engage different internalization mechanisms in neurons were compared to rank order of Emax values for cyclase assays in HEK cells. Comparison revealed a significant reversal in rank order for cyclase Emax values and βarr-dependent internalization in neurons, indicating that these responses were ligand-specific. Despite this evidence, and because kinases involved in internalization were not the same across cellular backgrounds, it is not possible to assert if the magnitude and nature of bias revealed by rank orders of maximal responses is the same as the one measured in HEK cells. PMID:24022593

  3. Delta-nucleus dynamics: proceedings of symposium

    Energy Technology Data Exchange (ETDEWEB)

    Lee, T.S.H.; Geesaman, D.F.; Schiffer, J.P. (eds.)


    The appreciation of the role in nuclear physics of the first excited state of the nucleon, the delta, has grown rapidly in the past decade. The delta resonance dominates nuclear reactions induced by intermediate energy pions, nucleons, and electromagnetic probes. It is also the most important non-nucleonic degree of freedom needed to resolve many fundamental problems encountered in the study of low-energy nuclear phenomena. Clearly, a new phase of nuclear physics has emerged and conventional thinking must be extended to account for this new dimension of nuclear dynamics. The most challenging problem we are facing is how a unified theory can be developed to describe dynamics at all energies. In exploring this new direction, it is important to have direct discussions among researchers with different viewpoints. Separate entries were prepared for the 49 papers presented. (WHK)

  4. On the origin of delta spots

    International Nuclear Information System (INIS)

    Tang, F.


    Mount Wilson sunspot drawings from 1966 through 1980 were used in conjunction with Hα filtergrams from Big Bear Solar Observatory to examine the origin of delta spots, spots with bipolar umbrae within one penumbra. Of the six cases we studied, five were formed by the union of non-paired spots. They are either shoved into one another by two neighboring growing bipoles or by a new spot born piggy-back style on an existing spot of opposite polarity. Proper motions of the growing spots take on curvilinear paths around one another to avoid a collision. This is the shear motion observed in delta spots (Tanaka, 1979). In the remaining case, the delta spot was formed by spots that emerged as a pair. Our findings indicate no intrinsic differences in the formation or the behavior between delta spots of normal magnetic configuration. (orig.)

  5. Holocene evolution of the western Orinoco Delta, Venezuela (United States)

    Aslan, A.; White, W.A.; Warne, A.G.; Guevara, E.H.


    The pristine nature of the Orinoco Delta of eastern Venezuela provides unique opportunities to study the geologic processes and environments of a major tropical delta. Remote-sensing images, shallow cores, and radiocarbon-dating of organic remains form the basis for describing deltaic environments and interpreting the Holocene history of the delta. The Orinoco Delta can be subdivided into two major sectors. The southeast sector is dominated by the Rio Grande-the principal distributary-and complex networks of anastomosing fluvial and tidal channels. The abundance of siliciclastic deposits suggests that fluvial processes such as over-bank flooding strongly influence this part of the delta. In contrast, the northwest sector is represented by few major distributaries, and overbank sedimentation is less widespread relative to the southeast sector. Peat is abundant and occurs in herbaceous and forested swamps that are individually up to 200 km2 in area. Northwest-directed littoral currents transport large volumes of suspended sediment and produce prominent mudcapes along the northwest coast. Mapping of surface sediments, vegetation, and major landforms identified four principal geomorphic systems within the western delta plain: (1) distributary channels, (2) interdistributary flood basins, (3) fluvial-marine transitional environments, and (4) marine-influenced coastal environments. Coring and radiocarbon dating of deltaic deposits show that the northern delta shoreline has prograded 20-30 km during the late Holocene sea-level highstand. Progradation has been accomplished by a combination of distributary avulsion and mudcape progradation. This style of deltaic progradation differs markedly from other deltas such as the Mississippi where distributary avulsion leads to coastal land loss, rather than shoreline progradation. The key difference is that the Orinoco Delta coastal zone receives prodigious amounts of sediment from northwest-moving littoral currents that transport

  6. Nonlinear Delta-f Particle Simulations of Collective Effects in High-Intensity Bunched Beams

    CERN Document Server

    Qin, Hong; Hudson, Stuart R; Startsev, Edward


    The collective effects in high-intensity 3D bunched beams are described self-consistently by the nonlinear Vlasov-Maxwell equations.* The nonlinear delta-f method,** a particle simulation method for solving the nonlinear Vlasov-Maxwell equations, is being used to study the collective effects in high-intensity 3D bunched beams. The delta-f method, as a nonlinear perturbative scheme, splits the distribution function into equilibrium and perturbed parts. The perturbed distribution function is represented as a weighted summation over discrete particles, where the particle orbits are advanced by equations of motion in the focusing field and self-consistent fields, and the particle weights are advanced by the coupling between the perturbed fields and the zero-order distribution function. The nonlinear delta-f method exhibits minimal noise and accuracy problems in comparison with standard particle-in-cell simulations. A self-consistent 3D kinetic equilibrium is first established for high intensity bunched beams. The...

  7. Complexities in human herpesvirus-6A and -6B binding to host cells

    International Nuclear Information System (INIS)

    Pedersen, Simon Metz; Hoellsberg, Per


    Human herpesvirus-6A and -6B uses the cellular receptor CD46 for fusion and infection of the host cell. The viral glycoprotein complex gH-gL from HHV-6A binds to the short consensus repeat 2 and 3 in CD46. Although all the major isoforms of CD46 bind the virus, certain isoforms may have higher affinity than others for the virus. Within recent years, elucidation of the viral complex has identified additional HHV-6A and -6B specific glycoproteins. Thus, gH-gL associates with a gQ1-gQ2 dimer to form a heterotetrameric complex. In addition, a novel complex consisting of gH-gL-gO has been described that does not bind CD46. Accumulating evidence suggests that an additional HHV-6A and -6B receptor exists. The previous simple picture of HHV-6A/B-host cell contact therefore includes more layers of complexities on both the viral and the host cell side of the interaction

  8. Super high precision 200 ppi liquid crystal display series; Chokoseido 200 ppi ekisho display series

    Energy Technology Data Exchange (ETDEWEB)



    In mobile equipment, in demand is a high precision liquid crystal display (LCD) having the power of expression equivalent to printed materials like magazines because of the necessity of displaying a large amount of information on a easily potable small screen. In addition, with the spread and high-quality image of digital still cameras, it is strongly desired to display photographed digital image data in high quality. Toshiba Corp., by low temperature polysilicone (p-Si) technology, commercialized the liquid crystal display series of 200 ppi (pixels per inch) precision dealing with the rise of the high-precision high-image quality LCD market. The super high precision of 200 ppi enables the display of smooth beautiful animation comparable to printed sheets of magazines and photographs. The display series are suitable for the display of various information services such as electronic books and electronic photo-viewers including internet. The screen sizes lined up are No. 4 type VGA (640x480 pixels) of a small pocket notebook size and No. 6.3 type XGA (1,024x768 pixels) of a paperback size, with a larger screen to be furthered. (translated by NEDO)

  9. Effects of track structure and cell inactivation on the calculation of heavy ion mutation rates in mammalian cells (United States)

    Cucinotta, F. A.; Wilson, J. W.; Shavers, M. R.; Katz, R.


    It has long been suggested that inactivation severely effects the probability of mutation by heavy ions in mammalian cells. Heavy ions have observed cross sections of inactivation that approach and sometimes exceed the geometric size of the cell nucleus in mammalian cells. In the track structure model of Katz the inactivation cross section is found by summing an inactivation probability over all impact parameters from the ion to the sensitive sites within the cell nucleus. The inactivation probability is evaluated using the dose-response of the system to gamma-rays and the radial dose of the ions and may be equal to unity at small impact parameters for some ions. We show how the effects of inactivation may be taken into account in the evaluation of the mutation cross sections from heavy ions in the track structure model through correlation of sites for gene mutation and cell inactivation. The model is fit to available data for HPRT mutations in Chinese hamster cells and good agreement is found. The resulting calculations qualitatively show that mutation cross sections for heavy ions display minima at velocities where inactivation cross sections display maxima. Also, calculations show the high probability of mutation by relativistic heavy ions due to the radial extension of ions track from delta-rays in agreement with the microlesion concept. The effects of inactivation on mutations rates make it very unlikely that a single parameter such as LET or Z*2/beta(2) can be used to specify radiation quality for heavy ion bombardment.

  10. The establishment of Saccharomyces boulardii surface display system using a single expression vector. (United States)

    Wang, Tiantian; Sun, Hui; Zhang, Jie; Liu, Qing; Wang, Longjiang; Chen, Peipei; Wang, Fangkun; Li, Hongmei; Xiao, Yihong; Zhao, Xiaomin


    In the present study, an a-agglutinin-based Saccharomyces boulardii surface display system was successfully established using a single expression vector. Based on the two protein co-expression vector pSP-G1 built by Partow et al., a S. boulardii surface display vector-pSDSb containing all the display elements was constructed. The display results of heterologous proteins were confirmed by successfully displaying enhanced green fluorescent protein (EGFP) and chicken Eimeria tenella Microneme-2 proteins (EtMic2) on the S. boulardii cell surface. The DNA sequence of AGA1 gene from S. boulardii (SbAGA1) was determined and used as the cell wall anchor partner. This is the first time heterologous proteins have been displayed on the cell surface of S. boulardii. Because S. boulardii is probiotic and eukaryotic, its surface display system would be very valuable, particularly in the development of a live vaccine against various pathogenic organisms especially eukaryotic pathogens such as protistan parasites. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Nitrous oxide-induced slow and delta oscillations. (United States)

    Pavone, Kara J; Akeju, Oluwaseun; Sampson, Aaron L; Ling, Kelly; Purdon, Patrick L; Brown, Emery N


    Switching from maintenance of general anesthesia with an ether anesthetic to maintenance with high-dose (concentration >50% and total gas flow rate >4 liters per minute) nitrous oxide is a common practice used to facilitate emergence from general anesthesia. The transition from the ether anesthetic to nitrous oxide is associated with a switch in the putative mechanisms and sites of anesthetic action. We investigated whether there is an electroencephalogram (EEG) marker of this transition. We retrospectively studied the ether anesthetic to nitrous oxide transition in 19 patients with EEG monitoring receiving general anesthesia using the ether anesthetic sevoflurane combined with oxygen and air. Following the transition to nitrous oxide, the alpha (8-12 Hz) oscillations associated with sevoflurane dissipated within 3-12 min (median 6 min) and were replaced by highly coherent large-amplitude slow-delta (0.1-4 Hz) oscillations that persisted for 2-12 min (median 3 min). Administration of high-dose nitrous oxide is associated with transient, large amplitude slow-delta oscillations. We postulate that these slow-delta oscillations may result from nitrous oxide-induced blockade of major excitatory inputs (NMDA glutamate projections) from the brainstem (parabrachial nucleus and medial pontine reticular formation) to the thalamus and cortex. This EEG signature of high-dose nitrous oxide may offer new insights into brain states during general anesthesia. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  12. Combat vehicle crew helmet-mounted display: next generation high-resolution head-mounted display (United States)

    Nelson, Scott A.


    The Combat Vehicle Crew Head-Mounted Display (CVC HMD) program is an ARPA-funded, US Army Natick Research, Development, and Engineering Center monitored effort to develop a high resolution, flat panel HMD for the M1 A2 Abrams main battle tank. CVC HMD is part of the ARPA High Definition Systems (HDS) thrust to develop and integrate small (24 micrometers square pels), high resolution (1280 X 1024 X 6-bit grey scale at 60 frame/sec) active matrix electroluminescent (AMEL) and active matrix liquid crystal displays (AMLCD) for head mounted and projection applications. The Honeywell designed CVC HMD is a next generation head-mounted display system that includes advanced flat panel image sources, advanced digital display driver electronics, high speed (> 1 Gbps) digital interconnect electronics, and light weight, high performance optical and mechanical designs. The resulting dramatic improvements in size, weight, power, and cost have already led to program spin offs for both military and commercial applications.

  13. Fluvial sediment supply to a mega-delta reduced by shifting tropical-cyclone activity. (United States)

    Darby, Stephen E; Hackney, Christopher R; Leyland, Julian; Kummu, Matti; Lauri, Hannu; Parsons, Daniel R; Best, James L; Nicholas, Andrew P; Aalto, Rolf


    The world's rivers deliver 19 billion tonnes of sediment to the coastal zone annually, with a considerable fraction being sequestered in large deltas, home to over 500 million people. Most (more than 70 per cent) large deltas are under threat from a combination of rising sea levels, ground surface subsidence and anthropogenic sediment trapping, and a sustainable supply of fluvial sediment is therefore critical to prevent deltas being 'drowned' by rising relative sea levels. Here we combine suspended sediment load data from the Mekong River with hydrological model simulations to isolate the role of tropical cyclones in transmitting suspended sediment to one of the world's great deltas. We demonstrate that spatial variations in the Mekong's suspended sediment load are correlated (r = 0.765, P sediment load reaching the delta is delivered by runoff generated by rainfall associated with tropical cyclones. Furthermore, we estimate that the suspended load to the delta has declined by 52.6 ± 10.2 megatonnes over recent years (1981-2005), of which 33.0 ± 7.1 megatonnes is due to a shift in tropical-cyclone climatology. Consequently, tropical cyclones have a key role in controlling the magnitude of, and variability in, transmission of suspended sediment to the coast. It is likely that anthropogenic sediment trapping in upstream reservoirs is a dominant factor in explaining past, and anticipating future, declines in suspended sediment loads reaching the world's major deltas. However, our study shows that changes in tropical-cyclone climatology affect trends in fluvial suspended sediment loads and thus are also key to fully assessing the risk posed to vulnerable coastal systems.

  14. Hot deformation behavior of delta-processed superalloy 718

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Y., E-mail: [State Key Laboratory of Powder Metallurgy, Central South University, Changsha 410083 (China); School of Aeronautics and Astronautics, Central South University, Changsha 410083 (China); Shao, W.Z.; Zhen, L.; Zhang, B.Y. [School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001 (China)


    Research highlights: {yields} The peak stress for hot deformation can be described by the Z parameter. {yields} The grain size of DRX was inversely proportional to the Z parameter. {yields} The dissolution of {delta} phases was greatly accelerated under hot deformation. {yields}The {delta} phase stimulated nucleation can serve as the main DRX mechanism. - Abstract: Flow stress behavior and microstructures during hot compression of delta-processed superalloy 718 at temperatures from 950 to 1100 deg. C with strain rates of 10{sup -3} to 1 s{sup -1} were investigated by optical microscopy (OM), electron backscatter diffraction (EBSD) technique and transmission electron microscopy (TEM). The relationship between the peak stress and the deformation conditions can be expressed by a hyperbolic-sine type equation. The activation energy for the delta-processed superalloy 718 is determined to be 467 kJ/mol. The change of the dominant deformation mechanisms leads to the decrease of stress exponent and the increase of activation energy with increasing temperature. The dynamically recrystallized grain size is inversely proportional to the Zener-Hollomon (Z) parameter. It is found that the dissolution rate of {delta} phases under hot deformation conditions is much faster than that under static conditions. Dislocation, vacancy and curvature play important roles in the dissolution of {delta} phases. The main nucleation mechanisms of dynamic recrystallization (DRX) for the delta-processed superalloy 718 include the bulging of original grain boundaries and the {delta} phase stimulated DRX nucleation, which is closely related to the dissolution behavior of {delta} phases under certain deformation conditions.

  15. Primary production in the Delta: Then and now (United States)

    Cloern, James E.; Robinson, April; Richey, Amy; Grenier, Letitia; Grossinger, Robin; Boyer, Katharyn E.; Burau, Jon; Canuel, Elizabeth A.; DeGeorge, John F.; Drexler, Judith Z.; Enright, Chris; Howe, Emily R.; Kneib, Ronald; Mueller-Solger, Anke; Naiman, Robert J.; Pinckney, James L.; Safran, Samuel M.; Schoellhamer, David H.; Simenstad, Charles A.


    To evaluate the role of restoration in the recovery of the Delta ecosystem, we need to have clear targets and performance measures that directly assess ecosystem function. Primary production is a crucial ecosystem process, which directly limits the quality and quantity of food available for secondary consumers such as invertebrates and fish. The Delta has a low rate of primary production, but it is unclear whether this was always the case. Recent analyses from the Historical Ecology Team and Delta Landscapes Project provide quantitative comparisons of the areal extent of 14 habitat types in the modern Delta versus the historical Delta (pre-1850). Here we describe an approach for using these metrics of land use change to: (1) produce the first quantitative estimates of how Delta primary production and the relative contributions from five different producer groups have been altered by large-scale drainage and conversion to agriculture; (2) convert these production estimates into a common currency so the contributions of each producer group reflect their food quality and efficiency of transfer to consumers; and (3) use simple models to discover how tidal exchange between marshes and open water influences primary production and its consumption. Application of this approach could inform Delta management in two ways. First, it would provide a quantitative estimate of how large-scale conversion to agriculture has altered the Delta's capacity to produce food for native biota. Second, it would provide restoration practitioners with a new approach—based on ecosystem function—to evaluate the success of restoration projects and gauge the trajectory of ecological recovery in the Delta region.

  16. Disparate effects of p24alpha and p24delta on secretory protein transport and processing.

    Directory of Open Access Journals (Sweden)

    Jeroen R P M Strating

    Full Text Available BACKGROUND: The p24 family is thought to be somehow involved in endoplasmic reticulum (ER-to-Golgi protein transport. A subset of the p24 proteins (p24alpha(3, -beta(1, -gamma(3 and -delta(2 is upregulated when Xenopus laevis intermediate pituitary melanotrope cells are physiologically activated to produce vast amounts of their major secretory cargo, the prohormone proopiomelanocortin (POMC. METHODOLOGY/PRINCIPAL FINDINGS: Here we find that transgene expression of p24alpha(3 or p24delta(2 specifically in the Xenopus melanotrope cells in both cases causes an effective displacement of the endogenous p24 proteins, resulting in severely distorted p24 systems and disparate melanotrope cell phenotypes. Transgene expression of p24alpha(3 greatly reduces POMC transport and leads to accumulation of the prohormone in large, ER-localized electron-dense structures, whereas p24delta(2-transgenesis does not influence the overall ultrastructure of the cells nor POMC transport and cleavage, but affects the Golgi-based processes of POMC glycomaturation and sulfation. CONCLUSIONS/SIGNIFICANCE: Transgenic expression of two distinct p24 family members has disparate effects on secretory pathway functioning, illustrating the specificity and non-redundancy of our transgenic approach. We conclude that members of the p24 family furnish subcompartments of the secretory pathway with specific sets of machinery cargo to provide the proper microenvironments for efficient and correct secretory protein transport and processing.

  17. Magneto-optical spectroscopy of diluted magnetic oxides TiO{sub 2-{delta}}: Co

    Energy Technology Data Exchange (ETDEWEB)

    Gan' shina, E.A. [Faculty of Physics, Moscow State M.V. Lomonosov University, Moscow 119991 (Russian Federation)], E-mail:; Granovsky, A.B. [Faculty of Physics, Moscow State M.V. Lomonosov University, Moscow 119991 (Russian Federation); Orlov, A.F. [State Research Institute for the Rare-Metal Industry, Moscow 119017 (Russian Federation); Perov, N.S.; Vashuk, M.V. [Faculty of Physics, Moscow State M.V. Lomonosov University, Moscow 119991 (Russian Federation)


    We report an experimental study on transversal Kerr effect (TKE) in magnetic oxide semiconductors TiO{sub 2-{delta}}:Co. The TiO{sub 2-{delta}}: Co thin films were deposited on LaAlO{sub 3} (0 0 1) substrates by magnetron sputtering in the argon-oxygen atmosphere at oxygen partial pressure of 2x10{sup -6}-2x10{sup -4} Torr. It was obtained that TKE spectra in ferromagnetic samples are extremely sensitive to the Co-volume fraction, the crystalline structure, and technology parameters. The observed well-pronounced peaks in TKE spectra for anatase Co-doped TiO{sub 2-{delta}} films at low Co (<1%) volume fraction are not representative for bulk Co or Co clusters in TiO{sub 2-{delta}} matrix that indicates on intrinsic ferromagnetism in these samples. With increase of Co-volume fraction up to 5-8% the fine structure of TKE spectra disappears and magneto-optical response in reflection mode becomes larger than that for thick Co films.

  18. Modeling Anthropogenic Impact on Sediment Balance and Relative Sea-Level Rise in Contemporary and Future Deltas (United States)

    Tessler, Z. D.; Vorosmarty, C. J.; Overeem, I.; Syvitski, J. P.


    Modern deltas are dependent on human-mediated freshwater and sediment fluxes. Changes to these fluxes impact delta biogeophysical functioning, and affect the long-term sustainability of these landscapes for both human and natural systems. Here we present contemporary estimates of long-term mean sediment balance and relative sea-level rise across 46 global deltas. We model ongoing development and scenarios of future water resource management and hydropower infrastructure in upstream river basins to explore how changing sediment fluxes impact relative sea-level in coastal delta systems. Model results show that contemporary sediment fluxes, anthropogenic drivers of land subsidence, a