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Sample records for newly synthesized mpl-i

  1. Congenital amegakaryocytic thrombocytopenia iPS cells exhibit defective MPL-mediated signaling.

    Science.gov (United States)

    Hirata, Shinji; Takayama, Naoya; Jono-Ohnishi, Ryoko; Endo, Hiroshi; Nakamura, Sou; Dohda, Takeaki; Nishi, Masanori; Hamazaki, Yuhei; Ishii, Ei-ichi; Kaneko, Shin; Otsu, Makoto; Nakauchi, Hiromitsu; Kunishima, Shinji; Eto, Koji

    2013-09-01

    Congenital amegakaryocytic thrombocytopenia (CAMT) is caused by the loss of thrombopoietin receptor-mediated (MPL-mediated) signaling, which causes severe pancytopenia leading to bone marrow failure with onset of thrombocytopenia and anemia prior to leukopenia. Because Mpl(-/-) mice do not exhibit the human disease phenotype, we used an in vitro disease tracing system with induced pluripotent stem cells (iPSCs) derived from a CAMT patient (CAMT iPSCs) and normal iPSCs to investigate the role of MPL signaling in hematopoiesis. We found that MPL signaling is essential for maintenance of the CD34+ multipotent hematopoietic progenitor (MPP) population and development of the CD41+GPA+ megakaryocyte-erythrocyte progenitor (MEP) population, and its role in the fate decision leading differentiation toward megakaryopoiesis or erythropoiesis differs considerably between normal and CAMT cells. Surprisingly, complimentary transduction of MPL into normal or CAMT iPSCs using a retroviral vector showed that MPL overexpression promoted erythropoiesis in normal CD34+ hematopoietic progenitor cells (HPCs), but impaired erythropoiesis and increased aberrant megakaryocyte production in CAMT iPSC-derived CD34+ HPCs, reflecting a difference in the expression of the transcription factor FLI1. These results demonstrate that impaired transcriptional regulation of the MPL signaling that normally governs megakaryopoiesis and erythropoiesis underlies CAMT.

  2. Mouse monoclonal antibodies against human c-Mpl and characterization for flow cytometry applications.

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    Abbott, Christina; Huang, Guo; Ellison, Aaron R; Chen, Ching; Arora, Taruna; Szilvassy, Stephen J; Wei, Ping

    2010-04-01

    Mouse monoclonal antibodies (MAbs) against human c-Mpl, the cognate receptor for thrombopoietin (TPO), were generated using hybridoma technology and characterized by various assays to demonstrate their specificity and affinity. Two such MAbs, 1.6 and 1.75, were determined to be superior for flow cytometry studies and exhibited double-digit picomolar (pM) affinities to soluble human c-Mpl protein. Both MAbs specifically bound to cells engineered to overexpress human c-Mpl protein, immortalized human hematopoietic cell lines that express endogenous c-Mpl, primary human bone marrow and peripheral blood-derived CD34(+) cells, and purified human platelets. No binding was detected on cell lines that did not express c-Mpl. Receptor competition and siRNA knock-down studies further confirmed the specificity of antibodies 1.6 and 1.75 for human c-Mpl. In contrast to these newly generated MAbs, none of eight commercially available anti-c-Mpl antibodies tested were found to bind specifically to human c-Mpl and were thus shown to be unsuitable for flow cytometry studies. Monoclonal antibodies 1.6 and 1.75 will therefore be useful flow cytometry reagents to detect cell surface c-Mpl expression.

  3. Expression pattern of the thrombopoietin receptor (Mpl) in the murine central nervous system.

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    Ivanova, Anna; Wuerfel, Jens; Zhang, Juan; Hoffmann, Olaf; Ballmaier, Matthias; Dame, Christof

    2010-07-28

    Thrombopoietin (Thpo) and its receptor (Mpl), which regulate megakaryopoiesis, are expressed in the central nervous system (CNS), where Thpo is thought to exert pro-apoptotic effects on newly generated neurons. Mpl expression has been analysed in brain tissue on transcript level and in cultured primary rat neurons and astrocytes on protein level. Herein, we analysed Mpl expression in the developing and adult murine CNS by immunohistochemistry and investigated the brain of mice with homozygous Mpl deficiency (Mpl-/-) by MRI. Mpl was not detectable at developmental stages E12 to E15 in any resident cells of the CNS. From E18 onwards, robust Mpl expression was found in various brain areas, including cerebral cortex, olfactory bulb, thalamus, hypothalamus, medulla, pons, and the grey matter of spinal cord. However, major developmental changes became obvious: In the subventricular zone of the cerebral cortex Mpl expression occurred only during late gestation, while in the hippocampus Mpl expression was detectable for first time at stage P4. In the white matter of the cerebellum Mpl expression was restricted to the perinatal period. In the adult cerebellum, Mpl expression switched to Purkinje cell. The majority of other Mpl-positive cells were NeuN-positive neurons. None of the cells could be double-labelled with astrocyte marker GFAP. Mpl-/- mice showed no gross abnormalities of the brain. Our data locate Mpl expression to neurons at different subdivisions of the spinal cord, rhombencephalon, midbrain and prosencephalon. Besides neuronal cells Mpl protein is also expressed in Purkinje cells of the adult cerebellum.

  4. [Expression of c-MPL in leukemic stem cells from acute myeloid leukemia patients].

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    Yu, Pei; Qiu, Shao-Wei; Rao, Qing; Lin, Dong; Xing, Hai-Yan; Tang, Ke-Jing; Tian, Zheng; Wang, Min; Wang, Jian-Xiang

    2012-10-01

    This study was aimed to investigate the expression of c-MPL in acute myeloid leukemia (AML) and the correlation of the c-MPL expression with CD34 and CD38, so as to define the expression of c-MPL in leukemic stem cells. The expression levels of CD34, CD38 and c-MPL were detected by flow cytometry in bone marrow cells from 29 newly diagnosed AML patients. The relationship of c-MPL positive cell ratio with clinical parameters and correlation of c-MPL with CD34 and CD38 expression in AML patients were analyzed. The results showed that expression level of c-MPL in AML patients was significantly higher than that of normal controls (P MPL did not correlate with age, sex, white blood cell count, AML1-ETO fusion gene and remission after chemotherapy, but the expression of c-MPL in M2 and M5 patients was higher than that of normal control (P MPL in CD34 positive AML patients was obviously higher than that in CD34 negative AML patients (P MPL was significantly higher expressed in CD34(+) cells than that in CD34(-) cells (P MPL expression was not significantly different between CD34(+)CD38(-) and CD34(+)CD38(-) cell groups. Positive correlation between c-MPL and CD34 expression was observed (r = 0.380, P = 0.042). It is concluded that expression of c-MPL is higher in AML patients, and positively correlates with the expression level of CD34. The c-MPL expresses in leukemic stem cells.

  5. Lentiviral gene transfer regenerates hematopoietic stem cells in a mouse model for Mpl-deficient aplastic anemia.

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    Heckl, Dirk; Wicke, Daniel C; Brugman, Martijn H; Meyer, Johann; Schambach, Axel; Büsche, Guntram; Ballmaier, Matthias; Baum, Christopher; Modlich, Ute

    2011-04-07

    Thpo/Mpl signaling plays an important role in the maintenance of hematopoietic stem cells (HSCs) in addition to its role in megakaryopoiesis. Patients with inactivating mutations in Mpl develop thrombocytopenia and aplastic anemia because of progressive loss of HSCs. Yet, it is unknown whether this loss of HSCs is an irreversible process. In this study, we used the Mpl knockout (Mpl(-/-)) mouse model and expressed Mpl from newly developed lentiviral vectors specifically in the physiologic Mpl target populations, namely, HSCs and megakaryocytes. After validating lineage-specific expression in vivo using lentiviral eGFP reporter vectors, we performed bone marrow transplantation of transduced Mpl(-/-) bone marrow cells into Mpl(-/-) mice. We show that restoration of Mpl expression from transcriptionally targeted vectors prevents lethal adverse reactions of ectopic Mpl expression, replenishes the HSC pool, restores stem cell properties, and corrects platelet production. In some mice, megakaryocyte counts were atypically high, accompanied by bone neo-formation and marrow fibrosis. Gene-corrected Mpl(-/-) cells had increased long-term repopulating potential, with a marked increase in lineage(-)Sca1(+)cKit(+) cells and early progenitor populations in reconstituted mice. Transcriptome analysis of lineage(-)Sca1(+)cKit(+) cells in Mpl-corrected mice showed functional adjustment of genes involved in HSC self-renewal.

  6. Generation of human iPSCs from an essential thrombocythemia patient carrying a V501L mutation in the MPL gene.

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    Liu, Senquan; Ye, Zhaohui; Gao, Yongxing; He, Chaoxia; Williams, Donna W; Moliterno, Alison; Spivak, Jerry; Huang, He; Cheng, Linzhao

    2017-01-01

    Activating point mutations in the MPL gene encoding the thrombopoietin receptor are found in 3%-10% of essential thrombocythemia (ET) and myelofibrosis patients. Here, we report the derivation of induced pluripotent stem cells (iPSCs) from an ET patient with a heterozygous MPL V501L mutation. Peripheral blood CD34 + progenitor cells were reprogrammed by transient plasmid expression of OCT4, SOX2, KLF4, c-MYC plus BCL2L1 (BCL-xL) genes. The derived line M494 carries a MPL V501L mutation, displays typical iPSC morphology and characteristics, are pluripotent and karyotypically normal. Upon differentiation, the iPSCs are able to differentiate into cells derived from three germ layers. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Cross-Linking Mast Cell Specific Gangliosides Stimulates the Release of Newly Formed Lipid Mediators and Newly Synthesized Cytokines

    Directory of Open Access Journals (Sweden)

    Edismauro Garcia Freitas Filho

    2016-01-01

    Full Text Available Mast cells are immunoregulatory cells that participate in inflammatory processes. Cross-linking mast cell specific GD1b derived gangliosides by mAbAA4 results in partial activation of mast cells without the release of preformed mediators. The present study examines the release of newly formed and newly synthesized mediators following ganglioside cross-linking. Cross-linking the gangliosides with mAbAA4 released the newly formed lipid mediators, prostaglandins D2 and E2, without release of leukotrienes B4 and C4. The effect of cross-linking these gangliosides on the activation of enzymes in the arachidonate cascade was then investigated. Ganglioside cross-linking resulted in phosphorylation of cytosolic phospholipase A2 and increased expression of cyclooxygenase-2. Translocation of 5-lipoxygenase from the cytosol to the nucleus was not induced by ganglioside cross-linking. Cross-linking of GD1b derived gangliosides also resulted in the release of the newly synthesized mediators, interleukin-4, interleukin-6, and TNF-α. The effect of cross-linking the gangliosides on the MAP kinase pathway was then investigated. Cross-linking the gangliosides induced the phosphorylation of ERK1/2, JNK1/2, and p38 as well as activating both NFκB and NFAT in a Syk-dependent manner. Therefore, cross-linking the mast cell specific GD1b derived gangliosides results in the activation of signaling pathways that culminate with the release of newly formed and newly synthesized mediators.

  8. JAK and MPL mutations in myeloid malignancies.

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    Tefferi, Ayalew

    2008-03-01

    The Janus family of non-receptor tyrosine kinases (JAK1, JAK2, JAK3 and tyrosine kinase 2) transduces signals downstream of type I and II cytokine receptors via signal transducers and activators of transcription (STATs). JAK3 is important in lymphoid and JAK2 in myeloid cell proliferation and differentiation. The thrombopoietin receptor MPL is one of several JAK2 cognate receptors and is essential for myelopoiesis in general and megakaryopoiesis in particular. Germline loss-of-function (LOF) JAK3 and MPL mutations cause severe combined immunodeficiency and congenital amegakaryocytic thrombocytopenia, respectively. Germline gain-of-function (GOF) MPL mutation (MPLS505N) causes familial thrombocytosis. Somatic JAK3 (e.g. JAK3A572V, JAK3V722I, JAK3P132T) and fusion JAK2 (e.g. ETV6-JAK2, PCM1-JAK2, BCR-JAK2) mutations have respectively been described in acute megakaryocytic leukemia and acute leukemia/chronic myeloid malignancies. However, current attention is focused on JAK2 (e.g. JAK2V617F, JAK2 exon 12 mutations) and MPL (e.g. MPLW515L/K/S, MPLS505N) mutations associated with myeloproliferative neoplasms (MPNs). A JAK2 mutation, primarily JAK2V617F, is invariably associated with polycythemia vera (PV). The latter mutation also occurs in the majority of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). MPL mutational frequency in MPNs is substantially less (<10%). In general, despite a certain degree of genotype - phenotype correlations, the prognostic relevance of harbouring one of these mutations, or their allele burden when present, remains dubious. Regardless, based on the logical assumption that amplified JAK-STAT signalling is central to the pathogenesis of PV, ET and PMF, several anti-JAK2 tyrosine kinase inhibitors have been developed and are currently being tested in humans with these disorders.

  9. Novel thrombopoietin mimetic peptides bind c-Mpl receptor: Synthesis, biological evaluation and molecular modeling.

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    Liu, Yaquan; Tian, Fang; Zhi, Dejuan; Wang, Haiqing; Zhao, Chunyan; Li, Hongyu

    2017-02-01

    Thrombopoietin (TPO) acts in promoting the proliferation of hematopoietic stem cells and by initiating specific maturation events in megakaryocytes. Now, TPO-mimetic peptides with amino acid sequences unrelated to TPO are of considerable pharmaceutical interest. In the present paper, four new TPO mimetic peptides that bind and activate c-Mpl receptor have been identified, synthesized and tested by Dual-Luciferase reporter gene assay for biological activities. The molecular modeling research was also approached to understand key molecular mechanisms and structural features responsible for peptide binding with c-Mpl receptor. The results presented that three of four mimetic peptides showed significant activities. In addition, the molecular modeling approaches proved hydrophobic interactions were the driven positive forces for binding behavior between peptides and c-Mpl receptor. TPO peptide residues in P7, P13 and P7' positions were identified by the analysis of hydrogen bonds and energy decompositions as the key ones for benefiting better biological activities. Our data suggested the synthesized peptides have considerable potential for the future development of stable and highly active TPO mimetic peptides. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. The thrombopoietin receptor, c-Mpl, is a selective surface marker for human hematopoietic stem cells

    Directory of Open Access Journals (Sweden)

    Kerr William G

    2006-02-01

    Full Text Available Abstract Background Thrombopoietin (TPO, the primary cytokine regulating megakaryocyte proliferation and differentiation, exerts significant influence on other hematopoietic lineages as well, including erythroid, granulocytic and lymphoid lineages. We previously demonstrated that the receptor for TPO, c-mpl, is expressed by a subset of human adult bone marrow hematopoietic stem/progenitor cells (HSC/PC that are enriched for long-term multilineage repopulating ability in the SCID-hu Bone in vivo model of human hematopoiesis. Methods Here, we employ flow cytometry and an anti-c-mpl monoclonal antibody to comprehensively define the surface expression pattern of c-mpl in four differentiation stages of human CD34+ HSC/PC (I: CD34+38--, II: CD34+38dim, III: CD34+38+, IV: CD34dim38+ for the major sources of human HSC: fetal liver (FL, umbilical cord blood (UCB, adult bone marrow (ABM, and cytokine-mobilized peripheral blood stem cells (mPBSC. We use a surrogate in vivo model of human thymopoiesis, SCID-hu Thy/Liv, to compare the capacity of c-mpl+ vs. c-mpl-- CD34+38--/dim HSC/PC for thymocyte reconstitution. Results For all tissue sources, the percentage of c-mpl+ cells was significantly highest in stage I HSC/PC (FL 72 ± 10%, UCB 67 ± 19%, ABM 82 ± 16%, mPBSC 71 ± 15%, and decreased significantly through stages II, III, and IV ((FL 3 ± 3%, UCB 8 ± 13%, ABM 0.6 ± 0.6%, mPBSC 0.2 ± 0.1% [ANOVA: P I, decreasing through stage IV [ANOVA: P + cells [P = 0.89] or intensity of c-mpl expression [P = 0.21]. Primary Thy/Liv grafts injected with CD34+38--/dimc-mpl+ cells showed slightly higher levels of donor HLA+ thymocyte reconstitution vs. CD34+38--/dimc-mpl---injected grafts and non-injected controls (c-mpl+ vs. c-mpl--: CD2+ 6.8 ± 4.5% vs. 2.8 ± 3.3%, CD4+8-- 54 ± 35% vs. 31 ± 29%, CD4--8+ 29 ± 19% vs. 18 ± 14%. Conclusion These findings support the hypothesis that the TPO receptor, c-mpl, participates in the regulation of primitive human HSC

  11. C-Mannosylation of thrombopoietin receptor (c-Mpl) regulates thrombopoietin-dependent JAK-STAT signaling.

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    Sasazawa, Yukiko; Sato, Natsumi; Suzuki, Takehiro; Dohmae, Naoshi; Simizu, Siro

    The thrombopoietin receptor, also known as c-Mpl, is a member of the cytokine superfamily, which regulates the differentiation of megakaryocytes and formation of platelets by binding to its ligand, thrombopoietin (TPO), through Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling. The loss-of-function mutations of c-Mpl cause severe thrombocytopenia due to impaired megakaryocytopoiesis, and gain-of-function mutations cause thrombocythemia. c-Mpl contains two Trp-Ser-Xaa-Trp-Ser (Xaa represents any amino acids) sequences, which are characteristic sequences of type I cytokine receptors, corresponding to C-mannosylation consensus sequences: Trp-Xaa-Xaa-Trp/Cys. C-mannosylation is a post-translational modification of tryptophan residue in which one mannose is attached to the first tryptophan residue in the consensus sequence via C-C linkage. Although c-Mpl contains some C-mannosylation sequences, whether c-Mpl is C-mannosylated or not has been uninvestigated. We identified that c-Mpl is C-mannosylated not only at Trp(269) and Trp(474), which are putative C-mannosylation site, but also at Trp(272), Trp(416), and Trp(477). Using C-mannosylation defective mutant of c-Mpl, the C-mannosylated tryptophan residues at four sites (Trp(269), Trp(272), Trp(474), and Trp(477)) are essential for c-Mpl-mediated JAK-STAT signaling. Our findings suggested that C-mannosylation of c-Mpl is a possible therapeutic target for platelet disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. MPL mutations in myeloproliferative disorders

    DEFF Research Database (Denmark)

    Beer, Philip A.; Campbell, Peter J.; Scott, Linda M.

    2008-01-01

    Activating mutations of MPL exon 10 have been described in a minority of patients with idiopathic myelofibrosis (IMF) or essential thrombocythemia (ET), but their prevalence and clinical significance are unclear. Here we demonstrate that MPL mutations outside exon 10 are uncommon in platelet c......DNA and identify 4 different exon 10 mutations in granulocyte DNA from a retrospective cohort of 200 patients with ET or IMF. Allele-specific polymerase chain reaction was then used to genotype 776 samples from patients with ET entered into the PT-1 studies. MPL mutations were identified in 8.5% of JAK2 V617F......(-) patients and a single V617F(+) patient. Patients carrying the W515K allele had a significantly higher allele burden than did those with the W515L allele, suggesting a functional difference between the 2 variants. Compared with V617F(+) ET patients, those with MPL mutations displayed lower hemoglobin...

  13. Novel anti-c-Mpl monoclonal antibodies identified multiple differentially glycosylated human c-Mpl proteins in megakaryocytic cells but not in human solid tumors.

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    Zhan, Jinghui; Felder, Barbara; Ellison, Aaron R; Winters, Aaron; Salimi-Moosavi, Hossein; Scully, Sheila; Turk, James R; Wei, Ping

    2013-06-01

    Thrombopoietin and its cognate receptor, c-Mpl, are the primary molecular regulators of megakaryocytopoiesis and platelet production. To date the pattern of c-Mpl expression in human solid tumors and the distribution and biochemical properties of c-Mpl proteins in hematopoietic tissues are largely unknown. We have recently developed highly specific mouse monoclonal antibodies (MAb) against human c-Mpl. In this study we used these antibodies to demonstrate the presence of full-length and truncated human c-Mpl proteins in various megakaryocytic cell types, and their absence in over 100 solid tumor cell lines and in the 12 most common primary human tumor types. Quantitative assays showed a cell context-dependent distribution of full-length and truncated c-Mpl proteins. All forms of human c-Mpl protein were found to be modified with extensive N-linked glycosylation but different degrees of sialylation and O-linked glycosylation. Of note, different variants of full-length c-Mpl protein exhibiting differential glycosylation were expressed in erythromegakaryocytic leukemic cell lines and in platelets from healthy human donors. This work provides a comprehensive analysis of human c-Mpl mRNA and protein expression on normal and malignant hematopoietic and non-hematopoietic cells and demonstrates the multiple applications of several novel anti-c-Mpl antibodies.

  14. Brief Reports: Nfix Promotes Survival of Immature Hematopoietic Cells via Regulation of c-Mpl.

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    Hall, Trent; Walker, Megan; Ganuza, Miguel; Holmfeldt, Per; Bordas, Marie; Kang, Guolian; Bi, Wenjian; Palmer, Lance E; Finkelstein, David; McKinney-Freeman, Shannon

    2018-02-12

    Hematopoietic stem and progenitor cells (HSPCs) are necessary for life-long blood production and replenishment of the hematopoietic system during stress. We recently reported that nuclear factor I/X (Nfix) promotes HSPC survival post-transplant. Here, we report that ectopic expression of Nfix in primary mouse HSPCs extends their ex vivo culture from about 20 to 40 days. HSPCs overexpressing Nfix display hypersensitivity to supportive cytokines and reduced apoptosis when subjected to cytokine deprivation relative to controls. Ectopic Nfix resulted in elevated levels of c-Mpl transcripts and cell surface protein on primary murine HSPCs as well as increased phosphorylation of STAT5, which is known to be activated down-stream of c-MPL. Blocking c-MPL signaling by removal of thrombopoietin or addition of a c-MPL neutralizing antibody negated the antiapoptotic effect of Nfix overexpression on cultured HSPCs. Furthermore, NFIX was capable of binding to and transcriptionally activating a proximal c-Mpl promoter fragment. In sum, these data suggest that NFIX-mediated upregulation of c-Mpl transcription can protect primitive hematopoietic cells from stress ex vivo. Stem Cells 2018. © AlphaMed Press 2018.

  15. Localization and movement of newly synthesized cholesterol in rat ovarian granulosa cells

    International Nuclear Information System (INIS)

    Lange, Y.; Schmit, V.M.; Schreiber, J.R.

    1988-01-01

    The distribution and movement of cholesterol were studied in granulosa cells from the ovaries of estrogen-stimulated hypophysectomized immature rats cultured in serum-free medium. Plasma membrane cholesterol was distinguished from intracellular cholesterol with cholesterol oxidase, an enzyme that converts cell surface cholesterol to cholestenone, leaving intracellular cholesterol untouched. Using this approach we showed that 82% of unesterified cholesterol was associated with the plasma membrane in granulosa cells cultured for 48 h in serum-free medium in both the presence and absence of added androstenedione and FSH. FSH and androstenedione stimulated a marked increase in steroid hormone (progestin) production. The movement of newly synthesized cholesterol to the plasma membrane also was followed using cholesterol oxidase. Newly synthesized cholesterol reached the plasma membrane too rapidly to be measured in unstimulated cells (t1/2 less than 20 min); however, in cells stimulated by FSH and androstenedione, this rate was considerably slower (t1/2 approximately 2h). Therefore, cholesterol movement to the plasma membrane appears to be regulated by gonadotropins in these cells. We tested whether steroid biosynthesis used all cell cholesterol pools equally. To this end we administered [3H]acetate and [14C]acetate at different times and determined their relative specific contents in various steroids after defined intervals. The relative ages of the steroids (youngest to oldest) were: lanosterol, progestins, intracellular cholesterol, and plasma membrane cholesterol. This finding suggests that progestins use newly synthesized intracellular cholesterol in preference to preexisting intracellular or cell surface cholesterol

  16. Genetic Alterations of the Thrombopoietin/MPL/JAK2 Axis Impacting Megakaryopoiesis.

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    Plo, Isabelle; Bellanné-Chantelot, Christine; Mosca, Matthieu; Mazzi, Stefania; Marty, Caroline; Vainchenker, William

    2017-01-01

    Megakaryopoiesis is an original and complex cell process which leads to the formation of platelets. The homeostatic production of platelets is mainly regulated and controlled by thrombopoietin (TPO) and the TPO receptor (MPL)/JAK2 axis. Therefore, any hereditary or acquired abnormality affecting this signaling axis can result in thrombocytosis or thrombocytopenia. Thrombocytosis can be due to genetic alterations that affect either the intrinsic MPL signaling through gain-of-function (GOF) activity ( MPL, JAK2, CALR ) and loss-of-function (LOF) activity of negative regulators ( CBL, LNK ) or the extrinsic MPL signaling by THPO GOF mutations leading to increased TPO synthesis. Alternatively, thrombocytosis may paradoxically result from mutations of MPL leading to an abnormal MPL trafficking, inducing increased TPO levels by alteration of its clearance. In contrast, thrombocytopenia can also result from LOF THPO or MPL mutations, which cause a complete defect in MPL trafficking to the cell membrane, impaired MPL signaling or stability, defects in the TPO/MPL interaction, or an absence of TPO production.

  17. The Micro-Pulse Lidar Network (MPL-Net)

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    Welton, Ellsworth J.; Campbell, James R.; Berkoff, Timothy A.; Spinhirne, James D.; Tsay, Si-Chee; Holben, Brent; Shiobara, Masataka; Starr, David OC. (Technical Monitor)

    2002-01-01

    In the early 1990s, the first small, eye-safe, and autonomous lidar system was developed, the Micro-pulse Lidar (MPL). The MPL has proven to be useful in the field because it can be automated, runs continuously (day and night), is eye-safe, can easily be transported and set up, and has a small field-of-view which limits multiple scattering concerns. The MPL acquires signal profiles of backscattered laser light from aerosols and clouds. The signals are analyzed to yield multiple layer heights, optical depths of each layer, average extinction-to-backscatter ratio of each layer, and profiles of extinction in each layer. The MPL has been used in a wide variety of field studies over the past 10 years, leading to nearly 20 papers and many conference presentations. In 2000, a new project using MPL systems was started at NASA Goddard Space Flight Center. The MPL-Net project is currently working to establish a worldwide network of MPL systems, all co-located with NASA's AERONET sunphotometers for joint measurements of optical depth and sky radiance. Automated processing algorithms have been developed to produce data products on a next day basis for all sites and some field experiments. Initial results from the first several sites are shown, along with aerosol data collected during several major field campaigns. Measurements of the aerosol extinction-to-backscatter ratio at several different geographic regions, and for various aerosol types are shown. This information is used to improve the construction of look up tables of the ratio, needed to process aerosol profiles acquired with satellite based lidars.

  18. MPL W515L/K Mutations in Chronic Myeloproliferative Neoplasms.

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    Akpınar, Timur Selçuk; Hançer, Veysel Sabri; Nalçacı, Meliha; Diz-Küçükkaya, Reyhan

    2013-03-01

    The MPL gene encodes the thrombopoietin receptor. Recently MPL mutations (MPL W515L or MPL W515K) were described in patients with essential thrombocythemia (ET) and primary (idiopathic) myelofibrosis (PMF). The prevalence and the clinical importance of these mutations are not clear. In the present study, we aimed to investigate the frequency and clinical significance of MPL W515L/K mutations in our patients with ET and PMF. A total of 77 patients (66 were diagnosed with ET and 11 with PMF) and 42 healthy controls were included in the study. Using peripheral blood samples, the presence of MPL W515L/K mutations and JAK-2 V617F mutation were analyzed by real-time polymerase chain reaction. In our study, MPL W515L/K or JAK-2 V617F mutations were not observed in healthy controls. JAK-2 V617F mutation was present in 35 patients, of whom 29 had ET (43.9%, 29/66) and 6 had PMF (54.5%, 6/11). In the patient group, MPL W515L/K mutations were found in only 2 PMF cases, and these cases were negative for JAK-2 V617F mutation. The prevalence of MPL W515L/K mutations in the patient group was 2.6%, and the prevalence of MPL W515L/K mutations among the cases negative for the JAK-2 V617F mutation was found to be 4.8%. The 2 cases with MPL W515L/K mutations had long follow-up times (124 months and 71 months, respectively), had no thrombotic or hemorrhagic complications, and had no additional cytogenetic anomalies. MPL W515L/K mutations may be helpful for identifying clonal disease in MPN patients with no established Ph chromosome or JAK-2 V617F mutation. None declared.

  19. Initial Results From The Micro-pulse Lidar Network (MPL-Net)

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    Welton, E. J.; Campbell, J. R.; Berkoff, T. A.; Spinhirne, J. D.; Ginoux, P.

    2001-12-01

    The micro-pulse lidar system (MPL) was developed in the early 1990s and was the first small, eye-safe, and autonomous lidar built for fulltime monitoring of cloud and aerosol vertical distributions. In 2000, a new project using MPL systems was started at NASA Goddard Space Flight Center. This new project, the Micro-pulse Lidar Network or MPL-Net, was created to provide long-term observations of aerosol and cloud vertical profiles at key sites around the world. This is accomplished using both NASA operated sites and partnerships with other organizations owning MPL systems. The MPL-Net sites are co-located with NASA AERONET sunphotometers to provide aerosol optical depth data needed for calibration of the MPL. In addition to the long-term sites, MPL-Net provides lidar support for a limited number of field experiments and ocean cruises each year. We will present an overview of the MPL-Net project and show initial results from the first two MPL-Net sites at the South Pole and at Goddard Space Flight Center. Observations of dust layers transported from the desert regions of China, across the Pacific Ocean, to the east coast of the United States will also be shown. MPL-Net affiliated instruments were in place at the desert source region in China, on a research vessel in the Sea of Japan, at ARM sites in Alaska and Oklahoma, and finally at our home site in Maryland (GSFC) during the massive dust storms that occurred in April 2001. The MPL observations of dust layers at each location are shown in comparison to dust layers predicted using the Georgia Tech/Goddard Global Ozone Chemistry Aerosol Radiation and Transport model (GOCART). Finally, the MPL-Net project is the primary ground-validation program for the Geo-Science Laser Altimeter System (GLAS) satellite lidar project (launch date 2002). We will present an overview demonstrating how MPL-Net results are used to help prepare the GLAS data processing algorithms and assist in the calibration/validation of the GLAS data

  20. Initial Results from the Micro-pulse Lidar Network (MPL-Net)

    Science.gov (United States)

    Welton, Ellsworth J.; Campbell, James R.; Berkoff, Timothy A.; Spinhirne, James D.; Ginoux, Paul; Starr, David OC. (Technical Monitor)

    2001-01-01

    The micro-pulse lidar system (MPL) was developed in the early 1990s and was the first small, eye-safe, and autonomous lidar built for full time monitoring of cloud and aerosol vertical distributions. In 2000, a new project using MPL systems was started at NASA Goddard Space Flight Center. This new project, the Micro-pulse Lidar Network or MPL-Net, was created to provide long-term observations of aerosol and cloud vertical profiles at key sites around the world. This is accomplished using both NASA operated sites and partnerships with other organizations owning MPL systems. The MPL-Net sites are co-located with NASA AERONET sunphotometers to provide aerosol optical depth data needed for calibration of the MPL. In addition to the long-term sites, MPL-Net provides lidar support for a limited number of field experiments and ocean cruises each year. We will present an overview of the MPL-Net project and show initial results from the first two MPL-Net sites at the South Pole and at Goddard Space Flight Center. Observations of dust layers transported from the Gobi desert, across the Pacific Ocean, to the east coast of the United States will also be shown. MPL-Net affiliated instruments were in place at the desert source region in China, on a research vessel in the Sea of Japan, at ARM sites in Alaska and Oklahoma, and finally at our home site in Maryland (GSFC) during the massive dust storms that occurred in April 2001. The MPL observations of dust layers at each location are shown in comparison to dust layers predicted using the Georgia Tech/Goddard Global Ozone Chemistry Aerosol Radiation and Transport model (GOCART). Finally, the MPL-Net project is the primary ground-validation program for the Geo-Science Laser Altimeter System (GLAS) satellite lidar project (launch date 2002). We will present an overview demonstrating how MPL-Net results are used to help prepare the GLAS data processing algorithms and assist in the calibration/validation of the GLAS data products.

  1. Bioorthogonal Chemistry for the Isolation and Study of Newly Synthesized Histones and Their Modifications.

    Science.gov (United States)

    Arnaudo, Anna M; Link, A James; Garcia, Benjamin A

    2016-03-18

    The nucleosome is an octamer containing DNA wrapped around one histone H3-H4 tetramer and two histone H2A-H2B dimers. Within the nucleosome, histones are decorated with post-translational modifications. Previous studies indicate that the H3-H4 tetramer is conserved during DNA replication, suggesting that old tetramers serve as a template for the modification of newly synthesized tetramers. Here, we present a method that merges bioorthogonal chemistry with mass spectrometry for the study of modifications on newly synthesized histones in mammalian cells. HeLa S3 cells are dually labeled with the methionine analog azidohomoalanine and heavy (13)C6,(15)N4 isotope labeled arginine. Heavy amino acid labeling marks newly synthesized histones while azidohomoalanine incorporation allows for their isolation using bioorthogonal ligation. Labeled mononucleosomes were covalently linked via a copper catalyzed reaction to a FLAG-GGR-alkyne peptide, immunoprecipitated, and subjected to mass spectrometry for quantitative modification analysis. Mononucleosomes containing new histones were successfully isolated using this approach. Additionally, the development of this method highlights the potential deleterious effects of azidohomoalanine labeling on protein PTMs and cell cycle progression, which should be considered for future studies utilizing bioorthogonal labeling strategies in mammalian cells.

  2. MPL W515L/K Mutations in Chronic Myeloproliferative Neoplasms

    Directory of Open Access Journals (Sweden)

    Timur Selçuk Akpınar

    2013-03-01

    Full Text Available OBJECTIVE: The MPL gene encodes the thrombopoietin receptor. Recently MPL mutations (MPL W515L or MPL W515K were described in patients with essential thrombocythemia (ET and primary (idiopathic myelofibrosis (PMF. The prevalence and the clinical importance of these mutations are not clear. In the present study, we aimed to investigate the frequency and clinical significance of MPL W515L/K mutations in our patients with ET and PMF. METHODS: A total of 77 patients (66 were diagnosed with ET and 11 with PMF and 42 healthy controls were included in the study. Using peripheral blood samples, the presence of MPL W515L/K mutations and JAK-2 V617F mutation were analyzed by real-time polymerase chain reaction. RESULTS: In our study, MPL W515L/K or JAK-2 V617F mutations were not observed in healthy controls. JAK-2 V617F mutation was present in 35 patients, of whom 29 had ET (43.9%, 29/66 and 6 had PMF (54.5%, 6/11. In the patient group, MPL W515L/K mutations were found in only 2 PMF cases, and these cases were negative for JAK-2 V617F mutation. The prevalence of MPL W515L/K mutations in the patient group was 2.6%, and the prevalence of MPL W515L/K mutations among the cases negative for the JAK-2 V617F mutation was found to be 4.8%. The 2 cases with MPL W515L/K mutations had long follow-up times (124 months and 71 months, respectively, had no thrombotic or hemorrhagic complications, and had no additional cytogenetic anomalies. CONCLUSION: MPL W515L/K mutations may be helpful for identifying clonal disease in MPN patients with no established Ph chromosome or JAK-2 V617F mutation.

  3. Vibrational imaging of newly synthesized proteins in live cells by stimulated Raman scattering microscopy

    Science.gov (United States)

    Wei, Lu; Yu, Yong; Shen, Yihui; Wang, Meng C.; Min, Wei

    2013-01-01

    Synthesis of new proteins, a key step in the central dogma of molecular biology, has been a major biological process by which cells respond rapidly to environmental cues in both physiological and pathological conditions. However, the selective visualization of a newly synthesized proteome in living systems with subcellular resolution has proven to be rather challenging, despite the extensive efforts along the lines of fluorescence staining, autoradiography, and mass spectrometry. Herein, we report an imaging technique to visualize nascent proteins by harnessing the emerging stimulated Raman scattering (SRS) microscopy coupled with metabolic incorporation of deuterium-labeled amino acids. As a first demonstration, we imaged newly synthesized proteins in live mammalian cells with high spatial–temporal resolution without fixation or staining. Subcellular compartments with fast protein turnover in HeLa and HEK293T cells, and newly grown neurites in differentiating neuron-like N2A cells, are clearly identified via this imaging technique. Technically, incorporation of deuterium-labeled amino acids is minimally perturbative to live cells, whereas SRS imaging of exogenous carbon–deuterium bonds (C–D) in the cell-silent Raman region is highly sensitive, specific, and compatible with living systems. Moreover, coupled with label-free SRS imaging of the total proteome, our method can readily generate spatial maps of the quantitative ratio between new and total proteomes. Thus, this technique of nonlinear vibrational imaging of stable isotope incorporation will be a valuable tool to advance our understanding of the complex spatial and temporal dynamics of newly synthesized proteome in vivo. PMID:23798434

  4. Potential of Start Codon Targeted (SCoT) markers for DNA fingerprinting of newly synthesized tritordeums and their respective parents.

    Science.gov (United States)

    Cabo, Sandra; Ferreira, Luciana; Carvalho, Ana; Martins-Lopes, Paula; Martín, António; Lima-Brito, José Eduardo

    2014-08-01

    Hexaploid tritordeum (H(ch)H(ch)AABB; 2n = 42) results from the cross between Hordeum chilense (H(ch)H(ch); 2n = 14) and cultivated durum wheat (Triticum turgidum ssp. durum (AABB; 2n = 28). Morphologically, tritordeum resembles the wheat parent, showing promise for agriculture and wheat breeding. Start Codon Targeted (SCoT) polymorphism is a recently developed technique that generates gene-targeted markers. Thus, we considered it interesting to evaluate its potential for the DNA fingerprinting of newly synthesized hexaploid tritordeums and their respective parents. In this study, 60 SCoT primers were tested, and 18 and 19 of them revealed SCoT polymorphisms in the newly synthesized tritordeum lines HT27 and HT22, respectively, and their parents. An analysis of the presence/absence of bands among tritordeums and their parents revealed three types of polymorphic markers: (i) shared by tritordeums and one of their parents, (ii) exclusively amplified in tritordeums, and (iii) exclusively amplified in the parents. No polymorphism was detected among individuals of each parental species. Three SCoT markers were exclusively amplified in tritordeums of lines HT22 and HT27, being considered as polyploidization-induced rearrangements. About 70% of the SCoT markers of H. chilense origin were not transmitted to the allopolyploids of both lines, and most of the SCoTs scored in the newly synthesized allopolyploids originated from wheat, reinforcing the potential use of tritordeum as an alternative crop.

  5. MPL in Context: Some Questions

    Directory of Open Access Journals (Sweden)

    Adail Sobral

    2016-09-01

    Full Text Available The Brazilian translation (2015 of Patrick Sériot's Preface to the French translation (2010 of Marxism and the Philosophy of Language (MPL provides a good opportunity to discuss this work and its relevance for the field of Human Sciences, considering different possible interpretations. In this sense, this work presents a discussion on questions that deserve, in our opinion, to be addressed both in Sériot's work (taken as an example of MPL's interpretation and in Voloshinov's.

  6. Identification of MPL R102P Mutation in Hereditary Thrombocytosis.

    Science.gov (United States)

    Bellanné-Chantelot, Christine; Mosca, Matthieu; Marty, Caroline; Favier, Rémi; Vainchenker, William; Plo, Isabelle

    2017-01-01

    The molecular basis of hereditary thrombocytosis is germline mutations affecting the thrombopoietin (TPO)/TPO receptor (MPL)/JAK2 signaling axis. Here, we report one family presenting two cases with a mild thrombocytosis. By sequencing JAK2 and MPL coding exons, we identified a germline MPL R102P heterozygous mutation in the proband and his daughter. Concomitantly, we detected high TPO levels in the serum of these two patients. The mutation was not found in three other unaffected cases from the family except in another proband's daughter who did not present thrombocytosis but had a high TPO level. The MPL R102P mutation was first described in congenital amegakaryocytic thrombocytopenia in a homozygous state with a loss-of-function activity. It was previously shown that MPL R102P was blocked in the endoplasmic reticulum without being able to translocate to the plasma membrane. Thus, this case report identifies for the first time that MPL R102P mutation can differently impact megakaryopoiesis: thrombocytosis or thrombocytopenia depending on the presence of the heterozygous or homozygous state, respectively. The paradoxical effect associated with heterozygous MPL R102P may be due to subnormal cell-surface expression of wild-type MPL in platelets inducing a defective TPO clearance. As a consequence, increased TPO levels may activate megakaryocyte progenitors that express a lower, but still sufficient level of MPL for the induction of proliferation.

  7. Identification of MPL R102P Mutation in Hereditary Thrombocytosis

    Directory of Open Access Journals (Sweden)

    Christine Bellanné-Chantelot

    2017-09-01

    Full Text Available The molecular basis of hereditary thrombocytosis is germline mutations affecting the thrombopoietin (TPO/TPO receptor (MPL/JAK2 signaling axis. Here, we report one family presenting two cases with a mild thrombocytosis. By sequencing JAK2 and MPL coding exons, we identified a germline MPL R102P heterozygous mutation in the proband and his daughter. Concomitantly, we detected high TPO levels in the serum of these two patients. The mutation was not found in three other unaffected cases from the family except in another proband’s daughter who did not present thrombocytosis but had a high TPO level. The MPL R102P mutation was first described in congenital amegakaryocytic thrombocytopenia in a homozygous state with a loss-of-function activity. It was previously shown that MPL R102P was blocked in the endoplasmic reticulum without being able to translocate to the plasma membrane. Thus, this case report identifies for the first time that MPL R102P mutation can differently impact megakaryopoiesis: thrombocytosis or thrombocytopenia depending on the presence of the heterozygous or homozygous state, respectively. The paradoxical effect associated with heterozygous MPL R102P may be due to subnormal cell-surface expression of wild-type MPL in platelets inducing a defective TPO clearance. As a consequence, increased TPO levels may activate megakaryocyte progenitors that express a lower, but still sufficient level of MPL for the induction of proliferation.

  8. Mpl traffics to the cell surface through conventional and unconventional routes.

    Science.gov (United States)

    Cleyrat, Cédric; Darehshouri, Anza; Steinkamp, Mara P; Vilaine, Mathias; Boassa, Daniela; Ellisman, Mark H; Hermouet, Sylvie; Wilson, Bridget S

    2014-09-01

    Myeloproliferative neoplasms (MPNs) are often characterized by JAK2 or calreticulin (CALR) mutations, indicating aberrant trafficking in pathogenesis. This study focuses on Mpl trafficking and Jak2 association using two model systems: human erythroleukemia cells (HEL; JAK2V617F) and K562 myeloid leukemia cells (JAK2WT). Consistent with a putative chaperone role for Jak2, Mpl and Jak2 associate on both intracellular and plasma membranes (shown by proximity ligation assay) and siRNA-mediated knockdown of Jak2 led to Mpl trapping in the endoplasmic reticulum (ER). Even in Jak2 sufficient cells, Mpl accumulates in punctate structures that partially colocalize with ER-tracker, the ER exit site marker (ERES) Sec31a, the autophagy marker LC3 and LAMP1. Mpl was fused to miniSOG, a genetically encoded tag for correlated light and electron microscopy. Results suggest that a fraction of Mpl is taken up into autophagic structures from the ER and routed to autolyososomes. Surface biotinylation shows that both immature and mature Mpl reach the cell surface; in K562 cells Mpl is also released in exosomes. Both forms rapidly internalize upon ligand addition, while recovery is primarily attributed to immature Mpl. Mpl appears to reach the plasma membrane via both conventional ER-Golgi and autolysosome secretory pathways, as well as recycling. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Molecular mechanisms associated with leukemic transformation of MPL-mutant myeloproliferative neoplasms

    DEFF Research Database (Denmark)

    Beer, Philip A; Ortmann, Christina A; Stegelmann, Frank

    2010-01-01

    Somatic activating mutations in MPL, the thrombopoietin receptor, occur in the myeloproliferative neoplasms, although virtually nothing is known about their role in evolution to acute myeloid leukemia. In this study, the MPL T487A mutation, identified in de novo acute myeloid leukemia......, was not detected in 172 patients with a myeloproliferative neoplasm. In patients with a prior MPL W515L-mutant myeloproliferative neoplasm, leukemic transformation was accompanied by MPL-mutant leukemic blasts, was seen in the absence of prior cytoreductive therapy and often involved loss of wild-type MPL...

  10. Identification of a new Mpl-interacting protein, Atp5d.

    Science.gov (United States)

    Liu, Hongyan; Zhao, Zhenhu; Zhong, Yuxu; Shan, Yajun; Sun, Xiaohong; Mao, Bingzhi; Cong, Yuwen

    2014-06-01

    Thrombopoietin (TPO) can regulate hematopoiesis and megakaryopoiesis via activation of its receptor, c-Mpl, and multiple downstream signal transduction pathways. Using the cytoplasmic domain of Mpl as bait, we performed yeast two-hybrid screening, and found that the protein Atp5d might associate with Mpl. Atp5d is known as the δ subunit of mitochondrial ATP synthase, but little is known about the function of dissociative Atp5d. The interaction between Mpl and Atp5d was confirmed by the yeast two-hybrid system, mammalian two-hybrid assay, pull-down experiment, and co-immunoprecipitation study in vivo and in vitro. An additional immunofluorescence assay showed that the two proteins can colocalize along the plasma membrane in the cytoplasm. Using the yeast two-hybrid system, we tested a series of cytoplasmic truncated mutations for their ability to bind Atp5d and found an association between Atp5d and the Aa98-113 domain of Mpl. The dissociation of Atp5d from Mpl after TPO stimulation suggests that Atp5d may be a new component of TPO signaling.

  11. Phosphorylated c-Mpl tyrosine 591 regulates thrombopoietin-induced signaling.

    Science.gov (United States)

    Sangkhae, Veena; Saur, Sebastian Jonas; Kaushansky, Alexis; Kaushansky, Kenneth; Hitchcock, Ian Stuart

    2014-06-01

    Thrombopoietin (TPO) is the primary regulator of platelet production, affecting cell survival, proliferation, and differentiation through binding to and stimulation of the cell surface receptor the cellular myeloproliferative leukemia virus oncogene (c-Mpl). Activating mutations in c-Mpl constitutively stimulate downstream signaling pathways, leading to aberrant hematopoiesis, and contribute to development of myeloproliferative neoplasms. Several studies have mapped the tyrosine residues within the cytoplasmic domain of c-Mpl that mediate these cellular signals; however, secondary signaling pathways are incompletely understood. In this study, we focused on c-Mpl tyrosine 591 (Y591). We found Y591 of wild-type c-Mpl to be phosphorylated in the presence of TPO. Additionally, eliminating Y591 phosphorylation by mutation to Phe resulted in decreased total receptor phosphorylation. Using a Src homology 2/phosphotyrosine-binding (SH2/PTB) domain binding microarray, we identified novel c-Mpl binding partners for phosphorylated Y591, including Src homology region 2 domain-containing phosphatase-1 (SHP-1), spleen tyrosine kinase (SYK) and Bruton's tyrosine kinase (BTK). The functional significance of binding partners was determined through small interfering RNA treatment of Ba/F3-Mpl cells, confirming that the increase in pERK1/2 resulting from removal of Y591 may be mediated by spleen tyrosine kinase. These findings identify a novel negative regulatory pathway that controls TPO-mediated signaling, advancing our understanding of the mechanisms required for successful maintenance of hematopoietic stem cells and megakaryocyte development. Copyright © 2014 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

  12. Adaptor protein Lnk negatively regulates the mutant MPL, MPLW515L associated with myeloproliferative disorders

    OpenAIRE

    Gery, Sigal; Gueller, Saskia; Chumakova, Katya; Kawamata, Norihiko; Liu, Liqin; Koeffler, H. Phillip

    2007-01-01

    Recently, activating myeloproliferative leukemia virus oncogene (MPL) mutations, MPLW515L/K, were described in myeloproliferative disorder (MPD) patients. MPLW515L leads to activation of downstream signaling pathways and cytokine-independent proliferation in hematopoietic cells. The adaptor protein Lnk is a negative regulator of several cytokine receptors, including MPL. We show that overexpression of Lnk in Ba/F3-MPLW515L cells inhibits cytokine-independent growth, while suppression of Lnk i...

  13. Different mutations of the human c-mpl gene indicate distinct haematopoietic diseases.

    Science.gov (United States)

    He, Xin; Chen, Zhigang; Jiang, Yangyan; Qiu, Xi; Zhao, Xiaoying

    2013-01-25

    The human c-mpl gene (MPL) plays an important role in the development of megakaryocytes and platelets as well as the self-renewal of haematopoietic stem cells. However, numerous MPL mutations have been identified in haematopoietic diseases. These mutations alter the normal regulatory mechanisms and lead to autonomous activation or signalling deficiencies. In this review, we summarise 59 different MPL mutations and classify these mutations into four different groups according to the associated diseases and mutation rates. Using this classification, we clearly distinguish four diverse types of MPL mutations and obtain a deep understand of their clinical significance. This will prove to be useful for both disease diagnosis and the design of individual therapy regimens based on the type of MPL mutations.

  14. GATA-dependent regulation of TPO-induced c-mpl gene expression during megakaryopoiesis.

    Science.gov (United States)

    Sunohara, Masataka; Morikawa, Shigeru; Fuse, Akira; Sato, Iwao

    2014-01-01

    Thrombopoietin (TPO) and its receptor, c-Mpl, play the crucial role during megakaryocytopoiesis. Previously, we have shown that the promoter activity of c-mpl induced by TPO is modulated by transcription through a PKC-dependent pathway and that GATA(-77) is involved as a positive regulatory element in TPO-induced c-mpl gene expression in the megakaryoblastic CMK cells. In this research, to examine participating possibility of GATA promoter element in TPO- induced c-mpl gene expression through a PKC-independent pathway, the promoter activity of site-directed mutagenesis and the effect of potein kinase C modulator were measured by a transient transfection assay system. Together with our previous results on the TPO-induced c-mpl promoter, this study indicates destruction of -77GATA in c-mpl promoter decreased the activity by 47.3% under existence of GF109203. These results suggest that GATA promoter element plays significant role in TPO-induced c-mpl gene expression through a PKC-independent pathway.

  15. Interaction Studies between Newly Synthesized Photosensitive Polymer and Ionic Liquids

    Directory of Open Access Journals (Sweden)

    In Tae Kim

    2015-01-01

    Full Text Available In this information age, different kinds of photosensitive materials have been used in the manufacture of information storage devices. But these photosensitive materials have the bane of low diffraction efficiency. In order to solve this problem, we have synthesized a novel photosensitive polymer from epoxy-based azopolymers (with three types of azochromophores. Furthermore, we have studied the interaction between this newly synthesized azopolymer and ionic liquids (ILs. For this purpose, we have used the ammonium and imidazolium families of ILs, such as diethylammonium dihydrogen phosphate (DEAP, tributylammonium methyl sulfate (TBMS, triethylammonium 4-aminotoluene-3-sulfonic acid (TASA, and 1-methylimidazolium chloride ([Mim]Cl. To investigate the molecular interaction between azopolymer and ILs, we have used the following spectroscopic methods of analysis: UV-visible spectroscopy, photoluminescence (PL spectroscopy, Fourier transformed infrared spectroscopy (FT-IR, and confocal Raman spectroscopy. In this study, we have developed new photosensitive materials by combining polymer with ILs.

  16. Release of newly synthesized nucleoplasmic ribosomal subunits or their precursor particles from isolated nuclei of regenerating rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Usami, K; Ogata, K [Niigata Univ. (Japan). School of Medicine

    1930-06-16

    The authors present the time course of the labeling of RNA and protein moieties of these particles in vivo as well as the pattern of one-dimensional acrylamide gel electrophoresis of their protein moieties labeled with (/sup 35/S)methionine in vivo, which shows that released 60 S particles are newly synthesized ribosomal large subunits or their precursor particles in the nucleoplasm on their way from the nucleolus to the cytoplasm. It appears likely that released 40 S particles contain newly synthesized ribosomal small subunits or their precursors in the nucleoplasm.

  17. Role of promoter element in c-mpl gene expression induced by TPO.

    Science.gov (United States)

    Sunohara, Masataka; Morikawa, Shigeru; Fuse, Akira; Sato, Iwao

    2013-01-01

    Thrombopoietin (TPO) and its receptor, c-Mpl, play the crucial role for the development of megakaryocyte and considered to regulate megakaryocytopoiesis. Previously we reported that TPO increased the c-mpl promoter activity determined by a transient expression system using a vector containing the luciferase gene as a reporter and the expression of the c-mpl gene is modulated by transcription through a protein kinase C (PKC)-dependent pathway in the megakaryoblastic cells. In this research, to elucidate the required elements in c-mpl promoter, the promoter activity of the deletion constructs and site-directed mutagenesis were measured by a transient transfection assay system. Destruction of -77GATA in c-mpl promoter decreased the activity by 22.8%. Our study elucidated that -77GATA involved in TPO-induced c-mpl gene expression in a human megakaryoblastic cell line, CMK.

  18. An incomplete trafficking defect to the cell-surface leads to paradoxical thrombocytosis for human and murine MPL P106L.

    Science.gov (United States)

    Favale, Fabrizia; Messaoudi, Kahia; Varghese, Leila N; Boukour, Siham; Pecquet, Christian; Gryshkova, Vitalina; Defour, Jean Philippe; Albu, Roxana-Irina; Bluteau, Olivier; Ballerini, Paola; Leverger, Guy; Plo, Isabelle; Debili, Najet; Raslova, Hana; Favier, Remi; Constantinescu, Stefan N; Vainchenker, William

    2016-12-29

    The mechanisms behind the hereditary thrombocytosis induced by the thrombopoietin (THPO) receptor MPL P106L mutant remain unknown. A complete trafficking defect to the cell surface has been reported, suggesting either weak constitutive activity or nonconventional THPO-dependent mechanisms. Here, we report that the thrombocytosis phenotype induced by MPL P106L belongs to the paradoxical group, where low MPL levels on platelets and mature megakaryocytes (MKs) lead to high serum THPO levels, whereas weak but not absent MPL cell-surface localization in earlier MK progenitors allows response to THPO by signaling and amplification of the platelet lineage. MK progenitors from patients showed no spontaneous growth and responded to THPO, and MKs expressed MPL on their cell surface at low levels, whereas their platelets did not respond to THPO. Transduction of MPL P106L in CD34 + cells showed that this receptor was more efficiently localized at the cell surface on immature than on mature MKs, explaining a proliferative response to THPO of immature cells and a defect in THPO clearance in mature cells. In a retroviral mouse model performed in Mpl -/- mice, MPL P106L could induce a thrombocytosis phenotype with high circulating THPO levels. Furthermore, we could select THPO-dependent cell lines with more cell-surface MPL P106L localization that was detected by flow cytometry and [ 125 I]-THPO binding. Altogether, these results demonstrate that MPL P106L is a receptor with an incomplete defect in trafficking, which induces a low but not absent localization of the receptor on cell surface and a response to THPO in immature MK cells. © 2016 by The American Society of Hematology.

  19. Influence of secretagogues on asynchronous secretion of newly synthesized pancreatic proteins in the conscious rat

    International Nuclear Information System (INIS)

    Keim, V.; Rohr, G.

    1987-01-01

    The secretion of newly synthesized pancreatic enzymes was studied in pancreatic duct cannulated rats after intravenous injection of 100 microCi of [ 35 S]methionine. Secretion rate was stimulated by intravenous infusion of either cerulein (0.2 microgram/kg h) or carbachol (10 nmol/kg h) starting simultaneously with or 180 min before the injection of the labeled methionine. Secretory proteins were analyzed by sodium dodecyl sulfate (SDS) gel electrophoresis or by nondenaturing gel electrophoresis followed by determination of the radioactivity associated with the individual proteins. Similar to unstimulated controls in all experiments, an early secretion of newly synthesized trypsinogen and chymotrypsinogen was found, whereas amylase and lipase were secreted only after a certain lag period. The results suggest that the intracellular transit of endoproteases is faster than that of other enzymes, irrespective of whether or not secretagogues were applied

  20. Direct measurement of newly synthesized ATP dissociation kinetics in sarcoplasmic reticulum ATPase

    International Nuclear Information System (INIS)

    Teruel-Puche, J.; Kurzmack, M.; Inesi, G.

    1987-01-01

    Incubation of SR vesicles with Ca 2+ and ( 32 P)acetylphosphate, yields steady state levels of ( 32 P)phosphorylated enzyme (ATPase) intermediate and high concentrations of Ca 2+ in the lumen of the vesicles. At this time, addition of ADP (and EGTA to lower the Ca 2+ concentration in the medium outside the vesicles) results in single cycle formation of (γ- 32 P)ATP by transfer of ( 32 P)phosphate from the enzyme intermediate to ADP. The phosphoenzyme decay and ATP formation exhibit a fast component within the first 20 msec following addition of ADP, and a slower component reaching an asymptote in approximately 100 msec. They have now measured by a rapid filtration method the fraction of newly synthesized ATP which is bound to the enzyme, as opposed to the fraction dissociated into the medium. They find that nearly all the ATP formed during the initial burst is still bound to the enzyme within the initial 20 msec of reaction. Dissociation of newly synthesized ATP occurs then with approximately 13 sec -1 rate constant, permitting reequilibration of the system and further formation of ATP. The rate limiting effect of ATP dissociation and other partial reactions on the slow component of single cycle ATP synthesis is evaluated by appropriate kinetic simulations

  1. Severe Clinical Course in a Patient with Congenital Amegakaryocytic Thrombocytopenia Due to a Missense Mutation of the c-MPL Gene.

    Science.gov (United States)

    Ok Bozkaya, İkbal; Yaralı, Neşe; Işık, Pamir; Ünsal Saç, Rukiye; Tavil, Betül; Tunç, Bahattin

    2015-06-01

    Congenital amegakaryocytic thrombocytopenia (CAMT) generally begins at birth with severe thrombocytopenia and progresses to pancytopenia. It is caused by mutations in the thrombopoietin receptor gene, the myeloproliferative leukemia virus oncogene (c-MPL). The association between CAMT and c-MPL mutation type has been reported in the literature. Patients with CAMT have been categorized according to their clinical symptoms caused by different mutations. Missense mutations of c-MPL have been classified as type II and these patients have delayed onset of bone marrow failure compared to type I patients. Here we present a girl with severe clinical course of CAMT II having a missense mutation in exon 4 of the c-MPL gene who was admitted to our hospital with intracranial hemorrhage during the newborn period.

  2. Inactivated HSV-2 in MPL/alum adjuvant provides nearly complete protection against genital infection and shedding following long term challenge and rechallenge.

    Science.gov (United States)

    Morello, Christopher S; Kraynyak, Kimberly A; Levinson, Michael S; Chen, Zhijiang; Lee, Kuo-Fen; Spector, Deborah H

    2012-10-12

    Herpes Simplex Virus Type 2 (HSV-2) infection can result in life-long recurrent genital disease, asymptomatic virus shedding, and transmission. No vaccine to date has shown significant protection clinically. Here, we used a mouse model of genital HSV-2 infection to test the efficacy of a vaccine consisting of whole, formalin-inactivated HSV-2 (FI-HSV2) formulated with monophosphoryl lipid A (MPL) and alum adjuvants. Vaccine components were administered alone or as a prime-boost immunization together with DNA vaccines encoding a truncated glycoprotein D2 (gD2t) and two conserved HSV-2 genes necessary for virus replication, UL5 (DNA helicase) and UL30 (DNA polymerase). Our results show: (1) compared with mock immunized controls, mice immunized with FI-HSV2 plus MPL/alum consistently showed protection against disease burden and total viral shedding while the mice immunized with gD2t protein with MPL/alum did not; (2) protection against genital disease and viral replication correlated with the type of boost in a prime-boost immunization with little advantage afforded by a DNA prime; (3) intramuscular (i.m.) immunization with FI-HSV2 in MPL/Alhydrogel adjuvant provided nearly complete protection against vaginal HSV-2 shedding after a lethal intravaginal (i.vag.) short-term challenge and long-term rechallenge; (4) single formulation immunization with DNA vaccines, FI-HSV2, and MPL in an aluminum phosphate (Adju-Phos) adjuvant did not increase protection relative to FI-HSV2/MPL/Adju-Phos alone; and (5) addition of MPL/alum to the FI-HSV2 was required for optimal protection against disease, viral replication, and latent virus load in the dorsal root ganglia (DRG). Most notably, an optimized vaccine formulation of FI-HSV2 MPL/Alhydrogel given i.m. completely protected against detectable vaginal HSV-2 shedding in the majority of animals and HSV-2 latent DNA in the DRG of all animals. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Functional characterization of c-Mpl ectodomain mutations that underlie congenital amegakaryocytic thrombocytopenia.

    Science.gov (United States)

    Varghese, Leila N; Zhang, Jian-Guo; Young, Samuel N; Willson, Tracy A; Alexander, Warren S; Nicola, Nicos A; Babon, Jeffrey J; Murphy, James M

    2014-02-01

    Activation of the cell surface receptor, c-Mpl, by the cytokine, thrombopoietin (TPO), underpins megakaryocyte and platelet production in mammals. In humans, mutations in c-Mpl have been identified as the molecular basis of Congenital Amegakaryocytic Thrombocytopenia (CAMT). Here, we show that CAMT-associated mutations in c-Mpl principally lead to defective receptor presentation on the cell surface. In contrast, one CAMT mutant c-Mpl, F104S, was expressed on the cell surface, but showed defective TPO binding and receptor activation. Using mutational analyses, we examined which residues adjacent to F104 within the membrane-distal cytokine receptor homology module (CRM) of c-Mpl comprise the TPO-binding epitope, revealing residues within the predicted Domain 1 E-F and A-B loops and Domain 2 F'-G' loop as key TPO-binding determinants. These studies underscore the importance of the c-Mpl membrane-distal CRM to TPO-binding and suggest that mutations within this CRM that perturb TPO binding could give rise to CAMT.

  4. Developmental Stage-Specific Manifestations of Absent TPO/c-MPL Signalling in Newborn Mice.

    Science.gov (United States)

    Lorenz, Viola; Ramsey, Haley; Liu, Zhi-Jian; Italiano, Joseph; Hoffmeister, Karin; Bihorel, Sihem; Mager, Donald; Hu, Zhongbo; Slayton, William B; Kile, Benjamin T; Sola-Visner, Martha; Ferrer-Marin, Francisca

    2017-12-01

    Congenital amegakaryocytic thrombocytopaenia (CAMT) is a disorder caused by c-MPL mutations that impair thrombopoietin (TPO) signalling, resulting in a near absence of megakaryocytes (MKs). While this phenotype is consistent in adults, neonates with CAMT can present with severe thrombocytopaenia despite normal MK numbers. To investigate this, we characterized MKs and platelets in newborn c-MPL –/– mice. Liver MKs in c-MPL –/– neonates were reduced in number and size compared with wild-type (WT) age-matched MKs, and exhibited ultrastructural abnormalities not found in adult c-MPL –/– MKs. Platelet counts were lower in c-MPL –/– compared with WT mice at birth and did not increase over the first 2 weeks of life. In vivo biotinylation revealed a significant reduction in the platelet half-life of c-MPL –/– newborn mice (P2) compared with age-matched WT pups, which was not associated with ultrastructural abnormalities. Genetic deletion of the pro-apoptotic Bak did not rescue the severely reduced platelet half-life of c-MPL –/– newborn mice, suggesting that it was due to factors other than platelets entering apoptosis early. Indeed, adult GFP+ (green fluorescent protein transgenic) platelets transfused into thrombocytopenic c-MPL –/– P2 pups also had a shortened lifespan, indicating the importance of cell-extrinsic factors. In addition, neonatal platelets from WT and c-MPL –/– mice exhibited reduced P-selectin surface expression following stimulation compared with adult platelets of either genotype, and platelets from c-MPL –/– neonates exhibited reduced glycoprotein IIb/IIIa (GPIIb/IIIa) activation in response to thrombin compared with age-matched WT platelets. Taken together, our findings indicate that c-MPL deficiency is associated with abnormal maturation of neonatal MKs and developmental stage-specific defects in platelet function.

  5. Gene editing rescue of a novel MPL mutant associated with congenital amegakaryocytic thrombocytopenia.

    Science.gov (United States)

    Cleyrat, Cédric; Girard, Romain; Choi, Eun H; Jeziorski, Éric; Lavabre-Bertrand, Thierry; Hermouet, Sylvie; Carillo, Serge; Wilson, Bridget S

    2017-09-26

    Thrombopoietin (Tpo) and its receptor (Mpl) are the principal regulators of early and late thrombopoiesis and hematopoietic stem cell maintenance. Mutations in MPL can drastically impair its function and be a contributing factor in multiple hematologic malignancies, including congenital amegakaryocytic thrombocytopenia (CAMT). CAMT is characterized by severe thrombocytopenia at birth, which progresses to bone marrow failure and pancytopenia. Here we report unique familial cases of CAMT that presented with a previously unreported MPL mutation: T814C (W272R) in the background of the activating MPL G117T (K39N or Baltimore) mutation. Confocal microscopy, proliferation and surface biotinylation assays, co-immunoprecipitation, and western blotting analysis were used to elucidate the function and trafficking of Mpl mutants. Results showed that Mpl protein bearing the W272R mutation, alone or together with the K39N mutation, lacks detectable surface expression while being strongly colocalized with the endoplasmic reticulum (ER) marker calreticulin. Both WT and K39N-mutated Mpl were found to be signaling competent, but single or double mutants bearing W272R were unresponsive to Tpo. Function of the deficient Mpl receptor could be rescued by using 2 separate approaches: (1) GRASP55 overexpression, which partially restored Tpo-induced signaling of mutant Mpl by activating an autophagy-dependent secretory pathway and thus forcing ER-trapped immature receptors to traffic to the cell surface; and (2) CRISPR-Cas9 gene editing used to repair MPL T814C mutation in transfected cell lines and primary umbilical cord blood-derived CD34 + cells. We demonstrate proof of principle for rescue of mutant Mpl function by using gene editing of primary hematopoietic stem cells, which indicates direct therapeutic applications for CAMT patients.

  6. [Identification of a novel aberrant spliceosome of MPL gene (MPLL391-V392ins12)in patients with myeloproliferative neoplasms].

    Science.gov (United States)

    Tian, Ruiyuan; Chen, Xiuhua; Chang, Jianmei; Zhang, Na; Tan, Yanhong; Xu, Zhifang; Ren, Fanggang; Zhao, Junxia; Pan, Jie; Guo, Haixiu; Wang, Xiaojuan; Wang, Hongwei

    2015-07-01

    To identify the MPL L391-V392ins12 spliceosome and analyze its frequencies in patients with myeloproliferative neoplasms (MPN). MPL aberrant spliceosome was identified through reverse transcription polymerase chain reaction (RT-PCR)combined with cloning sequencing. The mutation of this spliceosome in 248 MPN patients and 200 normal people was determined by allele-specific polymerase chain reaction (AS-PCR). A novel aberrant spliceosome of MPL gene (MPL L391-V392ins12)was identified, i.e. 36 bp intron was retained between exon7 and exon8, and there were 12 amino acids (EGLKLLPADIPV)inserted. MPL L391-V392ins12 mutation was detected in 19 (7.66%)of the 248 patients with MPN, including 1 (1.92%) of 52 patients with PV, 14 (9.66%) of 145 with ET, and 4 (7.84%) of 51 with PMF. And the mutation was not detected in the group of 200 normal people. MPL L391-V392ins12 spliceosome is an aberrant spliceosome present in the MPN. It can be detected in PV, ET and PMF, and more frequently in ET and PMF. This mutation may play an important role in the process of MPN.

  7. JAK2 and MPL protein levels determine TPO-induced megakaryocyte proliferation vs differentiation.

    Science.gov (United States)

    Besancenot, Rodolphe; Roos-Weil, Damien; Tonetti, Carole; Abdelouahab, Hadjer; Lacout, Catherine; Pasquier, Florence; Willekens, Christophe; Rameau, Philippe; Lecluse, Yann; Micol, Jean-Baptiste; Constantinescu, Stefan N; Vainchenker, William; Solary, Eric; Giraudier, Stéphane

    2014-09-25

    Megakaryopoiesis is a 2-step differentiation process, regulated by thrombopoietin (TPO), on binding to its cognate receptor myeloproliferative leukemia (MPL). This receptor associates with intracytoplasmic tyrosine kinases, essentially janus kinase 2 (JAK2), which regulates MPL stability and cell-surface expression, and mediates TPO-induced signal transduction. We demonstrate that JAK2 and MPL mediate TPO-induced proliferation arrest and megakaryocytic differentiation of the human megakaryoblastic leukemia cell line UT7-MPL. A decrease in JAK2 or MPL protein expression, and JAK2 chemical inhibition, suppress this antiproliferative action of TPO. The expression of JAK2 and MPL, which progressively increases along normal human megakaryopoiesis, is decreased in platelets of patients diagnosed with JAK2- or MPL-mutated essential thrombocytemia and primary myelofibrosis, 2 myeloproliferative neoplasms in which megakaryocytes (MKs) proliferate excessively. Finally, low doses of JAK2 chemical inhibitors are shown to induce a paradoxical increase in MK production, both in vitro and in vivo. We propose that JAK2 and MPL expression levels regulate megakaryocytic proliferation vs differentiation in both normal and pathological conditions, and that JAK2 chemical inhibitors could promote a paradoxical thrombocytosis when used at suboptimal doses. © 2014 by The American Society of Hematology.

  8. Inhibition of Thrombopoietin/Mpl Signaling in Adult Hematopoiesis Identifies New Candidates for Hematopoietic Stem Cell Maintenance.

    Science.gov (United States)

    Kohlscheen, Saskia; Wintterle, Sabine; Schwarzer, Adrian; Kamp, Christel; Brugman, Martijn H; Breuer, Daniel C; Büsche, Guntram; Baum, Christopher; Modlich, Ute

    2015-01-01

    Thrombopoietin (Thpo) signals via its receptor Mpl and regulates megakaryopoiesis, hematopoietic stem cell (HSC) maintenance and post-transplant expansion. Mpl expression is tightly controlled and deregulation of Thpo/Mpl-signaling is linked to hematological disorders. Here, we constructed an intracellular-truncated, signaling-deficient Mpl protein which is presented on the cell surface (dnMpl). The transplantation of bone marrow cells retrovirally transduced to express dnMpl into wildtype mice induced thrombocytopenia, and a progressive loss of HSC. The aplastic BM allowed the engraftment of a second BM transplant without further conditioning. Functional analysis of the truncated Mpl in vitro and in vivo demonstrated no internalization after Thpo binding and the inhibition of Thpo/Mpl-signaling in wildtype cells due to dominant-negative (dn) effects by receptor competition with wildtype Mpl for Thpo binding. Intracellular inhibition of Mpl could be excluded as the major mechanism by the use of a constitutive-dimerized dnMpl. To further elucidate the molecular changes induced by Thpo/Mpl-inhibition on the HSC-enriched cell population in the BM, we performed gene expression analysis of Lin-Sca1+cKit+ (LSK) cells isolated from mice transplanted with dnMpl transduced BM cells. The gene expression profile supported the exhaustion of HSC due to increased cell cycle progression and identified new and known downstream effectors of Thpo/Mpl-signaling in HSC (namely TIE2, ESAM1 and EPCR detected on the HSC-enriched LSK cell population). We further compared gene expression profiles in LSK cells of dnMpl mice with human CD34+ cells of aplastic anemia patients and identified similar deregulations of important stemness genes in both cell populations. In summary, we established a novel way of Thpo/Mpl inhibition in the adult mouse and performed in depth analysis of the phenotype including gene expression profiling.

  9. C-Mpl Is Expressed on Osteoblasts and Osteoclasts and Is Important in Regulating Skeletal Homeostasis.

    Science.gov (United States)

    Meijome, Tomas E; Baughman, Jenna T; Hooker, R Adam; Cheng, Ying-Hua; Ciovacco, Wendy A; Balamohan, Sanjeev M; Srinivasan, Trishya L; Chitteti, Brahmananda R; Eleniste, Pierre P; Horowitz, Mark C; Srour, Edward F; Bruzzaniti, Angela; Fuchs, Robyn K; Kacena, Melissa A

    2016-04-01

    C-Mpl is the receptor for thrombopoietin (TPO), the main megakaryocyte (MK) growth factor, and c-Mpl is believed to be expressed on cells of the hematopoietic lineage. As MKs have been shown to enhance bone formation, it may be expected that mice in which c-Mpl was globally knocked out (c-Mpl(-/-) mice) would have decreased bone mass because they have fewer MKs. Instead, c-Mpl(-/-) mice have a higher bone mass than WT controls. Using c-Mpl(-/-) mice we investigated the basis for this discrepancy and discovered that c-Mpl is expressed on both osteoblasts (OBs) and osteoclasts (OCs), an unexpected finding that prompted us to examine further how c-Mpl regulates bone. Static and dynamic bone histomorphometry parameters suggest that c-Mpl deficiency results in a net gain in bone volume with increases in OBs and OCs. In vitro, a higher percentage of c-Mpl(-/-) OBs were in active phases of the cell cycle, leading to an increased number of OBs. No difference in OB differentiation was observed in vitro as examined by real-time PCR and functional assays. In co-culture systems, which allow for the interaction between OBs and OC progenitors, c-Mpl(-/-) OBs enhanced osteoclastogenesis. Two of the major signaling pathways by which OBs regulate osteoclastogenesis, MCSF/OPG/RANKL and EphrinB2-EphB2/B4, were unaffected in c-Mpl(-/-) OBs. These data provide new findings for the role of MKs and c-Mpl expression in bone and may provide insight into the homeostatic regulation of bone mass as well as bone loss diseases such as osteoporosis. © 2015 Wiley Periodicals, Inc.

  10. PP32 and SET/TAF-Iβ proteins regulate the acetylation of newly synthesized histone H4.

    Science.gov (United States)

    Saavedra, Francisco; Rivera, Carlos; Rivas, Elizabeth; Merino, Paola; Garrido, Daniel; Hernández, Sergio; Forné, Ignasi; Vassias, Isabelle; Gurard-Levin, Zachary A; Alfaro, Iván E; Imhof, Axel; Almouzni, Geneviève; Loyola, Alejandra

    2017-11-16

    Newly synthesized histones H3 and H4 undergo a cascade of maturation steps to achieve proper folding and to establish post-translational modifications prior to chromatin deposition. Acetylation of H4 on lysines 5 and 12 by the HAT1 acetyltransferase is observed late in the histone maturation cascade. A key question is to understand how to establish and regulate the distinct timing of sequential modifications and their biological significance. Here, we perform proteomic analysis of the newly synthesized histone H4 complex at the earliest time point in the cascade. In addition to known binding partners Hsp90 and Hsp70, we also identify for the first time two subunits of the histone acetyltransferase inhibitor complex (INHAT): PP32 and SET/TAF-Iβ. We show that both proteins function to prevent HAT1-mediated H4 acetylation in vitro. When PP32 and SET/TAF-Iβ protein levels are down-regulated in vivo, we detect hyperacetylation on lysines 5 and 12 and other H4 lysine residues. Notably, aberrantly acetylated H4 is less stable and this reduces the interaction with Hsp90. As a consequence, PP32 and SET/TAF-Iβ depleted cells show an S-phase arrest. Our data demonstrate a novel function of PP32 and SET/TAF-Iβ and provide new insight into the mechanisms regulating acetylation of newly synthesized histone H4. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. Screening for MPL mutations in essential thrombocythemia and primary myelofibrosis: normal Mpl expression and absence of constitutive STAT3 and STAT5 activation in MPLW515L-positive platelets.

    Science.gov (United States)

    Glembotsky, Ana C; Korin, Laura; Lev, Paola R; Chazarreta, Carlos D; Marta, Rosana F; Molinas, Felisa C; Heller, Paula G

    2010-05-01

    To evaluate the frequency of MPL W515L, W515K and S505N mutations in essential thrombocythemia (ET) and primary myelofibrosis (PMF) and to determine whether MPLW515L leads to impaired Mpl expression, constitutive STAT3 and STAT5 activation and enhanced response to thrombopoietin (TPO). Mutation detection was performed by allele-specific PCR and sequencing. Platelet Mpl expression was evaluated by flow cytometry, immunoblotting and real-time RT-PCR. Activation of STAT3 and STAT5 before and after stimulation with increasing concentrations of TPO was studied by immunoblotting. Plasma TPO was measured by ELISA. MPLW515L was detected in 1 of 100 patients with ET and 1 of 11 with PMF. Platelets from the PMF patient showed 100% mutant allele, which was Mpl surface and total protein expression were normal, and TPO levels were mildly increased in the MPLW515L-positive ET patient, while MPL transcripts did not differ from controls in both MPLW515L-positive patients. Constitutive STAT3 and STAT5 phosphorylation was absent and dose response to TPO-induced phosphorylation was not enhanced. The low frequency of MPL mutations in this cohort is in agreement with previous studies. The finding of normal Mpl levels in MPLW515L-positive platelets indicates this mutation does not lead to dysregulated Mpl expression, as frequently shown for myeloproliferative neoplasms. The lack of spontaneous STAT3 and STAT5 activation and the normal response to TPO is unexpected as MPLW515L leads to constitutive receptor activation and hypersensitivity to TPO in experimental models.

  12. Electrochemical Study on Newly Synthesized Chlorocurcumin as an Inhibitor for Mild Steel Corrosion in Hydrochloric Acid

    Directory of Open Access Journals (Sweden)

    Ahmed A. Al-Amiery

    2013-11-01

    Full Text Available A new curcumin derivative, i.e., (1E,4Z,6E-5-chloro-1,7-bis(4-hydroxy-3-methoxyphenylhepta-1,4,6-trien-3-one (chlorocurcumin, was prepared starting with the natural compound curcumin. The newly synthesized compound was characterized by elemental analysis and spectral studies (IR, 1H-NMR and 13C-NMR. The corrosion inhibition of mild steel in 1 M HCl by chlorocurcumin has been studied using potentiodynamic polarization (PDP measurements and electrochemical impedance spectroscopy (EIS. The inhibition efficiency increases with the concentration of the inhibitor but decreases with increases in temperature. The potentiodynamic polarization reveals that chlorocurcumin is a mixed-type inhibitor. The kinetic parameters for mild steel corrosion were determined and discussed.

  13. Electrochemical Study on Newly Synthesized Chlorocurcumin as an Inhibitor for Mild Steel Corrosion in Hydrochloric Acid

    Science.gov (United States)

    Al-Amiery, Ahmed A.; Kadhum, Abdul Amir H.; Mohamad, Abu Bakar; Musa, Ahmed Y.; Li, Cheong Jiun

    2013-01-01

    A new curcumin derivative, i.e., (1E,4Z,6E)-5-chloro-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,4,6-trien-3-one (chlorocurcumin), was prepared starting with the natural compound curcumin. The newly synthesized compound was characterized by elemental analysis and spectral studies (IR, 1H-NMR and 13C-NMR). The corrosion inhibition of mild steel in 1 M HCl by chlorocurcumin has been studied using potentiodynamic polarization (PDP) measurements and electrochemical impedance spectroscopy (EIS). The inhibition efficiency increases with the concentration of the inhibitor but decreases with increases in temperature. The potentiodynamic polarization reveals that chlorocurcumin is a mixed-type inhibitor. The kinetic parameters for mild steel corrosion were determined and discussed. PMID:28788402

  14. Whole-exome sequencing identifies novel MPL and JAK2 mutations in triple-negative myeloproliferative neoplasms.

    Science.gov (United States)

    Milosevic Feenstra, Jelena D; Nivarthi, Harini; Gisslinger, Heinz; Leroy, Emilie; Rumi, Elisa; Chachoua, Ilyas; Bagienski, Klaudia; Kubesova, Blanka; Pietra, Daniela; Gisslinger, Bettina; Milanesi, Chiara; Jäger, Roland; Chen, Doris; Berg, Tiina; Schalling, Martin; Schuster, Michael; Bock, Christoph; Constantinescu, Stefan N; Cazzola, Mario; Kralovics, Robert

    2016-01-21

    Essential thrombocythemia (ET) and primary myelofibrosis (PMF) are chronic diseases characterized by clonal hematopoiesis and hyperproliferation of terminally differentiated myeloid cells. The disease is driven by somatic mutations in exon 9 of CALR or exon 10 of MPL or JAK2-V617F in >90% of the cases, whereas the remaining cases are termed "triple negative." We aimed to identify the disease-causing mutations in the triple-negative cases of ET and PMF by applying whole-exome sequencing (WES) on paired tumor and control samples from 8 patients. We found evidence of clonal hematopoiesis in 5 of 8 studied cases based on clonality analysis and presence of somatic genetic aberrations. WES identified somatic mutations in 3 of 8 cases. We did not detect any novel recurrent somatic mutations. In 3 patients with clonal hematopoiesis analyzed by WES, we identified a somatic MPL-S204P, a germline MPL-V285E mutation, and a germline JAK2-G571S variant. We performed Sanger sequencing of the entire coding region of MPL in 62, and of JAK2 in 49 additional triple-negative cases of ET or PMF. New somatic (T119I, S204F, E230G, Y591D) and 1 germline (R321W) MPL mutation were detected. All of the identified MPL mutations were gain-of-function when analyzed in functional assays. JAK2 variants were identified in 5 of 57 triple-negative cases analyzed by WES and Sanger sequencing combined. We could demonstrate that JAK2-V625F and JAK2-F556V are gain-of-function mutations. Our results suggest that triple-negative cases of ET and PMF do not represent a homogenous disease entity. Cases with polyclonal hematopoiesis might represent hereditary disorders. © 2016 by The American Society of Hematology.

  15. Defining the requirements for the pathogenic interaction between mutant calreticulin and MPL in MPN.

    Science.gov (United States)

    Elf, Shannon; Abdelfattah, Nouran S; Baral, April J; Beeson, Danielle; Rivera, Jeanne F; Ko, Amy; Florescu, Natalie; Birrane, Gabriel; Chen, Edwin; Mullally, Ann

    2018-02-15

    Mutations in calreticulin ( CALR ) are phenotypic drivers in the pathogenesis of myeloproliferative neoplasms. Mechanistic studies have demonstrated that mutant CALR binds to the thrombopoietin receptor MPL, and that the positive electrostatic charge of the mutant CALR C terminus is required for mutant CALR-mediated activation of JAK-STAT signaling. Here we demonstrate that although binding between mutant CALR and MPL is required for mutant CALR to transform hematopoietic cells; binding alone is insufficient for cytokine independent growth. We further show that the threshold of positive charge in the mutant CALR C terminus influences both binding of mutant CALR to MPL and activation of MPL signaling. We find that mutant CALR binds to the extracellular domain of MPL and that 3 tyrosine residues within the intracellular domain of MPL are required to activate signaling. With respect to mutant CALR function, we show that its lectin-dependent function is required for binding to MPL and for cytokine independent growth, whereas its chaperone and polypeptide-binding functionalities are dispensable. Together, our findings provide additional insights into the mechanism of the pathogenic mutant CALR-MPL interaction in myeloproliferative neoplasms. © 2018 by The American Society of Hematology.

  16. Constitutive activation of a variant of the env-mpl oncogene product by disulfide-linked homodimerization.

    OpenAIRE

    Courtois, G; Bénit, L; Mikaeloff, Y; Pauchard, M; Charon, M; Varlet, P; Gisselbrecht, S

    1995-01-01

    The myeloproliferative leukemia retrovirus (MPLV) has the v-mpl cellular sequences transduced in frame with the deleted and rearranged Friend murine leukemia virus env gene. The resulting env-mpl fusion oncogene is responsible for an acute myeloproliferative disorder induced in mice by MPLV. v-mpl is a truncated form of the c-mpl gene which encodes the receptor for thrombopoietin. We investigated the contribution of the Env-Mpl extracellular domain in the constitutive activation of this trunc...

  17. MPL-Net Measurements of Aerosol and Cloud Vertical Distributions at Co-Located AERONET Sites

    Science.gov (United States)

    Welton, Ellsworth J.; Campbell, James R.; Berkoff, Timothy A.; Spinhirne, James D.; Tsay, Si-Chee; Holben, Brent; Starr, David OC. (Technical Monitor)

    2002-01-01

    In the early 1990s, the first small, eye-safe, and autonomous lidar system was developed, the Micropulse Lidar (MPL). The MPL acquires signal profiles of backscattered laser light from aerosols and clouds. The signals are analyzed to yield multiple layer heights, optical depths of each layer, average extinction-to-backscatter ratios for each layer, and profiles of extinction in each layer. In 2000, several MPL sites were organized into a coordinated network, called MPL-Net, by the Cloud and Aerosol Lidar Group at NASA Goddard Space Flight Center (GSFC) using funding provided by the NASA Earth Observing System. tn addition to the funding provided by NASA EOS, the NASA CERES Ground Validation Group supplied four MPL systems to the project, and the NASA TOMS group contributed their MPL for work at GSFC. The Atmospheric Radiation Measurement Program (ARM) also agreed to make their data available to the MPL-Net project for processing. In addition to the initial NASA and ARM operated sites, several other independent research groups have also expressed interest in joining the network using their own instruments. Finally, a limited amount of EOS funding was set aside to participate in various field experiments each year. The NASA Sensor Intercomparison and Merger for Biological and Interdisciplinary Oceanic Studies (SIMBIOS) project also provides funds to deploy their MPL during ocean research cruises. All together, the MPL-Net project has participated in four major field experiments since 2000. Most MPL-Net sites and field experiment locations are also co-located with sunphotometers in the NASA Aerosol Robotic Network. (AERONET). Therefore, at these locations data is collected on both aerosol and cloud vertical structure as well as column optical depth and sky radiance. Real-time data products are now available from most MPL-Net sites. Our real-time products are generated at times of AERONET aerosol optical depth (AOD) measurements. The AERONET AOD is used as input to our

  18. MPL mutation profile in JAK2 mutation-negative patients with myeloproliferative disorders.

    Science.gov (United States)

    Ma, Wanlong; Zhang, Xi; Wang, Xiuqiang; Zhang, Zhong; Yeh, Chen-Hsiung; Uyeji, Jennifer; Albitar, Maher

    2011-03-01

    Mutations in the thrombopoietin receptor gene (myeloproliferative leukemia, MPL) have been reported in patients with JAK2 V617F-negative chronic myeloproliferative disorders (MPDs). We evaluated the prevalence of MPL mutations relative to JAK2 mutations in patients with suspected MPDs. A total of 2790 patient samples submitted for JAK2 mutation analysis were tested using real-time polymerase chain reaction and bidirectional sequencing of plasma RNA. JAK2 V617F-negative samples were tested for JAK2 exons 12 to 14 mutations, and those with negative results were then tested for mutations in MPL exons 10 and 11. Of the 2790 patients, 529 (18.96%) had V617F, 12 (0.43%) had small insertions or deletions in exon 12, and 7 (0.25%) had other JAK2 mutations in exons 12 to 14. Of the 2242 JAK2 mutation-negative patients, 68 (3.03%) had MPL mutations. W515L was the predominant MPL mutation (n=46; 68%), and 10 (15%) patients had other W515 variants. The remaining MPL mutations (n=12, 17%) were detected at other locations in exons 10 and 11 and included 3 insertion/deletion mutations. The S505N mutation, associated with familial MPD, was detected in 3 patients. Overall, for every 100 V617F mutations in patients with suspected MPDs, there were 12.9 MPL mutations, 2.3 JAK2 exon 12 mutations, and 1.3 JAK2 exons 13 to 14 mutations. These findings suggest that MPL mutation screening should be performed before JAK2 exons 12 to 14 testing in JAK2 V617F-negative patients with suspected MPDs.

  19. Growth promotion of genetically modified hematopoietic progenitors using an antibody/c-Mpl chimera.

    Science.gov (United States)

    Kawahara, Masahiro; Chen, Jianhong; Sogo, Takahiro; Teng, Jinying; Otsu, Makoto; Onodera, Masafumi; Nakauchi, Hiromitsu; Ueda, Hiroshi; Nagamune, Teruyuki

    2011-09-01

    Thrombopoietin is a potent cytokine that exerts proliferation of hematopoietic stem cells (HSCs) through its cognate receptor, c-Mpl. Therefore, mimicry of c-Mpl signaling by a receptor recognizing an artificial ligand would be attractive to attain specific expansion of genetically modified HSCs. Here we propose a system enabling selective expansion of genetically modified cells using an antibody/receptor chimera that can be activated by a specific antigen. We constructed an antibody/c-Mpl chimera, in which single-chain Fv (ScFv) of an anti-fluorescein antibody was tethered to the extracellular D2 domain of the erythropoietin receptor and transmembrane/cytoplasmic domains of c-Mpl. When the chimera was expressed in interleukin (IL)-3-dependent pro-B cell line Ba/F3, genetically modified cells were selectively expanded in the presence of fluorescein-conjugated BSA (BSA-FL) as a specific antigen. Furthermore, highly purified mouse HSCs transduced with the retrovirus carrying antibody/c-Mpl chimera gene proliferated in vitro in response to BSA-FL, and the cells retained in vivo long-term repopulating abilities. These results demonstrate that the antibody/c-Mpl chimera is capable of signal transduction that mimics wild-type c-Mpl signaling. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Requirement of TPO/c-mpl for IL-17A-induced granulopoiesis and megakaryopoiesis.

    Science.gov (United States)

    Tan, Weihong; Liu, Bainan; Barsoum, Adel; Huang, Weitao; Kolls, Jay K; Schwarzenberger, Paul

    2013-12-01

    IL-17A is a critical, proinflammatory cytokine essential to host defense and is induced in response to microbial invasion. It stimulates granulopoiesis, leading to neutrophilia, neutrophil activation, and mobilization. TPO synergizes with other cytokines in stimulating and expanding hematopoietic progenitors, also leading to granulopoiesis and megakaryopoiesis, and is required for thrombocytopoiesis. We investigated the effects of in vivo expression of IL-17A on granulopoiesis and megakaryopoiesis in TPO receptor c-mpl-/- mice. IL-17A expression expanded megakaryocytes by 2.5-fold in normal mice but had no such effect in c-mpl-/- mice. The megakaryocyte expansion did not result in increased peripheral platelet counts. IL-17A expression did not impact bone marrow precursors in c-mpl-/- mice; however, it expanded splenic precursors, although to a lesser extent compared with normal controls (CFU-HPP). No peripheral neutrophil expansion was observed in c-mpl-/- mice. Moreover, in c-mpl-/- mice, release of IL-17A downstream cytokines was reduced significantly (KC, MIP-2, GM-CSF). The data suggest that IL-17A requires the presence of functional TPO/c-mpl to exert its effects on granulopoiesis and megakaryopoiesis. Furthermore, IL-17A and its downstream cytokines are important regulators and synergistic factors for the physiologic function of TPO/c-mpl on hematopoiesis.

  1. ATAD2 is an epigenetic reader of newly synthesized histone marks during DNA replication.

    Science.gov (United States)

    Koo, Seong Joo; Fernández-Montalván, Amaury E; Badock, Volker; Ott, Christopher J; Holton, Simon J; von Ahsen, Oliver; Toedling, Joern; Vittori, Sarah; Bradner, James E; Gorjánácz, Mátyás

    2016-10-25

    ATAD2 (ATPase family AAA domain-containing protein 2) is a chromatin regulator harboring an AAA+ ATPase domain and a bromodomain, previously proposed to function as an oncogenic transcription co-factor. Here we suggest that ATAD2 is also required for DNA replication. ATAD2 is co-expressed with genes involved in DNA replication in various cancer types and predominantly expressed in S phase cells where it localized on nascent chromatin (replication sites). Our extensive biochemical and cellular analyses revealed that ATAD2 is recruited to replication sites through a direct interaction with di-acetylated histone H4 at K5 and K12, indicative of newly synthesized histones during replication-coupled chromatin reassembly. Similar to ATAD2-depletion, ectopic expression of ATAD2 mutants that are deficient in binding to these di-acetylation marks resulted in reduced DNA replication and impaired loading of PCNA onto chromatin, suggesting relevance of ATAD2 in DNA replication. Taken together, our data show a novel function of ATAD2 in cancer and for the first time identify a reader of newly synthesized histone di-acetylation-marks during replication.

  2. [Role of anti c-mpl antibody in systemic lupus erythematosus with thrombocytopenia].

    Science.gov (United States)

    Yang, Tuo; Huang, Ci Bo; Lai, Bei; Zhao, Li Ke; Chen, Ying Juan; Zhao, Yue Tao; Zhang, Chun Mei; Zeng, Xiao Feng

    2012-04-18

    To determine whether anti-thrompoietin receptor (TPO-R, c-mpl) antibody contributes to thrombocytopenia in systemic lupus erytematosus (SLE) and explore the pathogenic role of this antibody. Sera from 24 SLE patients with thrombocytopenia, 27 SLE patients having normal platelet counts with a history of thrombocytopenia, 18 SLE patients with neither thrombocytopenia nor post thrombocytopenia and 18 healthy controls were collected. Anti c-mpl antibodies were detected by an indirected ELISA assay. The serum TPO levels were measured by an ELISA assay. Clinical findings, autoantibody profiles, and SLEDAI were evaluated. Serum anti c-mpl antibodies were detected in 18.8% of the SLE patientis. The frequency of this antibody in SLE with thrombocytopenia, SLE with a history of thrombocytopenia and SLE without thrombocytopenia were of no difference (P=0.600). In the patients with anti c-mpl antibodies, their platelet counts were decreased(P=0.025) and serum TPO levels elevated(P=0.038) than those in the patients without, while there were no differences between the two groups in C3, C4, ESR, CRP level, the frequency of ANA, dsDNA, ANCA and SLEDAI. Anti c-mpl antibody contributes to SLE-associated thrombocytopenia by functionally blocking an interaction between thrombopoietin and c-mpl, which might inhibit TPO-dependent megakaryocyte proliferation and differentiation.

  3. Promoter motifs required for c-mpl gene expression induced by thrombopoietin in CMK cells.

    Science.gov (United States)

    Sunohara, Masataka; Sato, Iwao; Morikawa, Shigeru

    2017-11-30

    Thrombopoietin (TPO) and its receptor, c-Mpl, are the central regulators of megakaryocyte development and platelet production and are also crucial to regulate megakaryocytopoiesis. TPO remarkably elevated c-mpl promoter activity, while the protein kinase C (PKC) inhibitors, GF109203, H7 and Calphostin C, clearly reduced the steady level of its promoter activity.  In the present study, motifs crucial for c-mpl promoter activity induced by TPO treatment have been analyzed using a human megakaryoblastic cell line, CMK. Destruction of the -107Sp1 and the -57Sp1 sites in the c-mpl promoter enhancer region resulted in decrease of the promoter activity by 53.1% and 64.4%, respectively, and destruction of -69Ets and -28Ets elements dramatically decreased the promoter activity by 96.4% and 87.8%, respectively, while mutation of -77GATA moderately reduced the activity by 31.4%. The result was in agreement with our previous report that showed the crucial motifs in the c-mpl promoter for the promoter activity induced by PMA-treatment. This indicates that TPO-induced activation of the c-mpl promoter activity is fully modulated by transcription through a PKC-dependent pathway and the two Sp1 and two Ets motifs are crucial for the activation of the c-mpl promoter activity rather than a GATA motif in the c-mpl promoter of CMK cells.

  4. Deep sequencing reveals double mutations in cis of MPL exon 10 in myeloproliferative neoplasms.

    Science.gov (United States)

    Pietra, Daniela; Brisci, Angela; Rumi, Elisa; Boggi, Sabrina; Elena, Chiara; Pietrelli, Alessandro; Bordoni, Roberta; Ferrari, Maurizio; Passamonti, Francesco; De Bellis, Gianluca; Cremonesi, Laura; Cazzola, Mario

    2011-04-01

    Somatic mutations of MPL exon 10, mainly involving a W515 substitution, have been described in JAK2 (V617F)-negative patients with essential thrombocythemia and primary myelofibrosis. We used direct sequencing and high-resolution melt analysis to identify mutations of MPL exon 10 in 570 patients with myeloproliferative neoplasms, and allele specific PCR and deep sequencing to further characterize a subset of mutated patients. Somatic mutations were detected in 33 of 221 patients (15%) with JAK2 (V617F)-negative essential thrombocythemia or primary myelofibrosis. Only one patient with essential thrombocythemia carried both JAK2 (V617F) and MPL (W515L). High-resolution melt analysis identified abnormal patterns in all the MPL mutated cases, while direct sequencing did not detect the mutant MPL in one fifth of them. In 3 cases carrying double MPL mutations, deep sequencing analysis showed identical load and location in cis of the paired lesions, indicating their simultaneous occurrence on the same chromosome.

  5. Adipokines induce catabolism of newly synthesized matrix in cartilage and meniscus tissues.

    Science.gov (United States)

    Nishimuta, James F; Levenston, Marc E

    Altered synovial levels of various adipokines (factors secreted by fat as well as other tissues) have been associated with osteoarthritis (OA) onset and progression. However, the metabolic effects of adipokines on joint tissues, in particular the fibrocartilaginous menisci, are not well understood. This study investigated effects of several adipokines on release of recently synthesized extracellular matrix in bovine cartilage and meniscus tissue explants. After labeling newly synthesized proteins and sulfated glycosaminoglycans (sGAGs) with 3 H-proline and 35 S-sulfate, respectively; bovine cartilage and meniscus tissue explants were cultured for 6 days in basal medium (control) or media supplemented with adipokines (1 µg/ml of leptin, visfatin, adiponectin, or resistin) or 20 ng/ml interleukin-1 (IL-1). Release of radiolabel and sGAG to the media during culture and the final explant water, DNA, sGAG, and retained radiolabel were measured. Matrix metalloproteinase (MMP-2) and MMP-3 activities were assessed using gelatin and casein zymography, respectively. Water and DNA contents were not significantly altered by any treatment. Visfatin, adiponectin, resistin, and IL-1 stimulated sGAG release from meniscus, whereas only IL-1 stimulated sGAG release from cartilage. Release of 3 H and 35 S was stimulated not only by resistin and IL-1 in meniscus but also by IL-1 in cartilage. Retained 3 H was unaltered by any treatment, while retained 35 S was reduced by visfatin, resistin, and IL-1 in meniscus and by only IL-1 in cartilage. Resistin and IL-1 elevated active MMP-2 and total MMP-3 in meniscus, whereas cartilage MMP-3 activity was elevated by only IL-1. Resistin stimulated rapid and extensive catabolism of meniscus tissue, similar to IL-1, whereas adipokines minimally affected cartilage. Release of newly synthesized matrix was similar to overall release in both tissues. These observations provide further indications that meniscal tissue is more sensitive to pro

  6. Detection of MPL mutations by a novel allele-specific PCR-based strategy.

    Science.gov (United States)

    Furtado, Larissa V; Weigelin, Helmut C; Elenitoba-Johnson, Kojo S J; Betz, Bryan L

    2013-11-01

    MPL mutation testing is recommended in patients with suspected primary myelofibrosis or essential thrombocythemia who lack the JAK2 V617F mutation. MPL mutations can occur at allelic levels below 15%, which may escape detection by commonly used mutation screening methods such as Sanger sequencing. We developed a novel multiplexed allele-specific PCR assay capable of detecting most recurrent MPL exon 10 mutations associated with primary myelofibrosis and essential thrombocythemia (W515L, W515K, W515A, and S505N) down to a sensitivity of 2.5% mutant allele. Test results were reviewed from 15 reference cases and 1380 consecutive specimens referred to our laboratory for testing. Assay performance was compared to Sanger sequencing across a series of 58 specimens with MPL mutations. Positive cases consisted of 45 with W515L, 6 with S505N, 5 with W515K, 1 with W515A, and 1 with both W515L and S505N. Seven cases had mutations below 5% that were undetected by Sanger sequencing. Ten additional cases had mutation levels between 5% and 15% that were not consistently detected by sequencing. All results were easily interpreted in the allele-specific test. This assay offers a sensitive and reliable solution for MPL mutation testing. Sanger sequencing appears insufficiently sensitive for robust MPL mutation detection. Our data also suggest the relative frequency of S505N mutations may be underestimated, highlighting the necessity for inclusion of this mutation in MPL test platforms. Copyright © 2013 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  7. c-MPL provides tumor-targeted T-cell receptor-transgenic T cells with costimulation and cytokine signals.

    Science.gov (United States)

    Nishimura, Christopher D; Brenner, Daniel A; Mukherjee, Malini; Hirsch, Rachel A; Ott, Leah; Wu, Meng-Fen; Liu, Hao; Dakhova, Olga; Orange, Jordan S; Brenner, Malcolm K; Lin, Charles Y; Arber, Caroline

    2017-12-21

    Adoptively transferred T-cell receptor (TCR)-engineered T cells depend on host-derived costimulation and cytokine signals for their full and sustained activation. However, in patients with cancer, both signals are frequently impaired. Hence, we developed a novel strategy that combines both essential signals in 1 transgene by expressing the nonlymphoid hematopoietic growth factor receptor c-MPL (myeloproliferative leukemia), the receptor for thrombopoietin (TPO), in T cells. c-MPL signaling activates pathways shared with conventional costimulatory and cytokine receptor signaling. Thus, we hypothesized that host-derived TPO, present in the tumor microenvironment, or pharmacological c-MPL agonists approved by the US Food and Drug Administration could deliver both signals to c-MPL-engineered TCR-transgenic T cells. We found that c-MPL + polyclonal T cells expand and proliferate in response to TPO, and persist longer after adoptive transfer in immunodeficient human TPO-transgenic mice. In TCR-transgenic T cells, c-MPL activation enhances antitumor function, T-cell expansion, and cytokine production and preserves a central memory phenotype. c-MPL signaling also enables sequential tumor cell killing, enhances the formation of effective immune synapses, and improves antileukemic activity in vivo in a leukemia xenograft model. We identify the type 1 interferon pathway as a molecular mechanism by which c-MPL mediates immune stimulation in T cells. In conclusion, we present a novel immunotherapeutic strategy using c-MPL-enhanced transgenic T cells responding to either endogenously produced TPO (a microenvironment factor in hematologic malignancies) or c-MPL-targeted pharmacological agents. © 2017 by The American Society of Hematology.

  8. Tyrosine 625 plays a key role and cooperates with tyrosine 630 in MPL W515L-induced signaling and myeloproliferative neoplasms.

    Science.gov (United States)

    Yu, Chunjie; Yang, Qiong; Chen, Yuhong; Wang, Demin; Levine, Ross; Crispino, John; Wen, Qiang; Huang, Zan

    2016-01-01

    Myeloproliferative neoplasms (MPN) are a group of blood cancers that boost normal blood cell production in the bone marrow. Abnormal mutations in stem cells were found accompanying with the occurrence of MPN. It has been shown that MPL mutations (MPL W515L or MPL W515K) were involved in patients with MPN. Since tyrosine residues 625 and 630 mediate normal MPL signaling, whether them affect MPL W515L-induced myeloproliferative neoplasms (MPNs) is unknown. In this study, we further tested their functions in MPL W515L-induced myeloproliferative neoplasms (MPNs) by substituting either or both of them with phenylalanine in MPL W515L (termed as MPL515/625, MPL515/630 and MPL515/625/630, respectively). In vitro, MPL515/630 but not MPL515/625 or MPL515/625/630 retained the ability to induce TPO-independent proliferation and increase colony-forming unit megakaryocytes (CFU-Mk). Accordingly, differential activation of the downstream signaling by four mutants was observed and constitutively active STAT5 or AKT instead of STAT3 partially compensated MPL515/625/630 function. Further support this, STAT5-deficiency impaired MPL W515L-induced CFU-Mk expansion. In vivo, MPL515/630 but not MPL515/625 or MPL515/625/630 induced typical features of MPNs with high WBC and platelet counts, splenomegaly, hepatomegaly and hypercellularity in the bone marrow. Surprisingly, MPL515/625 also caused hypercellularity of bone marrow and splenomegaly without any other significant features. We also observed differential effects of the four mutants on progenitors, myeloid cells and megakaryocytes. Our studies have revealed distinct features of tyrosine sites 625 and 630 in mediating MPL W515L-induced megakaryocyte hyperproliferation and MPNs. Our study also suggests that MPL cytosolic phosphorylated Y625 and flanking amino acids could become targets for pharmacologic inhibition in MPNs.

  9. JAK2, MPL, and CALR mutations in Chinese Han patients with essential thrombocythemia.

    Science.gov (United States)

    Wang, Jing; Zhang, Biao; Chen, Bing; Zhou, Rong-Fu; Zhang, Qi-Guo; Li, Juan; Yang, Yong-Gong; Zhou, Min; Shao, Xiao-Yan; Xu, Yong; Xu, Xi-Hui; Ouyang, Jian; Xu, Jingyan; Ye, Qing

    2017-04-01

    Mutations in Janus kinase 2 (JAK2), myeloproliferative leukemia (MPL), and CALR are highly relevant to Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms. Assessing the prevalence of molecular mutations in Chinese Han patients with essential thrombocythemia (ET), and correlating their mutational profile with disease characteristics/phenotype. Of the 110 subjects studied, 62 carried the JAK2 V617F mutation, 21 had CALR mutations, one carried an MPL (W515) mutation, and 28 had non-mutated JAK2, CALR, and MPL (so-called triple-negative ET). Mutations in JAK2 exon 12 were not detected in any patient. Two ET patients had both CALR and JAK2 V617F mutations. Comparing the hematological parameters of the patients with JAK2 mutations with those of the patients with CALR mutations showed that the ET patients with CALR mutations were younger (p = 0.045) and had higher platelet counts (p = 0.043). Genotyping for CALR could be a useful diagnostic tool for JAK2/MPL-negative ET, since the data suggest that CALR is much more prevalent than MPL, therefore testing for CALR should be considered in patients who are JAK2 negative as its frequency is almost 20 times that of MPL mutation.

  10. The thrombopoietin receptor, MPL, is critical for development of a JAK2V617F-induced myeloproliferative neoplasm.

    Science.gov (United States)

    Sangkhae, Veena; Etheridge, S Leah; Kaushansky, Kenneth; Hitchcock, Ian S

    2014-12-18

    The most frequent contributing factor in Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) is the acquisition of a V617F mutation in Janus kinase 2 (JAK2) in hematopoietic stem cells (HSCs). Recent evidence has demonstrated that to drive MPN transformation, JAK2V617F needs to directly associate with a functional homodimeric type I cytokine receptor, suggesting that, although acquiring JAK2V617F may promote disease, there are additional cellular components necessary for MPN development. Here we show that loss of the thrombopoietin (TPO) receptor (MPL) significantly ameliorates MPN development in JAK2V617F(+) transgenic mice, whereas loss of TPO only mildly affects the disease phenotype. Specifically, compared with JAK2V617F(+) mice, JAK2V617F(+)Mpl(-/-) mice exhibited reduced thrombocythemia, neutrophilia, splenomegaly, and neoplastic stem cell pool. The importance of MPL is highlighted as JAK2V617FMpl(+/-) mice displayed a significantly reduced MPN phenotype, indicating that Mpl level may have a substantial effect on MPN development and severity. Splenomegaly and the increased neoplastic stem cell pool were retained in JAK2V617F(+)Tpo(-/-) mice, although thrombocytosis was reduced compared with JAK2V617F(+) mice. These results demonstrate that Mpl expression, but not Tpo, is fundamental in the development of JAK2V617F(+) MPNs, highlighting an entirely novel target for therapeutic intervention. © 2014 by The American Society of Hematology.

  11. Novel pathways to erythropoiesis induced by dimerization of intracellular C-Mpl in human hematopoietic progenitors.

    Science.gov (United States)

    Parekh, Chintan; Sahaghian, Arineh; Kim, William; Scholes, Jessica; Ge, Shundi; Zhu, Yuhua; Asgharzadeh, Shahab; Hollis, Roger; Kohn, Donald; Ji, Lingyun; Malvar, Jemily; Wang, Xiaoyan; Crooks, Gay

    2012-04-01

    The cytokine thrombopoietin (Tpo) plays a critical role in hematopoiesis by binding to the extracellular domain and inducing homodimerization of the intracellular signaling domain of its receptor, c-Mpl. Mpl homodimerization can also be accomplished by binding of a synthetic ligand to a constitutively expressed fusion protein F36VMpl consisting of a ligand binding domain (F36V) and the intracellular signaling domain of Mpl. Unexpectedly, in contrast to Tpo stimulation, robust erythropoiesis is induced after dimerization of F36VMpl in human CD34+ progenitor cells. The goal of this study was to define the hematopoietic progenitor stages at which dimerization of intracellular Mpl induces erythropoiesis and the downstream molecular events that mediate this unanticipated effect. Dimerization (in the absence of erythropoietin and other cytokines) in human common myeloid progenitors and megakaryocytic erythroid progenitors caused a significant increase in CD34+ cells (p Mpl in human myeloerythroid progenitors induces progenitor expansion and erythropoiesis through molecular mechanisms that are not shared by Tpo stimulation of endogenous Mpl. Copyright © 2012 AlphaMed Press.

  12. The Metalloprotease Mpl Supports Listeria monocytogenes Dissemination through Resolution of Membrane Protrusions into Vacuoles.

    Science.gov (United States)

    Alvarez, Diego E; Agaisse, Hervé

    2016-06-01

    Listeria monocytogenes is an intracellular pathogen that disseminates within the intestinal epithelium through acquisition of actin-based motility and formation of plasma membrane protrusions that project into adjacent cells. The resolution of membrane protrusions into vacuoles from which the pathogen escapes results in bacterial spread from cell to cell. This dissemination process relies on the mlp-actA-plcB operon, which encodes ActA, a bacterial nucleation-promoting factor that mediates actin-based motility, and PlcB, a phospholipase that mediates vacuole escape. Here we investigated the role of the metalloprotease Mpl in the dissemination process. In agreement with previous findings showing that Mpl is required for PlcB activation, infection of epithelial cells with the ΔplcB or Δmpl strains resulted in the formation of small infection foci. As expected, the ΔplcB strain displayed a strong defect in vacuole escape. However, the Δmpl strain showed an unexpected defect in the resolution of protrusions into vacuoles, in addition to the expected but mild defect in vacuole escape. The Δmpl strain displayed increased levels of ActA on the bacterial surface in protrusions. We mapped an Mpl-dependent processing site in ActA between amino acid residues 207 to 238. Similar to the Δmpl strain, the ΔactA207-238 strain displayed increased levels of ActA on the bacterial surface in protrusions. Although the ΔactA207-238 strain displayed wild-type actin-based motility, it formed small infection foci and failed to resolve protrusions into vacuoles. We propose that, in addition to its role in PlcB processing and vacuole escape, the metalloprotease Mpl is required for ActA processing and protrusion resolution. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  13. Calreticulin and Jak2 as Chaperones for MPL: Insights into MPN Pathogenesis

    Science.gov (United States)

    2016-09-01

    stimulated calcium mobilization will be evaluated in megakaryocyte cell lines expressing WT and mutant calreticulin using ratio imaging methods. Using both...Mpl, fitting well with Aim 2 of this project. Highlights from the new manuscript showed this novel mutation results in entrapment of the mutant Mpl

  14. Clinical utility of routine MPL exon 10 analysis in the diagnosis of essential thrombocythaemia and primary myelofibrosis.

    Science.gov (United States)

    Boyd, Elaine M; Bench, Anthony J; Goday-Fernández, Andrea; Anand, Shubha; Vaghela, Krishna J; Beer, Phillip; Scott, Mike A; Bareford, David; Green, Anthony R; Huntly, Brian; Erber, Wendy N

    2010-04-01

    Approximately 50% of essential thrombocythaemia and primary myelo-fibrosis patients do not have a JAK2 V617F mutation. Up to 5% of these are reported to have a MPL exon 10 mutation but testing for MPL is not routine as there are multiple mutation types. The ability to routinely assess both JAK2 and MPL mutations would be beneficial in the differential diagnosis of unexplained thrombocytosis or myelofibrosis. We developed and applied a high resolution melt (HRM) assay, capable of detecting all known MPL mutations in a single analysis, for the detection of MPL exon 10 mutations. We assessed 175 ET and PMF patients, including 67 that were JAK2 V617F-negative by real time polymerase chain reaction (PCR). Overall, 19/175 (11%) patients had a MPL exon 10 mutation, of whom 16 were JAK2 V617F-negative (16/67; 24%). MPL mutation types were W515L (11), W515K (4), W515R (2) and W515A (1). One patient had both W515L and S505N MPL mutations and these were present in the same haemopoietic colonies. Real time PCR for JAK2 V617F analysis and HRM for MPL exon 10 status identified one or more clonal marker in 71% of patients. This combined genetic approach increases the sensitivity of meeting the World Health Organization diagnostic criteria for these myeloproliferative neoplasms.

  15. Calreticulin mutants in mice induce an MPL-dependent thrombocytosis with frequent progression to myelofibrosis.

    Science.gov (United States)

    Marty, Caroline; Pecquet, Christian; Nivarthi, Harini; El-Khoury, Mira; Chachoua, Ilyas; Tulliez, Micheline; Villeval, Jean-Luc; Raslova, Hana; Kralovics, Robert; Constantinescu, Stefan N; Plo, Isabelle; Vainchenker, William

    2016-03-10

    Frameshift mutations in the calreticulin (CALR) gene are seen in about 30% of essential thrombocythemia and myelofibrosis patients. To address the contribution of the CALR mutants to the pathogenesis of myeloproliferative neoplasms, we engrafted lethally irradiated recipient mice with bone marrow cells transduced with retroviruses expressing these mutants. In contrast to wild-type CALR, CALRdel52 (type I) and, to a lesser extent, CALRins5 (type II) induced thrombocytosis due to a megakaryocyte (MK) hyperplasia. Disease was transplantable into secondary recipients. After 6 months, CALRdel52-, in contrast to rare CALRins5-, transduced mice developed a myelofibrosis associated with a splenomegaly and a marked osteosclerosis. Monitoring of virus-transduced populations indicated that CALRdel52 leads to expansion at earlier stages of hematopoiesis than CALRins5. However, both mutants still specifically amplified the MK lineage and platelet production. Moreover, a mutant deleted of the entire exon 9 (CALRdelex9) did not induce a disease, suggesting that the oncogenic property of CALR mutants was related to the new C-terminus peptide. To understand how the CALR mutants target the MK lineage, we used a cell-line model and demonstrated that the CALR mutants, but not CALRdelex9, specifically activate the thrombopoietin (TPO) receptor (MPL) to induce constitutive activation of Janus kinase 2 and signal transducer and activator of transcription 5/3/1. We confirmed in c-mpl- and tpo-deficient mice that expression of Mpl, but not of Tpo, was essential for the CALR mutants to induce thrombocytosis in vivo, although Tpo contributes to disease penetrance. Thus, CALR mutants are sufficient to induce thrombocytosis through MPL activation. © 2016 by The American Society of Hematology.

  16. MPL expression on AML blasts predicts peripheral blood neutropenia and thrombocytopenia.

    Science.gov (United States)

    Rauch, Philipp J; Ellegast, Jana M; Widmer, Corinne C; Fritsch, Kristin; Goede, Jeroen S; Valk, Peter J M; Löwenberg, Bob; Takizawa, Hitoshi; Manz, Markus G

    2016-11-03

    Although the molecular pathways that cause acute myeloid leukemia (AML) are increasingly well understood, the pathogenesis of peripheral blood cytopenia, a major cause of AML mortality, remains obscure. A prevailing assumption states that AML spatially displaces nonleukemic hematopoiesis from the bone marrow. However, examining an initial cohort of 223 AML patients, we found no correlation between bone marrow blast content and cytopenia, questioning the displacement theory. Measuring serum concentration of thrombopoietin (TPO), a key regulator of hematopoietic stem cells and megakaryocytes, revealed loss of physiologic negative correlation with platelet count in AML cases with blasts expressing MPL, the thrombopoietin (scavenging) receptor. Mechanistic studies demonstrated that MPL hi blasts could indeed clear TPO, likely therefore leading to insufficient cytokine levels for nonleukemic hematopoiesis. Microarray analysis in an independent multicenter study cohort of 437 AML cases validated MPL expression as a central predictor of thrombocytopenia and neutropenia in AML. Moreover, t(8;21) AML cases demonstrated the highest average MPL expression and lowest average platelet and absolute neutrophil counts among subgroups. Our work thus explains the pathophysiology of peripheral blood cytopenia in a relevant number of AML cases. © 2016 by The American Society of Hematology.

  17. MPL W515L expression induces TGFβ secretion and leads to an increase in chemokinesis via phosphorylation of THOC5.

    Science.gov (United States)

    Whetton, Anthony D; Azmi, Norhaida Che; Pearson, Stella; Jaworska, Ewa; Zhang, Liqun; Blance, Rognvald; Kendall, Alexandra C; Nicolaou, Anna; Taylor, Samuel; Williamson, Andrew J K; Pierce, Andrew

    2016-03-08

    The thrombopoietin receptor (MPL) has been shown to be mutated (MPL W515L) in myelofibrosis and thrombocytosis yet new approaches to treat this disorder are still required. We have previously shown that transcriptome and proteomic effects do not correlate well in oncogene-mediated leukemogenesis. We therefore investigated the effects of MPL W515L using proteomics. The consequences of MPL W515L expression on over 3300 nuclear and 3500 cytoplasmic proteins were assessed using relative quantification mass spectrometry. We demonstrate that MPL W515L expression markedly modulates the CXCL12/CXCR4/CD45 pathway associated with stem and progenitor cell chemotactic movement. We also demonstrated that MPL W515L expressing cells displayed increased chemokinesis which required the MPL W515L-mediated dysregulation of MYC expression via phosphorylation of the RNA transport protein THOC5 on tyrosine 225. In addition MPL W515L expression induced TGFβ secretion which is linked to sphingosine 1-phosphate production and the increased chemokinesis. These studies identify several pathways which offer potential targets for therapeutic intervention in the treatment of MPL W515L-driven malignancy. We validate our approach by showing that CD34+ cells from MPL W515L positive patients display increased chemokinesis and that treatment with a combination of MYC and sphingosine kinase inhibitors leads to the preferential killing of MPL W515L expressing cells.

  18. Size and frequency of gaps in newly synthesized DNA of xeroderma pigmentosum human cells irradiated with ultraviolet light

    International Nuclear Information System (INIS)

    Meneghini, R.; Cordeiro-Stone, M.; Schumacher, R.I.

    1981-01-01

    Native newly synthesized DNA from human cells (xeroderma pigmentosum type) irradiated with ultraviolet light releases short pieces of DNA (L-DNA) when incubated with the single-strand specific S 1 nuclease. This is not observed in the case of unirradiated cells. Previous experiments had shown that the L-DNA resulted from the action of S 1 nuclease upon gaps, i.e., single-stranded DNA discontinuities in larger pieces of double-stranded DNA. We verified that the duplex L-DNA, that arises from the inter-gap regions upon S 1 nuclease treatment, has a size which approximates the distance between two pyrimidine dimers on the same strand. A method was devised to measure the size of the gaps. These parameters have been considered in the proposition of a model for DNA synthesis on a template containing pyrimidine dimers

  19. Fungal lectin MpL enables entry of protein drugs into cancer cells and their subcellular targeting.

    Science.gov (United States)

    Å Urga, Simon; Nanut, Milica Perišić; Kos, Janko; Sabotič, Jerica

    2017-04-18

    Lectins have been recognized as promising carrier molecules for targeted drug delivery. They specifically bind carbohydrate moieties on cell membranes and trigger cell internalization. Fungal lectin MpL (Macrolepiota procera lectin) does not provoke cancer cell cytotoxicity but is able to bind aminopeptidase N (CD13) and integrin α3β1, two glycoproteins that are overexpressed on the membrane of tumor cells. Upon binding, MpL is endocytosed in a clathrin-dependent manner and accumulates initially in the Golgi apparatus and, finally, in the lysosomes. For effective binding and internalization a functional binding site on the α-repeat is needed. To test the potential of MpL as a carrier for delivering protein drugs to cancer cells we constructed fusion proteins consisting of MpL and the cysteine peptidase inhibitors cystatin C and clitocypin. The fused proteins followed the same endocytic route as the unlinked MpL. Peptidase inhibitor-MpL fusions impaired both the intracellular degradation of extracellular matrix and the invasiveness of cancer cells. MpL is thus shown in vitro to be a lectin that can enable protein drugs to enter cancer cells, enhance their internalization and sort them to lysosomes and the Golgi apparatus.

  20. Primary myelofibrosis with or without mutant MPL: comparison of survival and clinical features involving 603 patients.

    Science.gov (United States)

    Pardanani, A; Guglielmelli, P; Lasho, T L; Pancrazzi, A; Finke, C M; Vannucchi, A M; Tefferi, A

    2011-12-01

    MPL and JAK2V617F mutation analysis was performed in 603 patients with primary myelofibrosis (PMF) seen at the Mayo Clinic, USA (n=329) or University of Florence, Italy (n=274). Mutant MPL was detected in 49 (8.1%) patients and JAK2V617F in 350 (58%); 4 patients showed both mutations. MPLW515L/K was the commonest mutation; 2 patients showed novel mutations (L513ins and Q516-P518insAAAA). The US and Italy patient cohorts were separately analyzed for comparison of survival and clinical features between MPL-mutated, JAK2-mutated and JAK2/MPL-unmutated cases. JAK2/MPL-unmutated patients were significantly younger than their JAK2-mutated counterparts, in both patient cohorts (PMPL was associated with older age (PMPL has narrow and inconsistent phenotypic effect in PMF and does not influence overall or leukemia-free survival.

  1. Genetic Alterations of the Thrombopoietin/MPL/JAK2 Axis Impacting Megakaryopoiesis

    OpenAIRE

    Plo, Isabelle; Bellanné-Chantelot, Christine; Mosca, Matthieu; Mazzi, Stefania; Marty, Caroline; Vainchenker, William

    2017-01-01

    Megakaryopoiesis is an original and complex cell process which leads to the formation of platelets. The homeostatic production of platelets is mainly regulated and controlled by thrombopoietin (TPO) and the TPO receptor (MPL)/JAK2 axis. Therefore, any hereditary or acquired abnormality affecting this signaling axis can result in thrombocytosis or thrombocytopenia. Thrombocytosis can be due to genetic alterations that affect either the intrinsic MPL signaling through gain-of-function (GOF) act...

  2. Live-cell visualization of intracellular interaction between a nuclear migration protein (hNUDC) and the thrombopoietin receptor (Mpl).

    Science.gov (United States)

    Zheng, Yuan-Bin; Xiao, Ying-Ying; Tan, Peng; Zhang, Qing; Xu, Peilin

    2012-01-01

    We previously demonstrated that endogenous hNUDC and Mpl co-localized in the perinuclear and cytoplasmic regions of megakaryocyte cells by indirect immunofluorescence. We further reported that hNUDC accumulated in the Golgi when NIH 3T3 cells were transfected with an hNUDC expression vector alone. However, co-transfection with hNUDC and Mpl expression vectors caused both proteins to co-localize predominantly in the cytosol. These observations led us to hypothesize that a complex containing hNUDC and Mpl may alter hNUDC subcellular location and induce its secretion. In the present study, we test this hypothesis by employing bimolecular fluorescence complementation (BiFC) to detect and visualize the complex formation of hNUDC/Mpl in living cells. We further examined in detail the subcellular locations of the hNUDC/Mpl complex by co-transfection of BiFC chimeras with known subcellular markers. The distribution of hNUDC/Mpl in the endoplasmic reticulum (ER), Golgi and cell surface was determined. Furthermore, the N-terminal 159 amino acids of hNUDC, but not C-terminal half, bound to Mpl in vivo and exhibited a similar localization pattern to that of full-length hNUDC in Cos-1 cells. Adenovirus-mediated overexpression of hNUDC or its N-terminal 159 residues in a human megakaryocyte cell line (Dami) resulted in increased levels of hNUDC or hNUDC(1-159) secretion. In contrast, depletion of Mpl by transfecting Dami cells with adenovirus bearing Mpl-targeting siRNA significantly blocked hNUDC secretion. Thus, we provide the first evidence that the N-terminal region of hNUDC contains all of the necessary information to complex with Mpl and traffic through the secretory pathway.

  3. Live-cell visualization of intracellular interaction between a nuclear migration protein (hNUDC and the thrombopoietin receptor (Mpl.

    Directory of Open Access Journals (Sweden)

    Yuan-Bin Zheng

    Full Text Available We previously demonstrated that endogenous hNUDC and Mpl co-localized in the perinuclear and cytoplasmic regions of megakaryocyte cells by indirect immunofluorescence. We further reported that hNUDC accumulated in the Golgi when NIH 3T3 cells were transfected with an hNUDC expression vector alone. However, co-transfection with hNUDC and Mpl expression vectors caused both proteins to co-localize predominantly in the cytosol. These observations led us to hypothesize that a complex containing hNUDC and Mpl may alter hNUDC subcellular location and induce its secretion. In the present study, we test this hypothesis by employing bimolecular fluorescence complementation (BiFC to detect and visualize the complex formation of hNUDC/Mpl in living cells. We further examined in detail the subcellular locations of the hNUDC/Mpl complex by co-transfection of BiFC chimeras with known subcellular markers. The distribution of hNUDC/Mpl in the endoplasmic reticulum (ER, Golgi and cell surface was determined. Furthermore, the N-terminal 159 amino acids of hNUDC, but not C-terminal half, bound to Mpl in vivo and exhibited a similar localization pattern to that of full-length hNUDC in Cos-1 cells. Adenovirus-mediated overexpression of hNUDC or its N-terminal 159 residues in a human megakaryocyte cell line (Dami resulted in increased levels of hNUDC or hNUDC(1-159 secretion. In contrast, depletion of Mpl by transfecting Dami cells with adenovirus bearing Mpl-targeting siRNA significantly blocked hNUDC secretion. Thus, we provide the first evidence that the N-terminal region of hNUDC contains all of the necessary information to complex with Mpl and traffic through the secretory pathway.

  4. Mpl expression on megakaryocytes and platelets is dispensable for thrombopoiesis but essential to prevent myeloproliferation.

    Science.gov (United States)

    Ng, Ashley P; Kauppi, Maria; Metcalf, Donald; Hyland, Craig D; Josefsson, Emma C; Lebois, Marion; Zhang, Jian-Guo; Baldwin, Tracey M; Di Rago, Ladina; Hilton, Douglas J; Alexander, Warren S

    2014-04-22

    Thrombopoietin (TPO) acting via its receptor, the cellular homologue of the myeloproliferative leukemia virus oncogene (Mpl), is the major cytokine regulator of platelet number. To precisely define the role of specific hematopoietic cells in TPO-dependent hematopoiesis, we generated mice that express the Mpl receptor normally on stem/progenitor cells but lack expression on megakaryocytes and platelets (Mpl(PF4cre/PF4cre)). Mpl(PF4cre/PF4cre) mice displayed profound megakaryocytosis and thrombocytosis with a remarkable expansion of megakaryocyte-committed and multipotential progenitor cells, the latter displaying biological responses and a gene expression signature indicative of chronic TPO overstimulation as the underlying causative mechanism, despite a normal circulating TPO level. Thus, TPO signaling in megakaryocytes is dispensable for platelet production; its key role in control of platelet number is via generation and stimulation of the bipotential megakaryocyte precursors. Nevertheless, Mpl expression on megakaryocytes and platelets is essential to prevent megakaryocytosis and myeloproliferation by restricting the amount of TPO available to stimulate the production of megakaryocytes from the progenitor cell pool.

  5. Spectral, stoichiometric ratio, physicochemical, polarity and photostability studies of newly synthesized chalcone dye in organized media

    International Nuclear Information System (INIS)

    Marwani, Hadi M.; Asiri, Abdullah M.; Khan, Salman A.

    2013-01-01

    The main focus of this study was to investigate spectroscopic properties, stoichiometric ratios, physicochemical parameters, polarity and photostability behaviors of newly synthesized chalcone dye in organized media. The chalcone dye, 1-(2,5-Dimethyl-thiophen-3-yl)-3-(9-etnyl-9H-carbazol-3-yl)-propenone (DTEP), was prepared by the reaction of carbazole aldehyde with 3-acetyl-2,5-dimethythiophene. Data obtained from FT-IR, 1 H-–NMR, 13 C-NMR and elemental analysis were consistent with chemical structure of newly prepared DTEP. Increases in fluorescence intensities of DTEP with cetyltrimethyl ammonium bromide (CTAB) were observed. In comparison of fluorescence intensities for DTEP with CTAB, reductions in fluorescence intensities for DTEP with sodium dodecyl sulfate (SDS) were noticed under the same experimental and instrumental conditions. Additionally, Benesi–Hildebrand method was applied to determine stoichiometric ratios and association constants of DTEP with CTAB and SDS. Stern–Volmer plot was used in order to further confirm the stoichiometric ratio and association constant of DTEP with SDS. Physicochemical parameters such as singlet absorption, molar absorptivity, oscillator strength, dipole moment and fluorescence quantum yield of DTEP were also determined. Fluorescence polarity study displayed that DTEP was sensitive to the polarity of the microenvironment provided by different solvents. Finally, fluorescence steady-state measurements revealed that DTEP has high photostability against photobleaching. -- Highlights: ► Mechanistic understanding of molecular structure of newly synthesized chalcone dye. ► Exploring spectral behaviors and physicochemical parameters of chalcone dye. ► Determination of stoichiometric ratios and association constants of chalcone dye. ► Determination of fluorescence quantum yield in different solvents. ► High photostability against photobleaching of chalcone dye was observed

  6. JAK2 and MPL gene mutations in V617F-negative myeloproliferative neoplasms.

    NARCIS (Netherlands)

    Siemiatkowska, A.M.; Bieniaszewska, M.; Hellmann, A.; Limon, J.

    2010-01-01

    We report three novel mutations in JAK2 exons 12, 19 and 25 in V617F-negative patients with polycythemia vera, essential thrombocythemia and idiopathic myelofibrosis. Scanning of JAK2 exons 12-25 and MPL exon 10 revealed the presence of JAK2 alterations in six and MPL W515L/K mutations in five of 34

  7. CD34 Antigen and the MPL Receptor Expression Defines a Novel Class of Human Cord Blood-Derived Primitive Hematopoietic Stem Cells.

    Science.gov (United States)

    Matsuoka, Yoshikazu; Takahashi, Masaya; Sumide, Keisuke; Kawamura, Hiroshi; Nakatsuka, Ryusuke; Fujioka, Tatsuya; Sonoda, Yoshiaki

    2017-06-09

    In the murine hematopoietic stem cell (HSC) compartment, thrombopoietin (THPO)/MPL (THPO receptor) signaling plays an important role in the maintenance of adult quiescent HSCs. However, the role of THPO/MPL signaling in the human primitive HSC compartment has not yet been elucidated. We have identified very primitive human cord blood (CB)-derived CD34- severe combined immunodeficiency (SCID)-repopulating cells (SRCs) using the intra-bone marrow injection method. In this study, we investigated the roles of the MPL expression in the human primitive HSC compartment. The SRC activities of the highly purified CB-derived 18Lin-CD34+/-MPL+/- cells were analyzed using NOG mice. In the primary recipient mice, nearly all mice that received CD34+/-MPL+/- cells were repopulated with human CD45+ cells. Nearly all of these mice that received CD34+MPL+/- and CD34-MPL- cells showed a secondary repopulation. Interestingly, the secondary recipient mice that received CD34+/-MPL- cells showed a distinct tertiary repopulation. These results clearly indicate that the CD34+/- SRCs not expressing MPL sustain a long-term (LT) (>1 year) human cell repopulation in NOG mice. Moreover, CD34- SRCs generate CD34+CD38-CD90+ SRCs in vitro and in vivo. These findings provide a new concept that CD34-MPL- SRCs reside at the apex of the human HSC hierarchy.

  8. Tyrosine 625 plays a key role and cooperates with tyrosine 630 in MPL W515L-induced signaling and myeloproliferative neoplasms

    OpenAIRE

    Yu, Chunjie; Yang, Qiong; Chen, Yuhong; Wang, Demin; Levine, Ross; Crispino, John; Wen, Qiang; Huang, Zan

    2016-01-01

    Background Myeloproliferative neoplasms (MPN) are a group of blood cancers that boost normal blood cell production in the bone marrow. Abnormal mutations in stem cells were found accompanying with the occurrence of MPN. It has been shown that MPL mutations (MPL W515L or MPL W515K) were involved in patients with MPN. Since tyrosine residues 625 and 630 mediate normal MPL signaling, whether them affect MPL W515L-induced myeloproliferative neoplasms (MPNs) is unknown. Results In this study, we f...

  9. Antibacterial activity of three newly-synthesized chalcones & synergism with antibiotics against clinical isolates of methicillin-resistant Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Dragana D Bozic

    2014-01-01

    Interpretation & conclusions: o0 ur study demonstrated that three newly-synthesized chalcones exhibited significant anti-MRSA effect and synergism with non-β-lactam antibiotics. The most effective compound was 1,3-Bis-(2-hydroxy-phenyl-propenone. Our results provide useful information for future research of possible application of chalcones in combination with conventional anti-MRSA therapy as promising new antimicrobial agents.

  10. Thrombopoietin/MPL participates in initiating and maintaining RUNX1-ETO acute myeloid leukemia via PI3K/AKT signaling.

    Science.gov (United States)

    Pulikkan, John Anto; Madera, Dmitri; Xue, Liting; Bradley, Paul; Landrette, Sean Francis; Kuo, Ya-Huei; Abbas, Saman; Zhu, Lihua Julie; Valk, Peter; Castilla, Lucio Hernán

    2012-07-26

    Oncogenic mutations in components of cytokine signaling pathways elicit ligand-independent activation of downstream signaling, enhancing proliferation and survival in acute myeloid leukemia (AML). The myeloproliferative leukemia virus oncogene, MPL, a homodimeric receptor activated by thrombopoietin (THPO), is mutated in myeloproliferative disorders but rarely in AML. Here we show that wild-type MPL expression is increased in a fraction of human AML samples expressing RUNX1-ETO, a fusion protein created by chromosome translocation t(8;21), and that up-regulation of Mpl expression in mice induces AML when coexpressed with RUNX1-ETO. The leukemic cells are sensitive to THPO, activating survival and proliferative responses. Mpl expression is not regulated by RUNX1-ETO in mouse hematopoietic progenitors or leukemic cells. Moreover, we find that activation of PI3K/AKT but not ERK/MEK pathway is a critical mediator of the MPL-directed antiapoptotic function in leukemic cells. Hence, this study provides evidence that up-regulation of wild-type MPL levels promotes leukemia development and maintenance through activation of the PI3K/AKT axis, and suggests that inhibitors of this axis could be effective for treatment of MPL-positive AML.

  11. Cytogenetics, JAK2 and MPL mutations in polycythemia vera, primary myelofibrosis and essential thrombocythemia

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    Leonardo Caires dos Santos

    2011-12-01

    Full Text Available BACKGROUND: The detection of molecular and cytogenetic alterations is important for the diagnosis, prognosis and classification of myeloproliferative neoplasms. OBJECTIVE: The aim of this study was to detect the following mutations: JAK2 V617F, JAK2 exon 12 and MPL W515K/L, besides chromosomal abnormalities. Furthermore, molecular and cytogenetic alterations were correlated with the leukocyte and platelet counts, hemoglobin levels and age in all patients and with the degree of fibrosis in primary myelofibrosis cases. METHODS: Twenty cases of polycythemia vera, 17 of essential thrombocythemia and 21 of primary myelofibrosis were selected in the Hematology Department of the Universidade Federal de São Paulo (UNIFESP between February 2008 and December 2009. The JAK2 V617F, JAK2 exon 12 mutations, MPL W515K and MPL W515L mutations were investigated by real-time PCR and direct sequencing. G-band karyotyping and fluorescence in situ hybridization were used to detect chromosomal abnormalities. RESULTS: Chromosomal abnormalities were observed only in polycythemia vera (11.8% and primary myelofibrosis cases (17.6%, without correlation to clinical data. Chromosomal abnormalities were not detected by fluorescence in situ hybridization. The JAK2 V617F mutation was observed in polycythemia vera (90%, primary myelofibrosis (42.8% and essential thrombocythemia (47%. Patients with JAK2 V617F-negative polycythemia vera had lower platelet and leukocyte counts compared to V617F-positive polycythemia vera (p-value = 0.0001 and p-value = 0.023, respectively. JAK2 V617F-positive and MPL W515L-positive primary myelofibrosis cases had a higher degree of fibrosis than V617F-negative cases (p-value = 0.022. JAK2 exon 12 mutations were not detected in polycythemia vera patients. The MPL W515L mutation was observed in one case of primary myelofibrosis and in one of essential thrombocythemia. The MPL W515K mutation was not found in patients with essential thrombocythemia

  12. Cytogenetics, JAK2 and MPL mutations in polycythemia vera, primary myelofibrosis and essential thrombocythemia.

    Science.gov (United States)

    Dos Santos, Leonardo Caires; Ribeiro, Juliana Corrêa da Costa; Silva, Neusa Pereira; Cerutti, Janete; da Silva, Maria Regina Regis; Chauffaille, Maria de Lourdes Lopes Ferrari

    2011-01-01

    The detection of molecular and cytogenetic alterations is important for the diagnosis, prognosis and classification of myeloproliferative neoplasms. THE AIM OF THIS STUDY WAS TO DETECT THE FOLLOWING MUTATIONS: JAK2 V617F, JAK2 exon 12 and MPL W515K/L, besides chromosomal abnormalities. Furthermore, molecular and cytogenetic alterations were correlated with the leukocyte and platelet counts, hemoglobin levels and age in all patients and with the degree of fibrosis in primary myelofibrosis cases. Twenty cases of polycythemia vera, 17 of essential thrombocythemia and 21 of primary myelofibrosis were selected in the Hematology Department of the Universidade Federal de São Paulo (UNIFESP) between February 2008 and December 2009. The JAK2 V617F, JAK2 exon 12 mutations, MPL W515K and MPL W515L mutations were investigated by real-time PCR and direct sequencing. G-band karyotyping and fluorescence in situ hybridization were used to detect chromosomal abnormalities. Chromosomal abnormalities were observed only in polycythemia vera (11.8%) and primary myelofibrosis cases (17.6%), without correlation to clinical data. Chromosomal abnormalities were not detected by fluorescence in situ hybridization. The JAK2 V617F mutation was observed in polycythemia vera (90%), primary myelofibrosis (42.8%) and essential thrombocythemia (47%). Patients with JAK2 V617F-negative polycythemia vera had lower platelet and leukocyte counts compared to V617F-positive polycythemia vera (p-value = 0.0001 and p-value = 0.023, respectively). JAK2 V617F-positive and MPL W515L-positive primary myelofibrosis cases had a higher degree of fibrosis than V617F-negative cases (p-value = 0.022). JAK2 exon 12 mutations were not detected in polycythemia vera patients. The MPL W515L mutation was observed in one case of primary myelofibrosis and in one of essential thrombocythemia. The MPL W515K mutation was not found in patients with essential thrombocythemia or primary myelofibrosis. The MPL W515L

  13. Effects of clinically relevant MPL mutations in the transmembrane domain revealed at the atomic level through computational modeling.

    Science.gov (United States)

    Lee, Tai-Sung; Kantarjian, Hagop; Ma, Wanlong; Yeh, Chen-Hsiung; Giles, Francis; Albitar, Maher

    2011-01-01

    Mutations in the thrombopoietin receptor (MPL) may activate relevant pathways and lead to chronic myeloproliferative neoplasms (MPNs). The mechanisms of MPL activation remain elusive because of a lack of experimental structures. Modern computational biology techniques were utilized to explore the mechanisms of MPL protein activation due to various mutations. Transmembrane (TM) domain predictions, homology modeling, ab initio protein structure prediction, and molecular dynamics (MD) simulations were used to build structural dynamic models of wild-type and four clinically observed mutants of MPL. The simulation results suggest that S505 and W515 are important in keeping the TM domain in its correct position within the membrane. Mutations at either of these two positions cause movement of the TM domain, altering the conformation of the nearby intracellular domain in unexpected ways, and may cause the unwanted constitutive activation of MPL's kinase partner, JAK2. Our findings represent the first full-scale molecular dynamics simulations of the wild-type and clinically observed mutants of the MPL protein, a critical element of the MPL-JAK2-STAT signaling pathway. In contrast to usual explanations for the activation mechanism that are based on the relative translational movement between rigid domains of MPL, our results suggest that mutations within the TM region could result in conformational changes including tilt and rotation (azimuthal) angles along the membrane axis. Such changes may significantly alter the conformation of the adjacent and intrinsically flexible intracellular domain. Hence, caution should be exercised when interpreting experimental evidence based on rigid models of cytokine receptors or similar systems.

  14. Structure and function of the first full-length murein peptide ligase (Mpl) cell wall recycling protein.

    Science.gov (United States)

    Das, Debanu; Hervé, Mireille; Feuerhelm, Julie; Farr, Carol L; Chiu, Hsiu-Ju; Elsliger, Marc-André; Knuth, Mark W; Klock, Heath E; Miller, Mitchell D; Godzik, Adam; Lesley, Scott A; Deacon, Ashley M; Mengin-Lecreulx, Dominique; Wilson, Ian A

    2011-03-18

    Bacterial cell walls contain peptidoglycan, an essential polymer made by enzymes in the Mur pathway. These proteins are specific to bacteria, which make them targets for drug discovery. MurC, MurD, MurE and MurF catalyze the synthesis of the peptidoglycan precursor UDP-N-acetylmuramoyl-L-alanyl-γ-D-glutamyl-meso-diaminopimelyl-D-alanyl-D-alanine by the sequential addition of amino acids onto UDP-N-acetylmuramic acid (UDP-MurNAc). MurC-F enzymes have been extensively studied by biochemistry and X-ray crystallography. In gram-negative bacteria, ∼30-60% of the bacterial cell wall is recycled during each generation. Part of this recycling process involves the murein peptide ligase (Mpl), which attaches the breakdown product, the tripeptide L-alanyl-γ-D-glutamyl-meso-diaminopimelate, to UDP-MurNAc. We present the crystal structure at 1.65 Å resolution of a full-length Mpl from the permafrost bacterium Psychrobacter arcticus 273-4 (PaMpl). Although the Mpl structure has similarities to Mur enzymes, it has unique sequence and structure features that are likely related to its role in cell wall recycling, a function that differentiates it from the MurC-F enzymes. We have analyzed the sequence-structure relationships that are unique to Mpl proteins and compared them to MurC-F ligases. We have also characterized the biochemical properties of this enzyme (optimal temperature, pH and magnesium binding profiles and kinetic parameters). Although the structure does not contain any bound substrates, we have identified ∼30 residues that are likely to be important for recognition of the tripeptide and UDP-MurNAc substrates, as well as features that are unique to Psychrobacter Mpl proteins. These results provide the basis for future mutational studies for more extensive function characterization of the Mpl sequence-structure relationships.

  15. Structure and function of the first full-length murein peptide ligase (Mpl cell wall recycling protein.

    Directory of Open Access Journals (Sweden)

    Debanu Das

    2011-03-01

    Full Text Available Bacterial cell walls contain peptidoglycan, an essential polymer made by enzymes in the Mur pathway. These proteins are specific to bacteria, which make them targets for drug discovery. MurC, MurD, MurE and MurF catalyze the synthesis of the peptidoglycan precursor UDP-N-acetylmuramoyl-L-alanyl-γ-D-glutamyl-meso-diaminopimelyl-D-alanyl-D-alanine by the sequential addition of amino acids onto UDP-N-acetylmuramic acid (UDP-MurNAc. MurC-F enzymes have been extensively studied by biochemistry and X-ray crystallography. In gram-negative bacteria, ∼30-60% of the bacterial cell wall is recycled during each generation. Part of this recycling process involves the murein peptide ligase (Mpl, which attaches the breakdown product, the tripeptide L-alanyl-γ-D-glutamyl-meso-diaminopimelate, to UDP-MurNAc. We present the crystal structure at 1.65 Å resolution of a full-length Mpl from the permafrost bacterium Psychrobacter arcticus 273-4 (PaMpl. Although the Mpl structure has similarities to Mur enzymes, it has unique sequence and structure features that are likely related to its role in cell wall recycling, a function that differentiates it from the MurC-F enzymes. We have analyzed the sequence-structure relationships that are unique to Mpl proteins and compared them to MurC-F ligases. We have also characterized the biochemical properties of this enzyme (optimal temperature, pH and magnesium binding profiles and kinetic parameters. Although the structure does not contain any bound substrates, we have identified ∼30 residues that are likely to be important for recognition of the tripeptide and UDP-MurNAc substrates, as well as features that are unique to Psychrobacter Mpl proteins. These results provide the basis for future mutational studies for more extensive function characterization of the Mpl sequence-structure relationships.

  16. The fate and role of macromolecules synthesized during mammalian oocyte meiotic maturation. I. Autoradiographic topography of newly synthesized RNA and protein in the germinal vesicle of the pig and rabbit

    International Nuclear Information System (INIS)

    Motlik, J.; Kopecny, V.; Pivko, J.

    1978-01-01

    Pig and rabbit oocytes were cytoautoradiographically checked for their synthetic activities during meiotic maturation. Tritiated uridine and lysine or 35 S-methionine were introduced into the culture medium in which the oocytes were maintained either immediately at the beginning of the germinal vesicle breakdown in vitro or after reaching a more advanced stage of this process in vitro or in vivo. Some oocytes were maintained thereafter in a cold medium to trace the metabolism of the labelled protein. In addition to uridine- 3 H incorporation into the nucleolus and nucleoplasm, during pig oocyte maturation it was found that an intensive RNA synthesis site appeared in association with condensing chromocentres of the GV II. A considerable proportion of oocytes from slaughterhouse material did not show intensive GV activity in RNA synthesis during maturation in vitro. In the pig and rabbit oocyte it was shown that the newly synthesized 3 H-lysine-labelled protein accumulated to a high degree in the GV and in the nucleolus. The labelled protein accumulated in the GV up to the stage of GV IV (pig) and persisted during the chase period in the ooplasm; it was found to be associated with chromosomes of metaphase I (pig) or metaphase II (rabbit) of the meiotic division. The process of protein accumulation in the GV was not influenced by meiotic arrest during oocyte culture in autologous follicular fluid. A similar accumulation of the label in the GV was detected in oocytes which were cultured in a medium enriched by 35 S-methionine. In some oocytes the labelled protein failed to accumulate in the nucleolar area during maturation in vitro

  17. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients.

    Science.gov (United States)

    Pardanani, Animesh D; Levine, Ross L; Lasho, Terra; Pikman, Yana; Mesa, Ruben A; Wadleigh, Martha; Steensma, David P; Elliott, Michelle A; Wolanskyj, Alexandra P; Hogan, William J; McClure, Rebecca F; Litzow, Mark R; Gilliland, D Gary; Tefferi, Ayalew

    2006-11-15

    Recently, a gain-of-function MPL mutation, MPLW515L, was described in patients with JAK2V617F-negative myelofibrosis with myeloid metaplasia (MMM). To gain more information on mutational frequency, disease specificity, and clinical correlates, genomic DNA from 1182 patients with myeloproliferative and other myeloid disorders and 64 healthy controls was screened for MPL515 mutations, regardless of JAK2V617F mutational status: 290 with MMM, 242 with polycythemia vera, 318 with essential thrombocythemia (ET), 88 with myelodysplastic syndrome, 118 with chronic myelomonocytic leukemia, and 126 with acute myeloid leukemia (AML). MPL515 mutations, either MPLW515L (n = 17) or a previously undescribed MPLW515K (n = 5), were detected in 20 patients. The diagnosis of patients with mutant MPL alleles at the time of molecular testing was de novo MMM in 12 patients, ET in 4, post-ET MMM in 1, and MMM in blast crisis in 3. Six patients carried the MPLW515L and JAK2V617F alleles concurrently. We conclude that MPLW515L or MPLW515K mutations are present in patients with MMM or ET at a frequency of approximately 5% and 1%, respectively, but are not observed in patients with polycythemia vera (PV) or other myeloid disorders. Furthermore, MPL mutations may occur concurrently with the JAK2V617F mutation, suggesting that these alleles may have functional complementation in myeloproliferative disease.

  18. The TPO/c-MPL pathway in the bone marrow may protect leukemia cells from chemotherapy in AML Patients.

    Science.gov (United States)

    Dong-Feng, Zeng; Ting, Liu; Yong, Zhang; Cheng, Chang; Xi, Zhang; Pei-Yan, Kong

    2014-04-01

    Accumulating evidence indicates that the interaction of human LSCs (leukemic stem cells) with the hematopoietic microenvironment, mediated by the thrombopoietin (TPO)/c-MPL pathway, may be an underlying mechanism for resistance to cell cycle-dependent cytotoxic chemotherapy. However, the role of TPO/c-MPL signaling in AML (acute myelogenous leukemia) chemotherapy resistance hasn't been fully understood. The c-MPL and TPO levels in different AML samples were measured by flow cytometry and ELISA. We also assessed the TPO levels in the osteoblasts derived from bone mesenchymal stem cells (BMSCs). The survival rate of an AML cell line that had been co-cultured with different BMSC-derived osteoblasts was measured to determine the IC50 of an AML chemotherapy drug daunorubicin (DNR). The levels of TPO/c-MPL in the initial and relapse AML patients were significantly higher than that in the control (P MPL expression was found in the bone marrow mononuclear cells of the relapse AML patients. More importantly, the IC50 of DNR in the HEL + AML-derived osteoblasts was the highest among all co-culture systems. High level of TPO/c-MPL signaling may protect LSCs from chemotherapy in AML. The effects of inhibition of the TPO/c-MPL pathway on enhancing the chemotherapy sensitivity of AML cells, and on their downstream effector molecules that direct the interactions between patient-derived blasts and leukemia repopulating cells need to be further studied.

  19. Detection of MPL exon10 mutations in 103 Chinese patients with JAK2V617F-negative myeloproliferative neoplasms.

    Science.gov (United States)

    Chen, Xiuhua; Qi, Xiling; Tan, Yanhong; Xu, Zhifang; Xu, Aining; Zhang, Linlin; Wang, Hongwei

    2011-06-15

    JAK2V617F mutation has been reported in 90% of patients with polycythemia vera (PV) and about 50% of patients with essential thromobocythemia (ET) and primary myelofibrosis (PMF). Recently, acquired mutations in the transmembrane-juxtamembrane region of MPL (MPLW515 mutations) have been reported in approximately 5% of JAK2V617F-negative PMF and about 1% of all cases of ET. MPL is the receptor for thrombopoietin that regulates the production of platelets by bone marrow. It is likely that some mutations more closely related to ET in MPL exon10 may have been missed by current assays. We inferred that there might be other mutations in MPL exon10 for MPN patients in addition to MPLW515 mutations. To investigate its mutation types and prevalence in Chinese patients with myeloproliferative neoplasms (MPN), we performed mutation detection on MPL exon10 in 103 JAK2V617F-negative MPN patients by single strand conformation polymorphism (SSCP) and allele-specific PCR (AS-PCR) combined with sequencing. As a result, one previously unrecognized MPL mutation (12-bp in-frame insertion) was identified in one patient with ET in addition to an MPLW515K mutation identified in one PMF patient. This confirms our hypothesis that BCR/ABL negative and JAK2V617F-negative MPN patients have other mutations besides W515 mutation in MPL exon10 and mutations other than single nucleotide exchange also exist. In addition, MPL mutation was associated with Chinese MPN patients. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Interference RNA (RNAi)-based silencing of endogenous thrombopoietin receptor (Mpl) in Dami cells resulted in decreased hNUDC-mediated megakaryocyte proliferation and differentiation

    International Nuclear Information System (INIS)

    Pang, Shi-Feng; Li, Xiao-Kun; Zhang, Qiang; Yang, Fang; Xu, Peilin

    2009-01-01

    Recently our laboratory reported evidence showing that hNUDC acts as an additional cytokine for thrombopoietin receptor (Mpl). Previously known as the human homolog of a fungal nuclear migration protein, hNUDC plays a critical role in megakaryocyte differentiation and maturation. Here we sought to further clarify the hNUDC-Mpl ligand-receptor relationship by utilizing interference RNA (RNAi) to knockdown Mpl expression in a megakaryocyte cell line. We created U6 promoter driven constructs to express short hairpin RNAs (shRNA) with affinity for different sites on Mpl mRNA. By including Mpl-EGFP fusion protein in these constructs, we were able to effectively screen the shRNA that was most efficient in inhibiting Mpl mRNA expression. This shRNA was subsequently transferred into a lentivirus vector and transduced into Dami cells, a cell line which constitutively expresses endogenous Mpl. This lentiviral vector was also designed to simultaneously express EGFP to monitor transfection efficiency. Our results show that lentivirus can be used to effectively deliver shRNAs into Dami cells and cause specific inhibition of Mpl protein expression after transduction. Furthermore, we show the functional effects of shRNA-mediated Mpl silencing by demonstrating reduced hNUDC stimulated megakaryocyte proliferation and differentiation. Thus, the use of a RNAi knockdown strategy has allowed us to pinpoint the connection of hNUDC with Mpl in the regulation of megakaryocyte maturation.

  1. Truncated C-terminus of fibrillin-1 induces Marfanoid-progeroid-lipodystrophy (MPL) syndrome in rabbit.

    Science.gov (United States)

    Chen, Mao; Yao, Bing; Yang, Qiangbing; Deng, Jichao; Song, Yuning; Sui, Tingting; Zhou, Lina; Yao, HaoBing; Xu, Yuanyuan; Ouyang, Hongsheng; Pang, Daxin; Li, Zhanjun; Lai, Liangxue

    2018-04-09

    Various clinical differences have been observed between patients with the FBN1 gene mutation and those with the classical Marfan phenotype. Although FBN1 knockout (KO) or dominant-negative mutant mice are widely used as an animal model for Marfan syndrome (MFS), these mice cannot recapitulate the genotype/phenotype relationship of Marfanoid-progeroid-lipodystrophy (MPL) syndrome, which is caused by a mutation in the C-terminus of fibrillin-1, the penultimate exon of the FBN1 gene. Here, we describe the generation of a rabbit MPL model with C-terminal truncation of fibrillin-1 using a CRISPR/Cas9 system. FBN1 heterozygous ( FBN1 Het) rabbits faithfully recapitulated the phenotypes of MFS, including muscle wasting and impaired connective tissue, ocular syndrome and aortic dilation. Moreover, skin symptoms, lipodystrophy, growth retardation and dysglycemia were also seen in these FBN1 Het rabbits, and have not been reported in other animal models. In conclusion, this novel rabbit model mimics the histopathological changes and functional defects of MPL syndrome, and could become a valuable model for studies of pathogenesis and drug screening for MPL syndrome. © 2018. Published by The Company of Biologists Ltd.

  2. Green methodology for the recovery of Cr (VI from tannery effluent using newly synthesized quaternary ammonium salt

    Directory of Open Access Journals (Sweden)

    K.S. Yoganand

    2017-02-01

    Full Text Available Leather tanning industries release effluents into the river through various canals. These effluents contain chromium (VI contaminating the river and the ground water as well. To fix a solution for this issue a simple and selective solvent extraction method has been applied by using a newly synthesized quaternary ammonium salt viz 2-benzoylethylheptyldimethylammonium bromide. By varying the parameters such as quaternary ammonium salts, sulfuric acid, pH, solvents, equilibration time and aqueous organic ratio the extraction efficiency has been determined.

  3. Expression of CALR mutants causes mpl-dependent thrombocytosis in zebrafish.

    Science.gov (United States)

    Lim, K-H; Chang, Y-C; Chiang, Y-H; Lin, H-C; Chang, C-Y; Lin, C-S; Huang, L; Wang, W-T; Gon-Shen Chen, C; Chou, W-C; Kuo, Y-Y

    2016-10-07

    CALR mutations are identified in about 30% of JAK2/MPL-unmutated myeloproliferative neoplasms (MPNs) including essential thrombocythemia (ET) and primary myelofibrosis. Although the molecular pathogenesis of CALR mutations leading to MPNs has been studied using in vitro cell lines models, how mutant CALR may affect developmental hematopoiesis remains unknown. Here we took advantage of the zebrafish model to examine the effects of mutant CALR on early hematopoiesis and model human CALR-mutated MPNs. We identified three zebrafish genes orthologous to human CALR, referred to as calr, calr3a and calr3b. The expression of CALR-del52 and CALR-ins5 mutants caused an increase in the hematopoietic stem/progenitor cells followed by thrombocytosis without affecting normal angiogenesis. The expression of CALR mutants also perturbed early developmental hematopoiesis in zebrafish. Importantly, morpholino knockdown of mpl but not epor or csf3r could significantly attenuate the effects of mutant CALR. Furthermore, the expression of mutant CALR caused jak-stat signaling activation in zebrafish that could be blocked by JAK inhibitors (ruxolitinib and fedratinib). These findings showed that mutant CALR activates jak-stat signaling through an mpl-dependent mechanism to mediate pathogenic thrombopoiesis in zebrafish, and illustrated that the signaling machinery related to mutant CALR tumorigenesis are conserved between human and zebrafish.

  4. MPL-net at ARM Sites

    Science.gov (United States)

    Spinhirne, J. D.; Welton, E. J.; Campbell, J. R.; Berkoff, T. A.; Starr, David OC. (Technical Monitor)

    2002-01-01

    The NASA MPL-net project goal is consistent data products of the vertical distribution of clouds and aerosol from globally distributed lidar observation sites. The four ARM micro pulse lidars are a basis of the network to consist of over twelve sites. The science objective is ground truth for global satellite retrievals and accurate vertical distribution information in combination with surface radiation measurements for aerosol and cloud models. The project involves improvement in instruments and data processing and cooperation with ARM and other partners.

  5. Synergy of anti-CD40, CpG and MPL in activation of mouse macrophages.

    Science.gov (United States)

    Shi, Yongyu; Felder, Mildred A R; Sondel, Paul M; Rakhmilevich, Alexander L

    2015-08-01

    Activation of macrophages is a prerequisite for their antitumor effects. Several reagents, including agonistic anti-CD40 monoclonal antibody (anti-CD40), CpG oligodeoxynucleotides (CpG) and monophosphoryl lipid A (MPL), can stimulate activation of macrophages. Our previous studies showed synergy between anti-CD40 and CpG and between anti-CD40 and MPL in macrophage activation and antitumor efficacy in mice. In the present study, we asked whether there was synergy among these three reagents. The activation of adherent peritoneal exudate cells (PEC) obtained from mice injected with anti-CD40 and then treated with CpG and/or MPL in vitro was determined by their ability to suppress proliferation of tumor cells and to produce various cytokines and chemokines in vitro. Cell sorting and histology followed by functional testing showed that macrophages were the main cell population in PEC activated by CD40 ligation in vivo. A combination of anti-CD40, CpG or MPL activated PEC to suppress proliferation of B16 cells and produce nitric oxide far greater than the single reagents or any of the double combinations of these reagents. In addition, the combination of all three reagents activated PEC to secrete IL-12, IFN-γ and MCP-1 to a greater degree than any single reagent or any two combined reagents. These results demonstrate that macrophages can be synergistically activated by anti-CD40, CpG and MPL, suggesting that this novel combined approach might be further investigated as potential cancer therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Synergy of anti-CD40, CpG and MPL in activation of mouse macrophages

    Science.gov (United States)

    Shi, Yongyu; Felder, Mildred A.R.; Sondel, Paul M.; Rakhmilevich, Alexander L.

    2015-01-01

    Activation of macrophages is a prerequisite for their antitumor effects. Several reagents, including agonistic anti-CD40 monoclonal antibody (anti-CD40), CpG oligodeoxynucleotides (CpG) and monophosphoryl lipid A (MPL), can stimulate activation of macrophages. Our previous studies showed synergy between anti-CD40 and CpG and between anti-CD40 and MPL in macrophage activation and antitumor efficacy in mice. In the present study, we asked whether there was synergy among these three reagents. The activation of adherent peritoneal exudate cells (PEC) obtained from mice injected with anti-CD40 and then treated with CpG and/or MPL in vitro was determined by their ability to suppress proliferation of tumor cells and to produce various cytokines and chemokines in vitro. Cell sorting and histology followed by functional testing showed that macrophages were the main cell population in PEC activated by CD40 ligation in vivo. A combination of anti-CD40, CpG or MPL activated PEC to suppress proliferation of B16 cells and produce nitric oxide far greater than the single reagents or any of the double combinations of these reagents. In addition, the combination of all three reagents activated PEC to secrete IL-12, IFN-γ and MCP-1 to a greater degree than any single reagent or any two combined reagents. These results demonstrate that macrophages can be synergistically activated by anti-CD40, CpG and MPL, suggesting that this novel combined approach might be further investigated as potential cancer therapy. PMID:25829245

  7. Ott1 (Rbm15) regulates thrombopoietin response in hematopoietic stem cells through alternative splicing of c-Mpl.

    Science.gov (United States)

    Xiao, Nan; Laha, Suparna; Das, Shankar P; Morlock, Kayla; Jesneck, Jonathan L; Raffel, Glen D

    2015-02-05

    Thrombopoietin (Thpo) signaling through the c-Mpl receptor promotes either quiescence or proliferation of hematopoietic stem cells (HSCs) in a concentration-dependent manner; however, in vivo Thpo serum levels are responsive to platelet mass rather than HSC demands, suggesting additional regulation exists. Ott1 (Rbm15), a spliceosomal component originally identified as a fusion partner in t(1;22)-associated acute megakaryocytic leukemia, is also essential for maintaining HSC quiescence under stress. Ott1 controls the alternative splicing of a dominant negative isoform, Mpl-TR, capable of inhibiting HSC engraftment and attenuating Thpo signaling. Ott1, which associates with Hdac3 and the histone methyltransferase, Setd1b, binds to both c-Mpl RNA and chromatin and regulates H4 acetylation and H3K4me3 marks. Histone deacetylase or histone methyltransferase inhibition also increases Mpl-TR levels, suggesting that Ott1 uses an underlying epigenetic mechanism to control alternative splicing of c-Mpl. Manipulation of Ott1-dependent alternative splicing may therefore provide a novel pharmacologic avenue for regulating HSC quiescence and proliferation in response to Thpo. © 2015 by The American Society of Hematology.

  8. Acquired copy-neutral loss of heterozygosity of chromosome 1p as a molecular event associated with marrow fibrosis in MPL-mutated myeloproliferative neoplasms.

    Science.gov (United States)

    Rumi, Elisa; Pietra, Daniela; Guglielmelli, Paola; Bordoni, Roberta; Casetti, Ilaria; Milanesi, Chiara; Sant'Antonio, Emanuela; Ferretti, Virginia; Pancrazzi, Alessandro; Rotunno, Giada; Severgnini, Marco; Pietrelli, Alessandro; Astori, Cesare; Fugazza, Elena; Pascutto, Cristiana; Boveri, Emanuela; Passamonti, Francesco; De Bellis, Gianluca; Vannucchi, Alessandro; Cazzola, Mario

    2013-05-23

    We studied mutations of MPL exon 10 in patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF), first investigating a cohort of 892 consecutive patients. MPL mutation scanning was performed on granulocyte genomic DNA by using a high-resolution melt assay, and the mutant allele burden was evaluated by using deep sequencing. Somatic mutations of MPL, all but one involving codon W515, were detected in 26/661 (4%) patients with ET, 10/187 (5%) with PMF, and 7/44 (16%) patients with post-ET myelofibrosis. Comparison of JAK2 (V617F)-mutated and MPL-mutated patients showed only minor phenotypic differences. In an extended group of 62 MPL-mutated patients, the granulocyte mutant allele burden ranged from 1% to 95% and was significantly higher in patients with PMF or post-ET myelofibrosis compared with those with ET. Patients with higher mutation burdens had evidence of acquired copy-neutral loss of heterozygosity (CN-LOH) of chromosome 1p in granulocytes, consistent with a transition from heterozygosity to homozygosity for the MPL mutation in clonal cells. A significant association was found between MPL-mutant allele burden greater than 50% and marrow fibrosis. These observations suggest that acquired CN-LOH of chromosome 1p involving the MPL location may represent a molecular mechanism of fibrotic transformation in MPL-mutated myeloproliferative neoplasms.

  9. Low frequency of c-MPL gene mutations in Iranian patients with Philadelphia-negative myeloproliferative disorders.

    Science.gov (United States)

    Ghotaslou, A; Nadali, F; Chahardouli, B; Alizad Ghandforosh, N; Rostami, S H; Alimoghaddam, K; Ghavamzadeh, A

    2015-01-01

    Myeloproliferative disorders are a group of diseases characterized by increased proliferation of myeloid lineage. In addition to JAK2V617F mutation, several mutations in the c-MPL gene have been reported in patients with philadelphia-negative chronic myeloproliferative disorders that could be important in the pathogenesis of diseases. The aim of the present study was to investigate the frequency of c-MPL and JAK2V617F mutations in Iranian patients with Philadelphia-negativemyeloproliferative disorders. Peripheral blood samples were collected from 60 patients with Philadelphia-negative MPD) Subgroups ET and PMF) and 25 healthy subjects as control group. The mutation status of c-MPL and Jak2V617F were investigated by using Amplification-refractory mutation system (ARMS) and Allele-Specific PCR (AS-PCR), respectively. The results were confirmed by sequencing. Among 60 patients, 34 (56.6%) and 1(1.7%) had Jak2V617F and c-MPL mutation, respectively. Patients with Jak2V617F mutation had higher WBC counts and hemoglobin concentration than those without the mutation (p= 0.005, p=0.003). In addition, for all healthy subjects in control group, mutations were negative. The present study revealed that the c-MPL mutations unlike the Jak2V617F mutations are rare in Iranian patients with Ph-negative MPNs and the low mutation rate should be considered in the design of screening strategies of MPD patients.

  10. Identification and characterization of an alternative splice variant of Mpl with a high affinity for TPO and its activation of ERK1/2 signaling.

    Science.gov (United States)

    Wang, Qiong; Sun, Rui; Wu, Leyan; Huang, Junfeng; Wang, Ping; Yuan, Hailong; Qiu, Feifei; Xu, Xiaohong; Wu, Di; Yu, Ying; Liu, Xin; Zhang, Qing

    2013-12-01

    The thrombopoietin receptor is a crucial element in thrombopoietin-initiated signaling pathways, which stimulates the differentiation of normal hematopoietic progenitor cells, the maturation of megakaryocytes, and the generation of platelets. In this study, we identified a novel activating variant of thrombopoietin receptor, termed Mpl-D, in human megakaryoblastic leukemia Dami cells and demonstrated that the binding affinity of the Mpl-D receptor for thrombopoietin is enhanced. Cell cycle analysis revealed that in the presence of thrombopoietin, most Mpl-D expressing NIH3T3 (NIH3T3/Mpl-D) cells were prevalent in G1 phase while the S and G2/M populations were less frequently observed. Unexpectedly, thrombopoietin induced strong and prolonged ERK1/2 signaling in NIH3T3/Mpl-D cells compared with its receptor wild-type expressing NIH3T3 (NIH3T3/Mpl-F) cells. Further analysis of the mRNA levels of cyclin D1/D2 in NIH3T3/Mpl-D cells demonstrated markedly down-regulated expression compared to NIH3T3/Mpl-F cells in the presence of thrombopoietin. Thus, the prolonged activation of ERK1/2 by Mpl-D might lead to G1 cell cycle arrest through a profound reduction of cyclin D1/D2 in order to support cell survival without proliferation. We also provided tertiary structural basis for the Mpl-D and thrombopoietin interaction, which might provide insights into how Mpl-D effectively increases binding to thrombopoietin and significantly contributes to its specific signaling pathway. These results suggest a new paradigm for the regulation of cytokine receptor expression and function through the alternative splicing variant of Mpl in Dami cells, which may play a role in the pathogenesis of megakaryoblastic leukemia. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Detection of CALR and MPL Mutations in Low Allelic Burden JAK2 V617F Essential Thrombocythemia.

    Science.gov (United States)

    Usseglio, Fabrice; Beaufils, Nathalie; Calleja, Anne; Raynaud, Sophie; Gabert, Jean

    2017-01-01

    Myeloproliferative neoplasms are clonal hematopoietic stem cell disorders characterized by aberrant proliferation and an increased tendency toward leukemic transformation. The genes JAK2, MPL, and CALR are frequently altered in these syndromes, and their mutations are often a strong argument for diagnosis. We analyzed the mutational profiles of these three genes in a cohort of 164 suspected myeloproliferative neoplasms. JAK2 V617F mutation was detected by real-time PCR, whereas high-resolution melting analysis followed by Sanger sequencing were used for searching for mutations in JAK2 exon 12, CALR, and MPL. JAK2 V617F mutation was associated with CALR (n = 4) and MPL (n = 4) mutations in 8 of 103 essential thrombocytosis patients. These cases were harboring a JAK2 V617F allelic burden of MPL genes in myeloproliferative neoplasms and suggest that CALR and MPL should be analyzed not only in JAK2-negative patients but also in low V617F mutation patients. Follow-up of these double-mutation cases will be important for determining whether this group of patients presents particular evolution or complications. Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  12. Measurement of T-lymphocyte responses in whole-blood cultures using newly synthesized DNA and ATP.

    Science.gov (United States)

    Sottong, P R; Rosebrock, J A; Britz, J A; Kramer, T R

    2000-03-01

    The proliferative response is most frequently determined by estimating the amount of [(3)H]thymidine incorporated into newly synthesized DNA. The [(3)H]thymidine procedure requires the use of radioisotopes as well as lengthy periods of incubation (>72 h). An alternative method of assessing T-lymphocyte activation in whole-blood cultures involves the measurement of the nucleotide ATP instead of [(3)H]thymidine incorporation. In addition, the Luminetics assay of T-cell activation measures specific T-lymphocyte subset responses through the use of paramagnetic particles coated with monoclonal antibodies against CD antigens. This assay permits rapid (24 h) analysis of lymphocyte subset activation responses to mitogens and recall antigens in small amounts of blood.

  13. Association with β-COP Regulates the Trafficking of the Newly Synthesized Na,K-ATPase*

    Science.gov (United States)

    Morton, Michael J.; Farr, Glen A.; Hull, Michael; Capendeguy, Oihana; Horisberger, Jean-Daniel; Caplan, Michael J.

    2010-01-01

    Plasma membrane expression of the Na,K-ATPase requires assembly of its α- and β-subunits. Using a novel labeling technique to identify Na,K-ATPase partner proteins, we detected an interaction between the Na,K-ATPase α-subunit and the coat protein, β-COP, a component of the COP-I complex. When expressed in the absence of the Na,K-ATPase β-subunit, the Na,K-ATPase α-subunit interacts with β-COP, is retained in the endoplasmic reticulum, and is targeted for degradation. In the presence of the Na,K-ATPase β-subunit, the α-subunit does not interact with β-COP and traffics to the plasma membrane. Pulse-chase experiments demonstrate that in cells expressing both the Na,K-ATPase α- and β-subunits, newly synthesized α-subunit associates with β-COP immediately after its synthesis but that this interaction does not constitute an obligate intermediate in the assembly of the α- and β-subunits to form the pump holoenzyme. The interaction with β-COP was reduced by mutating a dibasic motif at Lys54 in the Na,K-ATPase α-subunit. This mutant α-subunit is not retained in the endoplasmic reticulum and reaches the plasma membrane, even in the absence of Na,K-ATPase β-subunit expression. Although the Lys54 α-subunit reaches the cell surface without need for β-subunit assembly, it is only functional as an ion-transporting ATPase in the presence of the β-subunit. PMID:20801885

  14. Aerosol Extinction Profile Mapping with Lognormal Distribution Based on MPL Data

    Science.gov (United States)

    Lin, T. H.; Lee, T. T.; Chang, K. E.; Lien, W. H.; Liu, G. R.; Liu, C. Y.

    2017-12-01

    This study intends to challenge the profile mapping of aerosol vertical distribution by mathematical function. With the similarity in distribution pattern, lognormal distribution is examined for mapping the aerosol extinction profile based on MPL (Micro Pulse LiDAR) in situ measurements. The variables of lognormal distribution are log mean (μ) and log standard deviation (σ), which will be correlated with the parameters of aerosol optical depht (AOD) and planetary boundary layer height (PBLH) associated with the altitude of extinction peak (Mode) defined in this study. On the base of 10 years MPL data with single peak, the mapping results showed that the mean error of Mode and σ retrievals are 16.1% and 25.3%, respectively. The mean error of σ retrieval can be reduced to 16.5% under the cases of larger distance between PBLH and Mode. The proposed method is further applied to MODIS AOD product in mapping extinction profile for the retrieval of PM2.5 in terms of satellite observations. The results indicated well agreement between retrievals and ground measurements when aerosols under 525 meters are well-mixed. The feasibility of proposed method to satellite remote sensing is also suggested by the case study. Keyword: Aerosol extinction profile, Lognormal distribution, MPL, Planetary boundary layer height (PBLH), Aerosol optical depth (AOD), Mode

  15. Biodistribution of newly synthesized PHEA-based polymer-coated SPION in Sprague Dawley rats as magnetic resonance contrast agent

    Directory of Open Access Journals (Sweden)

    Park J

    2013-10-01

    Full Text Available Junsung Park,1,2,* Wonkyung Cho,1,2,* Hee Jun Park,1,2 Kwang-Ho Cha,1,2 Dae-Chul Ha,2,5 Youn-Woong Choi,5 Ha-Young Lee,3 Sun-Hang Cho,5 Sung-Joo Hwang1,4 1Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea; 2College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea; 3Biomaterials Laboratory, Korea Research Institutes of Chemical Technology, Daejeon, Republic of Korea; 4College of Pharmacy, Yonsei University, Incheon, Republic of Korea; 5Korea United Pharm Inc, Seoul, Republic of Korea *These authors contributed equally to this work Objectives: The purpose of this study was to observe the pharmacokinetic behavior of newly synthesized biocompatible polymers based on polyhydroxyethylaspartamide (PHEA to be used to coat an iron oxide core to make superparamagnetic iron oxide nanoparticles (SPION. Materials and methods: The isotopes [14C] and [59Fe] were used to label the polymer backbone (CLS and iron oxide core (FLS, respectively. In addition, unradiolabeled cold superparamagnetic iron oxide nanoparticles (SPION/ULS were synthesized to characterize particle size by dynamic light scattering, morphology by transmission electron microscopy, and in vivo magnetic resonance imaging (MRI. CLS and FLS were used separately to investigate the behavior of both the synthesized polymer and [Fe] in Sprague Dawley (SD rats, respectively. Because radioactivity of the isotopes was different by β for CLS and γ for FLS, synthesis of the samples had to be separately prepared. Results: The mean particle size of the ULS was 66.1 nm, and the biodistribution of CLS concentrations in various organs, in rank order of magnitude, was liver > kidney > small intestine > other. The biodistribution of FLS concentrations was liver > spleen > lung > other. These rank orders show that synthesized SPION mainly accumulates in the liver. The differences in the distribution were caused by the SPION metabolism. Radiolabeled

  16. CALR, JAK2 and MPL mutation status in Argentinean patients with BCR-ABL1- negative myeloproliferative neoplasms.

    Science.gov (United States)

    Ojeda, Mara Jorgelina; Bragós, Irma Margarita; Calvo, Karina Lucrecia; Williams, Gladis Marcela; Carbonell, María Magdalena; Pratti, Arianna Flavia

    2018-05-01

    To establish the frequency of JAK2, MPL and CALR mutations in Argentinean patients with BCR-ABL1-negative  myeloproliferative neoplasms (MPN) and to compare their clinical and haematological features. Mutations of JAK2V617F, JAK2 exon 12, MPL W515L/K and CALR were analysed in 439 Argentinean patients with BCR-ABL1-negative MPN, including 176 polycythemia vera (PV), 214 essential thrombocythemia (ET) and 49 primary myelofibrosis (PMF). In 94.9% of PV, 85.5% ET and 85.2% PMF, we found mutations in JAK2, MPL or CALR. 74.9% carried JAK2V617F, 12.3% CALR mutations, 2.1% MPL mutations and 10.7% were triple negative. In ET, nine types of CALR mutations were identified, four of which were novel. PMF patients were limited to types 1 and 2, type 2 being more frequent. In ET, patients with CALR mutation were younger and had higher platelet counts than those with JAK2V617F and triple negative. In addition, JAK2V617F patients had high leucocyte and haemoglobin values compared with CALR-mutated and triple-negative patients. In PMF, patients with mutant CALR were associated with higher platelet counts. Our study underscores the importance of JAK2, MPL and CALR genotyping for accurate diagnosis of patients with BCR-ABL1-negative MPN.

  17. PRV-1, erythroid colonies and platelet Mpl are unrelated to thrombosis in essential thrombocythaemia

    DEFF Research Database (Denmark)

    Vannucchi, Alessandro M; Pancrazzi, Alessandro; Antonioli, Elisabetta

    2004-01-01

    markers of ET, namely PRV-1 overexpression, endogenous erythroid colony (EEC) formation, and reduced platelet Mpl content. Fifty-three (60%) of 88 subjects studied had monoclonal myelopoiesis and presented a 32% incidence of major thrombosis compared with 6% of polyclonal subjects (P = 0.......009). The frequency of abnormalities of PRV-1, EEC, or Mpl was similar in monoclonal and polyclonal subjects (respectively, 28%, 48%, 75%, and 37%, 27%, 63%), and none of them correlated with thrombosis. We conclude that the exploited epigenetic markers constitute independent phenotypic variations...

  18. The role of MPL and imiquimod adjuvants in enhancement of immune response and protection in BALB/c mice immunized with soluble Leishmania antigen (SLA) encapsulated in nanoliposome.

    Science.gov (United States)

    Emami, Tara; Rezayat, Seyed Mahdi; Khamesipour, Ali; Madani, Rasool; Habibi, Gholamreza; Hojatizade, Mansure; Jaafari, Mahmoud Reza

    2018-04-01

    Adjuvants play an essential role in the induction of immunity against leishmaniasis. In this study, monophosphoryl lipid A (MPL) and imiquimod (IMQ) were used as TLR ligands adjuvants to enhance immunogenicity and rate of protection against leishmaniasis. Nanoliposomes containing soluble Leishmania antigens (SLA) and adjuvants were consisted of DSPC, DSPG and Chol prepared by using lipid film method followed by bath sonication. The size of nanoliposomes was around 95 nm and their zeta potential was negative. BALB/c mice were immunized by liposomal formulations of lip/SLA, lip/MPL/SLA, lip/IMQ/SLA, lip/MPL/IMQ/SLA, lip/SLA + lip/IMQ, lip/SLA + lip/MPL, lip/SLA + lip/MPL/IMQ and five controls of SLA, lip/MPL, lip/IMQ, lip/MPL/IMQ and buffer by subcutaneously (SC) injections, three times in 2 weeks intervals. The synergic effect of two adjuvants when they are used in one formulation showed significantly (p MPL and IMQ adjuvants and antigen in nanoliposome carrier could be an appropriate delivery system to induce cellular immunity pathway against leishmaniasis.

  19. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis.

    Science.gov (United States)

    Rumi, Elisa; Pietra, Daniela; Pascutto, Cristiana; Guglielmelli, Paola; Martínez-Trillos, Alejandra; Casetti, Ilaria; Colomer, Dolors; Pieri, Lisa; Pratcorona, Marta; Rotunno, Giada; Sant'Antonio, Emanuela; Bellini, Marta; Cavalloni, Chiara; Mannarelli, Carmela; Milanesi, Chiara; Boveri, Emanuela; Ferretti, Virginia; Astori, Cesare; Rosti, Vittorio; Cervantes, Francisco; Barosi, Giovanni; Vannucchi, Alessandro M; Cazzola, Mario

    2014-08-14

    We studied the impact of driver mutations of JAK2, CALR, (calreticulin gene) or MPL on clinical course, leukemic transformation, and survival of patients with primary myelofibrosis (PMF). Of the 617 subjects studied, 399 (64.7%) carried JAK2 (V617F), 140 (22.7%) had a CALR exon 9 indel, 25 (4.0%) carried an MPL (W515) mutation, and 53 (8.6%) had nonmutated JAK2, CALR, and MPL (so-called triple-negative PMF). Patients with CALR mutation had a lower risk of developing anemia, thrombocytopenia, and marked leukocytosis compared with other subtypes. They also had a lower risk of thrombosis compared with patients carrying JAK2 (V617F). At the opposite, triple-negative patients had higher incidence of leukemic transformation compared with either CALR-mutant or JAK2-mutant patients. Median overall survival was 17.7 years in CALR-mutant, 9.2 years in JAK2-mutant, 9.1 years in MPL-mutant, and 3.2 years in triple-negative patients. In multivariate analysis corrected for age, CALR-mutant patients had better overall survival than either JAK2-mutant or triple-negative patients. The impact of genetic lesions on survival was independent of current prognostic scoring systems. These observations indicate that driver mutations define distinct disease entities within PMF. Accounting for them is not only relevant to clinical decision-making, but should also be considered in designing clinical trials. © 2014 by The American Society of Hematology.

  20. Multivalent presentation of MPL by porous silicon microparticles favors T helper 1 polarization enhancing the anti-tumor efficacy of doxorubicin nanoliposomes.

    Science.gov (United States)

    Meraz, Ismail M; Hearnden, Claire H; Liu, Xuewu; Yang, Marie; Williams, Laura; Savage, David J; Gu, Jianhua; Rhudy, Jessica R; Yokoi, Kenji; Lavelle, Ed C; Serda, Rita E

    2014-01-01

    Porous silicon (pSi) microparticles, in diverse sizes and shapes, can be functionalized to present pathogen-associated molecular patterns that activate dendritic cells. Intraperitoneal injection of MPL-adsorbed pSi microparticles, in contrast to free MPL, resulted in the induction of local inflammation, reflected in the recruitment of neutrophils, eosinophils and proinflammatory monocytes, and the depletion of resident macrophages and mast cells at the injection site. Injection of microparticle-bound MPL resulted in enhanced secretion of the T helper 1 associated cytokines IFN-γ and TNF-α by peritoneal exudate and lymph node cells in response to secondary stimuli while decreasing the anti-inflammatory cytokine IL-10. MPL-pSi microparticles independently exhibited anti-tumor effects and enhanced tumor suppression by low dose doxorubicin nanoliposomes. Intravascular injection of the MPL-bound microparticles increased serum IL-1β levels, which was blocked by the IL-1 receptor antagonist Anakinra. The microparticles also potentiated tumor infiltration by dendritic cells, cytotoxic T lymphocytes, and F4/80+ macrophages, however, a specific reduction was observed in CD204+ macrophages.

  1. PERSEPSI MAHASISWA PENDIDIKAN MATEMATIKA TENTANG PELAKSANAAN MAGANG TERAPAN OLEH STKIP MPL TAHUN AKADEMIK 2015-2016

    Directory of Open Access Journals (Sweden)

    Noerhasmalina Noerhasmalina

    2018-02-01

    Full Text Available Abstract In the academic year 2015-2016 for the first time STKIP Muhammadiyah Pringsewu Lampung (STKIP MPL implementing Applied Internship program (MT. Applied internship is mandatory for students after graduation internship Basic (MD and the Advanced Apprenticeship (ML. MT This is a new program and the suspect will be perceived together with Field Experience Practice program (PPL. The purpose of this study was to describe the mathematics education students' perceptions about the implementation of MT by STKIP MPL. The population in this study were all students STKIP MPL trainees applied consisting of four courses. Determination of the study sample was using technique purposive sampling. Retrieved mathematics education courses as a sample followed by 60 participants. To obtain data on students' perceptions conducted questionnaire. Furthermore, the data were analyzed descriptively. Based on the analysis and discussion of the perception expressed obtained 7 student interns applied academic year 2015-2016. Keywords:.Applied Internship, Student Perceptions

  2. Fungal lectin MpL enables entry of protein drugs into cancer cells and their subcellular targeting

    OpenAIRE

    ?urga, Simon; Nanut, Milica Peri?i?; Kos, Janko; Saboti?, Jerica

    2017-01-01

    Lectins have been recognized as promising carrier molecules for targeted drug delivery. They specifically bind carbohydrate moieties on cell membranes and trigger cell internalization. Fungal lectin MpL (Macrolepiota procera lectin) does not provoke cancer cell cytotoxicity but is able to bind aminopeptidase N (CD13) and integrin ?3?1, two glycoproteins that are overexpressed on the membrane of tumor cells. Upon binding, MpL is endocytosed in a clathrin-dependent manner and accumulates initia...

  3. Identification of Newly Synthesized Proteins by Echinococcus granulosus Protoscoleces upon Induction of Strobilation.

    Directory of Open Access Journals (Sweden)

    João Antonio Debarba

    2015-09-01

    Full Text Available The proteins responsible for the key molecular events leading to the structural changes between the developmental stages of Echinococcus granulosus remain unknown. In this work, azidohomoalanine (AHA-specific labeling was used to identify proteins expressed by E. granulosus protoscoleces (PSCs upon the induction of strobilar development.The in vitro incorporation of AHA with different tags into newly synthesized proteins (NSPs by PSCs was analyzed using SDS-PAGE and confocal microscopy. The LC-MS/MS analysis of AHA-labeled NSPs by PSCs undergoing strobilation allowed for the identification of 365 proteins, of which 75 were differentially expressed in comparison between the presence or absence of strobilation stimuli and 51 were expressed exclusively in either condition. These proteins were mainly involved in metabolic, regulatory and signaling processes.After the controlled-labeling of proteins during the induction of strobilar development, we identified modifications in protein expression. The changes in the metabolism and the activation of control and signaling pathways may be important for the correct parasite development and be target for further studies.

  4. Complexes cobalt(II, zinc(II and copper(II with some newly synthesized benzimidazole derivatives and their antibacterial activity

    Directory of Open Access Journals (Sweden)

    S. O. PODUNAVAC-KUZMANOVIC

    1999-05-01

    Full Text Available The preparation and properties of some complexes of cobalt(II, zinc(II and copper(II with several newly synthesized benzimidazole derivatives (L are reported. The complexes, of the general formula [MCl2L2] (M=Co(II, Zn(II and [CuCl2L(H2O], have a tetrahedral structure. The complexes were characterized by elemental analysis, molar conductivity, magnetic susceptibility measurements, IR and absorption electronic spectra. The antibacterial activitiy of the benzimidazoles and their complexes was evaluated against Erwinia carotovora subsp. carotovora and Erwinia amylovora. The complexes were found to be more toxic than the ligands.

  5. An MPL W515L mutation in refractory anemia with ringed sideroblasts associated with marked thrombocytosis: A case report.

    Science.gov (United States)

    Hao, Lin; Sen, Sandeep; Sugumar, Dhivya

    2015-02-01

    The current study presents the case of a 63-year-old patient exhibiting refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T), who was positive for the MPL W515L mutation, but negative for the JAK2 V617F mutation. Following diagnosis, the patient remained asymptomatic for over three years, however, in August 2012, the patient relapsed and was administered with supportive treatment in the form of subcutaneous darbepoetin α at a dose of 300 μg/week, which resulted in an increased hemoglobin concentration, allowing the patient to remain transfusion-independent. The MPL W515L mutation has been reported in two previous cases of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) with ringed sideroblasts, however, to the best of our knowledge, the current report is the first to present a case of RARS-T with an MPL W515L mutation. A clinical trial designed to evaluate the efficacy of a targeted agent against the JAK2 V617F mutation is currently ongoing, with the aim of providing a novel therapeutic strategy for treating MDS/MPN patients. As MPL is located upstream of the JAK-STAT signaling pathway, it is a possible therapeutic target in MDS/MPN patients positive for an MPL W515L mutation, but negative for a JAK2 V617F mutation.

  6. VEGF controls lung Th2 inflammation via the miR-1-Mpl (myeloproliferative leukemia virus oncogene)-P-selectin axis.

    Science.gov (United States)

    Takyar, Seyedtaghi; Vasavada, Hema; Zhang, Jian-ge; Ahangari, Farida; Niu, Naiqian; Liu, Qing; Lee, Chun Geun; Cohn, Lauren; Elias, Jack A

    2013-09-23

    Asthma, the prototypic Th2-mediated inflammatory disorder of the lung, is an emergent disease worldwide. Vascular endothelial growth factor (VEGF) is a critical regulator of pulmonary Th2 inflammation, but the underlying mechanism and the roles of microRNAs (miRNAs) in this process have not been defined. Here we show that lung-specific overexpression of VEGF decreases miR-1 expression in the lung, most prominently in the endothelium, and a similar down-regulation occurs in lung endothelium in Th2 inflammation models. Intranasal delivery of miR-1 inhibited inflammatory responses to ovalbumin, house dust mite, and IL-13 overexpression. Blocking VEGF inhibited Th2-mediated lung inflammation, and this was restored by antagonizing miR-1. Using mRNA arrays, Argonaute pull-down assays, luciferase expression assays, and mutational analysis, we identified Mpl as a direct target of miR-1 and showed that VEGF controls the expression of endothelial Mpl during Th2 inflammation via the regulation of miR-1. In vivo knockdown of Mpl inhibited Th2 inflammation and indirectly inhibited the expression of P-selectin in lung endothelium. These experiments define a novel VEGF-miR-1-Mpl-P-selectin effector pathway in lung Th2 inflammation and herald the utility of miR-1 and Mpl as potential therapeutic targets for asthma.

  7. JAK2 V617F, MPL W515L and JAK2 Exon 12 Mutations in Chinese Patients with Primary Myelofibrosis.

    Science.gov (United States)

    Xia, Jun; Lu, Mi-Ze; Jiang, Yuan-Qiang; Yang, Guo-Hua; Zhuang, Yun; Sun, Hong-Li; Shen, Yun-Feng

    2012-03-01

    JAK2 V617F, MPL W515L and JAK2 exon 12 mutations are novel acquired mutations that induce constitutive cytokine-independent activation of the JAK-STAT pathway in myeloproliferative disorders (MPD). The discovery of these mutations provides novel mechanism for activation of signal transduction in hematopoietic malignancies. This research was to investigate their prevalence in Chinese patients with primary myelofibrosis (PMF). We introduced allele-specific PCR (AS-PCR) combined with sequence analysis to simultaneously screen JAK2 V617F, MPL W515L and JAK2 exon 12 mutations in 30 patients with PMF. Fifteen PMF patients (50.0%) carried JAK2 V617F mutation, and only two JAK2 V617F-negative patients (6.7%) harbored MPL W515L mutation. None had JAK2 exon 12 mutations. Furthermore, these three mutations were not detected in 50 healthy controls. MPL W515L and JAK2 V617F mutations existed in PMF patients but JAK2 exon 12 mutations not. JAK2 V617F and MPL W515L and mutations might contribute to the primary molecular pathogenesis in patients with PMF.

  8. Characteristics and clinical correlates of MPL 515W>L/K mutation in essential thrombocythemia.

    Science.gov (United States)

    Vannucchi, Alessandro M; Antonioli, Elisabetta; Guglielmelli, Paola; Pancrazzi, Alessandro; Guerini, Vittoria; Barosi, Giovanni; Ruggeri, Marco; Specchia, Giorgina; Lo-Coco, Francesco; Delaini, Federica; Villani, Laura; Finotto, Silvia; Ammatuna, Emanuele; Alterini, Renato; Carrai, Valentina; Capaccioli, Gloria; Di Lollo, Simonetta; Liso, Vincenzo; Rambaldi, Alessandro; Bosi, Alberto; Barbui, Tiziano

    2008-08-01

    Among 994 patients with essential thrombocythemia (ET) who were genotyped for the MPLW515L/K mutation, 30 patients carrying the mutation were identified (3.0%), 8 of whom also displayed the JAK2V671F mutation. MPLW515L/K patients presented lower hemoglobin levels and higher platelet counts than did wild type (wt) MPL; these differences were highly significant compared with MPLwt/JAK2V617F-positive patients. Reduced hemoglobin and increased platelet levels were preferentially associated with the W515L and W515K alleles, respectively. MPL mutation was a significant risk factor for microvessel disturbances, suggesting platelet hyperreactivity associated with constitutively active MPL; arterial thromboses were increased only in comparison to MPLwt/JAK2wt patients. MPLW515L/K patients presented reduced total and erythroid bone marrow cellularity, whereas the numbers of megakaryocytes, megakaryocytic clusters, and small-sized megakaryocytes were all significantly increased. These data indicate that MPLW515L/K mutations do not define a distinct phenotype in ET, although some differences depended on the JAK2V617F mutational status of the counterpart.

  9. Hypomethylation mediated by decreased DNMTs involves in the activation of proto-oncogene MPL in TK6 cells treated with hydroquinone.

    Science.gov (United States)

    Liu, Linhua; Ling, Xiaoxuan; Liang, Hairong; Gao, Yuting; Yang, Hui; Shao, Junli; Tang, Huanwen

    2012-03-25

    Hydroquinone (HQ), one of the most important metabolites derived from benzene, is known to be associated with acute myelogenous leukemia (AML) risk, however, its carcinogenic mechanism remains unclear. In this study, the epigenetic mechanism of HQ exposure was investigated. We characterized the epigenomic response of TK6 cells to HQ exposure, and examined the mRNA expression of DNA methyltransferases (DNMTs) including DNMT1, DNMT3a and DNMT3b, methyl-CpG-binding domain protein 2 (MBD2) and six proto-oncogenes (MPL, RAF1, MYB, MYC, ERBB2 and BRAF). Compared to the control cells, HQ exposure (2.5, 5.0, 10.0 and 20.0 μM for 48 h) resulted in the decrease of DNMTs and MBD2 expression, the global hypomethylation and increase of MPL at mRNA level. Meanwhile, most of these changes were in dose-dependent manner. Moreover, inhibition of DNMTs induced by 5-aza-2'-deoxycytidine (5-AZA), an identified DNMT inhibitor, caused more induction of MPL expression at mRNA level compared to the HQ (10.0 μM) pre-treated group. Furthermore, treatment of HQ potentially led to MPL itself hypomethylation (10.0 and 20.0 μM reduced by 47% and 44%, respectively), further revealing that the activation of proto-oncogene MPL was related to hypomethylation in its DNA sequences. In conclusion, hypomethylation, including global and specific hypomethylation, might be involved in the activation of MPL, and the hypomethylation could be induced by decreased DNMTs in TK6 cells exposed to HQ. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  10. A newly synthesized macakurzin C-derivative attenuates acute and chronic skin inflammation: The Nrf2/heme oxygenase signaling as a potential target

    Energy Technology Data Exchange (ETDEWEB)

    Akram, Muhammad [College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan (Korea, Republic of); Shin, Iljin [College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon (Korea, Republic of); Kim, Kyeong-A; Noh, Dabi [College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan (Korea, Republic of); Baek, Seung-Hoon; Chang, Sun-Young [College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon (Korea, Republic of); Kim, Hyoungsu, E-mail: hkimajou@ajou.ac.kr [College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon (Korea, Republic of); Bae, Ok-Nam, E-mail: onbae@hanyang.ac.kr [College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan (Korea, Republic of)

    2016-09-15

    Impaired immune responses in skin play a pivotal role in the development and progression of chemical-associated inflammatory skin disorders. In this study, we synthesized new flavonoid derivatives from macakurzin C, and identified in vitro and in vivo efficacy of a potent anti-inflammatory flavonoid, Compound 14 (CPD 14), with its underlying mechanisms. In lipopolysaccharide (LPS)-stimulated murine macrophages and IFN-γ/TNF-α-stimulated human keratinocytes, CPD 14 significantly inhibited the release of inflammatory mediators including nitric oxide (NO), prostaglandins, and cytokines (IC{sub 50} for NO inhibition in macrophages: 4.61 μM). Attenuated NF-κB signaling and activated Nrf2/HO-1 pathway were responsible for the anti-inflammatory effects of CPD 14. The in vivo relevance was examined in phorbol 12-myristate 13-acetate (TPA)-induced acute skin inflammation and oxazolone-induced atopic dermatitis models. Topically applied CPD 14 significantly protected both irritation- and sensitization-associated skin inflammation by suppressing the expression of inflammatory mediators. In summary, we demonstrated that a newly synthesized flavonoid, CPD 14, has potent inhibitory effects on skin inflammation, suggesting it is a potential therapeutic candidate to treat skin disorders associated with excessive inflammation. - Highlights: • An anti-inflammatory flavonoid CPD 14 was newly synthesized from macakurzin C. • CPD 14 potently inhibited inflammatory reaction in keratinocytes and macrophages. • Dermal toxicity by irritation or sensitization in rats was protected by CPD 14. • Attenuated NF-κB and activated Nrf2/HO-1 were main mechanisms of CPD 14 action.

  11. Increased frequency of co-existing JAK2 exon-12 or MPL exon-10 mutations in patients with low JAK2(V617F) allelic burden.

    Science.gov (United States)

    Nussenzveig, Roberto H; Pham, Ha T; Perkins, Sherrie L; Prchal, Josef T; Agarwal, Archana M; Salama, Mohamed E

    2016-01-01

    The frequency of co-existing JAK2(V617F)/MPL and JAK2(V617F)/JAK2 exon-12 mutations has not been previously investigated in MPNs. Poor survival was reported in primary myelofibrosis with low JAK2(V617F) allelic burden. However, mutational status of JAK2 exon-12 or MPL were not reported in these patients. This study developed a cost-effective multiplex high resolution melt assay that screens for mutations in JAK2 gene exons-12 and -14 ((V617F)) and MPL gene exon-10. Co-existing mutations with JAK2(V617F) were detected in 2.9% (6/208; two JAK2 exon-12 and four MPL exon-10) patient specimens with known JAK2(V617F) (allelic-burden range: 0.1-96.8%). Co-existing mutations were detected in specimens with MPL exon-10 mutation should be pursued.

  12. The Effect of Micro-Channels in the MPL on the Predicted Membrane Water Content in a PEMFC – A Modeling Study

    DEFF Research Database (Denmark)

    Berning, Torsten

    2014-01-01

    The micro-porous layer (MPL) in a proton exchange membrane fuel cell is frequently believed to constitute a barrier for the liquid water owing to its low hydraulic permeability compared to the porous substrate. When micro-channels are carved into the MPL on the side facing the catalyst layer, liq...

  13. Adaptor protein Lnk negatively regulates the mutant MPL, MPLW515L associated with myeloproliferative disorders.

    Science.gov (United States)

    Gery, Sigal; Gueller, Saskia; Chumakova, Katya; Kawamata, Norihiko; Liu, Liqin; Koeffler, H Phillip

    2007-11-01

    Recently, activating myeloproliferative leukemia virus oncogene (MPL) mutations, MPLW515L/K, were described in myeloproliferative disorder (MPD) patients. MPLW515L leads to activation of downstream signaling pathways and cytokine-independent proliferation in hematopoietic cells. The adaptor protein Lnk is a negative regulator of several cytokine receptors, including MPL. We show that overexpression of Lnk in Ba/F3-MPLW515L cells inhibits cytokine-independent growth, while suppression of Lnk in UT7-MPLW515L cells enhances proliferation. Lnk blocks the activation of Jak2, Stat3, Erk, and Akt in these cells. Furthermore, MPLW515L-expressing cells are more susceptible to Lnk inhibitory functions than their MPL wild-type (MPLWT)-expressing counterparts. Lnk associates with activated MPLWT and MPLW515L and colocalizes with the receptors at the plasma membrane. The SH2 domain of Lnk is essential for its binding and for its down-regulation of MPLWT and MPLW515L. Lnk itself is tyrosine-phosphorylated following thrombopoietin stimulation. Further elucidating the cellular pathways that attenuate MPLW515L will provide insight into the pathogenesis of MPD and could help develop specific therapeutic approaches.

  14. Laboratory practice guidelines for detecting and reporting JAK2 and MPL mutations in myeloproliferative neoplasms: a report of the Association for Molecular Pathology.

    Science.gov (United States)

    Gong, Jerald Z; Cook, James R; Greiner, Timothy C; Hedvat, Cyrus; Hill, Charles E; Lim, Megan S; Longtine, Janina A; Sabath, Daniel; Wang, Y Lynn

    2013-11-01

    Recurrent mutations in JAK2 and MPL genes are genetic hallmarks of BCR-ABL1-negative myeloproliferative neoplasms. Detection of JAK2 and MPL mutations has been incorporated into routine diagnostic algorithms for these diseases. This Special Article summarizes results from a nationwide laboratory survey of JAK2 and MPL mutation analysis. Based on the current practice pattern and the literature, this Special Article provides recommendations and guidelines for laboratory practice for detection of mutations in the JAK2 and MPL genes, including clinical manifestations for prompting the mutation analysis, current and recommended methodologies for testing the mutations, and standardization for reporting the test results. This Special Article also points to future directions for genomic testing in BCR-ABL1-negative myeloproliferative neoplasms. Copyright © 2013 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  15. Presence of atypical thrombopoietin receptor (MPL) mutations in triple-negative essential thrombocythemia patients.

    Science.gov (United States)

    Cabagnols, Xénia; Favale, Fabrizia; Pasquier, Florence; Messaoudi, Kahia; Defour, Jean Philippe; Ianotto, Jean Christophe; Marzac, Christophe; Le Couédic, Jean Pierre; Droin, Nathalie; Chachoua, Ilyas; Favier, Remi; Diop, M'boyba Khadija; Ugo, Valérie; Casadevall, Nicole; Debili, Najet; Raslova, Hana; Bellanné-Chantelot, Christine; Constantinescu, Stefan N; Bluteau, Olivier; Plo, Isabelle; Vainchenker, William

    2016-01-21

    Mutations in signaling molecules of the cytokine receptor axis play a central role in myeloproliferative neoplasm (MPN) pathogenesis. Polycythemia vera is mainly related to JAK2 mutations, whereas a wider mutational spectrum is detected in essential thrombocythemia (ET) with mutations in JAK2, the thrombopoietin (TPO) receptor (MPL), and the calreticulin (CALR) genes. Here, we studied the mutational profile of 17 ET patients negative for JAK2V617F, MPLW515K/L, and CALR mutations, using whole-exome sequencing and next-generation sequencing (NGS) targeted on JAK2 and MPL. We found several signaling mutations including JAK2V617F at very low allele frequency, 1 homozygous SH2B3 mutation, 1 MPLS505N, 1 MPLW515R, and 2 MPLS204P mutations. In the remaining patients, 4 presented a clonal and 7 a polyclonal hematopoiesis, suggesting that certain triple-negative ETs are not MPNs. NGS on 26 additional triple-negative ETs detected only 1 MPLY591N mutation. Functional studies on MPLS204P and MPLY591N revealed that they are weak gain-of-function mutants increasing MPL signaling and conferring either TPO hypersensitivity or independence to expressing cells, but with a low efficiency. Further studies should be performed to precisely determine the frequency of MPLS204 and MPLY591 mutants in a bigger cohort of MPN. © 2016 by The American Society of Hematology.

  16. The mutation profile of JAK2, MPL and CALR in Mexican patients with Philadelphia chromosome-negative myeloproliferative neoplasms.

    Science.gov (United States)

    Labastida-Mercado, Nancy; Galindo-Becerra, Samantha; Garcés-Eisele, Javier; Colunga-Pedraza, Perla; Guzman-Olvera, Valeria; Reyes-Nuñez, Virginia; Ruiz-Delgado, Guillermo J; Ruiz-Argüelles, Guillermo J

    2015-03-01

    By using molecular markers, it is possible to gain information on both the classification and etiopathogenesis of chronic myeloproliferative neoplasias (MPN). In a group of 27 Mexican mestizo patients with MPNs, we studied seven molecular markers: the BCR/ABL1 fusion gene, the JAK2 V617F mutation, the JAK2 exon 12 mutations, the MPL W515L mutation, the MPL W515K mutation, and the calreticulin (CALR) exon 9 deletion or insertion. Patients with the BCR/ABL1 fusion gene were excluded. We studied 14 patients with essential thrombocythemia (ET), eight with polycythemia vera (PV), four with primary myelofibrosis (MF), and one with undifferentiated MPN. We found twelve individuals with the JAK2 V617F mutation; five of them had been clinically classified as PV, five as ET, and one as MF. One patient with the MPL W515L was identified with a clinical picture of ET. Five patients with the CALR mutation were identified, four ET and one MF. No individuals with either the MPL W515K mutation or the JAK2 exon 12 mutations were identified. The most consistent relationship was that between PV and the JAK2 V617F mutation (p=.01). Despite its small size, the study shows much less prevalence of JAK2 mutation in PV, ET and MF, which does not match international data. Copyright © 2015 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

  17. Mouse prenatal platelet-forming lineages share a core transcriptional program but divergent dependence on MPL.

    Science.gov (United States)

    Potts, Kathryn S; Sargeant, Tobias J; Dawson, Caleb A; Josefsson, Emma C; Hilton, Douglas J; Alexander, Warren S; Taoudi, Samir

    2015-08-06

    The thrombopoietic environment of the neonate is established during prenatal life; therefore, a comprehensive understanding of platelet-forming cell development during embryogenesis is critical to understanding the etiology of early-onset thrombocytopenia. The recent discovery that the first platelet-forming cells of the conceptus are not megakaryocytes (MKs) but diploid platelet-forming cells (DPFCs) revealed a previously unappreciated complexity in thrombopoiesis. This raises important questions, including the following. When do conventional MKs appear? Do pathogenic genetic lesions of adult MKs affect DPFCs? What role does myeloproliferative leukemia virus (MPL), a key regulator of adult megakaryopoiesis, play in prenatal platelet-forming lineages? We performed a comprehensive study to determine the spatial and temporal appearance of prenatal platelet-forming lineages. We demonstrate that DPFCs originate in the yolk sac and then rapidly migrate to other extra- and intraembryonic tissues. Using gene disruption models of Gata1 and Nfe2, we demonstrate that perturbing essential adult MK genes causes an analogous phenotype in the early embryo before the onset of hematopoietic stem/progenitor cell-driven (definitive) hematopoiesis. Finally, we present the surprising finding that DPFC and MK commitment from their respective precursors is MPL independent in vivo but that completion of MK differentiation and establishment of the prenatal platelet mass is dependent on MPL expression. © 2015 by The American Society of Hematology.

  18. Concomitant BCR-ABL1 positive chronic myelogenous leukemia emerging in a patient with MPL W515L associated primary myelofibrosis

    Directory of Open Access Journals (Sweden)

    Juan C. Gomez-Gelvez, MD

    2016-03-01

    Full Text Available Myeloproliferative neoplasms (MPNs are clonal hematopoietic stem cell disorders characterized by proliferation of one or more cell lineages in the bone marrow. At present, the main criterion in the 2008 World Health Organization classification of MPNs is the presence of an underlying genetic abnormality. These mutations are generally mutually exclusive except for rare reports in the literature. We report for the first time a detailed analysis of the clinical, histologic and cytogenetic/molecular features of a patient who initially presented with MPL W515L positive primary myelofibrosis and over the course of five years developed an MPN associated with both BCR-ABL1 and MPL W515L mutation. We discuss the diagnostic challenges and therapeutic implications of concomitant BCR-ABL1 translocation with MPL W515L mutation. Multiple genetic alterations may simultaneously coexist in patients exhibiting features of myeloproliferative disorders.

  19. The Prevalence of JAK2, MPL, and CALR Mutations in Chinese Patients With BCR-ABL1-Negative Myeloproliferative Neoplasms.

    Science.gov (United States)

    Lin, Yani; Liu, Enbin; Sun, Qi; Ma, Jiao; Li, QingHua; Cao, Zeng; Wang, Jun; Jia, Yujiao; Zhang, Hongju; Song, Zhen; Ai, Xiaofei; Shi, Lihui; Feng, Xiaofang; Li, Chenwei; Wang, Jianxiang; Ru, Kun

    2015-07-01

    To evaluate the mutation frequency of JAK2 V617F, JAK2 exon 12, MPL exon 10, and CALR exon 9 and the value of the combined tests in the diagnosis of BCR-ABL1-negative myeloproliferative neoplasms (MPNs). In the current study, mutations of JAK2 V617F, JAK2 exon 12, MPL exon 10, and CALR exon 9 were analyzed in 929 Chinese patients with BCR-ABL1-negative MPN, including 234 cases of polycythemia vera (PV), 428 ETs, 187 PMFs, and 80 unclassifiable MPNs (MPN-Us). Our result showed that the positive rate of any of four mutations in patients with PV, ET, PMF, and MPN-U was 89.3%, 83.4%, 87.2%, and 77.5%, respectively, which significantly improved the diagnostic rate, especially in ET and PMF. Meanwhile, we also found that the patients without any of four mutations were younger than those with one or more mutations. Unexpectedly, the coexistence of JAK2 V617F and CALR exon 9 was identified in six (0.6%) patients, and JAK2 V617F and MPL exon 10 were present simultaneously in two (0.2%) patients. In addition, we also identified several novel mutation types in CALR exon 9. The combined genetic tests of JAK2 V617F, JAK2 exon 12, MPL exon 10, and CALR exon 9 help improve the diagnostic rate for BCR-ABL1-negative MPN. Copyright© by the American Society for Clinical Pathology.

  20. Potentiating Effects of MPL on DSPC Bearing Cationic Liposomes Promote Recombinant GP63 Vaccine Efficacy: High Immunogenicity and Protection

    Science.gov (United States)

    Mazumder, Saumyabrata; Maji, Mithun; Ali, Nahid

    2011-01-01

    Background Vaccines that activate strong specific Th1-predominant immune responses are critically needed for many intracellular pathogens, including Leishmania. The requirement for sustained and efficient vaccination against leishmaniasis is to formulate the best combination of immunopotentiating adjuvant with the stable antigen (Ag) delivery system. The aim of the present study is to evaluate the effectiveness of an immunomodulator on liposomal Ag through subcutaneous (s.c.) route of immunization, and its usefulness during prime/boost against visceral leishmaniasis (VL) in BALB/c mice. Methodology/Principal Findings Towards this goal, we formulated recombinant GP63 (rGP63)-based vaccines either with monophosphoryl lipid A-trehalose dicorynomycolate (MPL-TDM) or entrapped within cationic liposomes or both. Combinatorial administration of liposomes with MPL-TDM during prime confers activation of dendritic cells, and induces an early robust T cell response. To investigate whether the combined formulation is required for optimum immune response during boost as well, we chose to evaluate the vaccine efficacy in mice primed with combined adjuvant system followed by boosting with either rGP63 alone, in association with MPL-TDM, liposomes or both. We provide evidences that the presence of either liposomal rGP63 or combined formulations during boost is necessary for effective Th1 immune responses (IFN-γ, IL-12, NO) before challenge infection. However, boosting with MPL-TDM in conjugation with liposomal rGP63 resulted in a greater number of IFN-γ producing effector T cells, significantly higher levels of splenocyte proliferation, and Th1 responses compared to mice boosted with liposomal rGP63, after virulent Leishmania donovani (L. donovani) challenge. Moreover, combined formulations offered superior protection against intracellular amastigote replication in macrophages in vitro, and hepatic and splenic parasite load in vivo. Conclusion Our results define the

  1. Spectroscopic and structural study of the newly synthesized heteroligand complex of copper with creatinine and urea.

    Science.gov (United States)

    Gangopadhyay, Debraj; Singh, Sachin Kumar; Sharma, Poornima; Mishra, Hirdyesh; Unnikrishnan, V K; Singh, Bachcha; Singh, Ranjan K

    2016-02-05

    Study of copper complex of creatinine and urea is very important in life science and medicine. In this paper, spectroscopic and structural study of a newly synthesized heteroligand complex of copper with creatinine and urea has been discussed. Structural studies have been carried out using DFT calculations and spectroscopic analyses were carried out by FT-IR, Raman, UV-vis absorption and fluorescence techniques. The copper complex of creatinine and the heteroligand complex were found to have much increased water solubility as compared to pure creatinine. The analysis of FT-IR and Raman spectra helps to understand the coordination properties of the two ligands and to determine the probable structure of the heteroligand complex. The LIBS spectra of the heteroligand complex reveal that the complex is free from other metal impurities. UV-visible absorption spectra and the fluorescence emission spectra of the aqueous solution of Cu-Crn-urea heteroligand complex at different solute concentrations have been analyzed and the complex is found to be rigid and stable in its monomeric form at very low concentrations. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. The Human Nuclear Exosome Targeting Complex Is Loaded onto Newly Synthesized RNA to Direct Early Ribonucleolysis

    Directory of Open Access Journals (Sweden)

    Michal Lubas

    2015-01-01

    Full Text Available The RNA exosome complex constitutes the major nuclear eukaryotic 3′-5′ exonuclease. Outside of nucleoli, the human nucleoplasmic exosome is directed to some of its substrates by the nuclear exosome targeting (NEXT complex. How NEXT targets RNA has remained elusive. Using an in vivo crosslinking approach, we report global RNA binding sites of RBM7, a key component of NEXT. RBM7 associates broadly with RNA polymerase II-derived RNA, including pre-mRNA and short-lived exosome substrates such as promoter upstream transcripts (PROMPTs, enhancer RNAs (eRNAs, and 3′-extended products from snRNA and replication-dependent histone genes. Within pre-mRNA, RBM7 accumulates at the 3′ ends of introns, and pulse-labeling experiments demonstrate that RBM7/NEXT defines an early exosome-targeting pathway for 3′-extended snoRNAs derived from such introns. We propose that RBM7 is generally loaded onto newly synthesized RNA to accommodate exosome action in case of available unprotected RNA 3′ ends.

  3. Newly synthesized proteins in seminiferous intertubular and intratubular compartments of the rat testis

    International Nuclear Information System (INIS)

    Shabanowitz, R.B.; Kierszenbaum, A.L.

    1986-01-01

    Two-dimensional gel electrophoresis combined with autoradiography and Western blot procedures have been used to characterize newly synthesized proteins in testicular intertubular fluid (TIF) and seminiferous tubular fluid (SNF). Fluids were collected following in vivo and in vitro intratesticular injection of [ 35 S]methionine into control and hypophysectomized adult rats. A discrete number of [ 35 S]methionine-labeled proteins were detected within TIF and SNF. Their presence and relative abundance varied according to in vivo and in vitro labeling conditions. While two major blood plasma proteins, albumin and transferrin, were radioactively labeled after in vivo labeling, these two proteins were insignificantly labeled in samples collected after in vitro labeling. Three acidic proteins, possibly secreted by Sertoli cells (Mr = 72,000, 45,000 and 35,000), were more abundant in TIF samples collected after in vitro [ 35 S]methionine labeling than after in vivo labeling. Incubated seminiferous tubules and TIF of hypophysectomized rats showed a decrease in [35S]methionine-labeling intensity of the Mr = 72,000 acidic protein, possibly reflecting changes in the seminiferous epithelium caused by pituitary hormonal deprivation. Autoradiographs of TIF and most remarkably, of SNF, showed many protein spots that suggested cell breakage and leakage during sample collection. Results of this study suggest that most albumin and transferrin found in TIF and SNF have an extratesticular origin and that proteins secreted by the Sertoli cell can gain access to both TIF and SNF

  4. P5 HER2/neu-derived peptide conjugated to liposomes containing MPL adjuvant as an effective prophylactic vaccine formulation for breast cancer.

    Science.gov (United States)

    Shariat, Sheida; Badiee, Ali; Jalali, Seyed Amir; Mansourian, Mercedeh; Yazdani, Mona; Mortazavi, Seyed Alireza; Jaafari, Mahmoud Reza

    2014-12-01

    Vaccines containing synthetic peptides derived from tumor-associated antigens (TAA) can elicit potent cytotoxic T lymphocyte (CTL) response if they are formulated in an optimal vaccine delivery system. The aim of this study was to develop a simple and effective lipid-based vaccine delivery system using P5 HER2/neu-derived peptide conjugated to Maleimide-PEG2000-DSPE. The conjugated lipid was then incorporated into liposomes composed of DMPC:DMPG:Chol:DOPE containing Monophosphoryl lipid A (MPL) (Lip-DOPE-P5-MPL). Different liposome formulations were prepared and characterized for their physicochemical properties. To evaluate anti-tumoral efficacy, BALB/c mice were immunized subcutaneously 3 times in two-week intervals and the generated immune response was studied. The results demonstrated that Lip-DOPE-P5-MPL induced a significantly higher IFN-γ production by CD8+ T cells intracellularly which represents higher CTL response in comparison with other control formulations. CTL response induced by this formulation caused the lowest tumor size and the longest survival time in a mice model of TUBO tumor. The encouraging results achieved by Lip-DOPE-P5-MPL formulation could make it a promising candidate in developing effective vaccines against Her2 positive breast cancers. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. The thrombopoietin/MPL/Bcl-xL pathway is essential for survival and self-renewal in human preleukemia induced by AML1-ETO

    Science.gov (United States)

    Chou, Fu-Sheng; Griesinger, Andrea; Wunderlich, Mark; Lin, Shan; Link, Kevin A.; Shrestha, Mahesh; Goyama, Susumu; Mizukawa, Benjamin; Shen, Shuhong; Marcucci, Guido

    2012-01-01

    AML1-ETO (AE) is a fusion product of translocation (8;21) that accounts for 40% of M2 type acute myeloid leukemia (AML). In addition to its role in promoting preleukemic hematopoietic cell self-renewal, AE represses DNA repair genes, which leads to DNA damage and increased mutation frequency. Although this latter function may promote leukemogenesis, concurrent p53 activation also leads to an increased baseline apoptotic rate. It is unclear how AE expression is able to counterbalance this intrinsic apoptotic conditioning by p53 to promote survival and self-renewal. In this report, we show that Bcl-xL is up-regulated in AE cells and plays an essential role in their survival and self-renewal. Further investigation revealed that Bcl-xL expression is regulated by thrombopoietin (THPO)/MPL-signaling induced by AE expression. THPO/MPL-signaling also controls cell cycle reentry and mediates AE-induced self-renewal. Analysis of primary AML patient samples revealed a correlation between MPL and Bcl-xL expression specifically in t(8;21) blasts. Taken together, we propose that survival signaling through Bcl-xL is a critical and intrinsic component of a broader self-renewal signaling pathway downstream of AML1-ETO–induced MPL. PMID:22337712

  6. VEGF controls lung Th2 inflammation via the miR-1–Mpl (myeloproliferative leukemia virus oncogene)–P-selectin axis

    Science.gov (United States)

    Vasavada, Hema; Zhang, Jian-ge; Ahangari, Farida; Niu, Naiqian; Liu, Qing; Lee, Chun Geun; Cohn, Lauren

    2013-01-01

    Asthma, the prototypic Th2-mediated inflammatory disorder of the lung, is an emergent disease worldwide. Vascular endothelial growth factor (VEGF) is a critical regulator of pulmonary Th2 inflammation, but the underlying mechanism and the roles of microRNAs (miRNAs) in this process have not been defined. Here we show that lung-specific overexpression of VEGF decreases miR-1 expression in the lung, most prominently in the endothelium, and a similar down-regulation occurs in lung endothelium in Th2 inflammation models. Intranasal delivery of miR-1 inhibited inflammatory responses to ovalbumin, house dust mite, and IL-13 overexpression. Blocking VEGF inhibited Th2-mediated lung inflammation, and this was restored by antagonizing miR-1. Using mRNA arrays, Argonaute pull-down assays, luciferase expression assays, and mutational analysis, we identified Mpl as a direct target of miR-1 and showed that VEGF controls the expression of endothelial Mpl during Th2 inflammation via the regulation of miR-1. In vivo knockdown of Mpl inhibited Th2 inflammation and indirectly inhibited the expression of P-selectin in lung endothelium. These experiments define a novel VEGF–miR-1–Mpl–P-selectin effector pathway in lung Th2 inflammation and herald the utility of miR-1 and Mpl as potential therapeutic targets for asthma. PMID:24043765

  7. Newly Synthesized Doxorubicin Complexes with Selected Metals—Synthesis, Structure and Anti-Breast Cancer Activity

    Directory of Open Access Journals (Sweden)

    Agata Jabłońska-Trypuć

    2017-07-01

    Full Text Available Doxorubicin (DOX is very effective chemotherapeutic agent, however it has several major drawbacks. Therefore the motivation for developing novel drug complexes as anticancer agents with different mechanism of action has arisen. The aim of the present study was to evaluate the influence of newly synthesized DOX complexes with selected metals (Mg, Mn, Co, Ni, Fe, Cu, Zn on apoptosis, cell cycle, viability, proliferation and cytotoxicity in the breast cancer cell line MCF-7. Complexation of DOX with metals has likewise been the subject of our research. The current work showed that the tested bivalent metals at a given pH condition formed metal:DOX complexes in a ratio of 2:1, while iron complexes with DOX in a ratio of 3:1. The studies also showed that selected metal-DOX complexes (Mg-DOX, Mn-DOX, Ni-DOX at 0.5 µM concentration significantly decreased cell viability and proliferation, however they increased caspase 7 activity. Results also indicated that studied metal-DOX complexes showed high cytotoxicity in MCF-7 cells. Therefore they were chosen for cell cycle check-points and apoptosis/necrosis analysis studied by flow cytometry. Obtained results suggest that doxorubicin complexed by specified metals can be considered as a potential anti-breast cancer agent, which is characterized by a higher efficacy than a parent drug.

  8. Measurements at FP3 in support of pecan scientific objectives using MPL-111 lidar

    Science.gov (United States)

    Pozsonyi, Kristen; Midzak, Natalie; Prestine, Christina; Clark, Richard

    2018-04-01

    This paper will report on the data collected by a Sigma Space Micropulse Lidar (MPL-111), and how these measurements, when integrated with other data, helps to inform our analysis of two cases of the Great Plains nocturnal Low-Level Jet (LLJ) in the vicinity of FP3.

  9. A recombinant anchorless respiratory syncytial virus (RSV) fusion (F) protein/monophosphoryl lipid A (MPL) vaccine protects against RSV-induced replication and lung pathology.

    Science.gov (United States)

    Blanco, Jorge C G; Boukhvalova, Marina S; Pletneva, Lioubov M; Shirey, Kari Ann; Vogel, Stefanie N

    2014-03-14

    We previously demonstrated that the severe cytokine storm and pathology associated with RSV infection following intramuscular vaccination of cotton rats with FI-RSV Lot 100 could be completely abolished by formulating the vaccine with the mild TLR4 agonist and adjuvant, monophosphoryl lipid A (MPL). Despite this significant improvement, the vaccine failed to blunt viral replication in the lungs. Since MPL is a weak TLR4 agonist, we hypothesized that its adjuvant activity was mediated by modulating the innate immune response of respiratory tract resident macrophages. Therefore, we developed a new vaccine preparation with purified, baculovirus expressed, partially purified, anchorless RSV F protein formulated with synthetic MPL that was administered to cotton rats intranasally, followed by an intradermal boost. This novel formulation and heterologous "prime/boost" route of administration resulted in decreased viral titers compared to that seen in animals vaccinated with F protein alone. Furthermore, animals vaccinated by this route showed no evidence of enhanced lung pathology upon RSV infection. This indicates that MPL acts as an immune modulator that protects the host from vaccine-enhanced pathology, and reduces RSV replication in the lower respiratory tract when administered by a heterologous prime/boost immunization regimen. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Measurements at FP3 in support of pecan scientific objectives using MPL-111 lidar

    Directory of Open Access Journals (Sweden)

    Pozsonyi Kristen

    2018-01-01

    Full Text Available This paper will report on the data collected by a Sigma Space Micropulse Lidar (MPL-111, and how these measurements, when integrated with other data, helps to inform our analysis of two cases of the Great Plains nocturnal Low-Level Jet (LLJ in the vicinity of FP3.

  11. Fluorescence quenching of newly synthesized biologically active coumarin derivative by aniline in binary solvent mixtures

    International Nuclear Information System (INIS)

    Evale, Basavaraj G.; Hanagodimath, S.M.

    2009-01-01

    The fluorescence quenching of newly synthesized coumarin (chromen-2-one) derivative, 4-(5-methyl-3-furan-2-yl-benzofuran-2-yl)-7-methyl-chromen-2-one (MFBMC) by aniline in different solvent mixtures of benzene and acetonitrile was determined at room temperature (296 K) by steady-state fluorescence measurements. The quenching is found to be appreciable and positive deviation from linearity was observed in the Stern-Volmer (S-V) plots in all the solvent mixtures. This could be explained by static and dynamic quenching models. The positive deviation in the S-V plot is interpreted in terms of ground-state complex formation model and sphere of action static quenching model. Various rate parameters for the fluorescence quenching process have been determined by using the modified Stern-Volmer equation. The sphere of action static quenching model agrees very well with experimental results. The dependence of Stern-Volmer constant K SV , on dielectric constant ε of the solvent mixture suggests that the fluorescence quenching is diffusion-limited. Further with the use of finite sink approximation model, it is concluded that these bimolecular quenching reactions are diffusion-limited. Using lifetime (τ o ) data, the distance parameter R' and mutual diffusion coefficient D are estimated independently.

  12. Thrombopoietin/MPL signaling confers growth and survival capacity to CD41-positive cells in a mouse model of Evi1 leukemia.

    Science.gov (United States)

    Nishikawa, Satoshi; Arai, Shunya; Masamoto, Yosuke; Kagoya, Yuki; Toya, Takashi; Watanabe-Okochi, Naoko; Kurokawa, Mineo

    2014-12-04

    Ecotropic viral integration site 1 (Evi1) is a transcription factor that is highly expressed in hematopoietic stem cells and is crucial for their self-renewal capacity. Aberrant expression of Evi1 is observed in 5% to 10% of de novo acute myeloid leukemia (AML) patients and predicts poor prognosis, reflecting multiple leukemogenic properties of Evi1. Here, we show that thrombopoietin (THPO) signaling is implicated in growth and survival of Evi1-expressing cells using a mouse model of Evi1 leukemia. We first identified that the expression of megakaryocytic surface molecules such as ITGA2B (CD41) and the THPO receptor, MPL, positively correlates with EVI1 expression in AML patients. In agreement with this finding, a subpopulation of bone marrow and spleen cells derived from Evi1 leukemia mice expressed both CD41 and Mpl. CD41(+) Evi1 leukemia cells induced secondary leukemia more efficiently than CD41(-) cells in a serial bone marrow transplantation assay. Importantly, the CD41(+) cells predominantly expressing Mpl effectively proliferated and survived on OP9 stromal cells in the presence of THPO via upregulating BCL-xL expression, suggesting an essential role of the THPO/MPL/BCL-xL cascade in enhancing the progression of Evi1 leukemia. These observations provide a novel aspect of the diverse functions of Evi1 in leukemogenesis. © 2014 by The American Society of Hematology.

  13. Vasorelaxant Effect of a Newly Synthesized Dihydropyridine Ethyl Ester (DHPEE on Rat Thoracic Aorta: Dual Mechanism of Action

    Directory of Open Access Journals (Sweden)

    Hossein Babaei

    2011-06-01

    Full Text Available Introduction: DHPEE is a newly synthesized compound by merging the key structural elements in an angiotensin receptor blocker (Telmisartan with key structural elements in 1,4- dihydropyridine calcium channel blocker (Nifedipine. In this study, we examined dual calcium channel blocking and AT1 antagonist activity for DHPEE. Methods: The functional inhibitory characteristics of DHPEE were studied in vitro in rat thoracic aorta preparations precontracted by phenylephrine (1µM or KCl (80µM or Ang II in normal or calcium-free solutions. Results: Concentration–dependent significant relaxation was observed in aortic rings precontracted with phenylephrine, KCl or Ang II. The tension increment produced by increasing external calcium was also reduced by DHPEE. DHPEE caused a marked decrease in the maximal contractile response of the vasoactive agents and shifted their concentration-response curves to the right. Conclusion: DHPEE possesses dual characteristics and cause vasorelaxation by blocking the L-type calcium channels and blocking Ang II receptors (AT1 in rat aortic smooth muscle.

  14. Efficacy and tolerability of short-term specific immunotherapy with pollen allergoids adjuvanted by monophosphoryl lipid A (MPL) for children and adolescents.

    Science.gov (United States)

    Drachenberg, K J; Heinzkill, M; Urban, E; Woroniecki, S R

    2003-01-01

    Specific immunotherapy (SIT) with pollen allergoids formulated with the Th1-inducing adjuvant 3-deacylated monophosphoryl lipid A (MPL adjuvant, Corixa) has shown good efficacy and tolerability in the treatment of pollen allergies in adults. The aim of this study was to evaluate this treatment in children and adolescents aged 6-17 years old who were sensitive to grass/rye or tree pollens. An open, multicenter study was performed using 90 children and adolescents. The patients received four subcutaneous injections of grass/rye (n = 64) or tree pollen allergoids (n = 26) adsorbed to L-tyrosine and containing MPL adjuvant. Efficacy was measured by symptom and medication scoring, skin prick test reactivity and IgG/IgE antibody responses. Tolerability was monitored by recording adverse events. Both grass/rye and tree pollen treatment groups showed significant reductions in symptom scores and anti-allergic medication use compared with the previous pollen seasons (p allergoids adsorbed to L-tyrosine and with MPL adjuvant was shown to be effective with good tolerability. The treatment compared favorably with previous studies in adults.

  15. Functional analysis of single amino-acid mutations in the thrombopoietin-receptor Mpl underlying congenital amegakaryocytic thrombocytopenia

    NARCIS (Netherlands)

    Tijssen, Marloes R.; di Summa, Franca; van den Oudenrijn, Sonja; Zwaginga, Jaap Jan; van der Schoot, C. Ellen; Voermans, Carlijn; de Haas, Masja

    2008-01-01

    Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare disorder that presents with severe thrombocytopenia and absence of megakaryocytes in the bone marrow. The disease may develop into bone marrow aplasia. Genetic defects in the gene encoding the thrombopoietin (Tpo) receptor, MPL, are the

  16. Deposition of newly synthesized histones: new histones H2A and H2B do not deposit in the same nucleosome with new Histones H3 and H4

    International Nuclear Information System (INIS)

    Jackson, V.

    1987-01-01

    The authors have developed procedures to study histone-histone interactions during the deposition of histones in replicating cells. Cells are labeled for 60 min with dense amino acids, and subsequently, the histones within the nucleosomes are cross-linked into an octameric complex with formaldehyde. These complexes are sedimented to equilibrium in density gradients and octamer and dioctamer complexes separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. With reversal of the cross-link, the distribution of the individual density-labeled histones in the octamer is determined. Newly synthesized H3 and H4 deposits as a tetramer and are associated with old H2A and H2B. Newly synthesized H2A and H2B deposit as a dimer associated with old H2A, H2B, H3, and H4. The significance of these results with respect to the dynamics of histone interactions in the nucleus is discussed. Control experiments are presented to test for artifactual formation of these complexes during preparative procedures. In addition, reconstitution experiments were performed to demonstrate that the composition of these octameric complexes can be determined from their distribution of density gradients

  17. The attenuated inflammation of MPL is due to the lack of CD14-dependent tight dimerization of the TLR4/MD2 complex at the plasma membrane.

    Science.gov (United States)

    Tanimura, Natsuko; Saitoh, Shin-Ichiroh; Ohto, Umeharu; Akashi-Takamura, Sachiko; Fujimoto, Yukari; Fukase, Koichi; Shimizu, Toshiyuki; Miyake, Kensuke

    2014-06-01

    TLR4/MD-2 senses lipid A, activating the MyD88-signaling pathway on the plasma membrane and the TRIF-signaling pathway after CD14-mediated TLR4/MD-2 internalization into endosomes. Monophosphoryl lipid A (MPL), a detoxified derivative of lipid A, is weaker than lipid A in activating the MyD88-dependent pathway. Little is known, however, about mechanisms underlying the attenuated activation of MyD88-dependent pathways. We here show that MPL was impaired in induction of CD14-dependent TLR4/MD-2 dimerization compared with lipid A. Impaired TLR4/MD-2 dimerization decreased CD14-mediated TNFα production. In contrast, MPL was comparable to lipid A in CD14-independent MyD88-dependent TNFα production and TRIF-dependent responses including cell surface CD86 up-regulation and IFNβ induction. Although CD86 up-regulation is dependent on TRIF signaling, it was induced by TLR4/MD-2 at the plasma membrane. These results revealed that the attenuated MPL responses were due to CD14-initiated responses at the plasma membrane, but not just to responses initiated by MyD88, that is, MPL was specifically unable to induce CD14-dependent TLR4/MD-2 dimerization that selectively enhances MyD88-mediated responses at the plasma membrane. © The Japanese Society for Immunology. 2013. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Global transgenerational gene expression dynamics in two newly synthesized allohexaploid wheat (Triticum aestivum lines

    Directory of Open Access Journals (Sweden)

    Qi Bao

    2012-01-01

    Full Text Available Abstract Background Alteration in gene expression resulting from allopolyploidization is a prominent feature in plants, but its spectrum and extent are not fully known. Common wheat (Triticum aestivum was formed via allohexaploidization about 10,000 years ago, and became the most important crop plant. To gain further insights into the genome-wide transcriptional dynamics associated with the onset of common wheat formation, we conducted microarray-based genome-wide gene expression analysis on two newly synthesized allohexaploid wheat lines with chromosomal stability and a genome constitution analogous to that of the present-day common wheat. Results Multi-color GISH (genomic in situ hybridization was used to identify individual plants from two nascent allohexaploid wheat lines between Triticum turgidum (2n = 4x = 28; genome BBAA and Aegilops tauschii (2n = 2x = 14; genome DD, which had a stable chromosomal constitution analogous to that of common wheat (2n = 6x = 42; genome BBAADD. Genome-wide analysis of gene expression was performed for these allohexaploid lines along with their parental plants from T. turgidum and Ae. tauschii, using the Affymetrix Gene Chip Wheat Genome-Array. Comparison with the parental plants coupled with inclusion of empirical mid-parent values (MPVs revealed that whereas the great majority of genes showed the expected parental additivity, two major patterns of alteration in gene expression in the allohexaploid lines were identified: parental dominance expression and non-additive expression. Genes involved in each of the two altered expression patterns could be classified into three distinct groups, stochastic, heritable and persistent, based on their transgenerational heritability and inter-line conservation. Strikingly, whereas both altered patterns of gene expression showed a propensity of inheritance, identity of the involved genes was highly stochastic, consistent with the involvement of diverse Gene Ontology (GO

  19. F104S c-Mpl responds to a transmembrane domain-binding thrombopoietin receptor agonist: proof of concept that selected receptor mutations in congenital amegakaryocytic thrombocytopenia can be stimulated with alternative thrombopoietic agents.

    Science.gov (United States)

    Fox, Norma E; Lim, Jihyang; Chen, Rose; Geddis, Amy E

    2010-05-01

    To determine whether specific c-Mpl mutations might respond to thrombopoietin receptor agonists. We created cell line models of type II c-Mpl mutations identified in congenital amegakaryocytic thrombocytopenia. We selected F104S c-Mpl for further study because it exhibited surface expression of the receptor. We measured proliferation of cell lines expressing wild-type or F104S c-Mpl in response to thrombopoietin receptor agonists targeting the extracellular (m-AMP4) or transmembrane (LGD-4665) domains of the receptor by 1-methyltetrazole-5-thiol assay. We measured thrombopoietin binding to the mutant receptor using an in vitro thrombopoietin uptake assay and identified F104 as a potentially critical residue for the interaction between the receptor and its ligand by aligning thrombopoietin and erythropoietin receptors from multiple species. Cells expressing F104S c-Mpl proliferated in response to LGD-4665, but not thrombopoietin or m-AMP4. Compared to thrombopoietin, LGD-4665 stimulates signaling with delayed kinetics in both wild-type and F104S c-Mpl-expressing cells. Although F104S c-Mpl is expressed on the cell surface in our BaF3 cell line model, the mutant receptor does not bind thrombopoietin. Comparison to the erythropoietin receptor suggests that F104 engages in hydrogen-bonding interactions that are critical for binding to thrombopoietin. These findings suggest that a small subset of patients with congenital amegakaryocytic thrombocytopenia might respond to treatment with thrombopoietin receptor agonists, but that responsiveness will depend on the type of mutation and agonist used. We postulate that F104 is critical for thrombopoietin binding. The kinetics of signaling in response to a transmembrane domain-binding agonist are delayed in comparison to thrombopoietin. 2010 ISEH Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

  20. Essential oils-oriented fenvalerate analogues: syntheses, characterization and biological evaluation

    International Nuclear Information System (INIS)

    Su, H.; Li, H.

    2016-01-01

    A series of essential oils oriented ester derivatives have been designed, synthesized and characterized based on the skeleton of fenvalerate. The preliminary bioassay results indicated that some of the newly synthesized compounds showed better insecticidal activities against Pyrausta nubilalis and Heliothis armigera than that of the control trans-prallethrin chloride. (author)

  1. Multi-wavelength spectrophotometric determination of acidity constant of some newly synthesized Schiff bases and their QSPR study

    Science.gov (United States)

    Hemmateenejad, Bahram; Emami, Leila; Sharghi, Hashem

    2010-01-01

    The acidity constants of some newly synthesized Schiff base derivatives were determined by hard-model based multivariate data analysis of the spectrophotometric data in the course of pH-metric titration in 50% (v/v) methanol-water binary solvent. The employed data analysis method was also able to extract the pure spectra and pH-dependent concentration profiles of the acid-base species. The molecules that possess different substituents (both electron donating and withdrawing) on the ortho-, meta- and para-positions of one of the phenyl ring showed variable acidity constants ranging from 8.77 to 11.07 whereas the parent molecule had an acidity constant of 10.25. To investigate the quantitative effects of changing of substitution pattern on the acidity constant, a quantitative structure-property relation analysis was conducted using substituent constants and molecular descriptor. Some models with high statistical quality (measured by cross-validation Q2) were obtained. It was found that the acidity constant of the studied molecules in the methanol-water mixed solvent not only is affected by electronic features of the solutes but also by the lipophilic interaction between methanol part of solvent and the deprotonated solutes.

  2. In vitro studies of immunoglobulin heavy-chain binding protein (BiP, GRP78). Interactions of BiP with newly synthesized proteins and adenine nucleotides

    International Nuclear Information System (INIS)

    Kassenbrock, C.K.

    1988-01-01

    Here we examine the interaction of BiP with newly synthesized polypeptides in an in vitro protein translations-translocation system. We find that BiP forms tight complexes with nonglycosylated yeast invertase and incorrectly disulfide-bonded prolactin but not with glycosylated invertase or correctly disulfide-bonded prolactin. Moreover, BiP associates detectably only with completed chains of prolactin, not with chains undergoing synthesis. We conclude that BiP recognizes and binds with high affinity to aberrantly folded or aberrantly glycosylated polypeptides in vitro, but not to all nascent chains as they are folding. BiP also binds APT and can be purified by APT affinity chromatography. We show that submicromolar levels of ATP or ADP decrease the rate of absorption of 125 I-BiP to nitrocellulose filters coated with protein or nonionic detergents. ATP and ADP also protect portions of BiP from proteolytic degradation. In contrast, micromolar levels of AMP increase the rate of adsorption and the rate of proteolytic degradation of BiP. We also show that an ATPase activity co-purifies with BiP, but its slow turnover number suggests a regulatory, rather than a functional role. The BiP-associated ATPase shares several properties with the related cytoplasmic protein, HSC70/clathrin uncoating ATPase

  3. Calreticulin and Jak2 as Chaperones for MPL: Insights into MPN Pathogenesis

    Science.gov (United States)

    2017-11-01

    neoplasms (MPNs) as classified by the world health organization. One of the biggest challenges is to understand how Jak2, MPL and CALR mutant proteins...7/Tpo cells using genetic engineering. The left panel in Fig.2 show the presence of a sub- population of UT-7/Tpo cells that express the T1 mutant...lower panels) cells at day 5 post-editing. The homozygous K39N mutation could be found in both populations , as expected. However, in the edited

  4. [Clinical significance of JAK2、CALR and MPL gene mutations in 1 648 Philadelphia chromosome negative myeloproliferative neoplasms patients from a single center].

    Science.gov (United States)

    Li, M Y; Chao, H Y; Sun, A N; Qiu, H Y; Jin, Z M; Tang, X W; Han, Y; Fu, C C; Chen, S N; Wu, D P

    2017-04-14

    Objective: To explore the prevalences of JAK2, CALR and MPL gene mutations and the mutation types in patients with Philadelphia chromosome negative myeloproliferative neoplasms (MPNs) , and to compare their clinical characteristics of different mutation types with each other and mutation negative group. Methods: The mutations of JAK2 V617F, JAK2 gene at exon 12, CALR gene at exon 9 and MPL gene at exon 10 in 1 648 Ph negative MPNs patients were detected by direct sequencing. Results: ① The JAK2V617F mutation was found in 471 (92.7%) of 508 PV patients, 819 (78.1%) of 1 049 ET patients and 74 (81.3%) of 91 PMF patients respectively, with the total mutation rate as 82.8% (1 364/1 648) . The JAK2 exon12 mutation was found in 9 (1.7%) of 508 PV patients, none was found in ET or PMF patients, with the total mutation rate as 0.5% (9/1 648) . The CALR mutation was found in 132 (12.6%) of 1 049 ET patients and 11 (12.1%) of 91 PMF patients respectively, with the total mutation rate as 8.7% (143/1 648) ; the MPL mutation was found in 9 (0.9%) of 1 049 ET patients and 1 (1.1%) of 91 PMF patients respectively, with the total mutation rate as 0.6% (10/1 648) . The co-occurrence of any two types of driver gene mutations was not detected by direct sequencing. ②The median onset age of patients with JAK2V617F[61 (15-95) y] was significant higher than of with JAK2 exon12 mutation[49 (33-62) y] or without mutations[42 (3-78) y] ( P MPL mutation[59 (22-71) y] ( P >0.05) . Patients with JAK2V617F had higher white blood cell count and hemoglobin level ( P MPL mutation ( P =0.013) . The platelet count of patients with CALR mutation was significantly higher than of with JAK2V617F[966 (400-2 069) ×10(9)/L vs 800 (198-3 730) ×10(9)/L, P MPL gene mutation revealed normal karyotype. Conclusions: Driver gene mutations detection could ensure the diagnosis and prognosis judgment of MPN more reliable, different subtypes of MPNs had different profiles of driver gene mutations, the latter

  5. Status of the NASA Micro Pulse Lidar Network (MPLNET): overview of the network and future plans, new version 3 data products, and the polarized MPL

    Science.gov (United States)

    Welton, Ellsworth J.; Stewart, Sebastian A.; Lewis, Jasper R.; Belcher, Larry R.; Campbell, James R.; Lolli, Simone

    2018-04-01

    The NASA Micro Pulse Lidar Network (MPLNET) is a global federated network of Micro-Pulse Lidars (MPL) co-located with the NASA Aerosol Robotic Network (AERONET). MPLNET began in 2000, and there are currently 17 long-term sites, numerous field campaigns, and more planned sites on the way. We have developed a new Version 3 processing system including the deployment of polarized MPLs across the network. Here we provide an overview of Version 3, the polarized MPL, and current and future plans.

  6. Formation of newly synthesized adeno-associated virus capsids in the cell nucleus.

    Science.gov (United States)

    Bell, Peter; Vandenberghe, Luk H; Wilson, James M

    2014-06-01

    Adeno-associated virus (AAV) particles inside the nucleus of a HEK 293 cell are shown by electron microscopy. Cells have been triple-transfected for vector production and were analyzed for capsid formation three days later. Newly assembled particle are visible as seemingly unstructured conglomerates or crystal-like arrays.

  7. Development of a new knock-in mouse model and evaluation of pharmacological activities of lusutrombopag, a novel, nonpeptidyl small-molecule agonist of the human thrombopoietin receptor c-Mpl.

    Science.gov (United States)

    Yoshida, Hiroshi; Yamada, Hajime; Nogami, Wataru; Dohi, Keiji; Kurino-Yamada, Tomomi; Sugiyama, Koji; Takahashi, Koji; Gahara, Yoshinari; Kitaura, Motoji; Hasegawa, Minoru; Oshima, Itsuki; Kuwabara, Kenji

    2018-03-01

    Lusutrombopag (S-888711), an oral small-molecule thrombopoietin receptor (TPOR) agonist, has gained first approval as a drug to treat thrombocytopenia of chronic liver disease in patients undergoing elective invasive procedures in Japan. Preclinical studies were performed to evaluate its efficacy against megakaryopoiesis and thrombopoiesis. To investigate the proliferative activity and efficacy of megakaryocytic colony formation via human TPOR, lusutrombopag was applied to cultured human c-Mpl-expressing Ba/F3 (Ba/F3-hMpl) cells and human bone marrow-derived CD34-positive cells, respectively. Lusutrombopag caused a robust increase in Ba/F3-hMpl cells by activating pathways in a manner similar to that of thrombopoietin and induced colony-forming units-megakaryocyte and polyploid megakaryocytes in human CD34-positive cells. Because lusutrombopag has high species specificity for human TPOR, there was no suitable experimental animal model for drug evaluation, except for immunodeficient mouse-based xenograft models. Therefore, a novel genetically modified knock-in mouse, TPOR-Ki/Shi, was developed by replacing mouse Mpl with human-mouse chimera Mpl. In TPOR-Ki/Shi mice, lusutrombopag significantly increased circulating platelets in a dose-dependent manner during 21-day repeated oral administration. Histopathological study of the TPOR-Ki/Shi mice on day 22 also revealed a significant increase in megakaryocytes in the bone marrow. These results indicate that lusutrombopag acts on human TPOR to upregulate differentiation and proliferation of megakaryocytic cells, leading to platelet production. Copyright © 2018 ISEH – Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

  8. Emergence of MPLW515 mutation in a patient with CALR deletion: Evidence of secondary acquisition of MPL mutation in the CALR clone.

    Science.gov (United States)

    Partouche, Nicolas; Conejero, Carole; Barathon, Quentin; Moroch, Julien; Tulliez, Michel; Cordonnier, Catherine; Giraudier, Stephane

    2018-02-01

    Myeloproliferative neoplasms are characterized by transduction pathway recognized as mutually exclusive molecular abnormalities such as BCR-ABL translocation, JAK2V617F or JAK2 exon 12 mutations, MPL w515, and CALR mutations. However, in some rare cases, associations of such mutations are found in 1 patient. This can be related to 2 pathologies (at least 2 different clones harboring 2 mutations) or associated mutations in 1 clone. We describe here such an association of CALR and MPL mutations in a patient harboring the second mutation in a subclone during the phenotypic evolution of the myeloproliferative neoplasms. Copyright © 2017 John Wiley & Sons, Ltd.

  9. Thrombopoietin/MPL participates in initiating and maintaining RUNX1-ETO acute myeloid leukemia via PI3K/AKT signaling

    NARCIS (Netherlands)

    J.A. Pulikkan (John); D. Madera (Dmitri); L. Xue (Liting); P. Bradley (Paul); S.F. Landrette (Sean Francis); Y.-H. Kuo (Ya-Huei); S. Abbas (Saman); L.J. Zhu (Lihua Julie); P.J.M. Valk (Peter); L.H. Castilla (Lucio)

    2012-01-01

    textabstractOncogenic mutations in components of cytokine signaling pathways elicit ligand-independent activation of downstream signaling, enhancing proliferation and survival in acute myeloid leukemia (AML). The myeloproliferative leukemia virus oncogene, MPL, a homodimeric receptor activated by

  10. Comparison of BCG, MPL and cationic liposome adjuvant systems in leishmanial antigen vaccine formulations against murine visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Bhowmick Sudipta

    2010-06-01

    Full Text Available Abstract Background The development of an effective vaccine against visceral leishmaniasis (VL caused by Leishmania donovani is an essential aim for controlling the disease. Use of the right adjuvant is of fundamental importance in vaccine formulations for generation of effective cell-mediated immune response. Earlier we reported the protective efficacy of cationic liposome-associated L. donovani promastigote antigens (LAg against experimental VL. The aim of the present study was to compare the effectiveness of two very promising adjuvants, Bacille Calmette-Guerin (BCG and Monophosphoryl lipid A (MPL plus trehalose dicorynomycolate (TDM with cationic liposomes, in combination with LAg, to confer protection against murine VL. Results All the three formulations afforded significant protection against L. donovani in both the visceral organs, liver and spleen. Although comparable level of protection was observed in BCG+LAg and MPL-TDM+LAg immunized mice, highest level of protection was exhibited by the liposomal LAg immunized group. Significant increase in anti-LAg IgG levels were detected in both MPL-TDM+LAg and liposomal LAg immunized animals with higher levels of IgG2a than IgG1. But BCG+LAg failed to induce any antibody response. As an index of cell-mediated immunity DTH responses were measured and significant response was observed in mice vaccinated with all the three different formulations. However, highest responses were observed with liposomal vaccine immunization. Comparative evaluation of IFN-γ and IL-4 responses in immunized mice revealed that MPL-TDM+LAg group produced the highest level of IFN-γ but lowest IL-4 level, while BCG+LAg demonstrated generation of suboptimum levels of both IFN-γ and IL-4 response. Elicitation of moderate levels of prechallenge IFN-γ along with optimum IL-4 corresponds with successful vaccination with liposomal LAg. Conclusion This comparative study reveals greater effectiveness of the liposomal vaccine for

  11. Status of the NASA Micro Pulse Lidar Network (MPLNET: overview of the network and future plans, new version 3 data products, and the polarized MPL

    Directory of Open Access Journals (Sweden)

    Welton Ellsworth J.

    2018-01-01

    Full Text Available The NASA Micro Pulse Lidar Network (MPLNET is a global federated network of Micro-Pulse Lidars (MPL co-located with the NASA Aerosol Robotic Network (AERONET. MPLNET began in 2000, and there are currently 17 long-term sites, numerous field campaigns, and more planned sites on the way. We have developed a new Version 3 processing system including the deployment of polarized MPLs across the network. Here we provide an overview of Version 3, the polarized MPL, and current and future plans.

  12. Monoclonal antibody 1.6.1 against human MPL receptor allows HSC enrichment of CB and BM CD34(+)CD38(-) populations.

    Science.gov (United States)

    Petit Cocault, Laurence; Fleury, Maud; Clay, Denis; Larghero, Jérôme; Vanneaux, Valérie; Souyri, Michèle

    2016-04-01

    Thrombopoietin (TPO) and its receptor Mpl (CD110) play a crucial role in the regulation of hematopoietic stem cells (HSCs). Functional study of Mpl-expressing HSCs has, however, been hampered by the lack of efficient monoclonal antibodies, explaining the very few data available on Mpl(+) HSCs during human embryonic development and after birth. Investigating the main monoclonal antibodies used so far to sort CD110(+) cells from cord blood (CB) and adult bone marrow (BM), we found that only the recent monoclonal antibody 1.6.1 engineered by Immunex Corporation was specific. Using in vitro functional assays, we found that this antibody can be used to sort a CD34(+)CD38(-)CD110(+) population enriched in hematopoietic progenitor stem cells, both in CB and in adult BM. In vivo injection into NSG mice further indicated that the CB CD34(+)CD38(-)CD110(+) population is highly enriched in HSCs compared with both CD34(+)CD38(-)CD110(-) and CD34(+)CD38(-) populations. Together our results validate MAb1.6.1 as an important tool, which has so far been lacking, in the HSC field. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  13. CH3 NH3 PbI3 and HC(NH2 )2 PbI3 Powders Synthesized from Low-Grade PbI2 : Single Precursor for High-Efficiency Perovskite Solar Cells.

    Science.gov (United States)

    Zhang, Yong; Kim, Seul-Gi; Lee, Do-Kyoung; Park, Nam-Gyu

    2018-05-09

    High-efficiency perovskite solar cells are generally fabricated by using highly pure (>99.99 %) PbI 2 mixed with an organic iodide in polar aprotic solvents. However, the use of such an expensive chemical may impede progress toward large-scale industrial applications. Here, we report on the synthesis of perovskite powders by using inexpensive low-grade (99 %) PbI 2 and on the photovoltaic performance of perovskite solar cells prepared from a powder-based single precursor. Pure APbI 3 [A=methylammonium (MA) or formamidinium (FA)] perovskite powders were synthesized by treating low-grade PbI 2 with MAI or FAI in acetonitrile at ambient temperature. The structural phase purity was confirmed by X-ray diffraction. The solar cell with a MAPbI 3 film prepared from the synthesized perovskite powder demonstrated a power conversion efficiency (PCE) of 17.14 %, which is higher than the PCE of MAPbI 3 films prepared by using both MAI and PbI 2 as precursors (PCE=13.09 % for 99 % pure PbI 2 and PCE=16.39 % for 99.9985 % pure PbI 2 ). The synthesized powder showed better absorption and photoluminescence, which were responsible for the better photovoltaic performance. For the FAPbI 3 powder, a solution with a yellow non-perovskite δ-FAPbI 3 powder synthesized at room temperature was found to lead to a black perovskite film, whereas a solution with the black perovskite α-FAPbI 3 powder synthesized at 150 °C was not transformed into a black perovskite film. The α↔δ transition between the powder and film was assumed to correlate with the difference in the iodoplumbates in the powder-dissolved solution. An average PCE of 17.21 % along with a smaller hysteresis [ΔPCE=PCE reverse -PCE forward )=1.53 %] was demonstrated from the perovskite solar cell prepared by using δ-FAPbI 3 powder; this PCE is higher than the average PCE of 17.05 % with a larger hysteresis (ΔPCE=2.71 %) for a device based on a conventional precursor solution dissolving MAI with high

  14. Fibronectin-synthesizing activity of free and membrane-bound polyribosomes from human embryonic fibroblasts and chick embryos

    International Nuclear Information System (INIS)

    Belkin, V.M.; Volodarskaya, S.M.

    1986-01-01

    The fibronectin-synthesizing activity of membrane-bound and free polyribosomes in a cell-free system was studied using immunochemical methods. It was found that fibronectin biosynthesis on membrane-bound polyribosomes from human embryonic fibroblasts accounts for 4.9% and those from 10-day-old chick embryos for 1.1% of the total amount of newly synthesized proteins, whereas on free polyribosomes it is 1.0 and 0.3%, respectively. Fibronectin monomers with a molecular weight of 220,000 were found only in the material of the cell-free system containing heavy fractions of membrane-bound polyribosomes newly synthesized in the presence of spermidine. Thus, it was shown that fibronectin is synthesized primarily on membrane-bound polyribosomes

  15. Intranasal immunization with fusion protein MrpH·FimH and MPL adjuvant confers protection against urinary tract infections caused by uropathogenic Escherichia coli and Proteus mirabilis.

    Science.gov (United States)

    Habibi, Mehri; Asadi Karam, Mohammad Reza; Shokrgozar, Mohammad Ali; Oloomi, Mana; Jafari, Anis; Bouzari, Saeid

    2015-04-01

    Urinary tract infections (UTIs) caused by Uropathogenic Escherichia coli (UPEC) and Proteus mirabilis are among the most common infections in the world. Currently there are no vaccines available to confer protection against UTI in humans. In this study, the immune responses and protection of FimH of UPEC with MrpH antigen of P. mirabilis in different vaccine formulations with and without MPL adjuvant were assessed. Mice intranasally immunized with the novel fusion protein MrpH·FimH induced a significant increase in IgG and IgA in serum, nasal wash, vaginal wash, and urine samples. Mice immunized with fusion MrpH·FimH also showed a significant boost in cellular immunity. Addition of MPL as the adjuvant enhanced FimH and MrpH specific humoral and cellular responses in both systemic and mucosal samples. Vaccination with MrpH·FimH alone or in combination with MPL showed the highest efficiency in clearing bladder and kidney infections in mice challenged with UPEC and P. mirabilis. These findings may indicate that the protection observed correlates with the systemic, mucosal and cellular immune responses induced by vaccination with these preparations. Our data suggest MrpH·FimH fusion protein with or without MPL as adjuvant could be potential vaccine candidates for elimination of UPEC and P. mirabilis. These data altogether are promising and these formulations are good candidates for elimination of UPEC and P. mirabilis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Peptide nucleic acid probe-based fluorescence melting curve analysis for rapid screening of common JAK2, MPL, and CALR mutations.

    Science.gov (United States)

    Park, Joonhong; Song, Minsik; Jang, Woori; Chae, Hyojin; Lee, Gun Dong; Kim, KyungTak; Park, Heekyung; Kim, Myungshin; Kim, Yonggoo

    2017-02-01

    We developed and evaluated the feasibility of peptide nucleic acid (PNA)-based fluorescence melting curve analysis (FMCA) to detect common mutations in myeloproliferative neoplasms (MPNs). We have set up two separate reactions of PNA-based FMCA: JAK2 V617F &CALR p.Leu367fs*46 (set A) and MPL W515L/K &CALR p.Lys385fs*47 (set B). Clinical usefulness was validated with allele-specific real-time PCR, fragment analysis, Sanger sequencing in 57 BCR-ABL1-negative MPNs. The limit of detection (LOD) of PNA-based FMCA was approximately 10% for each mutation and interference reactions using mixtures of different mutations were not observed. Non-specific amplification was not observed in normal control. PNA-based FMCA was able to detect all JAK2 V617F (n=20), CALR p.Leu367fs*46 (n=10) and p.Lys385fs*47 (n=8). Three of six MPL mutations were detected except three samples with low mutant concentration in out of LOD. JAK2 exon 12 mutations (n=7) were negative without influencing V617F results. Among six variant CALR exon 9 mutations, two were detected by this method owing to invading of probe binding site. PNA-based FMCA for detecting common JAK2, MPL, and CALR mutations is a rapid, simple, and sensitive technique in BCR-ABL1-negative MPNs with >10% mutant allele at the time of initial diagnosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. JAK2 V617F, MPL, and CALR mutations in essential thrombocythaemia and major thrombotic complications: a single-institute retrospective analysis.

    Science.gov (United States)

    Pósfai, Éva; Marton, Imelda; Király, Péter Attila; Kotosz, Balázs; Kiss-László, Zsuzsanna; Széll, Márta; Borbényi, Zita

    2015-07-01

    Thrombo-haemorrhagic events are the main cause of morbidity and mortality in essential thrombocythemia. The aim of this study was to estimate the incidence of thrombotic events and the impact of the JAK2V617F, MPL (W515L, W515K, W515R, W515A and S505N) and CALR (type-1, type-2) mutations on 101 essential thrombocythaemia patients (72 females and 29 males with a mean age of 61 years) diagnosed in a Southern Hungarian regional academic centre. The incidence of major thrombosis was 13.86 %. Sixty percent of the patients carried the JAK2V617F mutation. The MPL mutations were analysed by sequencing and the W515L was the only one we could identify with an incidence of 3.96 %. Type-2 CALR mutation could be identified in 3 cases among the patients who had JAK2/MPL-unmutated ET. Statistical analyses revealed that the JAK2V617F mutation was associated with significantly increased levels of platelet (p = 0.042), haemoglobin (p = 0.000), red blood cell (p = 0.000) and haematocrit (p = 0.000) and hepatomegaly (p = 0.045) at diagnosis compared to JAK2V617F negative counterparts, however there was no significant association between the JAK2V617F mutation status (relative risk: 1.297, 95 % CI 0.395-4.258; p = 0.668) and subsequent thrombotic complications. The impact of JAK2V617F, MPL W515L and CALR mutations on the clinical findings at the diagnosis of ET was obvious, but their statistically significant role in the prediction of thrombotic events could not be proven in this study. Our results indirectly support the concept that, besides the quantitative and qualitative changes in the platelets, the mechanisms leading to thrombosis are more complex and multifactorial.

  18. Evaluation of the effect of MPL and delivery route on immunogenicity and protectivity of different formulations of FimH and MrpH from uropathogenic Escherichia coli and Proteus mirabilis in a UTI mouse model.

    Science.gov (United States)

    Habibi, Mehri; Asadi Karam, Mohammad Reza; Bouzari, Saeid

    2015-09-01

    Urinary tract infections (UTIs) caused by Escherichia coli and Proteus mirabilis are an important cause of morbidity and with the high rate of relapse and spread of multi-drug resistant pathogens, pose a significant public health challenge worldwide. Lack of an efficacious commercial vaccine targeting both uropathogens makes development of a combined vaccine highly desirable. In this study the immunogenicity and protective efficacy of different formulations of FimH of UPEC, MrpH of P. mirabilis and their fusion protein (MrpH.FimH) subcutaneously administered with and without Monophosphoryl lipid A (MPL) adjuvant were evaluated. Our data showed that the subcutaneously administered proteins induced both serum and mucosal IgG, which MPL significantly improved developing a mixed Th1 and Th2 immune response. However, the preparations induced a higher systemic and mucosal IgG and IL-2 levels by this route compared to the intranasal. Immunization of mice with MrpH.FimH fusion with MPL or a mixture of FimH, MrpH and MPL conferred the highest protection of the bladder and kidneys when challenged with UPEC and P. mirabilis in a UTI mouse model. Therefore considering these results MrpH.FimH fusion with MPL administered subcutaneously or intranasally could be a promising vaccine candidate for elimination of UTIs caused by UPEC and P. mirabilis. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. A non-catalytic histidine residue influences the function of the metalloprotease of Listeria monocytogenes.

    Science.gov (United States)

    Forster, Brian M; Bitar, Alan Pavinski; Marquis, Hélène

    2014-01-01

    Mpl, a thermolysin-like metalloprotease, and PC-PLC, a phospholipase C, are synthesized as proenzymes by the intracellular bacterial pathogen Listeria monocytogenes. During intracellular growth, L. monocytogenes is temporarily confined in a membrane-bound vacuole whose acidification leads to Mpl autolysis and Mpl-mediated cleavage of the PC-PLC N-terminal propeptide. Mpl maturation also leads to the secretion of both Mpl and PC-PLC across the bacterial cell wall. Previously, we identified negatively charged and uncharged amino acid residues within the N terminus of the PC-PLC propeptide that influence the ability of Mpl to mediate the maturation of PC-PLC, suggesting that these residues promote the interaction of the PC-PLC propeptide with Mpl. In the present study, we identified a non-catalytic histidine residue (H226) that influences Mpl secretion across the cell wall and its ability to process PC-PLC. Our results suggest that a positive charge at position 226 is required for Mpl functions other than autolysis. Based on the charge requirement at this position, we hypothesize that this residue contributes to the interaction of Mpl with the PC-PLC propeptide.

  20. Applications Performance Under MPL and MPI on NAS IBM SP2

    Science.gov (United States)

    Saini, Subhash; Simon, Horst D.; Lasinski, T. A. (Technical Monitor)

    1994-01-01

    On July 5, 1994, an IBM Scalable POWER parallel System (IBM SP2) with 64 nodes, was installed at the Numerical Aerodynamic Simulation (NAS) Facility Each node of NAS IBM SP2 is a "wide node" consisting of a RISC 6000/590 workstation module with a clock of 66.5 MHz which can perform four floating point operations per clock with a peak performance of 266 Mflop/s. By the end of 1994, 64 nodes of IBM SP2 will be upgraded to 160 nodes with a peak performance of 42.5 Gflop/s. An overview of the IBM SP2 hardware is presented. The basic understanding of architectural details of RS 6000/590 will help application scientists the porting, optimizing, and tuning of codes from other machines such as the CRAY C90 and the Paragon to the NAS SP2. Optimization techniques such as quad-word loading, effective utilization of two floating point units, and data cache optimization of RS 6000/590 is illustrated, with examples giving performance gains at each optimization step. The conversion of codes using Intel's message passing library NX to codes using native Message Passing Library (MPL) and the Message Passing Interface (NMI) library available on the IBM SP2 is illustrated. In particular, we will present the performance of Fast Fourier Transform (FFT) kernel from NAS Parallel Benchmarks (NPB) under MPL and MPI. We have also optimized some of Fortran BLAS 2 and BLAS 3 routines, e.g., the optimized Fortran DAXPY runs at 175 Mflop/s and optimized Fortran DGEMM runs at 230 Mflop/s per node. The performance of the NPB (Class B) on the IBM SP2 is compared with the CRAY C90, Intel Paragon, TMC CM-5E, and the CRAY T3D.

  1. Fabrication of copper-selective PVC membrane electrode based on newly synthesized copper complex of Schiff base as carrier

    Directory of Open Access Journals (Sweden)

    Sulekh Chandra

    2016-09-01

    Full Text Available The newly synthesized copper(II complex of Schiff base p-hydroxyacetophenone semicarbazone was explored as neutral ionophore for the fabrication of poly(vinylchloride (PVC based membrane electrode selective to Cu(II ions. The electrode shows a Nernstian slope of 29.8 ± 0.3 mV/decade with improved linear range of 1.8 × 10−7 to 1.0 × 10−1 M, comparatively lower detection limit 5.7 × 10−8 M between pH range of 2.0–8.0, giving a relatively fast response within 5s and can be used for at least 16 weeks without any divergence in potential. The selectivity coefficient was calculated using the fixed interference method (FIM. The electrode can also be used in partially non-aqueous media having up to 25% (v/v methanol, ethanol or acetone content with no significant change in the value of slope or working concentration range. It was successfully applied for the direct determination of copper content in water and tea samples with satisfactory results. The electrode has been used in the potentiometric titration of Cu2+ with EDTA.

  2. MPL-A program for computations with iterated integrals on moduli spaces of curves of genus zero

    Science.gov (United States)

    Bogner, Christian

    2016-06-01

    We introduce the Maple program MPL for computations with multiple polylogarithms. The program is based on homotopy invariant iterated integrals on moduli spaces M0,n of curves of genus 0 with n ordered marked points. It includes the symbol map and procedures for the analytic computation of period integrals on M0,n. It supports the automated computation of a certain class of Feynman integrals.

  3. Synthesis of Zeolite from Fly Ash and Removal of Heavy Metal Ions from Newly Synthesized Zeolite

    OpenAIRE

    Solanki, Parag; Gupta, Vikal; Kulshrestha, Ruchi

    2010-01-01

    Coal fly ash was used to synthesize X-type zeolite by alkali fusion followed by hydrothermal treatment. Characteristics of the various Fly ash samples were carried out. Coal proximate analysis was done. Batch experiment was carried out for the adsorption of some heavy metal ions on to synthesized Zeolite. The cost of synthesized zeolite was estimated to be almost one-fifth of that of commercial 13X zeolite available in the market.

  4. Dissection of Signaling Events Downstream of the c-Mpl Receptor in Murine Hematopoietic Stem Cells Via Motif-Engineered Chimeric Receptors.

    Science.gov (United States)

    Saka, Koichiro; Lai, Chen-Yi; Nojima, Masanori; Kawahara, Masahiro; Otsu, Makoto; Nakauchi, Hiromitsu; Nagamune, Teruyuki

    2018-02-01

    Hematopoietic stem cells (HSCs) are a valuable resource in transplantation medicine. Cytokines are often used to culture HSCs aiming at better clinical outcomes through enhancement of HSC reconstitution capability. Roles for each signal molecule downstream of receptors in HSCs, however, remain puzzling due to complexity of the cytokine-signaling network. Engineered receptors that are non-responsive to endogenous cytokines represent an attractive tool for dissection of signaling events. We here tested a previously developed chimeric receptor (CR) system in primary murine HSCs, target cells that are indispensable for analysis of stem cell activity. Each CR contains tyrosine motifs that enable selective activation of signal molecules located downstream of the c-Mpl receptor upon stimulation by an artificial ligand. Signaling through a control CR with a wild-type c-Mpl cytoplasmic tail sufficed to enhance HSC proliferation and colony formation in cooperation with stem cell factor (SCF). Among a series of CRs, only one compatible with selective Stat5 activation showed similar positive effects. The HSCs maintained ex vivo in these environments retained long-term reconstitution ability following transplantation. This ability was also demonstrated in secondary recipients, indicating effective transmission of stem cell-supportive signals into HSCs via these artificial CRs during culture. Selective activation of Stat5 through CR ex vivo favored preservation of lymphoid potential in long-term reconstituting HSCs, but not of myeloid potential, exemplifying possible dissection of signals downstream of c-Mpl. These CR systems therefore offer a useful tool to scrutinize complex signaling pathways in HSCs.

  5. Unstable structure of ribosomal particles synthesized in. gamma. -irradiated Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Fujita, H; Morita, K [National Inst. of Radiological Sciences, Chiba (Japan)

    1975-06-01

    Stability of Escherichia coli ribosomes newly synthesized after ..gamma..-irradiation was compared with that of normal ribosomes. The ribosomal particles around 70-S synthesized in irradiated cells were more sensitive to digestion by pancreatic ribonuclease A. A larger number of the salt-unstable '50-S' precursor particles existed in the extract from irradiated cells than in the extract from unirradiated cells. These facts suggest that ribosomal particles, synthesized during an earlier stage in irradiated cells, maintain an incomplete structure even though they are not distinguishable from normal ribosomes by means of sucrose density-gradient centrifugation.

  6. Organo-Functionalization of Silicon Nanocrystals Synthesized by Inductively Coupled Plasma Chemical Vapor Deposition

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Don-Sung; Choe, Dong-Hoe; Jeong, Hyun-Dam [Chonnam National University, Gwangju (Korea, Republic of); Yoo, Seung-Wan; Kim, Jung-Hyung [Korea Research Institute of Standards and Science, Daejeon (Korea, Republic of)

    2016-05-15

    Octadecyl-terminated silicon nanocrystals (ODE-Si NCs) are obtained via a surface-initiated thermal hydrosilylation reaction on hydride-terminated Si NCs (H-Si NCs). Pristine Si NCs were synthesized at the gram scale by using inductively coupled plasma chemical vapor deposition (ICP-CVD) . The H-Si NCs were produced through a chemical etching process with hydrofluoric acid (HF), ethanol (EtOH), and distilled water (d-H{sub 2}O). The results obtained from X-ray diffraction (XRD) and field emission scanning electron microscopy (FE-SEM) indicate that the synthesized Si NCs obtained via ICP-CVD have diamond cubic-structured silicon with a grain size of 10 nm and a densely packed Si NC array consisting of individual NCs. Organo-functionalized Si NCs, i.e., ODE-Si NCs, are well soluble in organic solvent whereas pristine Si NCs synthesized through ICP-CVD are not. The surface chemistry of the ODE-Si NCs was confirmed via Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy ({sup 1}H-NMR), and field emission transmission electron microscopy (FE-TEM). Thereby, these newly synthesized and scalable organo-functionalized Si NCs are applicable as raw materials for practical use in devices by tuning the surface chemistry with various capping molecules.

  7. Effects of two newly synthesized analogues of lidocaine on rat arterial blood pressure and heart rate.

    Science.gov (United States)

    Al Rasheed, N M; Al Sayed, M I; Al Zuhair, H H; Al Obaid, A R; Fatani, A J

    2001-04-01

    Two new analogues of lidocaine were synthesized at the College of Pharmacy, King Saud University: compound I (Methyl-2-[2-(N,N-diethylamino) acetamido]-3-cyano-4,5-dimethylbenzoate) and compound II (Methyl-2-[2-(piperidino) acetamido]-3-cyano-4,5-dimethylbenzoate). Their influence on the arterial blood pressure and the heart rate of urethane-anaesthetized rats was studied and compared with the actions of lidocaine. Compounds I, II and lidocaine induced significant dose-dependent decreases in the arterial blood pressure and heart rate, which usually returned to basal values within 3-5 min. There were significant differences in the potency of the three compounds in producing their effects on blood pressure and heart rate (Plidocaine and compound I, respectively. The results of this study also indicated the ineffectiveness of antagonists of autonomic, histaminergic and 5-HT receptor, and various vasodilators in blocking the actions of the three compounds on blood pressure and heart rate. Pretreatment with CaCl(2)significantly reduced the hypotension and bradycardia induced by the three compounds, suggesting the involvement of calcium channels, probably of the L type. Several possible mechanisms are postulated. In conclusion, the results direct attention to the capability of the two new compounds to decrease blood pressure and heart rate; affects that may have clinical potential. Copyright 2001 Academic Press.

  8. Solvothermal syntheses and characterization of three new silver(I)/copper(I)-thioarsenates based on As{sup 2+}/As{sup 3+} ions

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Hua-Gang, E-mail: hgyao@gdpu.edu.cn [School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan 528458 (China); Guangdong Cosmetics Engineering & Technology Research Center, Zhongshan 528458 (China); Tang, Cheng-Fei [School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan 528458 (China); An, Yong-Lin [Department of Chemistry, Dalian University of Technology, Dalian 116024 (China); Ou, Zi-Jian; Wu, Guo-Hao; Lan, Pei; Zheng, Yi-Long [School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan 528458 (China)

    2017-02-15

    Three new silver(I)/copper(I)-thioarsenates KAgAs{sup II}S{sub 2} (1), RbCu{sub 2}As{sup III}S{sub 3} (2) and RbCu{sub 4}As{sup III}S{sub 4} (3) have been solvothermally synthesized and structurally characterized. 1 exhibits a two-dimensional anionic network built up by As−As bond connecting the left- and right-handed helical [AgS{sub 2}]{sup 4−} chains, and represents the first examples of thioarsenates(II). The structure of 2 consists of two kinds of helical [Cu{sub 2}S{sub 3}]{sup 4–} chains linked by the arsenic atoms to form double layers with rubidium ions between the layers. Compound 3 is built up of infinite [Cu{sub 2}S{sub 2}]{sup 2–} chain and layered [Cu{sub 6}As{sub 2}S{sub 6}] linked to form a three-dimensional anionic framework, [Cu{sub 4}AsS{sub 4}]{sup –}, and containing channels in which the rubidium cations reside. The optical properties of 1–3 have been investigated by UV–vis spectroscopy. - Graphical abstract: Three new silver(I)/copper(I)-thioarsenates have been solvothermally synthesized and structurally characterized. 1 represents the first examples of thioarsenates(II) while compounds 2 and 3 possess noncondensed pyramidal AsS{sub 3}{sup 3–} unit.

  9. [Prognostic value of JAK2, MPL and CALR mutations in Chinese patients with primary myelofibrosis].

    Science.gov (United States)

    Xu, Z F; Li, B; Liu, J Q; Li, Y; Ai, X F; Zhang, P H; Qin, T J; Zhang, Y; Wang, J Y; Xu, J Q; Zhang, H L; Fang, L W; Pan, L J; Hu, N B; Qu, S Q; Xiao, Z J

    2016-07-01

    To evaluate the prognostic value of JAK2, MPL and CALR mutations in Chinese patients with primary myelofibrosis (PMF). Four hundred and two Chinese patients with PMF were retrospectively analyzed. The Kaplan-Meier method, the Log-rank test, the likelihood ratio test and the Cox proportional hazards regression model were used to evaluate the prognostic scoring system. This cohort of patients included 209 males and 193 females with a median age of 55 years (range: 15- 89). JAK2V617F mutations were detected in 189 subjects (47.0% ), MPLW515 mutations in 13 (3.2%) and CALR mutations in 81 (20.1%) [There were 30 (37.0%) type-1, 48 (59.3%) type-2 and 3 (3.7%) less common CALR mutations], respectively. 119 subjects (29.6%) had no detectable mutation in JAK2, MPL or CALR. Univariate analysis indicated that patients with CALR type-2 mutations or no detectable mutations had inferior survival compared to those with JAK2, MPL or CALR type- 1 or other less common CALR mutations (the median survival was 74vs 168 months, respectively [HR 2.990 (95% CI 1.935-4.619),P<0.001]. Therefore, patients were categorized into the high-risk with CALR type- 2 mutations or no detectable driver mutations and the low- risk without aforementioned mutations status. The DIPSS-Chinese molecular prognostic model was proposed by adopting mutation categories and DIPSS-Chinese risk group. The median survival of patients classified in low risk (132 subjects, 32.8% ), intermediate- 1 risk (143 subjects, 35.6%), intermediate- 2 risk (106 subjects, 26.4%) and high risk (21 subjects, 5.2%) were not reached, 156 (95% CI 117- 194), 60 (95% CI 28- 91) and 22 (95% CI 10- 33) months, respectively, and there was a statistically significant difference in overall survival among the four risk groups (P<0.001). There was significantly higher predictive power for survival according to the DIPSS-Chinese molecular prognostic model compared with the DIPSS-Chinese model (P=0.005, -2 log-likelihood ratios of 855.6 and 869

  10. Investigation of formation constant of complex of a new synthesized ...

    African Journals Online (AJOL)

    The complex formation between a newly synthesized tripodal ligand and the cation Cu2+ in water and surfactant media was studied spectrophotometrically using rank annihilation factor analysis (RAFA). According to molar ratio data the stoichiometry of complexation between the ligand and the cation Cu2+ was 1:1.

  11. Newly synthesized bis-benzimidazole compound 8 induces apoptosis, autophagy and reactive oxygen species generation in HeLa cells.

    Science.gov (United States)

    Chu, Naying; Yao, Guodong; Liu, Yuan; Cheng, Maosheng; Ikejima, Takashi

    2016-09-01

    Compound 8 (C8) is a newly synthesized bis-benzimidazole derivative and exerts significant anti-tumor activity in vitro. Previous studies demonstrated that C8 induced apoptosis and autophagy in human promyelocytic leukemia HL60 cells. However, cytotoxicity study on human peripheral blood mononuclear cells (hPBMC) showed that C8 exhibited less toxicity in normal cells. In this study, the molecular mechanism of C8 on human cervical carcinoma HeLa cells was investigated. The results showed that C8 inhibited the growth of HeLa cells and triggered both apoptotic and autophagic cell death. Subsequent experiment also indicated that reactive oxygen species (ROS) generation was induced in C8-treated HeLa cells. Since ROS scavenger decreased the ratio of apoptotic and autophagic cells, ROS generation contributed to C8-induced apoptosis and autophagy. Furthermore, inhibitors of apoptosis and autophagy also reduced ROS generation, respectively. Autophagy inhibition increased cell growth compared to C8-treated group and attenuated apoptotic cell death, indicating that C8-induced autophagy promoted apoptosis for cell death. However, the percentage of autophagic cells was enhanced when limiting apoptosis process. Taken together, C8 induced ROS-mediated apoptosis and autophagy in HeLa cells, autophagy promoted apoptosis but the former was antagonized by the latter. The data also gave us a new perspective on the anti-tumor effect of C8. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Cirrus clouds properties derived from polarized micro pulse lidar (p-mpl) observations at the atmospheric observatory `el arenosillo' (sw iberian peninsula): a case study for radiative implications

    Science.gov (United States)

    Águila, Ana del; Gómez, Laura; Vilaplana, José Manuel; Sorribas, Mar; Córdoba-Jabonero, Carmen

    2018-04-01

    Cirrus (Ci) clouds are involved in Climate Change concerns since they affect the radiative balance of the atmosphere. Recently, a polarized Micro Pulse Lidar (P-MPL), standard system within NASA/MPLNET has been deployed at the INTA/Atmospheric Observatory `El Arenosillo' (ARN), located in the SW Iberian Peninsula. Hence, the INTA/P-MPL system is used for Ci detection over that station for the first time. Radiative effects of a Ci case observed over ARN are examined, as reference for future long-term Ci observations. Optical and macrophysical properties are retrieved, and used for radiative transfer simulations. Data are compared to the measured surface radiation levels and all-sky images simultaneously performed at the ARN station.

  13. Newly synthesized MgAl2Ge2: A first-principles comparison with its silicide and carbide counterparts

    Science.gov (United States)

    Tanveer Karim, A. M. M.; Hadi, M. A.; Alam, M. A.; Parvin, F.; Naqib, S. H.; Islam, A. K. M. A.

    2018-06-01

    Using plane-wave pseudopotential density functional theory (DFT), the first-principle calculations are performed to investigate the structural aspects, mechanical behaviors and electronic features of the newly synthesized CaAl2Si2-prototype intermetallic compound, MgAl2Ge2 for the first time and the results are compared with those calculated for its silicide and carbide counterparts MgAl2Si2 and MgAl2C2. The calculated lattice constants agree fairly well with their corresponding experimental values. The estimated elastic tensors satisfy the mechanical stability conditions for MgAl2Ge2 along with MgAl2Si2 and MgAl2C2. The level of elastic anisotropy increases following the sequence of X-elements Ge → Si → C. MgAl2Ge2 and MgAl2Si2 are expected to be ductile and damage tolerant, while MgAl2C2 is a brittle one. MgAl2Ge2 and MgAl2Si2 should exhibit better thermal shock resistance and low thermal conductivity and accordingly these can be used as thermal barrier coating (TBC) materials. The Debye temperature of MgAl2Ge2 is lowest among three intermetallic compounds. MgAl2Ge2 and MgAl2Si2 should exhibit metallic conductivity; while the dual characters of weak-metals and semiconductors are expected for MgAl2C2. The values of theoretical Vickers hardness for MgAl2Ge2, MgAl2Si2, and MgAl2C2 are 3.3, 2.7, and 7.7 GPa, respectively, indicating that these three intermetallics are soft and easily machinable.

  14. Development of a Targeted Next-Generation Sequencing Assay to Detect Diagnostically Relevant Mutations of JAK2, CALR, and MPL in Myeloproliferative Neoplasms.

    Science.gov (United States)

    Frawley, Thomas; O'Brien, Cathal P; Conneally, Eibhlin; Vandenberghe, Elisabeth; Percy, Melanie; Langabeer, Stephen E; Haslam, Karl

    2018-02-01

    The classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), consisting of polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are a heterogeneous group of neoplasms that harbor driver mutations in the JAK2, CALR, and MPL genes. The detection of mutations in these genes has been incorporated into the recent World Health Organization (WHO) diagnostic criteria for MPN. Given a pressing clinical need to screen for mutations in these genes in a routine diagnostic setting, a targeted next-generation sequencing (NGS) assay for the detection of MPN-associated mutations located in JAK2 exon 14, JAK2 exon 12, CALR exon 9, and MPL exon 10 was developed to provide a single platform alternative to reflexive, stepwise diagnostic algorithms. Polymerase chain reaction (PCR) primers were designed to target mutation hotspots in JAK2 exon 14, JAK2 exon 12, MPL exon 10, and CALR exon 9. Multiplexed PCR conditions were optimized by using qualitative PCR followed by NGS. Diagnostic genomic DNA from 35 MPN patients, known to harbor driver mutations in one of the target genes, was used to validate the assay. One hundred percent concordance was observed between the previously-identified mutations and those detected by NGS, with no false positives, nor any known mutations missed (specificity = 100%, CI = 0.96, sensitivity = 100%, CI = 0.89). Improved resolution of mutation sequences was also revealed by NGS analysis. Detection of diagnostically relevant driver mutations of MPN is enhanced by employing a targeted multiplex NGS approach. This assay presents a robust solution to classical MPN mutation screening, providing an alternative to time-consuming sequential analyses.

  15. From iTE to NQT: Evaluating Newly Qualified Teachers' Use of Mobile Technology in Their First Two Years of Teaching

    Science.gov (United States)

    Mac Mahon, Brendan; Ó'Grádaigh, Seán; Ghuidhir, Sinéad Ni

    2018-01-01

    This article outlines a study to examine if newly qualified teachers (NQTs) who had incorporated iPad within pedagogical practice during initial teacher education, continued to do so in their first two years of teaching, and also to identify the challenges to integration that emerged. Findings show that use of iPad in teaching, learning and…

  16. Increased therapeutic efficacy of a newly synthesized tyrosinase inhibitor by solid lipid nanoparticles in the topical treatment of hyperpigmentation

    Directory of Open Access Journals (Sweden)

    Al-Amin M

    2016-12-01

    Full Text Available Md Al-Amin, Jiafu Cao, Muhammad Naeem, Hasanul Banna, Min-Soo Kim, Yunjin Jung, Hae Young Chung, Hyung Ryong Moon, Jin-Wook Yoo College of Pharmacy, Pusan National University, Busan, South Korea Abstract: Hyperpigmentation caused by melanin overproduction is a major skin disorder in humans. Inhibition of tyrosinase, a key regulator of melanin production, has been used as an effective strategy to treat hyperpigmentation. In this study, we investigated the use of solid lipid nanoparticles (SLNs as a highly effective and nontoxic means to deliver a newly synthesized potent tyrosinase inhibitor, MHY498, and to target melanocytes through the skin. MHY498-loaded SLNs (MHY-SLNs were prepared by an oil-in-water emulsion solvent-evaporation method, and their morphological and physicochemical properties were characterized. MHY-SLNs showed a prolonged drug-release profile and higher skin permeation than that of MHY solution. In an in vivo evaluation of antimelanogenic activity, MHY-SLNs showed a prominent inhibitory effect against ultraviolet B-induced melanogenesis, resulting in no change in the skin color of C57BL/6 mouse, compared with that observed in an MHY solution-treated group and an untreated control group. The antimelanogenic effect of MHY-SLNs was further confirmed through Fontana–Masson staining. Importantly, MHY-SLNs did not induce any toxic effects in the L929 cell line. Overall, these data indicate that MHY-SLNs show promise in the topical treatment of hyperpigmentation. Keywords: melanogenesis, hyperpigmentation, MHY498, solid lipid nanoparticles, skin delivery

  17. Screening and monitoring of MPL W515L mutation with real-time PCR in patients with myelofibrosis undergoing allogeneic-SCT.

    Science.gov (United States)

    Alchalby, H; Badbaran, A; Bock, O; Fehse, B; Bacher, U; Zander, A R; Kröger, N

    2010-09-01

    Monitoring of minimal residual disease (MRD) after allogeneic (allo)-SCT for myelofibrosis (MF) allows recognizing the depth of remission and thus guides application of appropriate therapeutic interventions. MPL W515L/K mutations, which are detected in 5-10% of JAK2V617F-negative patients, may be useful for this purpose. Using a highly sensitive quantitative PCR method, we tested 90 patients with MF who underwent allo-SCT for the presence of MPL W515L/K mutations. Two patients with primary MF were found to harbor MPLW515L while no patient was positive for MPLW515K mutation. Both patients were JAK2V617F negative and cleared the mutation rapidly after allo-SCT and remained negative for a median follow-up of 19 months. The results of molecular monitoring correlated well with other remission parameters such as normalization of peripheral blood counts and morphology and complete donor chimerism. We conclude that MPLW515L can be cleared after allo-SCT and hence may be used as an MRD marker in a proportion of JAK2V617F-negative MF patients.

  18. Growth hormone-releasing peptide-biotin conjugate stimulates myocytes differentiation through insulin-like growth factor-1 and collagen type I.

    Science.gov (United States)

    Lim, Chae Jin; Jeon, Jung Eun; Jeong, Se Kyoo; Yoon, Seok Jeong; Kwon, Seon Deok; Lim, Jina; Park, Keedon; Kim, Dae Yong; Ahn, Jeong Keun; Kim, Bong-Woo

    2015-09-01

    Based on the potential beneficial effects of growth hormone releasing peptide (GHRP)-6 on muscle functions, a newly synthesized GHRP-6-biotin conjugate was tested on cultured myoblast cells. Increased expression of myogenic marker proteins was observed in GHRP-6-biotin conjugate-treated cells. Additionally, increased expression levels of insulin-like growth factor-1 and collagen type I were observed. Furthermore, GHRP-6-biotin conjugate-treated cells showed increased metabolic activity, as indicated by increased concentrations of energy metabolites, such as ATP and lactate, and increased enzymatic activity of lactate dehydrogenase and creatine kinase. Finally, binding protein analysis suggested few candidate proteins, including desmin, actin, and zinc finger protein 691 as potential targets for GHRP6-biotin conjugate action. These results suggest that the newly synthesized GHRP-6-biotin conjugate has myogenic stimulating activity through, at least in part, by stimulating collagen type I synthesis and several key proteins. Practical applications of the GHRP-6-biotin conjugate could include improving muscle condition.

  19. Changes Of Hydration Level In Type I Collagen And Glycosaminoglycans Synthesized In The Rat’s Skin Under The Mechanical Stress

    Directory of Open Access Journals (Sweden)

    Alexandr M. Ponomarenko

    2013-01-01

    Full Text Available Changes of Hydratation Level Of Type I Collagen And Glycosaminoglycans That Are Synthesized In The Rat’s Skin Under The Mechanical Stress. The effect of the mechanical stress on the levels of hydratation of type I collagen and glycosaminoglycans that are synthesized in it, has been studied in vitro using the rats’ skin. The measured hydration of isotherms has shown that mechanical stress in the skin increases and decreases the amount of absorbed water in glycosaminoglycans and in collagen, respectively. Сalculated the average amounts of water molecules in collagen tripeptide and glycosaminoglycans disaccharide unit in the inside and outside layers of their hydrate shells

  20. Cirrus clouds properties derived from polarized micro pulse lidar (p-mpl observations at the atmospheric observatory ‘el arenosillo’ (sw iberian peninsula: a case study for radiative implications

    Directory of Open Access Journals (Sweden)

    Águila Ana del

    2018-01-01

    Full Text Available Cirrus (Ci clouds are involved in Climate Change concerns since they affect the radiative balance of the atmosphere. Recently, a polarized Micro Pulse Lidar (P-MPL, standard system within NASA/MPLNET has been deployed at the INTA/Atmospheric Observatory ‘El Arenosillo’ (ARN, located in the SW Iberian Peninsula. Hence, the INTA/P-MPL system is used for Ci detection over that station for the first time. Radiative effects of a Ci case observed over ARN are examined, as reference for future long-term Ci observations. Optical and macrophysical properties are retrieved, and used for radiative transfer simulations. Data are compared to the measured surface radiation levels and all-sky images simultaneously performed at the ARN station.

  1. Molecular Docking and Anticonvulsant Activity of Newly Synthesized Quinazoline Derivatives

    Directory of Open Access Journals (Sweden)

    Hatem A. Abuelizz

    2017-06-01

    Full Text Available A new series of quinazoline-4(3H-ones are evaluated for anticonvulsant activity. After intraperitoneal (ip injection to albino mice at a dose of 100 mg/kg body weight, synthesized quinazolin-4(3H-ones (1–24 were examined in the maximal electroshock (MES induced seizures and subcutaneous pentylenetetrazole (scPTZ induced seizure models in mice. The Rotarod method was applied to determine the neurotoxicity. Most of the compounds displayed anticonvulsant activity in the scPTZ screen at a dose range of 0.204–0.376 mmol/mL. Out of twenty-four, compounds 8, 13 and 19 proved to be the most active with a remarkable protection (100% against PTZ induced convulsions and four times more potent activity than ethosuximide. The structure-activity relationship concluded valuable pharmacophoric information, which was confirmed by the molecular docking studies using the target enzyme human carbon anhydrase II (HCA II. The studied quinazoline analogues suggested that the butyl substitution at position 3 has a significant effect on preventing the spread of seizure discharge and on raising the seizure threshold. However, benzyl substitution at position 3 has shown a strong anticonvulsant activity but with less seizure prevention compared to the butyl substitution.

  2. Immunization of C57BL/6 Mice with GRA2 Combined with MPL Conferred Partial Immune Protection against Toxoplasma gondii

    Science.gov (United States)

    Babaie, Jalal; Amiri, Samira; Homayoun, Robab; Azimi, Ebrahim; Mohabati, Reyhaneh; Berizi, Mahboobe; Sadaie, M. Reza; Golkar, Majid

    2018-01-01

    We have previously reported that immunization with GRA2 antigen of Toxoplasma gondii induces protective immunity in CBA/J (H2k) and BALB/c mice (H2d). We aimed to examine whether immunization of a distinct strain of rodent with recombinant dense granule antigens (GRA2) combined with monophosphorryl lipid A (MPL) adjuvant elicits protective immune response against T. gondii. C57BL/6 (H2b haplotype) mice were immunized with GRA2, formulated in MPL adjuvant. Strong humoral response, predominantly of IgG1 subclass and cellular response, IFN-γ, was detected at three weeks post immunization. Mice immunized with GRA2 had significantly (p < 0.01) fewer brain cysts than those in the adjuvant group, upon challenge infection. Despite the production of a strong antibody response, IFN-γ production and brain cyst reduction were not significant when the immunized mice were infected four months after the immunization. We can conclude that GRA2 immunization partially protects against T. gondii infection in C57BL/6 mice, though the potency and longevity of this antigen as a standalone vaccine may vary in distinct genetic backgrounds. This observation further emphasizes the utility of GRA2 for incorporation into a multi-antigenic vaccine against T. gondii.

  3. A 1.5 V 7.656 GHz PLL with I/Q outputs for a UWB synthesizer

    International Nuclear Information System (INIS)

    Chen Pufeng; Zhang Haiying; Ye Tianchun

    2010-01-01

    A fully integrated CMOS phase-locked loop (PLL) which can synthesize a quadrature output frequency of 7.656 GHz is presented. The proposed PLL can be employed as a building block for an MB-OFDM UWB frequency synthesizer. To achieve fast loop settling, integer- N architecture operating with 66 MHz reference frequency and wideband QVCO are implemented. I/Q carriers are generated by two bottom-series cross-coupled LC VCOs. Realized in 0.18 μm CMOS technology, this PLL consumes 16 mA current (including buffers) from a 1.5 V supply and the phase noise is -109.6 dBc/Hz at 1 MHz offset. The measured oscillation frequency shows that the QVCO has a range of 6.95 to 8.73 GHz. The core circuit occupies an area of 1 x 0.5 mm 2 . (semiconductor integrated circuits)

  4. A 1.5 V 7.656 GHz PLL with I/Q outputs for a UWB synthesizer

    Energy Technology Data Exchange (ETDEWEB)

    Chen Pufeng; Zhang Haiying; Ye Tianchun, E-mail: chenpufeng@ime.ac.c [Institute of Microelectronics, Chinese Academy of Sciences, Beijing 100029 (China)

    2010-06-15

    A fully integrated CMOS phase-locked loop (PLL) which can synthesize a quadrature output frequency of 7.656 GHz is presented. The proposed PLL can be employed as a building block for an MB-OFDM UWB frequency synthesizer. To achieve fast loop settling, integer- N architecture operating with 66 MHz reference frequency and wideband QVCO are implemented. I/Q carriers are generated by two bottom-series cross-coupled LC VCOs. Realized in 0.18 {mu}m CMOS technology, this PLL consumes 16 mA current (including buffers) from a 1.5 V supply and the phase noise is -109.6 dBc/Hz at 1 MHz offset. The measured oscillation frequency shows that the QVCO has a range of 6.95 to 8.73 GHz. The core circuit occupies an area of 1 x 0.5 mm{sup 2}. (semiconductor integrated circuits)

  5. Anti-inflammatory and antinociceptive evaluation of newly synthesized 4-(substituted ethanoyl amino-3-mercapto-5-(4-methoxy phenyl-1,2,4-triazoles

    Directory of Open Access Journals (Sweden)

    Neeraj Upmanyu

    2011-01-01

    Full Text Available Introduction: 1,2,4-triazoles and its derivatives have been reported to possess anti-inflammatory, analgesic, antimicrobial, anticancer, antitumor, antitubercular, anticonvulsant, openers of Ca-activated potassium (Maxi-K channels, antiviral properties, hypoglycemic, anxiolytic and antidepressant activity. Therefore, 1,2,4-triazole seems to be an important pharmacophore. Materials and Methods: The synthesis of 4-(substituted ethanoyl amino-3-mercapto-5-(4-methoxy phenyl-1,2,4-triazoles (6a-o were prepared following six step starting 4-methoxy benzoic acid and using different secondary amines and were characterized with the help of FT-IR, 1 H, 13 C NMR, FAB Mass and nitrogen analysis. These synthesized compounds (6a-o were then evaluated for anti-inflammatory activity by carrageenan induced paw edema method.Out of these synthesized compounds, some (6f, i and k were evaluated for antinociceptive activity by Hot plate method and Tail immersion method. Results and Discussion: The synthesis of 4-(substituted amino-3-mercapto-5-(4-methoxy phenyl-1,2,4-triazoles (6a-o was accomplished. The IR spectra exhibited characteristic bands for C-N, C=N, SH and C=O at 1350-1360, 1511-1548, 2520-2594.3 and 1650-1719 cm -1 . The C-O-C asymmetric and symmetric str. was at 1250-1254 and 1027-1079.3 cm -1 respectively. In 1 H-NMR spectra, a singlet of CONH was found in the range of δ 9.92-10.18 ppm and another singlet of thiol group was observed in the range of δ 8.63-9.92 ppm. A singlet of Ar-OCH 3 was also found between δ 3.57-3.91 ppm. In 13 C- NMR spectra, C-3 and C-5 of the 1,2,4 - triazole nucleus were observed in the range of δ 147-166.9 ppm. Carbonyl carbon and methylene carbon of -NHCOCH 2 N< were found between δ 166.5-177.5 and δ 47.1-62 ppm respectively. Acute toxicity study was donr following OECD-423 and cut-off dose was found to be between 1000-1500 mg/kg body weight. At the dose level of 100 mg/kg, 6f, 6i and 6k exhibited appreciable inhibition

  6. Phase transformations of high-purity PbI{sub 2} nanoparticles synthesized from lead-acid accumulator anodes

    Energy Technology Data Exchange (ETDEWEB)

    Malevu, T.D., E-mail: malevutd@ufs.ac.za; Ocaya, R.O.; Tshabalala, K.G.

    2016-09-01

    High-purity hexagonal lead iodide nanoparticles have been synthesized from a depleted sealed lead acid battery anode. The synthesized product was found to consist of the rare 6R polytype form of PbI{sub 2} that is thought to have good potential in photovoltaic applications. We investigate the effects of annealing time and post-melting temperature on the structure and optical properties using 1.5418 Å CuKα radiation. Photoluminescence measurements were done under 150 W/221 nm wavelength xenon excitation. Phase transformation was observed through XRD peaks when annealing time increased from 0.5–5 h. The nanoparticle grain size and inter-planar distance appeared to be independent of annealing time. PL measurements show three broad peaks in a range of 400 nm to 700 nm that are attributed to excitonic, donor–acceptor pair and luminescence bands from the deep levels.

  7. Mitochondrial nucleoid clusters protect newly synthesized mtDNA during Doxorubicin- and Ethidium Bromide-induced mitochondrial stress

    Energy Technology Data Exchange (ETDEWEB)

    Alán, Lukáš, E-mail: lukas.alan@fgu.cas.cz; Špaček, Tomáš; Pajuelo Reguera, David; Jabůrek, Martin; Ježek, Petr

    2016-07-01

    Mitochondrial DNA (mtDNA) is compacted in ribonucleoprotein complexes called nucleoids, which can divide or move within the mitochondrial network. Mitochondrial nucleoids are able to aggregate into clusters upon reaction with intercalators such as the mtDNA depletion agent Ethidium Bromide (EB) or anticancer drug Doxorobicin (DXR). However, the exact mechanism of nucleoid clusters formation remains unknown. Resolving these processes may help to elucidate the mechanisms of DXR-induced cardiotoxicity. Therefore, we addressed the role of two key nucleoid proteins; mitochondrial transcription factor A (TFAM) and mitochondrial single-stranded binding protein (mtSSB); in the formation of mitochondrial nucleoid clusters during the action of intercalators. We found that both intercalators cause numerous aberrations due to perturbing their native status. By blocking mtDNA replication, both agents also prevented mtDNA association with TFAM, consequently causing nucleoid aggregation into large nucleoid clusters enriched with TFAM, co-existing with the normal nucleoid population. In the later stages of intercalation (> 48 h), TFAM levels were reduced to 25%. In contrast, mtSSB was released from mtDNA and freely distributed within the mitochondrial network. Nucleoid clusters mostly contained nucleoids with newly replicated mtDNA, however the nucleoid population which was not in replication mode remained outside the clusters. Moreover, the nucleoid clusters were enriched with p53, an anti-oncogenic gatekeeper. We suggest that mitochondrial nucleoid clustering is a mechanism for protecting nucleoids with newly replicated DNA against intercalators mediating genotoxic stress. These results provide new insight into the common mitochondrial response to mtDNA stress and can be implied also on DXR-induced mitochondrial cytotoxicity. - Highlights: • The mechanism for mitochondrial nucleoid clustering is proposed. • DNA intercalators (Doxorubicin or Ethidium Bromide) prevent TFAM

  8. Solid-phase extraction of the alcohol abuse biomarker phosphatidylethanol using newly synthesized polymeric sorbent materials containing quaternary heterocyclic groups.

    Science.gov (United States)

    Duarte, Mariana; Jagadeesan, Kishore Kumar; Billing, Johan; Yilmaz, Ecevit; Laurell, Thomas; Ekström, Simon

    2017-10-13

    Phosphatidylethanol (PEth) is an interesting biomarker finding increased use for detecting long term alcohol abuse with high specificity and sensitivity. Prior to detection, sample preparation is an unavoidable step in the work-flow of PEth analysis and new protocols may facilitate it. Solid-phase extraction (SPE) is a versatile sample preparation method widely spread in biomedical laboratories due to its simplicity of use and the possibility of automation. In this work, SPE was used for the first time to directly extract PEth from spiked human plasma and spiked human blood. A library of polymeric SPE materials with different surface functionalities was screened for PEth extraction in order to identify the surface characteristics that control PEth retention and recovery. The plasma samples were diluted 1:10 (v/v) in water and spiked at different concentrations ranging from 0.3 to 5μM. The library of SPE materials was then evaluated using the proposed SPE method and detection was done by LC-MS/MS. One SPE material efficiently retained and recovered PEth from spiked human plasma. With this insight, four new SPE materials were formulated and synthesized based on the surface characteristics of the best SPE material found in the first screening. These new materials were tested with spiked human blood, to better mimic a real clinical sample. All the newly synthetized materials outperformed the pre-existing commercially available materials. Recovery values for the new SPE materials were found between 29.5% and 48.6% for the extraction of PEth in spiked blood. A material based on quaternized 1-vinylimidazole with a poly(trimethylolpropane trimethacrylate) backbone was found suitable for PEth extraction in spiked blood showing the highest analyte recovery in this experiment, 48.6%±6.4%. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. LW-214, a newly synthesized flavonoid, induces intrinsic apoptosis pathway by down-regulating Trx-1 in MCF-7 human breast cells.

    Science.gov (United States)

    Pan, Di; Li, Wei; Miao, Hanchi; Yao, Jing; Li, Zhiyu; Wei, Libin; Zhao, Li; Guo, Qinglong

    2014-02-15

    In this study, the anticancer effect of LW-214, a newly synthesized flavonoid, against MCF-7 human breast cancer cells and the underlying mechanisms were investigated. LW-214 triggered the mitochondrial apoptotic pathway by increasing Bax/Bcl-2 ratio, loss of mitochondrial membrane potential (ΔΨm) and caspase-9 activation, degradation of poly (ADP-ribose) polymerase (PARP), cytochrome c (Cyt c) release and apoptosis-inducing factor (AIF) transposition. Further research revealed that both the reactive oxygen species (ROS) generation and the apoptosis signal regulating kinase 1 (ASK1) activation by LW-214 were induced by down-regulating the thioredoxin-1 (Trx-1) expression. The ROS elevation and ASK1 activation induced a sustained phosphorylation of c-Jun N-terminal kinase (JNK), while SP600125, as known as JNK inhibitor, almost reversed LW-214-induced apoptosis in MCF-7 cells. Overexpression of Trx-1 in MCF-7 cells attenuated LW-214-mediated apoptosis as well as the JNK activation and reversed the expression of mitochondrial apoptosis-related protein. Accordingly, the in vivo study showed that LW-214 exhibited a potential antitumor effect in BALB/c species mice inoculated MCF-7 tumor with low systemic toxicity, and the mechanism was the same as in vitro study. Taken together, these findings indicated that LW-214 may down-regulated Trx-1 function, causing intracellular ROS generation and releasing the ASK1, and lead to JNK activation, which consequently induced the mitochondrial apoptosis in vitro and in vivo. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. The Semi-automatic Synthesis of 18F-fluoroethyl-choline by Domestic FDG Synthesizer

    Directory of Open Access Journals (Sweden)

    ZHOU Ming

    2016-02-01

    Full Text Available As an important complementary imaging agent for 18F-FDG, 18F-fluoroethyl-choline (18F-FECH has been demonstrated to be promising in brain and prostate cancer imaging. By using domestic PET-FDG-TI-I CPCU synthesizer, 18F-FECH was synthesized by different reagents and consumable supplies. The C18 column was added before the product collection bottle to remove K2.2.2. The 18F-FECH was synthesized by PET-FDG-IT-I synthesizer efficiently about 30 minutes by radiochemical yield of 42.0% (no decay corrected, n=5, and the radiochemical purity was still more than 99.0% after 6 hours. The results showed the domestic PET-FDG-IT-I synthesizer could semi-automatically synthesize injectable 18F-FECH in high efficiency and radiochemical purity

  11. A Physicochemical and Pharmacological Study of the Newly Synthesized Complex of Albendazole and the Polysaccharide Arabinogalactan from Larch Wood.

    Science.gov (United States)

    Chistyachenko, Yulia S; Meteleva, Elizaveta S; Pakharukova, Maria Y; Katokhin, Aleksey V; Khvostov, Mikhail V; Varlamova, Anastasiya I; Glamazdin, Igor I; Khalikov, Salavat S; Polyakov, Nikolay E; Arkhipov, Ivan A; Tolstikova, Tatyana G; Mordvinov, Viatcheslav A; Dushkin, Alexander V; Lyakhov, Nikolay Z

    2015-01-01

    Inclusion complexes of albendazole (ABZ) with the polysaccharide arabinogalactan from larch wood Larix sibirica and Larix gmelinii were synthesized using a solid-state mechanochemical technology. We investigated physicochemical properties of the synthesized complexes in the solid state and in aqueous solutions as well as their anthelmintic activity against Trichinella spiralis, Hymenolepis nаna, Fasciola hepatica, Opisthorchis felineus, and mixed nematodoses of sheep. Formation of the complexes was demonstrated by means of intrinsic solubility and the NMR relaxation method. The mechanochemically synthesized complexes were more stable in comparison with the complex produced by mixing solutions of the components. The complexes of ABZ showed anthelmintic activity at 10-fold lower doses than did free ABZ. The complexes also showed lower acute toxicity and hepatotoxicity. These results suggest that it is possible to design new drugs on the basis of the ABZ:arabinogalactan complex that are safer and more effective than albendazole.

  12. Hypoactivation of reward motivational system in patients with newly diagnosed hypertension grade I-II.

    Science.gov (United States)

    Aftanas, L I; Brak, I V; Gilinskaya, O M; Korenek, V V; Pavlov, S V; Reva, N V

    2014-08-01

    In patients with newly diagnosed untreated grade I-II hypertension, EEG oscillations were recorded under conditions activation of the two basic motivational systems, defensive motivational system and positive reinforcement system, evoked by recall of personally meaningful emotional events. The 64-channel EEG and cardiovascular reactivity (beat-by-beat technology) were simultaneously recorded. At rest, hypertensive patients had significantly reduced platelet serotonin concentrations in comparison with healthy individuals. The patients experiencing emotional activation were characterized by significantly lower intensity of positive emotions associated with more pronounced suppression of EEG activity in the delta (2-4 Hz) and theta (ranges of frequency 4-6 and 6-8 Hz) oscillators in the parieto-occipital cortex (zones P and PO) in both hemispheres of the brain. The findings attest to insufficient function of the brain serotonin system and hypoactivation of the reward/reinforcement system in patients with primary hypertension.

  13. Newly developed chitosan-silver hybrid nanoparticles: biosafety and apoptosis induction in HepG2 cells

    International Nuclear Information System (INIS)

    El-Sherbiny, Ibrahim M.; Salih, Ehab; Yassin, Abdelrahman M.; Hafez, Elsayed E.

    2016-01-01

    The present study reports the biosafety assessment, the exact molecular effects, and apoptosis induction of newly developed chitosan-silver hybrid nanoparticles (Cs–Ag NPs) in HepG2 cells. The investigated hybrid NPs were green synthesized using Cs/grape leaves aqueous extract (Cs/GLE) or Cs/GLE NPs as reducing and stabilizing agents. The successful formation of Cs/GLE NPs and Cs–Ag hybrid NPs has been confirmed by UV–Vis spectrophotometry, FTIR spectroscopy, XRD, and HRTEM. From the TEM analysis, the prepared Cs/GLE NPs are uniform and spherical with an average size of 150 nm, and the AgNPs (5–10 nm) were formed mainly on their surface. The UV–Vis spectra of Cs–Ag NPs showed a surface plasmon resonance (SPR) peak at about 450 nm confirming their formation. The synthesized Cs–Ag NPs were found to be crystalline as shown by XRD patterns with fcc phase oriented along the (111), (200), (220), and (311) planes. The cytotoxicity patterns, the antiproliferative activities, and the possible mechanisms of anticancer activity at molecular level of the newly developed Cs–Ag hybrid NPs were investigated. Cytotoxicity patterns of all the preparations demonstrated that the nontoxic treatment concentrations are ranged from 0.39 to 50 %, and many of the newly prepared Cs–Ag hybrid NPs showed high anticancer activities against HpG2 cells, and induced cellular apoptosis by downregulating BCL2 gene and upregulating P53.Graphical Abstract

  14. Newly developed chitosan-silver hybrid nanoparticles: biosafety and apoptosis induction in HepG2 cells

    Energy Technology Data Exchange (ETDEWEB)

    El-Sherbiny, Ibrahim M., E-mail: ielsherbiny@Zewailcity.edu.eg; Salih, Ehab [Zewail City of Science and Technology, Center for Materials Science (Egypt); Yassin, Abdelrahman M. [Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technology Applications, Biopharmaceutical Product Research Department (Egypt); Hafez, Elsayed E. [City of Scientific Research and Technology Applications, Plant Protection and Biomolecular Diagnosis Department (Egypt)

    2016-07-15

    The present study reports the biosafety assessment, the exact molecular effects, and apoptosis induction of newly developed chitosan-silver hybrid nanoparticles (Cs–Ag NPs) in HepG2 cells. The investigated hybrid NPs were green synthesized using Cs/grape leaves aqueous extract (Cs/GLE) or Cs/GLE NPs as reducing and stabilizing agents. The successful formation of Cs/GLE NPs and Cs–Ag hybrid NPs has been confirmed by UV–Vis spectrophotometry, FTIR spectroscopy, XRD, and HRTEM. From the TEM analysis, the prepared Cs/GLE NPs are uniform and spherical with an average size of 150 nm, and the AgNPs (5–10 nm) were formed mainly on their surface. The UV–Vis spectra of Cs–Ag NPs showed a surface plasmon resonance (SPR) peak at about 450 nm confirming their formation. The synthesized Cs–Ag NPs were found to be crystalline as shown by XRD patterns with fcc phase oriented along the (111), (200), (220), and (311) planes. The cytotoxicity patterns, the antiproliferative activities, and the possible mechanisms of anticancer activity at molecular level of the newly developed Cs–Ag hybrid NPs were investigated. Cytotoxicity patterns of all the preparations demonstrated that the nontoxic treatment concentrations are ranged from 0.39 to 50 %, and many of the newly prepared Cs–Ag hybrid NPs showed high anticancer activities against HpG2 cells, and induced cellular apoptosis by downregulating BCL2 gene and upregulating P53.Graphical Abstract.

  15. Substitution of conventional high-temperature syntheses of inorganic compounds by near-room-temperature syntheses in ionic liquids

    KAUST Repository

    Groh, Matthias Friedrich

    2013-01-01

    The high-temperature syntheses of the low-valent halogenides P2I4, Te2Br, α-Te4I4, Te4(Al2Cl7)2, Te4(Bi6Cl20), Te8(Bi4Cl14),Bi8(AlCl4)2, Bi6Cl7,and Bi6Br7, as well as of WSCl4 andWOCl4 have been replaced by resource-efficient low-temperature syntheses in room temperature ionic liquids (RTILs). The simple one-pot syntheses generally do not require elaborate equipment such as twozone furnaces or evacuated silica ampoules. Compared to the published conventional approaches, reduction of reaction time (up to 80%) and temperature (up to 500 K) and, simultaneously, an increase in yield were achieved. In the majority of cases, the solid products were phase-pure. X-Ray diffraction on single crystals (redetermination of 11 crystal structures) has demonstrated that the quality of the crystals from RTILs is comparable to that of products obtained by chemical transport reactions. © 2013 Verlag der Zeitschrift für Naturforschung, Tübingen.

  16. A Multiplex Snapback Primer System for the Enrichment and Detection of JAK2 V617F and MPL W515L/K Mutations in Philadelphia-Negative Myeloproliferative Neoplasms

    Directory of Open Access Journals (Sweden)

    Zhiyuan Wu

    2014-01-01

    Full Text Available A multiplex snapback primer system was developed for the simultaneous detection of JAK2 V617F and MPL W515L/K mutations in Philadelphia chromosome- (Ph- negative myeloproliferative neoplasms (MPNs. The multiplex system comprises two snapback versus limiting primer sets for JAK2 and MPL mutation enrichment and detection, respectively. Linear-After exponential (LATE PCR strategy was employed for the primer design to maximize the amplification efficiency of the system. Low ionic strength buffer and rapid PCR protocol allowed for selective amplification of the mutant alleles. Amplification products were analyzed by melting curve analysis for mutation identification. The multiplex system archived 0.1% mutation load sensitivity and <5% coefficient of variation inter-/intra-assay reproducibility. 120 clinical samples were tested by the multiplex snapback primer assay, and verified with amplification refractory system (ARMS, quantitative PCR (qPCR and Sanger sequencing method. The multiplex system, with a favored versatility, provided the molecular diagnosis of Ph-negative MPNs with a suitable implement and simplified the genetic test process.

  17. A Multiplex Snapback Primer System for the Enrichment and Detection of JAK2 V617F and MPL W515L/K Mutations in Philadelphia-Negative Myeloproliferative Neoplasms

    Science.gov (United States)

    Zhang, Yunqing; Zhang, Xinju; Xu, Xiao; Kang, Zhihua; Li, Shibao; Zhang, Chen; Su, Bing

    2014-01-01

    A multiplex snapback primer system was developed for the simultaneous detection of JAK2 V617F and MPL W515L/K mutations in Philadelphia chromosome- (Ph-) negative myeloproliferative neoplasms (MPNs). The multiplex system comprises two snapback versus limiting primer sets for JAK2 and MPL mutation enrichment and detection, respectively. Linear-After exponential (LATE) PCR strategy was employed for the primer design to maximize the amplification efficiency of the system. Low ionic strength buffer and rapid PCR protocol allowed for selective amplification of the mutant alleles. Amplification products were analyzed by melting curve analysis for mutation identification. The multiplex system archived 0.1% mutation load sensitivity and <5% coefficient of variation inter-/intra-assay reproducibility. 120 clinical samples were tested by the multiplex snapback primer assay, and verified with amplification refractory system (ARMS), quantitative PCR (qPCR) and Sanger sequencing method. The multiplex system, with a favored versatility, provided the molecular diagnosis of Ph-negative MPNs with a suitable implement and simplified the genetic test process. PMID:24729973

  18. Evolutionary selection of enzymatically synthesized semiconductors from biomimetic mineralization vesicles.

    Science.gov (United States)

    Bawazer, Lukmaan A; Izumi, Michi; Kolodin, Dmitriy; Neilson, James R; Schwenzer, Birgit; Morse, Daniel E

    2012-06-26

    The way nature evolves and sculpts materials using proteins inspires new approaches to materials engineering but is still not completely understood. Here, we present a cell-free synthetic biological platform to advance studies of biologically synthesized solid-state materials. This platform is capable of simultaneously exerting many of the hierarchical levels of control found in natural biomineralization, including genetic, chemical, spatial, structural, and morphological control, while supporting the evolutionary selection of new mineralizing proteins and the corresponding genetically encoded materials that they produce. DNA-directed protein expression and enzymatic mineralization occur on polystyrene microbeads in water-in-oil emulsions, yielding synthetic surrogates of biomineralizing cells that are then screened by flow sorting, with light-scattering signals used to sort the resulting mineralized composites differentially. We demonstrate the utility of this platform by evolutionarily selecting newly identified silicateins, biomineralizing enzymes previously identified from the silica skeleton of a marine sponge, for enzyme variants capable of synthesizing silicon dioxide (silica) or titanium dioxide (titania) composites. Mineral composites of intermediate strength are preferentially selected to remain intact for identification during cell sorting, and then to collapse postsorting to expose the encoding genes for enzymatic DNA amplification. Some of the newly selected silicatein variants catalyze the formation of crystalline silicates, whereas the parent silicateins lack this ability. The demonstrated bioengineered route to previously undescribed materials introduces in vitro enzyme selection as a viable strategy for mimicking genetic evolution of materials as it occurs in nature.

  19. Accumulation of operational history through emulation test to meet proven technology requirement for newly developed I and C technology

    International Nuclear Information System (INIS)

    Yeong Cheol, Shin; Sung Kon, Kang; Han Seong, Son

    2006-01-01

    As new advanced digital I and C technology with potential benefits of higher functionality and better cost effectiveness is available in the market, NPP (Nuclear Power Plant) operators are inclined to use the new technology for the construction of new plant and the upgrade of existing plants. However, this new technology poses risks to the NPP operators at the same time. These risks are mainly due to the poor reliability of newly developed technology. KHNP's past experiences with the new equipment shows many cases of reliability problems. And their consequences include unintended plant trips, lowered acceptance of the new digital technology by the plant I and C maintenance crew, and increased licensing burden in answering for questions from the nuclear regulatory body. Considering the fact that the risk of these failures in the nuclear plant operation is far greater than those in other industry, nuclear power plant operators want proven technology for I and C systems. This paper presents an approach for the emulation of operational history through which a newly developed technology becomes a proven technology. One of the essential elements of this approach is the feedback scheme of running the new equipment in emulated environment, gathering equipment failure, and correcting the design(and test bed). The emulation of environment includes normal and abnormal events of the new equipment such as reconfiguration of control system due to power failure, plant operation including full spectrum of credible scenarios in an NPP. Emulation of I and C equipment execution mode includes normal operation, initialization and termination, abnormal operation, hardware maintenance and maintenance of algorithm/software. Plant specific simulator is used to create complete profile of plant operational conditions that I and C equipment is to experience in the real plant. Virtual operating crew technology is developed to run the simulator scenarios without involvement of actual operators

  20. Three new Ag(I) coordination architectures based on mixed ligands: Syntheses, structures and photoluminescent properties

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yamin, E-mail: liyamin@henu.edu.cn [Institute of Molecular and Crystal Engineering, College of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan 475004 (China); State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002 (China); Xiao, Changyu; Li, Shu; Chen, Qi; Li, Beibei; Liao, Qian; Niu, Jingyang [Institute of Molecular and Crystal Engineering, College of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan 475004 (China)

    2013-04-15

    Three new silver (I) coordination complexes, [Ag{sub 2}(1,2-bdc)(phdat)]{sub n} (1), [Ag{sub 2}(NO{sub 2}-bdc)(phdat)]{sub n} (2), [Ag{sub 4}(nta){sub 3}(phdat)NO{sub 3}]{sub n} (3) (1,2-bdc=phthalic acid dianion, NO{sub 2}-bdc=5-nitro-1,3-benzenedicarboxylic acid dianion, nta=nicotinic acid anion, phdat=2,4-diamine-6-phenyl-1,3,5-triazine) have been hydrothermally synthesized by the reactions of silver nitrate and phdat with the homologous ligands 1,2-H{sub 2}bdc, NO{sub 2}-H{sub 2}bdc, and Hnta, respectively, and characterized by single-crystal X-ray diffractions, IR spectra, elemental analyses thermogravimetric analyses (TGA). The compound 1 exhibits a chiral 3D network with cbs/CrB self-dual topological net, which contains two kinds of single helical chains. For compound 2, the 3D network is comprised of two kinds of similar 2D sheets with the topological symbol of sql-type packed in AABBAA mode by Ag–N/O weakly contacts. And compound 3 has 2D double layer architecture, consisting of the 2D plane with hcb-type topological symbol connected by Ag–O weakly coordinations. The photoluminescent properties associated with the crystal structures of three compounds have also been measured. - Graphical abstract: Three new silver(I) coordination complexes 1–3 have been synthesized and characterized by single-crystal X-ray diffractions, IR spectra, elemental analyses, thermogravimetric analyses (TGA) and photoluminescent spectra. Highlights: ► The compound 1 exhibits a novel chiral 3D network with two kinds of single helical chains. ► 3D or 2D new Ag coordination complexes. ► The photoluminescent properties have been measured.

  1. Newly diagnosed and previously known diabetes mellitus and 1-year outcomes of acute myocardial infarction: the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial

    DEFF Research Database (Denmark)

    Aguilar, David; Solomon, Scott D; Køber, Lars

    2004-01-01

    cardiovascular events associated with previously known and newly diagnosed diabetes by studying 14,703 patients with acute MI enrolled in the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial. Patients were grouped by diabetic status: previously known diabetes (insulin use or diagnosis of diabetes before...

  2. Nano magnetic solid phase extraction for preconcentration of lead ions in environmental samples by a newly synthesized reagent.

    Science.gov (United States)

    Golshekan, Mostafa; Shariati, Shahab

    2013-01-01

    In this study, magnetite nanoparticles with particle size lower than 47 nm were synthesized and were applied for preconcentration of Pb2+ ions from aqueous solutions. To preconcentrate the Pb2+ ions, the surface of the synthesized nano particles was modified with sodium dodecyl sulfate (SDS) as an anionic surfactant. A new chelating agent (2-((E)-2-amino-4,5-dinitrophenylimino)methyl)phenol) was synthesized and used to form a very stable complex with Pb2+ ions. The lead ions formed complexes and were quantitatively extracted with SDS-coated magnetite nanoparticles. After magnetic separation of adsorbent, the adsorbent was eluted with 0.5% (v/v) HC1 in dimethyl sulfoxide (DMSO) prior to analysis by flame atomic absorption spectrometry (FAAS). Orthogonal array design (OAD) was used to study and optimize the different experimental parameters. Under the optimum conditions, enhancement factor up to 63.5 was achieved for extraction from only 10 mL of sample solution and the relative standard deviation (RSD %) of the method was lower than 2.8%. The obtained calibration curve was linear in the range of 1-300 pg L-' with reasonable linearity (r2 > 0.998). The limit of detection (LOD) based on S/N = 3 was 0.04 microg L(-1) for 10 mL sample volumes. Finally, applicability of the proposed method was successfully confirmed by preconcentration and determination of trace amounts of lead ions in environmental samples and satisfactory results were obtained.

  3. Nye sygdomsmarkører ved de kroniske myeloproliferative neoplasier

    DEFF Research Database (Denmark)

    Holmström, Morten Orebo; Ocias, Lukas Frans; Kallenbach, Klaus

    2015-01-01

    The chaperone and calcium storing protein calreticulin is coded by CALR, and newly identified mutations in CALR are found in respectively 49-70% and 56-88% of JAK2- and MPL-negative patients with essential thrombocytaemia (ET) and primary myelofibrosis (PMF). A total of 41 mutations have been...

  4. Characterization and Prognosis Significance of JAK2 (V617F), MPL, and CALR Mutations in Philadelphia-Negative Myeloproliferative Neoplasms

    Science.gov (United States)

    Singdong, Roongrudee; Siriboonpiputtana, Teerapong; Chareonsirisuthigul, Takol; Kongruang, Adcharee; Limsuwanachot, Nittaya; Sirirat, Tanasan; Chuncharunee, Suporn; Rerkamnuaychoke, Budsaba

    2016-10-01

    Background: The discovery of somatic acquired mutations of JAK2 (V617F) in Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) has not only improved rational disease classification and prognostication but also brings new understanding insight into the pathogenesis of diseases. Dosage effects of the JAK2 (V617F) allelic burden in Ph-negative MPNs may partially influence clinical presentation, disease progression, and treatment outcome. Material and Methods: Pyrosequencing was performed to detect JAK2 (V617F) and MPL (W515K/L) and capillary electrophoresis to identify CALR exon 9.0 mutations in 100.0 samples of Ph-negative MPNs (38.0 PV, 55 ET, 4 PMF, and 3 MPN-U). Results: The results showed somatic mutations of JAK2 (V617F) in 94.7% of PV, 74.5% of ET, 25.0% of PMF, and all MPN-U. A high proportion of JAK2 (V617F) mutant allele burden (mutational load > 50.0%) was predominantly observed in PV when compared with ET. Although a high level of JAK2 (V617F) allele burden was strongly associated with high WBC counts in both PV and ET, several hematological parameters (hemoglobin, hematocrit, and platelet count) were independent of JAK2 (V617F) mutational load. MPL (W515K/L) mutations could not be detected whereas CALR exon 9.0 mutations were identified in 35.7% of patients with JAK2 negative ET and 33.3% with JAK2 negative PMF. Conclusions: The JAK2 (V617F) allele burden may be involved in progression of MPNs. Furthermore, a high level of JAK2 (V617F) mutant allele appears strongly associated with leukocytosis in both PV and ET. Creative Commons Attribution License

  5. Morphological Findings in Trophozoites during Amoebic Abscess Development in Misoprostol-Treated BALB/c Mice

    Directory of Open Access Journals (Sweden)

    Andrés Aceves-Cano

    2015-01-01

    Full Text Available During amoebic liver abscess (ALA formation in susceptible animals, immune response is regulated by prostaglandin E2 (PGE2 dependent mechanisms. The aim of this study was to analyze the effect of misoprostol (MPL, a PGE1 analogue, on ALA formation in BALB/c mice. Male mice from BALB/c strain were intrahepatically infected with 7.5×105 trophozoites of E. histolytica strain HM1:IMSS and treated with 10−4 M of MPL daily until sacrifice at 2, 4, and 7 days postinfection (p.i.. ALA formation was evaluated at 2, 4, and 7 days postinfection; trophozoite morphology was analyzed using immunohistochemistry and image analysis. Results showed an increase in frequency of ALA formation in infected and MPL-treated mice only at 2 days p.i. (P=0.03. A significant diminution in the size of trophozoites was detected in abscesses from mice independently of MPL treatment (from 5.8±1.1 µm at 2 days p.i. to 2.7±1.9 µm at 7 days p.i. compared with trophozoites dimensions observed in susceptible hamsters (9.6±2.7 µm (P<0.01. These results suggest that MPL treatment may modify the adequate control of inflammatory process to allow the persistence of trophozoites in the liver; however, natural resistance mechanisms cannot be discarded.

  6. Thermal conductivity of a graphite bipolar plate (BPP) and its thermal contact resistance with fuel cell gas diffusion layers: Effect of compression, PTFE, micro porous layer (MPL), BPP out-of-flatness and cyclic load

    Science.gov (United States)

    Sadeghifar, Hamidreza; Djilali, Ned; Bahrami, Majid

    2015-01-01

    This paper reports on measurements of thermal conductivity of a graphite bipolar plate (BPP) as a function of temperature and its thermal contact resistance (TCR) with treated and untreated gas diffusion layers (GDLs). The thermal conductivity of the BPP decreases with temperature and its thermal contact resistance with GDLs, which has been overlooked in the literature, is found to be dominant over a relatively wide range of compression. The effects of PTFE loading, micro porous layer (MPL), compression, and BPP out-of-flatness are also investigated experimentally. It is found that high PTFE loadings, MPL and even small BPP out-of-flatness increase the BPP-GDL thermal contact resistance dramatically. The paper also presents the effect of cyclic load on the total resistance of a GDL-BPP assembly, which sheds light on the behavior of these materials under operating conditions in polymer electrolyte membrane fuel cells.

  7. Substitution of conventional high-temperature syntheses of inorganic compounds by near-room-temperature syntheses in ionic liquids

    KAUST Repository

    Groh, Matthias Friedrich; Mü llera, Ulrike; Ahmed, Ejaz; Rothenberger, Alexander; Ruck, Michael J.

    2013-01-01

    The high-temperature syntheses of the low-valent halogenides P2I4, Te2Br, α-Te4I4, Te4(Al2Cl7)2, Te4(Bi6Cl20), Te8(Bi4Cl14),Bi8(AlCl4)2, Bi6Cl7,and Bi6Br7, as well as of WSCl4 andWOCl4 have been replaced by resource-efficient low

  8. Application of dopant-free hole transport materials for perovskite solar cells

    International Nuclear Information System (INIS)

    Franckevincius, M.; Gulbinas, V.; Gratzel, M.; Zakeeruddin, S.; Pauerle, P.; Mishra, A.; Steck, C.

    2015-01-01

    In this work we present the synthesis, characterization and application of a series of additive and dopant free hole transport materials (HTM) for solid-state perovskite-based solar cells. Newly synthesized HTMs showed strong absorption in the visible spectral range and suitable HOMO-LUMO energy levels for the application for methylammonium lead(II) iodide (CH_3NH_3PbI_3) perovskite. Dopant-free perovskite solar cells have been fabricated using CH_3NH_3PbI_3 perovskite and the newly synthesized HTMs following sequential deposition method, which allows us to reach power conversion efficiencies as high as 11.4 %. The easy of synthesis, low cost and relatively high performance of newly synthesized HTMs has great prospects for commercial applications in the near-future. (authors)

  9. Cytoplasmic assembly of snRNP particles from stored proteins and newly transcribed snRNA's in L929 mouse fibroblasts

    International Nuclear Information System (INIS)

    Sauterer, R.A.; Feeney, R.J.; Zieve, G.W.

    1988-01-01

    Newly synthesized snRNAs appear transiently in the cytoplasm where they assemble into ribonucleoprotein particles, the snRNP particles, before returning permanently to the interphase nucleus. In this report, bona fide cytoplasmic fractions, prepared by cell enucleation, are used for a quantitative analysis of snRNP assembly in growing mouse fibroblasts. The half-lives and abundances of the snRNP precursors in the cytoplasm and the rates of snRNP assembly are calculated in L929 cells. With the exception of U6, the major snRNAs are stable RNA species; U1 is almost totally stable while U2 has a half-life of about two cell cycles. In contrast, the majority of newly synthesized U6 decays with a half-life of about 15 h. The relative abundances of the newly synthesized snRNA species U1, U2, U3, U4 and U6 in the cytoplasm are determined by Northern hybridization using cloned probes and are approximately 2% of their nuclear abundance. The half-lives of the two major snRNA precursors in the cytoplasm (U1 and U2) are approximately 20 min as determined by labeling to steady state. The relative abundance of the snRNP B protein in the cytoplasm is determined by Western blotting with the Sm class of autoantibodies and is approximately 25% of the nuclear abundance. Kinetic studies, using the Sm antiserum to immunoprecipitate the methionine-labeled snRNP proteins, suggest that the B protein has a half-life of 90 to 120 min in the cytoplasm. These data are discussed and suggest that there is a large pool of more stable snRNP proteins in the cytoplasm available for assembly with the less abundant but more rapidly turning-over snRNAs

  10. Discovery Strategies of Bioactive Compounds Synthesized by Nonribosomal Peptide Synthetases and Type-I Polyketide Synthases Derived from Marine Microbiomes

    Science.gov (United States)

    Amoutzias, Grigoris D.; Chaliotis, Anargyros; Mossialos, Dimitris

    2016-01-01

    Considering that 70% of our planet’s surface is covered by oceans, it is likely that undiscovered biodiversity is still enormous. A large portion of marine biodiversity consists of microbiomes. They are very attractive targets of bioprospecting because they are able to produce a vast repertoire of secondary metabolites in order to adapt in diverse environments. In many cases secondary metabolites of pharmaceutical and biotechnological interest such as nonribosomal peptides (NRPs) and polyketides (PKs) are synthesized by multimodular enzymes named nonribosomal peptide synthetases (NRPSes) and type-I polyketide synthases (PKSes-I), respectively. Novel findings regarding the mechanisms underlying NRPS and PKS evolution demonstrate how microorganisms could leverage their metabolic potential. Moreover, these findings could facilitate synthetic biology approaches leading to novel bioactive compounds. Ongoing advances in bioinformatics and next-generation sequencing (NGS) technologies are driving the discovery of NRPs and PKs derived from marine microbiomes mainly through two strategies: genome-mining and metagenomics. Microbial genomes are now sequenced at an unprecedented rate and this vast quantity of biological information can be analyzed through genome mining in order to identify gene clusters encoding NRPSes and PKSes of interest. On the other hand, metagenomics is a fast-growing research field which directly studies microbial genomes and their products present in marine environments using culture-independent approaches. The aim of this review is to examine recent developments regarding discovery strategies of bioactive compounds synthesized by NRPS and type-I PKS derived from marine microbiomes and to highlight the vast diversity of NRPSes and PKSes present in marine environments by giving examples of recently discovered bioactive compounds. PMID:27092515

  11. Discovery Strategies of Bioactive Compounds Synthesized by Nonribosomal Peptide Synthetases and Type-I Polyketide Synthases Derived from Marine Microbiomes

    Directory of Open Access Journals (Sweden)

    Grigoris D. Amoutzias

    2016-04-01

    Full Text Available Considering that 70% of our planet’s surface is covered by oceans, it is likely that undiscovered biodiversity is still enormous. A large portion of marine biodiversity consists of microbiomes. They are very attractive targets of bioprospecting because they are able to produce a vast repertoire of secondary metabolites in order to adapt in diverse environments. In many cases secondary metabolites of pharmaceutical and biotechnological interest such as nonribosomal peptides (NRPs and polyketides (PKs are synthesized by multimodular enzymes named nonribosomal peptide synthetases (NRPSes and type-I polyketide synthases (PKSes-I, respectively. Novel findings regarding the mechanisms underlying NRPS and PKS evolution demonstrate how microorganisms could leverage their metabolic potential. Moreover, these findings could facilitate synthetic biology approaches leading to novel bioactive compounds. Ongoing advances in bioinformatics and next-generation sequencing (NGS technologies are driving the discovery of NRPs and PKs derived from marine microbiomes mainly through two strategies: genome-mining and metagenomics. Microbial genomes are now sequenced at an unprecedented rate and this vast quantity of biological information can be analyzed through genome mining in order to identify gene clusters encoding NRPSes and PKSes of interest. On the other hand, metagenomics is a fast-growing research field which directly studies microbial genomes and their products present in marine environments using culture-independent approaches. The aim of this review is to examine recent developments regarding discovery strategies of bioactive compounds synthesized by NRPS and type-I PKS derived from marine microbiomes and to highlight the vast diversity of NRPSes and PKSes present in marine environments by giving examples of recently discovered bioactive compounds.

  12. Fibronectin synthesized by a human hepatoma cell line

    International Nuclear Information System (INIS)

    Glasgow, J.E.; Colman, R.W.

    1984-01-01

    Fibronectin is a family of immunologically similar glycoproteins which mediate a variety of cell-cell and cell-substratum interactions. It is a constituent of the extracellular matrix of connective tissue and circulates in plasma. When suspension and adherent cultures of a human hepatoma cell line (SK-HEP-1) were incubated in serum-free medium, the resulting conditioned medium contained material which was specifically immunoprecipitated by antisera to human plasma fibronectin. By double immunodiffusion, a component in the conditioned culture medium was shown to form a line of identity with fibronectin in human plasma and to migrate as an alpha 2- to beta-globulin during immunoelectrophoresis. Human fibronectin was quantified in conditioned medium by electroimmunodiffusion, and was found to increase for at least three days at about 0.1 micrograms/10(6) cells/day. Adherent cultures of SK-HEP-1 cells were incubated with L-[ 35 S]methionine to label newly synthesized proteins. Labeled fibronectin in conditioned medium or in cell extracts comigrated with fibronectin in human plasma as shown by autoradiography following crossed-immunoelectrophoresis. Fibronectin was demonstrated in the extra-cellular matrix of adherent SK-HEP-1 cultures by immunofluorescence. It was shown previously that SK-HEP-1 cells synthesize alpha 1-protease inhibitor, one of the products of normal hepatocytes. The finding that these hepatoma cells also synthesize fibronectin supports the concept that the hepatocyte may be one source of circulating fibronectin, a possibility consistent with the established role of this cell type in blood plasma protein synthesis

  13. Characterization of Newly Synthesized ZrFe2O5 Nanomaterial and Investigations of Its Tremendous Photocatalytic Properties under Visible Light Irradiation

    Directory of Open Access Journals (Sweden)

    Shaukat Ali Shahid

    2013-01-01

    Full Text Available High functional ZrFe2O5 nanoparticles were synthesized using coprecipitation technique. The chemical composition of nanomaterials was studied by energy-dispersive X-ray (EDX. To observe the morphology, field emission scanning electron microscopy (FE-SEM was used. X-ray diffraction (XRD technique was utilized to appraise the structure of the synthesized material. The photocatalytic behavior of ZrFe2O5 nano-particles was investigated by measuring the degradation rate of toluidine blue O (TBO dye in aqueous solution in the presence of ZrFe2O5 nano-particles under visible light irradiation. A steady decrease in absorption peak under visible light irradiation was observed by increasing exposure time. The degradation efficiency was observed as 92% after 140 min of exposure to visible light. Besides, ZrFe2O5 nanophotocatalyst could be recovered and recycled easily. The rate of TBO and total organic carbon (TOC removal under visible light irradiation decreased by only 5% and 10%, respectively, after seven cycles of use, demonstrating the high photostability of the synthesized nano-photocatalyst material.

  14. Newly Synthesized Water Soluble Cholinium-Purpurin Photosensitizers and Their Stabilized Gold Nanoparticles as Promising Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Young Key Shim

    2008-05-01

    Full Text Available For possible future use in Photodynamic Therapy (PDT and/or Photothermal Therapy (PTT of cancer and screening of cancer cells a new type of ionic liquid photosensitizer –Cholinium-Purpurin-18 (Chol-Pu-18 – was synthesized and small gold (Au nanoparticles, stabilized by this photosensitizer were prepared without adding any particular reducing agents and CTAB. UV-Vis spectroscopy and Transmission Electron Microscopy (TEM were used for characterization of the nanoparticles and FAB-MS and NMR of the ionic liquid choline hydroxide, purpurin carboxylate and their ionic liquid type of photosensitizer were obtained.

  15. The effect of insulin-like growth factor I on proteoglycan metabolism in immature and adult bovine articular cartilage

    International Nuclear Information System (INIS)

    Barone-Varelas, J.

    1989-01-01

    Explants of articular cartilage from calf (15 weeks old) and steer (18-24 months old) were cultured for up to 19 days in medium containing either insulin-like growth factor (IGF-I) or 20% fetal bovine serum (FBS). Explants cultured in medium alone were controls. 35 S-proteoglycans (PGs) synthesized on day 7 of culture during a 5-hour pulse with 35 S-sulfate were isolated, quantified and characterized. Lower concentrations of IGF-I were required for maximal stimulation of PG synthesis in calf than in steer (10 vs 20 ng/ml). In calf, IGF-I was as effective as 20% FABS in stimulating PG synthesis. In steer, PG synthesis in the presence of IGF-I reached its maximum at a rate that was half that obtained with 20% FBS. The stimulation by IGF-I or FBS was not accompanied at either age by alterations in the size and composition of the aggregating PGs nor by changes in the relative proportions of the CS-rich and CS-poor PG subpopulations. Importantly, the newly synthesized calf and steer PGs retained marked age-related differences in composition regardless of the culture conditions. The effects of exogenously added IGF-I and FBS on the rate of turnover of cartilage PGs was also studied. In calf, IGF-I and FBS did not significantly alter the rate of turnover of either the 35 S-PGs synthesized in vitro or of the unlabeled PGs representing mostly molecules synthesize and organized into the matrix in vivo. In steer, explants cultured in the absence of IGF-I or FBS exhibited very fast rates of turnover which resulted in severe depletion of matrix PG with time. Importantly, IGF-I and FBS were equally effective in reducing the turnover rate of 35 S-PGs and unlabeled PGs and in preventing PG depletion. These results demonstrate age-related differences in the effect of IGF-I on PG synthesis by articular chondrocytes

  16. Intensity-modulated radiation therapy followed by GDP chemotherapy for newly diagnosed stage I/II extranodal natural killer/T cell lymphoma, nasal type.

    Science.gov (United States)

    Huang, Yu; Yang, Jianliang; Liu, Peng; Zhou, Shengyu; Gui, Lin; He, Xiaohui; Qin, Yan; Zhang, Changgong; Yang, Sheng; Xing, Puyuan; Sun, Yan; Shi, Yuankai

    2017-09-01

    Extranodal natural killer (NK)/T cell lymphoma, nasal type (ENKTL) is an aggressive non-Hodgkin lymphoma and the majority of ENKTL cases are diagnosed at the localized stage. Radiotherapy in combination with chemotherapy has been used for localized ENKTL, but the optimal combination treatment modality and the best first-line chemotherapy regimen have not been defined. In this retrospective study, 44 patients with newly diagnosed, stages I/II ENKTL were enrolled and received intensity-modulated radiation therapy (IMRT, 50-56 Gy) followed by GDP (gemcitabine, dexamethasone, and cisplatin) chemotherapy. The median number of chemotherapy cycles per patient was 4 (range, 2-6 cycles). At the end of treatment, the overall response rate was 95% (42/44), including 39 patients (89%) who attained complete response. Two patients developed systemic progression after IMRT. With a median follow-up of 37.5 months, the 3-year overall survival (OS) rate and progression-free survival (PFS) rate were 85% (95% CI, 74 to 96%) and 77% (95% CI, 64 to 91%), respectively. Locoregional and systemic failure rates for this treatment were 9% (4/44) and 14% (6/44), respectively. The most common grades 3 to 4 adverse events included leukopenia (37%), neutropenia (34%), and mucositis (25%). No treatment-related deaths were observed. This study suggested high efficacy and low toxicity of IMRT followed by GDP regimen chemotherapy for newly diagnosed stage I/II ENKTL patients. These results require further investigation in prospective trials.

  17. Scintigraphic localization of a disseminated malignant pheochromocytoma with the use of 131I-meta-iodobenzylguanidine

    International Nuclear Information System (INIS)

    Troncone, L.; Maini, L.M.; Rufini, V.; Bonifazi, N.; De Rosa, G.; Corsello, S.M.; Mattei, O.

    1984-01-01

    Preliminary clinical studies with 131 I-meta-iodo-benzylguanidine, a newly synthesized radiopharmaceutical and guanethidine analog capable of imaging the adrenal medulla, have led to the identification, of a case of disseminated malignant pheochromocytoma with the localization of brain and bone metastases. The result is of particular interest as the symptomatology in this case appeared rather equivocal and various investigations had led to a completely different diagnosis. This new scintigraphic technique has proved to be safe, specific and noninvasive, and it may have a clinical application as a complementary or alternative technique to conventional diagnostic tests. (orig.)

  18. Combined spectroscopic, DFT, TD-DFT and MD study of newly synthesized thiourea derivative

    Science.gov (United States)

    Menon, Vidya V.; Sheena Mary, Y.; Shyma Mary, Y.; Panicker, C. Yohannan; Bielenica, Anna; Armaković, Stevan; Armaković, Sanja J.; Van Alsenoy, Christian

    2018-03-01

    A novel thiourea derivative, 1-(3-bromophenyl)-3-[3-(trifluoromethyl)phenyl]thiourea (ANF-22) is synthesized and characterized by FTIR, FT-Raman and NMR spectroscopy experimentally and theoretically. A detailed conformational analysis of the title molecule has been conducted in order to locate the lowest energy geometry, which was further subjected to the detailed investigation of spectroscopic, reactive, degradation and docking studies by density functional theory (DFT) calculations and molecular dynamics (MD) simulations. Time dependent DFT (TD-DFT) calculations have been used also in order to simulate UV spectra and investigate charge transfer within molecule. Natural bond orbital analysis has been performed analyzing the charge delocalization and using HOMO and LUMO energies the electronic properties are analyzed. Molecular electrostatic potential map is used for the quantitative measurement of active sites in the molecule. In order to determine the locations possibly prone to electrophilic attacks we have calculated average local ionization energies and mapped them to the electron density surface. Further insight into the local reactivity properties have been obtained by calculation of Fukui functions, also mapped to the electron density surface. Possible degradation properties by the autoxidation mechanism have been assessed by calculations of bond dissociation energies for hydrogen abstraction. Atoms of title molecule with significant interactions with water molecules have been determined by calculations of radial distribution functions. The title compound can be a lead compound for developing new analgesic drug.

  19. Syntheses of copper complexes of nicotinohydroxamic and ...

    African Journals Online (AJOL)

    Nicotinohydroxamic acid (NHA) and isonicotinohydroxamic acid (INHA) were synthesized, characterized by electronic and spectral studies,magnetic measurements and their pKa determined spectrophotometrically as 8.68 ± 0.02 in aqueous medium of 0.1mol dm-3 I=ionic strength. The composition of the complexes was ...

  20. Significance of combined detection of JAK2V617F, MPL and CALR gene mutations in patients with essential thrombocythemia.

    Science.gov (United States)

    Ji, Liying; Qian, Mengyao; Wu, Nana; Wu, Jianmin

    2017-03-01

    The aim of this study was to analyze the mutation rate of JAK2V617F, MPLW515L/K and CALR genes in adult patients with essential thrombocythemia (ET) and the accuracy of the combined detection by the receiver operating curve. Three hundred and forty-two cases with high-platelets (≥300×10 9 /l) were consecutively selected. The patients were analyzed for routine blood examination, bone marrow biopsy and genetic testing. One hundred and fifty-four cases (45.03%) were diagnosed with ET and 188 cases of secondary thrombocythemia according to the hematopoietic and lymphoid tissue tumor classification standards of 2008. It was found that the mutant type of three genes showed three bands, whereas only one band for wild-type. The JAK2V617F and MPL mutations did not cause a change in the open reading frame and the CALR mutation resulted in its change. The mutation rate of JAK2V617F and CALR in ET group was significantly higher than that in the secondary thrombocythemia group (p<0.05). The positive mutation rate of MPL was only 4.55%. JAK2V617F-positive mutation alone was used to diagnose with ET. The area under the curve (AUC) was 0.721. The sensitivity was 72.4%, the specificity was 79.5% and the cut-off value was 0.25. When CALR-positive mutation alone was used to diagnose ET, the AUC, sensitivity, specificity and cut-off value were 0.664, 68.4, 82.4 and 0.09%, respectively. JAK2V617F combined with CALR mutation were used for diagnosis of ET. The AUC was 0.862, the sensitivity was 85.9%, the specificity was 87.8%, and the cut-off values were 0.21 and 0.07. In conclusion, the positive mutation rate of JAK2V617F and CALR in ET was higher, and the sensitivity, specificity and accuracy of the diagnosis of ET were significantly improved using the detection of JAK2V617F and CALR.

  1. Phase I Trial of Gross Total Resection, Permanent Iodine-125 Brachytherapy, and Hyperfractionated Radiotherapy for Newly Diagnosed Glioblastoma Multiforme

    International Nuclear Information System (INIS)

    Chen, Allen M.; Chang, Susan; Pouliot, Jean; Sneed, Penny K.; Prados, Michael D.; Lamborn, Kathleen R.; Malec, Mary K.; McDermott, Michael W.; Berger, Mitchell S.; Larson, David A.

    2007-01-01

    Purpose: To evaluate the feasibility of gross total resection and permanent I-125 brachytherapy followed by hyperfractionated radiotherapy for patients with newly diagnosed glioblastoma. Methods and Materials: From April 1999 to May 2002, 21 patients with glioblastoma multiforme were enrolled on a Phase I protocol investigating planned gross total resection and immediate placement of permanent I-125 seeds, followed by postoperative hyperfractionated radiotherapy to a dose of 60 Gy at 100 cGy b.i.d., 5 days per week. Median age and Karnofsky performance status were 50 years (range, 32-65 years) and 90 (range, 70-100), respectively. Toxicity was assessed according to Radiation Therapy Oncology Group criteria. Results: Eighteen patients completed treatment according to protocol. The median preoperative tumor volume on magnetic resonance imaging was 18.6 cm 3 (range, 4.4-41.2 cm 3 ). The median brachytherapy dose measured 5 mm radially outward from the resection cavity was 400 Gy (range, 200-600 Gy). Ten patients underwent 12 reoperations, with 11 of 12 reoperations demonstrating necrosis without evidence of tumor. Because of high toxicity, the study was terminated early. Median progression-free survival and overall survival were 57 and 114 weeks, respectively, but not significantly improved compared with historical patients treated at University of California, San Francisco, with gross total resection and radiotherapy without brachytherapy. Conclusions: Treatment with gross total resection and permanent I-125 brachytherapy followed by hyperfractionated radiotherapy as performed in this study results in high toxicity and reoperation rates, without demonstrated improvement in survival

  2. Total syntheses of hyperforin and papuaforins A-C, and formal synthesis of nemorosone through a gold(I)-catalyzed carbocyclization.

    Science.gov (United States)

    Bellavance, Gabriel; Barriault, Louis

    2014-06-23

    The remarkable biological activities of polyprenylated polycyclic acylphloroglucinols (PPAPs) combined with their highly decorated bicyclo[3.3.1]nonane-2,4,9-trione frameworks have inspired synthetic organic chemists over the last decade. The concise total syntheses of four natural products PPAPs; hyperforin and papuaforins A-C, and the formal synthesis of nemorosone are reported. Key to the realization of this strategy is the short and scalable synthesis of densely substituted PPAP scaffolds through a gold(I)-catalyzed 6-endo-dig carbocyclization of cyclic enol ethers for late-stage functionalization. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Studies on the site of protein and RNA syntheses in poxvirus-infected cells

    Energy Technology Data Exchange (ETDEWEB)

    Sakaue, Y [Osaka Univ. (Japan). Research Inst. for Microbial Diseases

    1974-04-01

    Pulse labelling of short time and the chase of it were conducted to Poxvirus-infected cells using /sup 3/H-uridine and /sup 3/H-leucine with high concentration, and autoradiography (AR) was taken. As the result, protein synthesis, which was in accordance with ''B''-type inclusion, was markedly observed in one-minute labelling at the site of protein synthesis of infected cells. Although the protein synthesis was observed at the peripheral site of ''A''-type inclusion, it was not found within inclusions. However, it was found from the experiment of chase that protein collected markedly within ''B''-type inclusion. They were found that ''B''-type inclusion is the site of Virus DNA synthesis as well as the site of Virus mRNA synthesis, and that it is also absolutely possible for ''B''-type inclusion to synthesize Virus protein. In addition, it was found that ''A''-type inclusion is not the site of synthesis, but newly-synthesized protein.

  4. Studies on the site of protein and RNA syntheses in poxvirus-infected cells

    International Nuclear Information System (INIS)

    Sakaue, Yoshihiro

    1974-01-01

    Pulse labelling of short time and the chase of it were conducted to Poxvirus-infected cells using 3 H-uridine and 3 H-leucine with high concentration, and autoradiography (AR) was taken. As the result, protein synthesis, which was in accordance with ''B''-type inclusion, was markedly observed in one-minute labelling at the site of protein synthesis of infected cells. Although the protein synthesis was observed at the peripheral site of ''A''-type inclusion, it was not found within inclusions. However, it was found from the experiment of chase that protein collected markedly within ''B''-type inclusion. They were found that ''B''-type inclusion is the site of Virus DNA synthesis as well as the site of Virus mRNA synthesis, and that it is also absolutely possible for ''B''-type inclusion to synthesize Virus protein. In addition, it was found that ''A''-type inclusion is not the site of synthesis, but newly-synthesized protein. (Ichikawa, K.)

  5. Target language use in Modern Language classrooms: perception and change among newly qualified teachers in Scotland

    OpenAIRE

    Lynch, Michael Patrick

    2015-01-01

    In this thesis I investigate the practices and perceptions of some Newly Qualified Teachers (NQTs) of modern foreign languages (MFL) in Scotland in relation to how they use the target language (L2). I seek to answer the questions “In what different ways do student teachers of modern languages use the target language in Scottish secondary school classrooms?’, ‘What reasons do they give for how they use it?” and “In what way(s), if any, do newly qualified teachers of modern language...

  6. A fractional-N frequency synthesizer-based multi-standard I/Q carrier generation system in 0.13 μm CMOS

    International Nuclear Information System (INIS)

    Lou Wenfeng; Geng Zhiqing; Feng Peng; Wu Nanjian

    2011-01-01

    This paper proposes a sigma-delta fractional-N frequency synthesizer-based multi-standard I/Q carrier generation system. With reasonable frequency planning, the system can be used in multi-standard wireless communication applications (GSM, WCDMA, GPRS, TD-SCDMA, WLAN (802.11a/b/g)). The implementation is achieved by a 0.13 μm RF CMOS process. The measured results demonstrate that three quadrature VCOs (QVCO) continuously cover the frequency from 3.1 to 6.1 GHz (65.2%), and through the successive divide-by-2 prescalers to achieve the frequency from 0.75 to 6.1 GHz continuously. The chip was fully integrated with the exception of an off-chip filter. The entire chip area is only 3.78 mm 2 , and the system consumes a 21.7 mA - 1.2 V supply without output buffers. The lock-in time of the PLL frequency synthesizer is less than 4 μs over the entire frequency range with a direct frequency presetting technique and the auxiliary non-volatile memory (NVM) can store the digital configuration signal of the system, including presetting signals to avoid the calibration process case by case. (semiconductor integrated circuits)

  7. A fractional-N frequency synthesizer-based multi-standard I/Q carrier generation system in 0.13 {mu}m CMOS

    Energy Technology Data Exchange (ETDEWEB)

    Lou Wenfeng; Geng Zhiqing; Feng Peng; Wu Nanjian, E-mail: nanjian@semi.ac.cn [Institute of Semiconductors, Chinese Academy of Sciences, Beijing 100083 (China)

    2011-06-15

    This paper proposes a sigma-delta fractional-N frequency synthesizer-based multi-standard I/Q carrier generation system. With reasonable frequency planning, the system can be used in multi-standard wireless communication applications (GSM, WCDMA, GPRS, TD-SCDMA, WLAN (802.11a/b/g)). The implementation is achieved by a 0.13 {mu}m RF CMOS process. The measured results demonstrate that three quadrature VCOs (QVCO) continuously cover the frequency from 3.1 to 6.1 GHz (65.2%), and through the successive divide-by-2 prescalers to achieve the frequency from 0.75 to 6.1 GHz continuously. The chip was fully integrated with the exception of an off-chip filter. The entire chip area is only 3.78 mm{sup 2}, and the system consumes a 21.7 mA - 1.2 V supply without output buffers. The lock-in time of the PLL frequency synthesizer is less than 4 {mu}s over the entire frequency range with a direct frequency presetting technique and the auxiliary non-volatile memory (NVM) can store the digital configuration signal of the system, including presetting signals to avoid the calibration process case by case. (semiconductor integrated circuits)

  8. Syntheses of several 99mTc and 131I labeled neoglycoalbumins and their differential uptake patterns in animal biodistribution experiments

    International Nuclear Information System (INIS)

    Sarkar, Himadri S.; Sen, Asish K.; Mukherjee, Manasi; Banerji, Nilima; Banerjee, Somenath

    1995-01-01

    Several glycoconjugates, α-d-mannopyranosyl, β-l-fucopyranosyl, α-l-rhamnopyranosyl, β-d-glucopyranosyl and β-d-galactopyranosyl human serum albumin, were synthesized using C 9 -tether and radiolabeled with 99m Tc and 131 I. Both 99m Tc and 131 I radiolabeled neoglycoalbumins had considerable stability and exhibited similar biodistribution patterns within the experimental limits. The results of biodistribution studies can be explained from the in vitro observations that 99m Tc-β-d-galactopyranosyl albumin binds to hepatic binding protein in liver in a dose-dependent fashion. The radiolabeled glycoalbumins derived from d-mannopyranose and l-fucopyranose also bind in a dose-dependent fashion to the receptors present in the liver sinusoidal cells and spleen macrophages. The β-d-glucopyranosyl and α-l-rhamnopyranosyl neoglycoalbumins accumulate nonspecifically in liver and spleen

  9. WHO-defined 'myelodysplastic syndrome with isolated del(5q)' in 88 consecutive patients: survival data, leukemic transformation rates and prevalence of JAK2, MPL and IDH mutations.

    Science.gov (United States)

    Patnaik, M M; Lasho, T L; Finke, C M; Gangat, N; Caramazza, D; Holtan, S G; Pardanani, A; Knudson, R A; Ketterling, R P; Chen, D; Hoyer, J D; Hanson, C A; Tefferi, A

    2010-07-01

    The 2008 World Health Organization (WHO) criteria were used to identify 88 consecutive Mayo Clinic patients with 'myelodysplastic syndrome with isolated del(5q)' (median age 74 years; 60 females). In all, 60 (68%) patients were followed up to the time of their death. Overall median survival was 66 months; leukemic transformation was documented in five (5.7%) cases. Multivariable analysis identified age >or=70 years (P=0.01), transfusion need at diagnosis (P=0.04) and dysgranulopoiesis (P=0.02) as independent predictors of shortened survival; the presence of zero (low risk), one (intermediate risk) or >or=2 (high risk) risk factors corresponded to median survivals of 102, 52 and 27 months, respectively. Janus kinase 2 (JAK2), thrombopoietin receptor (MPL), isocitrate dehydrogenase 1 (IDH1) and IDH2 mutational analysis was performed on archived bone marrows in 78 patients; JAK2V617F and MPLW515L mutations were shown in five (6.4%) and three (3.8%) patients, respectively, and did not seem to affect phenotype or prognosis. IDH mutations were not detected. Survival was not affected by serum ferritin and there were no instances of death directly related to iron overload. The current study is unique in its strict adherence to WHO criteria for selecting study patients and providing information on long-term survival, practical prognostic factors, baseline risk of leukemic transformation and the prevalence of JAK2, MPL and IDH mutations.

  10. Determination of Silver(I by Differential Pulse Voltammetry Using a Glassy Carbon Electrode Modified with Synthesized N-(2-Aminoethyl-4,4'-Bipyridine

    Directory of Open Access Journals (Sweden)

    Gabriel Lucian Radu

    2010-12-01

    Full Text Available A new modified glassy carbon electrode (GCE based on a synthesized N-(2-aminoethyl-4,4'-bipyridine (ABP was developed for the determination of Ag(I by differential pulse voltammetry (DPV. ABP was covalently immobilized on GC electrodes surface using 4-nitrobenzendiazonium (4-NBD and glutaraldehyde (GA. The Ag(I ions were preconcentrated by chemical interaction with bipyridine under a negative potential (−0.6 V; then the reduced ions were oxidized by differential pulse voltammetry and a peak was observed at 0.34 V. The calibration curve was linear in the concentration range from 0.05 μM to 1 μM Ag(I with a detection limit of 0.025 μM and RSD = 3.6%, for 0.4 μM Ag(I. The presence of several common ions in more than 125-fold excess had no effect on the determination of Ag(I. The developed sensor was applied to the determination of Ag(I in water samples using a standard addition method.

  11. Syntheses and anti-microbial evaluation of new quinoline scaffold derived pyrimidine derivatives

    Directory of Open Access Journals (Sweden)

    Shikha S. Dave

    2016-09-01

    Full Text Available A series of diversely substituted chalcones derived from a quinoline scaffold, e.g. (E-3-(2-chloroquinolin-3-yl-1-(2-hydroxyphenyl prop-2-en-1-one and its pyrimidine analogues e.g. 2-[2-amino-6-(2-chloroquinolin-3-yl-5,6-dihydropyrimidin-4-yl]phenols have been prepared by condensation of 2-chloro-3-formyl quinoline with differently substituted 2-hydroxy acetophenones and further treatment with guanidine carbonate. All the newly synthesized compounds have been evaluated for their in vitro growth inhibitory activity against Escherichia coli, Pseudomonas vulgaris, Bacillus subtilis, Staphylococcus aureus, Staphylococcus typhi, Candida albicans, Aspergillus niger and Pseudomonas chrysogenum.

  12. 6,6″-Dimethyl-2,2':6',2″-terpyridine revisited: new fluorescent silver(I) helicates with in vitro antiproliferative activity via selective nucleoli targeting.

    Science.gov (United States)

    Fik, Marta A; Gorczyński, Adam; Kubicki, Maciej; Hnatejko, Zbigniew; Fedoruk-Wyszomirska, Agnieszka; Wyszko, Eliza; Giel-Pietraszuk, Małgorzata; Patroniak, Violetta

    2014-10-30

    6,6″-Dimethyl-2,2':6',2″-terpyridine ligand (L) reacts in equimolar ratio with Ag(I) ions what results in formation of dinuclear double helicates, which differ in terms of framework and complexity in accordance to counterions and solvent applied. Obtained complexes were thoroughly studied in terms of their biological activity, with the positive antiproliferative outcome on three human cancer cell lines: human breast cancer (T47D), human cervical carcinoma (HeLa) and human lung cancer (A-549). Performed DNA binding experiments showed that given Ag(I) species specifically interact with DNA double helix via intercalation and were visualized by confocal microscopy to specifically bind to the nuclei. All newly synthesized helical systems exhibit promising antimicrobial activity against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacterial strains. Spectrophotometric properties were described as fulfilment of structural studies of newly presented complexes confirming their helical structure in solution. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  13. Syntheses, crystal Structures and electronic Structures of new metal chalcoiodides Bi2CuSe3I and Bi6Cu3S10I

    International Nuclear Information System (INIS)

    Liang, I-Chu; Bilc, Daniel I.; Manoli, Maria; Chang, Wei-Yun; Lin, Wen-Fu; Kyratsi, Theodora; Hsu, Kuei-Fang

    2016-01-01

    Two new metal chalcoiodides were synthesized by solid-state reactions at 400 °C. Crystal Data: Bi 2 CuSe 3 I, 1, monoclinic, C2/m, a=14.243(2) Å, b=4.1937(7) Å, c=14.647(2) Å, β=116.095(2)°, V=785.7(2) Å 3 , and Z=4; Bi 6 Cu 3 S 10 I, 2, orthorhombic, Pnma, a=17.476(2) Å, b=4.0078(4) Å, c=27.391(2) Å, V=1918.5(3) Å 3 , and Z=4. Compound 1 adopts a three-dimensional structure formed by two alternative layers, which consist of BiSe 5 square pyramids, BiSe 4 I 2 octahedra, CuSe 4 tetrahedra, and CuSe 2 I 2 tetrahedra. Compound 2 possesses a new open framework built up of BiS 5 square pyramides, BiS 6 octahedra, BiS 8 polyhedra, and CuS 4 tetrahedra where I − anions are uniquely trapped within the tunnels. Both electronic structures reveal that bismuth and chalcogenide orbitals dominate the bandgaps. The Cu d and I p states contribute to the top of valence bands, in which the distribution of I orbitals may correspond to the relative bonding interactions in 1 and 2. The optical bandgaps determined by the diffuse reflectance spectra are 0.68 eV and 0.72 eV for 1 and 2, respectively. 1 is a p-type semiconductor with high Seebeck coefficients of 460–575 μV/K in the temperature range of 300–425 K. The electrical conductivity is 0.02 S/cm at 425 K for the undoped sample. The thermal conductivity is 0.22 W/mK at 425 K. - Graphical abstract: The hybridization of chalcogenides and iodides produces two new solids Bi2CuSe3I and Bi6Cu3S10I. The I − anions participate in distinct bonding interactions within the two structures and that is consistent with the analyses of density of states. 1 is a p-type semiconductor with an optical bandgap of 0.68 eV, which possesses high Seebeck coefficient and low lattice thermal conductivity in 300–425 K.

  14. WHO-defined ‘myelodysplastic syndrome with isolated del(5q)' in 88 consecutive patients: survival data, leukemic transformation rates and prevalence of JAK2, MPL and IDH mutations

    Science.gov (United States)

    Patnaik, M M; Lasho, T L; Finke, C M; Gangat, N; Caramazza, D; Holtan, S G; Pardanani, A; Knudson, R A; Ketterling, R P; Chen, D; Hoyer, J D; Hanson, C A; Tefferi, A

    2010-01-01

    The 2008 World Health Organization (WHO) criteria were used to identify 88 consecutive Mayo Clinic patients with ‘myelodysplastic syndrome with isolated del(5q)' (median age 74 years; 60 females). In all, 60 (68%) patients were followed up to the time of their death. Overall median survival was 66 months; leukemic transformation was documented in five (5.7%) cases. Multivariable analysis identified age ⩾70 years (P=0.01), transfusion need at diagnosis (P=0.04) and dysgranulopoiesis (P=0.02) as independent predictors of shortened survival; the presence of zero (low risk), one (intermediate risk) or ⩾2 (high risk) risk factors corresponded to median survivals of 102, 52 and 27 months, respectively. Janus kinase 2 (JAK2), thrombopoietin receptor (MPL), isocitrate dehydrogenase 1 (IDH1) and IDH2 mutational analysis was performed on archived bone marrows in 78 patients; JAK2V617F and MPLW515L mutations were shown in five (6.4%) and three (3.8%) patients, respectively, and did not seem to affect phenotype or prognosis. IDH mutations were not detected. Survival was not affected by serum ferritin and there were no instances of death directly related to iron overload. The current study is unique in its strict adherence to WHO criteria for selecting study patients and providing information on long-term survival, practical prognostic factors, baseline risk of leukemic transformation and the prevalence of JAK2, MPL and IDH mutations. PMID:20485371

  15. Yield evaluation and stability analysis in newly selected `KSA' cotton ...

    African Journals Online (AJOL)

    Yield evaluation and stability analysis in newly selected `KSA' cotton cultivars in Western Kenya. R M Opondo, G A Ombakho. Abstract. (African Crop Science Journal, 1997 5(2): 119-126). http://dx.doi.org/10.4314/acsj.v5i2.27854 · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians ...

  16. Biomimetic Syntheses of Callistrilones A-E via an Oxidative [3 + 2] Cycloaddition.

    Science.gov (United States)

    Guo, Yonghong; Zhang, Yuhan; Xiao, Mingxing; Xie, Zhixiang

    2018-04-16

    Concise total syntheses of callistrilones A-E have been achieved from 7 and commercially available α-phellandrene (8). The synthetic strategy, which was primarily inspired by the biogenetic hypothesis, was enabled by an oxidative [3 + 2] cycloaddition followed by a Michael addition and an intramolecular nucleophilic addition to construct the target molecules. Moreover, viminalin I was also synthesized, and its absolute configuration was unambiguously confirmed.

  17. Chemical phase analysis of seed mediated synthesized anisotropic silver nanoparticles

    International Nuclear Information System (INIS)

    Bharti, Amardeep; Goyal, Navdeep; Singh, Suman; Singla, M. L.

    2015-01-01

    Noble-metal nanoparticles are of great interest because of its broad applications almost in every stream (i.e. biology, chemistry and engineering) due to their unique size/shape dependant properties. In this paper, chemical phase of seed mediated synthesized anisotropic silver nanoparticle (AgNPs) has been investigated via fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA). These nanaoparticles were synthesized by seed-growth method controlled by urea and dextrose results to highly stable 12-20 nm particle size revealed by zeta potential and transmission electron microscopy (TEM)

  18. Practicing on Newly Dead

    Directory of Open Access Journals (Sweden)

    Jewel Abraham

    2015-07-01

    Full Text Available A newly dead cadaver simulation is practiced on the physical remains of the dead before the onset of rigor mortis. This technique has potential benefits for providing real-life in-situ experience for novice providers in health care practices. Evolving ethical views in health care brings into question some of the ethical aspects associated with newly dead cadaver simulation in terms of justification for practice, autonomy, consent, and the need of disclosure. A clear statement of policies and procedures on newly dead cadaver simulation has yet to be implemented. Although there are benefits and disadvantages to an in-situ cadaver simulation, such practices should not be carried out in secrecy as there is no compelling evidence that suggests such training as imperative. Secrecy in these practices is a violation of honor code of nursing ethics. As health care providers, practitioners are obliged to be ethically honest and trustworthy to their patients. The author explores the ethical aspects of using newly dead cadaver simulation in training novice nursing providers to gain competency in various lifesaving skills, which otherwise cannot be practiced on a living individual. The author explores multiple views on cadaver simulation in relation to ethical theories and practices such as consent and disclosure to family.

  19. Newly synthesized quinazolinone HMJ-38 suppresses angiogenetic responses and triggers human umbilical vein endothelial cell apoptosis through p53-modulated Fas/death receptor signaling

    Energy Technology Data Exchange (ETDEWEB)

    Chiang, Jo-Hua [Department of Life Sciences, National Chung Hsing University, 250, Kuo-Kuang Road, Taichung 402, Taiwan (China); Yang, Jai-Sing [Department of Pharmacology, China Medical University, Taichung 404, Taiwan (China); Lu, Chi-Cheng [Department of Life Sciences, National Chung Hsing University, 250, Kuo-Kuang Road, Taichung 402, Taiwan (China); Hour, Mann-Jen; Chang, Shu-Jen [School of Pharmacy, China Medical University, Taichung 40402, Taiwan (China); Lee, Tsung-Han, E-mail: thlee@email.nchu.edu.tw [Department of Life Sciences, National Chung Hsing University, 250, Kuo-Kuang Road, Taichung 402, Taiwan (China); Department of Biological Science and Technology, China Medical University, 91, Hsueh-Shih Road, Taichung 404, Taiwan (China); Chung, Jing-Gung, E-mail: jgchung@mail.cmu.edu.tw [Department of Biological Science and Technology, China Medical University, 91, Hsueh-Shih Road, Taichung 404, Taiwan (China); Department of Biotechnology, Asia University, Taichung 413, Taiwan (China)

    2013-06-01

    The current study aims to investigate the antiangiogenic responses and apoptotic death of human umbilical vein endothelial cells (HUVECs) by a newly synthesized compound named 2-(3′-methoxyphenyl)-6-pyrrolidinyl-4-quinazolinone (HMJ-38). This work attempted to not only explore the effects of angiogenesis on in vivo and ex vivo studies but also hypothesize the implications for HUVECs (an ideal cell model for angiogenesis in vitro) and further undermined apoptotic experiments to verify the underlying molecular signaling by HMJ-38. Our results demonstrated that HMJ-38 significantly inhibited blood vessel growth and microvessel formation by the mouse Matrigel plug assay of angiogenesis, and the suppression of microsprouting from the rat aortic ring assay was observed after HMJ-38 exposure. In addition, HMJ-38 disrupted the tube formation and blocked the ability of HUVECs to migrate in response to VEGF. We also found that HMJ-38 triggered cell apoptosis of HUVECs in vitro. HMJ-38 concentration-dependently suppressed viability and induced apoptotic damage in HUVECs. HMJ-38-influenced HUVECs were performed by determining the oxidative stress (ROS production) and ATM/p53-modulated Fas and DR4/DR5 signals that were examined by flow cytometry, Western blotting, siRNA and real-time RT-PCR analyses, respectively. Our findings demonstrate that p53-regulated extrinsic pathway might fully contribute to HMJ-38-provoked apoptotic death in HUVECs. In view of these observations, we conclude that HMJ-38 reduces angiogenesis in vivo and ex vivo as well as induces apoptosis of HUVECs in vitro. Overall, HMJ-38 has a potent anti-neovascularization effect and could warrant being a vascular targeting agent in the future. - Highlights: • HMJ-38 suppresses angiogenic actions in vivo and ex vivo. • Inhibitions of blood vessel and microvessel formation by HMJ-38 are acted. • Cytotoxic effects of HUVECs occur by HMJ-38 challenge. • p53-modulated extrinsic pathway contributes to HMJ-38

  20. Concurrent MPL515 and JAK2V617F mutations in myelofibrosis: chronology of clonal emergence and changes in mutant allele burden over time.

    Science.gov (United States)

    Lasho, Terra L; Pardanani, Animesh; McClure, Rebecca F; Mesa, Ruben A; Levine, Ross L; Gilliland, D Gary; Tefferi, Ayalew

    2006-12-01

    MPLW515L/K and JAK2V617F can co-exist in myelofibrosis with myeloid metaplasia (MMM). The chronology of clonal emergence was studied in three such cases using serially stored bone marrow. At diagnosis, a major MPL515 mutant clone was accompanied by a minor JAK2V617F clone in all three instances. At 25 time points over a period of 4-8 years, allele burden fluctuated but remained high for MPLW515L/K and low for JAK2V617F. We conclude that MPLW515L/K and JAK2V617F are both early events in MMM and allele burden, rather than the mere presence of these mutations, might be relevant to phenotypic variation in myeloproliferative disorders.

  1. Superiority of radiobinding assay over ELISA for detection of IAAs in newly diagnosed type I diabetic children

    International Nuclear Information System (INIS)

    Levy-Marchal, C.; Bridel, M.P.; Sodoyez-Goffaux, F.; Koch, M.; Tichet, J.; Czernichow, P.; Sodoyez, J.C.

    1991-01-01

    Liquid- or solid-phase assays have been used for insulin autoantibody (IAA) determination, and the method of IAA measurement has not been standardized. IAAs were determined by radiobinding assay (RBA) and enzyme-linked immunosorbent assay (ELISA) in two large age-matched groups of nondiabetic and newly diagnosed insulin-dependent (type I) diabetic children. Positivity for IAA by RBA (greater than or equal to nondiabetic mean + 3SD) was 2 of 178 (1.1%) and 55 of 173 (32%) in nondiabetic and diabetic children, respectively. Prevalence of IAA by RBA was significantly higher in the youngest age-group (63% between 0-4 yr). Positivity for IAA by ELISA was 1 of 178 (0.6%) and 8 of 169 (4.7%) in nondiabetic and diabetic children, respectively. Concordance rates between both assays were 0 of 3 (0%) in control subjects and 5 of 58 (8.6%) in diabetic children. We conclude that RBA is more appropriate than ELISA for IAA detection at the onset of the disease. In addition, because available data suggest that IAAs detected by RBA only are high-affinity antibodies, it is tempting to speculate that IAAs reflect a mature immune reaction against endogenous insulin

  2. A fractional-N frequency synthesizer for wireless sensor network nodes

    International Nuclear Information System (INIS)

    Ma Xiao; Du Zhankun; Liu Chang; Liu Ke; Yan Yuepeng; Ye Tianchun

    2014-01-01

    This paper presents a fractional-N frequency synthesizer for wireless sensor network (WSN) nodes. The proposed frequency synthesizer adopts a phase locked loop (PLL) based structure, which employs an LC voltage-controlled oscillator (VCO) with small VCO gain (K VCO ) and frequency step (f step ) variations, a charge pump (CP) with current changing in proportion with the division ratio and a 20-bit ΔΣ modulator, etc. To realize constant K VCO and f step , a novel capacitor sub-bands grouping method is proposed. The VCO sub-groups' sizes are arranged according to the maximal allowed K VCO variation of the system. Besides, a current mode logic divide-by-2 circuit with inside-loop buffers ensures the synthesizer generates I/Q quadrature signals robustly. This synthesizer is implemented in a 0.13 μm CMOS process. Measurement results show that the frequency synthesizer has a frequency span from 2.07 to 3.11 GHz and the typical phase noise is −86.34 dBc/Hz at 100 kHz offset and −114.17 dBc/Hz at 1 MHz offset with a loop bandwidth of about 200 kHz, which meet the WSN nodes' requirements. (semiconductor integrated circuits)

  3. The Influence of Aerosol Hygroscopicity on Retrieving the Aerosol Extincting Coefficient from MPL Data

    Science.gov (United States)

    Zhao, G.; Zhao, C.

    2016-12-01

    Micro-pulse Lidar (MPL) measurements have been widely used to profile the ambient aerosol extincting coefficient(). Lidar Ratio (LR) ,which highly depends on the particle number size distribution (PNSD) and aerosol hygroscopicity, is the most important factor to retrieve the profile. A constant AOD constrained LR is usually used in current algorithms, which would lead to large bias when the relative humidity (RH) in the mixed layer is high. In this research, the influences of PNSD, aerosol hygroscopicity and RH profiles on the vertical variation of LR were investigated based on the datasets from field measurements in the North China Plain (NCP). Results show that LR can have an enhancement factor of more than 120% when the RH reaches to 92%. A new algorithm of retrieving the profile is proposed based on the variation of LR due to aerosol hygroscopicity. The magnitude and vertical structures of retrieved using this method can be significantly different to that of the fiexed LR method. The relative difference can reach up to 40% when the RH in the mixed layer is higher than 90% . Sensitivity studies show that RH profile and PNSD affect most on the retrieved by fiexed LR method. In view of this, a scheme of LR enhancement factor by RH is proposed in the NCP. The relative differnce of the calculated between using this scheme and the new algorithm with the variable LR can be less than 10%.

  4. Newly graduated nurses' use of knowledge sources

    DEFF Research Database (Denmark)

    Voldbjerg, Siri Lygum; Grønkjaer, Mette; Sørensen, Erik Elgaard

    2016-01-01

    AIM: To advance evidence on newly graduated nurses' use of knowledge sources. BACKGROUND: Clinical decisions need to be evidence-based and understanding the knowledge sources that newly graduated nurses use will inform both education and practice. Qualitative studies on newly graduated nurses' use...... underscoring progression in knowledge use and perception of competence and confidence among newly graduated nurses. CONCLUSION: The transition phase, feeling of confidence and ability to use critical thinking and reflection, has a great impact on knowledge sources incorporated in clinical decisions....... The synthesis accentuates that for use of newly graduated nurses' qualifications and skills in evidence-based practice, clinical practice needs to provide a supportive environment which nurtures critical thinking and questions and articulates use of multiple knowledge sources....

  5. Phase I/II trial of vorinostat combined with temozolomide and radiation therapy for newly diagnosed glioblastoma: results of Alliance N0874/ABTC 02.

    Science.gov (United States)

    Galanis, Evanthia; Anderson, S Keith; Miller, C Ryan; Sarkaria, Jann N; Jaeckle, Kurt; Buckner, Jan C; Ligon, Keith L; Ballman, Karla V; Moore, Dennis F; Nebozhyn, Michael; Loboda, Andrey; Schiff, David; Ahluwalia, Manmeet Singh; Lee, Eudocia Q; Gerstner, Elizabeth R; Lesser, Glenn J; Prados, Michael; Grossman, Stuart A; Cerhan, Jane; Giannini, Caterina; Wen, Patrick Y

    2018-03-27

    Vorinostat, a histone deacetylase (HDAC) inhibitor, has shown radiosensitizing properties in preclinical studies. This open-label, single-arm trial evaluated the maximum tolerated dose (MTD; phase I) and efficacy (phase II) of vorinostat combined with standard chemoradiation in newly diagnosed glioblastoma. Patients received oral vorinostat (300 or 400 mg/day) on days 1-5 weekly during temozolomide chemoradiation. Following a 4- to 6-week rest, patients received up to 12 cycles of standard adjuvant temozolomide and vorinostat (400 mg/day) on days 1-7 and 15-21 of each 28-day cycle. Association between vorinostat response signatures and progression-free survival (PFS) and overall survival (OS) was assessed based on RNA sequencing of baseline tumor tissue. Phase I and phase II enrolled 15 and 107 patients, respectively. The combination therapy MTD was vorinostat 300 mg/day and temozolomide 75 mg/m2/day. Dose-limiting toxicities were grade 4 neutropenia and thrombocytopenia and grade 3 aspartate aminotransferase elevation, hyperglycemia, fatigue, and wound dehiscence. The primary efficacy endpoint in the phase II cohort, OS rate at 15 months, was 55.1% (median OS 16.1 mo), and consequently, the study did not meet its efficacy objective. Most common treatment-related grade 3/4 toxicities in the phase II component were lymphopenia (32.7%), thrombocytopenia (28.0%), and neutropenia (21.5%). RNA expression profiling of baseline tumors (N = 76) demonstrated that vorinostat resistance (sig-79) and sensitivity (sig-139) signatures had a reverse and positive association with OS/PFS, respectively. Vorinostat combined with standard chemoradiation had acceptable tolerability in newly diagnosed glioblastoma. Although the primary efficacy endpoint was not met, vorinostat sensitivity and resistance signatures could facilitate patient selection in future trials.

  6. SYNTH: A spectrum synthesizer

    International Nuclear Information System (INIS)

    Hensley, W.K.; McKinnon, A.D.; Miley, H.S.; Panisko, M.E.; Savard, R.M.

    1994-07-01

    A computer code has been written at the Pacific Northwest Laboratory (PNL) to synthesize the results of typical gamma-ray spectroscopy experiments. The code, dubbed SYNTH, allows a use r to specify physical characteristics of a gamma-ray source, the quantity of the nuclides producing the radiation, the source-to-detector distance and the type and thickness of absorbers, the size and composition of the detector (Ge or NaI), and the electronic set up used to gather the data. In the process of specifying the parameters needed to synthesize a spectrum, several interesting intermediate results are produced, including a photopeak transmission function vs energy, a detector efficiency curve, and a weighted list of gamma and x rays produced from a set of nuclides. All of these intermediate results are available for graphical inspection and for printing. SYNTH runs on personal computers. It is menu driven and can be customized to user specifications. SYNTH contains robust support for coaxial germanium detectors and some support for sodium iodide detectors. SYNTH is not a finished product. A number of additional developments are planned. However, the existing code has been compared carefully to spectra obtained from National Institute for Standards and Technology (NIST) certified standards with very favorable results. Examples of the use of SYNTH and several spectral results will be presented

  7. Ascomycin macrolactam derivative SDZ ASM 981 inhibits the release of granule-associated mediators and of newly synthesized cytokines in RBL 2H3 mast cells in an immunophilin-dependent manner.

    Science.gov (United States)

    Hultsch, T; Müller, K D; Meingassner, J G; Grassberger, M; Schopf, R E; Knop, J

    1998-09-01

    Mast cells play an important role in the pathological development of many inflammatory and allergic diseases and inhibition of mast cell activation is a potential target for therapeutic intervention. Therefore, the effect of the novel ascomycin macrolactam derivative SDZ ASM 981 on Fc epsilonRI-mediated activation of rat basophilic leukemia (RBL) cells, as a model for mast cell activation, was investigated. First, the ability to inhibit different mast cell immunophilins in vitro was tested. Using recombinant macrophilin-12 (FKBP-12), inhibition of rotamase activity with an IC50 of approximately 6 nM was observed. The rotamase activity of cyclophilin A (18 kDa) was not affected. Secondly, the effect of SDZ ASM 981 on Fc epsilonRI-mediated mast cell activation was investigated in the RBL cell model. SDZ ASM 981 inhibited exocytosis of preformed mediators (e.g. serotonin) with an IC50 of approximately 30 nM. Transcription and release of newly synthesized mediators (e.g. TNF-alpha) was inhibited with an IC50 of approximately 100 nM. The inhibitory effect of SDZ ASM 981 was antagonized by rapamycin. We conclude that SDZ ASM 981 is a potent inhibitor of Fc epsilonRI-mediated activation of mast cells in vitro. The mechanism of action involves formation of (calcineurin) inhibitory complexes with macrophilins. We suggest that this inhibitory action on mast cells might contribute to the antiinflammatory effect of SDZ ASM 981 observed in vivo (e.g. in aptopic dermatitis and psoriasis).

  8. Differential staining of Western blots of human secreted glycoproteins from serum, milk, saliva, and seminal fluid using lectins displaying diverse sugar specificities.

    Science.gov (United States)

    Gilboa-Garber, Nechama; Lerrer, Batya; Lesman-Movshovich, Efrat; Dgani, Orly

    2005-12-01

    Human milk, serum, saliva, and seminal fluid glycoproteins (gps) nourish and protect newborn and adult tissues. Their saccharides, which resemble cell membrane components, may block pathogen adhesion and infection. In the present study, they were examined by a battery of lectins from plants, animals, and bacteria, using hemagglutination inhibition and Western blot analyses. The lectins included galactophilic ones from Aplysia gonad, Erythrina corallodendron, Maclura pomifera (MPL), peanut, and Pseudomonas aeruginosa (PA-IL); fucose-binding lectins from Pseudomonas aeruginosa (PA-IIL), Ralstonia solanacearum (RSL), and Ulex europaeus (UEA-I), and mannose/glucose-binding Con A. The results demonstrated the chosen lectin efficiency for differential analysis of human secreted gps as compared to CBB staining. They unveiled the diversity of these body fluid gp glycans (those of the milk and seminal fluid being highest): the milk gps interacted most strongly with PA-IIL, followed by RSL; the saliva gps with RSL, followed by PA-IIL and MPL; the serum gps with Con A and MPL, followed by PA-IIL and RSL, and the seminal plasma gps with RSL and MPL, followed by UEA-I and PA-IIL. The potential usage of these lectins as probes for scientific, industrial, and medical purposes, and for quality control of the desired gps is clearly indicated.

  9. EFFECT OF TEFLON AND NAFION LOADING AT ANODE IN DIRECT FORMIC ACID FUEL CELL (DFAFC

    Directory of Open Access Journals (Sweden)

    M. S. MASDAR

    2016-08-01

    Full Text Available DFAFC has extensive hydrophilic nature and will cause problems in a limited mass transport in the anode side of electrode. Thus, the microporous layer (MPL of DFAFC needs a different in structure and morphology compared with that of PEMFC and DMFC because it will directly affect the performance. Therefore, in this study, the formulation of anode’s MPL has been investigated by varying the amount of Teflon and Nafion. Different loading of Teflon in MPL and Nafion in catalyst layer, i.e., 0 to 40% in weight, were used to fabricate the anode’s DFAFC. The characteristic of MPLs and anode (MPL with catalyst layer such as surface morphologies and resistivity, i.e., electrical impedance, have been analyzed using field emission scanning electron microscopy (FESEM and contact angle measurements as well as electrochemical impedance spectra (EIS. Meanwhile, the performance of fabricated anode was measured using cyclic voltammetry (CV technique with a half cell of DFAFC. From the result, it was obtained that the optimum content for both Teflon and Nafion on anode’s DFAFC was 20 wt% as shown in a highest electro-activity in electrode. The single cell DFAFC with optimum MEA formulation showed a good performance and hence, it is possible to apply the electricity power for electronic devices.

  10. Micro-computed tomography newly developed for in vivo small animal imaging

    International Nuclear Information System (INIS)

    Arai, Yoshinori; Ninomiya, Tadashi; Kato, Takafumi; Masuda, Yuji

    2005-01-01

    The aim of this paper is to report a newly developed micro-computed tomography system for in vivo use. The system was composed of a micro-focus X-ray tube and an image intensifier (I.I.), both of which rotated around the object stage. A guinea pig and a rat were examined. The anesthetized animal was set on the secure object stage. Images of the head of the guinea pig and the tibia knee joint of the rat were taken. In addition, an image of the rat's tail was taken. The reconstruction and the image viewing were carried out using I-View software. The voxel matrix was 512 x 512 x 384. The voxel sizes ranged from 10 x 10 x 10 μm to 100 x 100 x 100 μm. The exposure time was 17 s, and the reconstruction time was 150 s. The head of the guinea pig and the tibia/knee joint of the rat were observed clearly under 100-μm and 30μm voxels, respectively. The trabecular bone of the tail was also observed clearly under a 10 μm voxel. The newly developed micro-computed tomography system makes it possible to obtain images of anesthetized animals set on a secure object stage. Clear bone images of the small animals could be obtained within a short time. (author)

  11. Recycling endosomes in human cytotoxic T lymphocytes constitute an auxiliary intracellular trafficking pathway for newly synthesized perforin

    Science.gov (United States)

    Lesteberg, Kelsey E.; Orange, Jordan S.; Makedonas, George

    2018-01-01

    Background Although cytotoxic T lymphocytes (CTLs) store perforin within cytoplasmic secretory granules for immediate use, perforin is synthesized anew within hours of TCR stimulation. Previously, we observed new perforin protein at an immunologic synapse independent of secretory lysosomes; herein we aimed to determine how new perforin transits to the synapse if not via lytic granules. Results We analyzed antigen-specific human CTLs via imaging flow cytometry and high-resolution confocal microscopy, with attention to intracellular trafficking components and new perforin. The recycling endosome compartments identified by rab8, rab11a, rab4, and rab37 co-localized with new perforin, as well as the SNAREs vti1b and VAMP4. After ablating the function of the recycling endosome pathway, we observed a relative accumulation of new perforin in rab8 vesicles. Conclusions The recycling endosome pathway may serve as an auxiliary intracellular route for the delivery of new perforin to an immunologic synapse in order to perpetuate a cytotoxic response. PMID:28822075

  12. Newly introduced sample preparation techniques: towards miniaturization.

    Science.gov (United States)

    Costa, Rosaria

    2014-01-01

    Sampling and sample preparation are of crucial importance in an analytical procedure, representing quite often a source of errors. The technique chosen for the isolation of analytes greatly affects the success of a chemical determination. On the other hand, growing concerns about environmental and human safety, along with the introduction of international regulations for quality control, have moved the interest of scientists towards specific needs. Newly introduced sample preparation techniques are challenged to meet new criteria: (i) miniaturization, (ii) higher sensitivity and selectivity, and (iii) automation. In this survey, the most recent techniques introduced in the field of sample preparation will be described and discussed, along with many examples of applications.

  13. Patients with newly diagnosed Rheumatoid Arthritis are at increased risk of Diabetes Mellitus

    DEFF Research Database (Denmark)

    Emamifar, Amir; Levin, Klaus; Jensen Hansen, Inger Marie

    2018-01-01

    -C-reactive protein (DAS28-CRP) at the time of diagnosis and after 4 months (±1-2 months) of treatment initiation were extracted from Danbio Registry. To reveal the presence of DM, patients' electronic medical records were reviewed. The prevalence of DM in our patients was compared (using an age- and gender......-matched analysis) with that expected from Danish population. RESULTS: of 439 included patients, 60.1% were female, mean of age 64.6±15.0 years and RA disease duration 2.6±1.7 years. Prevalence of DM was 57/439 (12.9%), herein type II DM 52 (91.2%) and type I DM 5 (8.8%). Except for two patients, diagnosis of DM......AIMS: To reveal the prevalence of Diabetes Mellitus (DM) in patients with newly diagnosed Rheumatoid Arthritis (RA) and evaluate the association between clinical characteristics of RA and DM as well as treatment response in newly diagnosed RA patients with DM. METHODS: Newly diagnosed, adult, RA...

  14. Imine derivatives of lathonones. Part I -- Reactions of neodymium (III) isopropoxide with monofunctional bidendtate and bifunctional tridentate aldimines and ketamines

    International Nuclear Information System (INIS)

    Mital, S.P.; Singh, R.V.; Tandon, J.P.

    1980-01-01

    Nd(OPrsup(i))sub(2) (SB) and Nd(Oprsup(i))(SB)sub(2) [where SBH represents the molecule of monofunctional bidentate aldimine] type of derivatives have been synthesised by 1:1 and 1:2 molar reactions of neodymium isopropoxide with the aldimines having the donor system NOH and formed by the condensation of salicylaldehyde with alkylamines. However, bifunctional tridentate Schiff bases (LH) 2 have been found to yield Nd(OPrsup(i)) (L) and Nd 2 (L) 3 type of complexes in 1:1 and 2:3 molar ratio respectively. The isopropoxy groups of the 1:1 complexes have been found to undergo replacement reactions with excess of t-butanol and the resulting complexes are hydrolytically stable. All the newly synthesized complexes have been characterized on the basis of elemental analyses, molecular weight determinations, conductance measurements and infrared and proton magnetic resonance spectral studies. (auth.)

  15. NLRC5: a newly discovered MHC class I transactivator (CITA)

    OpenAIRE

    Meissner, Torsten B.; Li, Amy; Kobayashi, Koichi S.

    2011-01-01

    Major histocompatibility complex (MHC) class I and class II are crucial for the function of the human adaptive immune system. An NLR protein, CIITA (MHC class II transactivator), is a master regulator of MHC class II gene expression as well as of some of the genes involved in MHC class II antigen presentation. It has recently been discovered that another member of the NLR protein family, NLRC5, transcriptionally activates MHC class I genes, and thus acts as “CITA” (MHC class I transactivator)...

  16. Chromosome anomalies in bone marrow as primary cause of aplastic or hypoplastic conditions and peripheral cytopenia: disorders due to secondary impairment of RUNX1 and MPL genes

    Directory of Open Access Journals (Sweden)

    Marletta Cristina

    2012-10-01

    Full Text Available Abstract Background Chromosome changes in the bone marrow (BM of patients with persistent cytopenia are often considered diagnostic for a myelodysplastic syndrome (MDS. Comprehensive cytogenetic evaluations may give evidence of the real pathogenetic role of these changes in cases with cytopenia without morphological signs of MDS. Results Chromosome anomalies were found in the BM of three patients, without any morphological evidence of MDS: 1 an acquired complex rearrangement of chromosome 21 in a boy with severe aplastic anaemia (SAA; the rearrangement caused the loss of exons 2–8 of the RUNX1 gene with subsequent hypoexpression. 2 a constitutional complex rearrangement of chromosome 21 in a girl with congenital thrombocytopenia; the rearrangement led to RUNX1 disruption and hypoexpression. 3 an acquired paracentric inversion of chromosome 1, in which two regions at the breakpoints were shown to be lost, in a boy with aplastic anaemia; the MPL gene, localized in chromosome 1 short arms was not mutated neither disrupted, but its expression was severely reduced: we postulate that the aplastic anaemia was due to position effects acting both in cis and in trans, and causing Congenital Amegakaryocytic Thrombocytopenia (CAMT. Conclusions A clonal anomaly in BM does not imply per se a diagnosis of MDS: a subgroup of BM hypoplastic disorders is directly due to chromosome structural anomalies with effects on specific genes, as was the case of RUNX1 and MPL in the patients here reported with diagnosis of SAA, thrombocytopenia, and CAMT. The anomaly may be either acquired or constitutional, and it may act by deletion/disruption of the gene, or by position effects. Full cytogenetic investigations, including a-CGH, should always be part of the diagnostic evaluation of patients with BM aplasia/hypoplasia and peripheral cytopenias.

  17. Critical thinking dispositions among newly graduated nurses

    Science.gov (United States)

    Wangensteen, Sigrid; Johansson, Inger S; Björkström, Monica E; Nordström, Gun

    2010-01-01

    wangensteen s., johansson i.s., björkström m.e. & nordström g. (2010) Critical thinking dispositions among newly graduated nurses. Journal of Advanced Nursing66(10), 2170–2181. Aim The aim of the study was to describe critical thinking dispositions among newly graduated nurses in Norway, and to study whether background data had any impact on critical thinking dispositions. Background Competence in critical thinking is one of the expectations of nursing education. Critical thinkers are described as well-informed, inquisitive, open-minded and orderly in complex matters. Critical thinking competence has thus been designated as an outcome for judging the quality of nursing education programmes and for the development of clinical judgement. The ability to think critically is also described as reducing the research–practice gap and fostering evidence-based nursing. Methods A cross-sectional descriptive study was performed. The data were collected between October 2006 and April 2007 using the California Critical Thinking Disposition Inventory. The response rate was 33% (n= 618). Pearson’s chi-square tests were used to analyse the data. Results Nearly 80% of the respondents reported a positive disposition towards critical thinking. The highest mean score was on the Inquisitiveness subscale and the lowest on the Truth-seeking subscale. A statistically significant higher proportion of nurses with high critical thinking scores were found among those older than 30 years, those with university education prior to nursing education, and those working in community health care. Conclusion Nurse leaders and nurse teachers should encourage and nurture critical thinking among newly graduated nurses and nursing students. The low Truth-seeking scores found may be a result of traditional teaching strategies in nursing education and might indicate a need for more student-active learning models. PMID:20384637

  18. Proteomic Profiling of De Novo Protein Synthesis in Starvation-Induced Autophagy Using Bioorthogonal Noncanonical Amino Acid Tagging.

    Science.gov (United States)

    Zhang, J; Wang, J; Lee, Y-M; Lim, T-K; Lin, Q; Shen, H-M

    2017-01-01

    Autophagy is an intracellular degradation process activated by stress factors such as nutrient starvation to maintain cellular homeostasis. There is emerging evidence demonstrating that de novo protein synthesis is involved in the autophagic process. However, up-to-date characterizing of these de novo proteins is technically difficult. In this chapter, we describe a novel method to identify newly synthesized proteins during starvation-mediated autophagy by bioorthogonal noncanonical amino acid tagging (BONCAT), in conjunction with isobaric tagging for relative and absolute quantification (iTRAQ)-based quantitative proteomics. l-azidohomoalanine (AHA) is an analog of methionine, and it can be readily incorporated into the newly synthesized proteins. The AHA-containing proteins can be enriched with avidin beads after a "click" reaction between alkyne-bearing biotin and the azide moiety of AHA. The enriched proteins are then subjected to iTRAQ™ labeling for protein identification and quantification using liquid chromatography-tandem mass spectrometry (LC-MS/MS). By using this technique, we have successfully profiled more than 700 proteins that are synthesized during starvation-induced autophagy. We believe that this approach is effective in identification of newly synthesized proteins in the process of autophagy and provides useful insights to the molecular mechanisms and biological functions of autophagy. © 2017 Elsevier Inc. All rights reserved.

  19. A Lipid Based Antigen Delivery System Efficiently Facilitates MHC Class-I Antigen Presentation in Dendritic Cells to Stimulate CD8+ T Cells

    Science.gov (United States)

    Maji, Mithun; Mazumder, Saumyabrata; Bhattacharya, Souparno; Choudhury, Somsubhra Thakur; Sabur, Abdus; Shadab, Md.; Bhattacharya, Pradyot; Ali, Nahid

    2016-06-01

    The most effective strategy for protection against intracellular infections such as Leishmania is vaccination with live parasites. Use of recombinant proteins avoids the risks associated with live vaccines. However, due to low immunogenicity, they fail to trigger T cell responses particularly of CD8+ cells requisite for persistent immunity. Previously we showed the importance of protein entrapment in cationic liposomes and MPL as adjuvant for elicitation of CD4+ and CD8+ T cell responses for long-term protection. In this study we investigated the role of cationic liposomes on maturation and antigen presentation capacity of dendritic cells (DCs). We observed that cationic liposomes were taken up very efficiently by DCs and transported to different cellular sites. DCs activated with liposomal rgp63 led to efficient presentation of antigen to specific CD4+ and CD8+ T cells. Furthermore, lymphoid CD8+ T cells from liposomal rgp63 immunized mice demonstrated better proliferative ability when co-cultured ex vivo with stimulated DCs. Addition of MPL to vaccine enhanced the antigen presentation by DCs and induced more efficient antigen specific CD8+ T cell responses when compared to free and liposomal antigen. These liposomal formulations presented to CD8+ T cells through TAP-dependent MHC-I pathway offer new possibilities for a safe subunit vaccine.

  20. Vertical separation of the atmospheric aerosol components by using poliphon retrieval in polarized micro pulse lidar (P-MPL) measurements: case studies of specific climate-relevant aerosol types

    Science.gov (United States)

    Córdoba-Jabonero, Carmen; Sicard, Michaël; Ansmann, Albert; Águila, Ana del; Baars, Holger

    2018-04-01

    POLIPHON (POlarization-LIdar PHOtometer Networking) retrieval consists in the vertical separation of two/three particle components in aerosol mixtures, highlighting their relative contributions in terms of the optical properties and mass concentrations. This method is based on the specific particle linear depolarization ratio given for different types of aerosols, and is applied to the new polarized Micro-Pulse Lidar (P-MPL). Case studies of specific climate-relevant aerosols (dust particles, fire smoke, and pollen aerosols, including a clean case as reference) observed over Barcelona (Spain) are presented in order to evaluate firstly the potential of P-MPLs measurements in combination with POLIPHON for retrieving the vertical separation of those particle components forming aerosol mixtures and their properties.

  1. Comparative Survival in Patients With Postresection Recurrent Versus Newly Diagnosed Non-Small-Cell Lung Cancer Treated With Radiotherapy

    International Nuclear Information System (INIS)

    Cai Xuwei; Xu Luying; Wang Li; Hayman, James A.; Chang, Andrew C.; Pickens, Allan; Cease, Kemp B.; Orringer, Mark B.; Kong, F.-M.

    2010-01-01

    Purpose: To compare the survival of postresection recurrent vs. newly diagnosed non-small-cell lung cancer (NSCLC) patients treated with radiotherapy or chemoradiotherapy. Methods and Materials: The study population consisted of 661 consecutive patients with NSCLC registered in the radiation oncology databases at two medical centers in the United States between 1992 and 2004. Of the 661 patients, 54 had postresection recurrent NSCLC and 607 had newly diagnosed NSCLC. Kaplan-Meier and Cox regression models were used for the survival analyses. Results: The distribution of relevant clinical factors between these two groups was similar. The median survival time and 5-year overall survival rates were 19.8 months (95% confidence interval [CI], 13.9-25.7) and 14.8% (95% confidence interval, 5.4-24.2%) vs. 12.2 months (95% CI, 10.8-13.6) and 11.0% (95% CI, 8.5-13.5%) for recurrent vs. newly diagnosed patients, respectively (p = .037). For Stage I-III patients, no significant difference was observed in the 5-year overall survival (p = .297) or progression-free survival (p = .935) between recurrent and newly diagnosed patients. For the 46 patients with Stage I-III recurrent disease, multivariate analysis showed that chemotherapy was a significant prognostic factor for 5-year progression-free survival (hazard ratio, 0.45; 95% CI, 0.224-0.914; p = .027). Conclusion: Our institutional data have shown that patients with postresection recurrent NSCLC achieved survival comparable to that of newly diagnosed NSCLC patients when they were both treated with radiotherapy or chemoradiotherapy. These findings suggest that patients with postresection recurrent NSCLC should be treated as aggressively as those with newly diagnosed disease.

  2. Production of gaseous radiotracers CH3I and I2 through Na123I salt

    International Nuclear Information System (INIS)

    Candeiro, R.E.M.; Pereira, W.P.

    2011-01-01

    The objective of the present work was to develop, separately, methodology for production of two gaseous tracers through the sodium iodide NaI marked with 123 I. Found in the nature in form different, the iodine has been used in diverse works in the area of the industry and health. These two forms of the gaseous iodine, the methyl iodide, CH 3 I, and molecular iodine, I 2 , are very unstable and volatile in the ambient temperature and presents different problems in clean-up and monitoring systems. The syntheses were processed with sodium iodide (NaI) 1M aqueous solution marked with 1 23I . The production of gas I 2 was realized with in chlorine acid (HCl) and sodium iodate salt (NaIO 3 ) and the CH 3 I was used, the salt of NaI and the reagent (CH 3 ) 2 SO 4 . The production of gases was initially realized through in unit in glass with an inert material and the purpose was to study the kinetic of reaction and to determine the efficiency of production. The two synthesis occurs in the reaction bottle and after of produced, the gas is stored in the collect bottle that contains a starch solution for fixed the I 2 , and in syntheses of CH 3 I contains a silver nitrate solution for your fixation. To determine the efficiency of production of gases, analytic tests were realized, where the consumption of iodide ions of the bottle of reaction are measured. The optimization of production of the each gaseous tracer was studied varying parameter as: concentration of iodide, concentration of acid and temperature. After, the syntheses of the radiotracers were realized in the compact unit, having been used as main reagent the salt radiated of sodium iodide, Na 123 I. The transportation of elementary iodine and methyl iodine was studied by a scintillation detector NaI (2 x 2)' positioned in the reaction bottle. (author)

  3. Antitumor activity of newly synthesized oxo and ethylidene derivatives of bile acids and their amides and oxazolines.

    Science.gov (United States)

    Bjedov, Srđan; Jakimov, Dimitar; Pilipović, Ana; Poša, Mihalj; Sakač, Marija

    2017-04-01

    Bile acid derivatives with modifications in side chain and modifications on steroid skeleton were synthetized and their antitumor activity against five human cancer cell lines was investigated. Modifications in side chain include amid group, formed in reaction with 2-amino-2-methylpropanol, and 4,4-dimethyloxazoline group, obtained after cyclization of amides. In the steroid skeleton oxo groups were introduced in position 7 (2, 2a, 2b) and 7,12 (3, 3a, 3b). Ethylidene groups were introduced regio- and stereoselectively on C-7, and/or without stereoselectivity on C-3 by Wittig reaction. By combination of these modifications, a series of 19 bile acid derivatives were synthesized. Compounds containing both C-7 ethylidene and C-12 carbonyl groups (6, 6a, 6b) shown very good antitumor activity with IC 50 amide or oxazoline group has positive effect on cytotoxicity. Different molecular descriptors were determined in silico and after principal component analysis was found that molecular descriptor BLTF96 can be used for fast assessment of experimental cytotoxicity of bile acid derivatives. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. 131I Metaiodobenzylguanidine scintigraphy

    International Nuclear Information System (INIS)

    Izumi, Motomori; Morimoto, Isao; Yamashita, Shunichi; Hirayu, Hideshi; Nagataki, Shigenobu

    1988-01-01

    A newly developed radiopharmaceutical agent, 131 I-metaiodobenzylguanidine ( 131 I-MIBG) has been reported to be very useful for locating pheochromocytoma and to be specific for pheochromocytoma and safe for humans. The first 131 I-MIBG scintiscanning in Japan which has been carried out in our clinic and the analysis of clinical experience of 131 I-MIBG scanning in Japan are presented

  5. What Did They Take Away?: Examining Newly Qualified U.S. Teachers' Visions of Learning and Teaching Science in K-8 Classrooms

    Science.gov (United States)

    Roberts-Harris, Deborah

    2014-01-01

    This study investigated newly qualified K-8 teachers' visions of science learning and teaching after they had completed preparation in a science teaching methods course I taught. What visions of science learning and teaching were these newly qualified teachers taking away from my course? How did these visions compare with those advocated by reform…

  6. Newly Homeless Youth Typically Return Home

    OpenAIRE

    Milburn, Norweeta G.; Rosenthal, Doreen; Rotheram-Borus, Mary Jane; Mallett, Shelley; Batterham, Philip; Rice, Eric; Solorio, Rosa

    2007-01-01

    165 newly homeless adolescents from Melbourne, Australia and 261 from Los Angeles, United States were surveyed and followed for two years. Most newly homeless adolescents returned home (70% U.S., 47% Australia) for significant amounts of time (39% U.S., 17% Australia more than 12 months) within two years of becoming homeless.

  7. Kulanaokuaiki Tephra (ca, A.D. 400-1000): Newly recognized evidence for highly explosive eruptions at Kilauea Volcano, Hawai'i

    Science.gov (United States)

    Fiske, R.S.; Rose, T.R.; Swanson, D.A.; Champion, D.E.; McGeehin, J.P.

    2009-01-01

    K??lauea may be one of the world's most intensively monitored volcanoes, but its eruptive history over the past several thousand years remains rather poorly known. Our study has revealed the vestiges of thin basaltic tephra deposits, overlooked by previous workers, that originally blanketed wide, near-summit areas and extended more than 17 km to the south coast of Hawai'i. These deposits, correlative with parts of tephra units at the summit and at sites farther north and northwest, show that K??lauea, commonly regarded as a gentle volcano, was the site of energetic pyroclastic eruptions and indicate the volcano is significantly more hazardous than previously realized. Seventeen new calibrated accelerator mass spectrometry (AMS) radiocarbon ages suggest these deposits, here named the Kulanaokuaiki Tephra, were emplaced ca. A.D. 400-1000, a time of no previously known pyroclastic activity at the volcano. Tephra correlations are based chiefly on a marker unit that contains unusually high values of TiO2 and K2O and on paleomagnetic signatures of associated lava flows, which show that the Kulanaokuaiki deposits are the time-stratigraphic equivalent of the upper part of a newly exhumed section of the Uw??kahuna Ash in the volcano's northwest caldera wall. This section, thought to have been permanently buried by rockfalls in 1983, is thicker and more complete than the previously accepted type Uw??kahuna at the base of the caldera wall. Collectively, these findings justify the elevation of the Uw??kahuna Ash to formation status; the newly recognized Kulanaokuaiki Tephra to the south, the chief focus of this study, is defined as a member of the Uw??kahuna Ash. The Kulanaokuaiki Tephra is the product of energetic pyroclastic falls; no surge- or pyroclastic-flow deposits were identified with certainty, despite recent interpretations that Uw??kahuna surges extended 10-20 km from K??lauea's summit. ?? 2009 Geological Society of America.

  8. Impact of Interfacial Water Transport in PEMFCs on Cell Performance

    International Nuclear Information System (INIS)

    Kotaka, Toshikazu; Tabuchi, Yuichiro; Pasaogullari, Ugur; Wang, Chao-Yang

    2014-01-01

    Coupled cell performance evaluation, liquid water visualization by neutron radiography (NRG) and numerical modeling based on multiphase mixture (M2) model were performed with three types of GDMs: Micro Porous Layer (MPL) free; Carbon Paper (CP) with MPL; and CP free to investigate interfacial liquid water transport phenomena in PEMFCs and its effect on cell performance. The visualized results of MPL free GDM with different wettability of bi-polar plates (BPPs) showed hydrophilic BPP improved liquid water transport at the interface between CP and channel. Numerical modeling results indicated that this difference with BPP wettability was caused by the liquid water coverage difference on CP surface. Thus, controlling liquid water coverage is the one of the key strategies for improving cell performance. Additionally, liquid water distributions across the cell for three types of GDMs were compared and significant difference in liquid water content at the interface between Catalyst Layer (CL) and GDM was observed. Numerical modeling suggests this difference is influenced by the gap at the interface and that the MPL could minimize this effect. The CP free cell (i.e. only MPL) showed the best performance and the lowest liquid water content. There were multiple impacts of interfacial liquid water transport both at CL-GDM and GDM-channel interfaces. High hydrophobicity and fine structure of MPLs contributed to enhanced liquid water transport at GDM-channel interface and as a result reduced the liquid water coverage. At the same time, MPL improves contact at the CL-GDM interface in the same manner as seen in CP with MPL case. Thus, the CP free concept showed the best performance. It is suggested that the design of the interface between each component of the PEMFC has a great impact on cell performance and plays a significant role in achievement of high current density operation and cost reduction in FCEVs

  9. Forms of Knowledge Incorporated in Clinical Decision-making among Newly-Graduated Nurses: A Metasynthesis

    DEFF Research Database (Denmark)

    Voldbjerg, Siri; Elgaard Sørensen, Erik; Grønkjær, Mette

    2014-01-01

    Clinical-decision-making is of decisive importance to how evidence-based practice is put into practice. Schools of Nursing have a responsibility to teach and train nursing students to make clinical decisions within a frame of evidence-based practice. Clinical decision-making among nurses has been...... explored from numerous angles using a diversity of methodologies. Existing research has mainly focused on promoting and inhibiting factors for implementation of evidence-based practice and incorporation of research evidence in the clinical-decision. Little attention has been given to the nurses' behavior......, including the knowledge that actually informs the newly graduated nurses’ clinical decision. The aim of the study is to combine and synthesize results from qualitative research. Noblit and Hare’s meta-ethnographic approach is used to conduct a metasynthesis of qualitative research that has studied...

  10. NEWLY IDENTIFIED EXTENDED GREEN OBJECTS (EGOs) FROM THE SPITZER GLIMPSE II SURVEY. II. MOLECULAR CLOUD ENVIRONMENTS

    Energy Technology Data Exchange (ETDEWEB)

    Chen Xi; Gan Conggui; Shen Zhiqiang [Key Laboratory for Research in Galaxies and Cosmology, Shanghai Astronomical Observatory, Chinese Academy of Sciences, Shanghai 200030 (China); Ellingsen, Simon P.; Titmarsh, Anita [School of Mathematics and Physics, University of Tasmania, Hobart, Tasmania (Australia); He Jinhua, E-mail: chenxi@shao.ac.cn [Key Laboratory for the Structure and Evolution of Celestial Objects, Yunnan Astronomical Observatory/National Astronomical Observatory, Chinese Academy of Sciences, P.O. Box 110, Kunming 650011, Yunnan Province (China)

    2013-06-01

    We have undertaken a survey of molecular lines in the 3 mm band toward 57 young stellar objects using the Australia Telescope National Facility Mopra 22 m radio telescope. The target sources were young stellar objects with active outflows (extended green objects (EGOs)) newly identified from the GLIMPSE II survey. We observe a high detection rate (50%) of broad line wing emission in the HNC and CS thermal lines, which combined with the high detection rate of class I methanol masers toward these sources (reported in Paper I) further demonstrates that the GLIMPSE II EGOs are associated with outflows. The physical and kinematic characteristics derived from the 3 mm molecular lines for these newly identified EGOs are consistent with these sources being massive young stellar objects with ongoing outflow activity and rapid accretion. These findings support our previous investigations of the mid-infrared properties of these sources and their association with other star formation tracers (e.g., infrared dark clouds, methanol masers and millimeter dust sources) presented in Paper I. The high detection rate (64%) of the hot core tracer CH{sub 3}CN reveals that the majority of these new EGOs have evolved to the hot molecular core stage. Comparison of the observed molecular column densities with predictions from hot core chemistry models reveals that the newly identified EGOs from the GLIMPSE II survey are members of the youngest hot core population, with an evolutionary time scale of the order of 10{sup 3} yr.

  11. Histological evaluation of tissue reactions to newly synthetized calcium silicate- and hydroxyapatite-based bioactive materials: in vivo study

    Directory of Open Access Journals (Sweden)

    Opačić-Galić Vanja

    2017-01-01

    Full Text Available Introduction/Objective. Development of materials which could be used as biological bone substitutes is one of the most valuable and active fields of biomaterial research. The goal of the study was to research the reaction of tissue on calcium silicate- (CS and hydroxyapatitebased (CS-HA newly synthesized nanomaterials, after being implanted into the subcutaneous tissue of a rats and direct pulp capping of rabbit teeth. Methods. The tested materials were implanted in 40 Wistar male rats, sacrificed after seven, 15, 30, and 60 days. The direct pulp capping was performed on the teeth of rabbits. Cavities were prepared on the vestibular surface of the incisors. The animals were sacrificed after 10 and 15 days. The control material was mineral trioxide aggregate (MTA. Histological analysis covered the tracking of inflammatory reaction cellular components, presence of gigantic cells, and necrosis of the tissue. Results. Seven days after the implantation, the strongest inflammatory response was given by the MTA (3.3 Ѓ} 0.48, while CS and CS-HA scored 3 ± 0.71. After 60 days, the rate of inflammatory reactions dropped, which was the least visible with CS-HA (0.2 ± 0.45. The least visible inflammatory reaction of the rabbits’ pulp tissue was spotted with the CS (1.83 ± 0.75, than with the MTA and CS-HA (2.67 ± 1.53, 3 ± 0.63. Conclusion. The newly synthesized materials caused a slight reaction of the subcutaneous tissue. CS-HA showed the best tissue tolerance. Nanostructural biomaterials caused a slight to moderate inflammatory reaction of the rabbits’ pulp tissue only in the immediate vicinity of the implanted material.

  12. Annual reports in inorganic and general syntheses 1974

    CERN Document Server

    Niedenzu, Kurt

    1975-01-01

    Annual Reports in Inorganic and General Syntheses-1974 presents an organized annual summary of synthetic developments in inorganic chemistry and its related areas. The book discusses the chemistry of simple and complex metal hydrides of main groups I, II, and III, boron, aluminium, gallium, indium, thallium, silicon, germanium, tin, lead, phosphorus, arsenic, antimony, bismuth, chalcogens, halogens, and pseudohalogens. The text also describes the chemistry of scandium, yttrium, lanthanides, actinides, titanium, zirconium, hafnium, vanadium, niobium, tantalum, chromium, molybdenum, tungsten, ma

  13. Baseline staging tests based on molecular subtype is necessary for newly diagnosed breast cancer.

    Science.gov (United States)

    Chen, Xuesong; Sun, Lichun; Cong, Yingying; Zhang, Tingting; Lin, Qiushi; Meng, Qingwei; Pang, Hui; Zhao, Yanbin; Li, Yu; Cai, Li; Dong, Xiaoqun

    2014-03-17

    Bone scanning (BS), liver ultrasonography (LUS), and chest radiography (CXR) are commonly recommended for baseline staging in patients with newly diagnosed breast cancer. The purpose of this study is to demonstrate whether these tests are indicated for specific patient subpopulation based on clinical staging and molecular subtype. A retrospective study on 5406 patients with newly diagnosed breast cancer was conducted to identify differences in occurrence of metastasis based on clinical staging and molecular subtypes. All patients had been evaluated by BS, LUS and CXR at diagnosis. Complete information on clinical staging was available in 5184 patients. For stage I, II, and III, bone metastasis rate was 0%, 0.6% and 2.7%, respectively (P diagnosed breast cancer.

  14. Understanding newly discovered oscillation modes in magnetically shielded Hall thrusters utilizing state of the art high speed diagnostics.

    Data.gov (United States)

    National Aeronautics and Space Administration — I propose to investigate the newly discovered oscillation modes specific to Magnetically Shied (MS) Hall Effect Thrusters (HET). Although HETs are classified as a...

  15. Immunoparesis in newly diagnosed Multiple Myeloma patients

    DEFF Research Database (Denmark)

    Sorrig, Rasmus; Klausen, Tobias W.; Salomo, Morten

    2017-01-01

    Immunoparesis (hypogammaglobulinemia) is associated to an unfavorable prognosis in newly diagnosed Multiple myeloma (MM) patients. However, this finding has not been validated in an unselected population-based cohort. We analyzed 2558 newly diagnosed MM patients in the Danish Multiple Myeloma...

  16. X-ray Tomographic Analysis of Porosity Distributions in Gas Diffusion Layers of Proton Exchange Membrane Fuel Cells

    International Nuclear Information System (INIS)

    Odaya, S.; Phillips, R.K.; Sharma, Y.; Bellerive, J.; Phillion, A.B.; Hoorfar, M.

    2015-01-01

    This paper describes a method to characterize the structure of polytetrafluoroethylene (PTFE) treated gas diffusion layers (GDLs) with and without microporous layers (MPLs) using 3D X-ray micro computed tomographic (μCT) microscopy. In this work, the structure of single and dual layer GDLs is evaluated via μCT for various GDL samples (such as Toray TGP-H-060 and AvCarb EP40) loaded with different MPLs. A new method is presented for separating, or segmenting, the various phases of the GDL, i.e., void space, carbon fiber (including binder and PTFE), and MPL. Through analysis, it was found that the variation in bulk porosity and the average pore diameter of the GDLs depends highly on the GDL series manufacturing and treatment processes. Using advanced image analysis techniques, routines were developed to accurately segment the GDL fibers (including binder/PTFE) and the MPL. The percentage of the intruding MPL material into the carbon fiber paper as a function of the GDL thickness was successfully found for dual layer GDLs, with varying PTFE content and areal weight loading in the MPL. This analysis provides invaluable insight into the physical microstructure of paper-based GDLs, emphasizing the heterogeneous porosity distribution of single layer GDLs and the interaction of the MPL with the carbon fiber paper of dual layer GDLs

  17. Operation and Maintenance of the Research Platform FLIP

    Science.gov (United States)

    2013-12-17

    by FLIP 2006 15Aug-11 Sept PI R. Pinkel, MPL , ONR, AESOP 02 Oct-04 Nov PI J. Hildebrand, MPL ONR Marine Mammal 2007 21 Feb-16Mar T. Golfinos ONR...Dry Dock in ARCO 30 Oct-29 Nov PIJ. Hildebrand, MPL ONR/N45 Marine Mammal 2008 03-25 Sep PI K. Melville, MPL ONR RaDyo Program 13 0ct-12Nov PI J...Hildebrand, MPL ONR Marine Mammal Research 2009 6-7 May PI K. Melville, MPL ONR Sea Trials 06-14 Jul PI K. Melville, MPL ONR ONR HiRes 03-13 Aug T

  18. Reversed-phase high-performance liquid chromatographic analyses of insulin biosynthesis in isolated rat and mouse islets

    DEFF Research Database (Denmark)

    Linde, S; Hansen, Bruno A.; Welinder, B S

    1989-01-01

    deletion compared to rat C-peptide I. A marked species difference in the ratio between insulin I and II was observed, i.e., 2:1 in the rat and 1:2 in the mouse. Pulse-chase experiments in rat islets have demonstrated that the ratio between insulin I and II in newly synthesized insulin is higher than...

  19. Production of gaseous radiotracers CH{sub 3}I and I{sub 2} through Na{sup 123}I salt

    Energy Technology Data Exchange (ETDEWEB)

    Candeiro, R.E.M., E-mail: ricardocandeiro@cnen.gov.b [Comissao Nacional de Energia Nuclear (DIFOR/CNEN-CE), Fortaleza, CE (Brazil). Distrito de Fortaleza; Brandao, L.B. [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Pereira, W.P. [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil)

    2011-07-01

    The objective of the present work was to develop, separately, methodology for production of two gaseous tracers through the sodium iodide NaI marked with {sup 123}I. Found in the nature in form different, the iodine has been used in diverse works in the area of the industry and health. These two forms of the gaseous iodine, the methyl iodide, CH{sub 3}I, and molecular iodine, I{sub 2}, are very unstable and volatile in the ambient temperature and presents different problems in clean-up and monitoring systems. The syntheses were processed with sodium iodide (NaI) 1M aqueous solution marked with 1{sup 23I}. The production of gas I{sub 2} was realized with in chlorine acid (HCl) and sodium iodate salt (NaIO{sub 3}) and the CH{sub 3}I was used, the salt of NaI and the reagent (CH{sub 3}){sub 2}SO{sub 4}. The production of gases was initially realized through in unit in glass with an inert material and the purpose was to study the kinetic of reaction and to determine the efficiency of production. The two synthesis occurs in the reaction bottle and after of produced, the gas is stored in the collect bottle that contains a starch solution for fixed the I{sub 2}, and in syntheses of CH{sub 3}I contains a silver nitrate solution for your fixation. To determine the efficiency of production of gases, analytic tests were realized, where the consumption of iodide ions of the bottle of reaction are measured. The optimization of production of the each gaseous tracer was studied varying parameter as: concentration of iodide, concentration of acid and temperature. After, the syntheses of the radiotracers were realized in the compact unit, having been used as main reagent the salt radiated of sodium iodide, Na{sup 123}I. The transportation of elementary iodine and methyl iodine was studied by a scintillation detector NaI (2 x 2)' positioned in the reaction bottle. (author)

  20. Risk Assessment for CPAP Nonadherence in Adults with Newly-diagnosed Obstructive Sleep Apnea: Preliminary Testing of the Index for Nonadherence to PAP (I-NAP)

    Science.gov (United States)

    Sawyer, Amy M.; King, Tonya S.; Hanlon, Alexandra; Richards, Kathy C.; Sweer, Leon; Rizzo, Albert; Weaver, Terri E.

    2014-01-01

    Purpose Identification of risk for CPAP nonadherence prior to home treatment is an opportunity to deliver targeted, adherence interventions. Study objectives included (1) test a risk screening questionnaire to prospectively identify CPAP nonadherence risk among adults with newly-diagnosed OSA; (2) reduce the questionnaire to a minimum item set that effectively identifies 1-month CPAP nonadherence; and (3) examine the diagnostic utility of the screening index. Methods A prospective, longitudinal study at two clinical sleep centers in the U.S. included adults with newly diagnosed OSA (n=97; AHI ≥ 5 events/hr) by polysomnogram (PSG) consecutively recruited to participate. After baseline participant and OSA characteristics were collected, a risk screening questionnaire was administered immediately following CPAP titration polysomnogram. One-month objective CPAP use was collected. Results Predominantly white (87%) males (55%) and females (45%) with obesity (BMI 38.3 kg/m2; SD 9.3) and severe OSA (AHI 36.8; SD 19.7) were included. One-month CPAP use was 4.25hrs/night (SD 2.35). Nineteen questionnaire items (I-NAP) reliably identified nonadherers defined at CPAP use (Wald X2[8] =34.67, p60% (63%). Conclusion A risk screening questionnaire employed immediately after titration PSG may reliably identify CPAP nonadherers and permit the delivery of targeted interventions to prevent or reduce nonadherence. This novel approach may enhance cost-effectiveness of care and permit appropriate allocation of resources for CPAP adherence. PMID:24595715

  1. 76 FR 30417 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2011-05-25

    ... order entry size of a Mid-Point Passive Liquidity Order (``MPL Order'') from 100 shares to one share... minimum order entry size of an MPL Order from 100 shares to one share. MPL Orders were initially designed... implementing MPL Orders to permit Users to enter MPL Orders for smaller sized order flow, including orders of...

  2. Generational differences among newly licensed registered nurses.

    Science.gov (United States)

    Keepnews, David M; Brewer, Carol S; Kovner, Christine T; Shin, Juh Hyun

    2010-01-01

    Responses of 2369 newly licensed registered nurses from 3 generational cohorts-Baby Boomers, Generation X, and Generation Y-were studied to identify differences in their characteristics, work-related experiences, and attitudes. These responses revealed significant differences among generations in: job satisfaction, organizational commitment, work motivation, work-to-family conflict, family-to-work conflict, distributive justice, promotional opportunities, supervisory support, mentor support, procedural justice, and perceptions of local job opportunities. Health organizations and their leaders need to anticipate intergenerational differences among newly licensed nurses and should provide for supportive working environments that recognize those differences. Orientation and residency programs for newly licensed nurses should be tailored to the varying needs of different generations. Future research should focus on evaluating the effectiveness of orientation and residency programs with regard to different generations so that these programs can be tailored to meet the varying needs of newly licensed nurses at the start of their careers. Copyright 2010 Mosby, Inc. All rights reserved.

  3. Accumulation of noncrystalline cellulose in Physarum microplasmodia

    OpenAIRE

    Ogawa, Kyoko; Maki, Hisae; Sato, Mamiko; Ashihara, Hiroshi; Kaneko, Takako S.

    2013-01-01

    Physarum plasmodium lives as a slimy mass of protoplast in the dark fragments into small multinucleated microplasmodia (mPL) in a liquid medium. When mPL are exposed to several unfavorable environments, they transform into ?spherules? with a cell wall. Using a synchronous spherule-induction system for mPL, we examined the effect of 2,6-dichlorobenzonitrile on the synthesis of cellulose in mPL, by observing mPL under a fluorescence microscope, and isolated cellulose from mPL to identify them m...

  4. OPTIMIZATION OF TRANSESTERIFICATION PARAMETERS FOR OPTIMAL BIODIESEL YIELD FROM CRUDE JATROPHA OIL USING A NEWLY SYNTHESIZED SEASHELL CATALYST

    Directory of Open Access Journals (Sweden)

    A. N. R. REDDY

    2017-10-01

    Full Text Available Heterogeneous catalysts are promising catalysts for optimal biodiesel yield from transesterification of vegetable oils. In this work calcium oxide (CaO heterogeneous catalyst was synthesized from Polymedosa erosa seashell. Calcination was carried out at 900ºC for 2h and characterized using Fourier transform infrared spectroscopy. Catalytic efficiency of CaO was testified in transesterification of crude Jatropha oil (CJO. A response surface methodology (RSM based on five-level-two-factor central composite design (CCD was employed to optimize two critical transesterification parameters catalyst concentration to pretreated CJO (0.01-0.03 w/w % and the reaction time (90 min - 150 min. A JB yield of 96.48% was estimated at 0.023 w/w% catalyst and 125.76 min reaction using response optimizer. The legitimacy of the predicted model was verified through the experiments. The validation experiments conformed a yield of JB 96.4%±0.01% as optimal at 0.023 w/w% catalyst to pretreated oil ratio and 126 min reaction time.

  5. Effects of microstructure characteristics of gas diffusion layer and microporous layer on the performance of PEMFC

    Energy Technology Data Exchange (ETDEWEB)

    Tseng, C.-J., E-mail: cjtseng@ncu.edu.t [Department of Mechanical Engineering, National Central University, Chungli, Taoyuan 320, Taiwan (China); Lo, S.-K. [Department of Mechanical Engineering, National Central University, Chungli, Taoyuan 320, Taiwan (China)

    2010-04-15

    Water management is an important issue in proton exchange membrane (PEM) fuel cell design and operation. The purpose of this work is to investigate the effects of the microstructure characteristics of the gas diffusion layer (GDL) and microporous layer (MPL), including pore size distribution, hydrophobic treatment, gas permeability, and other factors, on the water management and performance of a PEM fuel cell. A commercial catalyst-coated membrane with an active area of 25 cm{sup 2} is used along with a GDL and an MPL for assembling a single cell. The effects of the MPL, the thickness of the MPL, the PTFE loading of carbon paper and MPL, and the baking time of the MPL have been investigated. Results show that the addition of MPL increases cell performance in the high current density region due to the elimination of mass transfer limitation. There exists an optimum thickness of MPL. Furthermore, increasing the MPL baking time enhances cell performance due to enlarged pore size and permeability.

  6. Effects of microstructure characteristics of gas diffusion layer and microporous layer on the performance of PEMFC

    Energy Technology Data Exchange (ETDEWEB)

    Chung-Jen Tseng; Shih-Kun Lo [Department of Mechanical Engineering, National Central University, Chungli, Taoyuan 320 (China)

    2010-04-15

    Water management is an important issue in proton exchange membrane (PEM) fuel cell design and operation. The purpose of this work is to investigate the effects of the microstructure characteristics of the gas diffusion layer (GDL) and microporous layer (MPL), including pore size distribution, hydrophobic treatment, gas permeability, and other factors, on the water management and performance of a PEM fuel cell. A commercial catalyst-coated membrane with an active area of 25 cm{sup 2} is used along with a GDL and an MPL for assembling a single cell. The effects of the MPL, the thickness of the MPL, the PTFE loading of carbon paper and MPL, and the baking time of the MPL have been investigated. Results show that the addition of MPL increases cell performance in the high current density region due to the elimination of mass transfer limitation. There exists an optimum thickness of MPL. Furthermore, increasing the MPL baking time enhances cell performance due to enlarged pore size and permeability. (author)

  7. Effects of microstructure characteristics of gas diffusion layer and microporous layer on the performance of PEMFC

    International Nuclear Information System (INIS)

    Tseng, C.-J.; Lo, S.-K.

    2010-01-01

    Water management is an important issue in proton exchange membrane (PEM) fuel cell design and operation. The purpose of this work is to investigate the effects of the microstructure characteristics of the gas diffusion layer (GDL) and microporous layer (MPL), including pore size distribution, hydrophobic treatment, gas permeability, and other factors, on the water management and performance of a PEM fuel cell. A commercial catalyst-coated membrane with an active area of 25 cm 2 is used along with a GDL and an MPL for assembling a single cell. The effects of the MPL, the thickness of the MPL, the PTFE loading of carbon paper and MPL, and the baking time of the MPL have been investigated. Results show that the addition of MPL increases cell performance in the high current density region due to the elimination of mass transfer limitation. There exists an optimum thickness of MPL. Furthermore, increasing the MPL baking time enhances cell performance due to enlarged pore size and permeability.

  8. Speciation analysis of I-127,129 in the crop field soil contaminated by the Fukushima Dai-ichi nuclear power plant accident with newly developed chemical separation techniques

    Science.gov (United States)

    Honda, Maki; Matsuzaki, Hiroyuki; Saito, Takumi; Nagai, Hisao

    2014-05-01

    In previous study, we investigated the depth profile of the accident derived I-129 and downward migration speed in soils of near-field of Fukushima Dai-ichi Nuclear Power Plant, including crop fields and man-made fields. I-129 in soil was measured by AMS and stable iodine (I-127) was measured by ICP-MS at MALT (Micro Analysis Laboratory, Tandem accelerator), The University of Tokyo. It was found that I-129 was concentrated near surface but distributed deeper compared with Cs-137. It was also found that I-129 seems to move downward more quickly than Cs-137. To investigate the adsorption mechanism and the elemental process of migration of the accident derived I-129 in soil, it is important to know what kind of component the I-129 combines with. Recent studies on the X-ray absorption fine structure (XAFS), especially near edge structure (XANES), reported that the stable iodine (I-127) in soil existed as an organic component. However, it had not yet been proved that it was also the case with the accident derived I-129 because it had been incorporated in the soil system only recently and the abundance of I-129 in soil was more than 8 orders of magnitude smaller than sub-ppm level stable iodine (I-127). In this study a progressive sequential extraction method including the dialysis and the dynamic headspace method was newly developed to obtain only the iodine sticking to the soil organic component. The stable iodine can be quantified by direct analysis of the fraction and I-129 can be quantified by AMS method of the fraction added with carrier. The fraction of the organic component for I-127 and I-129 can be evaluated respectively by comparing with the other fraction and/or with the total concentration obtained by the bulk analysis (e.g. by the pyrohydrolysis).

  9. Big earth-observation data analytics for modelling pan-tropical land-use change trajectories for newly deforested areas

    Science.gov (United States)

    Coca Castro, Alejandro; Reymondin, Louis; Rebetez, Julien; Fabio Satizabal Mejia, Hector; Perez-Uribe, Andres; Mulligan, Mark; Smith, Thomas; Hyman, Glenn

    2017-04-01

    Global land use monitoring is important to the the Sustainable Development Goals (SDGs). The latest advances in storage and manipulation of big earth-observation data have been key to developing multiple operational forest monitoring initiatives such as FORMA, Terra-i and Global Forest Change. Although the data provided by these systems are useful for identifying and estimating newly deforested areas (from 2000), they do not provide details about the land use to which these deforested areas are transitioned. This information is critical to understand the biodiversity and ecosystem services impact of deforestation and the resulting impacts on human wellbeing, locally and downstream. With the aim of contributing to current forest monitoring initiatives, this research presents a set of experimental case studies in Latin America which integrate existing land-change information derived from remote sensing image and aerial photography/ground datasets, high-temporal resolution MODIS data, advanced machine learning (i.e deep learning) and big data technologies (i.e. Hadoop and Spark) to assess land-use change trajectories in newly deforested areas in near real time.

  10. From Dignity to Employment - Newly arrived immigrants and refugees’ interpretations of opportunities to improve labor market participation through the Introduction Program

    OpenAIRE

    Ediassen, Tora

    2016-01-01

    Master i International Social Welfare and Health Policy The aim of this thesis is to explore how newly arrived immigrants and refugees interpret their opportunities to improve labor market participation through the Introduction Program. The thesis is based on qualitative interviews with six former participants of the program situated in Oslo, Norway. The Introduction Program is an activation program designed to qualify newly arrived immigrants and refugees for economic indep...

  11. PULSE SYNTHESIZING GENERATOR

    Science.gov (United States)

    Kerns, Q.A.

    1963-08-01

    >An electronlc circuit for synthesizing electrical current pulses having very fast rise times includes several sinewave generators tuned to progressively higher harmonic frequencies with signal amplitudes and phases selectable according to the Fourier series of the waveform that is to be synthesized. Phase control is provided by periodically triggering the generators at precisely controlled times. The outputs of the generators are combined in a coaxial transmission line. Any frequency-dependent delays that occur in the transmission line can be readily compensated for so that the desired signal wave shape is obtained at the output of the line. (AEC)

  12. Syntheses, crystal structures and properties of series of 4d–4f ln(III)–Ag(I) heterometallic coordination polymers

    Energy Technology Data Exchange (ETDEWEB)

    Ran, Xing-Rui [School of Chemistry and Environment, South China Normal University, Guangzhou 510006 (China); Wang, Ning [School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798 (Singapore); Xie, Wei-Ping; Xiong, Yan-Ju; Cheng, Qian [School of Chemistry and Environment, South China Normal University, Guangzhou 510006 (China); Long, Yi [School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798 (Singapore); Yue, Shan-Tang, E-mail: yuesht@scnu.edu.cn [School of Chemistry and Environment, South China Normal University, Guangzhou 510006 (China); Guangzhou Key Laboratory of Materials for Energy Conversion and Storage, Guangzhou (China); Liu, Ying-Liang [College of Science, South China Agricultural University, Guangzhou 510642 (China)

    2015-05-15

    By control of the experimental parameters such as ligands, pH value and reacting temperature, series of three-dimensional (3D) 4d–4f Ln(III)–Ag(I) porous coordination polymers (PCPs) with interesting chain-layer construction, namely, ([Ln{sup III}Ag{sup I}(na)(ina)(ox)]·2(H{sub 2}O)){sub n} [Ln=Sm(1), Eu(2), Gd(3), Tb(4), Dy(5), Ho(6), Y(7), Yb(8)], have been successfully synthesized under hydrothermal conditions and structurally characterized. All the complexes are characterized by elemental analyses, FT-IR spectroscopy, Powder X-ray diffraction (PXRD) and thermogravimetric analyses (TGA). Furthermore, the luminescence properties of compounds 2 and 4 and the magsnetic properties of complexes 3 and 5 were also investigated in detail. - Graphical abstract: Series of three-dimensional (3D) 4d–4f Ln(III)–Ag(I) porous coordination polymers (PCPs) with interesting chain-layer construction which are featured by tetranuclear Ln{sub 2}Ag{sub 2} and ‘non-linear’ N–Ag–N linkages. - Highlights: • Complexes 1–8 are first built by three kinds of organic ligands based on nicotinic acid and isonicotinic acid. • PCPs 1–8 are featured by tetranuclear Ln{sub 2}Ag{sub 2} and ‘non-linear’ N–Ag–N linkages. • The total solvent-accessible volume of PCP 2 comprises 11.6% of the crystal volume after dislodging the free water molecules. • Complexes 2 and 4 exhibit characteristic lanthanide-centered luminescence, while compounds 3 and 5 show antiferromagnetic behaviors.

  13. Establishment probability in newly founded populations

    Directory of Open Access Journals (Sweden)

    Gusset Markus

    2012-06-01

    Full Text Available Abstract Background Establishment success in newly founded populations relies on reaching the established phase, which is defined by characteristic fluctuations of the population’s state variables. Stochastic population models can be used to quantify the establishment probability of newly founded populations; however, so far no simple but robust method for doing so existed. To determine a critical initial number of individuals that need to be released to reach the established phase, we used a novel application of the “Wissel plot”, where –ln(1 – P0(t is plotted against time t. This plot is based on the equation P0t=1–c1e–ω1t, which relates the probability of extinction by time t, P0(t, to two constants: c1 describes the probability of a newly founded population to reach the established phase, whereas ω1 describes the population’s probability of extinction per short time interval once established. Results For illustration, we applied the method to a previously developed stochastic population model of the endangered African wild dog (Lycaon pictus. A newly founded population reaches the established phase if the intercept of the (extrapolated linear parts of the “Wissel plot” with the y-axis, which is –ln(c1, is negative. For wild dogs in our model, this is the case if a critical initial number of four packs, consisting of eight individuals each, are released. Conclusions The method we present to quantify the establishment probability of newly founded populations is generic and inferences thus are transferable to other systems across the field of conservation biology. In contrast to other methods, our approach disaggregates the components of a population’s viability by distinguishing establishment from persistence.

  14. Syntheses, crystal Structures and electronic Structures of new metal chalcoiodides Bi{sub 2}CuSe{sub 3}I and Bi{sub 6}Cu{sub 3}S{sub 10}I

    Energy Technology Data Exchange (ETDEWEB)

    Liang, I-Chu [Department of Chemistry, and Center for Micro/Nano Science and Technology, National Cheng Kung University, Tainan 701, Taiwan (China); Bilc, Daniel I. [Department of Molecular & Biomolecular Physics, National Institute for Research & Development of Isotopic & Molecular Technologies, Cluj-Napoca 400293 (Romania); Manoli, Maria [Department of Mechanical and Manufacturing Engineering, University of Cyprus, 1678 Nicosia (Cyprus); Chang, Wei-Yun; Lin, Wen-Fu [Department of Chemistry, and Center for Micro/Nano Science and Technology, National Cheng Kung University, Tainan 701, Taiwan (China); Kyratsi, Theodora [Department of Mechanical and Manufacturing Engineering, University of Cyprus, 1678 Nicosia (Cyprus); Hsu, Kuei-Fang [Department of Chemistry, and Center for Micro/Nano Science and Technology, National Cheng Kung University, Tainan 701, Taiwan (China)

    2016-02-15

    Two new metal chalcoiodides were synthesized by solid-state reactions at 400 °C. Crystal Data: Bi{sub 2}CuSe{sub 3}I, 1, monoclinic, C2/m, a=14.243(2) Å, b=4.1937(7) Å, c=14.647(2) Å, β=116.095(2)°, V=785.7(2) Å{sup 3}, and Z=4; Bi{sub 6}Cu{sub 3}S{sub 10}I, 2, orthorhombic, Pnma, a=17.476(2) Å, b=4.0078(4) Å, c=27.391(2) Å, V=1918.5(3) Å{sup 3}, and Z=4. Compound 1 adopts a three-dimensional structure formed by two alternative layers, which consist of BiSe{sub 5} square pyramids, BiSe{sub 4}I{sub 2} octahedra, CuSe{sub 4} tetrahedra, and CuSe{sub 2}I{sub 2} tetrahedra. Compound 2 possesses a new open framework built up of BiS{sub 5} square pyramides, BiS{sub 6} octahedra, BiS{sub 8} polyhedra, and CuS{sub 4} tetrahedra where I{sup −} anions are uniquely trapped within the tunnels. Both electronic structures reveal that bismuth and chalcogenide orbitals dominate the bandgaps. The Cu d and I p states contribute to the top of valence bands, in which the distribution of I orbitals may correspond to the relative bonding interactions in 1 and 2. The optical bandgaps determined by the diffuse reflectance spectra are 0.68 eV and 0.72 eV for 1 and 2, respectively. 1 is a p-type semiconductor with high Seebeck coefficients of 460–575 μV/K in the temperature range of 300–425 K. The electrical conductivity is 0.02 S/cm at 425 K for the undoped sample. The thermal conductivity is 0.22 W/mK at 425 K. - Graphical abstract: The hybridization of chalcogenides and iodides produces two new solids Bi2CuSe3I and Bi6Cu3S10I. The I{sup −} anions participate in distinct bonding interactions within the two structures and that is consistent with the analyses of density of states. 1 is a p-type semiconductor with an optical bandgap of 0.68 eV, which possesses high Seebeck coefficient and low lattice thermal conductivity in 300–425 K.

  15. Testing Whether Defective Chromatin Assembly in S-Phase Contributes to Breast Cancer

    National Research Council Canada - National Science Library

    Adams, Peter

    2003-01-01

    .... We used a dominant negative mutant of (chromatin assembly factor-I) CAF1, a complex that assembles newly synthesized DNA into nucleosomes, to inhibit S-phase chromatin assembly and found that this induced S-phase arrest...

  16. Testing Whether Defective Chromatin Assembly in S-Phase Contributes to Breast Cancer

    National Research Council Canada - National Science Library

    Adams, Peter

    2004-01-01

    .... We used a dominant negative mutant of (chromatin assembly factor-I) CAF1, a complex that assembles newly synthesized DNA into nucleosomes, to inhibit S-phase chromatin assembly and found that this induced S-phase arrest...

  17. Structure and Plasmonic Properties of Thin PMMA Layers with Ion-Synthesized Ag Nanoparticles

    DEFF Research Database (Denmark)

    Popok, Vladimir; Hanif, Muhammad; Mackova, Anna

    2015-01-01

    nanoparticles above the surface. The synthesized nanoparticles can be split into two groups: (i) located at the surface and (ii) fully embedded in the shallow layer. These two groups provide corresponding spectral bands related to localized surface plasmon resonance. The bands demonstrate considerable intensity...

  18. Synthese von organischen und anorganischen Derivativen der Meldrumsäure

    OpenAIRE

    Al-Sheikh, Ahmad

    2004-01-01

    This dissertation concerns in the emphasis the synthesis and instrumental-analytic characterisation (NMR, X-ray, IR) of organic and inorganic derivatives of Meldrum's acid. The derivatives of Meldrum's acid classified as: 1.Zwitterionic derivatives of Meldrum's acid. 2. Salt derivatives of Meldrum's acid. 3. Neutral derivatives of Meldrum's acid Die Dissertation beschäftigt sich im Schwerpunkt mit der Synthese und instrumentell-analytischen Charakterisierung (NMR, X-ray, I...

  19. Syntheses and study of pyrrolidinic nitroxide free radicals. Preparation of a nitroxide-type stable bi-radical; Synthese et etudes de radicaux libres nitroxydes pyrrolidiniques. Preparation d'un biradical stable du type nitroxyde

    Energy Technology Data Exchange (ETDEWEB)

    Dupeyre, R M [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires, Laboratoire de chimie organique physique

    1967-12-01

    Syntheses and study of pyrrolidinic nitroxide free radicals: These radicals are obtained by oxidation, with hydrogen peroxide, of pyrrolidinic amines prepared from triacetonamine by ring contraction. The U. V,, I. R, and E.P.R. spectral characteristics have been determined. The oxidation of these amines with hydrogen peroxide has led also to rupture of the pentagonal ring; some of the decomposition products have been identified. The high chemical stability of the nitroxide group has made it possible to synthesize and study a stable bi-radical. (author) [French] Syntheses et etudes de radicaux libres nitroxydes pyrrolidiniques: Ces radicaux sont obtenus par oxydation l'eau oxygenee d'amines pyrrolidiniques preparees a partir de la triacetonamine par contraction de cycle. Les caracteristiques spectroscopiques ultra-violettes, infra-rouge et resonance paramagnetique sont determinees. Cependant, 1'oxydation de ces amines a l'eau oxygenee a entraine la coupure du cycle pentagonal et identification de certaines substances de decomposition obtenues. La grande stabilite chimique de groupement nitroxyde a permis la synthese et l'etude d'un biradical stable. (auteur)

  20. Study on synthesizing Mg/Al layered double hydroxides at different pHs

    Directory of Open Access Journals (Sweden)

    E Otgonjargal

    2014-12-01

    Full Text Available Mg/Al layered double hydroxide (LDH was successfully synthesized at different pHs values. The Mg/AL LDH was well characterized by X-Ray diffraction and Fourier transform infrared analysis. The morphology of the LDH was observed using Scanning electron microscopy with energy dispersive X-ray spectroscopy. The influence of pH values on the morphology of the Mg/Al LDHs were studied. The result showed that the well-synthesized Mg/Al LDHs could be obtained when the pH value was about 10.0 at room temperature.DOI: http://doi.dx.org/10.5564/mjc.v15i0.319 Mongolian Journal of Chemistry 15 (41, 2014, p36-39

  1. A newly development RIA for thyroid hormone autoantibodies (THAAb)

    International Nuclear Information System (INIS)

    Li Fengying; Gu Liqiong; Chen Xiayin; Jin Yan; Chen Shuxian; Zhang Qun; Qiu Hongxia; Yang Jingren; Zhao Yongju; Chen Mingdao

    2004-01-01

    Objective: To report a newly developed RIA for THAAb from this laboratory. Methods: The tested serum samples were cultured with labelled thyroid hormone analogous ( 125 I T 3 , 125 I T 4 ) for 16 hours. Antigen-antibody complex was precipitated with anti-human IgG (immune precipitation method) and radio-activity determined. Results: The mean positive rate of THAAb in healthy euthyroid controls (n=186) was only 1.07%. The mean positive rate in patients with thyroid disorders was 14.4% (mean rate 13.5% in hyperthyroid subjects, n=118 and mean rate 15.2% in hypothyroid subjects, n=72). The serum THAAb titer could be markedly lowered after adding non-labelled thyroid hormones (P 3 and FT 4 would be significantly lowered (P 3 , FT 4 levels. In patients with positive THAAb (about 14.4% in patients with all thyroid disorders), the FT 3 , FT 4 levels were best determined after PEG precipitation. (authors)

  2. LFG-500, a newly synthesized flavonoid, attenuates lipopolysaccharide-induced acute lung injury and inflammation in mice.

    Science.gov (United States)

    Li, Chenglin; Yang, Dan; Cao, Xin; Wang, Fan; Jiang, Haijing; Guo, Hao; Du, Lei; Guo, Qinglong; Yin, Xiaoxing

    2016-08-01

    Acute lung injury (ALI) often causes significant morbidity and mortality worldwide. Improved treatment and effective strategies are still required for ALI patients. Our previous studies demonstrated that LFG-500, a novel synthesized flavonoid, has potent anti-cancer activities, while its anti-inflammatory effect has not been revealed. In the present study, the in vivo protective effect of LFG-500 on the amelioration of lipopolysaccharide (LPS)-induced ALI and inflammation was detected. LFG-500 attenuated LPS-induced histological alterations, suppressed the infiltration of inflammatory cells in lung tissues and bronchoalveolar lavage fluid, as well as inhibited the secretion of several inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in lung tissues after LPS challenge. In addition, the in vitro effects and mechanisms were studied in LPS stimulated RAW 264.7 cells and THP-1 cells. LFG-500 significantly decreased the secretion and expression of TNF-α, IL-1β, and IL-6 through inhibiting the transcriptional activation of NF-κB. Moreover, overexpression of NF-κB p65 reversed the inhibitory effect of LFG-500 on LPS-induced NF-κB activation and inflammatory cytokine secretion. Further elucidation of the mechanism revealed that p38 and JNK MAPK pathways were involved in the anti-inflammation effect of LFG-500, through which LFG-500 inhibited the classical IKK-dependent pathway and led to inactivation of NF-κB. More importantly, LFG-500 suppressed the expression and nuclear localization of NF-κB in LPS-induced ALI mice. Taken together, these results demonstrated that LFG-500 could attenuate LPS-induced ALI and inflammation by suppressing NF-κB activation, which provides new evidence for the anti-inflammation activity of LFG-500. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Will heavy metals in the soils of newly submerged areas threaten the water quality of Danjiangkou Reservoir, China?

    Science.gov (United States)

    Song, Zhixin; Shan, Baoqing; Tang, Wenzhong; Zhang, Chao

    2017-10-01

    Soil heavy metal contents were measured in newly submerged areas of the Danjiangkou Reservoir, China. We aimed to determine the heavy metal distribution in this area and the associated ecological risk. Most of these heavy metal contents (except Pb and Mn) suggest enrichment compared with the background values of soils from Henan Province, especially As and Cd with mean geo-accumulation index (I geo ) values of 0.84 and 0.54. The spatial analysis results indicated that the highest heavy metal contents were distributed in the arable soils above 160m elevation, whereas low heavy metal contents were observed under other land-use types above 160m elevation. According to I geo and EF values, Cd was the major heavy metal contaminant in the newly submerged area, Cr, Pb and Mn mainly originated from natural geochemical sources. In contrast, Ni, Cd, As, Cu, and Zn mainly originated from anthropogenic sources. Evaluation using the potential ecological risk (PER) method indicated that PER of individual elements were low in the studied soils, and the comprehensive PER index was at a moderate level, indicating heavy metals in the soils of newly submerged areas may not threaten the water quality of Danjiangkou Reservoir, especially in winter. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. A newly developed Fe-doped calcium sulfide nanoparticles with magnetic property for cancer hyperthermia

    Science.gov (United States)

    Wu, Steven Yueh-Hsiu; Tseng, Ching-Li; Lin, Feng-Huei

    2010-05-01

    In this study, a magnetic iron-doped calcium sulfide (Fe-CaS) nanoparticle was newly developed and studied for the purpose of hyperthermia due to its promising magnetic property, adequate biodegradation rate, and relatively good biocompatibility. Fe-CaS nanoparticles were synthesized by a wet chemical co-precipitation process with heat treatment in a N2 atmosphere, and were subsequently cooled in N2 and exposed to air at a low temperature. The crystal structure of the Fe-CaS nanoparticles was similar to that of the CaS, which was identified by an X-ray diffractometer (XRD). The particle size was less than 40 nm based on a Debye-Scherrer equation and transmission electron microscope (TEM) examination. Magnetic properties obtained from the SQUID magnetometer demonstrated that the synthesized CaS was a diamagnetic property. Once the Fe ions were doped, the synthesized Fe-CaS converted into paramagnetism which showed no hysteresis loop. Having been heated above 600 °C in N2, the Fe-CaS showed a promising magnetic property to produce enough energy to increase the temperature for hyperthermia. 10 mg/ml of the Fe-CaS was able to generate heat to elevate the media temperature over 42.5 °C within 6 min. The area of the hysteresis loop increased with the increasing of the treated temperature, especially at 800 °C for 1 h. This is because more Fe ions replaced Ca ions in the lattice at the higher heat treatment temperature. The heat production was also increasing with the increasing of heat treatment temperature, which resulted in an adequate specific absorption ratio (SAR) value, which was found to be 45.47 W/g at 37 °C under an alternative magnetic field of f = 750 KHz , H = 10 Oe. The in vitro biocompatibility test of the synthesized Fe-CaS nanoparticles examined by the LDH assay showed no cytotoxicity to 3T3 fibroblast. The result of in vitro cell hyperthermia shows that under magnetic field the Fe-CaS nanoparticles were able to generate heat and kill the CT-26 cancer

  5. A newly developed Fe-doped calcium sulfide nanoparticles with magnetic property for cancer hyperthermia

    International Nuclear Information System (INIS)

    Wu, Steven Yueh-Hsiu; Tseng, Ching-Li; Lin, Feng-Huei

    2010-01-01

    In this study, a magnetic iron-doped calcium sulfide (Fe-CaS) nanoparticle was newly developed and studied for the purpose of hyperthermia due to its promising magnetic property, adequate biodegradation rate, and relatively good biocompatibility. Fe-CaS nanoparticles were synthesized by a wet chemical co-precipitation process with heat treatment in a N 2 atmosphere, and were subsequently cooled in N 2 and exposed to air at a low temperature. The crystal structure of the Fe-CaS nanoparticles was similar to that of the CaS, which was identified by an X-ray diffractometer (XRD). The particle size was less than 40 nm based on a Debye-Scherrer equation and transmission electron microscope (TEM) examination. Magnetic properties obtained from the SQUID magnetometer demonstrated that the synthesized CaS was a diamagnetic property. Once the Fe ions were doped, the synthesized Fe-CaS converted into paramagnetism which showed no hysteresis loop. Having been heated above 600 o C in N 2 , the Fe-CaS showed a promising magnetic property to produce enough energy to increase the temperature for hyperthermia. 10 mg/ml of the Fe-CaS was able to generate heat to elevate the media temperature over 42.5 o C within 6 min. The area of the hysteresis loop increased with the increasing of the treated temperature, especially at 800 o C for 1 h. This is because more Fe ions replaced Ca ions in the lattice at the higher heat treatment temperature. The heat production was also increasing with the increasing of heat treatment temperature, which resulted in an adequate specific absorption ratio (SAR) value, which was found to be 45.47 W/g at 37 o C under an alternative magnetic field of f = 750 KHz, H = 10 Oe. The in vitro biocompatibility test of the synthesized Fe-CaS nanoparticles examined by the LDH assay showed no cytotoxicity to 3T3 fibroblast. The result of in vitro cell hyperthermia shows that under magnetic field the Fe-CaS nanoparticles were able to generate heat and kill the CT-26

  6. Composites comprising biologically-synthesized nanomaterials

    Science.gov (United States)

    Curran, Seamus; Dias, Sampath; Blau, Werner; Wang, Jun; Oremland, Ronald S; Baesman, Shaun

    2013-04-30

    The present disclosure describes composite materials containing a polymer material and a nanoscale material dispersed in the polymer material. The nanoscale materials may be biologically synthesized, such as tellurium nanorods synthesized by Bacillus selenitireducens. Composite materials of the present disclosure may have optical limiting properties and find use in optical limiting devices.

  7. Thermoluminescence properties of Li2B4O7:Cu, B phosphor synthesized using solution combustion technique

    Science.gov (United States)

    Ozdemir, A.; Altunal, V.; Kurt, K.; Depci, T.; Yu, Y.; Lawrence, Y.; Nur, N.; Guckan, V.; Yegingil, Z.

    2017-12-01

    To determine the effects of various concentrations of the activators copper (Cu) and boron (B) on the thermoluminescence (TL) properties of lithium tetraborate, the phosphor was first synthesized and doped with five different concentrations of copper (0.1-0.005 wt%) using solution combustion method. 0.01 wt% Cu was the concentration which showed the most significant increase in the sensitivity of the phosphor. The second sort of Li2B4O7:Cu material was prepared by adding B (0.001-0.03 wt%) to it. The newly developed copper-boron activated lithium tetraborate (Li2B4O7:Cu, B) material with 0.01 wt% Cu and 0.001 wt% B impurity concentrations was shown to have promise as a TL phosphor. The material formation was examined using powder x-Ray Diffraction (XRD) analysis and Scanning Electron Microscope (SEM) imaging. Fourier Transform Infrared (FT-IR) spectrum of the synthesized polycrystalline powder sample was also recorded. The TL glow curves were analyzed to determine various dosimetric characteristics of the synthesized luminophosphors. The dose response increased in a ;linear; way with the beta-ray exposure between 0.1-20 Gy, a dose range being interested in medical dosimetry. The response with changing photon and electron energy was studied. The rate of decay of the TL signal was investigated both for dark storage and under direct sunlight. Li2B4O7:Cu, B showed no individual variation of response in 9 recycling measurements. The fluorescence spectrum was determined. The kinetic parameters were estimated by different methods and the results discussed. The studied properties of synthesized Li2B4O7:Cu, B were found all favorable for dosimetric purposes.

  8. The Metalloprotease of Listeria monocytogenes Is Activated by Intramolecular Autocatalysis▿ †

    OpenAIRE

    Bitar, Alan Pavinski; Cao, Min; Marquis, Hélène

    2007-01-01

    The metalloprotease (Mpl) of Listeria monocytogenes is a thermolysin-like protease that mediates the maturation of a broad-range phospholipase C, whose function contributes to the ability of this food-borne bacterial pathogen to survive intracellularly. Mpl is made as a proprotein that undergoes maturation by proteolytic cleavage of a large N-terminal prodomain. In this study, we identified the N terminus of mature Mpl and generated Mpl catalytic mutants to investigate the mechanism of Mpl ma...

  9. An oxidative cross-coupling reaction of 4-hydroxydithiocoumarin and amines/thiols using a combination of I2 and TBHP: access to lead molecules for biomedical applications.

    Science.gov (United States)

    Mahato, Karuna; Arora, Neha; Ray Bagdi, Prasanta; Gattu, Radhakrishna; Ghosh, Siddhartha Sankar; Khan, Abu T

    2018-02-06

    A metal-free I 2 /TBHP induced highly atom economic and operationally simple oxidative cross-coupling reaction has been developed for the direct synthesis of sulfenamides/sulfanes/disulfides from the reaction of 4-hydroxydithiocoumarin and amines/thiols. The novelties of the present protocol are unprecedented S-C bond formation in addition to S-N and S-S bonds, shorter reaction time, mild and environmentally benign reaction conditions, functional group tolerance and moderate to excellent yields. Moreover, the four newly synthesized compounds namely 4q, 6d, 6e and 7a exhibit anti-proliferative activity against the breast cancer cell line MCF7, and may be lead molecules for future drug development.

  10. Identification of the mpl gene encoding UDP-N-acetylmuramate: L-alanyl-gamma-D-glutamyl-meso-diaminopimelate ligase in Escherichia coli and its role in recycling of cell wall peptidoglycan.

    Science.gov (United States)

    Mengin-Lecreulx, D; van Heijenoort, J; Park, J T

    1996-01-01

    A gene, mpl, encoding UDP-N-acetylmuramate:L-alanyl-gamma-D-glutamyl-meso-diaminopimelat e ligase was recognized by its amino acid sequence homology with murC as the open reading frame yjfG present at 96 min on the Escherichia coli map. The existence of such an enzymatic activity was predicted from studies indicating that reutilization of the intact tripeptide L-alanyl-gamma-D-glutamyl-meso-diaminopimelate occurred and accounted for well over 30% of new cell wall synthesis. Murein tripeptide ligase activity could be demonstrated in crude extracts, and greatly increased activity was produced when the gene was cloned and expressed under control of the trc promoter. A null mutant totally lacked activity but was viable, showing that the enzyme is not essential for growth. PMID:8808921

  11. 78 FR 1917 - Commercial Space Transportation Advisory Committee-Public Teleconference

    Science.gov (United States)

    2013-01-09

    ... methodology for calculation of Maximum Probable Loss (MPL). The FAA/AST request to COMSTAC took place... FAA/AST to carry out periodic reviews of its MPL methodology. GAO further stated that FAA/ AST should consider using external experts in the course of an MPL review. The MPL represents an estimate of the...

  12. Photocatalytic activity of galvanically synthesized nanostructure SnO{sub 2} thin films

    Energy Technology Data Exchange (ETDEWEB)

    Jana, Sumanta, E-mail: sumantajana85@gmail.com [Department of Chemistry, Bengal Engineering and Science University, Botanic Garden, Howrah 711103, WB (India); Mitra, Bibhas Chandra [Department of Physics, Bengal Engineering and Science University, Botanic Garden, Howrah 711103, WB (India); Bera, Pulakesh [Department of Chemistry, Panskura Banamali College, Purba Medinipur, Panskura 721152, WB (India); Sikdar, Moushumi [Department of Chemistry, Bengal Engineering and Science University, Botanic Garden, Howrah 711103, WB (India); Mondal, Anup, E-mail: anupmondal2000@yahoo.co.in [Department of Chemistry, Bengal Engineering and Science University, Botanic Garden, Howrah 711103, WB (India)

    2014-07-25

    Graphical abstract: Nanostructured porous tin dioxide (SnO{sub 2}) thin films have been synthesized by simple and cost effective galvanic technique. The synthesized porous SnO{sub 2} thin films show excellent photocatalytic activity for degrading methyl orange (MO) dye under light irradiation. The porous morphological grain growth due to annealing is likely to play an active role for this degradation. - Highlights: • SnO{sub 2} thin films have been successfully synthesized by galvanic technique. • A drastic morphological change occurs after annealing as deposited SnO{sub 2} thin films. • Morphological advantage results enhanced photodegradation of dye. - Abstract: The study demonstrates an approach to synthesize nanostructure SnO{sub 2} thin films on TCO (transparent conducting oxide) coated glass substrates by galvanic technique. Aqueous solution of hydrated stannic chloride (SnCl{sub 4}⋅5H{sub 2}O) in potassium nitrate (KNO{sub 3}) solution was used as the working solution. The process involves no sophisticated reactor or toxic chemicals, and proceeds continuously under ambient condition; it provides an economic way of synthesizing nanostructure SnO{sub 2} semiconductor thin films. The influence of sintering temperature on crystalline structure, morphology, electrical and dielectric properties has been studied. A detail analysis of I−V, C−V and dielectrics for annealed SnO{sub 2} thin films have been carried out. The morphological advantage i.e. nanoporous flake like structure allows more efficient transport of reactant molecules to the active interfaces and results a strong photocatalytic activity for degrading methyl orange (MO) dye.

  13. Congenital Amegakaryocytic Thrombocytopenia: A Brief Review of the Literature

    Directory of Open Access Journals (Sweden)

    Fatma S. Al-Qahtani

    2010-01-01

    Full Text Available Congenital amegakaryocytic thrombocytopenia (CAMT is a rare inherited autosomal recessive disorder that presents with thrombocytopenia and absence of megakaryocytes. It presents with bleeding recognized on day 1 of life or at least within the first month. The cause for this disorder appears to be a mutation in the gene for the thrombopoeitin (TPO receptor, c-Mpl, despite high levels of serum TPO. Patients with severe Type I-CAMT carry nonsense Mpl mutations which causes a complete loss of the TPO receptor whereas those with Type II CAMT carry missense mutations in the Mpl gene affecting the extracellular domain of the TPO receptor. Differential diagnosis for severe CAMT includes thrombocytopenia with absent radii (TAR and Wiskott-Aldrich syndrome (WAS. The primary treatment for CAMT is bone marrow transplantation. Bone Marrow/Stem Cell Transplant (HSCT is the only thing that ultimately cures this genetic disease. Newer modalities are on the way, such as TPO-mimetics for binding towards partially functioning c-Mpl receptors and gene therapy. Prognosis of CAMT patients is poor, because all develop in childhood a tri-linear marrow aplasia that is always fatal when untreated. Thirty percent of patients with CAMT die due to bleeding complications and 20% -due to HSCT if it has been done.

  14. Post-translational Introduction of D-Alanine into Ribosomally Synthesized Peptides by the Dehydroalanine Reductase NpnJ.

    Science.gov (United States)

    Yang, Xiao; van der Donk, Wilfred A

    2015-10-07

    Ribosomally synthesized peptides are generally limited to L-amino acid building blocks. Given the advantageous properties of peptides containing D-amino acids such as stabilization of certain turns and against proteolytic degradation, methods to introduce D-stereocenters are valuable. Here we report the first in vitro reconstitution and characterization of a dehydrogenase that carries out the asymmetric reduction of dehydroalanine. NpnJA reduces dehydroalanine to D-Ala using NAPDH as cosubstrate. The enzyme displays high substrate tolerance allowing introduction of D-Ala into a range of non-native substrates. In addition to the in vitro reactions, we describe five examples of using Escherichia coli as biosynthetic host for D-alanine introduction into ribosomal peptides. A deuterium-label-based coupled-enzyme assay was used to rapidly determine the stereochemistry of the newly installed alanine.

  15. An Introduction to iPhone Hardware, Operating System, Applications and Development of iPhone Applications

    OpenAIRE

    Abdul Qadir, Yasir

    2010-01-01

    The aim of this thesis work is to discuss the newly popular mobile phone device named iPhone made by Apple Inc, iPhone operating system and iPhone Applications. Apple iPhone has recently become extremely popular and just within two years of its launch it has captured millions of customers around the world. Thousands of developers have been developing all kinds of mobile phone applications for iPhone and a new era of mobile phone applications development has started. Augmented reality applicat...

  16. 77 FR 24750 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-04-25

    ... Instructions Are Applicable to an MPL Order April 19, 2012. Pursuant to Section 19(b)(1) of the Securities... (``IOC'') time-in-force instructions are applicable to an MPL Order. The text of the proposed rule change... specify how the IOC time-in-force instructions are applicable to an MPL Order. Background An MPL Order is...

  17. Cyclophilin C Participates in the US2-Mediated Degradation of Major Histocompatibility Complex Class I Molecules.

    Science.gov (United States)

    Chapman, Daniel C; Stocki, Pawel; Williams, David B

    2015-01-01

    Human cytomegalovirus uses a variety of mechanisms to evade immune recognition through major histocompatibility complex class I molecules. One mechanism mediated by the immunoevasin protein US2 causes rapid disposal of newly synthesized class I molecules by the endoplasmic reticulum-associated degradation pathway. Although several components of this degradation pathway have been identified, there are still questions concerning how US2 targets class I molecules for degradation. In this study we identify cyclophilin C, a peptidyl prolyl isomerase of the endoplasmic reticulum, as a component of US2-mediated immune evasion. Cyclophilin C could be co-isolated with US2 and with the class I molecule HLA-A2. Furthermore, it was required at a particular expression level since depletion or overexpression of cyclophilin C impaired the degradation of class I molecules. To better characterize the involvement of cyclophilin C in class I degradation, we used LC-MS/MS to detect US2-interacting proteins that were influenced by cyclophilin C expression levels. We identified malectin, PDIA6, and TMEM33 as proteins that increased in association with US2 upon cyclophilin C knockdown. In subsequent validation all were shown to play a functional role in US2 degradation of class I molecules. This was specific to US2 rather than general ER-associated degradation since depletion of these proteins did not impede the degradation of a misfolded substrate, the null Hong Kong variant of α1-antitrypsin.

  18. Hierarchy problem, gauge coupling unification at the Planck scale, and vacuum stability

    Directory of Open Access Journals (Sweden)

    Naoyuki Haba

    2015-11-01

    Full Text Available From the point of view of the gauge hierarchy problem, introducing an intermediate scale in addition to TeV scale and the Planck scale (MPl=2.4×1018 GeV is unfavorable. In that way, a gauge coupling unification (GCU is expected to be realized at MPl. We explore possibilities of GCU at MPl by adding a few extra particles with TeV scale mass into the standard model (SM. When extra particles are fermions and scalars (only fermions with the same mass, the GCU at MPl can (not be realized. On the other hand, when extra fermions have different masses, the GCU can be realized around 8πMPl without extra scalars. This simple SM extension has two advantages that a vacuum becomes stable up to MPl (8πMPl and a proton lifetime becomes much longer than an experimental bound.

  19. A Survey for Low Surface Brightness Galaxies Around M31. II. The Newly Discovered Dwarf Andromeda VI

    OpenAIRE

    Armandroff, Taft E.; Jacoby, George H.; Davies, James E.

    1999-01-01

    We present B-, V-, and I-band images, as well as an H alpha image, of And VI. This is the second newly identified dwarf spheroidal (dSph) companion to M31 found using a digital filtering technique applied to the second Palomar Sky Survey for which 1550 square degrees now have been surveyed. And VI was confirmed to be a nearby dSph galaxy when it resolved into stars easily with a short 4-m V-band exposure. Sub-arcsec images taken at the Kitt Peak WIYN 3.5-m telescope provided (I,V-I) and (V,B-...

  20. The Mycobacterium tuberculosis phagosome is a HLA-I processing competent organelle.

    Directory of Open Access Journals (Sweden)

    Jeff E Grotzke

    2009-04-01

    Full Text Available Mycobacterium tuberculosis (Mtb resides in a long-lived phagosomal compartment that resists maturation. The manner by which Mtb antigens are processed and presented on MHC Class I molecules is poorly understood. Using human dendritic cells and IFN-gamma release by CD8(+ T cell clones, we examined the processing and presentation pathway for two Mtb-derived antigens, each presented by a distinct HLA-I allele (HLA-Ia versus HLA-Ib. Presentation of both antigens is blocked by the retrotranslocation inhibitor exotoxin A. Inhibitor studies demonstrate that, after reaching the cytosol, both antigens require proteasomal degradation and TAP transport, but differ in the requirement for ER-golgi egress and new protein synthesis. Specifically, presentation by HLA-B8 but not HLA-E requires newly synthesized HLA-I and transport through the ER-golgi. Phenotypic analysis of the Mtb phagosome by flow organellometry revealed the presence of Class I and loading accessory molecules, including TAP and PDI. Furthermore, loaded HLA-I:peptide complexes are present within the Mtb phagosome, with a pronounced bias towards HLA-E:peptide complexes. In addition, protein analysis also reveals that HLA-E is enriched within the Mtb phagosome compared to HLA-A2. Together, these data suggest that the phagosome, through acquisition of ER-localized machinery and as a site of HLA-I loading, plays a vital role in the presentation of Mtb-derived antigens, similar to that described for presentation of latex bead-associated antigens. This is, to our knowledge, the first description of this presentation pathway for an intracellular pathogen. Moreover, these data suggest that HLA-E may play a unique role in the presentation of phagosomal antigens.

  1. Development of an Intelligent System to Synthesize Petrophysical Well Logs

    Directory of Open Access Journals (Sweden)

    Morteza Nouri Taleghani

    2013-07-01

    Full Text Available Porosity is one of the fundamental petrophysical properties that should be evaluated for hydrocarbon bearing reservoirs. It is a vital factor in precise understanding of reservoir quality in a hydrocarbon field. Log data are exceedingly crucial information in petroleum industries, for many of hydrocarbon parameters are obtained by virtue of petrophysical data. There are three main petrophysical logging tools for the determination of porosity, namely neutron, density, and sonic well logs. Porosity can be determined by the use of each of these tools; however, a precise analysis requires a complete set of these tools. Log sets are commonly either incomplete or unreliable for many reasons (i.e. incomplete logging, measurement errors, and loss of data owing to unsuitable data storage. To overcome this drawback, in this study several intelligent systems such as fuzzy logic (FL, neural network (NN, and support vector machine are used to predict synthesized petrophysical logs including neutron, density, and sonic. To accomplish this, the petrophysical well logs data were collected from a real reservoir in one of Iran southwest oil fields. The corresponding correlation was obtained through the comparison of synthesized log values with real log values. The results showed that all intelligent systems were capable of synthesizing petrophysical well logs, but SVM had better accuracy and could be used as the most reliable method compared to the other techniques.

  2. Confidence in leadership among the newly qualified.

    Science.gov (United States)

    Bayliss-Pratt, Lisa; Morley, Mary; Bagley, Liz; Alderson, Steven

    2013-10-23

    The Francis report highlighted the importance of strong leadership from health professionals but it is unclear how prepared those who are newly qualified feel to take on a leadership role. We aimed to assess the confidence of newly qualified health professionals working in the West Midlands in the different competencies of the NHS Leadership Framework. Most respondents felt confident in their abilities to demonstrate personal qualities and work with others, but less so at managing or improving services or setting direction.

  3. The Volatile Composition of newly-discovered C/2017 E4 (Lovejoy) before its dissolutionas revealed by iSHELL at NASA/IRTF

    Science.gov (United States)

    Faggi, Sara; Villanueva, Geronimo Luis; Mumma, Michael J.; Paganini, Lucas

    2017-10-01

    In April 2017, we acquired comprehensive high-resolution spectra of newly-discovered comet C/2017 E4 (Lovejoy) as it approached perihelion, and before its disintegration. We detected many cometary emission lines across 4 customized instrument settings (L1-b, L3, Lp1-b and M1) in the (1 - 5) μm range, using iSHELL - the new near-IR high resolution immersion echelle spectrograph on NASA/IRTF (Mauna Kea, Hawaii).In M1, near 5μm, we detected multiple ro-vibrational lines of H2O, CO and the (X-X) system of CN; the latter data constitute a complete survey of CN at these wavelengths. We derived quantitative abundances for CN and addressed its origin by comparing with quantitative production rates for HCN. The ability to quantify both primary and product species eliminates systematic error that may be introduced when measurements are acquired with different astronomical techniques and instruments.In L1, around 3 μm, we detected fluorescence emission from HCN, C2H2, and water, prompt emission from OH, and many other features. Methane, ethane and methanol were detected both in L3 and Lp1 settings. These species are relevant to astrobiology, owing to questions regarding the origin of pre-biotic organics and water on terrestrial planets.The many water emission lines detected in L1-b (and M1) provided an opportunity to retrieve independent measures of rotational temperature for ortho- and para-H2O, thereby reducing systematic uncertainty in the derived ortho-para ratio and nuclear spin temperature. Deuterated species were also sought and results will be presented.The bright Oort cloud comet E4 Lovejoy combined with the new capabilities of iSHELL provided unique results. The individual iSHELL settings cover very wide spectral range with very high accuracy, eliminating many sources of systematic errors when retrieving molecular abundances; future comparisons amongst comets will clarify the nature and meaning of cosmogonic indicators based on composition.Acknowledgments NASA

  4. Microstructure of titanium oxide films synthesized by ion beam dynamic mixing

    International Nuclear Information System (INIS)

    Makino, Y.; Setsuhara, Y.; Miyake, S.

    1994-01-01

    The microstructure of titanium oxide films synthesized by the ion beam dynamic mixing (IBDM) method is investigated by glancing angle X-ray diffraction and multi-reflectance FT-IR methods. Titanium oxide films are identified as rutile phases having different degrees of (110) orientation. The IBDM rutile phase with a standard crystalline state is produced by controlling the ratio of the intensities between the (110) and (101) peaks of the rutile, I(110)/I(101), so as to approach the ratio to the value (=2.0) of ASTM standard rutile. The crystallite size of the rutile phase increases with increasing ratio of intensities of the two XRD peaks, I(110)/I(101). The increase of the crystallite size is suggested to be attributed to the increase of oxygen ion energy per Ti atom. From the dependence of the IR absorption near 500 cm -1 upon I(110)/I(101), it is indicated that the Ti-O bond strength is delicately affected by the degree of (110) orientation of the IBDM rultile phase. ((orig.))

  5. Newly synthesized benzanthrone derivatives as prospective fluorescent membrane probes

    International Nuclear Information System (INIS)

    Zhytniakivska, Olga; Trusova, Valeriya; Gorbenko, Galyna; Kirilova, Elena; Kalnina, Inta; Kirilov, Georgiy; Kinnunen, Paavo

    2014-01-01

    Fluorescence spectral properties of a series of novel benzanthrone derivatives have been explored in lipid bilayers composed of zwitterionic lipid phosphatidylcholine (PC) and its mixtures with cholesterol (Chol) and anionic phospholipid cardiolipin (CL). Analysis of partition coefficients showed that all the examined compounds possess rather high lipid-associating ability, with the amidino derivatives exhibiting stronger membrane partitioning compared with the aminobenzanthrones. To understand how benzanthrone partition properties correlate with their structure, quantitative structure property relationship (QSPR) analysis was performed involving a range of quantum chemical molecular descriptors. -- Highlights: • Benzanthrone partitioning into lipid bilayer correlates with lipophilicity of the dyes. • Partition properties of benzanthrones depend on the dye dipole moment. • Amidino derivatives exhibit higher membrane affinity than aminobenzanthrones

  6. EFFECTIVENESS OF MOTHER TONGUE-BASED STORY BOOKS IN DEVELOPING LISTENING COMPREHENSION SKILLS

    Directory of Open Access Journals (Sweden)

    Joe-Bren Lee Consuelo, Ed. D.

    2017-04-01

    Considering the garnered MPL of the experimental and control group in the four tested dimensions to determine the initial listening comprehension level of the subjects, it reveals that both of the experimental and control group fall under frustration level having an overall MPL 41.67 and 55.11, respectively. In literal dimension the subjects in the experimental and control group fall under instructional level having an MPL of 63.33 and 75.44 respectively. In lieu of this, it can be noted that there is a difference of 12.11 in the MPL of control group compared to the experimental group. For the interpretative dimension the experimental group got an MPL of 30.00 which means that pupils under this dimension belong to frustration level. In the control group under the interpretative level got ban MPL of 50.00 which also gives an indication that subjects are in frustration level under interpretative dimension. However, in critical dimension both the experimental and control group got an MPL of 43.34 respectively which means that the subjects in this dimension are under the frustration level. For vocabulary development an MPL of 30 was garnered by the experimental group, while the control group garnered an MPL of 46.67 which means that both the experimental and control group fall under the frustration level.

  7. CAMAC programmable-control frequency synthesizer

    International Nuclear Information System (INIS)

    Yumaguzin, T.Kh.; Vyazovkin, D.E.; Nazirov, Eh.P.; Tuktarov, R.F.

    1989-01-01

    Synthesizer allows to set frequency with 0.015% accuracy and to scan it with variable step. Frequency controlled divider with further summing-up of divided frequency with fundamental one is used in synthesizer, and it has allowed to use digit of the input code and to obtain 3-4 MHz frequency range. Variation of operation flowsheet in the other frequency range is possible. K-155 and K-531 series microcircuits were used during development

  8. Incorporating Embedded Microporous Layers into Topologically Equivalent Pore Network Models for Oxygen Diffusivity Calculations in Polymer Electrolyte Membrane Fuel Cell Gas Diffusion Layers

    International Nuclear Information System (INIS)

    Fazeli, Mohammadreza; Hinebaugh, James; Bazylak, Aimy

    2016-01-01

    Highlights: • Pore network model for modeling PEMFC MPL-coated GDL effective diffusivity. • Bilayered GDL (substrate and MPL) is modeled with a hybrid network of block MPL elements combined with discrete substrate pores. • Diffusivities of MPL-coated GDLs agree with analytical solutions. - Abstract: In this work, a voxel-based methodology is introduced for the hybridization of a pore network with interspersed nano-porous material elements allowing pore network based oxygen diffusivity calculations in a 3D image of a polymer electrolyte membrane (PEM) fuel cell gas diffusion layer (GDL) with an embedded microporous layer (MPL). The composite GDL is modeled by combining a hybrid network of block MPL elements with prescribed bulk material properties and a topologically equivalent network of larger discrete pores and throats that are directly derived from the 3D image of the GDL substrate. This hybrid network was incorporated into a pore network model, and effective diffusivity predictions of GDL materials with MPL coatings were obtained. Stochastically generated numerical models of carbon paper substrates with and without MPLs were used, and the pore space was directly extracted from this realistic geometry as the input for the pore network model. The effective diffusion coefficient of MPL-coated GDL materials was predicted from 3D images in a pore network modeling environment without resolving the nano-scale structure of the MPL. This method is particularly useful due to the disparate length scales that are involved when attempting to capture pore-scale transport in the GDL. Validation was performed by comparing our predicted diffusivity values to analytical predictions, and excellent agreement was observed. Upon conducting a mesh sensitivity study, it was determined that an MPL element size of 7 μm provided sufficiently high resolution for accurately describing the MPL nano-structure.

  9. Azido, triazolyl, and alkynyl complexes of gold(I): syntheses, structures, and ligand effects.

    Science.gov (United States)

    Robilotto, Thomas J; Deligonul, Nihal; Updegraff, James B; Gray, Thomas G

    2013-08-19

    Gold(I) triazolyl complexes are prepared in [3 + 2] cycloaddition reactions of (tertiary phosphine)gold(I) azides with terminal alkynes. Seven such triazolyl complexes, not previously prepared, are described. Reducible functional groups are accommodated. In addition, two new (N-heterocyclic carbene)gold(I) azides and two new gold(I) alkynyls are described. Eight complexes are crystallographically authenticated; aurophilic interactions appear in one structure only. The packing diagrams of gold(I) triazolyls all show intermolecular hydrogen bonding between N-1 of one molecule and N-3 of a neighbor. This hydrogen bonding permeates the crystal lattice. Density-functional theory calculations of (triphenylphosphine)gold(I) triazolyls and the corresponding alkynyls indicate that the triazolyl is a stronger trans-influencer than is the alkynyl, but the alkynyl is more electron-releasing. These results suggest that trans-influences in two-coordinate gold(I) complexes can be more than a simple matter of ligand donicity.

  10. Problems faced by newly diagnosed diabetes mellitus patients at ...

    African Journals Online (AJOL)

    Diabetes mellitus can be a frightening experience for newly diagnosed patients. The aim of this study was to determine and describe the problems faced by newly diagnosed diabetes mellitus patients at primary healthcare facilities at Mopani district, Limpopo Province. A qualitative, descriptive and contextual research ...

  11. Newly graduated nurses' use of knowledge sources in clinical decision-making

    DEFF Research Database (Denmark)

    Voldbjerg, Siri Lygum; Grønkjaer, Mette; Wiechula, Rick

    2017-01-01

    AIMS AND OBJECTIVES: To explore which knowledge sources newly graduated nurses' use in clinical decision-making and why and how they are used. BACKGROUND: In spite of an increased educational focus on skills and competencies within evidence based practice newly graduated nurses' ability to use...... approaches to strengthen the knowledgebase used in clinical decision-making. DESIGN AND METHODS: Ethnographic study using participant-observation and individual semi-structured interviews of nine Danish newly graduated nurses in medical and surgical hospital settings. RESULTS: Newly graduates use...... in clinical decision-making. If newly graduates are to be supported in an articulate and reflective use of a variety of sources, they have to be allocated to experienced nurses who model a reflective, articulate and balanced use of knowledge sources. This article is protected by copyright. All rights reserved....

  12. Value of a newly sequenced bacterial genome

    DEFF Research Database (Denmark)

    Barbosa, Eudes; Aburjaile, Flavia F; Ramos, Rommel Tj

    2014-01-01

    and annotation will not be undertaken. It is important to know what is lost when we settle for a draft genome and to determine the "scientific value" of a newly sequenced genome. This review addresses the expected impact of newly sequenced genomes on antibacterial discovery and vaccinology. Also, it discusses...... heightened expectations that NGS would boost antibacterial discovery and vaccine development. Although many possible drug and vaccine targets have been discovered, the success rate of genome-based analysis has remained below expectations. Furthermore, NGS has had consequences for genome quality, resulting...

  13. Lymphography and computed tomography of abdominal nodes in newly diagnosed patients with Hodgkin's disease in clinical stage I-III

    Energy Technology Data Exchange (ETDEWEB)

    Neumann, C.H.

    1986-10-01

    Between 1978 and 1983, 80 patients with Hodgkin's disease (HD) in clinical Stage I-III had computed tomography (CT) of the abdomen and pelvis and lymphography (LAG) prior to staging laparatomy with multiple lymph node biopsies at Stanford University Medical Center. There were 224 biopsied nodal sites. The sensitivity and specificity for CT to determine the status of biopsied paraortic and iliac nodes was .61 and .91 vs. .94 and .90 for LAG. CT appeared of even lower sensitivity (.13) in evaluating splenic hilar, celiac axis and portal nodes. Including all biopsy proven subdiaphragmatic nodal sites, CT's sensitivity to diagnose the presence of subdiaphragmatic adenopathy was .38 vs. .52 in LAG. Assessment of the final pathological stage was more successful by LAG (.61) than by CT (.49). Positive and negative predictive values of both tests indicate higher reliability of LAG results as regards individual intraabdominal nodes (LAG .71, .98 vs. CT .58, .86), the entire subdiaphragmatic nodal area (LAG .79, .77 vs. CT .61, .71) and prediction of final pathological stage. LAG appeared to be the more useful test during initial staging of newly diagnosed and untreated patients with HD. None of the test for itself or in combination can replace laparatomy when exact information is necessary for further clinical decisions.

  14. Carbon Nano-particle Synthesized by Pulsed Arc Discharge Method as a Light Emitting Device

    Science.gov (United States)

    Ahmadi, Ramin; Ahmadi, Mohamad Taghi; Ismail, Razali

    2018-04-01

    Owing to the specific properties such as high mobility, ballistic carrier transport and light emission, carbon nano-particles (CNPs) have been employed in nanotechnology applications. In the presented work, the CNPs are synthesized by using the pulsed arc discharge method between two copper electrodes. The rectifying behaviour of produced CNPs is explored by assuming an Ohmic contact between the CNPs and the electrodes. The synthesized sample is characterized by electrical investigation and modelling. The current-voltage (I-V) relationship is investigated and bright visible light emission from the produced CNPs was measured. The electroluminescence (EL) intensity was explored by changing the distance between two electrodes. An incremental behaviour on EL by a resistance gradient and distance reduction is identified.

  15. Challenges in Theorizing Interdisciplinarity at iSchools

    DEFF Research Database (Denmark)

    Madsen, Dorte

    which the newly formed iSchools Caucus defined as: ”an academic field of study and a professional career field that deals with all the issues, opportunities, and challenges we face in our emerging Information Age.… The iField addresses this fundamental issue: how do we harness that incredible flow...

  16. Illness-behaviour, attitude, and knowledge in newly diagnosed diabetics

    DEFF Research Database (Denmark)

    Holstein, B E; Vesterdal Jørgensen, H; Sestoft, L

    1986-01-01

    Sixty-five consecutive patients with newly diagnosed type I diabetes, aged 15-52, were exposed to a systematic educational programme and followed up by three-monthly controls for two to four years. In order to identify psychic, social and behavioural factors associated with good metabolic control...... and appropriate adaptation to illness, they were clinically tested and filled in a questionnaire. The study shows that the illness and the therapeutic regime created few problems regarding practical circumstances of daily living, but there were a vast number of psychological problems: perceived disability......, fatigue, fear, anger, strain, bad conscience, and perceived discrimination. The patients assessed the treatment regimen they had been taught as fair, but still the majority reported inadequate compliance and problems in relation to compliance, especially regarding dietary restrictions. The educational...

  17. Analyzing and synthesizing phylogenies using tree alignment graphs.

    Directory of Open Access Journals (Sweden)

    Stephen A Smith

    Full Text Available Phylogenetic trees are used to analyze and visualize evolution. However, trees can be imperfect datatypes when summarizing multiple trees. This is especially problematic when accommodating for biological phenomena such as horizontal gene transfer, incomplete lineage sorting, and hybridization, as well as topological conflict between datasets. Additionally, researchers may want to combine information from sets of trees that have partially overlapping taxon sets. To address the problem of analyzing sets of trees with conflicting relationships and partially overlapping taxon sets, we introduce methods for aligning, synthesizing and analyzing rooted phylogenetic trees within a graph, called a tree alignment graph (TAG. The TAG can be queried and analyzed to explore uncertainty and conflict. It can also be synthesized to construct trees, presenting an alternative to supertrees approaches. We demonstrate these methods with two empirical datasets. In order to explore uncertainty, we constructed a TAG of the bootstrap trees from the Angiosperm Tree of Life project. Analysis of the resulting graph demonstrates that areas of the dataset that are unresolved in majority-rule consensus tree analyses can be understood in more detail within the context of a graph structure, using measures incorporating node degree and adjacency support. As an exercise in synthesis (i.e., summarization of a TAG constructed from the alignment trees, we also construct a TAG consisting of the taxonomy and source trees from a recent comprehensive bird study. We synthesized this graph into a tree that can be reconstructed in a repeatable fashion and where the underlying source information can be updated. The methods presented here are tractable for large scale analyses and serve as a basis for an alternative to consensus tree and supertree methods. Furthermore, the exploration of these graphs can expose structures and patterns within the dataset that are otherwise difficult to

  18. Analyzing and synthesizing phylogenies using tree alignment graphs.

    Science.gov (United States)

    Smith, Stephen A; Brown, Joseph W; Hinchliff, Cody E

    2013-01-01

    Phylogenetic trees are used to analyze and visualize evolution. However, trees can be imperfect datatypes when summarizing multiple trees. This is especially problematic when accommodating for biological phenomena such as horizontal gene transfer, incomplete lineage sorting, and hybridization, as well as topological conflict between datasets. Additionally, researchers may want to combine information from sets of trees that have partially overlapping taxon sets. To address the problem of analyzing sets of trees with conflicting relationships and partially overlapping taxon sets, we introduce methods for aligning, synthesizing and analyzing rooted phylogenetic trees within a graph, called a tree alignment graph (TAG). The TAG can be queried and analyzed to explore uncertainty and conflict. It can also be synthesized to construct trees, presenting an alternative to supertrees approaches. We demonstrate these methods with two empirical datasets. In order to explore uncertainty, we constructed a TAG of the bootstrap trees from the Angiosperm Tree of Life project. Analysis of the resulting graph demonstrates that areas of the dataset that are unresolved in majority-rule consensus tree analyses can be understood in more detail within the context of a graph structure, using measures incorporating node degree and adjacency support. As an exercise in synthesis (i.e., summarization of a TAG constructed from the alignment trees), we also construct a TAG consisting of the taxonomy and source trees from a recent comprehensive bird study. We synthesized this graph into a tree that can be reconstructed in a repeatable fashion and where the underlying source information can be updated. The methods presented here are tractable for large scale analyses and serve as a basis for an alternative to consensus tree and supertree methods. Furthermore, the exploration of these graphs can expose structures and patterns within the dataset that are otherwise difficult to observe.

  19. Corrosion inhibition of mild steel in acidic media using newly synthesized heterocyclic organic molecules: Correlation between inhibition efficiency and chemical structure

    Energy Technology Data Exchange (ETDEWEB)

    Ouici, H. B., E-mail: ouici.houari@yahoo.fr; Guendouzi, A., E-mail: guendouzzi@yahoo.fr [Departement of Chimistry, Faculty of Sciences, University of Saïda (Algeria); Benali, O. [Department of Biology, Faculty of Science, University of Saida (Algeria)

    2015-03-30

    The corrosion inhibition of mild steel in 5% HCl solutions by some new synthesized organic compounds namely 3-(2-methoxyphenyl) 5-mercapto-1. 2. 4-triazole (2-MMT), 3-(3-methoxyphenyl) 5-mercapto-1. 2. 4-triazole (3-MMT) and 3-(2-hydroxyphenyl) 5-mercapto-1. 2. 4-triazole (2-HMT) was investigated using weight loss and potentiostatic polarization techniques. These measurements reveal that the inhibition efficiency obtained by these compounds increased by increasing their concentration. The inhibition efficiency follows the order 2-MMT >3-MMT >2-HMT. Polarization studies show that these compounds are of the mixed type but dominantly act as a cathodic inhibitors for mild steel in 5% HCl solutions. These inhibitors function through adsorption following Langmuir isotherm. Activation energy and Gibbs free energy for adsorption of inhibitors are calculated. Molecular modeling has been conducted to correlate the corrosion inhibition properties with the calculated quantum chemical parameters.

  20. Induction of CD8+ T-cell responses against subunit antigens by the novel cationic liposomal CAF09 adjuvant

    DEFF Research Database (Denmark)

    Korsholm, Karen Smith; Hansen, Jon; Karlsen, Kasper

    2014-01-01

    previously described CTL-inducing adjuvants, CAF05 (DDA/trehalose dibehenate (TDB)/Poly(I:C)), Aluminium/monophosphoryl lipid-A (MPL) and Montanide/CpG/IL-2. The optimal effect was obtained when the CAF09-adjuvanted vaccine was administered by the i.p. route, whereas s.c. administration primed limited CD8+ T...

  1. Photoresponse and DFT studies of new synthesized 2-benzylidene-3-hydroxy -1-(5,6-diphenyl-1,2,4-triazine-3-yl)hydrazine and optical sensor application

    Science.gov (United States)

    Taha, A.; Farag, A. A. M.; Adly, O. M. I.; Roushdy, N.; Shebl, Magdy; Ahmed, H. M.

    2017-08-01

    A newly Schiff base,2-benzylidene-3-hydroxy-1-(5,6-diphenyl-1,2,4-triazine-3-yl)hydrazine] (HBDHT) was synthesized and characterized on the basis of micro-analytical and spectroscopic studies. Basic parameters of the combined compound HBDHT were ascertained on the premise of DFT level actualized on Gaussian 09. Thin films of HBDHT were successfully prepared by spin coating technique and confirmed by atomic force microscopy (AFM). The optical attributes of the studied films were considered utilizing spectrophotometric estimations in a wide spectral range of 200-2500 nm. Some important optical parameters such as extinction index, refractive index, dispersion energy, oscillator energy and high-frequency dielectric constant were extracted. Analysis of the absorption coefficient near the fundamental absorption edge confirms an indirectly allowed transition with an energy gap of 1.7eV. The refractive index dispersion was estimated on basis of single oscillator model expressed by Wemple-Didomenico. Current-voltage (I-V) characteristics were studied in dark and under illumination of 100 mW/cm2 to clarify the sensitivity to light. Moreover, the photo-transient properties were also investigated to confirm that the prepared heterojunction based HBDHT can be operated as a photodiode.

  2. Application a territorial level of the ENEA - A.I.I.A.`s methodologies for the Emilia and Abruzzo Italian regions; Applicazione a livello territoriale delle metodologie ENEA- A.I.I.A. alle regioni Emilia-Romagna e Abruzzo

    Energy Technology Data Exchange (ETDEWEB)

    Lai, G [Italian Agency for New Technologies, Energy and the Environment, Centro Ricerche Casaccia, Rome (Italy); Riva, G; Fiala, M [Associazione Italiana di Ingegneria Agraria, Milan (Italy)

    1996-12-01

    This report is aimed to presenting the syntheses of the ENEA (Italian Agency for new Technologies and the Environment)- A.I.I.A.`s methodologies applications for the evaluation of the energy potential by vegetable biomass and Municipal Solid Wastes at four selected local realities, two for Emilia Region and two for Abruzzo. The methodologies, realized in the framework, of the activities of ERG-PROM Division of ENEA, are aimed to evaluate the economical profitability of the energy biomass production. The syntheses report the results of the applications realized using local data and information and, for each application, are described the conditions for the economical profitability of biomass energy plants.

  3. Synthesizing Modular Invariants for Synchronous Code

    Directory of Open Access Journals (Sweden)

    Pierre-Loic Garoche

    2014-12-01

    Full Text Available In this paper, we explore different techniques to synthesize modular invariants for synchronous code encoded as Horn clauses. Modular invariants are a set of formulas that characterizes the validity of predicates. They are very useful for different aspects of analysis, synthesis, testing and program transformation. We describe two techniques to generate modular invariants for code written in the synchronous dataflow language Lustre. The first technique directly encodes the synchronous code in a modular fashion. While in the second technique, we synthesize modular invariants starting from a monolithic invariant. Both techniques, take advantage of analysis techniques based on property-directed reachability. We also describe a technique to minimize the synthesized invariants.

  4. Analysis of the transient response and durability characteristics of a proton exchange membrane fuel cell with different micro-porous layer penetration thicknesses

    International Nuclear Information System (INIS)

    Cho, Junhyun; Park, Jaeman; Oh, Hwanyeong; Min, Kyoungdoug; Lee, Eunsook; Jyoung, Jy-Young

    2013-01-01

    Highlights: • The GDL which has a large MPL penetration showed a better transient response. • The transient response of the PEMFC was affected by the water balance of the GDL. • A large MPL penetration balanced the capillary pressure gradient through the GDL. • The carbon corrosion induced loss of the MPL penetration region. - Abstract: The optimal design of the gas diffusion layer (GDL) of proton exchange membrane fuel cells is crucial because it directly determines the mass transport mechanism of the reactants and products. In this study, the micro-porous layer (MPL) penetration thickness, which affects the pore size profile through the GDL, is varied as the design parameter of the GDL. The cell performance is investigated under various humidity conditions, and the water permeability characteristics are studied. In addition, the accelerated carbon corrosion stress test is conducted to determine the effect of MPL penetration on GDL degradation. GDLs with large MPL penetration thickness show better performance in the high-current–density region due to the enhanced management of water resulting from a balanced capillary pressure gradient. However, the loss of penetrated MPL parts is observed due to the low binding force between the MPL and the GDL substrate

  5. Oxidative Stability of Marine Phospholipids in the Liposomal Form and Their Applications

    DEFF Research Database (Denmark)

    Lu, Henna Fung Sieng; Nielsen, Nina Skall; Timm-Heinrich, M.

    2011-01-01

    Marine phospholipids (MPL) have attracted a great deal of attention recently as they are considered to have a better bioavailability, a better resistance towards oxidation and a higher content of eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) than oily triglycerides (fish oil) from the same...... source. Due to their tight intermolecular packing conformation at the sn-2 position and their synergism with α-tocopherol present in MPL extracts, they can form stable liposomes which are attractive ingredients for food or feed applications. However, MPL are still susceptible to oxidation as they contain...... large amounts polyunsaturated fatty acids and application of MPL in food and aquaculture industries is therefore a great challenge for researchers. Hence, knowledge on the oxidative stability of MPL and the behavior of MPL in food and feed systems is an important issue. For this reason, this review...

  6. A Phase I Dose Escalation Study of Hypofractionated IMRT Field-in-Field Boost for Newly Diagnosed Glioblastoma Multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Monjazeb, Arta M., E-mail: arta.monjazeb@ucdmc.ucdavis.edu [U.C. Davis School of Medicine, Department of Radiation Oncology, Sacramento, CA (United States); Ayala, Deandra; Jensen, Courtney [Radiation Oncology, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Case, L. Douglas [Biostatistical Sciences, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Bourland, J. Daniel; Ellis, Thomas L. [Neurosurgery, Wake Forest University Health Sciences, Winston-Salem, NC (United States); McMullen, Kevin P.; Chan, Michael D. [Radiation Oncology, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Tatter, Stephen B. [Neurosurgery, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Lesser, Glen J. [Hematology Oncology, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Shaw, Edward G. [Radiation Oncology, Wake Forest University Health Sciences, Winston-Salem, NC (United States)

    2012-02-01

    Objectives: To describe the results of a Phase I dose escalation trial for newly diagnosed glioblastoma multiforme (GBM) using a hypofractionated concurrent intensity-modulated radiotherapy (IMRT) boost. Methods: Twenty-one patients were enrolled between April 1999 and August 2003. Radiotherapy consisted of daily fractions of 1.8 Gy with a concurrent boost of 0.7 Gy (total 2.5 Gy daily) to a total dose of 70, 75, or 80 Gy. Concurrent chemotherapy was not permitted. Seven patients were enrolled at each dose and dose limiting toxicities were defined as irreversible Grade 3 or any Grade 4-5 acute neurotoxicity attributable to radiotherapy. Results: All patients experienced Grade 1 or 2 acute toxicities. Acutely, 8 patients experienced Grade 3 and 1 patient experienced Grade 3 and 4 toxicities. Of these, only two reversible cases of otitis media were attributable to radiotherapy. No dose-limiting toxicities were encountered. Only 2 patients experienced Grade 3 delayed toxicity and there was no delayed Grade 4 toxicity. Eleven patients requiring repeat resection or biopsy were found to have viable tumor and radiation changes with no cases of radionecrosis alone. Median overall and progression-free survival for this cohort were 13.6 and 6.5 months, respectively. One- and 2-year survival rates were 57% and 19%. At recurrence, 15 patients received chemotherapy, 9 underwent resection, and 5 received radiotherapy. Conclusions: Using a hypofractionated concurrent IMRT boost, we were able to safely treat patients to 80 Gy without any dose-limiting toxicity. Given that local failure still remains the predominant pattern for GBM patients, a trial of dose escalation with IMRT and temozolomide is warranted.

  7. A Phase I Dose Escalation Study of Hypofractionated IMRT Field-in-Field Boost for Newly Diagnosed Glioblastoma Multiforme

    International Nuclear Information System (INIS)

    Monjazeb, Arta M.; Ayala, Deandra; Jensen, Courtney; Case, L. Douglas; Bourland, J. Daniel; Ellis, Thomas L.; McMullen, Kevin P.; Chan, Michael D.; Tatter, Stephen B.; Lesser, Glen J.; Shaw, Edward G.

    2012-01-01

    Objectives: To describe the results of a Phase I dose escalation trial for newly diagnosed glioblastoma multiforme (GBM) using a hypofractionated concurrent intensity-modulated radiotherapy (IMRT) boost. Methods: Twenty-one patients were enrolled between April 1999 and August 2003. Radiotherapy consisted of daily fractions of 1.8 Gy with a concurrent boost of 0.7 Gy (total 2.5 Gy daily) to a total dose of 70, 75, or 80 Gy. Concurrent chemotherapy was not permitted. Seven patients were enrolled at each dose and dose limiting toxicities were defined as irreversible Grade 3 or any Grade 4–5 acute neurotoxicity attributable to radiotherapy. Results: All patients experienced Grade 1 or 2 acute toxicities. Acutely, 8 patients experienced Grade 3 and 1 patient experienced Grade 3 and 4 toxicities. Of these, only two reversible cases of otitis media were attributable to radiotherapy. No dose-limiting toxicities were encountered. Only 2 patients experienced Grade 3 delayed toxicity and there was no delayed Grade 4 toxicity. Eleven patients requiring repeat resection or biopsy were found to have viable tumor and radiation changes with no cases of radionecrosis alone. Median overall and progression-free survival for this cohort were 13.6 and 6.5 months, respectively. One- and 2-year survival rates were 57% and 19%. At recurrence, 15 patients received chemotherapy, 9 underwent resection, and 5 received radiotherapy. Conclusions: Using a hypofractionated concurrent IMRT boost, we were able to safely treat patients to 80 Gy without any dose-limiting toxicity. Given that local failure still remains the predominant pattern for GBM patients, a trial of dose escalation with IMRT and temozolomide is warranted.

  8. Newly Generated Liquid Waste Processing Alternatives Study, Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    Landman, William Henry; Bates, Steven Odum; Bonnema, Bruce Edward; Palmer, Stanley Leland; Podgorney, Anna Kristine; Walsh, Stephanie

    2002-09-01

    This report identifies and evaluates three options for treating newly generated liquid waste at the Idaho Nuclear Technology and Engineering Center of the Idaho National Engineering and Environmental Laboratory. The three options are: (a) treat the waste using processing facilities designed for treating sodium-bearing waste, (b) treat the waste using subcontractor-supplied mobile systems, or (c) treat the waste using a special facility designed and constructed for that purpose. In studying these options, engineers concluded that the best approach is to store the newly generated liquid waste until a sodium-bearing waste treatment facility is available and then to co-process the stored inventory of the newly generated waste with the sodium-bearing waste. After the sodium-bearing waste facility completes its mission, two paths are available. The newly generated liquid waste could be treated using the subcontractor-supplied system or the sodium-bearing waste facility or a portion of it. The final decision depends on the design of the sodium-bearing waste treatment facility, which will be completed in coming years.

  9. Design and syntheses of novel N-(benzothiazol-5-yl)-4,5,6,7-tetrahydro-1H-isoindole-1,3(2H)-dione and N-(benzothiazol-5-yl)isoindoline-1,3-dione as potent protoporphyrinogen oxidase inhibitors.

    Science.gov (United States)

    Jiang, Li-Li; Zuo, Yang; Wang, Zhi-Fang; Tan, Yin; Wu, Qiong-You; Xi, Zhen; Yang, Guang-Fu

    2011-06-08

    Discovery of protoporphyrinogen oxidase (PPO, EC 1.3.3.4) inhibitors has been one of the hottest research areas in the field of herbicide development for many years. As a continuation of our research work on the development of new PPO-inhibiting herbicides, a series of novel N-(benzothiazol-5-yl)-4,5,6,7-tetrahydro-1H-isoindole-1,3(2H)-diones (1a-p) and N-(benzothiazol-5-yl)isoindoline-1,3-diones (2a-h) were designed and synthesized according to the ring-closing strategy of two ortho-substituents. The bioassay results indicated that some newly synthesized compounds exhibited higher PPO inhibition activity than the control of sulfentrazone. Compound 1a, S-(5-(1,3-dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-6-fluorobenzothiazol-2-yl) O-methyl carbonothioate, was identified as the most potent inhibitor with k(i) value of 0.08 μM, about 9 times higher than that of sulfentrazone (k(i) = 0.72 μM). Further green house assay showed that compound 1b, methyl 2-((5-(1,3-dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-6-fluorobenzothiazol-2-yl)thio)acetate, exhibited herbicidal activity comparable to that of sulfentrazone even at a concentration of 37.5 g ai/ha. In addition, among six tested crops, wheat exhibited high tolerance to compound 1b even at a dosage of 300 g ai/ha. These results indicated that compound 1b might have the potential to be developed as a new herbicide for weed control of wheat field.

  10. Investigation of the Mesostructure of Transition-Metal Monogermanides Synthesized under Pressure

    Science.gov (United States)

    Safiulina, I. A.; Altynbaev, E. V.; Iashina, E. G.; Heinemann, A.; Fomicheva, L. N.; Tsvyashchenko, A. V.; Grigoriev, S. V.

    2018-04-01

    The mesostructure of transition-metal monogermanides Mn1 - x Co x Ge is studied by small-angle neutron scattering in a wide range of concentrations x = 0-0.95. These compounds were synthesized under high pressure and are metastable under normal conditions. The experimental dependences I( Q) obtained for the whole series of samples in the range of transferred momenta (6 × 10-2 nm-1 interesting to note that such defects are absent in the isostructural FeGe compound, i.e., the experimental dependences of the intensity are described well by the expression Q - n with an exponent n = 4.1 ± 0.1, which demonstrates the presence of crystallites with a uniform density distribution inside and a sharp boundary characterizing the surface.

  11. Observation of the bone mineral density of newly formed bone using rabbits. Compared with newly formed bone around implants and cortical bone

    International Nuclear Information System (INIS)

    Nakada, Hiroshi; Numata, Yasuko; Sakae, Toshiro; Tamaki, Hiroyuki; Kato, Takao

    2009-01-01

    There have been many studies reporting that newly formed bone around implants is spongy bone. However, although the morphology is reported as being like spongy bone, it is difficult to discriminate whether the bone quality of newly formed bone appears similar to osteoid or cortical bone; therefore, evaluation of bone quality is required. The aims of this study were to measure the bone mineral density (BMD) values of newly formed bone around implants after 4, 8, 16, 24 and 48 weeks, to represent these values on three-dimensional color mapping (3Dmap), and to evaluate the change in bone quality associated with newly formed bone around implants. The animal experimental protocol of this study was approved by the Ethics Committee for Animal Experiments of our University. This experiment used 20 surface treatment implants (Ti-6Al-4V alloy: 3.1 mm in diameter and 30.0 mm in length) by grit-blasting. They were embedded into surgically created flaws in femurs of 20 New Zealand white rabbits (16 weeks old, male). The rabbits were sacrificed with an ear intravenous overdose of pentobarbital sodium under general anesthesia each period, and the femurs were resected. We measured BMD of newly formed bone around implants and cortical bone using Micro-CT, and the BMD distribution map of 3Dmap (TRI/3D Bon BMD, Ratoc System Engineering). The BMD of cortical bone was 1,026.3±44.3 mg/cm 3 at 4 weeks, 1,023.8±40.9 mg/cm 3 at 8 weeks, 1,048.2±45.6 mg/cm 3 at 16 weeks, 1,067.2±60.2 mg/cm 3 at 24 weeks, and 1,069.3±50.7 mg/cm 3 at 48 weeks after implantation, showing a non-significant increase each period. The BMD of newly formed bone around implants was 296.8±25.6 mg/cm 3 at 4 weeks, 525.0±72.4 mg/cm 3 at 8 weeks, 691.2±26.0 mg/cm 3 at 16 weeks, 776.9±27.7 mg/cm 3 at 24 weeks, and 845.2±23.1 mg/cm 3 at 48 weeks after implantation, showing a significant increase after each period. It was revealed that the color scale of newly formed bone was Low level at 4 weeks, and then it

  12. Experimental and theoretical studies on tautomeric structures of a newly synthesized 2,2‧(hydrazine-1,2-diylidenebis(propan-1-yl-1-ylidene))diphenol

    Science.gov (United States)

    Karakurt, Tuncay; Cukurovali, Alaaddin; Subasi, Nuriye Tuna; Onaran, Abdurrahman; Ece, Abdulilah; Eker, Sıtkı; Kani, Ibrahim

    2018-02-01

    In the present study, a single crystal of a Schiff base, 2,2‧(hydrazine-1,2-diylidenebis(propan-1-yl-1-ylidene))diphenol, was synthesized. The structure of the synthesized crystal was confirmed by 1H and 13C NMR spectroscopic and X-ray diffraction analysis techniques. Experimental and theoretical studies were carried out on two tautomeric structures. It has been observed that the title compound studied can be in two different tautomeric forms, phenol-imine and keto-amine. Theoretical calculations have been performed to support experimental results. Accordingly, the geometric parameters of the compound were optimized by the density functional theory (DFT) method using the Gaussian 09 and Quantum Espresso (QE) packet program was used for periodic boundary conditions (PBC) studies. Furthermore, the compound was also tested for in vitro antifungal activity against Sclerotinia sclerotiorum, Alternaria solani, Fusarium oxysporum f. sp. lycopersici and Monilinia fructigena plant pathogens. Promising inhibition profiles were observed especially towards A. solani. Finally, molecular docking studies and post-docking procedure based on Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) were also carried out to get insight into the compound's binding interactions with the potential. Although theoretical calculations showed that the phenol-imine form was more stable, keto-amine form was predicted to have better binding affinity which was concluded to result from loss of rotational entropy in phenol-imine upon binding. The results obtained here from both experimental and computational methods might serve as a potential lead in the development of novel anti-fungal agents.

  13. Toxicity of upfront {sup 131}I-metaiodobenzylguanidine ({sup 131}I-MIBG) therapy in newly diagnosed neuroblastoma patients: a retrospective analysis

    Energy Technology Data Exchange (ETDEWEB)

    Bleeker, Gitta; Schoot, Reineke A.; Caron, Huib N.; Kraker, Jan de; Tytgat, Godelieve A. [Emma Children' s Hospital, Academic Medical Centre (AMC), Department of Paediatric Oncology, PO Box 22700, Amsterdam (Netherlands); Hoefnagel, Cees A. [National Cancer Institute (NKI-AvL), Department of Nuclear Medicine, Amsterdam (Netherlands); Eck, Berthe L. van [Academic Medical Centre (AMC), Department of Nuclear Medicine, Amsterdam (Netherlands)

    2013-10-15

    In the treatment of patients with high-risk neuroblastoma, different doses of {sup 131}I-metaiodobenzylguanidine ({sup 131}I-MIBG) are administered at different time points during treatment. Toxicity, mainly haematological (thrombocytopenia), from {sup 131}I-MIBG therapy is known to occur in extensively chemotherapy pretreated neuroblastoma patients. Up to now, acute toxicity from {sup 131}I-MIBG as initial treatment has never been studied in a large cohort. The aim of this retrospective study was to document acute toxicity related to upfront {sup 131}I-MIBG. All neuroblastoma patients (stages 1-4 and 4S) treated upfront with {sup 131}I-MIBG at the Emma Children's Hospital, Academic Medical Centre (1992 - 2008) were included in this retrospective analysis. The acute toxicity (during therapy) and short-term toxicity (1st month following therapy) of the first two {sup 131}I-MIBG therapies were studied. Of 66 patients (34 boys, 32 girls; median age 2.2 years, range 0.1 - 9.4 years), 49 had stage 4 disease, 5 stage 4S, 6 stage 3, 1 stage 2 and 5 stage 1. The median first dose was 441 MBq/kg (range 157 - 804 MBq/kg). The median second dose was 328 MBq/kg (range 113 - 727 MBq/kg). The most frequently observed symptoms were nausea and vomiting (21 %, maximum grade II). The main toxicity was grade IV haematological, occurring only in stage 4 patients, after the first and second {sup 131}I-MIBG therapies: anaemia (5 % and 4 %, respectively), leucocytopenia (3 % and 4 %) and thrombocytopenia (2 % and 4 %). No stem cell rescue was needed. The main acute toxicity observed was haematological followed by nausea and vomiting. One patient developed posterior reversible encephalopathy syndrome during {sup 131}I-MIBG therapy, possibly related to {sup 131}I-MIBG. We consider {sup 131}I-MIBG therapy to be a safe treatment modality. (orig.)

  14. The practical skills of newly qualified nurses.

    Science.gov (United States)

    Danbjørg, Dorthe Boe; Birkelund, Regner

    2011-02-01

    This paper reports the findings from a study of newly qualified nurses and which subjects the nurses regarded as the most important in order to be able to live up to the requirements of clinical practice, and how they experience their potential for developing practical and moral skills, after the decrease in practical training. A qualitative approach guided the research process and the analysis of the data. The data was collected by participant observation and qualitative interviews with four nurses as informants. The conclusions made in this study are based on the statements and the observations of the newly qualified nurses. Our findings are discussed in relation to the Aristotelian concept and other relevant literature. The main message is that the newly qualified nurses did not feel equipped when they finished their training. This could be interpreted as a direct consequence of the decrease in practical training. Our study also underlines that the way nursing theory is perceived and taught is problematic. The interviews revealed that the nurses think that nursing theories should be applied directly in practice. This misunderstanding is probably also applicable to the teachers of the theories. Copyright © 2010 Elsevier Ltd. All rights reserved.

  15. Newly graduated nurses' use of knowledge sources: a meta-ethnography.

    Science.gov (United States)

    Voldbjerg, Siri Lygum; Grønkjaer, Mette; Sørensen, Erik Elgaard; Hall, Elisabeth O C

    2016-08-01

    To advance evidence on newly graduated nurses' use of knowledge sources. Clinical decisions need to be evidence-based and understanding the knowledge sources that newly graduated nurses use will inform both education and practice. Qualitative studies on newly graduated nurses' use of knowledge sources are increasing though generated from scattered healthcare contexts. Therefore, a metasynthesis of qualitative research on what knowledge sources new graduates use in decision-making was conducted. Meta-ethnography. Nineteen reports, representing 17 studies, published from 2000-2014 were identified from iterative searches in relevant databases from May 2013-May 2014. Included reports were appraised for quality and Noblit and Hare's meta-ethnography guided the interpretation and synthesis of data. Newly graduated nurses' use of knowledge sources during their first 2-year postgraduation were interpreted in the main theme 'self and others as knowledge sources,' with two subthemes 'doing and following' and 'knowing and doing,' each with several elucidating categories. The metasynthesis revealed a line of argument among the report findings underscoring progression in knowledge use and perception of competence and confidence among newly graduated nurses. The transition phase, feeling of confidence and ability to use critical thinking and reflection, has a great impact on knowledge sources incorporated in clinical decisions. The synthesis accentuates that for use of newly graduated nurses' qualifications and skills in evidence-based practice, clinical practice needs to provide a supportive environment which nurtures critical thinking and questions and articulates use of multiple knowledge sources. © 2016 John Wiley & Sons Ltd.

  16. Synthesizing lattice structures in phase space

    International Nuclear Information System (INIS)

    Guo, Lingzhen; Marthaler, Michael

    2016-01-01

    In one dimensional systems, it is possible to create periodic structures in phase space through driving, which is called phase space crystals (Guo et al 2013 Phys. Rev. Lett. 111 205303). This is possible even if for particles trapped in a potential without periodicity. In this paper we discuss ultracold atoms in a driven optical lattice, which is a realization of such a phase space crystals. The corresponding lattice structure in phase space is complex and contains rich physics. A phase space lattice differs fundamentally from a lattice in real space, because its coordinate system, i.e., phase space, has a noncommutative geometry, which naturally provides an artificial gauge (magnetic) field. We study the behavior of the quasienergy band structure and investigate the dissipative dynamics. Synthesizing lattice structures in phase space provides a new platform to simulate the condensed matter phenomena and study the intriguing phenomena of driven systems far away from equilibrium. (paper)

  17. Assessment voice synthesizers for reading in digital books

    Directory of Open Access Journals (Sweden)

    Sérvulo Fernandes da Silva Neto

    2013-07-01

    Full Text Available The digital accessibility shows ways to information access in digital media that assist people with different types of disabilities to a better interaction with the computer independent of its limitations. Of these tools are composed by voice synthesizers, that supposedly simplifying their access to any recorded knowledge through digital technologies. However such tools have emerged originally in countries foreign language. Which brings us to the following research problem: the voice synthesizers are appropriate for reading digital books in the Portuguese language? The objective of this study was to analyze and classify different software tools voice synthesizers in combination with software digital book readers to support accessibility to e-books in Portuguese. Through literature review were identified applications software voice synthesizers, composing the sample analyzed in this work. We used a simplified version of the method of Multiple Criteria Decision Support - MMDA, to assess these. In the research 12 were considered readers of e-books and 11 software voice synthesizer, tested with six formats of e-books (E-pub, PDF, HTML, DOC, TXT, and Mobi. In accordance with the results, the software Virtual Vision achieved the highest score. Relative to formats, it was found that the PDF has measured a better score when summed the results of the three synthesizers. In the studied universe contacted that many synthesizers simply cannot be used because they did not support the Portuguese language.

  18. Perception of Paralinguistic Traits in Synthesized Voices

    DEFF Research Database (Denmark)

    Baird, Alice Emily; Hasse Jørgensen, Stina; Parada-Cabaleiro, Emilia

    2017-01-01

    Along with the rise of artificial intelligence and the internet-of-things, synthesized voices are now common in daily–life, providing us with guidance, assistance, and even companionship. From formant to concatenative synthesis, the synthesized voice continues to be defined by the same traits we...

  19. Investigation of concentration overpotential distribution in a polymer electrolyte fuel cell. Paper no. IGEC-1-081

    International Nuclear Information System (INIS)

    Tajiri, K.; Yang, X.-G.; Wang, C.-Y.; Shinohara, K.

    2005-01-01

    Simultaneous measurement of current and high frequency resistance (HFR) distributions has been performed using a segmented polymer electrolyte fuel cell operated with H 2 /air. Each flow plate consisted of twelve segments along a serpentine flow field. Two types of gas diffusion layer (GDL), a treated hydrophobic carbon cloth coated with a microporous layer (MPL) on one side, and an untreated hydrophilic carbon cloth without MPL, were studied and contrasted. The total voltage loss is divided into three overpotentials: the activation, ohmic and concentration; and the concentration overpotential and its distribution are analyzed in detail. While the fuel cell using the GDL with MPL features a nearly uniform concentration overpotential profile, the one without-MPL shows an increase in concentration overpotential along the cathode flow. When the local concentration overpotential is plotted against the local oxygen concentration, the carbon cloth GDL without MPL showed a steeply increasing concentration overpotential with decreasing oxygen concentration, indicating a high sensitivity to the oxygen content. The same trend was observed for the GDL without MPL under lower relative humidity gases. It is thus found that the increase in concentration overpotential with decreasing oxygen concentration is related to the absence of MPL. (author)

  20. The impact of organisational culture on the adaptation of newly ...

    African Journals Online (AJOL)

    Usually newly employed nurses find adjusting to a work setting a challenging experience. Their successful adaptation to their work situation is greatly influenced by the socialisation process inherent in the organisational culture. The newly employed nurse often finds that the norms are unclear, confusing and restrictive.

  1. Raman assisted lightwave synthesized frequency sweeper

    DEFF Research Database (Denmark)

    Pedersen, Anders Tegtmeier; Rottwitt, Karsten

    2010-01-01

    We present a Lightwave Synthesized Frequency Sweeper comprising a Raman amplifier for loss compensation. The generated pulse train contains 123 pulses and has a flat signal level as well as a low noise level.......We present a Lightwave Synthesized Frequency Sweeper comprising a Raman amplifier for loss compensation. The generated pulse train contains 123 pulses and has a flat signal level as well as a low noise level....

  2. Assessment for markers of nephropathy in newly diagnosed type 2 ...

    African Journals Online (AJOL)

    Objective: To assess for markers of nephropathy in newly diagnosed type 2 diabetics, using blood pressure levels, endogenous creatinine clearance and urinary protein excretion as markers of renal disease. Study design: Ninety newly diagnosed type 2 diabetics were studied within 6 weeks of diagnosis. They were in ...

  3. Effect of zinc oxide nanoparticles synthesized by a precipitation

    Indian Academy of Sciences (India)

    ZnO nanoparticles were synthesized by a precipitation method in aqueous media from zinc nitrate hexahydrate and sodium hydroxide. The synthesized ZnO nanoparticles exhibited a crystalline structure with hexagonal structure of the wurtzite. The morphology of the synthesized ZnO nanoparticles presented a spherical ...

  4. The effect of poly vinyl alcohol (PVA) surfactant on phase formation and magnetic properties of hydrothermally synthesized CoFe{sub 2}O{sub 4} nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Jalalian, M.; Mirkazemi, S.M., E-mail: mirkazemi@iust.ac.ir; Alamolhoda, S.

    2016-12-01

    Nanoparticles of CoFe{sub 2}O{sub 4} were synthesized by hydrothermal process at 190 °C with and without poly vinyl alcohol (PVA) addition using treatment durations of 1.5–6 h. The synthesized powders were characterized with X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscope (SEM), Field emission scanning electron microscope (FESEM) and vibration sample magnetometer (VSM) techniques. XRD results show presence of CoFe{sub 2}O{sub 4} as the main phase and Co{sub 3}O{sub 4} as the lateral phase in some samples. The results show that in the samples synthesized without PVA addition considerable amount of lateral phase is present after 3 h of hydrothermal treatment while with PVA addition this phase is undetectable in the XRD patterns of the sample synthesized at the same conditions. Microstructural studies represent increasing of particle size with increasing of hydrothermal duration and formation of coarser particles with PVA addition. The highest maximum magnetization (M{sub max}) values in both of the samples that were synthesized with and without PVA addition are about 59 emu/g that were obtained after 4.5 h of hydrothermal treatment. Intrinsic coercive field ({sub i}H{sub c}) value of the sample without PVA addition increases from 210 to 430 Oe. While with PVA addition the {sub i}H{sub c} value changes from 83 Oe to 493 Oe. The mechanism of changes in M{sub max} and {sub i}H{sub c} values has been explained. - Highlights: • Nanoparticles of CoFe{sub 2}O{sub 4} hydrothermally synthesized with and without PVA addition. • PVA addition facilitates formation of single phase cobalt ferrite. • Coarser particles would be obtained with PVA addition. • The highest M{sub max} values in the samples with and without PVA are equal to 59 emu/g. • The highest {sub i}H{sub c} values are equalt to 320 and 493 Oe without and with PVA respectively.

  5. 14 CFR 26.39 - Newly produced airplanes: Fuel tank flammability.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Newly produced airplanes: Fuel tank... Tank Flammability § 26.39 Newly produced airplanes: Fuel tank flammability. (a) Applicability: This... Series 767 Series (b) Any fuel tank meeting all of the criteria stated in paragraphs (b)(1), (b)(2) and...

  6. Chrysosplenium japonicum (Saxifragaceae, Newly Recorded from Taiwan

    Directory of Open Access Journals (Sweden)

    Tian-Chuan Hsu

    2011-11-01

    Full Text Available Chrysosplenium japonicum (Maxim. Makino (Saxifragaceae is newly recorded from northeastern Taiwan. Description, color photos and a key to the Chrysosplenium species in Taiwan are provided.

  7. Synthesizing exoplanet demographics from radial velocity and microlensing surveys. I. Methodology

    International Nuclear Information System (INIS)

    Clanton, Christian; Gaudi, B. Scott

    2014-01-01

    Motivated by the order of magnitude difference in the frequency of giant planets orbiting M dwarfs inferred by microlensing and radial velocity (RV) surveys, we present a method for comparing the statistical constraints on exoplanet demographics inferred from these methods. We first derive the mapping from the observable parameters of a microlensing-detected planet to those of an analogous planet orbiting an RV-monitored star. Using this mapping, we predict the distribution of RV observables for the planet population inferred from microlensing surveys, taking care to adopt reasonable priors for, and properly marginalize over, the unknown physical parameters of microlensing-detected systems. Finally, we use simple estimates of the detection limits for a fiducial RV survey to predict the number and properties of analogs of the microlensing planet population such an RV survey should detect. We find that RV and microlensing surveys have some overlap, specifically for super-Jupiter mass planets (m p ≳ 1 M Jup ) with periods between ∼3-10 yr. However, the steeply falling planetary mass function inferred from microlensing implies that, in this region of overlap, RV surveys should infer a much smaller frequency than the overall giant planet frequency (m p ≳ 0.1 M Jup ) inferred by microlensing. Our analysis demonstrates that it is possible to statistically compare and synthesize data sets from multiple exoplanet detection techniques in order to infer exoplanet demographics over wider regions of parameter space than are accessible to individual methods. In a companion paper, we apply our methodology to several representative microlensing and RV surveys to derive the frequency of planets around M dwarfs with orbits of ≲ 30 yr.

  8. New syntheses of No-carrier-added 123I-labeled agents via organoborane chemistry

    International Nuclear Information System (INIS)

    Kabalka, G.W.

    1985-01-01

    No-carrier-added 123 I-labeled agents are readily prepared via the reaction of organoboranes with sodium iodide- 123 I in the presence of mild oxidizing agents. The reactions are rapid and regiospecific, and they produce excellent yields of the labeled products. The organoboranes are readily prepared from alkenes and alkynes via the hydroboration reaction. A wide variety of functional groups are tolerated by the hydroboration-iodination sequence. The sequence has been utilized to prepare 123 I-labeled steroids and fatty acids, as well as a number of labeled esters, and aromatic derivatives

  9. Being a team leader: newly registered nurses relate their experiences.

    Science.gov (United States)

    Ekström, Louise; Idvall, Ewa

    2015-01-01

    This paper presents a study that explores how newly qualified registered nurses experience their leadership role in the ward-based nursing care team. A nurse's clinical leadership affects the quality of care provided. Newly qualified nurses experience difficulties during the transition period from student to qualified professional and find it challenging to lead nursing care. Twelve nurses were interviewed and the transcribed texts analysed using qualitative content analysis to assess both manifest and latent content. Five themes were identified: feeling stranded; forming well-functioning teams; learning to lead; having the courage, strength, and desire to lead; and ensuring appropriate care. The findings indicate that many factors limit nurses' leadership but some circumstances are supportive. The leadership prerequisites for newly registered nurses need to improve, emphasizing different ways to create a supportive atmosphere that promotes professional development and job satisfaction. To increase nurse retention and promote quality of care, nurse managers need to clarify expectations and guide and support newly qualified nurses in a planned way. © 2013 John Wiley & Sons Ltd.

  10. People newly in love are more responsive to positive feedback.

    Science.gov (United States)

    Brown, Cassandra L; Beninger, Richard J

    2012-06-01

    Passionate love is associated with increased activity in dopamine-rich regions of the brain. Increased dopamine in these regions is associated with a greater tendency to learn from reward in trial-and-error learning tasks. This study examined the prediction that individuals who were newly in love would be better at responding to reward (positive feedback). In test trials, people who were newly in love selected positive outcomes significantly more often than their single (not in love) counterparts but were no better at the task overall. This suggests that people who are newly in love show a bias toward responding to positive feedback, which may reflect a general bias towards reward-seeking.

  11. Study of photoconductor polymers synthesized by plasma

    International Nuclear Information System (INIS)

    Enriquez P, M.A.

    2007-01-01

    In this work the photoconductivity in poly thiophene (PTh), poly pyrrole (PPy) and doped poly pyrrole with iodine (PPy/I) is studied, whose structures depend of the intensity of the electric field applied during the synthesis by plasma. The conjugated organic polymers possess double alternated bonds in its chemical structure that its allow the one movement of π electrons through the polymeric chains. The plasma is produced by means of splendor discharges to 13.5 MHz, resistive coupling, at one pressure that oscillates in the interval from 2 to 3x10 -1 mbar, 180 min and powers of 10, 24, 40, 60 , 80 and 100 W. Its were used heteroaromatic polymers like PTh and PPy/I, due to their potential applications in optoelectronics. The influence of the iodine is evaluated as dopant in PPy and it is compared with their similar one without doping in the light absorption/emission processes. The polymers synthesized by plasma can ramify or to intersect due to the energy applied during the synthesis. However, if the polymer intersects, the aromaticity can continue through the polymeric chains. The absorptions obtained by infrared spectroscopy, suggest that the polymer conserves the aromatic structure of the monomer fundamentally with substitutions that indicate inter crossing and partial fragmentation. The structure of most of the polymers spreads to be amorphous because they don't possess any classification. However, the PPy/I and PTh synthesized by this technique present crystalline segments whose intensity diminishes with the power of the discharge. In PTh, the average crystallinity diminishes from 19.8% to 9.9%, and in PPy/I of 15.9% to 13.3% in the interval of 10 to 100 W of power. In this work, however, its were crystalline arrangements in all the studied powers. The classification of the polymeric structure favors the formation of trajectories of transfer of electric loads among the chains, that which influences in the global electric conductivity of the material. In UV

  12. Synthesis of (Ga 1–<i>x> Zn <i>x> )(N 1–<i>x> O <i>x> ) with Enhanced Visible-Light Absorption and Reduced Defects by Suppressing Zn Volatilization

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Dennis P.; Skrabalak, Sara E.

    2016-04-18

    (Ga1–<i>x>)(N1–<i>x> O <i>x>) (GZNO) particles with enhanced optical absorption were synthesized by topotactic transformation of Zn2+/Ga3+ layered double hydroxides. This outcome was achieved by suppressing Zn volatilization during nitridation by maintaining a low partial pressure of O2 (pO2). Zn-rich (x > 1/3) variants of GZNO were achieved and compared to those prepared by conventional ammonoylsis conditions. The optical absorption and structural properties of these samples were compared to those prepared in the absence of O2 by diffuse-reflectance spectroscopy and powder X-ray diffraction methods. Notably, suppression of Zn volatilization leads to smaller-band-gap materials (2.30 eV for x = 0.42 versus 2.71 eV for x = 0.21) and reduced structural defects. This synthetic route and set of characterizations provide useful structure–property studies of GZNO and potentially other oxynitrides of interest as photocatalysts.

  13. Detection of MPLW515L/K mutations and determination of allele frequencies with a single-tube PCR assay.

    Science.gov (United States)

    Takei, Hiraku; Morishita, Soji; Araki, Marito; Edahiro, Yoko; Sunami, Yoshitaka; Hironaka, Yumi; Noda, Naohiro; Sekiguchi, Yuji; Tsuneda, Satoshi; Ohsaka, Akimichi; Komatsu, Norio

    2014-01-01

    A gain-of-function mutation in the myeloproliferative leukemia virus (MPL) gene, which encodes the thrombopoietin receptor, has been identified in patients with essential thrombocythemia and primary myelofibrosis, subgroups of classic myeloproliferative neoplasms (MPNs). The presence of MPL gene mutations is a critical diagnostic criterion for these diseases. Here, we developed a rapid, simple, and cost-effective method of detecting two major MPL mutations, MPLW515L/K, in a single PCR assay; we termed this method DARMS (dual amplification refractory mutation system)-PCR. DARMS-PCR is designed to produce three different PCR products corresponding to MPLW515L, MPLW515K, and all MPL alleles. The amplicons are later detected and quantified using a capillary sequencer to determine the relative frequencies of the mutant and wild-type alleles. Applying DARMS-PCR to human specimens, we successfully identified MPL mutations in MPN patients, with the exception of patients bearing mutant allele frequencies below the detection limit (5%) of this method. The MPL mutant allele frequencies determined using DARMS-PCR correlated strongly with the values determined using deep sequencing. Thus, we demonstrated the potential of DARMS-PCR to detect MPL mutations and determine the allele frequencies in a timely and cost-effective manner.

  14. Detection of MPLW515L/K mutations and determination of allele frequencies with a single-tube PCR assay.

    Directory of Open Access Journals (Sweden)

    Hiraku Takei

    Full Text Available A gain-of-function mutation in the myeloproliferative leukemia virus (MPL gene, which encodes the thrombopoietin receptor, has been identified in patients with essential thrombocythemia and primary myelofibrosis, subgroups of classic myeloproliferative neoplasms (MPNs. The presence of MPL gene mutations is a critical diagnostic criterion for these diseases. Here, we developed a rapid, simple, and cost-effective method of detecting two major MPL mutations, MPLW515L/K, in a single PCR assay; we termed this method DARMS (dual amplification refractory mutation system-PCR. DARMS-PCR is designed to produce three different PCR products corresponding to MPLW515L, MPLW515K, and all MPL alleles. The amplicons are later detected and quantified using a capillary sequencer to determine the relative frequencies of the mutant and wild-type alleles. Applying DARMS-PCR to human specimens, we successfully identified MPL mutations in MPN patients, with the exception of patients bearing mutant allele frequencies below the detection limit (5% of this method. The MPL mutant allele frequencies determined using DARMS-PCR correlated strongly with the values determined using deep sequencing. Thus, we demonstrated the potential of DARMS-PCR to detect MPL mutations and determine the allele frequencies in a timely and cost-effective manner.

  15. Synthesis, characterization and photophysical studies of β ...

    Indian Academy of Sciences (India)

    synthesized in appreciable yields through a copper(I)-catalyzed “click” reaction of zinc(II) 2-azidomethyl-. 5,10,15,20-tetraphenylporphyrin ... C to form the corresponding free-base porphyrin analogues in good yields. The newly syn- thesized products ... nificance of these two classes of heterocycles, our aim was to connect ...

  16. Mosquitocidal and antibacterial activity of green-synthesized silver nanoparticles from Aloe vera extracts: towards an effective tool against the malaria vector Anopheles stephensi?

    Science.gov (United States)

    Dinesh, Devakumar; Murugan, Kadarkarai; Madhiyazhagan, Pari; Panneerselvam, Chellasamy; Kumar, Palanisamy Mahesh; Nicoletti, Marcello; Jiang, Wei; Benelli, Giovanni; Chandramohan, Balamurugan; Suresh, Udaiyan

    2015-04-01

    Mosquitoes represent an important threat for lives of millions of people worldwide, acting as vectors for devastating pathogens, such as malaria, yellow fever, dengue, and West Nile. In addition, pathogens and parasites polluting water also constitute a severe plague for populations of developing countries. Here, we investigated the mosquitocidal and antibacterial properties of Aloe vera leaf extract and silver nanoparticles synthesized using A. vera extract. Mosquitocidal properties were assessed in laboratory against larvae (I-IV instar) and pupae of the malaria vector Anopheles stephensi. Green-synthesized silver nanoparticles were tested against An. stephensi also in field conditions. Antibacterial properties of nanoparticles were evaluated against Bacillus subtilis, Klebsiella pneumoniae, and Salmonella typhi using the agar disk diffusion and minimum inhibitory concentration protocol. The synthesized silver nanoparticles were characterized by UV-vis spectrum, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray diffraction (XRD). In laboratory conditions, the A. vera extract was toxic against An. stephensi larvae and pupae, even at low dosages. LC50 were 48.79 ppm (I instar), 59.09 ppm (II instar), 70.88 ppm (III instar), 83.58 ppm (IV instar), and 152.55 ppm (pupae). Green-synthesized silver nanoparticles were highly toxic against An. stephensi. LC50 were 3.825 ppm (I instar), 4.119 ppm (II instar), 4.982 ppm (III instar), 5.711 ppm (IV instar), and 6.113 ppm (pupae). In field conditions, the application of A. vera-synthesized silver nanoparticles (10 × LC50) leads to An. stephensi larval reduction of 74.5, 86.6, and 97.7%, after 24, 48, and 72 h, respectively. Nanoparticles also showed antibacterial properties, and the maximum concentration tested (150 mg/L) evoked an inhibition zone wider than 80 mm in all tested bacterium species. This study adds knowledge about the use of green synthesis of nanoparticles in

  17. Oxidative stability of marine phospholipids

    DEFF Research Database (Denmark)

    Lu, Henna Fung Sieng; Nielsen, Nina Skall; Baron, Caroline Pascale

    Many studies have shown that marine phospholipids (MPL) provide more advantages than fish oil. They have better bioavailability, better resistance towards oxidation and higher content of eicosapentaenoic acids (EPA) and docosahexaenoic acids (DHA) than oily triglycerides (fish oil). The objective...... of this study is to investigate the oxidative and hydrolytic stability of MPL. In addition, this study also investigates the effect of chemical composition of MPL and Maillard reaction (interaction between lipids oxidation products with the residue of amino acids) on MPL emulsions’ stability. Firstly, MPL were...... was further investigated through measurement of secondary volatile compounds by Solid Phase Microextraction at several time intervals. On the other hand, the Maillard reaction was investigated through the measurement of color changes and pyrrole content before and after 32 days storage. Preliminary result...

  18. Thermoluminescence properties of Li2B4O7:Cu, B phosphor synthesized using solution combustion technique

    International Nuclear Information System (INIS)

    Ozdemir, A.; Altunal, V.; Kurt, K.; Depci, T.; Yu, Y.; Lawrence, Y.; Nur, N.; Guckan, V.; Yegingil, Z.

    2017-01-01

    To determine the effects of various concentrations of the activators copper (Cu) and boron (B) on the thermoluminescence (TL) properties of lithium tetraborate, the phosphor was first synthesized and doped with five different concentrations of copper (0.1–0.005 wt%) using solution combustion method. 0.01 wt% Cu was the concentration which showed the most significant increase in the sensitivity of the phosphor. The second sort of Li 2 B 4 O 7 :Cu material was prepared by adding B (0.001–0.03 wt%) to it. The newly developed copper-boron activated lithium tetraborate (Li 2 B 4 O 7 :Cu, B) material with 0.01 wt% Cu and 0.001 wt% B impurity concentrations was shown to have promise as a TL phosphor. The material formation was examined using powder x-Ray Diffraction (XRD) analysis and Scanning Electron Microscope (SEM) imaging. Fourier Transform Infrared (FT-IR) spectrum of the synthesized polycrystalline powder sample was also recorded. The TL glow curves were analyzed to determine various dosimetric characteristics of the synthesized luminophosphors. The dose response increased in a “linear” way with the beta-ray exposure between 0.1–20 Gy, a dose range being interested in medical dosimetry. The response with changing photon and electron energy was studied. The rate of decay of the TL signal was investigated both for dark storage and under direct sunlight. Li 2 B 4 O 7 :Cu, B showed no individual variation of response in 9 recycling measurements. The fluorescence spectrum was determined. The kinetic parameters were estimated by different methods and the results discussed. The studied properties of synthesized Li 2 B 4 O 7 :Cu, B were found all favorable for dosimetric purposes. - Highlights: • Li 2 B 4 O 7 :Cu, B synthesis using solution combustion method with various concentrations. • Structure analysis of Li 2 B 4 O 7 :Cu, B using XRD, SEM and FTIR methods. • Investigation of thermoluminescent properties of Li 2 B 4 O 7 :Cu, B. • Relatively good

  19. Workplace Violence and Job Outcomes of Newly Licensed Nurses

    OpenAIRE

    Chang, Hyoung Eun; Cho, Sung-Hyun

    2016-01-01

    Purpose: The purpose of this study was to examine the prevalence of workplace violence toward newly licensed nurses and the relationship between workplace violence and job outcomes. Methods: An online survey was conducted of newly licensed registered nurses who had obtained their license in 2012 or 2013 in South Korea and had been working for 5–12 months after first being employed. The sample consisted of 312 nurses working in hospitals or clinics. The Copenhagen Psychosocial Questionnaire...

  20. Estimating the impact of newly arrived foreign-born persons on tuberculosis in the United States.

    Directory of Open Access Journals (Sweden)

    Yecai Liu

    Full Text Available Among approximately 163.5 million foreign-born persons admitted to the United States annually, only 500,000 immigrants and refugees are required to undergo overseas tuberculosis (TB screening. It is unclear what extent of the unscreened nonimmigrant visitors contributes to the burden of foreign-born TB in the United States.We defined foreign-born persons within 1 year after arrival in the United States as "newly arrived", and utilized data from U.S. Department of Homeland Security, U.S. Centers for Disease Control and Prevention, and World Health Organization to estimate the incidence of TB among newly arrived foreign-born persons in the United States. During 2001 through 2008, 11,500 TB incident cases, including 291 multidrug-resistant TB incident cases, were estimated to occur among 20,989,738 person-years for the 1,479,542,654 newly arrived foreign-born persons in the United States. Of the 11,500 estimated TB incident cases, 41.6% (4,783 occurred among immigrants and refugees, 36.6% (4,211 among students/exchange visitors and temporary workers, 13.8% (1,589 among tourists and business travelers, and 7.3% (834 among Canadian and Mexican nonimmigrant visitors without an I-94 form (e.g., arrival-departure record. The top 3 newly arrived foreign-born populations with the largest estimated TB incident cases per 100,000 admissions were immigrants and refugees from high-incidence countries (e.g., 2008 WHO-estimated TB incidence rate of ≥100 cases/100,000 population/year; 235.8 cases/100,000 admissions, 95% confidence interval [CI], 228.3 to 243.3, students/exchange visitors and temporary workers from high-incidence countries (60.9 cases/100,000 admissions, 95% CI, 58.5 to 63.3, and immigrants and refugees from medium-incidence countries (e.g., 2008 WHO-estimated TB incidence rate of 15-99 cases/100,000 population/year; 55.2 cases/100,000 admissions, 95% CI, 51.6 to 58.8.Newly arrived nonimmigrant visitors contribute substantially to the burden of

  1. Estimating the impact of newly arrived foreign-born persons on tuberculosis in the United States.

    Science.gov (United States)

    Liu, Yecai; Painter, John A; Posey, Drew L; Cain, Kevin P; Weinberg, Michelle S; Maloney, Susan A; Ortega, Luis S; Cetron, Martin S

    2012-01-01

    Among approximately 163.5 million foreign-born persons admitted to the United States annually, only 500,000 immigrants and refugees are required to undergo overseas tuberculosis (TB) screening. It is unclear what extent of the unscreened nonimmigrant visitors contributes to the burden of foreign-born TB in the United States. We defined foreign-born persons within 1 year after arrival in the United States as "newly arrived", and utilized data from U.S. Department of Homeland Security, U.S. Centers for Disease Control and Prevention, and World Health Organization to estimate the incidence of TB among newly arrived foreign-born persons in the United States. During 2001 through 2008, 11,500 TB incident cases, including 291 multidrug-resistant TB incident cases, were estimated to occur among 20,989,738 person-years for the 1,479,542,654 newly arrived foreign-born persons in the United States. Of the 11,500 estimated TB incident cases, 41.6% (4,783) occurred among immigrants and refugees, 36.6% (4,211) among students/exchange visitors and temporary workers, 13.8% (1,589) among tourists and business travelers, and 7.3% (834) among Canadian and Mexican nonimmigrant visitors without an I-94 form (e.g., arrival-departure record). The top 3 newly arrived foreign-born populations with the largest estimated TB incident cases per 100,000 admissions were immigrants and refugees from high-incidence countries (e.g., 2008 WHO-estimated TB incidence rate of ≥100 cases/100,000 population/year; 235.8 cases/100,000 admissions, 95% confidence interval [CI], 228.3 to 243.3), students/exchange visitors and temporary workers from high-incidence countries (60.9 cases/100,000 admissions, 95% CI, 58.5 to 63.3), and immigrants and refugees from medium-incidence countries (e.g., 2008 WHO-estimated TB incidence rate of 15-99 cases/100,000 population/year; 55.2 cases/100,000 admissions, 95% CI, 51.6 to 58.8). Newly arrived nonimmigrant visitors contribute substantially to the burden of foreign

  2. The Impact of the Malaysian Minimum Cigarette Price Law: Findings from the ITC Malaysia Survey

    Science.gov (United States)

    Liber, Alex C.; Ross, Hana; Omar, Maizurah; Chaloupka, Frank J.

    2015-01-01

    Objectives Study the effects of the 2011 Malaysian minimum price law (MPL) on prices of licit and illicit cigarette brands. Identify barriers to the MPL achieving positive public health effects. Methods The International Tobacco Control Project's Southeast Asia survey collected information on Malaysian smokers' cigarette purchases (n=7,520) in five survey waves between 2005 and 2012. Consumption-weighted comparisons of proportions tests and adjusted Wald tests were used to evaluate changes over time in violation rates of the inflation-adjusted MPL, the proportion of illicit cigarette purchases, and mean prices. Results After the passage of the MPL, the proportion of licit brand cigarette purchases that were below the inflation-adjusted 2011 minimum price level fell substantially (before 3.9%, after 1.8%, p=0.002), while violation of the MPL for illicit brand cigarette purchases was unchanged (before 89.8%, after 91.9%, p=0.496). At the same time, the mean real price of licit cigarettes rose (p=0.006) while the mean real price of illicit cigarettes remained unchanged (p=0.134). The proportion of illicit cigarette purchases rose as well (before 13.4%, after 16.5%, p=0.041). Discussion The MPL appears not to have meaningfully changed cigarette prices in Malaysia, as licit brand prices remained well above and illicit brand prices remained well below the minimum price level before and after MPL's implementation. The increasing proportion of illicit cigarettes on the market may have undermined any positive health effects of the Malaysian MPL. The illicit cigarette trade must be addressed before a full evaluation of the Malaysian MPL's impact on public health can take place. The authors encourage the continued use of specific excise tax increases to reliably increase the price and decrease the consumption of cigarettes in Malaysia and elsewhere. PMID:25808666

  3. Enantioselective catalytic syntheses of alpha-branched chiral amines

    DEFF Research Database (Denmark)

    Brase, S.; Baumann, T.; Dahmen, S.

    2007-01-01

    Chiral amines play a pivotal role in fine chemical and natural product syntheses and the design of novel materials.......Chiral amines play a pivotal role in fine chemical and natural product syntheses and the design of novel materials....

  4. Highly Luminescent, Water-Soluble Lanthanide Fluorobenzoates: Syntheses, Structures and Photophysics, Part I: Lanthanide Pentafluorobenzoates.

    Science.gov (United States)

    Kalyakina, Alena S; Utochnikova, Valentina V; Bushmarinov, Ivan S; Ananyev, Ivan V; Eremenko, Igor L; Volz, Daniel; Rönicke, Franziska; Schepers, Ute; Van Deun, Rik; Trigub, Alexander L; Zubavichus, Yan V; Kuzmina, Natalia P; Bräse, Stefan

    2015-12-01

    Highly luminescent, photostable, and soluble lanthanide pentafluorobenzoates have been synthesized and thoroughly characterized, with a focus on Eu(III) and Tb(III) complexes as visible emitters and Nd(III) , Er(III) , and Yb(III) complexes as infrared emitters. Investigation of the crystal structures of the complexes in powder form and as single crystals by using X-ray diffraction revealed five different structural types, including monomeric, dimeric, and polymeric. The local structure in different solutions was studied by using X-ray absorption spectroscopy. The photoluminescence quantum yields (PLQYs) of terbium and europium complexes were 39 and 15 %, respectively; the latter value was increased almost twice by using the heterometallic complex [Tb0.5 Eu0.5 (pfb)3 (H2 O)] (Hpfb=pentafluorobenzoic acid). Due to the effectively utilized sensitization strategy (pfb)(-) →Tb→Eu, a pure europium luminescence with a PLQY of 29 % was achieved. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. In vitro Anti-Leishmania Activity and Safety of Newly Synthesized ...

    African Journals Online (AJOL)

    International Pharmaceutical Abstract, Chemical Abstracts, Embase, Index Copernicus, EBSCO, African. Index Medicus, JournalSeek ... virus (HAV), serotonin 5-HT6 receptor antagonist ..... Structure-activity relationships based on the obtained ...

  6. Acute toxicity and gastroprotection studies with a newly synthesized steroid.

    Science.gov (United States)

    Ketuly, Kamal A; Hadi, A Hamid A; Golbabapour, Shahram; Hajrezaie, Maryam; Hassandarvish, Pouya; Ali, Hapipah Mohd; Abdul Majid, Nazia; Abdulla, Mahmood A

    2013-01-01

    Synthetic steroids, such as 9α-bromobeclomethasonedipropionate, have shown gastroprotective activity. For example, the potent glucocorticoid steroid, beclomethasone dipropionate, has been used for treatment of bowel ulcerations. The purpose of the present study was to evaluate the effect of a synthetic steroid, (20S)-22-acetoxymethyl-6β-methoxy-3α,5-dihydro-3'H-cyclopropa[3α,5]-5α-pregnane (AMDCP), on ethanol-induced gastric mucosa injuries in rats. Rats were divided into 8 groups. The negative control and ethanol control groups were administered Tween 20 (10%v/v) orally. The reference control group, 20 mg/kg omeprazole (10% Tween 20, 5 mL/kg), was administrated orally. The experimental groups received 1, 5, 10, 15 or 20 mg/kg of the AMDCP compound (10% Tween 20, 5 mL/kg). After 60 min, Tween 20 and absolute ethanol was given orally (5 mL/kg) to the negative control group and to the rest of the groups, and the rats were sacrificed an hour later. The acidity of gastric content, gastric wall mucus and areas of mucosal lesions were assessed. In addition, histology and immunohistochemistry of the gastric wall were assessed. Prostaglandin E2 (PGE2) and malondialdehyde (MDA) content were also measured. The ethanol control group exhibited severe mucosal lesion compared with the experimental groups with fewer mucosal lesions along with a reduction of edema and leukocyte infiltration. Immunohistochemical staining of Hsp70 and Bax proteins showed over-expression and under-expression, respectively, in the experimental groups. The experimental groups also exhibited high levels of PGE2 as well as a reduced amount of MDA. AMDCP decreased the acidity and lipid peroxidation and increased the levels of antioxidant enzymes. The current investigation evaluated the gastroprotective effects of AMDCP on ethanol-induced gastric mucosal lesions in rats. This study also suggests that AMDCP might be useful as a gastroprotective agent.

  7. Spectroelectrochemical and electrochromic behaviors of newly synthesized poly[3′-(2-aminopyrimidyl)-2,2′:5′,2″-terthiophene

    International Nuclear Information System (INIS)

    Kim, Dong-Min; Shim, Kyu-Bin; Son, Jung Ik; Reddy, Sanapalli S.; Shim, Yoon-Bo

    2013-01-01

    The functionalized conductive polymer precursor of the terthiophene derivative, 3′-(2-aminopyrimidyl)-2,2′:5′,2″-terthiophene (PATT) was firstly synthesized and confirmed with FT-IR, 1 H NMR, 13 C NMR, and mass spectroscopy. The electrochemical and electronic properties of polyPATT film are investigated and compared with that of poly(2,2′:5′,2″-terthiophene-3′-p-benzoic acid) (polyTTBA), which has an electron-accepting group. The cyclic voltammograms (CVs) recorded for electrochemically grown polyPATT reveal the redox peaks at +1.1/+0.96 V, and the conductivity increases monotonically as the applying potential goes to the positive direction (0.11 S cm −1 at +1.4 V). The spectroelectrochemical analysis of polyPATT reveals the absorption bands at 456, 825 and 643 nm corresponding to the π–π* transition, polaron, and bipolaron formations, respectively. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels of the polyPATT film bearing an electron donating group are to be 3.60 and 5.54 eV, respectively. The polyPATT film shows reversible multiple color transition within 0.6 s (from brownish-yellow (at 0.0 V) to blue (at +1.4 V)) when the potential switches between the reduced and oxidized states

  8. Syntheses and modulations in the chromatin contents of histones H1/sup o/ and H1 during G1 and S phases in Chinese hamsters cells

    International Nuclear Information System (INIS)

    D'Anna, J.A.; Gurley, L.R.; Tobey, R.A.

    1982-01-01

    Flow cytometry, conventional autoradiography, and autoradiography employing high concentrations of high specific activity [ 3 H]thymidine indicate that (1) treatment of Chinese hamster ovary (line CHO) cells with butyrate truly blocks cells in G 1 and (2) cells blocked in G 1 by isoleucine deprivation remain blocked in G 1 when they are released into complete medium containing butyrate. Measurements of H1/sup o/ content relative to core histones and H1/sup o/:H1 ratios indicate that H1/sup o/ is enhanced somewhat in G 1 cells arrested by isoleucine deprivation; however, (1) treatment with butyrate greatly increases the H1/sup o/ content in G 1 -blocked cells, and (2) the enhancement is very sensitive to butyrate concentration. Measurements of relative histone contents in the isolated chromatin of synchronized cultures also suggest that the acid-soluble content of histone H1 (relative to core histones) becomes greatly depleted in the isolated chromatin when synchronized cells are blocked in early S phase by sequential use of isoleucine deprivation and hydroxyurea blockade. We also have measured [ 3 H]lysine incorporation, various protein ratios, and relative rates of deposition of newly synthesized H1/sup o/, H1, and H4 onto chromatin during G 1 and S in the absence of butyrate. The results suggest a dynamic picture of chromatin organization in which (1) newly synthesized histone H1/sup o/ binds to chromatin during traverse of G 1 and S phases and (2) histone H1 dissociates from (or becomes loosely bound to) chromatin during prolonged early S-phase block with hydroxyurea

  9. Aeon: Synthesizing Scheduling Algorithms from High-Level Models

    Science.gov (United States)

    Monette, Jean-Noël; Deville, Yves; van Hentenryck, Pascal

    This paper describes the aeon system whose aim is to synthesize scheduling algorithms from high-level models. A eon, which is entirely written in comet, receives as input a high-level model for a scheduling application which is then analyzed to generate a dedicated scheduling algorithm exploiting the structure of the model. A eon provides a variety of synthesizers for generating complete or heuristic algorithms. Moreover, synthesizers are compositional, making it possible to generate complex hybrid algorithms naturally. Preliminary experimental results indicate that this approach may be competitive with state-of-the-art search algorithms.

  10. The development of [18F]FDG synthesizer

    International Nuclear Information System (INIS)

    Hu, M. G.; Kim, S. W.; Lee, J. Y.; Yang, S. D.; Jun, G. S.

    2003-01-01

    The automatic system for [ 18 F]FDG production using for the diagnosis of cancer has been developed. This automation system was consisted of a synthesizer module, a PLC based controller and a PMU for graphic user interface. By this system, the radiochemical purity was over 98%, the production yield was over 30% after synthesize and elapsed time was 35 minute

  11. Application a territorial level of the ENEA - A.I.I.A.'s methodologies for the Emilia and Abruzzo Italian regions

    International Nuclear Information System (INIS)

    Lai, G.

    1996-12-01

    This report is aimed to presenting the syntheses of the ENEA (Italian Agency for new Technologies and the Environment)- A.I.I.A.'s methodologies applications for the evaluation of the energy potential by vegetable biomass and Municipal Solid Wastes at four selected local realities, two for Emilia Region and two for Abruzzo. The methodologies, realized in the framework, of the activities of ERG-PROM Division of ENEA, are aimed to evaluate the economical profitability of the energy biomass production. The syntheses report the results of the applications realized using local data and information and, for each application, are described the conditions for the economical profitability of biomass energy plants

  12. Exercise recommendations in patients with newly diagnosed fibromyalgia.

    Science.gov (United States)

    Wilson, Brad; Spencer, Horace; Kortebein, Patrick

    2012-04-01

    To evaluate exercise recommendations in patients newly diagnosed with fibromyalgia. A retrospective chart review. A public university rheumatology clinic. Patients newly diagnosed with fibromyalgia (N = 122). Frequency and type of exercise recommendations. The mean (standard deviation) age of these patients with fibromyalgia was 45 ± 12 years; 91% were women. Exercise was recommended as part of the documented treatment plan in 47% of these patients (57/122); only 3 patients had a documented contraindication for exercise. Aquatic exercise was most frequently recommended (56% [32/57]), followed by combined aquatic-aerobic exercise (26% [15/57]), and, infrequently, aerobic exercise only (5% [3/57]); only 7% of these patients (4/57) were referred for physical therapy. The primary method of communication was verbal discussion (94% [54/57]). Although there is well-documented evidence that exercise is beneficial for patients with fibromyalgia, we found that less than half of patients with newly diagnosed fibromyalgia in our study were provided recommendations to initiate an exercise program as part of their treatment plan. Further investigation of these findings are warranted, including evaluation of other university and community rheumatology practices as well as that of other physicians caring for patients with fibromyalgia. However, our findings indicate that there appears to be an opportunity to provide more specific and practical education regarding the implementation of an exercise regimen for patients with newly diagnosed fibromyalgia. Physiatrists may be particularly well suited to manage the exercise component of patients with fibromyalgia because of their specialized training in exercise prescription. Copyright © 2012 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  13. Bone sialoprotein II synthesized by cultured osteoblasts contains tyrosine sulfate

    International Nuclear Information System (INIS)

    Ecarot-Charrier, B.; Bouchard, F.; Delloye, C.

    1989-01-01

    Isolated mouse osteoblasts that retain their osteogenic activity in culture were incubated with [35S] sulfate. Two radiolabeled proteins, in addition to proteoglycans, were extracted from the calcified matrix of osteoblast cultures. All the sulfate label in both proteins was in the form of tyrosine sulfate as assessed by amino acid analysis and thin layer chromatography following alkaline hydrolysis. The elution behavior on DEAE-Sephacel of the major sulfated protein and the apparent Mr on sodium dodecyl sulfate gels were characteristic of bone sialoprotein II extracted from rat. This protein was shown to cross-react with an antiserum raised against bovine bone sialoprotein II, indicating that bone sialoprotein II synthesized by cultured mouse osteoblasts is a tyrosine-sulfated protein. The minor sulfated protein was tentatively identified as bone sialoprotein I or osteopontin based on its elution properties on DEAE-Sephacel and anomalous behavior on sodium dodecyl sulfate gels similar to those reported for rat bone sialoprotein I

  14. Syntheses and absorption-structure relationships of some new ...

    Indian Academy of Sciences (India)

    New biheterocyclic compound was synthesized as starting material to prepare new photosensitizers mono-, tri-, substituted tri-, azadimethine and mixed cyanine dyes. Absorption-structure relationship of the synthesized cyanine dyes were determined by studying their electronic spectral behaviour in ethanol. The structure of ...

  15. In silico binding analysis and SAR elucidations of newly designed benzopyrazine analogs as potent inhibitors of thymidine phosphorylase.

    Science.gov (United States)

    Taha, Muhammad; Ismail, Nor Hadiani; Imran, Syahrul; Rahim, Fazal; Wadood, Abdul; Al Muqarrabun, Laode Muhammad Ramadhan; Khan, Khalid Mohammed; Ghufran, Mehreen; Ali, Muhammad

    2016-10-01

    Thymidine phosphorylase (TP) is up regulated in wide variety of solid tumors and therefore presents a remarkable target for drug discovery in cancer. A novel class of extremely potent TPase inhibitors based on benzopyrazine (1-28) has been developed and evaluated against thymidine phosphorylase enzyme. Out of these twenty-eight analogs eleven (11) compounds 1, 4, 14, 15, 16, 17, 18, 19, 20, 24 and 28 showed potent thymidine phosphorylase inhibitory potentials with IC50 values ranged between 3.20±0.30 and 37.60±1.15μM when compared with the standard 7-Deazaxanthine (IC50=38.68±4.42μM). Structure-activity relationship was established and molecular docking studies were performed to determine the binding interactions of these newly synthesized compounds. Current studies have revealed that these compounds established stronger hydrogen bonding networks with active site residues as compare to the standard compound 7DX. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. bis-NHC complexes of R-BINOL scaffold

    Indian Academy of Sciences (India)

    SONALI RAMGOPAL MAHULE

    2017-09-04

    Sep 4, 2017 ... The newly synthesized bis-NHC ligand precursor (1g) and its corresponding {[L(L -NHC)2]Ag}Cl (1h) and .... -binaphthyl (1f) (0.500 g, 1.21 mmol) and 1-i-propyl- ... chloride (1g) (0.250 g, 0.340 mmol) and Ag2O (0.078 g, 0.340.

  17. 125I-labeled crosslinking reagent that is hydrophilic, photoactivatable, and cleavable through an azo linkage

    International Nuclear Information System (INIS)

    Denny, J.B.; Blobel, G.

    1984-01-01

    A radioactive crosslinking reagent, N-[4-(p-azido-m-[ 125 I]iodophenylazo)benzoyl]-3-aminopropyl-N'-oxysulfosuccinimide ester, has been synthesized. The reagent is photoactivatable, water-soluble, cleavable through an azo linkage, and labeled with 125 I at the carrier-free specific activity of 2000 Ci/mmol. Any protein derivatized with the reagent is thus converted into an 125 I-labeled photoaffinity probe. Crosslinks are formed following photolysis with 366-nm light, and cleavage by sodium dithionite results in the donation of radioactivity to the distal partner in crosslinked complexes. The newly labeled proteins are then analyzed by gel electrophoresis and autoradiography. The compound was prepared by iodination of N-[4-(p-aminophenylazo)benzoyl]-3-aminopropionic acid using carrier-free Na 125 I and chloramine-T, followed by azide formation and conversion to the water-soluble sulfosuccinimide ester. As a model system, protein A-Sepharose was derivatized with the reagent under subdued light. Each derivatized protein A molecule contained only one crosslinker. The derivatized protein A-Sepharose was then photolyzed in the presence of human serum and subsequently treated with sodium dithionite. Analysis of the serum by gel electrophoresis revealed that 1.1% of the radioactive label originally present on the protein A-Sepharose was transferred to the heavy chain of IgG, which was the most intensely labeled protein in the gel. The next most intensely labeled protein was IgG light chain, which incorporated radioactivity that was lower by a factor of 3.6 than that of the heavy chain. 36 references, 3 figures

  18. On the one pot syntheses of chromeno[4,3-b]pyridine-3-carboxylate and chromeno[3,4-c]pyridine-3-carboxylate and dihydropyridines

    Energy Technology Data Exchange (ETDEWEB)

    Navarrete-Encina, Patricio A.; Vega-Retter, Christian, E-mail: pnavarre@vtr.ne [Universidad de Chile, Santiago (Chile). Facultad de Ciencias Quimicas y Farmaceuticas. Lab. de Sintesis Organica y Fisicoquimica; Salazar, Ricardo; Perez, Karina; Squella, Juan A.; Nunez-Vergara, Luis J. [Universidad de Chile, Santiago (Chile). Fac. de Ciencias Quimicas y Farmaceuticas. Lab. de Bioelectroquimica

    2010-07-01

    Substituted chromenos, dihydropyridines and pyridines have been important in the syntheses of compounds having interesting pharmacological properties. Therefore, we found of interest to synthesize chromenopyridines and chromeno dihydropyridines (i.e., fused chromeno and dihydropyridine or pyridine rings) to further study their biological activity. Here, we propose one-pot syntheses for substituted ethyl-2,4-dimethyl-5-oxo-5H-chromeno[4,3-b]pyridine-3-carboxylates, ethyl-2,4-dimethyl-5-oxo-5H-chromeno[3,4-c]pyridine-3-carboxylates and their respective 1,4-dihydropyridines based on a modified Hantzsch pyridine synthesis using 2-hydroxyaryl aldehydes, with electron withdrawing and electron donating groups on the phenyl ring, as starting reactants. Sixteen compounds were synthesized by the described method and fully characterized. An average yield of 37% was obtained for the different derivatives. (author)

  19. On the one pot syntheses of chromeno[4,3-b]pyridine-3-carboxylate and chromeno[3,4-c]pyridine-3-carboxylate and dihydropyridines

    International Nuclear Information System (INIS)

    Navarrete-Encina, Patricio A.; Vega-Retter, Christian; Salazar, Ricardo; Perez, Karina; Squella, Juan A.; Nunez-Vergara, Luis J.

    2010-01-01

    Substituted chromenos, dihydropyridines and pyridines have been important in the syntheses of compounds having interesting pharmacological properties. Therefore, we found of interest to synthesize chromenopyridines and chromeno dihydropyridines (i.e., fused chromeno and dihydropyridine or pyridine rings) to further study their biological activity. Here, we propose one-pot syntheses for substituted ethyl-2,4-dimethyl-5-oxo-5H-chromeno[4,3-b]pyridine-3-carboxylates, ethyl-2,4-dimethyl-5-oxo-5H-chromeno[3,4-c]pyridine-3-carboxylates and their respective 1,4-dihydropyridines based on a modified Hantzsch pyridine synthesis using 2-hydroxyaryl aldehydes, with electron withdrawing and electron donating groups on the phenyl ring, as starting reactants. Sixteen compounds were synthesized by the described method and fully characterized. An average yield of 37% was obtained for the different derivatives. (author)

  20. MPLW515L mutation in acute megakaryoblastic leukaemia.

    Science.gov (United States)

    Hussein, K; Bock, O; Theophile, K; Schulz-Bischof, K; Porwit, A; Schlue, J; Jonigk, D; Kreipe, H

    2009-05-01

    The thrombopoietin receptor gene (MPL) is expressed in megakaryocytes and exhibits the gain of function point mutation W515K/L in approximately 5% of patients with primary myelofibrosis/idiopathic myelofibrosis (PMF) representing one subtype of the chronic myeloproliferative disorders (myeloproliferative neoplasm). A series of primary and secondary acute myeloid leukaemias (AML) with megakaryoblastic phenotype and myelofibrosis unrelated to PMF (n=12) was analysed for the MPL(W515K/L) mutation by pyrosequencing. In three cases (25%), MPL(W515L) was found and in two of these a combination with trisomy 21 or the Philadelphia chromosome occurred. None of the secondary AML cases evolving from pre-existing PMF showed MPL(W515K/L) (n=4). We conclude that MPL(W515L) occurs in a considerable proportion of acute megakaryoblastic leukaemias with myelofibrosis unrelated to PMF.

  1. Study of chronic kidney disease-mineral bone disorders in newly detected advanced renal failure patients: A Hospital-based cross-sectional study

    Directory of Open Access Journals (Sweden)

    Praveen Kumar Etta

    2017-01-01

    Full Text Available We aim to evaluate the disturbances in mineral metabolism, abnormalities in bone mineral density (BMD, and extraskeletal calcification in newly detected, untreated predialysis stage 4 and 5 chronic kidney disease (CKD patients at a tertiary care hospital in North India. This is cross-sectional observational study. A total of 95 (68 males, 27 females newly detected patients underwent clinical evaluation, biochemical assessment [serum calcium, phosphorus, alkaline phosphatase (ALP, albumin, creatinine, intact parathyroid hormone (iPTH, 25- hydroxyvitamin D (25(OHD], BMD measurement (at spine, hip, and forearm by dual-energy X-ray absorptiometry (DXA, lateral abdominal radiograph [for abdominal aortic calcification (AAC], skeletal survey (to look for any abnormality including fractures, and echocardiography [for any cardiac valvular calcification (CVC]. Symptoms related to CKD-mineral bone disorder were seen in 33.6% of the study patients. Prevalence of hypocalcemia, hyperphosphatemia, hyperparathyroidism, and hypovitaminosis D was 64.2%, 81.1%, 49.5%, and 89.5%, respectively. CVC was seen in 22.1% of patients on echocardiography, mostly involving the mitral valve. Patients with CVC were more likely to be males and smokers. There was no significant difference in iPTH levels between patients with or without CVC. AAC was seen in 10.5% of patients on lateral abdominal X-ray. Patients with AAC had higher levels of iPTH, phosphorus, and ALP and lower levels of calcium compared to patients without AAC. BMD by DXA showed a low bone mass in 41.05% of our patients and was more prevalent in CKD stage 5. Most of the study patients had hyperparathyroidism and low 25(OHD levels. Our study shows that newly detected, naïve Indian CKD patients have a high prevalence of disturbances of mineral metabolism including hyperparathyroidism, Vitamin D deficiency, abnormal BMD, and valvular and vascular calcification, even before initiating dialysis.

  2. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia

    DEFF Research Database (Denmark)

    Saglio, Giuseppe; Kim, Dong-Wook; Issaragrisil, Surapol

    2010-01-01

    Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib. We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase.......Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib. We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase....

  3. Revisiting the emissions-energy-trade nexus: evidence from the newly industrializing countries.

    Science.gov (United States)

    Ahmed, Khalid; Shahbaz, Muhammad; Kyophilavong, Phouphet

    2016-04-01

    This paper applies Pedroni's panel cointegration approach to explore the causal relationship between trade openness, carbon dioxide emissions, energy consumption, and economic growth for the panel of newly industrialized economies (i.e., Brazil, India, China, and South Africa) over the period of 1970-2013. Our panel cointegration estimation results found majority of the variables cointegrated and confirm the long-run association among the variables. The Granger causality test indicates bidirectional causality between carbon dioxide emissions and energy consumption. A unidirectional causality is found running from trade openness to carbon dioxide emission and energy consumption and economic growth to carbon dioxide emissions. The results of causality analysis suggest that the trade liberalization in newly industrialized economies induces higher energy consumption and carbon dioxide emissions. Furthermore, the causality results are checked using an innovative accounting approach which includes forecast-error variance decomposition test and impulse response function. The long-run coefficients are estimated using fully modified ordinary least square (FMOLS) method, and results conclude that the trade openness and economic growth reduce carbon dioxide emissions in the long run. The results of FMOLS test sound the existence of environmental Kuznets curve hypothesis. It means that trade liberalization induces carbon dioxide emission with increased national output, but it offsets that impact in the long run with reduced level of carbon dioxide emissions.

  4. Transformation of organic N newly added to red soil treated with different cultural practices

    Institute of Scientific and Technical Information of China (English)

    ZhangQin-Zheng; YeQing-Fu; 等

    1998-01-01

    By using 15N tracer method,transformation of organic N,which wqas newly added to red soil treated with different cultural practices,was studied under thelaboratory incubation condition.The experimental results showed that the transformation of N from newly added organic matter and soil native pool during incubation was influenced by cultural practice treatment beforeincubation.Fallow was favorable to the mineralization of newly added organic N and soil N compared with the planting wheat treatment.Planting wheat greatly increased the loss of soil N.Application of fertilizers stimulated the mineralization of newly added organic N and application of organic matter reduced the mineralization,but stimulated microbialtransformation of newly adde4d organic N.

  5. Endotoxin and cancer chemo-prevention.

    Science.gov (United States)

    Mastrangelo, Giuseppe; Fadda, Emanuela; Cegolon, Luca

    2013-10-01

    Reduced rates of lung cancer have been observed in several occupational groups exposed to high levels of organic dusts contaminated by endotoxin. The underlying anti-neoplastic mechanism of endotoxin may be an increased secretion of endogenous anti-neoplastic mediators and activation of the toll-like receptors (TLR). A detoxified endotoxin derivative, Monophosphoryl Lipid A (MPL(®)) is marketed in Europe since 1999 as part of the adjuvant systems in allergy vaccines for treatment of allergic rhino-conjunctivitis and allergic asthma. Over 200,000 patients have used them to date (nearly 70% in Germany). Since detailed exposure (MPL(®) dose and timing of administration) and individual data are potentially available, an observational follow-up study could be conducted in Germany to investigate the protective effect of MPL(®) against cancer, comparing cancer incidence in two groups of patients with allergic rhinitis: those treated with allergoids plus MPL(®) and those treated with a vaccine including the same allergoids but not MPL(®). The protective effect of MPL(®) could be quantified in ever and never smokers. If this proposed observational study provides evidence of protective effects, MPL(®) could be immediately used as a chemo-preventive agent since it is already in use as adjuvant in human vaccines against cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Electrochemically synthesized stretchable polypyrrole/fabric electrodes for supercapacitor

    International Nuclear Information System (INIS)

    Yue, Binbin; Wang, Caiyun; Ding, Xin; Wallace, Gordon G.

    2013-01-01

    Wearable electronics offer the combined advantages of both electronics and fabrics. Being an indispensable part of these electronics, lightweight, stretchable and wearable power sources are strongly demanded. Here we describe a daily-used cotton fabric coated with polypyrrole as electrode for stretchable supercapacitors. Polypyrrole was synthesized on the Au coated fabric via an electrochemical polymerization process with p-toluenesulfonic acid (p-TS) as dopant from acetonitrile solution. This material was characterized with FESEM, tensile stress, and studied as a supercapacitor electrode in 1.0 M NaCl. This conductive textile electrode can sustain up to 140% strain without electric failure. It delivers a high specific capacitance of 254.9 F g −1 at a scan rate of 10 mV s −1 , and keeps almost unchanged at an applied strain (i.e. 30% and 50%) but with an improved cycling stability

  7. Identification of GAD65 AA 114-122 reactive 'memory-like' NK cells in newly diagnosed Type 1 diabetic patients by HLA-class I pentamers.

    Science.gov (United States)

    Perri, Valentina; Gianchecchi, Elena; Cifaldi, Loredana; Pellegrino, Marsha; Giorda, Ezio; Andreani, Marco; Cappa, Marco; Fierabracci, Alessandra

    2017-01-01

    Type 1 diabetes is an autoimmune disease, in which pancreatic β cells are destroyed by autoreactive T cells in genetically predisposed individuals. Serum beta cell autoantibody specificities have represented the mainstay for classifying diabetes as autoimmune-mediated and for stratifying risk in first-degree relatives. In recent years, approaches were attempted to solve the difficult issue of detecting rare antigen-specific autoreactive T cells and their significance to etiopathogenesis such as the use of the MHC multimer technology. This tool allowed the specific detection of increased percentages of GAD65 autoreactive T cells by means of HLA A*02:01 GAD65 AA 114-122 pentamers in newly diagnosed diabetics. Here we provide evidence that GAD65 AA 114-122 pentamers can depict a GAD65 AA114-122 peptide expandable population of functionally and phenotypically skewed, preliminary characterized CD3-CD8dullCD56+ 'memory-like' NK cells in PBMC of newly diagnosed diabetics. Our data suggest that the NK cell subset could bind the HLA class I GAD65 AA 114-122 pentamer through ILT2 inhibitory receptor. CD107a expression revealed increased degranulation of CD3-CD8dullCD56+ NK cells in GAD65 AA 114-122 and FLU peptide expanded peripheral blood mononuclear cells of diabetics following GAD65 AA 114-122 peptide HLA A*02:01 presentation in respect to the unpulsed condition. CD107a expression was enriched in ILT2 positive NK cells. As opposite to basal conditions where similar percentages of CD3-CD56+ILT2+ cells were detected in diabetics and controls, CD3-CD56+CD107a+ and CD3-CD56+ILT2+CD107a+ cells were significantly increased in T1D PBMC either GAD65 AA 114-122 or FLU peptides stimulated after co-culture with GAD65 AA 114-122 pulsed APCs. As control, healthy donor NK cells showed similar degranulation against both GAD65 AA 114-122 pulsed and unpulsed APCs. The pathogenetic significance of the CD3-CD8dullCD56+ 'memory-like NK cell subset' with increased response upon secondary

  8. Synthesis of Sulochrin-125I and Its Binding Affinity as α-Glucosidase Inhibitor using Radioligand Binding Assay (RBA Method

    Directory of Open Access Journals (Sweden)

    W. Lestari

    2014-04-01

    Full Text Available Most of diabetics patients have type 2 diabetes mellitus or non insulin dependent diabetes mellitus. Treatment type 2 diabetes mellitus can be done by inhibiting α-glucosidase enzyme which converts carbohydrates into glucose. Sulochrin is one of the potential compounds which can inhibit the function of α-glucosidase enzyme. This study was carried out to obtain data of sulochrin binding with α-glucosidase enzyme as α-glucosidase inhibitor using Radioligand Binding Assay (RBA method. Primary reagent required in RBA method is labeled radioactive ligand (radioligand. In this study, the radioligand was sulochrin-125I and prior to sulochrin-125I synthesis, the sulochrin-I was synthesized. Sulochrin-I and sulochrin-125I were synthesized and their bindings were studied using Radioligand Binding Assay method. Sulochrin-I was synthesized with molecular formula C17H15O7I and molecular weight 457.9940. Sulochrin-125I was synthesized from sulochrin-I by isotope exchange method. From the RBA method, dissociation constant (Kd and maximum binding (Bmax were obtained 26.316 nM and Bmax 9.302 nM respectively. This low Kd indicated that sulochrin was can bind to α-glucosidase

  9. Effect of surfactant and surfactant blends on pseudoternary phase diagram behavior of newly synthesized palm kernel oil esters

    Directory of Open Access Journals (Sweden)

    Mahdi ES

    2011-06-01

    Full Text Available Elrashid Saleh Mahdi1, Mohamed HF Sakeena1, Muthanna F Abdulkarim1, Ghassan Z Abdullah1,3, Munavvar Abdul Sattar2, Azmin Mohd Noor11Department of Pharmaceutical Technology, 2Department of Physiology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang, Malaysia; 3Department of Pharmaceutical Technology, International Medical University, Bukit Jalil, Kuala Lumpur, MalaysiaBackground: The purpose of this study was to select appropriate surfactants or blends of surfactants to study the ternary phase diagram behavior of newly introduced palm kernel oil esters.Methods: Nonionic surfactant blends of Tween® and Tween®/Span® series were screened based on their solubilization capacity with water for palm kernel oil esters. Tween® 80 and five blends of Tween® 80/Span® 80 and Tween® 80/Span® 85 in the hydrophilic-lipophilic balance (HLB value range of 10.7–14.0 were selected to study the phase diagram behavior of palm kernel oil esters using the water titration method at room temperature.Results: High solubilization capacity was obtained by Tween® 80 compared with other surfactants of Tween® series. High HLB blends of Tween® 80/Span® 85 and Tween® 80/Span® 80 at HLB 13.7 and 13.9, respectively, have better solubilization capacity compared with the lower HLB values of Tween® 80/Span® 80. All the selected blends of surfactants were formed as water-in-oil microemulsions, and other dispersion systems varied in size and geometrical layout in the triangles. The high solubilization capacity and larger areas of the water-in-oil microemulsion systems were due to the structural similarity between the lipophilic tail of Tween® 80 and the oleyl group of the palm kernel oil esters.Conclusion: This study suggests that the phase diagram behavior of palm kernel oil esters, water, and nonionic surfactants is not only affected by the HLB value, but also by the structural similarity between palm kernel oil esters and the surfactant

  10. Solid phase syntheses of oligoureas

    Energy Technology Data Exchange (ETDEWEB)

    Burgess, K.; Linthicum, D.S.; Russell, D.H.; Shin, H.; Shitangkoon, A.; Totani, R.; Zhang, A.J.; Ibarzo, J. [Texas A& M Univ., College Station, TX (United States)

    1997-02-19

    Isocyanates 7 were formed from monoprotected diamines 3 or 6, which in turn can be easily prepared from commercially available N-BOC- or N-FMOC-protected amino acid derivatives. Isocyanates 7, formed in situ, could be coupled directly to a solid support functionalized with amine groups or to amino acids anchored on resins using CH{sub 2}Cl{sub 2} as solvent and an 11 h coupling time at 25 {degree}C. Such couplings afforded peptidomimetics with an N-phthaloyl group at the N-terminus. The optimal conditions identified for removal of the N-phthaloyl group were to use 60% hydrazine in DMF for 1-3 h. Several sequences of amino acids coupled to ureas (`peptidic ureas`) and of sequential urea units (`oligoureas`) were prepared via solid phase syntheses and isolated by HPLC. Partition coefficients were measured for two of these peptidomimetics, and their water solubilities were found to be similar to the corresponding peptides. A small library of 160 analogues of the YGGFL-amide sequence was prepared via Houghten`s tea bag methodology. This library was tested for binding to the anti-{beta}-endorphin monoclonal antibody. Overall, this paper describes methodology for solid phase syntheses of oligourea derivatives with side chains corresponding to some of the protein amino acids. The chemistry involved is ideal for high-throughput syntheses and screening operations. 51 refs., 3 figs., 2 tabs.

  11. Proteoglycon synthesis by articular chondrocytes in agarose culture

    International Nuclear Information System (INIS)

    Sweet, M.B.E.; Grisillo, A.; Coehlo, A.; Schnitzler, C.M.

    1987-01-01

    Articular chondrocytes were isolated from knee joints of full-term bovine foetuses and grown in long-term agarose cultures. At intervals, cultures were labelled with 35 S-[sulphate] or D[6- 3 H] glucosamine. Newly synthesized proteoglycans were extracted with 4 M guanidine HCl and purified by isopycnic density gradient centrifugation or on DEAE cellulose in the presence of 8 M urea. Characterization of the proteoglycans revealed them to be identical in size to those present in the tissue and to be similarly capable of aggregation with hyaluronate. Newly synthesized chondroitin sulphate chains were identical in size, but newly synthesized keratan sulphate chains were somewhat larger than those present in the tissue. The newly synthesized proteoglycans were shown to contain the same range of O-linked oligosaccharides identified in proteoglycans of the Swarm rat chondrosarcoma. Cartilage-specific proteoglycan continued to be synthesized by the chondrocytes for up to 60 days; however, with time, proportionately more of a small non-aggregating proteoglycan appeared

  12. New bioactive silver(I) complexes: Synthesis, characterization, anticancer, antibacterial and anticarbonic anhydrase II activities

    Science.gov (United States)

    Ozdemir, Ummuhan O.; Ozbek, Neslihan; Genc, Zuhal Karagoz; İlbiz, Firdevs; Gündüzalp, Ayla Balaban

    2017-06-01

    Silver(I) complexes of alkyl sulfonic acide hydrazides were newly synthesized as homologous series. Methanesulfonic acide hydrazide (L1), ethanesulfonic acide hydrazide (L2), propanesulfonic acide hydrazide (L3) and butanesulfonic acide hydrazide (L4) were used for complexation with Ag(I) ions. The silver complexes obtained in the mol ratio of 1:2 have the structural formula as Ag(L1)2NO3 (I), Ag(L2)2NO3 (II), Ag(L3)2NO3(III), (Ag(L4)2NO3 (IV). The Ag(I) complexes exhibit distorted linear two-fold coordination in [AgL2]+ cations with uncoordinated nitrates. Ligands are chelated with silver(I) ions through unsubstituted primary nitrogen in hydrazide group. Ag(I) complexes were characterized by using elemental analysis, spectroscopic methods (FT-IR, LC-MS), magnetic susceptibility and conductivity measurements. Silver(I) complexes were optimized using PBEPBE/LanL2DZ/DEF2SV basic set performed by DFT method with the Gaussian 09 program package. The geometrical parameters, frontier molecular orbitals (HOMOs and LUMOs) and molecular electrostatic potential (MEP) mapped surfaces of the optimized geometries were also determined by this quantum set. The anticancer activities of silver(I) complexes on MCF-7 human breast cancer cell line were investigated by comparing IC50 values. The antibacterial activities of complexes were studied against Gram positive bacteria; S. aureus ATCC 6538, B. subtilis ATCC 6633, B. cereus NRRL-B-3711, E. faecalis ATCC 29212 and Gram negative bacteria; E. coli ATCC 11230, P. aeruginosa ATCC 15442, K. pneumonia ATCC 70063 by using disc diffusion method. The inhibition activities of Ag(I) complexes on carbonic anhydrase II enzyme (hCA II) were also investigated by comparing IC50 and Ki values. The biological activity screening shows that Ag(I) complex of butanesulfonicacidehydrazide (IV) has the highest activity against tested breast cancer cell lines MCF-7, Gram positive/Gram negative bacteria and carbonic anhydrase II (hCA II) isoenzyme.

  13. Investigation of formation constant of complex of a new synthesized tripodal ligand with Cu2+ using rank annihilation factor analysis in surfactant media

    Directory of Open Access Journals (Sweden)

    R. Golbedaghi

    2014-01-01

    Full Text Available The complex formation between a newly synthesized tripodal ligand and the cation Cu2+ in water and surfactant media was studied spectrophotometrically using rank annihilation factor analysis (RAFA. According to molar ratio data the stoichiometry of complexation between the ligand and the cation Cu2+ was 1:1. Formation constant of this complex was derived using RAFA on spectrophotometric data. The performance of the method has been evaluated by using synthetic data. Also concentration and spectral profiles of ligand and complex can be obtained by using the stability constant and appropriate equations. The effect of surfactants such as sodium dodecyl sulfate (SDS, cetyltrimethylammonium bromide (CTAB and Triton X-100 on complex formation constant of Cu2+ with the ligand was investigated.

  14. Synthesis of Novel C-2- or C-15-Labeled BODIPY—Estrone Conjugates

    Directory of Open Access Journals (Sweden)

    Ildikó Bacsa

    2018-04-01

    Full Text Available Novel BODIPY–estrone conjugates were synthesized via Cu(I-catalyzed azide–alkyne cycloaddition (CuAAC. Estrone-alkynes or an estrone-azide as starting compounds were synthesized via Michael addition or Sonogashira reaction as key steps. Fluorescent dyes based on BODIPY-core were provided by azide or alkyne functional groups. Fluorescent labeling of estrone was efficiently achieved at the C-2 or C-15 position. The newly-elaborated coupling procedures might have a broad applicability in the synthesis of fluorescent-labeled estrone conjugates suitable for biological assays.

  15. Possible origin of Saturn's newly discovered outer ring

    International Nuclear Information System (INIS)

    Moehlmann, D.

    1986-01-01

    Within a planetogonic model the self-gravitationally caused formation of pre-planetary and pre-satellite rings from an earlier thin disk is reported. The theoretically derived orbital radii of these rings are compared with the orbital levels in the planetary system and the satellite systems of Jupiter, Saturn and Uranus. From this comparison it is concluded that at the radial position of Saturn's newly discovered outer ring an early pre-satellite ring of more or less evolved satellites could have existed. These satellites should have been disturbed in their evolution by the gravitation of the neighbouring massive satellite Titan. The comparison also may indicate similarities between the asteroidal belt and the newly discovered outer ring of Saturn

  16. Oral Cancer Knowledge Assessment: Newly Graduated versus Senior Dental Clinicians

    Science.gov (United States)

    Salgado de Souza, Ricardo; Gallego Arias Pecorari, Vanessa; Lauria Dib, Luciano

    2018-01-01

    The present study assessed the level of dentists' knowledge regarding oral cancer in the city of São Paulo, Brazil. A questionnaire was used to compare the level of knowledge among newly graduated and senior clinicians. A total of 20,154 e-mails were correctly delivered to the dentists registered in the database of the Regional Dentistry Council of São Paulo, and 477 (2.36%) responses were received. This sample consisted of 84 newly graduated clinicians and 105 senior clinicians. For the statistical analysis, the chi-square test and the logistic regression analysis were performed with α = 0.05, and the results were described herein. According to their knowledge level, the results were statistically different between the groups, since 19% of the newly graduated clinicians were evaluated with knowledge grade A (excellent) in comparison to 6.7% of the senior clinicians. In spite of the results indicated that newly graduated clinicians' knowledge regarding oral cancer was 2.1 times higher, 34.5% of the professionals in this group had regular or poor knowledge on the subject, and several questions relating to clinical characteristics and risk factors indicated that there still exist some knowledge gaps, demonstrating that there is a need for further studies and information activities addressing oral cancer. PMID:29666649

  17. Rat mesangial cells in vitro synthesize a spectrum of proteoglycan species including those of the basement membrane and interstitium

    DEFF Research Database (Denmark)

    Thomas, G J; Shewring, L; McCarthy, K J

    1995-01-01

    is localized in the mesangium but is not found in the pericapillary glomerular basement membrane (GBM). Further characterization of the proteoglycans synthesized by RMC in vitro revealed: (i) a second large CSPG, identified as versican; (ii) two small dermatan sulphate proteoglycans identified as biglycan...

  18. Appearance of newly formed mRNA and rRNA as ribonucleoprotein-particles in the cytoplasmic subribosomal fraction of pea embryos

    International Nuclear Information System (INIS)

    Takahashi, Noribumi; Takaiwa, Fumio; Fukuei, Keisuke; Sakamaki, Tadashi; Tanifuji, Shigeyuki

    1977-01-01

    Incorporation studies with 3 H-uridine or 3 H-adenosine showed that germinating pea embryos synthesize all types of poly A(+) RNA, rRNA and 4-5S RNA at the early stage of germination. After the pulse labeling for 30 min, only heterodisperse RNA and 4-5S RNA appeared in the cytoplasm as labeled RNA species. At this time the radioactivity was associated with cytoplasmic structures heavier than 80S and RNP particles of 68-70S, 52-55S, 36-38S and 20-22S which are presumed to be free mRNP particles in plants. When the pulse-labeled embryos were incubated for a further 60 min in an isotope-free medium, the labeled 17S and 25S rRNA emerged in the cytoplasm, together with labeled heterodisperse and 4-5S RNAs. More radioactivity accumulated in the regions of the polysome, 62-65S and 38-42S particles. The results of analysis of RNAs extracted from the whole cytoplasm, polysome or subribosomal fractions indicated that small subunits of newly formed ribosomes appear more rapidly in the cytoplasm than new large subunits, which accumulate for a while as free particles in the cytoplasm than are incorporated into polysomes. The actinomycin treatment which caused preferential inhibition of rRNA synthesis reduced the accumulation of free, newly formed ribosome subunits and partially permitted detection of the presumed mRNP particles in the subribosomal region even after the chase treatment. (auth.)

  19. Operational Design that Synthesizes Art and Science

    Science.gov (United States)

    2011-05-04

    FINAL 3. DATES COVERED (From - To) Feb - May 2011 4. TITLE AND SUBTITLE OPERATIONAL DESIGN THAT SYNTHESIZES ART AND SCIENCE 5a...TITLE AND SUBTITLE Operational Design That Synthesizes Art And Science 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR...proponents of EBO view warfare as only a science and not a combination of art and science . 9 Another main point of contention centered on the term

  20. Dynamics of L-H transition and I-phase in EAST

    DEFF Research Database (Denmark)

    Xu, G. S.; Wang, H. Q.; Xu, M.

    2014-01-01

    The turbulence and flows at the plasma edge during the L-I-H, L-I-L and single-step L-H transitions have been measured directly using two reciprocating Langmuir probe systems at the outer midplane with several newly designed probe arrays in the EAST superconducting tokamak. The E × B velocity, tu...

  1. Career Motivation in Newly Licensed Registered Nurses: What Makes Them Remain

    Science.gov (United States)

    Banks, Zarata Mann; Bailey, Jessica H.

    2010-01-01

    Despite vast research on newly licensed registered nurses (RNs), we don't know why some newly licensed registered nurses remain in their current jobs and others leave the nursing profession early in their career. Job satisfaction, the most significant factor emerging from the literature, plays a significant role in nurses' decisions to remain in…

  2. Fully automated parallel oligonucleotide synthesizer

    Czech Academy of Sciences Publication Activity Database

    Lebl, M.; Burger, Ch.; Ellman, B.; Heiner, D.; Ibrahim, G.; Jones, A.; Nibbe, M.; Thompson, J.; Mudra, Petr; Pokorný, Vít; Poncar, Pavel; Ženíšek, Karel

    2001-01-01

    Roč. 66, č. 8 (2001), s. 1299-1314 ISSN 0010-0765 Institutional research plan: CEZ:AV0Z4055905 Keywords : automated oligonucleotide synthesizer Subject RIV: CC - Organic Chemistry Impact factor: 0.778, year: 2001

  3. Meeting and activating the newly unemployed

    DEFF Research Database (Denmark)

    Rotger, Gabriel Pons

    -demanding activity. As intensive activation is usually accompanied by intensive search monitoring, it is important to disentangling the contribution of the costly activation programs from that of caseworker meetings. Using Danish data for the period 2010-13, the paper shows that requiring newly unemployed intensive...... activation, contrary to job search meetings, reduces employment and increases sickness benefit claims....

  4. Widely tunable THz synthesizer

    Science.gov (United States)

    Hindle, F.; Mouret, G.; Eliet, S.; Guinet, M.; Cuisset, A.; Bocquet, R.; Yasui, T.; Rovera, D.

    2011-09-01

    The generation of cw-THz radiation by photomixing is particularly suited to the high resolution spectroscopy of gases; nevertheless, until recently, it has suffered from a lack of frequency metrology. Frequency combs are a powerful tool that can transfer microwave frequency standards to optical frequencies and a single comb has permitted accurate (10-8) THz frequency synthesis with a limited tuning range. A THz synthesizer composed of three extended cavity laser diodes phase locked to a frequency comb has been constructed and its utility for high resolution gas phase spectroscopy demonstrated. The third laser diode allows a larger tuning range of up to 300 MHz to be achieved without the need for large frequency excursions, while the frequency comb provides a versatile link to be established from any traceable microwave frequency standard. The use of a single frequency comb as a reference for all of the cw-lasers eliminates the dependency of synthesized frequency on the carrier envelope offset frequency. This greatly simplifies the frequency comb stabilization requirements and leads to a reduced instrument complexity.

  5. Competence of newly qualified registered nurses from a nursing college

    Directory of Open Access Journals (Sweden)

    BG Morolong

    2005-09-01

    Full Text Available The South African education and training system, through its policy of outcomesbased education and training, has made competency a national priority. In compliance to this national requirement of producing competent learners, the South African Nursing Council ( 1999 B require that the beginner professional nurse practitioners and midwives have the necessary knowledge, skills, attitudes and values which will enable them to render efficient professional service. The health care system also demands competent nurse practitioners to ensure quality in health care. In the light of competency being a national priority and a statutory demand, the research question that emerges is, how competent are the newly qualified registered nurses from a specific nursing college in clinical nursing education? A quantitative, non-experimental contextual design was used to evaluate the competence of newly qualified registered nurses from a specific nursing college. The study was conducted in two phases. The first phase dealt with the development of an instrument together with its manual through the conceptualisation process. The second phase focused on the evaluation of the competency of newly qualified nurses using the instrument based on the steps of the nursing process. A pilot study was conducted to test the feasibility of the items of the instrument. During the evaluation phase, a sample of twenty-six newly qualified nurses was selected by simple random sampling from a target population of thirty-six newly qualified registered nurses. However, six participants withdrew from the study. Data was collected in two general hospitals where the newly qualified registered nurses were working. Observation and questioning were used as data collection techniques in accordance with the developed instrument. Measures were taken to ensure internal validity and reliability of the results. To protect the rights of the participants, the researcher adhered to DENOSA’S (1998

  6. The Arabidopsis nox mutant lacking carotene hydroxylase activity reveals a critical role for xanthophylls in photosystem I biogenesis.

    Science.gov (United States)

    Dall'Osto, Luca; Piques, Maria; Ronzani, Michela; Molesini, Barbara; Alboresi, Alessandro; Cazzaniga, Stefano; Bassi, Roberto

    2013-02-01

    Carotenes, and their oxygenated derivatives xanthophylls, are essential components of the photosynthetic apparatus. They contribute to the assembly of photosynthetic complexes and participate in light absorption and chloroplast photoprotection. Here, we studied the role of xanthophylls, as distinct from that of carotenes, by characterizing a no xanthophylls (nox) mutant of Arabidopsis thaliana, which was obtained by combining mutations targeting the four carotenoid hydroxylase genes. nox plants retained α- and β-carotenes but were devoid in xanthophylls. The phenotype included depletion of light-harvesting complex (LHC) subunits and impairment of nonphotochemical quenching, two effects consistent with the location of xanthophylls in photosystem II antenna, but also a decreased efficiency of photosynthetic electron transfer, photosensitivity, and lethality in soil. Biochemical analysis revealed that the nox mutant was specifically depleted in photosystem I function due to a severe deficiency in PsaA/B subunits. While the stationary level of psaA/B transcripts showed no major differences between genotypes, the stability of newly synthesized PsaA/B proteins was decreased and translation of psaA/B mRNA was impaired in nox with respect to wild-type plants. We conclude that xanthophylls, besides their role in photoprotection and LHC assembly, are also needed for photosystem I core translation and stability, thus making these compounds indispensable for autotrophic growth.

  7. The impact of the Malaysian minimum cigarette price law: findings from the ITC Malaysia Survey.

    Science.gov (United States)

    Liber, Alex C; Ross, Hana; Omar, Maizurah; Chaloupka, Frank J

    2015-07-01

    Study the effects of the 2011 Malaysian minimum price law (MPL) on prices of licit and illicit cigarette brands. Identify barriers to the MPL achieving positive public health effects. The International Tobacco Control Project's Southeast Asia survey collected information on Malaysian smokers' cigarette purchases (n=7520) in five survey waves between 2005 and 2012. Consumption-weighted comparisons of proportions tests and adjusted Wald tests were used to evaluate changes over time in violation rates of the inflation-adjusted MPL, the proportion of illicit cigarette purchases and mean prices. After the passage of the MPL, the proportion of licit brand cigarette purchases that were below the inflation-adjusted 2011 minimum price level fell substantially (before 3.9%, after 1.8%, p=0.002), while violation of the MPL for illicit brand cigarette purchases was unchanged (before 89.8%, after 91.9%, p=0.496). At the same time, the mean real price of licit cigarettes rose (p=0.006), while the mean real price of illicit cigarettes remained unchanged (p=0.134). The proportion of illicit cigarette purchases rose as well (before 13.4%, after 16.5%, p=0.041). The MPL appears not to have meaningfully changed cigarette prices in Malaysia, as licit brand prices remained well above and illicit brand prices remained well below the minimum price level before and after MPL's implementation. The increasing proportion of illicit cigarettes on the market may have undermined any positive health effects of the Malaysian MPL. The illicit cigarette trade must be addressed before a full evaluation of the Malaysian MPL's impact on public health can take place. The authors encourage the continued use of specific excise tax increases to reliably increase the price and decrease the consumption of cigarettes in Malaysia and elsewhere. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  8. Clinical heterogeneity in newly diagnosed Parkinson's disease

    NARCIS (Netherlands)

    Post, Bart; Speelman, Johannes D.; de Haan, Rob J.

    2008-01-01

    OBJECTIVE: To determine clinical heterogeneity in newly diagnosed Parkinson's disease using cluster analysis and to describe the subgroups in terms of impairment, disability, perceived quality of life, and use of dopaminergic therapy. METHODS: We conducted a k-means cluster analysis in a prospective

  9. Discovery of novel MHC-class I alleles and haplotypes in Filipino cynomolgus macaques (Macaca fascicularis) by pyrosequencing and Sanger sequencing: Mafa-class I polymorphism.

    Science.gov (United States)

    Shiina, Takashi; Yamada, Yukiho; Aarnink, Alice; Suzuki, Shingo; Masuya, Anri; Ito, Sayaka; Ido, Daisuke; Yamanaka, Hisashi; Iwatani, Chizuru; Tsuchiya, Hideaki; Ishigaki, Hirohito; Itoh, Yasushi; Ogasawara, Kazumasa; Kulski, Jerzy K; Blancher, Antoine

    2015-10-01

    Although the low polymorphism of the major histocompatibility complex (MHC) transplantation genes in the Filipino cynomolgus macaque (Macaca fascicularis) is expected to have important implications in the selection and breeding of animals for medical research, detailed polymorphism information is still lacking for many of the duplicated class I genes. To better elucidate the degree and types of MHC polymorphisms and haplotypes in the Filipino macaque population, we genotyped 127 unrelated animals by the Sanger sequencing method and high-resolution pyrosequencing and identified 112 different alleles, 28 at cynomolgus macaque MHC (Mafa)-A, 54 at Mafa-B, 12 at Mafa-I, 11 at Mafa-E, and seven at Mafa-F alleles, of which 56 were newly described. Of them, the newly discovered Mafa-A8*01:01 lineage allele had low nucleotide similarities (Filipino macaque population would identify these and other high-frequency Mafa-class I haplotypes that could be used as MHC control animals for the benefit of biomedical research.

  10. A frequency tracking synthesizer for beam diagnostic systems

    International Nuclear Information System (INIS)

    Peterson, D.; Marriner, J.

    1991-01-01

    In low and medium energy synchrotrons the beam revolution frequency changes by a large factor during the acceleration process. High production rates require that these machines cycle rapidly. In attempting to diagnose instabilities which develop during the acceleration process it is useful to be able to select some frequency segment between revolution harmonics for viewing. Most types of test equipment operating in the frequency domain, such as spectrum analyzers and network analyzers, are not suited to making direct measurements on such rapidly sweeping signals. Ideally, one would want to set the frequency frame of reference to the spot in the accelerating revolution harmonic domain where the measurements are to be made. A scheme using a direct digital synthesizer (DDS) was developed to provide this moving reference frame. This paper describes a synthesizer scheme combining digital and analog synthesizer techniques to allow tracking of signals during acceleration. Virtually any ratio of synthesizer to beam revolution frequency may be generated by this scheme. Details of hardware and measurement results are presented

  11. [Principles of nutrition in patients with newly appointed stoma].

    Science.gov (United States)

    Pachocka, Lucyna Małgorzata; Urbanik, Anna

    2016-01-01

    The treatment of intestinal stoma is often a difficult experience for patients and results in numerous problems in the physical, psychological and social aspects. Therefore, post-operative care of the patient with the newly appointed stoma should be taken by therapeutic team consisting of doctors, nurses, physiotherapists, dieticians, psychologists and social workers. Appropriate nutritional education of patients aims to improve their quality of life and to prevent from unpleasant ailments formed after the operation. The specific type of stoma may decide about certain dietary recommendations. The presented work provides a practical dietary recommendations for patients with newly appointed stoma.

  12. Pressure drop performance evaluation for test assemblies with the newly developed top and bottom nozzles

    International Nuclear Information System (INIS)

    Lee, S. K.; Park, N. K.; Su, J. M.; Kim, H. K.; Lee, J. N.; Kim, K. T.

    2003-01-01

    To perform the hydraulic test for the newly developed top and bottom nozzles, two kinds of test assemblies were manufactured i. e. one is the test assembly which has the newly developed top and bottom nozzles and the other is Guardian test assembly which is commercially in mass production now. The test results show that the test assembly with one top nozzle and two bottom nozzles has a greater pressure loss coefficient than Guardian test assembly by 60.9% and 90.4% at the bottom nozzle location. This cause is due to the debris filtering plate for bottom nozzle to improve a filtering efficiency aginst foreign material. In the region of mid grid and top nozzle, there is no difference in pressure loss coefficient between the test assemblies since the componet features in these regions are very similar or same each other. The loss coefficients are 14.2% and 21.9% for model A and B respectively in the scale of test assembly, and the value would be within the 10% in the scale of real fuel assembly. As a result of hydraulic performance evaluation, model A is superior to model B

  13. Two Newly Discovered Plants in Taiwan

    OpenAIRE

    Tian-Chuan Hsu; Jia-Jung Lin; Shih-Wen Chung

    2009-01-01

    Two herbs are newly discovered in Taiwan. Limnophila fragrans (G. Forst.) Seem. (Scrophulariaceae), native in SE Asia, is recognized from southern lowlands. Anagallis minima (L.) E. H. L. Krause (Primulaceae), native in N America and Europe, was found from northern mountainous region at low altitudes. In this study, descriptions, line drawings, color photos and a distribution map of the two species are provided.

  14. Newly-formed emotional memories guide selective attention processes: Evidence from event-related potentials.

    Science.gov (United States)

    Schupp, Harald T; Kirmse, Ursula; Schmälzle, Ralf; Flaisch, Tobias; Renner, Britta

    2016-06-20

    Emotional cues can guide selective attention processes. However, emotional stimuli can both activate long-term memory representations reflecting general world knowledge and engage newly formed memory representations representing specific knowledge from the immediate past. Here, the self-completion feature of associative memory was utilized to assess the regulation of attention processes by newly-formed emotional memory. First, new memory representations were formed by presenting pictures depicting a person either in an erotic pose or as a portrait. Afterwards, to activate newly-built memory traces, edited pictures were presented showing only the head region of the person. ERP recordings revealed the emotional regulation of attention by newly-formed memories. Specifically, edited pictures from the erotic compared to the portrait category elicited an early posterior negativity and late positive potential, similar to the findings observed for the original pictures. A control condition showed that the effect was dependent on newly-formed memory traces. Given the large number of new memories formed each day, they presumably make an important contribution to the regulation of attention in everyday life.

  15. Newly-formed emotional memories guide selective attention processes: Evidence from event-related potentials

    Science.gov (United States)

    Schupp, Harald T.; Kirmse, Ursula; Schmälzle, Ralf; Flaisch, Tobias; Renner, Britta

    2016-01-01

    Emotional cues can guide selective attention processes. However, emotional stimuli can both activate long-term memory representations reflecting general world knowledge and engage newly formed memory representations representing specific knowledge from the immediate past. Here, the self-completion feature of associative memory was utilized to assess the regulation of attention processes by newly-formed emotional memory. First, new memory representations were formed by presenting pictures depicting a person either in an erotic pose or as a portrait. Afterwards, to activate newly-built memory traces, edited pictures were presented showing only the head region of the person. ERP recordings revealed the emotional regulation of attention by newly-formed memories. Specifically, edited pictures from the erotic compared to the portrait category elicited an early posterior negativity and late positive potential, similar to the findings observed for the original pictures. A control condition showed that the effect was dependent on newly-formed memory traces. Given the large number of new memories formed each day, they presumably make an important contribution to the regulation of attention in everyday life. PMID:27321471

  16. A method for synthesizing response functions of NaI detectors to gamma rays

    International Nuclear Information System (INIS)

    Sie, S.H.

    1978-08-01

    A simple method of parametrizing the response function of NaI detectors to gamma rays is described, based on decomposition of the pulse-height spectrum into components associated with the actual detection processes. Smooth dependence of the derived parameters on the gamma-ray energy made it possible to generate a lineshape for any gamma-ray energy by suitable interpolation techniques. The method is applied in analysis of spectra measured with a 7.6 x 7.6 cm NaI detector in continuum gamma-ray study following (HI,xn) reaction

  17. A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme.

    Science.gov (United States)

    Rosenfeld, Myrna R; Ye, Xiaobu; Supko, Jeffrey G; Desideri, Serena; Grossman, Stuart A; Brem, Steven; Mikkelson, Tom; Wang, Daniel; Chang, Yunyoung C; Hu, Janice; McAfee, Quentin; Fisher, Joy; Troxel, Andrea B; Piao, Shengfu; Heitjan, Daniel F; Tan, Kay-See; Pontiggia, Laura; O'Dwyer, Peter J; Davis, Lisa E; Amaravadi, Ravi K

    2014-08-01

    Preclinical studies indicate autophagy inhibition with hydroxychloroquine (HCQ) can augment the efficacy of DNA-damaging therapy. The primary objective of this trial was to determine the maximum tolerated dose (MTD) and efficacy of HCQ in combination with radiation therapy (RT) and temozolomide (TMZ) for newly diagnosed glioblastoma (GB). A 3 + 3 phase I trial design followed by a noncomparative phase II study was conducted in GB patients after initial resection. Patients received HCQ (200 to 800 mg oral daily) with RT and concurrent and adjuvant TMZ. Quantitative electron microscopy and immunoblotting were used to assess changes in autophagic vacuoles (AVs) in peripheral blood mononuclear cells (PBMC). Population pharmacokinetic (PK) modeling enabled PK-pharmacodynamic correlations. Sixteen phase I subjects were evaluable for dose-limiting toxicities. At 800 mg HCQ/d, 3/3 subjects experienced Grade 3 and 4 neutropenia and thrombocytopenia, 1 with sepsis. HCQ 600 mg/d was found to be the MTD in this combination. The phase II cohort (n = 76) had a median survival of 15.6 mos with survival rates at 12, 18, and 24 mo of 70%, 36%, and 25%. PK analysis indicated dose-proportional exposure for HCQ. Significant therapy-associated increases in AV and LC3-II were observed in PBMC and correlated with higher HCQ exposure. These data establish that autophagy inhibition is achievable with HCQ, but dose-limiting toxicity prevented escalation to higher doses of HCQ. At HCQ 600 mg/d, autophagy inhibition was not consistently achieved in patients treated with this regimen, and no significant improvement in overall survival was observed. Therefore, a definitive test of the role of autophagy inhibition in the adjuvant setting for glioma patients awaits the development of lower-toxicity compounds that can achieve more consistent inhibition of autophagy than HCQ.

  18. Comparison of clinical grade type 1 polarized and standard matured dendritic cells for cancer immunotherapy

    DEFF Research Database (Denmark)

    Hansen, Morten; Hjortø, Gertrud Malene; Donia, Marco

    2013-01-01

    induction of type 1 effector T cells. Standard matured clinical grade DCs “sDCs” were compared with DCs matured with either of two type 1 polarizing maturation cocktails; the alpha-type-1 DCs “αDC1s” (TNF-α, IL-1β, IFN-γ, IFN-α, Poly(I:C)) and “mDCs” (monophosphoryl lipid A (MPL), IFN-γ) or a mixed cocktail...... – “mpDCs”, containing MPL, IFN-γ and PGE2. αDC1s and mDCs secreted IL-12 directly and following re-stimulation with CD40L-expressing cells and they mainly secreted the T effector cell attracting chemokines CXCL10 and CCL5 as opposed to sDCs that mainly secreted CCL22, known to attract regulatory T cells...

  19. The Propeptide of the Metalloprotease of Listeria monocytogenes Controls Compartmentalization of the Zymogen during Intracellular Infection▿

    OpenAIRE

    O'Neil, Heather S.; Forster, Brian M.; Roberts, Kari L.; Chambers, Andrew J.; Bitar, Alan Pavinski; Marquis, Hélène

    2009-01-01

    Integral to the virulence of the intracellular bacterial pathogen Listeria monocytogenes is its metalloprotease (Mpl). Mpl regulates the activity and compartmentalization of the bacterial broad-range phospholipase C (PC-PLC). Mpl is secreted as a proprotein that undergoes intramolecular autocatalysis to release its catalytic domain. In related proteases, the propeptide serves as a folding catalyst and can act either in cis or in trans. Propeptides can also influence protein compartmentalizati...

  20. Pollen parameters estimates of genetic variability among newly ...

    African Journals Online (AJOL)

    Pollen parameters estimates of genetic variability among newly selected Nigerian roselle (Hibiscus sabdariffa L.) genotypes. ... Estimates of some pollen parameters where used to assess the genetic diversity among ... HOW TO USE AJOL.

  1. Tricks of the trade: time management tips for newly qualified doctors.

    Science.gov (United States)

    Offiah, Gozie; Doherty, Eva

    2018-03-01

    The transition from medical student to doctor is an important milestone. The discovery that their time is no longer their own and that the demands of their job are greater than the time they have available is extremely challenging. At a recent surgical boot camp training programme, 60 first-year surgical trainees who had just completed their internship were invited to reflect on the lessons learnt regarding effective time management and to recommend tips for their newly qualified colleagues. They were asked to identify clinical duties that were considered urgent and important using the time management matrix and the common time traps encountered by newly qualified doctors. The surgical trainees identified several practical tips that ranged from writing a priority list to working on relationships within the team. These tips are generic and so applicable to all newly qualified medial doctors. We hope that awareness of these tips from the outset as against learning them through experience will greatly assist newly qualified doctors. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Chest Radiographic Findings in Newly Diagnosed Pulmonary ...

    African Journals Online (AJOL)

    Five hundred newly diagnosed cases of Pulmonary Tuberculosis were treated with directly observed short-course treatment and 100 of them had chest radiographic examination done. The various chest radiographic patterns in the 100 subjects were studied and included: Fluffy exudative changes 80(80%), fibrosis 70(70%) ...

  3. Transport stress induces heart damage in newly hatched chicks via blocking the cytoprotective heat shock response and augmenting nitric oxide production.

    Science.gov (United States)

    Sun, F; Zuo, Y-Z; Ge, J; Xia, J; Li, X-N; Lin, J; Zhang, C; Xu, H-L; Li, J-L

    2018-04-20

    Transport stress affects the animal's metabolism and psychological state. As a pro-survival pathway, the heat shock response (HSR) protects healthy cells from stressors. However, it is unclear whether the HSR plays a role in transport stress-induced heart damage. To evaluate the effects of transport stress on heart damage and HSR protection, newly hatched chicks were treated with transport stress for 2 h, 4 h and 8 h. Transport stress caused decreases in body weight and increases in serum creatine kinase (CK) activity, nitric oxide (NO) content in heart tissue, cardiac nitric oxide syntheses (NOS) activity and NOS isoforms transcription. The mRNA expression of heat shock factors (HSFs, including HSF1-3) and heat shock proteins (HSPs, including HSP25, HSP40, HSP47, HSP60, HSP70, HSP90 and HSP110) in the heart of 2 h transport-treated chicks was upregulated. After 8 h of transport stress in chicks, the transcription levels of the same HSPs and HSF2 were reduced in the heart. It was also found that the changes in the HSP60, HSP70 and HSP90 protein levels had similar tendencies. These results suggested that transport stress augmented NO generation through enhancing the activity of NOS and the transcription of NOS isoforms. Therefore, this study provides new evidence that transport stress induces heart damage in the newly hatched chicks by blocking the cytoprotective HSR and augmenting NO production.

  4. Newly graduated nurses' empowerment regarding professional competence and other work-related factors.

    Science.gov (United States)

    Kuokkanen, Liisa; Leino-Kilpi, Helena; Numminen, Olivia; Isoaho, Hannu; Flinkman, Mervi; Meretoja, Riitta

    2016-01-01

    Although both nurse empowerment and competence are fundamental concepts of describing newly graduated nurses' professional development and job satisfaction, only few studies exist on the relationship between these concepts. Therefore, the purpose of this study was to determine how newly graduated nurses assess their empowerment and to clarify professional competence compared to other work-related factors. A descriptive, cross-sectional and correlational design was applied. The sample comprised newly graduated nurses (n = 318) in Finland. Empowerment was measured using the 19-item Qualities of an Empowered Nurse scale and the Nurse Competence Scale measured nurses' self-assessed generic competence. In addition to demographic data, the background data included employment sector (public/private), job satisfaction, intent to change/leave job, work schedule (shifts/business hours) and assessments of the quality of care in the workplace. The data were analysed statistically by using Spearman's correlation coefficient as well as the One-Way and Multivariate Analysis of Variance. Cronbach's alpha coefficient was used to estimate the internal consistency. Newly graduated nurses perceived their level of empowerment and competence fairly high. The association between nurse empowerment and professional competence was statistically significant. Other variables correlating positively to empowerment included employment sector, age, job satisfaction, intent to change job, work schedule, and satisfaction with the quality of care in the work unit. The study indicates competence had the strongest effect on newly graduated nurses' empowerment. New graduates need support and career opportunities. In the future, nurses' further education and nurse managers' resources for supporting and empowering nurses should respond to the newly graduated nurses' requisites for attractive and meaningful work.

  5. Method of synthesizing pyrite nanocrystals

    Science.gov (United States)

    Wadia, Cyrus; Wu, Yue

    2013-04-23

    A method of synthesizing pyrite nanocrystals is disclosed which in one embodiment includes forming a solution of iron (III) diethyl dithiophosphate and tetra-alkyl-ammonium halide in water. The solution is heated under pressure. Pyrite nanocrystal particles are then recovered from the solution.

  6. 77 FR 15819 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-03-16

    ... to the Book that (1) provide liquidity of 0.60% or more of the US CADV, (2) maintain a ratio of... ratio of executed liquidity adding volume to total volume of greater than 50%. In addition, the Exchange... Schedule (``Fee Schedule'') to (i) Increase the fee for Mid-Point Passive Liquidity (``MPL'') orders...

  7. Two Newly Discovered Plants in Taiwan

    Directory of Open Access Journals (Sweden)

    Tian-Chuan Hsu

    2009-11-01

    Full Text Available Two herbs are newly discovered in Taiwan. Limnophila fragrans (G. Forst. Seem. (Scrophulariaceae, native in SE Asia, is recognized from southern lowlands. Anagallis minima (L. E. H. L. Krause (Primulaceae, native in N America and Europe, was found from northern mountainous region at low altitudes. In this study, descriptions, line drawings, color photos and a distribution map of the two species are provided.

  8. Optimisation of the microporous layer for a polybenzimidazole-based high temperature PEMFC - effect of carbon content

    Energy Technology Data Exchange (ETDEWEB)

    Lobato, J.; Canizares, P.; Rodrigo, M.A.; Ubeda, D.; Pinar, F.J.; Linares, J.J. [Department of Chemical Engineering, University of Castilla-La Mancha, Av. Camilo Jose Cela, n 12. 13071, Ciudad Real (Spain)

    2010-10-15

    This work aims at studying the role of the microporous layer (MPL) in electrodes prepared for high temperature PBI-based PEMFC. The two main components of this layer are carbon black and a polymeric binder (Teflon). This work addresses the effect of the MPL carbon amount on the performance of a high temperature PEMFC. Thus, gas diffusion layers (GDLs) containing MPL with different carbon contents (from 0.5 to 4 mg cm{sup -2}) were prepared. Firstly, they were physically characterised by Hg-porosimetry measuring pore size distribution, porosity, tortuosity and mean pore size. Permeability measurements were also performed. The higher the carbon content was the lower both porosity and permeability were. Afterwards, electrodes were prepared with these GDLs and were electrochemically characterised. Electrochemical surface area (ESA) was determined and fuel cell performance was evaluated under different fuel and comburent stoichiometries, supporting these results with impedance spectra. This made it possible to see the benefits of the MPL inclusion in the electrode structure, with a significant increase in the fuel cell performance and ESA. Once the goodness of the MPL was confirmed, result analysis led to an optimum MPL composition of 2 mg cm{sup -2} of carbon for both electrodes, anode and cathode. (Abstract Copyright [2010], Wiley Periodicals, Inc.)

  9. Diabetes education and self-management for ongoing and newly diagnosed (DESMOND)

    DEFF Research Database (Denmark)

    Skinner, T. Chas; Carey, Marian E.; Cradock, Sue

    2006-01-01

    diagnosed with Type 2 diabetes changes key illness beliefs and that these changes predict quality of life and metabolic control at 3-month follow-up. Practice implications: Newly diagnosed individuals are open to attending self-management programs and, if the program is theoretically driven, can......Objective: To determine the effects of a structured education program on illness beliefs, quality of life and physical activity in people newly diagnosed with Type 2 diabetes. Methods: Individuals attending a diabetes education and self-management for ongoing and newly diagnosed (DESMOND) program...... in 12 Primary Care Trusts completed questionnaire booklets assessing illness beliefs and quality of life at baseline and 3-month follow-up, metabolic control being assessed through assay of HbA1c. Results: Two hundred and thirty-six individuals attended the structured self-management education sessions...

  10. Flagellation of Pseudomonas aeruginosa in newly divided cells

    Science.gov (United States)

    Zhao, Kun; Lee, Calvin; Anda, Jaime; Wong, Gerard

    2015-03-01

    For monotrichous bacteria, Pseudomonas aeruginosa, after cell division, one daughter cell inherits the old flagellum from its mother cell, and the other grows a new flagellum during or after cell division. It had been shown that the new flagellum grows at the distal pole of the dividing cell when the two daughter cells haven't completely separated. However, for those daughter cells who grow new flagella after division, it still remains unknown at which pole the new flagellum will grow. Here, by combining our newly developed bacteria family tree tracking techniques with genetic manipulation method, we showed that for the daughter cell who did not inherit the old flagellum, a new flagellum has about 90% chances to grow at the newly formed pole. We proposed a model for flagellation of P. aeruginosa.

  11. Synthesis and Characterization of Some New Bis-Pyrazolyl-Thiazoles Incorporating the Thiophene Moiety as Potent Anti-Tumor Agents

    Directory of Open Access Journals (Sweden)

    Sobhi M. Gomha

    2016-09-01

    Full Text Available A new series of 1,4-bis(1-(5-(aryldiazenylthiazol-2-yl-5-(thiophen-2-yl-4,5-dihydro-1H-pyrazol-3-ylbenzenes 3a–i were synthesized via reaction of 5,5′-(1,4-phenylenebis(3-(thiophen-2-yl-4,5-dihydro-1H-pyrazole-1-carbothioamide (1 with hydrazonoyl halides 2a–i. In addition, reaction of 1 with ethyl chloroacetate afforded bis-thiazolone derivative 8 as the end product. Reaction of compound 8 with methyl glyoxalate gave bis-thiazolone derivative 10. The structures of the newly synthesized compounds were established on the basis of spectroscopic evidences and their alternative syntheses. All the synthesized compounds were evaluated for their anti-tumor activities against hepatocellular carcinoma (HepG2 cell lines, and the results revealed promising activities of compounds 3g, 5e, 3e, 10, 5f, 3i, and 3f with IC50 equal 1.37 ± 0.15, 1.41 ± 0.17, 1.62 ± 0.20, 1.86 ± 0.20, 1.93 ± 0.08, 2.03 ± 0.25, and 2.09 ± 0.19 μM, respectively.

  12. MoS{sub 2}–GO nanocomposites synthesized via a hydrothermal hydrogel method for solar light photocatalytic degradation of methylene blue

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Yong; Zhou, Yifeng, E-mail: yifengzhou@126.com; Nie, Wangyan; Chen, Pengpeng, E-mail: chenpp@ahu.edu.cn

    2015-12-01

    Graphical abstract: - Highlights: • The molybdenum disulfide–graphene oxide (MoS{sub 2}–GO) nanocomposite was synthesized via a one-step hydrothermal hydrogel method. • MoS{sub 2} and GO were composited fairly well in the obtained nanocomposites. • The electrons–hole pair recombination rate of MoS{sub 2} was greatly reduced via compositing with graphene. • The MoS{sub 2}–GO nanocomposite exhibited excellent photocatalytic performance for the degradation of methylene blue under solar light irradiation. - Abstract: In this work, molybdenum disulfide–graphene oxide (MoS{sub 2}–GO) composite hydrogel was prepared via a one-step hydrothermal method. The morphology and structure of the as-prepared hydrogels with different proportions of MoS{sub 2} and GO were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, electrochemical impedance spectra and UV–vis absorption spectroscopy. The photocatalytic performance of MoS{sub 2}–GO nanocomposites was studied toward the degradation of methylene blue (MB). Results showed that the MoS{sub 2}–GO nanocomposites exhibited improved photocatalytic activities in the degradation of MB with a maximum degradation rate of 99% under solar lights irradiation within 60 min. The synthesized MoS{sub 2}–GO composite hydrogel possesses great potential toward the development of newly synthesizable catalysts in the field of organic degradation in water.

  13. Nano-level monitoring of Yb(III) by fabrication of coated graphite electrode based on newly synthesized hexaaza macrocyclic ligand

    International Nuclear Information System (INIS)

    Singh, Ashok K.; Singh, Prerna

    2009-01-01

    The two macrocyclic ligands 2,12-(2-methoxyaniline) 2 -4,14-Me 2 -[20]-1,4,11,14-tetraene-1,5,8,11,15,18-N 6 (L 1 ) and 2,12-(2-methoxyaniline) 2 -4,14-Me 2 -8,18-dimethylacrylate-[20] -1,4,11,14-tetraene-1,5,8,11,15,18-N 6 (L 2 ) have been synthesized and explored as neutral ionophores for preparing poly(vinylchloride) (PVC) based membrane sensors selective to Yb(III) ions. Effects of various plasticizers and anion excluders were studied in detail and improved performance was observed. The best performance was obtained for the membrane sensor having a composition of L 2 :PVC:BA:NaTPB in the ratio of 5: 40: 52: 3 (w/w; mg). The performance of the membrane based on L 2 was compared with polymeric membrane electrode (PME) as well as with coated graphite electrode (CGE). The electrodes exhibit Nernstian slope for Yb 3+ ions with limits of detection of 4.3 x 10 -8 M for PME and 5.8 x 10 -9 M for CGE. The response time for PME and CGE was found to be 10 s and 8 s, respectively. The potentiometric responses are independent of the pH of the test solution in the pH range 3.0-8.0 for PME and 2.5-8.5 for CGE. The CGE has found to work satisfactorily in partially non-aqueous media upto 30% (v/v) content of methanol, ethanol and 20% (v/v) content of acetonitrile and could be used for a period of 5 months. The CGE was used as indicator electrode in the potentiometric titration of Yb 3+ ions with EDTA and in determination of fluoride ions in mouthwash samples. It can be used for determination of sulfite in red and white wine samples and also in determination of Yb 3+ in various binary mixtures with quantitative results.

  14. Nano-level monitoring of Yb(III) by fabrication of coated graphite electrode based on newly synthesized hexaaza macrocyclic ligand

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Ashok K., E-mail: akscyfcy@iitr.ernet.in [Department of Chemistry, Indian Institute of Technology-Roorkee, Roorkee 247667 (India); Singh, Prerna [Department of Chemistry, Indian Institute of Technology-Roorkee, Roorkee 247667 (India)

    2009-06-08

    The two macrocyclic ligands 2,12-(2-methoxyaniline){sub 2}-4,14-Me{sub 2}-[20]-1,4,11,14-tetraene-1,5,8,11,15,18-N{sub 6} (L{sub 1}) and 2,12-(2-methoxyaniline){sub 2}-4,14-Me{sub 2}-8,18-dimethylacrylate-[20] -1,4,11,14-tetraene-1,5,8,11,15,18-N{sub 6} (L{sub 2}) have been synthesized and explored as neutral ionophores for preparing poly(vinylchloride) (PVC) based membrane sensors selective to Yb(III) ions. Effects of various plasticizers and anion excluders were studied in detail and improved performance was observed. The best performance was obtained for the membrane sensor having a composition of L{sub 2}:PVC:BA:NaTPB in the ratio of 5: 40: 52: 3 (w/w; mg). The performance of the membrane based on L{sub 2} was compared with polymeric membrane electrode (PME) as well as with coated graphite electrode (CGE). The electrodes exhibit Nernstian slope for Yb{sup 3+} ions with limits of detection of 4.3 x 10{sup -8} M for PME and 5.8 x 10{sup -9} M for CGE. The response time for PME and CGE was found to be 10 s and 8 s, respectively. The potentiometric responses are independent of the pH of the test solution in the pH range 3.0-8.0 for PME and 2.5-8.5 for CGE. The CGE has found to work satisfactorily in partially non-aqueous media upto 30% (v/v) content of methanol, ethanol and 20% (v/v) content of acetonitrile and could be used for a period of 5 months. The CGE was used as indicator electrode in the potentiometric titration of Yb{sup 3+} ions with EDTA and in determination of fluoride ions in mouthwash samples. It can be used for determination of sulfite in red and white wine samples and also in determination of Yb{sup 3+} in various binary mixtures with quantitative results.

  15. Detection of anti-spermatozoal antibodies by a 125I-protein-A radioimmunological assay

    International Nuclear Information System (INIS)

    Czuppon, A.B.

    1985-01-01

    A newly developed solid-phase radioimmunobinding assay (RIBA) using detergent-solubilized sperm antigen has been used to evaluate anti-sperm antibodies. Results showed that none of the fertile females and males were positive in the RIBA, whereas approximately 6% of the females and 3% of the males with unexplained infertility were positive. These results are similar to those obtained using a chemically synthesized spermatozoal decapeptide antigen. The RIBA is simple to perform, requires no vital or intact spermatozoa, and large numbers of sera (up to 400) can be processed in one day with a total incubation time of 90 min. (Auth.)

  16. Cymbopogon citratus-synthesized gold nanoparticles boost the predation efficiency of copepod Mesocyclops aspericornis against malaria and dengue mosquitoes.

    Science.gov (United States)

    Murugan, Kadarkarai; Benelli, Giovanni; Panneerselvam, Chellasamy; Subramaniam, Jayapal; Jeyalalitha, Tirupathi; Dinesh, Devakumar; Nicoletti, Marcello; Hwang, Jiang-Shiou; Suresh, Udaiyan; Madhiyazhagan, Pari

    2015-06-01

    Plant-borne compounds can be employed to synthesize mosquitocidal nanoparticles that are effective at low doses. However, how they affect the activity of mosquito predators in the aquatic environment is unknown. In this study, we synthesized gold nanoparticles (AuN) using the leaf extract of Cymbopogon citratus, which acted as a reducing and capping agent. AuN were characterized by a variety of biophysical methods and sorted for size in order to confirm structural integrity. C. citratus extract and biosynthesized AuN were tested against larvae and pupae of the malaria vector Anopheles stephensi and the dengue vector Aedes aegypti. LC₅₀ of C. citratus extract ranged from 219.32 ppm to 471.36 ppm. LC₅₀ of AuN ranged from 18.80 ppm to 41.52 ppm. In laboratory, the predatory efficiency of the cyclopoid crustacean Mesocyclops aspericornis against A. stephensi larvae was 26.8% (larva I) and 17% (larva II), while against A. aegypti was 56% (I) and 35.1% (II). Predation against late-instar larvae was minimal. In AuN-contaminated environment,predation efficiency against A. stephensi was 45.6% (I) and 26.7% (II), while against A. aegypti was 77.3% (I) and 51.6% (II). Overall, low doses of AuN may help to boost the control of Anopheles and Aedes larval populations in copepod-based control programs. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Perceptions of the clinical competence of newly registered nurses in the North West province

    Directory of Open Access Journals (Sweden)

    M.R. Moeti

    2004-09-01

    Full Text Available The clinical competence of newly registered nurses relating to the care of individual Clients, depends on their ability to correlate theoretical knowledge learned in the classroom with practice and the development of clinical skills. Its foundation lies in the ability to identify and solve problems that emanate from critical thinking, analytical reasoning and reflective practice. It is clear that the quality of clinical exposure plays a leading role in the development of nursing professionals. Nursing skills alone cannot ensure quality care of clients without the application of theory. Facilitation of this theory to practice therefore remains an essential component of nursing education. This study was aimed at identifying areas of incompetence of newly registered nurses (1998- 2001 in the clinical area by determining the newly registered nurses1 and professional nurses1 perceptions of the competence of the newly registered nurses. A quantitative, non-experimental, descriptive survey was used to collect the data regarding the clinical competence of newly registered nurses (1998-2001.

  18. Mesenchymal Cell Reprogramming in Experimental MPLW515L Mouse Model of Myelofibrosis

    OpenAIRE

    Han, Ying; Yue, Lanzhu; Wei, Max; Ren, Xiubao; Shao, Zonghong; Zhang, Ling; Levine, Ross L.; Epling-Burnette, Pearlie K.

    2017-01-01

    Myelofibrosis is an indicator of poor prognosis in myeloproliferative neoplasms (MPNs), but the precise mechanism(s) contributing to extracellular matrix remodeling and collagen deposition in the bone marrow (BM) niche remains unanswered. In this study, we isolated mesenchymal stromal cells (MSCs) from mice transplanted with wild-type thrombopoietin receptor (MPL WT ) and MPL W515L retroviral-transduced bone marrow. Using MSCs derived from MPL W515 -transplant recipients, excessive collagen d...

  19. Syntheses, structures, photoluminescence and photocatalysis of 2D layered lanthanide-carboxylates with 2, 2′-dithiodibenzoic acid

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Ling; Zhong, Jie-Cen; Qiu, Xing-Tai; Sun, Yan-Qiong, E-mail: sunyq@fzu.edu.cn; Chen, Yi-Ping

    2017-02-15

    Two series of lanthanide-carboxylates, [Ln(2,2′-dtba)(2,2′-Hdtba)(EtOH)]{sub n} (I:Ln=Eu(1a), Dy(1b)) and [Ln(2,2′-dtba)(2,2′-Hdtba)(4,4′-bpy){sub 0.5}]{sub n} (II:Ln=Eu(2a), Dy(2b), Tb(2c) 2,2′-H{sub 2}dtba=2,2′-dithiodibenzoic acid, 4,4′-bpy=4,4′-bipyridine) have been synthesized under hydrothermal conditions. Interestingly, the H{sub 2}dtba organic ligand was generated by in situ S–S reaction of 2-mercaptobenzoic acid. Compounds I and II possess different 2D layered structures based on similar 1D [Ln(2,2′-dtba)]{sup +} chains. Photoluminescence studies reveal that compounds I and II exhibit strong lanthanide characteristic emission bands. Remarkably, Compounds 1b and 2a both exhibit good photocatalytic activity for degradation of Rhodamine-B (Rh-B) under the simulated sunlight irradiation. - Graphical abstract: Two series of lanthanide-carboxylates have been in situ synthesized under hydrothermal conditions. The lanthanide-carboxylates exhibit strong lanthanide characteristic emission bands and good photocatalytic activity for degradation of Rhodamine-B. - Highlights: • 2D layered lanthanide-carboxylates with 2,2′-dithiodibenzoic acid. • In situ S–S reaction of 2-mercaptobenzoic acid under hydrothermal condition. • The Emission spectra of I and II exhibit the characteristic transition of lanthanide ions. • Compounds 1b and 2a exhibit good photocatalytic activity for degradation of Rhodamine-B.

  20. 'Practising under your own Pin'- a description of the transition experiences of newly qualified midwives.

    Science.gov (United States)

    Avis, Mark; Mallik, Maggie; Fraser, Diane M

    2013-11-01

    Transition experiences of newly qualified midwives were examined in depth during the third phase of a UK evaluation study of midwifery education. The fitness to practise and the retention of newly qualified nursing and midwifery graduates are pressing concerns for health care managers. The advantages of preceptorship are reported in the literature but the content and timing of schemes remain unclear. A semi-structured diary was kept for up to 6 months by 35 newly qualified midwives in 18 work sites covering all countries in the UK. The preceptor and supervisor of midwives for each newly qualified midwife completed short questionnaires about their preceptee's performance, and a further sub-sample of newly qualified midwives and preceptors participated in a semi-structured interview. Data were analysed to elicit aspects of newly qualified midwives transition experiences. Findings confirm that structured preceptorship schemes are not widely available. Newly qualified midwives primarily obtained transition support from members of the midwifery team. Although perceived as competent, there is no demarcation point in becoming confident to practise as a registered practitioner. Implications for managers include the importance of a supportive culture within clinical teams for successful transition and the introduction of structured preceptorship schemes facilitated by appropriate rotation patterns. © 2012 John Wiley & Sons Ltd.

  1. Poli (metil azoteto de glicidila - GAP. I: síntese e caracterização Glycidyl azide polymer (GAP. I: syntheses and characterization

    Directory of Open Access Journals (Sweden)

    Sandro P. Ribeiro

    2012-01-01

    Full Text Available O poli (metil azoteto de glicidila - GAP - é um material energético que pode ser utilizado como aglutinante (binder e como plastificante energético em compostos explosivos e propulsores de foguetes. Neste trabalho, foi abordada a síntese do (GAP através da conversão direta da epicloridrina (ECH a GAP. Os reagentes utilizados foram azida de sódio, epicloridrina e vários álcoois extensores de cadeias, o etanodiol, o 1,4-butanodiol, o dietilenoglicol e o glicerol. Alguns parâmetros de operação foram avaliados, como o tempo de reação, a proporção entre os reagentes, dois tipos de solvente e a ordem de adição dos reagentes. A variável observada para a análise foi a massa molecular do GAP. Todos os materiais sintetizados também foram caracterizados por análises de FTIR, UV, RMN, DSC, análise elementar e TGA. Uma maior massa molecular, maior rendimento e uma melhor conversão do grupo azida a GAP foram obtidos com a adição de epicloridrina sobre a azida de sódio e usando DMF como solvente.GAP is an aliphatic polyether that includes hydroxyl groups and highly energetic azide groups. Thus, it is an energetic material that can be used as binder or plasticizing agent in propellants and explosive mixtures. The glycidyl azide polymer (GAP was synthesized and characterized by direct conversion of epichlorohydrin. GAP was synthesized by reaction of sodium azide, epichlorohydrin, and some extensor alcohols. The investigation focused on the effects of some key reaction parameters including reagent proportions, reaction time and two different solvents. The product was characterized by FTIR, UV, NMR, DSC, elemental analysis, TGA and GPC. The species were also evaluated through molecular weight (GPC, glass transition temperature (DSC, ignition time and sensitivity.

  2. A low-spurious fast-hopping MB-OFDM UWB synthesizer

    Energy Technology Data Exchange (ETDEWEB)

    Chen Danfeng; Li Wei; Li Ning; Ren Junyan, E-mail: w-li@fudan.edu.c [State Key Laboratory of ASIC and System, Fudan University, Shanghai 201203 (China)

    2010-06-15

    A frequency synthesizer for the ultra-wide band (UWB) group no. 1 is proposed. The synthesizer uses a phase-locked loop (PLL) and single-sideband (SSB) mixers to generate the three center frequencies of the first band group by mixing 4224 MHz with {+-}264 MHz and 792 MHz, respectively. A novel multi-QSSB mixer is designed to combine the function of frequency selection and frequency conversion for low power and high linearity. The synthesizer is fabricated in Jazz 0.18-{mu}m RF CMOS technology. The measured reference spur is as low as -69 dBc and the maximum spur is the LO leakage of -32 dBc. A low phase noise of -110 dBc/Hz - 1 MHz offset and an integrated phase noise of 1.86{sup 0} are achieved. The hopping time between different bands is less than 1.8 ns. The synthesizer consumes 30 mA from a 1.8 V supply. (semiconductor integrated circuits)

  3. A low-spurious fast-hopping MB-OFDM UWB synthesizer

    International Nuclear Information System (INIS)

    Chen Danfeng; Li Wei; Li Ning; Ren Junyan

    2010-01-01

    A frequency synthesizer for the ultra-wide band (UWB) group no. 1 is proposed. The synthesizer uses a phase-locked loop (PLL) and single-sideband (SSB) mixers to generate the three center frequencies of the first band group by mixing 4224 MHz with ±264 MHz and 792 MHz, respectively. A novel multi-QSSB mixer is designed to combine the function of frequency selection and frequency conversion for low power and high linearity. The synthesizer is fabricated in Jazz 0.18-μm RF CMOS technology. The measured reference spur is as low as -69 dBc and the maximum spur is the LO leakage of -32 dBc. A low phase noise of -110 dBc/Hz - 1 MHz offset and an integrated phase noise of 1.86 0 are achieved. The hopping time between different bands is less than 1.8 ns. The synthesizer consumes 30 mA from a 1.8 V supply. (semiconductor integrated circuits)

  4. Seaweed-synthesized silver nanoparticles: an eco-friendly tool in the fight against Plasmodium falciparum and its vector Anopheles stephensi?

    Science.gov (United States)

    Murugan, Kadarkarai; Samidoss, Christina Mary; Panneerselvam, Chellasamy; Higuchi, Akon; Roni, Mathath; Suresh, Udaiyan; Chandramohan, Balamurugan; Subramaniam, Jayapal; Madhiyazhagan, Pari; Dinesh, Devakumar; Rajaganesh, Rajapandian; Alarfaj, Abdullah A; Nicoletti, Marcello; Kumar, Suresh; Wei, Hui; Canale, Angelo; Mehlhorn, Heinz; Benelli, Giovanni

    2015-11-01

    Malaria, the most widespread mosquito-borne disease, affects 350-500 million people each year. Eco-friendly control tools against malaria vectors are urgently needed. This research proposed a novel method of plant-mediated synthesis of silver nanoparticles (AgNP) using a cheap seaweed extract of Ulva lactuca, acting as a reducing and capping agent. AgNP were characterized by UV-vis spectrophotometry, Fourier transform infrared (FTIR) spectroscopy, energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The U. lactuca extract and the green-synthesized AgNP were tested against larvae and pupae of the malaria vector Anopheles stephensi. In mosquitocidal assays, LC50 values of U. lactuca extract against A. stephensi larvae and pupae were 18.365 ppm (I instar), 23.948 ppm (II), 29.701 ppm (III), 37.517 ppm (IV), and 43.012 ppm (pupae). LC50 values of AgNP against A. stephensi were 2.111 ppm (I), 3.090 ppm (II), 4.629 ppm (III), 5.261 ppm (IV), and 6.860 ppm (pupae). Smoke toxicity experiments conducted against mosquito adults showed that U. lactuca coils evoked mortality rates comparable to the permethrin-based positive control (66, 51, and 41%, respectively). Furthermore, the antiplasmodial activity of U. lactuca extract and U. lactuca-synthesized AgNP was evaluated against CQ-resistant (CQ-r) and CQ-sensitive (CQ-s) strains of Plasmodium falciparum. Fifty percent inhibitory concentration (IC50) values of U. lactuca were 57.26 μg/ml (CQ-s) and 66.36 μg/ml (CQ-r); U. lactuca-synthesized AgNP IC50 values were 76.33 μg/ml (CQ-s) and 79.13 μg/ml (CQ-r). Overall, our results highlighted out that U. lactuca-synthesized AgNP may be employed to develop newer and safer agents for malaria control.

  5. Information Retrieval for Ecological Syntheses

    Science.gov (United States)

    Bayliss, Helen R.; Beyer, Fiona R.

    2015-01-01

    Research syntheses are increasingly being conducted within the fields of ecology and environmental management. Information retrieval is crucial in any synthesis in identifying data for inclusion whilst potentially reducing biases in the dataset gathered, yet the nature of ecological information provides several challenges when compared with…

  6. Combustion, performance and emissions characteristics of a newly ...

    Indian Academy of Sciences (India)

    of a newly developed CRDI single cylinder diesel engine. AVINASH ... In case of unit injector and unit pump systems, fuel injection pressure depends on ... nozzle hole diameters were effective in reducing smoke and PM emissions. However ...

  7. Yield and Adaptability Evaluation of Newly Introduced Tomato ...

    African Journals Online (AJOL)

    High yield is a major ambition to tomato plant breeders and farmers. The purpose of the ... Tabora Region on the growth and yield of newly introduced tomato varieties. The tested ..... (1985). Evaluation of some American tomatocultivars grown.

  8. Mentorship for newly appointed physicians: a strategy for enhancing patient safety?

    Science.gov (United States)

    Harrison, Reema; McClean, Serwaa; Lawton, Rebecca; Wright, John; Kay, Clive

    2014-09-01

    Mentorship is an increasingly popular innovation from business and industry that is being applied in health-care contexts. This paper explores the concept of mentorship for newly appointed physicians in their first substantive senior post, and specifically its utilization to enhance patient safety. Semi-structured face to face and telephone interviews with Medical Directors (n = 5), Deputy Medical Directors (n = 4), and Clinical Directors (n = 6) from 9 acute NHS Trusts in the Yorkshire and Humber region in the north of England. A focused thematic analysis was used. A number of beneficial outcomes were associated with mentorship for newly appointed physicians including greater personal and professional support, organizational commitment, and general well-being. Providing newly appointed senior physicians with support through mentorship was considered to enhance the safety of patient care. Mentorship may prevent or reduce active failures, be used to identify threats in the local working environment, and in the longer term, address latent threats to safety within the organization by encouraging a healthier safety culture. Offering mentorship to all newly appointed physicians in their first substantive post in health care may be a useful strategy to support the development of their clinical, professional, and personal skills in this transitional period that may also enhance the safety of patient care.

  9. Scaling up Evidence-Based Practices: Strategies from Investing in Innovation (i3)

    Science.gov (United States)

    DeWire, Tom; McKithen, Clarissa; Carey, Rebecca

    2017-01-01

    What can the Investing in Innovation (i3) grantees tell us about scaling innovative educational practices? The newly released white paper "Scaling Up Evidence-Based Practices: Strategies from Investing in Innovation (i3)" captures the experiences of nine grantees whose projects collectively have reached over 1.2 million students across…

  10. Newly elected IAEA Board of Governors

    International Nuclear Information System (INIS)

    2000-01-01

    The document gives information about the election of 11 Member States to the IAEA Board of Governors, the 35-member policy-making body, during the 44th regular session of the IAEA's General Conference (18 - 22 September 2000, Austria Center, Vienna). The newly elected Member States are: Argentina, Egypt, Ghana, Ireland, Libyan Arab Jamahiriya, Mexico, Pakistan, Peru, Switzerland, Thailand, Ukraine. The other 24 Member States of the Board are also given

  11. Field-Effect Transistors Based on Networks of Highly Aligned, Chemically Synthesized N = 7 Armchair Graphene Nanoribbons.

    Science.gov (United States)

    Passi, Vikram; Gahoi, Amit; Senkovskiy, Boris V; Haberer, Danny; Fischer, Felix R; Grüneis, Alexander; Lemme, Max C

    2018-03-28

    We report on the experimental demonstration and electrical characterization of N = 7 armchair graphene nanoribbon (7-AGNR) field effect transistors. The back-gated transistors are fabricated from atomically precise and highly aligned 7-AGNRs, synthesized with a bottom-up approach. The large area transfer process holds the promise of scalable device fabrication with atomically precise nanoribbons. The channels of the FETs are approximately 30 times longer than the average nanoribbon length of 30 nm to 40 nm. The density of the GNRs is high, so that transport can be assumed well-above the percolation threshold. The long channel transistors exhibit a maximum I ON / I OFF current ratio of 87.5.

  12. Planar geometry of 4-substituted-2,2'-bipyridines synthesized by Sonogashira and Suzuki cross-coupling reactions

    Energy Technology Data Exchange (ETDEWEB)

    Luong Thi, T. T., E-mail: thuyltt@hnue.edu.vn; Nguyen Bich, N.; Nguyen, H. [Hanoi National University of Education, Chemistry Department (Viet Nam); Van Meervelt, L., E-mail: luc.vanmeervelt@chem.kuleuven.be [KU Leuven, Chemistry Department (Belgium)

    2015-12-15

    Two 4-substituted 2,2'-bipyridines, namely 4-(ferrocenylethynyl)-2,2'-bipyridine (I) and 4-ferrocenyl-2,2'-bipyridine (II) have been synthesized and fully characterized via single-crystal X-ray diffraction and {sup 1}H and {sup 13}C NMR analyses. The π-conjugated system designed from 2,2'-bipyridine modified with the ferrocenylethynyl and ferrocenyl groups shows the desired planarity. In the crystal packing of I and II, the molecules arrange themselves in head-to-tail and head-to-head motifs, respectively, resulting in consecutive layers of ferrocene and pyridine moieties.

  13. Transport, Thermal, and Magnetic Properties of YbNi3X9 (X = Al, Ga): A Newly Synthesized Yb-Based Kondo Lattice System

    Science.gov (United States)

    Yamashita, Tetsuro; Miyazaki, Ryoichi; Aoki, Yuji; Ohara, Shigeo

    2012-03-01

    We have succeeded in synthesizing a new Yb-based Kondo lattice system, YbNi3X9 (X = Al, Ga). Our study reveals that YbNi3Al9 shows typical features of a heavy-fermion antiferromagnet with a Néel temperature of TN = 3.4 K. All of the properties reflect a competition between the Kondo effect and the crystalline electric field (CEF) effect. The moderate heavy-fermion state leads to an enhanced Sommerfeld coefficient of 100 mJ/(mol\\cdotK2), even if ordered antiferromagnetically. On the other hand, the isostructural gallide YbNi3Ga9 is an intermediate-valence system with a Kondo temperature of TK = 570 K. A large hybridization scale can overcome the CEF splitting energy, and a moderately heavy Fermi-liquid ground state with high local moment degeneracy should form at low temperatures. Note that the quality of single-crystalline YbNi3X9 is extremely high compared with those of other Yb-based Kondo lattice compounds. We conclude that YbNi3X9 is a suitable system for investigating the electronic structure of Yb-based Kondo lattice systems from a heavy-fermion system with an antiferromagnetically ordered ground state to an intermediate-valence system.

  14. Conformational, vibrational and DFT studies of a newly synthesized arylpiperazine-based drug and evaluation of its reactivity towards the human GABA receptor

    Science.gov (United States)

    Onawole, A. T.; Al-Ahmadi, A. F.; Mary, Y. S.; Panicker, C. Y.; Ullah, N.; Armaković, S.; Armaković, S. J.; Van Alsenoy, C.; Al-Saadi, A. A.

    2017-11-01

    This study reports a computational assessment of important biochemical properties and vibrational assignments for the synthesized 1-(4-(3-methoxy-4-nitrophenyl)piperazin-1-yl)ethanone (MNPE). MNPE is related to the commonly used arylpiperazine-based drugs that exhibit a wide range of pharmacological activities. The characterization of MNPE is based on the readily sighted 1363 cm-1 infrared band (associated with piperazine ring stretching), 1308 cm-1 Raman line (associated with the phenyl ring breathing), 1242 cm-1 Raman line and 1092 cm-1 infrared band (both associated with Csbnd N stretching) as key modes in its vibrational spectra. First principle calculations revealed that MNPE could exist in sixteen different plausible conformations, which were used as basis to understand the possible molecular docking mechanism of the molecule as an agonist in the human GABAA receptor. The best binding scenarios showed the presence of intramolecular hydrogen bonding in MNPE and was comparable with the most stable configuration. It was further evaluated for its reactivity properties by utilizing the concepts of Average Local Ionization Energies (ALIE) and Fukui functions. The autoxidation and hydrolysis degradation likelihood of MNPE estimated from the computed bond dissociation energies and radial distribution functions predicted that MNPE is to be readily biodegradable in aqueous solutions.