Identification of embryonic precursor cells that differentiate into thymic epithelial cells expressing autoimmune regulator

PubMed Central

Takizawa, Nobukazu; Miyauchi, Maki; Yanai, Hiromi; Tateishi, Ryosuke; Shinzawa, Miho; Yoshinaga, Riko; Kurihara, Masaaki; Yasuda, Hisataka; Sakamoto, Reiko; Yoshida, Nobuaki

2016-01-01

Medullary thymic epithelial cells (mTECs) expressing autoimmune regulator (Aire) are critical for preventing the onset of autoimmunity. However, the differentiation program of Aire-expressing mTECs (Aire+ mTECs) is unclear. Here, we describe novel embryonic precursors of Aire+ mTECs. We found the candidate precursors of Aire+ mTECs (pMECs) by monitoring the expression of receptor activator of nuclear factor-κB (RANK), which is required for Aire+ mTEC differentiation. pMECs unexpectedly expressed cortical TEC molecules in addition to the mTEC markers UEA-1 ligand and RANK and differentiated into mTECs in reaggregation thymic organ culture. Introduction of pMECs in the embryonic thymus permitted long-term maintenance of Aire+ mTECs and efficiently suppressed the onset of autoimmunity induced by Aire+ mTEC deficiency. Mechanistically, pMECs differentiated into Aire+ mTECs by tumor necrosis factor receptor-associated factor 6-dependent RANK signaling. Moreover, nonclassical nuclear factor-κB activation triggered by RANK and lymphotoxin-β receptor signaling promoted pMEC induction from progenitors exhibiting lower RANK expression and higher CD24 expression. Thus, our findings identified two novel stages in the differentiation program of Aire+ mTECs. PMID:27401343

Activation of the Cph1-Dependent MAP Kinase Signaling Pathway Induces White-Opaque Switching in Candida albicans

PubMed Central

Ramírez-Zavala, Bernardo; Weyler, Michael; Gildor, Tsvia; Schmauch, Christian; Kornitzer, Daniel; Arkowitz, Robert; Morschhäuser, Joachim

2013-01-01

Depending on the environmental conditions, the pathogenic yeast Candida albicans can undergo different developmental programs, which are controlled by dedicated transcription factors and upstream signaling pathways. C. albicans strains that are homozygous at the mating type locus can switch from the normal yeast form (white) to an elongated cell type (opaque), which is the mating-competent form of this fungus. Both white and opaque cells use the Ste11-Hst7-Cek1/Cek2 MAP kinase signaling pathway to react to the presence of mating pheromone. However, while opaque cells employ the transcription factor Cph1 to induce the mating response, white cells recruit a different downstream transcription factor, Tec1, to promote the formation of a biofilm that facilitates mating of opaque cells in the population. The switch from the white to the opaque cell form is itself induced by environmental signals that result in the upregulation of the transcription factor Wor1, the master regulator of white-opaque switching. To get insight into the upstream signaling pathways controlling the switch, we expressed all C. albicans protein kinases from a tetracycline-inducible promoter in a switching-competent strain. Screening of this library of strains showed that a hyperactive form of Ste11 lacking its N-terminal domain (Ste11ΔN467) efficiently stimulated white cells to switch to the opaque phase, a behavior that did not occur in response to pheromone. Ste11ΔN467-induced switching specifically required the downstream MAP kinase Cek1 and its target transcription factor Cph1, but not Cek2 and Tec1, and forced expression of Cph1 also promoted white-opaque switching in a Wor1-dependent manner. Therefore, depending on the activation mechanism, components of the pheromone-responsive MAP kinase pathway can be reconnected to stimulate an alternative developmental program, switching of white cells to the mating-competent opaque phase. PMID:24130492

Crucial role of SLP-76 and ADAP for neutrophil recruitment in mouse kidney ischemia-reperfusion injury.

PubMed

Block, Helena; Herter, Jan M; Rossaint, Jan; Stadtmann, Anika; Kliche, Stefanie; Lowell, Clifford A; Zarbock, Alexander

2012-02-13

Neutrophils trigger inflammation-induced acute kidney injury (AKI), a frequent and potentially lethal occurrence in humans. Molecular mechanisms underlying neutrophil recruitment to sites of inflammation have proved elusive. In this study, we demonstrate that SLP-76 (SH2 domain-containing leukocyte phosphoprotein of 76 kD) and ADAP (adhesion and degranulation promoting adaptor protein) are involved in E-selectin-mediated integrin activation and slow leukocyte rolling, which promotes ischemia-reperfusion-induced AKI in mice. By using genetically engineered mice and transduced Slp76(-/-) primary leukocytes, we demonstrate that ADAP as well as two N-terminal-located tyrosines and the SH2 domain of SLP-76 are required for downstream signaling and slow leukocyte rolling. The Tec family kinase Bruton tyrosine kinase is downstream of SLP-76 and, together with ADAP, regulates PI3Kγ (phosphoinositide 3-kinase-γ)- and PLCγ2 (phospholipase Cγ2)-dependent pathways. Blocking both pathways completely abolishes integrin affinity and avidity regulation. Thus, SLP-76 and ADAP are involved in E-selectin-mediated integrin activation and neutrophil recruitment to inflamed kidneys, which may underlie the development of life-threatening ischemia-reperfusion-induced AKI in humans.

IL-3R-alpha blockade inhibits tumor endothelial cell-derived extracellular vesicle (EV)-mediated vessel formation by targeting the β-catenin pathway.

PubMed

Lombardo, Giusy; Gili, Maddalena; Grange, Cristina; Cavallari, Claudia; Dentelli, Patrizia; Togliatto, Gabriele; Taverna, Daniela; Camussi, Giovanni; Brizzi, Maria Felice

2018-03-01

The proangiogenic cytokine Interleukin-3 (IL-3) is released by inflammatory cells in breast and ovarian cancer tissue microenvironments and also acts as an autocrine factor for human breast and kidney tumor-derived endothelial cells (TECs). We have previously shown that IL-3-treated endothelial cells (ECs) release extracellular vesicles (EVs), which serve as a paracrine mechanism for neighboring ECs, by transferring active molecules. The impact of an anti-IL-3R-alpha blocking antibody on the proangiogenic effect of EVs released from TECs (anti-IL-3R-EVs) has therefore been investigated in this study. We have found that anti-IL-3R-EV treatment prevented neovessel formation and, more importantly, also induced the regression of in vivo TEC-derived neovessels. Two miRs that target the canonical wingless (Wnt)/β-catenin pathway, at different levels, were found to be differentially regulated when comparing the miR-cargo of naive TEC-derived EVs (EVs) and anti-IL-3R-EVs. miR-214-3p, which directly targets β-catenin, was found to be upregulated, whereas miR-24-3p, which targets adenomatous polyposis coli (APC) and glycogen synthase kinase-3β (GSK3β), was found to be downregulated. In fact, upon their transfer into the cell, low β-catenin content and high levels of the two members of the "β-catenin destruction complex" were detected. Moreover, c-myc downregulation was found in TECs treated with anti-IL-3R-EVs, pre-miR-214-3p-EVs and antago-miR-24-3p-EVs, which is consistent with network analyses of miR-214-3p and miR-24-3p gene targeting. Finally, in vivo studies have demonstrated the impaired growth of vessels in pre-miR-214-3p-EV- and antago-miR-24-3p-EV-treated animals. These effects became much more evident when combo treatment was applied. The results of the present study identify the canonical Wnt/β-catenin pathway as a relevant mechanism of TEC-derived EV proangiogenic action. Furthermore, we herein provide evidence that IL-3R blockade may yield some significant advantages, than miR targeting, in inhibiting the proangiogenic effects of naive TEC-derived EVs by changing TEC-EV-miR cargo.

Bruton tyrosine kinase (Btk) suppresses osteoblastic differentiation.

PubMed

Kaneshiro, Shoichi; Ebina, Kosuke; Shi, Kenrin; Yoshida, Kiyoshi; Otsuki, Dai; Yoshikawa, Hideki; Higuchi, Chikahisa

2015-09-01

The Tec family of nonreceptor tyrosine kinases has been shown to play a key role in inflammation and bone destruction. Bruton tyrosine kinase (Btk) has been the most widely studied because of its critical role in B cells. Furthermore, recent evidence has demonstrated that blocking Btk signaling is effective in ameliorating lymphoma progression and experimental arthritis. The role of Btk in osteoblastic differentiation has not been well elucidated. In this study, we demonstrated the role of Btk in osteoblastic differentiation and investigated the effects of a Btk inhibitor on osteoblastic differentiation in mouse preosteoblastic MC3T3-E1 cells, primary calvarial osteoblasts, and bone marrow stromal ST2 cells. Btk expression was detected in all three cell lines. Btk inhibition stimulated mRNA expression of osteoblastic markers (alkaline phosphatase, osteocalcin, and osterix) and promoted mineralization of the extracellular matrix. In addition, Btk knockdown caused increased mRNA expression of osteoblastic markers. Furthermore, Btk inhibition suppressed the phosphorylation of mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NFκB), and protein kinase Cα (PKCα). Our results indicate that Btk may regulate osteoblastic differentiation through the MAPK, NFκB, and PKCα signaling pathways.

Bruton's tyrosine kinase (BTK) as a promising target in solid tumors.

PubMed

Molina-Cerrillo, J; Alonso-Gordoa, T; Gajate, P; Grande, E

2017-07-01

Bruton's tyrosine kinase (BTK) is a non-receptor intracellular kinase that belongs to the TEC-family tyrosine kinases together with bone marrow-expressed kinase (BMX), redundant-resting lymphocyte kinase (RLK), and IL-2 inducible T-Cell kinase (ITK). All these proteins play a key role in the intracellular signaling of both B and T lymphocytes. Recently, some preclinical data have demonstrated that BTK is present in certain tumor subtypes and in other relevant cells that are contributing to the tumor microenvironment such as dendritic cells, macrophages, myeloid derived suppressor cells and endothelial cells. Ibrutinib (PCI-32765) is an orally available small molecule that acts as an inhibitor of the BTK and is approved for the treatment of patients with some hematological malignancies. It has been suggested that ibrutinib may also have a potential antitumor activity in solid neoplasms. In this sense, ibrutinib has the ability to revert polarization of TCD4+ to Th1 lymphocytes to increase the cytotoxic ability of T CD8+ and to regulate tumor-induced immune tolerance by acting over tumor infiltrating cells activity and immunosuppressive cytokines release. Furthermore, based on its molecular activity and safety, ibrutinib has been considered as a partner for treatment combination with PI3K/AKT/mTOR inhibitors or with immune-checkpoint inhibitors, inhibiting immunosuppressive signals from the tumor microenvironment, and overcoming the immune resistance to current anti-PD1/PDL1 immunotherapeutic drugs by the CXCR4/CXCL2 pathway regulation. Currently, a broad range of different studies are evaluating the activity of ibrutinib either as single agent or in combination in patients with solid tumors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bisected, complex N-glycans and galectins in mouse mammary tumor progression and human breast cancer

PubMed Central

Miwa, Hazuki E; Koba, Wade R; Fine, Eugene J; Giricz, Orsi; Kenny, Paraic A; Stanley, Pamela

2013-01-01

Bisected, complex N-glycans on glycoproteins are generated by the glycosyltransferase MGAT3 and cause reduced cell surface binding of galectins. Previously, we showed that MGAT3 reduces growth factor signaling and retards mammary tumor progression driven by the Polyoma middle T antigen (PyMT) expressed in mammary epithelium under the mouse mammary tumor virus (MMTV) promoter. However, the penetrance of the tumor phenotype became variable in mixed FVB/N and C57BL/6 female mice and we therefore investigated a congenic C57BL/6 Mgat3−/−/MMTV-PyMT model. In the absence of MGAT3, C57BL/6 Mgat3−/−/MMTV-PyMT females exhibited accelerated tumor appearance and increased tumor burden, glucose uptake in tumors and lung metastasis. Nevertheless, activation of extracellular signal-regulated kinase (ERK)1/2 or protein kinase B (AKT) was reduced in ∼20-week C57BL/6 MMTV-PyMT tumors lacking MGAT3. Activation of focal adhesion kinase (FAK), protein tyrosine kinase Src, and p38 mitogen-activated protein kinase were similar to that of controls. All the eight mouse galectin genes were expressed in mammary tumors and tumor epithelial cells (TECs), but galectin-2 and -12 were not detected by western analysis in tumors, and galectin-7 was not detected in 60% of the TEC lines. From microarray data reported for human breast cancers, at least 10 galectin and 7 N-glycan N-acetylglucosaminyl (GlcNAc)-transferase (MGAT) genes are expressed in tumor tissue, and expression often varies significantly between different breast cancer subtypes. Thus, in summary, while MGAT3 and bisected complex N-glycans retard mouse mammary tumor progression, genetic background may modify this effect; identification of key galectins that promote mammary tumor progression in mice is not straightforward because all the eight galectin genes are expressed; and high levels of MGAT3, galectin-4, -8, -10, -13 and -14 transcripts correlate with better relapse-free survival in human breast cancer. PMID:24037315

Tyrosine kinase Btk regulates E-selectin-mediated integrin activation and neutrophil recruitment by controlling phospholipase C (PLC) gamma2 and PI3Kgamma pathways.

PubMed

Mueller, Helena; Stadtmann, Anika; Van Aken, Hugo; Hirsch, Emilio; Wang, Demin; Ley, Klaus; Zarbock, Alexander

2010-04-15

Selectins mediate leukocyte rolling, trigger beta(2)-integrin activation, and promote leukocyte recruitment into inflamed tissue. E-selectin binding to P-selectin glycoprotein ligand 1 (PSGL-1) leads to activation of an immunoreceptor tyrosine-based activation motif (ITAM)-dependent pathway, which in turn activates the spleen tyrosine kinase (Syk). However, the signaling pathway linking Syk to integrin activation after E-selectin engagement is unknown. To identify the pathway, we used different gene-deficient mice in autoperfused flow chamber, intravital microscopy, peritonitis, and biochemical studies. We report here that the signaling pathway downstream of Syk divides into a phospholipase C (PLC) gamma2- and phosphoinositide 3-kinase (PI3K) gamma-dependent pathway. The Tec family kinase Bruton tyrosine kinase (Btk) is required for activating both pathways, generating inositol-3,4,5-trisphosphate (IP(3)), and inducing E-selectin-mediated slow rolling. Inhibition of this signal-transduction pathway diminished Galpha(i)-independent leukocyte adhesion to and transmigration through endothelial cells in inflamed postcapillary venules of the cremaster. Galpha(i)-independent neutrophil recruitment into the inflamed peritoneal cavity was reduced in Btk(-/-) and Plcg2(-/-) mice. Our data demonstrate the functional importance of this newly identified signaling pathway mediated by E-selectin engagement.

Positive and Negative Regulatory Mechanisms for Fine-Tuning Cellularity and Functions of Medullary Thymic Epithelial Cells.

PubMed

Akiyama, Taishin; Tateishi, Ryosuke; Akiyama, Nobuko; Yoshinaga, Riko; Kobayashi, Tetsuya J

2015-01-01

Self-tolerant T cells and regulatory T cells develop in the thymus. A wide variety of cell-cell interactions in the thymus is required for the differentiation, proliferation, and repertoire selection of T cells. Various secreted and cell surface molecules expressed in thymic epithelial cells (TECs) mediate these processes. Moreover, cytokines expressed by cells of hematopoietic origin regulate the cellularity of TECs. Tumor necrosis factor (TNF) family RANK ligand, lymphotoxin, and CD40 ligand, expressed in T cells and innate lymphoid cells (ILCs), promote the differentiation and proliferation of medullary TECs (mTECs) that play critical roles in the induction of immune tolerance. A recent study suggests that interleukin-22 (IL-22) produced by ILCs promotes regeneration of TECs after irradiation. Intriguingly, tumor growth factor-β and osteoprotegerin limit cellularity of mTECs, thereby attenuating regulatory T cell generation. We will review recent insights into the molecular basis for cell-cell interactions regulating differentiation and proliferation of mTECs and also discuss about a perspective on use of mathematical models for understanding this complicated system.

Identification of new members of the MAPK gene family in plants shows diverse conserved domains and novel activation loop variants.

PubMed

Mohanta, Tapan Kumar; Arora, Pankaj Kumar; Mohanta, Nibedita; Parida, Pratap; Bae, Hanhong

2015-02-06

Mitogen Activated Protein Kinase (MAPK) signaling is of critical importance in plants and other eukaryotic organisms. The MAPK cascade plays an indispensible role in the growth and development of plants, as well as in biotic and abiotic stress responses. The MAPKs are constitute the most downstream module of the three tier MAPK cascade and are phosphorylated by upstream MAP kinase kinases (MAPKK), which are in turn are phosphorylated by MAP kinase kinase kinase (MAPKKK). The MAPKs play pivotal roles in regulation of many cytoplasmic and nuclear substrates, thus regulating several biological processes. A total of 589 MAPKs genes were identified from the genome wide analysis of 40 species. The sequence analysis has revealed the presence of several N- and C-terminal conserved domains. The MAPKs were previously believed to be characterized by the presence of TEY/TDY activation loop motifs. The present study showed that, in addition to presence of activation loop TEY/TDY motifs, MAPKs are also contain MEY, TEM, TQM, TRM, TVY, TSY, TEC and TQY activation loop motifs. Phylogenetic analysis of all predicted MAPKs were clustered into six different groups (group A, B, C, D, E and F), and all predicted MAPKs were assigned with specific names based on their orthology based evolutionary relationships with Arabidopsis or Oryza MAPKs. We conducted global analysis of the MAPK gene family of plants from lower eukaryotes to higher eukaryotes and analyzed their genomic and evolutionary aspects. Our study showed the presence of several new activation loop motifs and diverse conserved domains in MAPKs. Advance study of newly identified activation loop motifs can provide further information regarding the downstream signaling cascade activated in response to a wide array of stress conditions, as well as plant growth and development.

Absence of Tec Family Kinases Interleukin-2 Inducible T cell Kinase (Itk) and Bruton's Tyrosine Kinase (Btk) Severely Impairs FcϵRI-dependent Mast Cell Responses*

PubMed Central

Iyer, Archana S.; Morales, J. Luis; Huang, Weishan; Ojo, Folake; Ning, Gang; Wills, Elizabeth; Baines, Joel D.; August, Avery

2011-01-01

Mast cells are critical effector cells in the pathophysiology of allergic asthma and other IgE-mediated diseases. The Tec family of tyrosine kinases Itk and Btk serve as critical signal amplifiers downstream of antigen receptors. Although both kinases are expressed and activated in mast cells following FcϵRI stimulation, their individual contributions are not clear. To determine whether these kinases play unique and/or complementary roles in FcϵRI signaling and mast cell function, we generated Itk and Btk double knock-out mice. Analyses of these mice show decreased mast cell granularity and impaired passive systemic anaphylaxis responses. This impaired response is accompanied by a significant elevation in serum IgE in Itk/Btk double knock-out mice. In vitro analyses of bone marrow-derived mast cells (BMMCs) indicated that Itk/Btk double knock-out BMMCs are defective in degranulation and cytokine secretion responses downstream to FcϵRI activation. These responses were accompanied by a significant reduction in PLCγ2 phosphorylation and severely impaired calcium responses in these cells. This defect also results in altered NFAT1 nuclear localization in double knock-out BMMCs. Network analysis suggests that although they may share substrates, Itk plays both positive and negative roles, while Btk primarily plays a positive role in mast cell FcϵRI-induced cytokine secretion. PMID:21212279

Targeted deletion of c-Met in thymic epithelial cells leads to an autoimmune phenotype

PubMed Central

Su, Min; Hu, Rong; Song, Yinhong; Liu, Yalan; Lai, Laijun

2017-01-01

Hepatocyte growth factor (HGF) and its receptor c-Met signaling have been implicated in regulating various types of cells including epithelial cells. We have previously reported that c-Met is expressed by thymic epithelial cells (TECs), and that in vivo administration of hybrid cytokines containing IL-7 and the beta- or alpha-chain of HGF significantly increase the number of TECs. In order to study the role of c-Met signaling in TECs, we generated conditional knockout (cKO) mice in which c-Met was specifically deleted in TECs using a Foxn1-Cre transgene. We show here that c-Met deficiency in TECs results in age-progressive reduction in TEC number and reduced number of regulatory T cells. Consequently, c-Met TEC cKO mice displayed an autoimmune phenotype. Thus, c-Met signaling in TECs is important for the maintenance of TECs and immune self-tolerance. PMID:29363160

RB inactivation in keratin 18 positive thymic epithelial cells promotes non-cell autonomous T cell hyperproliferation in genetically engineered mice.

PubMed

Song, Yurong; Sullivan, Teresa; Klarmann, Kimberly; Gilbert, Debra; O'Sullivan, T Norene; Lu, Lucy; Wang, Sophie; Haines, Diana C; Van Dyke, Terry; Keller, Jonathan R

2017-01-01

Thymic epithelial cells (TEC), as part of thymic stroma, provide essential growth factors/cytokines and self-antigens to support T cell development and selection. Deletion of Rb family proteins in adult thymic stroma leads to T cell hyperplasia in vivo. To determine whether deletion of Rb specifically in keratin (K) 18 positive TEC was sufficient for thymocyte hyperplasia, we conditionally inactivated Rb and its family members p107 and p130 in K18+ TEC in genetically engineered mice (TgK18GT121; K18 mice). We found that thymocyte hyperproliferation was induced in mice with Rb inactivation in K18+ TEC, while normal T cell development was maintained; suggesting that inactivation of Rb specifically in K18+ TEC was sufficient and responsible for the phenotype. Transplantation of wild type bone marrow cells into mice with Rb inactivation in K18+ TEC resulted in donor T lymphocyte hyperplasia confirming the non-cell autonomous requirement for Rb proteins in K18+ TEC in regulating T cell proliferation. Our data suggests that thymic epithelial cells play an important role in regulating lymphoid proliferation and thymus size.

DKK1 mediated inhibition of Wnt signaling in postnatal mice leads to loss of TEC progenitors and thymic degeneration.

PubMed

Osada, Masako; Jardine, Logan; Misir, Ruth; Andl, Thomas; Millar, Sarah E; Pezzano, Mark

2010-02-08

Thymic epithelial cell (TEC) microenvironments are essential for the recruitment of T cell precursors from the bone marrow, as well as the subsequent expansion and selection of thymocytes resulting in a mature self-tolerant T cell repertoire. The molecular mechanisms, which control both the initial development and subsequent maintenance of these critical microenvironments, are poorly defined. Wnt signaling has been shown to be important to the development of several epithelial tissues and organs. Regulation of Wnt signaling has also been shown to impact both early thymocyte and thymic epithelial development. However, early blocks in thymic organogenesis or death of the mice have prevented analysis of a role of canonical Wnt signaling in the maintenance of TECs in the postnatal thymus. Here we demonstrate that tetracycline-regulated expression of the canonical Wnt inhibitor DKK1 in TECs localized in both the cortex and medulla of adult mice, results in rapid thymic degeneration characterized by a loss of DeltaNP63(+) Foxn1(+) and Aire(+) TECs, loss of K5K8DP TECs thought to represent or contain an immature TEC progenitor, decreased TEC proliferation and the development of cystic structures, similar to an aged thymus. Removal of DKK1 from DKK1-involuted mice results in full recovery, suggesting that canonical Wnt signaling is required for the differentiation or proliferation of TEC populations needed for maintenance of properly organized adult thymic epithelial microenvironments. Taken together, the results of this study demonstrate that canonical Wnt signaling within TECs is required for the maintenance of epithelial microenvironments in the postnatal thymus, possibly through effects on TEC progenitor/stem cell populations. Downstream targets of Wnt signaling, which are responsible for maintenance of these TEC progenitors may provide useful targets for therapies aimed at counteracting age associated thymic involution or the premature thymic degeneration associated with cancer therapy and bone marrow transplants.

Crucial role of SLP-76 and ADAP for neutrophil recruitment in mouse kidney ischemia-reperfusion injury

PubMed Central

Block, Helena; Herter, Jan M.; Rossaint, Jan; Stadtmann, Anika; Kliche, Stefanie; Lowell, Clifford A.

2012-01-01

Neutrophils trigger inflammation-induced acute kidney injury (AKI), a frequent and potentially lethal occurrence in humans. Molecular mechanisms underlying neutrophil recruitment to sites of inflammation have proved elusive. In this study, we demonstrate that SLP-76 (SH2 domain–containing leukocyte phosphoprotein of 76 kD) and ADAP (adhesion and degranulation promoting adaptor protein) are involved in E-selectin–mediated integrin activation and slow leukocyte rolling, which promotes ischemia-reperfusion–induced AKI in mice. By using genetically engineered mice and transduced Slp76−/− primary leukocytes, we demonstrate that ADAP as well as two N-terminal–located tyrosines and the SH2 domain of SLP-76 are required for downstream signaling and slow leukocyte rolling. The Tec family kinase Bruton tyrosine kinase is downstream of SLP-76 and, together with ADAP, regulates PI3Kγ (phosphoinositide 3-kinase–γ)- and PLCγ2 (phospholipase Cγ2)-dependent pathways. Blocking both pathways completely abolishes integrin affinity and avidity regulation. Thus, SLP-76 and ADAP are involved in E-selectin–mediated integrin activation and neutrophil recruitment to inflamed kidneys, which may underlie the development of life-threatening ischemia-reperfusion–induced AKI in humans. PMID:22291096

syk kinase activation by a src kinase-initiated activation loop phosphorylation chain reaction

PubMed Central

El-Hillal, O.; Kurosaki, T.; Yamamura, H.; Kinet, J.-P.; Scharenberg, A. M.

1997-01-01

Activation of the syk tyrosine kinase occurs almost immediately following engagement of many types of antigen receptors, including Fc receptors, but the mechanism through which syk is activated is currently unclear. Here we demonstrate that Fc receptor-induced syk activation occurs as the result of phosphorylation of the syk activation loop by both src family kinases and other molecules of activated syk, suggesting that syk activation occurs as the result of a src kinase-initiated activation loop phosphorylation chain reaction. This type of activation mechanism predicts that syk activation would exhibit exponential kinetics, providing a potential explanation for its rapid and robust activation by even weak antigen receptor stimuli. We propose that a similar mechanism may be responsible for generating rapid activation of other cytoplasmic tyrosine kinases, such as those of the Bruton tyrosine kinase/tec family, as well. PMID:9050880

ROS enhance angiogenic properties via regulation of NRF2 in tumor endothelial cells

PubMed Central

Towfik, Alam Mohammad; Akiyama, Kosuke; Ohga, Noritaka; Shindoh, Masanobu; Hida, Yasuhiro; Minowa, Kazuyuki; Fujisawa, Toshiaki; Hida, Kyoko

2017-01-01

Reactive oxygen species (ROS) are unstable molecules that activate oxidative stress. Because of the insufficient blood flow in tumors, the tumor microenvironment is often exposed to hypoxic condition and nutrient deprivation, which induces ROS accumulation. We isolated tumor endothelial cells (TECs) and found that they have various abnormalities, although the underlying mechanisms are not fully understood. Here we showed that ROS were accumulated in tumor blood vessels and ROS enhanced TEC migration with upregulation of several angiogenesis related gene expressions. It was also demonstrated that these genes were upregulated by regulation of Nuclear factor erythroid 2-related factor 2 (NRF2). Among these genes, we focused on Biglycan, a small leucine-rich proteoglycan. Inhibition of Toll-like receptors 2 and 4, known BIGLYCAN (BGN) receptors, cancelled the TEC motility stimulated by ROS. ROS inhibited NRF2 expression in TECs but not in NECs, and NRF2 inhibited phosphorylation of SMAD2/3, which activates transcription of BGN. These results indicated that ROS-induced BGN caused the pro-angiogenic phenotype in TECs via NRF2 dysregulation. PMID:28525375

Autocrine CSF-1 and CSF-1 Receptor Co-expression Promotes Renal Cell Carcinoma Growth

PubMed Central

Menke, Julia; Kriegsmann, Jörg; Schimanski, Carl Christoph; Schwartz, Melvin M.; Schwarting, Andreas; Kelley, Vicki R.

2011-01-01

Renal cell carcinoma is increasing in incidence but the molecular mechanisms regulating its growth remain elusive. Co-expression of the monocytic growth factor CSF-1 and its receptor CSF-1R on renal tubular epithelial cells (TEC) will promote proliferation and anti-apoptosis during regeneration of renal tubules. Here we show that a CSF-1-dependent autocrine pathway is also responsible for the growth of renal cell carcinoma (RCC). CSF-1 and CSF-1R were co-expressed in RCC and TEC proximally adjacent to RCC. CSF-1 engagement of CSF-1R promoted RCC survival and proliferation and reduced apoptosis, in support of the likelihood that CSF-1R effector signals mediate RCC growth. In vivo CSF-1R blockade using a CSF-1R tyrosine kinase inhibitor decreased RCC proliferation and macrophage infiltration in a manner associated with a dramatic reduction in tumor mass. Further mechanistic investigations linked CSF-1 and EGF signaling in RCC. Taken together, our results suggest that budding RCC stimulates the proximal adjacent microenvironment in the kidney to release mediators of CSF-1, CSF-1R and EGF expression in RCC. Further, our findings imply that targeting CSF-1/CSF-1R signaling may be therapeutically effective in RCC. PMID:22052465

Alternative Mating Type Configurations (a/α versus a/a or α/α) of Candida albicans Result in Alternative Biofilms Regulated by Different Pathways

PubMed Central

Srikantha, Thyagarajan; Huang, Guanghua; Garnaas, Adam M.; Soll, David R.

2011-01-01

Similar multicellular structures can evolve within the same organism that may have different evolutionary histories, be controlled by different regulatory pathways, and play similar but nonidentical roles. In the human fungal pathogen Candida albicans, a quite extraordinary example of this has occurred. Depending upon the configuration of the mating type locus (a/α versus a/a or α/α), C. albicans forms alternative biofilms that appear similar morphologically, but exhibit dramatically different characteristics and are regulated by distinctly different signal transduction pathways. Biofilms formed by a/α cells are impermeable to molecules in the size range of 300 Da to 140 kDa, are poorly penetrated by human polymorphonuclear leukocytes (PMNs), and are resistant to antifungals. In contrast, a/a or α/α biofilms are permeable to molecules in this size range, are readily penetrated by PMNs, and are susceptible to antifungals. By mutational analyses, a/α biofilms are demonstrated to be regulated by the Ras1/cAMP pathway that includes Ras1→Cdc35→cAMP(Pde2—|)→Tpk2(Tpk1)→Efg1→Tec1→Bcr1, and a/a biofilms by the MAP kinase pathway that includes Mfα→Ste2→ (Ste4, Ste18, Cag1)→Ste11→Hst7→Cek2(Cek1)→Tec1. These observations suggest the hypothesis that while the upstream portion of the newly evolved pathway regulating a/a and α/α cell biofilms was derived intact from the upstream portion of the conserved pheromone-regulated pathway for mating, the downstream portion was derived through modification of the downstream portion of the conserved pathway for a/α biofilm formation. C. albicans therefore forms two alternative biofilms depending upon mating configuration. PMID:21829325

Severe platelet dysfunction in NHL patients receiving ibrutinib is absent in patients receiving acalabrutinib

PubMed Central

Bye, Alexander P.; Unsworth, Amanda J.; Desborough, Michael J.; Hildyard, Catherine A. T.; Appleby, Niamh; Bruce, David; Kriek, Neline; Nock, Sophie H.; Sage, Tanya; Hughes, Craig E.

2017-01-01

The Bruton tyrosine kinase (Btk) inhibitor ibrutinib induces platelet dysfunction and causes increased risk of bleeding. Off-target inhibition of Tec is believed to contribute to platelet dysfunction and other side effects of ibrutinib. The second-generation Btk inhibitor acalabrutinib was developed with improved specificity for Btk over Tec. We investigated platelet function in patients with non-Hodgkin lymphoma (NHL) receiving ibrutinib or acalabrutinib by aggregometry and by measuring thrombus formation on collagen under arterial shear. Both patient groups had similarly dysfunctional aggregation responses to collagen and collagen-related peptide, and comparison with mechanistic experiments in which platelets from healthy donors were treated with the Btk inhibitors suggested that both drugs inhibit platelet Btk and Tec at physiological concentrations. Only ibrutinib caused dysfunctional thrombus formation, whereas size and morphology of thrombi following acalabrutinib treatment were of normal size and morphology. We found that ibrutinib but not acalabrutinib inhibited Src family kinases, which have a critical role in platelet adhesion to collagen that is likely to underpin unstable thrombus formation observed in ibrutinib patients. We found that platelet function was enhanced by increasing levels of von Willebrand factor (VWF) and factor VIII (FVIII) ex vivo by addition of intermediate purity FVIII (Haemate P) to blood from patients, resulting in consistently larger thrombi. We conclude that acalabrutinib avoids major platelet dysfunction associated with ibrutinib therapy, and platelet function may be enhanced in patients with B-cell NHL by increasing plasma VWF and FVIII. PMID:29296914

Ibrutinib Inhibits ERBB Receptor Tyrosine Kinases and HER2-Amplified Breast Cancer Cell Growth.

PubMed

Chen, Jun; Kinoshita, Taisei; Sukbuntherng, Juthamas; Chang, Betty Y; Elias, Laurence

2016-12-01

Ibrutinib is a potent, small-molecule Bruton tyrosine kinase (BTK) inhibitor developed for the treatment of B-cell malignancies. Ibrutinib covalently binds to Cys481 in the ATP-binding domain of BTK. This cysteine residue is conserved among 9 other tyrosine kinases, including HER2 and EGFR, which can be targeted. Screening large panels of cell lines demonstrated that ibrutinib was growth inhibitory against some solid tumor cells, including those inhibited by other HER2/EGFR inhibitors. Among sensitive cell lines, breast cancer lines with HER2 overexpression were most potently inhibited by ibrutinib (<100 nmol/L); in addition, the IC 50 s were lower than that of lapatinib and dacomitinib. Inhibition of cell growth by ibrutinib coincided with downregulation of phosphorylation on HER2 and EGFR and their downstream targets, AKT and ERK. Irreversible inhibition of HER2 and EGFR in breast cancer cells was established after 30-minute incubation above 100 nmol/L or following 2-hour incubation at lower concentrations. Furthermore, ibrutinib inhibited recombinant HER2 and EGFR activity that was resistant to dialysis and rapid dilution, suggesting an irreversible interaction. The dual activity toward TEC family (BTK and ITK) and ERBB family kinases was unique to ibrutinib, as ERBB inhibitors do not inhibit or covalently bind BTK or ITK. Xenograft studies with HER2 + MDA-MB-453 and BT-474 cells in mice in conjunction with determination of pharmacokinetics demonstrated significant exposure-dependent inhibition of growth and key signaling molecules at levels that are clinically achievable. Ibrutinib's unique dual spectrum of activity against both TEC family and ERBB kinases suggests broader applications of ibrutinib in oncology. Mol Cancer Ther; 15(12); 2835-44. ©2016 AACR. ©2016 American Association for Cancer Research.

Molecular checkpoint decisions made by subverted vascular niche transform indolent tumor cells into chemoresistant cancer stem cells

PubMed Central

Cao, Zhongwei; Scandura, Joseph M; Inghirami, Giorgio G.; Shido, Koji; Ding, Bi-Sen; Rafii, Shahin

2017-01-01

Summary Tumor-associated endothelial cells (TECs) regulate tumor cell aggressiveness. However, the “core” mechanism by which TECs confer stem cell-like activity to indolent tumors is unknown. Here, we used in vivo murine and human tumor models to identify tumor-suppressive checkpoint role of TEC-expressed insulin growth factor (IGF) binding protein-7 (IGFBP7/angiomodulin). During tumorigenesis, IGFBP7 blocks IGF1 and inhibits expansion and engraftment of tumor stem-like cells (TSCs) expressing IGF1-receptor (IGF1R). However, chemotherapy triggers TECs to suppress IGFBP7, and this stimulates IGF1R+ TSCs to express FGF4, inducing a feed-forward FGFR1-ETS2 angiocrine cascade that obviates TEC IGFBP7. Thus, loss of IGFBP7 and upregulation of IGF1 activates the FGF4-FGFR1-ETS2 pathway in TECs and converts naive tumor cells to chemoresistant TSCs, thereby facilitating their engraftment and progression. PMID:27989801

Molecular Checkpoint Decisions Made by Subverted Vascular Niche Transform Indolent Tumor Cells into Chemoresistant Cancer Stem Cells.

PubMed

Cao, Zhongwei; Scandura, Joseph M; Inghirami, Giorgio G; Shido, Koji; Ding, Bi-Sen; Rafii, Shahin

2017-01-09

Tumor-associated endothelial cells (TECs) regulate tumor cell aggressiveness. However, the core mechanism by which TECs confer stem cell-like activity to indolent tumors is unknown. Here, we used in vivo murine and human tumor models to identify the tumor-suppressive checkpoint role of TEC-expressed insulin growth factor (IGF) binding protein-7 (IGFBP7/angiomodulin). During tumorigenesis, IGFBP7 blocks IGF1 and inhibits expansion and aggresiveness of tumor stem-like cells (TSCs) expressing IGF1 receptor (IGF1R). However, chemotherapy triggers TECs to suppress IGFBP7, and this stimulates IGF1R + TSCs to express FGF4, inducing a feedforward FGFR1-ETS2 angiocrine cascade that obviates TEC IGFBP7. Thus, loss of IGFBP7 and upregulation of IGF1 activates the FGF4-FGFR1-ETS2 pathway in TECs and converts naive tumor cells to chemoresistant TSCs, thereby facilitating their invasiveness and progression. Copyright © 2017 Elsevier Inc. All rights reserved.

Neuropilin2 expressed in gastric cancer endothelial cells increases the proliferation and migration of endothelial cells in response to VEGF

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Woo Ho; Lee, Sun Hee; Jung, Myung Hwan

2009-08-01

The structure and characteristics of the tumor vasculature are known to be different from those of normal vessels. Neuropilin2 (Nrp2), which is expressed in non-endothelial cell types, such as neuronal or cancer cells, functions as a receptor for both semaphorin and vascular endothelial growth factor (VEGF). After isolating tumor and normal endothelial cells from advanced gastric cancer tissue and normal gastric mucosa tissues, respectively, we identified genes that were differentially expressed in gastric tumor endothelial (TEC) and normal endothelial cells (NEC) using DNA oligomer chips. Using reverse transcriptase-PCR, we confirmed the chip results by showing that Nrp2 gene expression ismore » significantly up-regulated in TEC. Genes that were found to be up-regulated in TEC were also observed to be up-regulated in human umbilical vein endothelial cells (HUVECs) that were co-cultured with gastric cancer cells. In addition, HUVECs co-cultured with gastric cancer cells showed an increased reactivity to VEGF-induced proliferation and migration. Moreover, overexpression of Nrp2 in HUVECs significantly enhanced the proliferation and migration induced by VEGF. Observation of an immunohistochemical analysis of various human tumor tissue arrays revealed that Nrp2 is highly expressed in the tumor vessel lining and to a lesser extent in normal tissue microvessels. From these results, we suggest that Nrp2 may function to increase the response to VEGF, which is more significant in TEC than in NEC given the differential expression, leading to gastric TEC with aggressive angiogenesis phenotypes.« less

Isolated tumor endothelial cells maintain specific character during long-term culture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsuda, Kohei; Oral Pathology and Biology, Hokkaido University Graduate School of Dental Medicine, N13 W7, Kita-ku, Sapporo 060-8586; Oral and Maxillofacial Surgery, Hokkaido University Graduate School of Dental Medicine, N13 W7, Kita-ku, Sapporo 060-8586

Tumor angiogenesis is necessary for solid tumor progression and metastasis. Increasing evidence indicates that tumor endothelial cells (TECs) are more relevant to the study of tumor angiogenesis than normal endothelial cells (NECs) because their morphologies and gene expression are different from NECs. However, it is challenging to isolate and culture large numbers of pure ECs from tumor tissue since the percentage of ECs is only about 1-2% and tumor cells and fibroblasts easily overgrow them. In addition, there has been concern that isolated TECs may lose their special phenotype once they are dissociated from tumor cells. In this study, wemore » have successfully purified murine TECs from four different human tumor xenografts and NECs from murine dermal tissue. Isolated ECs expressed endothelial markers, such as CD31, VE-cadherin (CD144), and endoglin (CD105), for more than 3 months after isolation. TECs maintained tumor endothelial-specific markers, such as tumor endothelial marker 8 (TEM8) and aminopeptidase N (APN), as in tumor blood vessels in vivo. In addition, TECs were more proliferative and motile than NECs. TECs showed a higher response to VEGF and higher expression of VEGF receptors-1 and -2 than NECs did. Stem cell antigen-1 was up-regulated in all four TECs, suggesting that they have a kind of stemness. Cultured TECs maintain distinct biological differences from NECs as in vivo. In conclusion, it was suggested that TECs are relevant material for tumor angiogenesis research.« less

Discovery of 8-Amino-imidazo[1,5- a ]pyrazines as Reversible BTK Inhibitors for the Treatment of Rheumatoid Arthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Jian; Guiadeen, Deodial; Krikorian, Arto

Bruton’s tyrosine kinase (BTK) is a Tec family kinase with a well-defined role in the B cell receptor (BCR) pathway. It has become an attractive kinase target for selective B cell inhibition and for the treatment of B cell related diseases. We report a series of compounds based on 8-amino-imidazo[1,5-a]pyrazine that are potent reversible BTK inhibitors with excellent kinase selectivity. Selectivity is achieved through specific interactions of the ligand with the kinase hinge and driven by aminopyridine hydrogen bondings with Ser538 and Asp539, and by hydrophobic interaction of trifluoropyridine in the back pocket. These interactions are evident in the X-raymore » crystal structure of the lead compounds 1 and 3 in the complex with the BTK enzyme. Our lead compounds show desirable PK profiles and efficacy in the preclinical rat collagen induced arthritis model.« less

Interleukin-1 stimulates zinc uptake by human thymic epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coto, J.A.; Hadden, J.W.

1991-03-15

Thymic epithelial cells (TEC) are known to secrete peptides which influence the differentiation and maturation of T-lymphocytes. These peptides include the thymic hormones thymulin, thymosin-{alpha}1, and thymopoietin. The biological activity of thymulin is dependent on the presence of zinc in an equimolar ratio. The authors have shown that both interleukin-1{alpha}(IL-1{alpha}) and interleukin-1{beta}(IL-1{beta}), which stimulate proliferation of TEC, stimulate the uptake of Zn-65 in-vitro independent of this proliferation. Mitomycin-C was used to inhibit the proliferation of TEC. Two other stimulators of proliferation of TEC, bovine pituitary extract (BPE) and epidermal growth factor (EGF), did not stimulate zinc uptake by the TECmore » independent of proliferation. They have also shown, utilizing in-situ hybridization, that IL-1 and zinc induce metallothionein(MT) mRNA expression in human thymic epithelial cells. The exact role of metallothionein is not clear, but it is thought to be involved in regulation of trace metal metabolism, especially in maintenance of zinc homeostasis. Their current hypothesis is that IL-1 stimulates uptake of zinc into the TEC, followed by its complexing with metallothionein. Zinc is then thought to be transferred from metallothionein to thymulin. Immunostaining, utilizing an antithymulin antibody and a fluoresceinated goat anti-rabbit second antibody, confirms the presence of thymulin in TEC and its dependence on zinc. Upon stimulation, thymulin is then secreted. Known stimulants for thymulin include progesterone, dexamethasone, estradiol, testosterone, and prolactin. None of these secretagogues increase zinc uptake, suggesting the priming of the zinc-thymulin complex is unrelated to the regulation of its secretion.« less

Osteoclast Inhibitory Peptide-1 Therapy for Paget’s Disease

DTIC Science & Technology

2010-08-01

Carolina 29425 Osteoclast inhibitory peptide-1 (OIP) is an autocrine/paracrine inhibitor of osteoclast differentia- tion, and mice that overexpress OIP-1...have previously identified and characterized theosteoclast inhibitory peptide-1 (OIP-1/hSca) as an autocrine/paracrine inhibitor of osteoclast...H, Takai T, Kodama T, Morio T, Geha RS, Kitamura D, Kurosaki T, Ellmeier W, Takayanagi H 2008 Tyrosine kinases Btk and Tec reg- ulate osteoclast

Small Molecule Reversible Inhibitors of Bruton’s Tyrosine Kinase (BTK): Structure–Activity Relationships Leading to the Identification of 7-(2-Hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9 H -carbazole-1-carboxamide (BMS-935177)

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Lucca, George V.; Shi, Qing; Liu, Qingjie

Bruton’s tyrosine kinase (BTK) belongs to the TEC family of nonreceptor tyrosine kinases and plays a critical role in multiple cell types responsible for numerous autoimmune diseases. This article will detail the structure–activity relationships (SARs) leading to a novel second generation series of potent and selective reversible carbazole inhibitors of BTK. With an excellent pharmacokinetic profile as well as demonstrated in vivo activity and an acceptable safety profile, 7-(2-hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide 6 (BMS-935177) was selected to advance into clinical development.

Regulation of Nucleocytoplasmic Shuttling of Bruton's Tyrosine Kinase (Btk) through a Novel SH3-Dependent Interaction with Ankyrin Repeat Domain 54 (ANKRD54)

PubMed Central

Hussain, Alamdar; Mohammad, Dara K.; Mohamed, Abdalla J.; Nguyen, Vivian; Metalnikov, Pavel; Colwill, Karen; Pawson, Tony; Nore, Beston F.

2012-01-01

Bruton's tyrosine kinase (Btk), belonging to the Tec family of tyrosine kinases (TFKs), is essential for B-lymphocyte development. Abrogation of Btk signaling causes human X-linked agammaglobulinemia (XLA) and murine X-linked immunodeficiency (Xid). We employed affinity purification of Flag-tagged Btk, combined with tandem mass spectrometry, to capture and identify novel interacting proteins. We here characterize the interaction with ankryin repeat domain 54 protein (ANKRD54), also known as Lyn-interacting ankyrin repeat protein (Liar). While Btk is a nucleocytoplasmic protein, the Liar pool was found to shuttle at a higher rate than Btk. Importantly, our results suggest that Liar mediates nuclear export of both Btk and another TFK, Txk/Rlk. Liar-mediated Btk shuttling was enriched for activation loop, nonphosphorylated Btk and entirely dependent on Btk's SH3 domain. Liar also showed reduced binding to an aspartic acid phosphomimetic SH3 mutant. Three other investigated nucleus-located proteins, Abl, estrogen receptor β (ERβ), and transcription factor T-bet, were all unaffected by Liar. We mapped the interaction site to the C terminus of the Btk SH3 domain. A biotinylated, synthetic Btk peptide, ARDKNGQEGYIPSNYVTEAEDS, was sufficient for this interaction. Liar is the first protein identified that specifically influences the nucleocytoplasmic shuttling of Btk and Txk and belongs to a rare group of known proteins carrying out this activity in a Crm1-dependent manner. PMID:22527282

Dynamics of the Tec‐family tyrosine kinase SH3 domains

PubMed Central

Roberts, Justin M.; Tarafdar, Sreya; Joseph, Raji E.; Andreotti, Amy H.; Smithgall, Thomas E.; Engen, John R.

2016-01-01

Abstract The Src Homology 3 (SH3) domain is an important regulatory domain found in many signaling proteins. X‐ray crystallography and NMR structures of SH3 domains are generally conserved but other studies indicate that protein flexibility and dynamics are not. We previously reported that based on hydrogen exchange mass spectrometry (HX MS) studies, there is variable flexibility and dynamics among the SH3 domains of the Src‐family tyrosine kinases and related proteins. Here we have extended our studies to the SH3 domains of the Tec family tyrosine kinases (Itk, Btk, Tec, Txk, Bmx). The SH3 domains of members of this family augment the variety in dynamics observed in previous SH3 domains. Txk and Bmx SH3 were found to be highly dynamic in solution by HX MS and Bmx was unstructured by NMR. Itk and Btk SH3 underwent a clear EX1 cooperative unfolding event, which was localized using pepsin digestion and mass spectrometry after hydrogen exchange labeling. The unfolding was localized to peptide regions that had been previously identified in the Src‐family and related protein SH3 domains, yet the kinetics of unfolding were not. Sequence alignment does not provide an easy explanation for the observed dynamics behavior, yet the similarity of location of EX1 unfolding suggests that higher‐order structural properties may play a role. While the exact reason for such dynamics is not clear, such motions can be exploited in intra‐ and intermolecular binding assays of proteins containing the domains. PMID:26808198

Comparative Phenotypic Analysis of the Major Fungal Pathogens Candida parapsilosis and Candida albicans

PubMed Central

Holland, Linda M.; Schröder, Markus S.; Turner, Siobhán A.; Taff, Heather; Andes, David; Grózer, Zsuzsanna; Gácser, Attila; Ames, Lauren; Haynes, Ken; Higgins, Desmond G.; Butler, Geraldine

2014-01-01

Candida parapsilosis and Candida albicans are human fungal pathogens that belong to the CTG clade in the Saccharomycotina. In contrast to C. albicans, relatively little is known about the virulence properties of C. parapsilosis, a pathogen particularly associated with infections of premature neonates. We describe here the construction of C. parapsilosis strains carrying double allele deletions of 100 transcription factors, protein kinases and species-specific genes. Two independent deletions were constructed for each target gene. Growth in >40 conditions was tested, including carbon source, temperature, and the presence of antifungal drugs. The phenotypes were compared to C. albicans strains with deletions of orthologous transcription factors. We found that many phenotypes are shared between the two species, such as the role of Upc2 as a regulator of azole resistance, and of CAP1 in the oxidative stress response. Others are unique to one species. For example, Cph2 plays a role in the hypoxic response in C. parapsilosis but not in C. albicans. We found extensive divergence between the biofilm regulators of the two species. We identified seven transcription factors and one protein kinase that are required for biofilm development in C. parapsilosis. Only three (Efg1, Bcr1 and Ace2) have similar effects on C. albicans biofilms, whereas Cph2, Czf1, Gzf3 and Ume6 have major roles in C. parapsilosis only. Two transcription factors (Brg1 and Tec1) with well-characterized roles in biofilm formation in C. albicans do not have the same function in C. parapsilosis. We also compared the transcription profile of C. parapsilosis and C. albicans biofilms. Our analysis suggests the processes shared between the two species are predominantly metabolic, and that Cph2 and Bcr1 are major biofilm regulators in C. parapsilosis. PMID:25233198

Itk tyrosine kinase substrate docking is mediated by a nonclassical SH2 domain surface of PLCgamma1.

PubMed

Min, Lie; Joseph, Raji E; Fulton, D Bruce; Andreotti, Amy H

2009-12-15

Interleukin-2 tyrosine kinase (Itk) is a Tec family tyrosine kinase that mediates signaling processes after T cell receptor engagement. Activation of Itk requires recruitment to the membrane via its pleckstrin homology domain, phosphorylation of Itk by the Src kinase, Lck, and binding of Itk to the SLP-76/LAT adapter complex. After activation, Itk phosphorylates and activates phospholipase C-gamma1 (PLC-gamma1), leading to production of two second messengers, DAG and IP(3). We have previously shown that phosphorylation of PLC-gamma1 by Itk requires a direct, phosphotyrosine-independent interaction between the Src homology 2 (SH2) domain of PLC-gamma1 and the kinase domain of Itk. We now define this docking interface using a combination of mutagenesis and NMR spectroscopy and show that disruption of the Itk/PLCgamma1 docking interaction attenuates T cell signaling. The binding surface on PLCgamma1 that mediates recognition by Itk highlights a nonclassical binding activity of the well-studied SH2 domain providing further evidence that SH2 domains participate in important signaling interactions beyond recognition of phosphotyrosine.

The Wnt signaling antagonist Kremen1 is required for development of thymic architecture.

PubMed

Osada, Masako; Ito, Emi; Fermin, Hector A; Vazquez-Cintron, Edwin; Venkatesh, Tadmiri; Friedel, Roland H; Pezzano, Mark

2006-01-01

Wnt signaling has been reported to regulate thymocyte proliferation and selection at several stages during T cell ontogeny, as well as the expression of FoxN1 in thymic epithelial cells (TECs). Kremen1 (Krm1) is a negative regulator of the canonical Wnt signaling pathway, and functions together with the secreted Wnt inhibitor Dickkopf (Dkk) by competing for the lipoprotein receptor-related protein (LRP)-6 co-receptor for Wnts. Here krm1 knockout mice were used to examine krm1 expression in the thymus and its function in thymocyte and TEC development. Krm1 expression was detected in both cortical and medullary TEC subsets, as well as in immature thymocyte subsets, beginning at the CD25+CD44+ (DN2) stage and continuing until the CD4+CD8+(DP) stage. Neonatal mice show elevated expression of krm1 in all TEC subsets. krm1(-/-) mice exhibit a severe defect in thymic cortical architecture, including large epithelial free regions. Much of the epithelial component remains at an immature Keratin 5+ (K5) Keratin 8(+)(K8) stage, with a loss of defined cortical and medullary regions. A TOPFlash assay revealed a 2-fold increase in canonical Wnt signaling in TEC lines derived from krm1(-/-) mice, when compared with krm1(+/+) derived TEC lines. Fluorescence activated cell sorting (FACS) analysis of dissociated thymus revealed a reduced frequency of both cortical (BP1(+)EpCAM(+)) and medullary (UEA-1(+) EpCAM(hi)) epithelial subsets, within the krm1(-/-) thymus. Surprisingly, no change in thymus size, total thymocyte number or the frequency of thymocyte subsets was detected in krm1(-/-) mice. However, our data suggest that a loss of Krm1 leads to a severe defect in thymic architecture. Taken together, this study revealed a new role for Krm1 in proper development of thymic epithelium.

Discovery of a potent, covalent BTK inhibitor for B-cell lymphoma.

PubMed

Wu, Hong; Wang, Wenchao; Liu, Feiyang; Weisberg, Ellen L; Tian, Bei; Chen, Yongfei; Li, Binhua; Wang, Aoli; Wang, Beilei; Zhao, Zheng; McMillin, Douglas W; Hu, Chen; Li, Hong; Wang, Jinhua; Liang, Yanke; Buhrlage, Sara J; Liang, Junting; Liu, Jing; Yang, Guang; Brown, Jennifer R; Treon, Steven P; Mitsiades, Constantine S; Griffin, James D; Liu, Qingsong; Gray, Nathanael S

2014-05-16

BTK is a member of the TEC family of non-receptor tyrosine kinases whose deregulation has been implicated in a variety of B-cell-related diseases. We have used structure-based drug design in conjunction with kinome profiling and cellular assays to develop a potent, selective, and irreversible BTK kinase inhibitor, QL47, which covalently modifies Cys481. QL47 inhibits BTK kinase activity with an IC50 of 7 nM, inhibits autophosphorylation of BTK on Tyr223 in cells with an EC50 of 475 nM, and inhibits phosphorylation of a downstream effector PLCγ2 (Tyr759) with an EC50 of 318 nM. In Ramos cells QL47 induces a G1 cell cycle arrest that is associated with pronounced degradation of BTK protein. QL47 inhibits the proliferation of B-cell lymphoma cancer cell lines at submicromolar concentrations.

Fatty acid-binding protein 4 (FABP4) and FABP5 modulate cytokine production in the mouse thymic epithelial cells.

PubMed

Adachi, Yasuhiro; Hiramatsu, Sumie; Tokuda, Nobuko; Sharifi, Kazem; Ebrahimi, Majid; Islam, Ariful; Kagawa, Yoshiteru; Koshy Vaidyan, Linda; Sawada, Tomoo; Hamano, Kimikazu; Owada, Yuji

2012-09-01

Thymic stromal cells, including cortical thymic epithelial cells (cTEC) produce many humoral factors, such as cytokines and eicosanoids to modulate thymocyte homeostasis, thereby regulating the peripheral immune responses. In this study, we identified fatty acid-binding protein (FABP4), an intracellular fatty acid chaperone, in the mouse thymus, and examined its role in the control of cytokine production in comparison with FABP5. By immunofluorescent staining, FABP4(+) cells enclosing the thymocytes were scattered throughout the thymic cortex with a spatial difference from the FABP5(+) cell that were distributed widely throughout the cTEC. The FABP4(+) cells were immunopositive for MHC class II, NLDC145 and cytokeratin 8, and were identified as part of cTEC. The FABP4(+) cells were identified as thymic nurse cells (TNC), a subpopulation of cTEC, by their active phagocytosis of apoptotic thymocytes. Furthermore, FABP4 expression was confirmed in the isolated TNC at the gene and protein levels. To explore the function of FABP in TNC, TSt-4/DLL1 cells stably expressing either FABP4 or FABP5 were established and the gene expressions of various cytokines were examined. The gene expression of interleukin (IL)-7 and IL-18 was increased both in FABP4 and FABP5 over-expressing cells compared with controls, and moreover, the increase in their expressions by adding of stearic acids was significantly enhanced in the FABP4 over-expressing cells. These data suggest that both FABPs are involved in the maintenance of T lymphocyte homeostasis through the modulation of cytokine production, which is possibly regulated by cellular fatty acid-mediated signaling in TEC, including TNC.

Are There Gender Differences in Emotion Comprehension? Analysis of the Test of Emotion Comprehension.

PubMed

Fidalgo, Angel M; Tenenbaum, Harriet R; Aznar, Ana

2018-01-01

This article examines whether there are gender differences in understanding the emotions evaluated by the Test of Emotion Comprehension (TEC). The TEC provides a global index of emotion comprehension in children 3-11 years of age, which is the sum of the nine components that constitute emotion comprehension: (1) recognition of facial expressions, (2) understanding of external causes of emotions, (3) understanding of desire-based emotions, (4) understanding of belief-based emotions, (5) understanding of the influence of a reminder on present emotional states, (6) understanding of the possibility to regulate emotional states, (7) understanding of the possibility of hiding emotional states, (8) understanding of mixed emotions, and (9) understanding of moral emotions. We used the answers to the TEC given by 172 English girls and 181 boys from 3 to 8 years of age. First, the nine components into which the TEC is subdivided were analysed for differential item functioning (DIF), taking gender as the grouping variable. To evaluate DIF, the Mantel-Haenszel method and logistic regression analysis were used applying the Educational Testing Service DIF classification criteria. The results show that the TEC did not display gender DIF. Second, when absence of DIF had been corroborated, it was analysed for differences between boys and girls in the total TEC score and its components controlling for age. Our data are compatible with the hypothesis of independence between gender and level of comprehension in 8 of the 9 components of the TEC. Several hypotheses are discussed that could explain the differences found between boys and girls in the belief component. Given that the Belief component is basically a false belief task, the differences found seem to support findings in the literature indicating that girls perform better on this task.

Regulation of tumorigenesis and metastasis of hepatocellular carcinoma tumor endothelial cells by microRNA-3178 and underlying mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Wei; Shen, Shiqiang, E-mail: shenshiqiang2014@hotmail.com; Wu, Shanmin

2015-08-28

This study explored the effects of microRNA-3178 (miR-3178) on hepatocellular carcinoma (HCC) tumor endothelial cells (TECs) and on the target mRNA. Real-time polymerase chain reaction (PCR) was performed to detect the differential expression of miR-3178 in hepatic sinusoidal endothelial cells (HSECs) and HCC TECs. Furthermore, HCC TECs were transfected with miR-3178 mimic/inhibitor or their respective negative controls. The expression of miR-3178 before and after transfection was confirmed through RT-PCR. The effects of miR-3178 on the proliferation, apoptosis, cell cycle, invasion, migration, and angiogenesis of HCC TECs were also investigated through methyl thiazol tetrazolium assay, flow cytometry, matrigel invasion assay, transwellmore » migration assay, and tube formation assay. Early growth responsive gene 3 (EGR3), as the putative target of miR-3178, was detected through RT-PCR and Western blot. Compared with HSECs, HCC TECs had lower miR-3178 expression levels (P < 0.001). MiR-3178 mimic inhibited proliferation, arrested cell cycle in G1 phase, and increased apoptosis. The numbers of migrated and invaded cells and capillary-like structures were significantly less in the mimic group than in the other groups. MiR-3178 mimic significantly decreased the mRNA and protein expression levels of EGR3. By contrast, miR-3178 inhibitor induced opposite effects. We conclude that miR-3178 was lowly expressed in HCC TECs, and miR-3178 mimic specifically inhibited the proliferation, migration, invasion, and angiogenesis and promoted the apoptosis and G1 phase arrest of HCC TECs in vitro through the inhibition of EGR3 expression. Thus, miR-3178 might be a critical target in HCC therapy. - Highlights: • MiR-3178 is significantly low-expression in HCC TECs. • MiR-3178 acts as a tumor suppressor to inhibit tumorigenesis and metastasis. • MiR-3178 inhibit angiogenesis of HCC TECs. • EGR3 may be a target gene of miR-3178. • MiR-3178 may have therapeutic application for treatment of HCC.« less

Identification and specificity studies of small-molecule ligands for SH3 protein domains.

PubMed

Inglis, Steven R; Stojkoski, Cvetan; Branson, Kim M; Cawthray, Jacquie F; Fritz, Daniel; Wiadrowski, Emma; Pyke, Simon M; Booker, Grant W

2004-10-21

The Src Homology 3 (SH3) domains are small protein-protein interaction domains that bind proline-rich sequences and mediate a wide range of cell-signaling and other important biological processes. Since deregulated signaling pathways form the basis of many human diseases, the SH3 domains have been attractive targets for novel therapeutics. High-affinity ligands for SH3 domains have been designed; however, these have all been peptide-based and no examples of entirely nonpeptide SH3 ligands have previously been reported. Using the mouse Tec Kinase SH3 domain as a model system for structure-based ligand design, we have identified several simple heterocyclic compounds that selectively bind to the Tec SH3 domain. Using a combination of nuclear magnetic resonance chemical shift perturbation, structure-activity relationships, and site-directed mutagenesis, the binding of these compounds at the proline-rich peptide-binding site has been characterized. The most potent of these, 2-aminoquinoline, bound with Kd = 125 microM and was able to compete for binding with a proline-rich peptide. Synthesis of 6-substituted-2-aminoquinolines resulted in ligands with up to 6-fold improved affinity over 2-aminoquinoline and enhanced specificity for the Tec SH3 domain. Therefore, 2-aminoquinolines may potentially be useful for the development of high affinity small molecule ligands for SH3 domains.

An Autoinhibitory Role for the Pleckstrin Homology Domain of Interleukin-2-Inducible Tyrosine Kinase and Its Interplay with Canonical Phospholipid Recognition.

PubMed

Devkota, Sujan; Joseph, Raji E; Boyken, Scott E; Fulton, D Bruce; Andreotti, Amy H

2017-06-13

Pleckstrin homology (PH) domains are well-known as phospholipid binding modules, yet evidence that PH domain function extends beyond lipid recognition is mounting. In this work, we characterize a protein binding function for the PH domain of interleukin-2-inducible tyrosine kinase (ITK), an immune cell specific signaling protein that belongs to the TEC family of nonreceptor tyrosine kinases. Its N-terminal PH domain is a well-characterized lipid binding module that localizes ITK to the membrane via phosphatidylinositol 3,4,5-trisphosphate (PIP 3 ) binding. Using a combination of nuclear magnetic resonance spectroscopy and mutagenesis, we have mapped an autoregulatory protein interaction site on the ITK PH domain that makes direct contact with the catalytic kinase domain of ITK, inhibiting the phospho-transfer reaction. Moreover, we have elucidated an important interplay between lipid binding by the ITK PH domain and the stability of the autoinhibitory complex formed by full length ITK. The ITK activation loop in the kinase domain becomes accessible to phosphorylation to the exogenous kinase LCK upon binding of the ITK PH domain to PIP 3 . By clarifying the allosteric role of the ITK PH domain in controlling ITK function, we have expanded the functional repertoire of the PH domain generally and opened the door to alternative strategies to target this specific kinase in the context of immune cell signaling.

CD6 and Linker of Activated T Cells are Potential Interaction Partners for T Cell-Specific Adaptor Protein.

PubMed

Hem, C D; Ekornhol, M; Granum, S; Sundvold-Gjerstad, V; Spurkland, A

2017-02-01

The T cell-specific adaptor protein (TSAd) contains several protein interaction domains, and is merging as a modulator of T cell activation. Several interaction partners for the TSAd proline-rich region and phosphotyrosines have been identified, including the Src and Tec family kinases lymphocyte-specific protein tyrosine kinase and interleukin 2-inducible T cell kinase. Via its Src homology 2 (SH2) domain, TSAd may thus function as a link between these enzymes and other signalling molecules. However, few binding partners to the TSAd SH2 domain in T cells are hitherto known. Through the use of in silico ligand prediction, peptide spot arrays, pull-down and immunoprecipitation experiments, we here report novel interactions between the TSAd SH2 domain and CD6 phosphotyrosine (pTyr) 629 and linker of activated T cells (LAT) pTyr 171 , pTyr 191 and pTyr 226 . © 2016 The Foundation for the Scandinavian Journal of Immunology.

Regulators of pseudohyphal differentiation in Saccharomyces cerevisiae identified through multicopy suppressor analysis in ammonium permease mutant strains.

PubMed Central

Lorenz, M C; Heitman, J

1998-01-01

Nitrogen-starved diploid cells of the yeast Saccharomyces cerevisiae differentiate into a filamentous, pseudohyphal growth form. Recognition of nitrogen starvation is mediated, at least in part, by the ammonium permease Mep2p and the Galpha subunit Gpa2p. Genetic activation of the pheromone-responsive MAP kinase cascade, which is also required for filamentous growth, only weakly suppresses the filamentation defect of Deltamep2/Deltamep2 and Deltagpa2/Deltagpa2 strain. Surprisingly, deletion of Mep1p, an ammonium permease not previously thought to regulate differentiation, significantly enhances the potency of MAP kinase activation, such that the STE11-4 allele induces filamentation to near wild-type levels in Deltamep1/Deltamep1 Deltamep2/Deltamep2 and Deltamep1/Deltamep1 Deltagpa2/Deltagpa2 strains. To identify additional regulatory components, we isolated high-copy suppressors of the filamentation defect of the Deltamep1/Deltamep1 Deltamep2/Deltamep2 mutant. Multicopy expression of TEC1, PHD1, PHD2 (MSS10/MSN1/FUP4), MSN5, CDC6, MSS11, MGA1, SKN7, DOT6, HMS1, HMS2, or MEP2 each restored filamentation in a Deltamep1/Deltamep1 Deltamep2/Deltamep2 strain. Overexpression of SRK1 (SSD1), URE2, DAL80, MEP1, or MEP3 suppressed only the growth defect of the Deltamep1/Deltamep1 Deltamep2/Deltamep2 mutant strain. Characterization of these genes through deletion analysis and epistasis underscores the complexity of this developmental pathway and suggests that stress conditions other than nitrogen deprivation may also promote filamentous growth. PMID:9832522

Signaling of the ITK (interleukin 2-inducible T cell kinase)-SYK (spleen tyrosine kinase) fusion kinase is dependent on adapter SLP-76 and on the adapter function of the kinases SYK and ZAP70.

PubMed

Hussain, Alamdar; Mohammad, Dara K; Gustafsson, Manuela O; Uslu, Merve; Hamasy, Abdulrahman; Nore, Beston F; Mohamed, Abdalla J; Smith, C I Edvard

2013-03-08

The inducible T cell kinase-spleen tyrosine kinase (ITK-SYK) oncogene consists of the Tec homology-pleckstrin homology domain of ITK and the kinase domain of SYK, and it is believed to be the cause of peripheral T cell lymphoma. We and others have recently demonstrated that this fusion protein is constitutively tyrosine-phosphorylated and is transforming both in vitro and in vivo. To gain a deeper insight into the molecular mechanism(s) underlying its activation and signaling, we mutated a total of eight tyrosines located in the SYK portion of the chimera into either phenylalanine or to the negatively charged glutamic acid. Although mutations in the interdomain-B region affected ITK-SYK kinase activity, they only modestly altered downstream signaling events. In contrast, mutations that were introduced in the kinase domain triggered severe impairment of downstream signaling. Moreover, we show here that SLP-76 is critical for ITK-SYK activation and is particularly required for the ITK-SYK-dependent phosphorylation of SYK activation loop tyrosines. In Jurkat cell lines, we demonstrate that expression of ITK-SYK fusion requires an intact SLP-76 function and significantly induces IL-2 secretion and CD69 expression. Furthermore, the SLP-76-mediated induction of IL-2 and CD69 could be further enhanced by SYK or ZAP-70, but it was independent of their kinase activity. Notably, ITK-SYK expression in SYF cells phosphorylates SLP-76 in the absence of SRC family kinases. Altogether, our data suggest that ITK-SYK exists in the active conformation state and is therefore capable of signaling without SRC family kinases or stimulation of the T cell receptor.

Signaling of the ITK (Interleukin 2-inducible T Cell Kinase)-SYK (Spleen Tyrosine Kinase) Fusion Kinase Is Dependent on Adapter SLP-76 and on the Adapter Function of the Kinases SYK and ZAP70*

PubMed Central

Hussain, Alamdar; Mohammad, Dara K.; Gustafsson, Manuela O.; Uslu, Merve; Hamasy, Abdulrahman; Nore, Beston F.; Mohamed, Abdalla J.; Smith, C. I. Edvard

2013-01-01

The inducible T cell kinase-spleen tyrosine kinase (ITK-SYK) oncogene consists of the Tec homology-pleckstrin homology domain of ITK and the kinase domain of SYK, and it is believed to be the cause of peripheral T cell lymphoma. We and others have recently demonstrated that this fusion protein is constitutively tyrosine-phosphorylated and is transforming both in vitro and in vivo. To gain a deeper insight into the molecular mechanism(s) underlying its activation and signaling, we mutated a total of eight tyrosines located in the SYK portion of the chimera into either phenylalanine or to the negatively charged glutamic acid. Although mutations in the interdomain-B region affected ITK-SYK kinase activity, they only modestly altered downstream signaling events. In contrast, mutations that were introduced in the kinase domain triggered severe impairment of downstream signaling. Moreover, we show here that SLP-76 is critical for ITK-SYK activation and is particularly required for the ITK-SYK-dependent phosphorylation of SYK activation loop tyrosines. In Jurkat cell lines, we demonstrate that expression of ITK-SYK fusion requires an intact SLP-76 function and significantly induces IL-2 secretion and CD69 expression. Furthermore, the SLP-76-mediated induction of IL-2 and CD69 could be further enhanced by SYK or ZAP-70, but it was independent of their kinase activity. Notably, ITK-SYK expression in SYF cells phosphorylates SLP-76 in the absence of SRC family kinases. Altogether, our data suggest that ITK-SYK exists in the active conformation state and is therefore capable of signaling without SRC family kinases or stimulation of the T cell receptor. PMID:23293025

Induction of epithelial to mesenchymal transition (EMT) and inhibition on adipogenesis: Two different sides of the same coin? Feasible roles and mechanisms of transforming growth factor β1 (TGF-β1) in age-related thymic involution.

PubMed

Tan, Jianxin; Wang, Yajun; Zhang, Nannan; Zhu, Xike

2016-08-01

Age-related thymic involution is characterized by a loss of thymic epithelial cells (TECs) and a concomitant increase in adipocytes, but the mechanisms involved in thymic adipogenesis are still not clear. Transforming growth factor β1 (TGF-β1) is a pleiotropic cytokine that has been reported to be up-regulated with age in thymic stromal cells in both human and mouse. However, the exact role of TGF-β1 in age-related thymic involution remains to be further elucidated. On the basis of previous findings, we propose a novel hypothesis that TGF-β1 functions a dual role in age-related thymic involution. On one hand, up-regulation of TGF-β1 promotes epithelial to mesenchymal transition (EMT) process in TECs via activating forkhead box protein C2 (FoxC2). On the other hand, TGF-β1 inhibits the transdifferentiation of EMT-derived mesenchymal cells to adipocytes in the thymus. If confirmed, our hypothesis will not only provide further evidence supporting that the transdifferentiation of TECs into pre-adipocytes represents a source of thymic adiposity during age-related thymic involution, but also uncover a unique role of TGF-β1 in the transdifferentiation of TECs into pre-adipocytes. Collectively, the inhibition of TGF-β1 may serve as a strategy to hinder age-related thymic involution or even to restore thymic function in the elderly. © 2016 International Federation for Cell Biology.

E-selectin engages PSGL-1 and CD44 through a common signaling pathway to induce integrin alphaLbeta2-mediated slow leukocyte rolling.

PubMed

Yago, Tadayuki; Shao, Bojing; Miner, Jonathan J; Yao, Longbiao; Klopocki, Arkadiusz G; Maeda, Kenichiro; Coggeshall, K Mark; McEver, Rodger P

2010-07-22

In inflamed venules, neutrophils rolling on E-selectin induce integrin alpha(L)beta(2)-dependent slow rolling on intercellular adhesion molecule-1 by activating Src family kinases (SFKs), DAP12 and Fc receptor-gamma (FcRgamma), spleen tyrosine kinase (Syk), and p38. E-selectin signaling cooperates with chemokine signaling to recruit neutrophils into tissues. Previous studies identified P-selectin glycoprotein ligand-1 (PSGL-1) as the essential E-selectin ligand and Fgr as the only SFK that initiate signaling to slow rolling. In contrast, we found that E-selectin engagement of PSGL-1 or CD44 triggered slow rolling through a common, lipid raft-dependent pathway that used the SFKs Hck and Lyn as well as Fgr. We identified the Tec kinase Bruton tyrosine kinase as a key signaling intermediate between Syk and p38. E-selectin engagement of PSGL-1 was dependent on its cytoplasmic domain to activate SFKs and slow rolling. Although recruiting phosphoinositide-3-kinase to the PSGL-1 cytoplasmic domain was reported to activate integrins, E-selectin-mediated slow rolling did not require phosphoinositide-3-kinase. Studies in mice confirmed the physiologic significance of these events for neutrophil slow rolling and recruitment during inflammation. Thus, E-selectin triggers common signals through distinct neutrophil glycoproteins to induce alpha(L)beta(2)-dependent slow rolling.

Developmental Regulation of an Adhesin Gene during Cellular Morphogenesis in the Fungal Pathogen Candida albicans▿ †

PubMed Central

Argimón, Silvia; Wishart, Jill A.; Leng, Roger; Macaskill, Susan; Mavor, Abigail; Alexandris, Thomas; Nicholls, Susan; Knight, Andrew W.; Enjalbert, Brice; Walmsley, Richard; Odds, Frank C.; Gow, Neil A. R.; Brown, Alistair J. P.

2007-01-01

Candida albicans expresses specific virulence traits that promote disease establishment and progression. These traits include morphological transitions between yeast and hyphal growth forms that are thought to contribute to dissemination and invasion and cell surface adhesins that promote attachment to the host. Here, we describe the regulation of the adhesin gene ALS3, which is expressed specifically during hyphal development in C. albicans. Using a combination of reporter constructs and regulatory mutants, we show that this regulation is mediated by multiple factors at the transcriptional level. The analysis of ALS3 promoter deletions revealed that this promoter contains two activation regions: one is essential for activation during hyphal development, while the second increases the amplitude of this activation. Further deletion analyses using the Renilla reniformis luciferase reporter delineate the essential activation region between positions −471 and −321 of the promoter. Further 5′ or 3′ deletions block activation. ALS3 transcription is repressed mainly by Nrg1 and Tup1, but Rfg1 contributes to this repression. Efg1, Tec1, and Bcr1 are essential for the transcriptional activation of ALS3, with Tec1 mediating its effects indirectly through Bcr1 rather than through the putative Tec1 sites in the ALS3 promoter. ALS3 transcription is not affected by Cph2, but Cph1 contributes to full ALS3 activation. The data suggest that multiple morphogenetic signaling pathways operate through the promoter of this adhesin gene to mediate its developmental regulation in this major fungal pathogen. PMID:17277173

Prostaglandin E(2) and insulin-like growth factor I interact to enhance proliferation of theca externa cells from chicken prehierarchical follicles.

PubMed

Jia, Yudong; Lin, Jinxing; Mi, Yuling; Zhang, Caiqiao

2013-10-01

The interactive effect of insulin-like growth factor I (IGF-I) and prostaglandin E2 (PGE2) on the proliferation of theca externa cells (TECs) was investigated in the prehierarchical small yellow follicles of laying hens. IGF-I manifested a proliferating effect like PGE2 on TECs, but this stimulating effect was restrained by AG1024 (IGF-IR inhibitor), KP372-1 (PKB/AKT inhibitor) or NS398 (COX-2 inhibitor). AG1024, KP372-1 or NS398 abolished IGF-I-stimulated COX-2 expression and PGE2 production. Meanwhile, KP372-1, NS398 or AG1024 depressed the PGE2-stimulated expression of COX-2 and IGF-IR mRNA. Therefore, the IGF-I receptor pathway up-regulates COX-2 expression and PGE2 synthesis via PKB signaling cascade, and then PGE2 stimulates IGF-IR mRNA expression to promote TEC proliferation in an autocrine pattern. Overall, the reciprocal stimulation of intracellular PGE2 and IGF-I may enhance TEC proliferation and facilitate the development of chicken prehierarchical follicles. Copyright © 2013 Elsevier Inc. All rights reserved.

Roadwaste : issues and options.

DOT National Transportation Integrated Search

1998-06-01

The Oregon Department of Transportation (ODOT) is conducting a study to determine roadwaste management options. Phase 1 consisted of a thorough review of regulations and standards, roadwaste characterization, current management practices, and new tec...

The orally available Btk inhibitor ibrutinib (PCI-32765) protects against osteoclast-mediated bone loss.

PubMed

Shinohara, Masahiro; Chang, Betty Y; Buggy, Joseph J; Nagai, Yusuke; Kodama, Tatsuhiko; Asahara, Hiroshi; Takayanagi, Hiroshi

2014-03-01

Bone-resorbing osteoclasts play an essential role in normal bone homeostasis, as well as in various bone disorders such as osteoporosis and rheumatoid arthritis. Previously we showed that the Tec family of tyrosine kinases is essential for the differentiation of osteoclasts and the inhibition of Btk is a promising strategy for the prevention of the bone loss in osteoclast-associated bone disorders. Here we demonstrate that an orally available Btk inhibitor, ibrutinib (PCI-32765), suppresses osteoclastic bone resorption by inhibiting both osteoclast differentiation and function. Ibrutinib downregulated the expression of NFATc1, the key transcription factor for osteoclastogenesis, and disrupted the formation of the actin ring in mature osteoclasts. In addition, genome-wide screening revealed that Btk regulates the expression of the genes involved in osteoclast differentiation and function in both an NFATc1-dependent and -independent manner. Finally, we showed that ibrutinib administration ameliorated the bone loss that developed in a RANKL-induced osteoporosis mouse model. Thus, this study suggests ibrutinib to be a promising therapeutic agent for osteoclast-associated bone diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

Comparison with IRI-PLUS and IRI-2012-TEC values of GPS-TEC values

NASA Astrophysics Data System (ADS)

Atıcı, Ramazan; Saǧır, Selçuk

2016-07-01

This study presents a comparison with IRI-PLUS and IRI-2012 Total Electron Content (TEC) values of Total Electron Content (TEC) values obtained from Ankara station (39,7 N; 32,76 E) of Global Position System (GPS) of Turkey on equinox and solstice days of 2009 year. For all days, it is observed that GPS-TEC values are greater than IRI-2012-TEC values, while IRI-PLUS-TEC values are very close to GPS-TEC values. When GPS-TEC values for both equinoxes are compared, it is seen that TEC values on September equinox are greater than one on March equinox. However, it is observed that GPS-TEC values on June solstice are greater than one on December solstice. Also, the relationship between GPS-TEC values and geomagnetic indexes is investigated.

Research on global plasmaspheric electron content by using LEO occultation and GPS data

NASA Astrophysics Data System (ADS)

Chen, Peng; Yao, Yibin

2015-05-01

This paper investigates the characteristics of global plasmaspheric electron content (pTEC) using COSMIC (Constellation Observing System for Meteorology, Ionosphere and Climate) occultation and GPS (Global Positioning System) data. The ionospheric electron content (iTEC) within 100-1000 km was obtained by fitting the COSMIC occultation electron density profiles, and the pTEC was obtained by subtracting the iTEC from CODE (Center for Orbit Determination in Europe) GIM (global ionosphere maps) TEC provided by University of Bern. This paper also investigates the characteristics of pTEC variations with local time, latitude and season. The results show that in 2011, the worldwide average of pTEC was 4.02 TECu, which is consistent with the findings of other studies. The pTEC shows significant diurnal variation characteristics, that is, pTEC is higher during daytime than during nighttime, but the percentage contribution of pTEC to GPS TEC is higher during nighttime than during daytime. The pTEC varies with the seasons, pTEC hemispheres symmetrically during spring and autumn, while pTEC in the summer hemisphere is higher than that in the winter hemisphere. Moreover, the percentage contribution of pTEC to GPS TEC (total electron content) is higher in winter hemisphere than in summer hemisphere.

Increased cFLIP expression in thymic epithelial tumors blocks autophagy via NF-κB signalling.

PubMed

Belharazem, Djeda; Grass, Albert; Paul, Cornelia; Vitacolonna, Mario; Schalke, Berthold; Rieker, Ralf J; Körner, Daniel; Jungebluth, Philipp; Simon-Keller, Katja; Hohenberger, Peter; Roessner, Eric M; Wiebe, Karsten; Gräter, Thomas; Kyriss, Thomas; Ott, German; Geserick, Peter; Leverkus, Martin; Ströbel, Philipp; Marx, Alexander

2017-10-27

The anti-apoptotic cellular FLICE-like inhibitory protein cFLIP plays a pivotal role in normal tissues homoeostasis and the development of many tumors, but its role in normal thymus (NT), thymomas and thymic carcinomas (TC) is largely unknown. Expression, regulation and function of cFLIP were analyzed in biopsies of NT, thymomas, thymic squamous cell carcinomas (TSCC), thymic epithelial cells (TECs) derived thereof and in the TC line 1889c by qRT-PCR, western blot, shRNA techniques, and functional assays addressing survival, senescence and autophagy. More than 90% of thymomas and TSCCs showed increased cFLIP expression compared to NT. cFLIP expression declined with age in NTs but not in thymomas. During short term culture cFLIP expression levels declined significantly slower in neoplastic than non-neoplastic primary TECs. Down-regulation of cFLIP by shRNA or NF-κB inhibition accelerated senescence and induced autophagy and cell death in neoplastic TECs. The results suggest a role of cFLIP in the involution of normal thymus and the development of thymomas and TSCC. Since increased expression of cFLIP is a known tumor escape mechanism, it may serve as tissue-based biomarker in future clinical trials, including immune checkpoint inhibitor trials in the commonly PD-L1 high thymomas and TCs.

Thermal performance of a multi-evaporator loop heat pipe with thermal masses and thermal electrical coolers

NASA Technical Reports Server (NTRS)

Ku, Jentung; Ottenstein, Laura; Birur, Gajanana

2004-01-01

This paper describes thermal performance of a loop heat pipe (LHP) with two evaporators and two condensers in ambient testing. Each evaporator has an outer diameter of 15mm and a length of 76mm, and has an integral compensation chamber (CC). An aluminum mass of 500 grams is attached to each evaporator to simulate the instrument mass. A thermal electric cooler (TEC) is installed on each CC to provide heating as well as cooling for CC temperature control. A flow regulator is installed in the condenser section to prevent vapor from going back to the evaporators in the event that one of condenser is fully utilized. Ammonia was used ad the working fluid. Tests conducted included start-up, power cycle, heat load sharing, sink temperature cycle, operating temperature control with TECs, and capillary limit tests. Experimental data showed that the loop could start with a heat load of less than 1OW even with added thermal masses. The loop operated stably with even and uneven evaporator heat loads, and even and uneven condenser sink temperatures. The operating temperature could be controlled within +/-0.5K of the set point temperature using either or both TECs, and the required TEC control heater power was less than 2W under most test conditions. Heat load sharing between the two evaporators was also successfully demonstrated. The loop had a heat transport capability of 120W to 140W, and could recover from a dry-out when the heat load was reduced. The 500-gram aluminum mass on each evaporator had a negligible effect on the loop operation. Existing LHPs servicing the orbiting spacecraft have a single evaporator with an outer diameter of about 25mm. Important performance characteristics demonstrated by this LHP included: 1) Operation of an LHP with 15mm diameter evaporators; 2) Robustness and reliability of an LHP with multiple evaporators and multiple condensers under various test conditions; 3) Heat load sharing among LHP evaporators; 4) Effectiveness of TECs in controlling the LHP operating temperature; and 5) Effectiveness of the flow regulator in preventing vapor from going back the evaporators.

Thermal Performance of a Multi-Evaporator Loop Heat Pipe with Thermal Masses and Thermoelectric Coolers

NASA Technical Reports Server (NTRS)

Ku, Jen-Tung; Ottenstein, Laura; Birur, Gajanana

2004-01-01

This paper describes thermal performance of a loop heat pipe (LHP) with two evaporators and two condensers in ambient testing. Each evaporator has an outer diameter of 15mm and a length of 76mm, and has an integral compensation chamber (CC). An aluminum mass of 500 grams is attached to each evaporator to simulate the instrument mass. A thermoelectric cooler (TEC) is installed on each CC to provide heating as well as cooling for CC temperature control. A flow regulator is installed in the condenser section to prevent vapor from going back to the evaporators in the event that one of the condensers is fully utilized. Ammonia was used as the working fluid. Tests conducted included start-up, power cycle, heat load sharing, sink temperature cycle, operating temperature control with TECs, and capillary limit tests. Experimental data showed that the loop could start with a heat load of less than 10W even with added thermal masses. The loop operated stably with even and uneven evaporator heat loads, and even and uneven condenser sink temperatures. The operating temperature could be controlled within +/- 0.5K of the set point temperature using either or both TECs, and the required TEC control heater power was less than 2W under most test conditions. Heat load sharing between the two evaporators was also successfully demonstrated. The loop had a heat transport capability of 120W to 140W, and could recover from a dry-out when the heat load was reduced. The 500-gram aluminum mass on each evaporator had a negligible effect on the loop operation. Existing LHPs servicing orbiting spacecraft have a single evaporator with an outer diameter of about 25mm. Important performance characteristics demonstrated by this LHP included: 1) Operation of an LHP with 15mm diameter evaporators; 2) Robustness and reliability of an LHP with multiple evaporators and multiple condensers under various test conditions; 3) Heat load sharing among LHP evaporators; 4) Effectiveness of TECs in controlling the LHP operating temperature; and 5 ) Effectiveness of the flow regulator in preventing vapor from going back the evaporators.

Total electron content (TEC) variability at Los Alamos, New Mexico: A comparative study: FORTE-derived TEC analysis

NASA Astrophysics Data System (ADS)

Huang, Zhen; Roussel-Dupré, Robert

2005-12-01

Data collected from Fast On-Orbit Recording of Transient Events (FORTE) satellite-received Los Alamos Portable Pulser (LAPP) signals during 1997-2002 are used to derive the total electron content (TEC) at Los Alamos, New Mexico. The LAPP-derived TECs at Los Alamos are analyzed for diurnal, seasonal, interannual, and 27-day solar cycle variations. Several aspects in deriving TEC are analyzed, including slant to vertical TEC conversion, quartic effects on transionosperic signals, and geomagnetic storm effects on the TEC variance superimposed on the averaged TEC values.

Comparison of GPS derived TEC with the TEC predicted by IRI 2012 model in the southern Equatorial Ionization Anomaly crest within the Eastern Africa region

NASA Astrophysics Data System (ADS)

Sulungu, Emmanuel D.; Uiso, Christian B. S.; Sibanda, Patrick

2018-04-01

We have compared the TEC obtained from the IRI-2012 model with the GPS derived TEC data recorded within southern crest of the EIA in the Eastern Africa region using the monthly means of the 5 international quiet days for equinoxes and solstices months for the period of 2012 - 2013. GPS-derived TEC data have been obtained from the Africa array and IGS network of ground based dual-frequency GPS receivers from four stations (Kigali (1.95°S, 30.09°E; Geom. Lat. 11.63°S), Malindi (2.99°S, 40.19°E; Geom. Lat. 12.42°S), Mbarara (0.60°S, 30.74°E; Geom. Lat. 10.22°S) and Nairobi (1.22°S, 36.89°E; Geom. Lat. 10.69°S)) located within the EIA crest in this region. All the three options for topside Ne of IRI-2012 model and ABT-2009 for bottomside thickness have been used to compute the IRI TEC. Also URSI coefficients were considered in this study. These results are compared with the TEC estimated from GPS measurements. Correlation Coefficients between the two sets of data, the Root-Mean Square Errors (RMSE) of the IRI-TEC from the GPS-TEC, and the percentage RMSE of the IRI-TEC from the GPS-TEC have been computed. Our general results show that IRI-2012 model with all three options overestimates the GPS-TEC for all seasons and at all stations, and IRI-2001 overestimates GPS-TEC more compared with other options. IRI-Neq and IRI-01-corr are closely matching in most of the time. The observation also shows that, GPS TEC are underestimated by TEC from IRI model during noon hours, especially during equinoctial months. Further, GPS-TEC values and IRI-TEC values using all the three topside Ne options show very good correlation (above 0.8). On the other hand, the TEC using IRI-Neq and IRI-01- corr had smaller deviations from the GPS-TEC compared to the IRI-2001.

Discovery of 6-Fluoro-5-(R)-(3-(S)-(8-fluoro-1-methyl-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-2-methylphenyl)-2-(S)-(2-hydroxypropan-2-yl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide (BMS-986142): A Reversible Inhibitor of Bruton's Tyrosine Kinase (BTK) Conformationally Constrained by Two Locked Atropisomers.

PubMed

Watterson, Scott H; De Lucca, George V; Shi, Qing; Langevine, Charles M; Liu, Qingjie; Batt, Douglas G; Beaudoin Bertrand, Myra; Gong, Hua; Dai, Jun; Yip, Shiuhang; Li, Peng; Sun, Dawn; Wu, Dauh-Rurng; Wang, Chunlei; Zhang, Yingru; Traeger, Sarah C; Pattoli, Mark A; Skala, Stacey; Cheng, Lihong; Obermeier, Mary T; Vickery, Rodney; Discenza, Lorell N; D'Arienzo, Celia J; Zhang, Yifan; Heimrich, Elizabeth; Gillooly, Kathleen M; Taylor, Tracy L; Pulicicchio, Claudine; McIntyre, Kim W; Galella, Michael A; Tebben, Andy J; Muckelbauer, Jodi K; Chang, ChiehYing; Rampulla, Richard; Mathur, Arvind; Salter-Cid, Luisa; Barrish, Joel C; Carter, Percy H; Fura, Aberra; Burke, James R; Tino, Joseph A

2016-10-13

Bruton's tyrosine kinase (BTK), a nonreceptor tyrosine kinase, is a member of the Tec family of kinases. BTK plays an essential role in B cell receptor (BCR)-mediated signaling as well as Fcγ receptor signaling in monocytes and Fcε receptor signaling in mast cells and basophils, all of which have been implicated in the pathophysiology of autoimmune disease. As a result, inhibition of BTK is anticipated to provide an effective strategy for the clinical treatment of autoimmune diseases such as lupus and rheumatoid arthritis. This article details the structure-activity relationships (SAR) leading to a novel series of highly potent and selective carbazole and tetrahydrocarbazole based, reversible inhibitors of BTK. Of particular interest is that two atropisomeric centers were rotationally locked to provide a single, stable atropisomer, resulting in enhanced potency and selectivity as well as a reduction in safety liabilities. With significantly enhanced potency and selectivity, excellent in vivo properties and efficacy, and a very desirable tolerability and safety profile, 14f (BMS-986142) was advanced into clinical studies.

Increased cFLIP expression in thymic epithelial tumors blocks autophagy via NF-κB signalling

PubMed Central

Belharazem, Djeda; Grass, Albert; Paul, Cornelia; Vitacolonna, Mario; Schalke, Berthold; Rieker, Ralf J.; Körner, Daniel; Jungebluth, Philipp; Simon-Keller, Katja; Hohenberger, Peter; Roessner, Eric M.; Wiebe, Karsten; Gräter, Thomas; Kyriss, Thomas; Ott, German; Geserick, Peter; Ströbel, Philipp; Marx, Alexander

2017-01-01

The anti-apoptotic cellular FLICE-like inhibitory protein cFLIP plays a pivotal role in normal tissues homoeostasis and the development of many tumors, but its role in normal thymus (NT), thymomas and thymic carcinomas (TC) is largely unknown. Expression, regulation and function of cFLIP were analyzed in biopsies of NT, thymomas, thymic squamous cell carcinomas (TSCC), thymic epithelial cells (TECs) derived thereof and in the TC line 1889c by qRT-PCR, western blot, shRNA techniques, and functional assays addressing survival, senescence and autophagy. More than 90% of thymomas and TSCCs showed increased cFLIP expression compared to NT. cFLIP expression declined with age in NTs but not in thymomas. During short term culture cFLIP expression levels declined significantly slower in neoplastic than non-neoplastic primary TECs. Down-regulation of cFLIP by shRNA or NF-κB inhibition accelerated senescence and induced autophagy and cell death in neoplastic TECs. The results suggest a role of cFLIP in the involution of normal thymus and the development of thymomas and TSCC. Since increased expression of cFLIP is a known tumor escape mechanism, it may serve as tissue-based biomarker in future clinical trials, including immune checkpoint inhibitor trials in the commonly PD-L1high thymomas and TCs. PMID:29163772

Short Term Single Station GNSS TEC Prediction Using Radial Basis Function Neural Network

NASA Astrophysics Data System (ADS)

Muslim, Buldan; Husin, Asnawi; Efendy, Joni

2018-04-01

TEC prediction models for 24 hours ahead have been developed from JOG2 GPS TEC data during 2016. Eleven month of TEC data were used as a training model of the radial basis function neural network (RBFNN) and 1 month of last data (December 2016) is used for the RBFNN model testing. The RBFNN inputs are the previous 24 hour TEC data and the minimum of Dst index during the previous 24 hours. Outputs of the model are 24 ahead TEC prediction. Comparison of model prediction show that the RBFNN model is able to predict the next 24 hours TEC is more accurate than the TEC GIM model.

The Response of Mid-Latitude Ionospheric TEC to Geomagnetic Storms and Solar Flares

NASA Astrophysics Data System (ADS)

Huang, Z.; Roussel-Dupre, R.

2004-12-01

The effects of geomagnetic storms and solar flares on the ionosphere are manifested as large magnitude sudden fluctuations in the Total Electron Content (TEC). In this study, the broadband VHF signal (30-100MHz) data from the Los Alamos Portable Pulser (LAPP) received by the FORTE (Fast Onboard Recording of Transient Events) satellite during the period of 1997-2002 are used to investigate the mean TEC variation response to geomagnetic storm. A total of 14 geomagnetic storms are selected where FORTE-LAPP data are available to derive average TECs during extended storm-time and non-storm time for a given storm. The variations in the ionospheric TECs at Los Alamos, New Mexico are investigated for the 14 selected geomagnetic storms. In most cases (12 out of 14), we see overall enhancements in TEC as a result of geomagnetic storm impact at Los Alamos. The relative enhancements in TEC at Los Alamos due to a geomagnetic storm can reach as high as 3-fold of the normal TEC values. The overall absolute enhancements in TEC at Los Alamos are up to about 30 TECU. The magnitude of TEC enhancements is diversified over all storm categories without a clean-cut relationship between the storm intensity and the TEC enhancement. The mean TEC variation response to geomagnetic storm can be complicated when several consecutive storms occurred in a row and a net TEC reduction may be seen. Data of continuous GPS TEC measurements are collected at a 1-minute time resolution during July 2004 when 5 X-class solar flares occurred from two Allen Osborne Associates ICS-4000Z GPS receivers mounted at the Physics Building at Los Alamos National Laboratory. In detecting effects of solar flares on the ionospheric TEC, we apply appropriate filtering to remove the linear trend of TEC and a coherent processing of TEC variations simultaneously for all the visible GPS satellites in a given time interval. The responses of ionospheric TEC at minute time scale to these powerful impulsive solar flares are investigated. The onset time of the ionospheric response and the magnitude of the TEC fluctuations and its time derivative are examined along with their relationships with the solar flux characteristics, duration of the flare and location of the flare on the Sun, X-ray emission variations during the flares, and local time of the flare occurrence.

The proangiogenic phenotype of tumor-derived endothelial cells is reverted by the overexpression of platelet-activating factor acetylhydrolase.

PubMed

Doublier, Sophie; Ceretto, Monica; Lupia, Enrico; Bravo, Stefania; Bussolati, Benedetta; Camussi, Giovanni

2007-10-01

We previously reported that human tumor-derived endothelial cells (TEC) have an angiogenic phenotype related to the autocrine production of several angiogenic factors. The purpose of the present study was to evaluate whether an enhanced synthesis of platelet-activating factor (PAF) might contribute to the proangiogenic characteristics of TEC and whether its inactivation might inhibit angiogenesis. To address the potential role of PAF in the proangiogenic characteristics of TEC, we engineered TEC to stably overexpress human plasma PAF-acetylhydrolase (PAF-AH), the major PAF-inactivating enzyme, and we evaluated in vitro and in vivo angiogenesis. TECs were able to synthesize a significantly enhanced amount of PAF compared with normal human microvascular endothelial cells when stimulated with thrombin, vascular endothelial growth factor, or soluble CD154. Transfection of TEC with PAF-AH (TEC-PAF-AH) significantly inhibited apoptosis resistance and spontaneous motility of TEC. In addition, PAF and vascular endothelial growth factor stimulation enhanced the motility and adhesion of TEC but not of TEC-PAF-AH. In vitro, TEC-PAF-AH lost the characteristic ability of TEC to form vessel-like structures when plated on Matrigel. Finally, when cells were injected s.c. within Matrigel in severe combined immunodeficiency mice or coimplanted with a renal carcinoma cell line, the overexpression of PAF-AH induced a significant reduction of functional vessel formation. These results suggest that inactivation of PAF, produced by TEC, by the overexpression of plasma PAF-AH affects survival, migration, and the angiogenic response of TEC both in vitro and in vivo.

Validation of the technique for absolute total electron content and differential code biases estimation

NASA Astrophysics Data System (ADS)

Mylnikova, Anna; Yasyukevich, Yury; Yasyukevich, Anna

2017-04-01

We have developed a technique for vertical total electron content (TEC) and differential code biases (DCBs) estimation using data from a single GPS/GLONASS station. The algorithm is based on TEC expansion into Taylor series in space and time (TayAbsTEC). We perform the validation of the technique using Global Ionospheric Maps (GIM) computed by Center for Orbit Determination in Europe (CODE) and Jet Propulsion Laboratory (JPL). We compared differences between absolute vertical TEC (VTEC) from GIM and VTEC evaluated by TayAbsTEC for 2009 year (solar activity minimum - sunspot number about 0), and for 2014 year (solar activity maximum - sunspot number 110). Since there is difference between VTEC from CODE and VTEC from JPL, we compare TayAbsTEC VTEC with both of them. We found that TayAbsTEC VTEC is closer to CODE VTEC than to JPL VTEC. The difference between TayAbsTEC VTEC and GIM VTEC is more noticeable for solar activity maximum (2014) than for solar activity minimum (2009) for both CODE and JPL. The distribution of VTEC differences is close to Gaussian distribution, so we conclude that results of TayAbsTEC are in the agreement with GIM VTEC. We also compared DCBs evaluated by TayAbsTEC and DCBs from GIM, computed by CODE. The TayAbsTEC DCBs are in good agreement with CODE DCBs for GPS satellites, but differ noticeable for GLONASS. We used DCBs to correct slant TEC to find out which DCBs give better results. Slant TEC correction with CODE DCBs produces negative and nonphysical TEC values. Slant TEC correction with TayAbsTEC DCBs doesn't produce such artifacts. The technique we developed is used for VTEC and DCBs calculation given only local GPS/GLONASS networks data. The evaluated VTEC data are in GIM framework which is handy when various data analyses are made.

2',3-dihydroxy-5-methoxybiphenyl suppresses fMLP-induced superoxide anion production and cathepsin G release by targeting the β-subunit of G-protein in human neutrophils.

PubMed

Liao, Hsiang-Ruei; Chen, Ih-Sheng; Liu, Fu-Chao; Lin, Shinn-Zhi; Tseng, Ching-Ping

2018-06-15

This study investigates the effect and the underlying mechanism of 2',3-dihydroxy-5-methoxybiphenyl (RIR-2), a lignan extracted from the roots of Rhaphiolepis indica (L.) Lindl. ex Ker var. tashiroi Hayata ex Matsum. & Hayata (Rosaceae), on N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-induced respiratory burst and cathepsin G in human neutrophils. Signaling pathways regulated by RIR-2 which modulated fMLP-induced respiratory burst were evaluated by an interaction between β subunit of G-protein (Gβ) with downstream signaling induced by fMLP and by immunoblotting analysis of the downstream targets of Gβ-protein. RIR-2 inhibited fMLP-induced superoxide anion production (IC 50 :2.57 ± 0.22 μM), cathepsin G release (IC 50 :18.72 ± 3.76 μM) and migration in a concentration dependent manner. RIR-2 specifically suppresses fMLP-induced Src family kinases phosphorylation by inhibiting the interaction between Gβ-protein with Src kinases without inhibiting Src kinases activities, therefore, RIR-2 attenuated the downstream targets of Src kinase, such as phosphorylation of Raf/ERK, AKT, P38, PLCγ2, PKC and translocation Tec, p47 ph ° x and P40 ph ° x from the cytosol to the inner leaflet of the plasma membrane. Furthermore, RIR-2 attenuated fMLP-induced intracellular calcium mobilization by inhibiting the interaction between Gβ-protein with PLCβ2. RIR-2 was not a competitive or allosteric antagonist of fMLP. On the contrary, phorbol 12-myristate 13-acetate (PMA)-induced phosphorylation of Src, AKT, P38, PKC and membrane localization of p47 ph ° x and P40 ph ° x remained unaffected. RIR-2 specifically modulates fMLP-mediated neutrophil superoxide anion production and cathepsin G release by inhibiting the interaction between Gβ-protein with downstream signaling which subsequently interferes with the activation of intracellular calcium, PLCγ2, AKT, p38, PKC, ERK, p47 ph ° x and p40 phox . Copyright © 2018 Elsevier B.V. All rights reserved.

High-resolution station-based diurnal ionospheric total electron content (TEC) from dual-frequency GPS observations

NASA Astrophysics Data System (ADS)

ćepni, Murat S.; Potts, Laramie V.; Miima, John B.

2013-09-01

electron content (TEC) estimates derived from Global Navigation Satellite System (GNSS) signal delays provide a rich source of information about the Earth's ionosphere. Networks of Global Positioning System (GPS) receivers data can be used to represent the ionosphere by a Global Ionospheric Map (GIM). Data input for GIMs is dual-frequency GNSS-only or a mixture of GNSS and altimetry observations. Parameterization of GNSS-only GIMs approaches the ionosphere as a single-layer model (SLM) to determine GPS TEC models over a region. Limitations in GNSS-only GIM TEC are due largely to the nonhomogenous global distribution of GPS tracking stations with large data gaps over the oceans. The utility of slant GPS ionospheric-induced path delays for high temporal resolution from a single-station data rate offers better representation of TEC over a small region. A station-based vertical TEC (TECV) approach modifies the traditional single-layer model (SLM) GPS TEC method by introducing a zenith angle weighting (ZAW) filter to capture signal delays from mostly near-zenith satellite passes. Comparison with GIMs shows the station-dependent TEC (SD-TEC) model exhibits robust performance under variable space weather conditions. The SD-TEC model was applied to investigate ionospheric TEC variability during the geomagnetic storm event of 9 March 2012 at midlatitude station NJJJ located in New Jersey, USA. The high temporal resolution TEC results suggest TEC production and loss rate differences before, during, and after the storm.

Performance evaluation of linear time-series ionospheric Total Electron Content model over low latitude Indian GPS stations

NASA Astrophysics Data System (ADS)

Dabbakuti, J. R. K. Kumar; Venkata Ratnam, D.

2017-10-01

Precise modeling of the ionospheric Total Electron Content (TEC) is a critical aspect of Positioning, Navigation, and Timing (PNT) services intended for the Global Navigation Satellite Systems (GNSS) applications as well as Earth Observation System (EOS), satellite communication, and space weather forecasting applications. In this paper, linear time series modeling has been carried out on ionospheric TEC at two different locations at Koneru Lakshmaiah University (KLU), Guntur (geographic 16.44° N, 80.62° E; geomagnetic 7.55° N) and Bangalore (geographic 12.97° N, 77.59° E; geomagnetic 4.53° N) at the northern low-latitude region, for the year 2013 in the 24th solar cycle. The impact of the solar and geomagnetic activity on periodic oscillations of TEC has been investigated. Results confirm that the correlation coefficient of the estimated TEC from the linear model TEC and the observed GPS-TEC is around 93%. Solar activity is the key component that influences ionospheric daily averaged TEC while periodic component reveals the seasonal dependency of TEC. Furthermore, it is observed that the influence of geomagnetic activity component on TEC is different at both the latitudes. The accuracy of the model has been assessed by comparing the International Reference Ionosphere (IRI) 2012 model TEC and TEC measurements. Moreover, the absence of winter anomaly is remarkable, as determined by the Root Mean Square Error (RMSE) between the linear model TEC and GPS-TEC. On the contrary, the IRI2012 model TEC evidently failed to predict the absence of winter anomaly in the Equatorial Ionization Anomaly (EIA) crest region. The outcome of this work will be useful for improving the ionospheric now-casting models under various geophysical conditions.

Comparison of GPS-derived TEC with IRI-2012 and IRI-2007 TEC predictions at Surat, a location around the EIA crest in the Indian sector, during the ascending phase of solar cycle 24

NASA Astrophysics Data System (ADS)

Patel, N. C.; Karia, S. P.; Pathak, K. N.

2017-07-01

This paper presents a comparison of GPS-derived TEC with IRI-2012 and IRI-2007 TEC Predictions at Surat (21.16°N Geographic latitude, 72.78°E Geographic longitude, 12.90°N Geomagnetic latitude) a location around the Equatorial Ionisation Anomaly (EIA) crest in the Indian sector, during the Ascending Phase of Solar Cycle 24, for a period of three years (January 2010-December 2012). In this comparison, plasmaspheric electron content (PEC) contribution to the GPS-TEC has been removed. It is observed that percentage PEC contribution to the GPS-TEC varies from about ∼15% (at the noon local time) to about ∼30% (at the morning local time). From the monthly comparison of GPS-TEC with IRI-TEC, it is observed that, TEC predicted by both the models overestimates in June-2012 and underestimates TEC in November-2011, December-2011 and March-2011. For all other months IRI estimates the TEC well. From the seasonal comparison, it is observed that the peak time appears ∼1-h later than the actual peak time in Winter 2010, Summer 2011, and Equinox 2010 and 2012 (the result suggest that it may be due to discrepancies/disagreement of both the versions of the IRI model in estimating the peak density as well as the thickness and shape parameters of the electron density profiles). For the Summer season, the IRI-TEC estimates the TEC well for all the years. Further, the seasonal variation of the GPS-TEC for all the three years matches well with IRI-2012 model compared to IRI-2007 model. Also, the mean annual TEC is predicted well by both the versions of the IRI model.

Radiation detector system having heat pipe based cooling

DOEpatents

Iwanczyk, Jan S.; Saveliev, Valeri D.; Barkan, Shaul

2006-10-31

A radiation detector system having a heat pipe based cooling. The radiation detector system includes a radiation detector thermally coupled to a thermo electric cooler (TEC). The TEC cools down the radiation detector, whereby heat is generated by the TEC. A heat removal device dissipates the heat generated by the TEC to surrounding environment. A heat pipe has a first end thermally coupled to the TEC to receive the heat generated by the TEC, and a second end thermally coupled to the heat removal device. The heat pipe transfers the heat generated by the TEC from the first end to the second end to be removed by the heat removal device.

CEDAR-GEM Challenge for Systematic Assessment of Ionosphere/Thermosphere Models in Predicting TEC During the 2006 December Storm Event

NASA Astrophysics Data System (ADS)

Shim, J. S.; Rastätter, L.; Kuznetsova, M.; Bilitza, D.; Codrescu, M.; Coster, A. J.; Emery, B. A.; Fedrizzi, M.; Förster, M.; Fuller-Rowell, T. J.; Gardner, L. C.; Goncharenko, L.; Huba, J.; McDonald, S. E.; Mannucci, A. J.; Namgaladze, A. A.; Pi, X.; Prokhorov, B. E.; Ridley, A. J.; Scherliess, L.; Schunk, R. W.; Sojka, J. J.; Zhu, L.

2017-10-01

In order to assess current modeling capability of reproducing storm impacts on total electron content (TEC), we considered quantities such as TEC, TEC changes compared to quiet time values, and the maximum value of the TEC and TEC changes during a storm. We compared the quantities obtained from ionospheric models against ground-based GPS TEC measurements during the 2006 AGU storm event (14-15 December 2006) in the selected eight longitude sectors. We used 15 simulations obtained from eight ionospheric models, including empirical, physics-based, coupled ionosphere-thermosphere, and data assimilation models. To quantitatively evaluate performance of the models in TEC prediction during the storm, we calculated skill scores such as RMS error, Normalized RMS error (NRMSE), ratio of the modeled to observed maximum increase (Yield), and the difference between the modeled peak time and observed peak time. Furthermore, to investigate latitudinal dependence of the performance of the models, the skill scores were calculated for five latitude regions. Our study shows that RMSE of TEC and TEC changes of the model simulations range from about 3 TECU (total electron content unit, 1 TECU = 1016 el m-2) (in high latitudes) to about 13 TECU (in low latitudes), which is larger than latitudinal average GPS TEC error of about 2 TECU. Most model simulations predict TEC better than TEC changes in terms of NRMSE and the difference in peak time, while the opposite holds true in terms of Yield. Model performance strongly depends on the quantities considered, the type of metrics used, and the latitude considered.

IκBNS induces Muc5ac expression in epithelial cells and causes airway hyper-responsiveness in murine asthma models.

PubMed

Yokota, M; Tamachi, T; Yokoyama, Y; Maezawa, Y; Takatori, H; Suto, A; Suzuki, K; Hirose, K; Takeda, K; Nakajima, H

2017-07-01

In allergic asthma, environmental allergens including house dust mite (HDM) trigger pattern recognition receptors and activate downstream signaling pathways including NF-κB pathways not only in immune cells but also in airway epithelial cells. Recent studies have shown that NF-κB activation is regulated positively or negatively depending on the cellular context by IκBNS (encoded by the gene Nfkbid), one of atypical IκB proteins, in the nucleus. Therefore, we hypothesized that IκBNS expressed in immune cells or epithelial cells is involved in the regulation of asthmatic responses. To determine the roles of IκBNS in HDM-induced asthmatic responses. Roles of IκBNS in HDM-induced airway inflammation and airway hyper-responsiveness (AHR) were examined by using IκBNS-deficient (Nfkbid -/- ) mice. Roles of IκBNS expressed in hematopoietic cells and nonhematopoietic cells were separately evaluated by bone marrow chimeric mice. Roles of IκBNS expressed in murine tracheal epithelial cells (mTECs) were examined by air-liquid interface culture. House dust mite-induced airway inflammation and AHR were exacerbated in mice lacking IκBNS in hematopoietic cells. In contrast, HDM-induced airway inflammation was exacerbated, but AHR was attenuated in mice lacking IκBNS in nonhematopoietic cells. The induction of Muc5ac, a representative mucin in asthmatic airways, was reduced in Nfkbid -/- mTEC, whereas the induction of Spdef, a master regulator of goblet cell metaplasia, was not impaired in Nfkbid -/- mTEC. Moreover, IκBNS bound to and activated the MUC5AC distal promoter in epithelial cells. IκBNS is involved in inducing Muc5ac expression in lung epithelial cells and causing AHR in HDM-induced asthma models. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High-level replication of human immunodeficiency virus in thymocytes requires NF-kappaB activation through interaction with thymic epithelial cells.

PubMed

Chêne, L; Nugeyre, M T; Barré-Sinoussi, F; Israël, N

1999-03-01

We have previously demonstrated that interaction of infected thymocytes with autologous thymic epithelial cells (TEC) is a prerequisite for a high level of human immunodeficiency virus type 1 (HIV-1) replication in thymocytes (M. Rothe, L. Chêne, M. Nugeyre, F. Barré-Sinoussi, and N. Israël, J. Virol. 72:5852-5861, 1998). We report here that this activation of HIV replication takes place at the transcriptional level through activation of the Rel/NF-kappaB transcription factors. We first demonstrate that an HIV-1 provirus (SF-2 strain) very effectively replicates in thymocytes cocultured with TEC whereas this provirus, with kappaB sites deleted, fails to replicate. We provide evidence that several NF-kappaB complexes are constitutively found in the nuclei of thymocytes either freshly isolated from the thymus or maintained in coculture with autologous or heterologous TEC. The prevalent complex is the heterodimer p50-p65. NF-kappaB activity is tightly correlated with the transcriptional activity of a long terminal repeat (LTR) of HIV-1 transfected in thymocytes. The cotransfection of this LTR with a mutated IkappaBalpha molecule formally demonstrates that LTR transactivation is regulated by members of the Rel/NF-kappaB family in thymocytes. We also showed that tumor necrosis factor (TNF) and to a lesser extent interleukin-1 (IL-1), secreted within the coculture, induce NF-kappaB activity and a correlative LTR transactivation. However IL-7, a crucial factor for thymopoiesis that is secreted mainly by TEC, is a necessary cofactor for NF-kappaB activation elicited by TNF or IL-1. Together, these data indicate that NF-kappaB activation, required for a high level of HIV replication in thymocytes, is regulated in a specific manner in the thymic microenvironment which provides the necessary cytokines: TNF, IL-1, and IL-7.

Temporal-Spatial Variation of Global GPS-Derived Total Electron Content, 1999–2013

PubMed Central

Guo, Jinyun; Li, Wang; Liu, Xin; Kong, Qiaoli; Zhao, Chunmei; Guo, Bin

2015-01-01

To investigate the temporal-spatial distribution and evolutions of global Total Electron Content (TEC), we estimate the global TEC data from 1999 to 2013 by processing the GPS data collected by the International Global Navigation Satellite System (GNSS) Service (IGS) stations, and robustly constructed the TEC time series at each of the global 5°×2.5° grids. We found that the spatial distribution of the global TEC has a pattern where the number of TECs diminishes gradually from a low-latitude region to high-latitude region, and anomalies appear in the equatorial crest and Greenland. Temporal variations show that the peak TEC appears in equinoctial months, and this corresponds to the semiannual variation of TEC. Furthermore, the winter anomaly is also observed in the equatorial area of the northern hemisphere and high latitudes of the southern hemisphere. Morlet wavelet analysis is used to determine periods of TEC variations and results indicate that the 1-day, 26.5-day, semi-annual and annual cycles are the major significant periods. The fitting results of a quadratic polynomial show that the effect of solar activity on TEC is stronger in low latitudes than in mid-high latitudes, and stronger in the southern hemisphere than in the northern hemisphere. But the effect in low latitudes in the northern hemisphere is stronger than that in low latitudes in the southern hemisphere. The effect of solar activity on TECs was analyzed with the cross wavelet analysis and the wavelet coherence transformation, and we found that there appears to be a strong coherence in the period of about 27 days. So the sunspot as one index of solar activity seriously affects the TEC variations with the sun’s rotation. We fit the TEC data with the least squares spectral analysis to study the periodic variations of TEC. The changing trend of TEC is generally -0.08 TECu per year from 1999 to 2013. So TECs decrease over most areas year by year, but TECs over the Arctic around Greenland maintained a rising trend during these 15 years. PMID:26193101

Total electron content anomalies associated with global VEI4 + volcanic eruptions during 2002-2015

NASA Astrophysics Data System (ADS)

Li, Wang; Guo, Jinyun; Yue, Jianping; Shen, Yi; Yang, Yang

2016-10-01

In previous studies, little attention has been paid to the total electron content (TEC) anomalies preceding the volcanic eruption. We analyze the coupling relationship between volcanic eruption and TEC anomalies, and discuss the spatial distribution of TEC anomalies associated with volcanic geographical location. We utilize the global ionosphere map (GIM) data from the Center for Orbit Determination in Europe (CODE) to analyze TEC variations before the global volcanic eruptions indicated by VEI (Volcanic Explosivity Index) 4 + from 2002 to 2015 with the sliding interquartile range method. The results indicate the occurrence rate of TEC anomalies before great volcanic eruptions is related with the volcanic type and geographical position. The occurrence rate of TEC anomalies before stratovolcano and caldera eruptions is higher than that before shield and pyroclastic shield eruptions, and the occurrence rate of TEC anomalies has a descending trend from low latitudes to high latitudes. The TEC anomalies before the volcanic eruptions in low-mid latitudes are within the volcanic affected areas, but do not coincide with the volcanic foci. The corresponding TEC anomalies could be observed in the conjugated region, and all the TEC anomalies in the volcanic affected areas are usually close to bounds of equatorial anomaly zones. However, the TEC anomalies preceding these eruptions in high latitudes usually surround the volcano, and no TEC anomalies appear in the conjugated region. These conclusions have potential applications to the prediction of great volcanic eruptions in the future.

An On-Site Thermoelectric Cooling Device for Cryotherapy and Control of Skin Blood Flow

PubMed Central

Mejia, Natalia; Dedow, Karl; Nguy, Lindsey; Sullivan, Patrick; Khoshnevis, Sepideh; Diller, Kenneth R.

2015-01-01

Cryotherapy involves the surface application of low temperatures to enhance the healing of soft tissue injuries. Typical devices embody a remote source of chilled water that is pumped through a circulation bladder placed on the treatment site. In contrast, the present device uses thermoelectric refrigeration modules to bring the cooling source directly to the tissue to be treated, thereby achieving significant improvements in control of therapeutic temperature while having a reduced size and weight. A prototype system was applied to test an oscillating cooling and heating protocol for efficacy in regulating skin blood perfusion in the treatment area. Data on 12 human subjects indicate that thermoelectric coolers (TECs) delivered significant and sustainable changes in perfusion for both heating (increase by (±SE) 173.0 ± 66.0%, P < 0.005) and cooling (decrease by (±SE) 57.7 ± 4.2%, P < 0.0005), thus supporting the feasibility of a TEC-based device for cryotherapy with local temperature regulation. PMID:26421089

An On-Site Thermoelectric Cooling Device for Cryotherapy and Control of Skin Blood Flow.

PubMed

Mejia, Natalia; Dedow, Karl; Nguy, Lindsey; Sullivan, Patrick; Khoshnevis, Sepideh; Diller, Kenneth R

2015-12-01

Cryotherapy involves the surface application of low temperatures to enhance the healing of soft tissue injuries. Typical devices embody a remote source of chilled water that is pumped through a circulation bladder placed on the treatment site. In contrast, the present device uses thermoelectric refrigeration modules to bring the cooling source directly to the tissue to be treated, thereby achieving significant improvements in control of therapeutic temperature while having a reduced size and weight. A prototype system was applied to test an oscillating cooling and heating protocol for efficacy in regulating skin blood perfusion in the treatment area. Data on 12 human subjects indicate that thermoelectric coolers (TECs) delivered significant and sustainable changes in perfusion for both heating (increase by (±SE) 173.0 ± 66.0%, P < 0.005) and cooling (decrease by (±SE) 57.7 ± 4.2%, P < 0.0005), thus supporting the feasibility of a TEC-based device for cryotherapy with local temperature regulation.

Anamolous ionospheric TEC variations prior to the Indonesian earthquake (M 7.1) of November 15, 2014

NASA Astrophysics Data System (ADS)

Alcay, Salih

2017-05-01

This paper investigates preearthquake ionospheric variations with the use of TEC of Global Ionospheric Maps (GIMs) and regional maps based on Precise Point Positioning (PPP) during the 7.1-M Indonesian earthquake that occurred on November 15, 2014. TEC maps corresponding to 10 days before to 4 days after the event were examined. In addition, a time series of TEC values according to the PPP maps were also evaluated. In addition to GIMs, it was possible to detect TEC variations with PPP maps. The results showed that ionospheric TEC decreased strikingly 4 days prior to the earthquake. This TEC variation was highly likely related to seismic activity.

Observing Traveling Ionospheric Disturbances Caused by Tsunamis Using GPS TEC Measurements

NASA Technical Reports Server (NTRS)

Galvan, David A.; Komjathy, Attila; Hickey, Michael; Foster, James; Mannucci, Anthony J.

2010-01-01

Ground-based Global Positioning System (GPS) measurements of ionospheric Total Electron Content (TEC) show variations consistent with atmospheric internal gravity waves caused by ocean tsunamis following two recent seismic events: the American Samoa earthquake of September 29, 2009, and the Chile earthquake of February 27, 2010. Fluctuations in TEC correlated in time, space, and wave properties with these tsunamis were observed in TEC estimates processed using JPL's Global Ionospheric Mapping Software. These TEC estimates were band-pass filtered to remove ionospheric TEC variations with wavelengths and periods outside the typical range of internal gravity waves caused by tsunamis. Observable variations in TEC appear correlated with the tsunamis in certain locations, but not in others. Where variations are observed, the typical amplitude tends to be on the order of 1% of the background TEC value. Variations with amplitudes 0.1 - 0.2 TECU are observable with periods and timing affiliated with the tsunami. These observations are compared to estimates of expected tsunami-driven TEC variations produced by Embry Riddle Aeronautical University's Spectral Full Wave Model, an atmosphere-ionosphere coupling model, and found to be in good agreement in some locations, though there are cases when the model predicts an observable tsunami-driven signature and none is observed. These TEC variations are not always seen when a tsunami is present, but in these two events the regions where a strong ocean tsunami was observed did coincide with clear TEC observations, while a lack of clear TEC observations coincided with smaller tsunami amplitudes. There exists the potential to apply these detection techniques to real-time GPS TEC data, providing estimates of tsunami speed and amplitude that may be useful for early warning systems.

Biological therapy and the immune system in patients with chronic myeloid leukemia.

PubMed

Rohon, Peter

2012-07-01

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of hematopoietic stem cells that has been recognized as a disease responsive to immunotherapy. Despite the huge success of the tyrosine kinase inhibitors (TKIs), CML remains for the most part incurable, probably due to treatment resistance of leukemic stem cells, which are responsible for rapid disease relapse after discontinuation of therapy. Only allogeneic stem cell transplantation enables disease eradication. In addition to the Bcr-Abl1 oncoprotein, TKIs also inhibit off-target kinases (e.g. c-kit, Src, Tec), some of them having physiological functions in immune responses. In vitro studies have implied immunomodulatory effects of TKIs and interferon-alpha (IFN-α), but comprehensive information from in vivo analyses is missing. This review summarizes the recent advances in the field of immunology of CML, including basic information about leukemia-associated antigens and peptide vaccines, that could lead to the incorporation of TKIs and IFN-α in future therapeutic, potentially curative, interventions for CML.

Comparison of Ionospheric TEC Derived from GPS and IRI 2012 Model during Geomagnetic Storms at Indonesia

NASA Astrophysics Data System (ADS)

Marlia, Dessi; Wu, Falin

2016-07-01

This paper investigates the variations of vertical Total Electron Content (VTEC) at Manado, Indonesia (geographic coordinates : lat 1.34 ° S and long 124.82 ° E) for period 2013. The GPS measured TEC is compared with the TEC derived from the IRI (International Reference Ionosphere) 2012 model. Vertical TEC measurements obtained from dual frequency GPS receiver that is GISTM (GPS Ionospheric Scintillations and TEC monitor). Variation of TEC validate to IRI 2012 model at Manado station has been compared with the model for three different topside of electron density namely NeQuick, IRI-01-Corr and IRI2001.There is a need to investigation on diurnal, seasonal variations, solar activity dependence of TEC and including effects of space weather related events to TEC and modeling of TEC. In this paper, diurnal and seasonal variations of VTEC and the effect of VTEC due to space weather events like Geomagnetic storms are analyzed. The result show that the TEC prediction using IRI-2001 model overestimated the GPS TEC measurements, while IRI-NeQuick and IRI-01-corr show a tendency to underestimates the observed TEC during the day time particularly in low latitude region in the maximum solar activity period (2013). The variations of VTEC during 17th March, 2013, 29th June, 2013 storms are analyzed. During 17th March,2013 storm enhancement in VTEC with Kp value 6 and Disturbance storm index (DST) -132 nT. During 29th June, 2013 storm VTEC depletion with value 7 and DST -98 nT. Significant deviations in VTEC during the main phase of the storms are observed. It is found that the response of ionospheric TEC consist of effects of both enhancement and depletions in ionospheric structures (positive and negative storm). Keywords: TEC ionosphere, GPS, GISTM, IRI 2012 model, solar activity, geomagnetic storm

Regional TEC model under quiet geomagnetic conditions and low-to-moderate solar activity based on CODE GIMs

NASA Astrophysics Data System (ADS)

Feng, Jiandi; Jiang, Weiping; Wang, Zhengtao; Zhao, Zhenzhen; Nie, Linjuan

2017-08-01

Global empirical total electron content (TEC) models based on TEC maps effectively describe the average behavior of the ionosphere. However, the accuracy of these global models for a certain region may not be ideal. Due to the number and distribution of the International GNSS Service (IGS) stations, the accuracy of TEC maps is geographically different. The modeling database derived from the global TEC maps with different accuracy is likely one of the main reasons that limits the accuracy of the new models. Moreover, many anomalies in the ionosphere are geographic or geomagnetic dependent, and as such the accuracy of global models can deteriorate if these anomalies are not fully incorporated into the modeling approach. For regional models built in small areas, these influences on modeling are immensely weakened. Thus, the regional TEC models may better reflect the temporal and spatial variations of TEC. In our previous work (Feng et al., 2016), a regional TEC model TECM-NEC is proposed for northeast China. However, this model is only directed against the typical region of Mid-latitude Summer Nighttime Anomaly (MSNA) occurrence, which is meaningless in other regions without MSNA. Following the technique of TECM-NEC model, this study proposes another regional empirical TEC model for other regions in mid-latitudes. Taking a small area BeiJing-TianJin-Tangshan (JJT) region (37.5°-42.5° N, 115°-120° E) in China as an example, a regional empirical TEC model (TECM-JJT) is proposed using the TEC grid data from January 1, 1999 to June 30, 2015 provided by the Center for Orbit Determination in Europe (CODE) under quiet geomagnetic conditions. The TECM-JJT model fits the input CODE TEC data with a bias of 0.11TECU and a root mean square error of 3.26TECU. Result shows that the regional model TECM-JJT is consistent with CODE TEC data and GPS-TEC data.

Dynamics of total electron content distribution during strong geomagnetic storms

NASA Astrophysics Data System (ADS)

Astafyeva, E. I.; Afraimovich, E. L.; Kosogorov, E. A.

We worked out a new method of mapping of total electron content TEC equal lines displacement velocity The method is based on the technique of global absolute vertical TEC value mapping Global Ionospheric Maps technique GIM GIM with 2-hours time resolution are available from Internet underline ftp cddisa gsfc nasa gov in standard IONEX-files format We determine the displacement velocity absolute value as well as its wave vector orientation from increments of TEC x y derivatives and TEC time derivative for each standard GIM cell 5 in longitude to 2 5 in latitude Thus we observe global traveling of TEC equal lines but we also can estimate the velocity of these line traveling Using the new method we observed anomalous rapid accumulation of the ionosphere plasma at some confined area due to the depletion of the ionization at the other spacious territories During the main phase of the geomagnetic storm on 29-30 October 2003 very large TEC enhancements appeared in the southwest of North America TEC value in that area reached up to 200 TECU 1 TECU 10 16 m -2 It was found that maximal velocity of TEC equal lines motion exceeded 1500 m s and the mean value of the velocity was about 400 m s Azimuth of wave vectors of TEC equal lines were orientated toward the center of region with anomaly high values of TEC the southwest of North America It should be noted that maximal TEC values during geomagnetically quiet conditions is about 60-80 TECU the value of TEC equal lines

Ultrastructural and mechanical changes in tubular epithelial cells by angiotensin II and aldosterone as observed with atomic force microscopy.

PubMed

Quan, Fu-Shi; Jeong, Kyung Hwan; Lee, Gi-Ja

2018-07-01

Tubular epithelial cells (TECs) play an important pathophysiological role in the promotion of renal fibrosis. Quantitative analysis of the mechanical changes in TECs may be helpful in evaluating novel pharmacological strategies. Atomic force microscopy (AFM) is a common nanotechnology tool used for imaging and measuring interaction forces in biological systems. In this study, we used AFM to study ultrastructural and mechanical changes in TECs mediated by the renin-angiotensin-aldosterone system. We quantitatively analyzed changes in the mechanical properties of TECs using three extrinsic factors, namely, chemical fixation, angiotensin II (AT II), and aldosterone (AD). Fixed TECs were 11 times stiffer at the cell body and 3 times stiffer at the cell-cell junction compared to live TECs. After stimulation with AT II, live TECs were four times stiffer at the junctional area than at the cell body, while fixed TECs after AT II stimulation were approximately two times stiffer at the both cell body and cell-cell junction compared to fixed unstimulated TECs. Fixed TECs also reflected changes in the mechanical properties of TECs at the cell body region after AD stimulation. Together, our results suggest that cell stiffness at the cell body region may serve as an effective index for evaluating drugs and stimulation, regardless of whether the cells are live or fixed at the time of analysis. In addition, studying the changes to the intrinsic mechanical property of TECs after application of external stimuli may be useful for investigating pathophysiologic mechanisms and effective therapeutic strategies for renal injury. Copyright © 2018 Elsevier Ltd. All rights reserved.

Method of Minimizing Size of Heat Rejection Systems for Thermoelectric Coolers to Cool Detectors in Space

NASA Technical Reports Server (NTRS)

Choi, Michael K.

2014-01-01

A thermal design concept of attaching the thermoelectric cooler (TEC) hot side directly to the radiator and maximizing the number of TECs to cool multiple detectors in space is presented. It minimizes the temperature drop between the TECs and radiator. An ethane constant conductance heat pipe transfers heat from the detectors to a TEC cold plate which the cold side of the TECs is attached to. This thermal design concept minimizes the size of TEC heat rejection systems. Hence it reduces the problem of accommodating the radiator within a required envelope. It also reduces the mass of the TEC heat rejection system. Thermal testing of a demonstration unit in vacuum verified the thermal performance of the thermal design concept.

Physiological, biochemical and molecular processes associated with gravitropism in roots of maize

NASA Astrophysics Data System (ADS)

Biermann, B.; Feldman, L. J.

1994-08-01

This research aims to characterize regulation of the principal cytosolic protein kinases in maize, cultivar `Merit' root tips, since much evidence indicates that stimuli which modulate the gravitropic response in this system act through regulation of activity of these enzymes. To this end, we have cloned a maize protein kinase belonging to a group of plant protein kinases with a catalytic domain similar in primary structure to the second messenger-regulated protein kinases known in animal and fungal systems. However, both the unique structural features conserved among plant protein kinases in this group, and lack of evidence for cyclic nucleotide signalling in plants point to operation of a novel protein kinase regulatory mechanism in plants. In order to test effects of possible regulators on protein kinase activity, we developed a sensitive method for detecting regulation of autophosphoryl labelling of protein kinases in unfractionated maize protein extracts. Regulation of protein kinase autophosphorylation in these extracts was different from that known in animals and fungi, further suggesting operation of unique protein kinase regulatory mechanisms in plants. Previous research has shown that light, or factors modulated by light, regulate plant protein kinase activity. We found that protein kinase activity was co-immunoprecipitated with the plant photoreceptor phytochrome, and was associated with phytochrome by high-affinity chemical interactions. Far-red reversibility of red-light regulation of phytochrome phosphorylation by the associated protein kinase indicates that it may modulate or transduce the light signals which lead to gravitropic sensitivity in `Merit' maize.

Curriculum Change Part 2a. Programme Development in Colleges. Part 2a: The Work Activities of Teachers on TEC Certificate Programmes.

ERIC Educational Resources Information Center

Dodd, S.; And Others

A study examined the day-to-day work activities of teachers of Technician Education Council (TEC) certificate programs in Great Britain. During the study, a detailed questionnaire dealing with the tasks performed by TEC teachers, the amount of time spent on TEC teachers on individual activities, and the impact of the TEC programs on teacher…

Method for thermoelectric cooler utilization using manufacturer's technical information

NASA Astrophysics Data System (ADS)

Ajiwiguna, Tri Ayodha; Nugroho, Rio; Ismardi, Abrar

2018-03-01

Thermoelectric cooler (TEC) module has been widely used for many applications. In this study, a procedure to use TEC module for specific requirement is developed based on manufacturer's technical data. For study case, the cooling system using TEC module is designed and tested to maintain 6.6 liter of water at 24 °C while surrounding temperature is 26 °C. First, cooling load estimation is performed empirically by observing the temperature change when cold water is inside the container. Second, the working temperature on hot side and cold side of TEC are determined. Third, the parameters of Seebeck coefficient, thermal resistance and electrical resistance are predicted by using information from the manufacturer. Fourth, the operating current is determined by the assumption the voltage across the TEC is 12V. Fifth, cooling capacity of TEC module is calculated by using energy balance equation of TEC. Sixth, the cooling load and cooling capacity are compared to determine the number of TEC module needed. The result of these calculations showed that one TEC module is enough for cooling system since the cooling load is 17.5 W while the cooling capacity is 18.87 W. From the experimental result, the set point temperature was achieved using one TEC module as predicted in calculations steps.

Quantitative Evaluation of Ionosphere Models for Reproducing Regional TEC During Geomagnetic Storms

NASA Astrophysics Data System (ADS)

Shim, J. S.; Kuznetsova, M.; Rastaetter, L.; Bilitza, D.; Codrescu, M.; Coster, A. J.; Emery, B.; Foster, B.; Fuller-Rowell, T. J.; Goncharenko, L. P.; Huba, J.; Mitchell, C. N.; Ridley, A. J.; Fedrizzi, M.; Scherliess, L.; Schunk, R. W.; Sojka, J. J.; Zhu, L.

2015-12-01

TEC (Total Electron Content) is one of the key parameters in description of the ionospheric variability that has influence on the accuracy of navigation and communication systems. To assess current TEC modeling capability of ionospheric models during geomagnetic storms and to establish a baseline against which future improvement can be compared, we quantified the ionospheric models' performance by comparing modeled vertical TEC values with ground-based GPS TEC measurements and Multi-Instrument Data Analysis System (MIDAS) TEC. The comparison focused on North America and Europe sectors during selected two storm events: 2006 AGU storm (14-15 Dec. 2006) and 2013 March storm (17-19 Mar. 2013). The ionospheric models used for this study range from empirical to physics-based, and physics-based data assimilation models. We investigated spatial and temporal variations of TEC during the storms. In addition, we considered several parameters to quantify storm impacts on TEC: TEC changes compared to quiet time, rate of TEC change, and maximum increase/decrease during the storms. In this presentation, we focus on preliminary results of the comparison of the models performance in reproducing the storm-time TEC variations using the parameters and skill scores. This study has been supported by the Community Coordinated Modeling Center (CCMC) at the Goddard Space Flight Center. Model outputs and observational data used for the study will be permanently posted at the CCMC website (http://ccmc.gsfc.nasa.gov) for the space science communities to use.

CoLiTec software - detection of the near-zero apparent motion

NASA Astrophysics Data System (ADS)

Khlamov, Sergii V.; Savanevych, Vadym E.; Briukhovetskyi, Olexandr B.; Pohorelov, Artem V.

2017-06-01

In this article we described CoLiTec software for full automated frames processing. CoLiTec software allows processing the Big Data of observation results as well as processing of data that is continuously formed during observation. The scope of solving tasks includes frames brightness equalization, moving objects detection, astrometry, photometry, etc. Along with the high efficiency of Big Data processing CoLiTec software also ensures high accuracy of data measurements. A comparative analysis of the functional characteristics and positional accuracy was performed between CoLiTec and Astrometrica software. The benefits of CoLiTec used with wide field and low quality frames were observed. The efficiency of the CoLiTec software was proved by about 700.000 observations and over 1.500 preliminary discoveries.

Receiver DCB estimation and GPS vTEC study at a low latitude station in the South Pacific

NASA Astrophysics Data System (ADS)

Prasad, Ramendra; Kumar, Sushil; Jayachandran, P. T.

2016-11-01

The statistical estimation of receiver differential code bias (DCB) of the GSV4004B receiver at a low latitude station, Suva (lat. 18.15°S, long. 178.45°E, Geomag. Lat. 21.07°S), Fiji, and the subsequent behaviour of vTEC, are presented. By means of least squares linear regression fitting technique, the receiver DCB was determined using the GPS vTEC data recorded during the year 2010, CODE TEC and IRI-2012 model for 2010. To substantiate the results, minimization of the standard deviation (SD) method was also used for GPS vTEC data. The overall monthly DCB was estimated to be in the range of 62.6 TECU. The vTEC after removing the resultant monthly DCB was consistent with other low latitude observations. The GPS vTEC 2010 data after eliminating the resultant DCB were lower in comparison to Faraday rotation vTEC measurements at Suva during 1984 primarily due to higher solar activity during 1984 as compared to 2010. Seasonally, vTEC was maximum during summer and minimum during winter. The winter showed least vTEC variability whereas equinox showed the largest daytime variability. The geomagnetic disturbances effect showed that both vTEC and its variability were higher on magnetically disturbed days as compared to quiet days with maximum variability in the daytime. Two geomagnetic storms of moderate strengths with main phases in the local daytime showed long duration (∼52 h) increase in vTEC by 33-67% which can be accounted by changes in E×B drifts due to prompt penetration of storm-time auroral electric field in the daytime and disturbance dynamo electric field in the nighttime to low latitudes.

Salient features of the dayside low latitude ionospheric response to the main phase step-I of the 17 March 2015 geomagnetic storm

NASA Astrophysics Data System (ADS)

Bagiya, Mala S.; Sunil, A. S.; Chakrabarty, D.; Sunda, Surendra

2017-10-01

Based on TEC observations by India's GPS Aided GEO Augmented Navigation (GAGAN) GPS network, we report the dayside low latitude ionospheric variations over the Indian region during the moderate main phase step-I of the 17 March 2015 geomagnetic storm. In addition, we assess the efficacy of GPS inferred TEC maps by International GNSS service (IGS) in capturing large scale diurnal features of equatorial ionization anomaly (EIA) over the Indian region during this period. Following the prompt penetration electric field (PPE) at ∼0605 UT, equatorial electrojet (EEJ) enhances by ∼55 nT over 75 ± 3oE longitudes where main phase step-I is coincided with local noon. Initial moderate EIA gradually strengthens with the storm commencement. Although GAGAN TEC exhibits more intense EIA evolution compare to IGS TEC maps, latitudinal extent of EIA are comparable in both. The enhanced EEJ reverses by ∼0918 UT under the effect of overshielding electric field, the later is accompanied by northward turning of interplanetary magnetic field (IMF) Bz. The weakening of well evolved EIA reflects in IGS TEC maps after ∼45 min of the overshielding occurrence. In contrary, GAGAN TEC shows the corresponding feature after ∼0115 h. Resurgence of EIA, following the PPE ∼1115 UT, shows up in GAGAN TEC but IGS TEC maps fails in capturing this feature. The observed low latitude TEC variations and EIA modulations are explained in terms of the varying storm time disturbance electric fields. The anomalies between the GAGAN TEC and IGS TEC maps are discussed in terms of the possible limitations of the IGS TEC maps in capturing storm time EIA variability over the Indian region.

Parametric performance analysis of steam-injected gas turbine with a thermionic-energy-converter-lined combustor

NASA Technical Reports Server (NTRS)

Choo, Y. K.; Burns, R. K.

1982-01-01

The performance of steam-injected gas turbines having combustors lined with thermionic energy converters (STIG/TEC systems) was analyzed and compared with that of two baseline systems; a steam-injected gas turbine (without a TEC-lined combustor) and a conventional combined gas turbine/steam turbine cycle. Common gas turbine parameters were assumed for all of the systems. Two configurations of the STIG/TEC system were investigated. In both cases, steam produced in an exhaust-heat-recovery boiler cools the TEC collectors. It is then injected into the gas combustion stream and expanded through the gas turbine. The STIG/TEC system combines the advantage of gas turbine steam injection with the conversion of high-temperature combustion heat by TEC's. The addition of TEC's to the baseline steam-injected gas turbine improves both its efficiency and specific power. Depending on system configuration and design parameters, the STIG/TEC system can also achieve higher efficiency and specific power than the baseline combined cycle.

Potentialities of TEC topping: A simplified view of parametric effects

NASA Technical Reports Server (NTRS)

Morris, J. F.

1980-01-01

An examination of the benefits of thermionic-energy-conversion (TEC)-topped power plants and methods of increasing conversion efficiency are discussed. Reductions in the cost of TEC modules yield direct decreases in the cost of electricity (COE) from TEC-topped central station power plants. Simplified COE, overall-efficiency charts presented illustrate this trend. Additional capital-cost diminution results from designing more compact furnaces with considerably increased heat transfer rates allowable and desirable for high temperature TEC and heat pipes. Such improvements can evolve of the protection from hot corrosion and slag as well as the thermal expansion compatibilities offered by silicon-carbide clads on TEC-heating surfaces. Greater efficiencies and far fewer modules are possible with high-temperature, high-power-density TEC: This decreases capital and fuel costs much more and substantially increases electric power outputs for fixed fuel inputs. In addition to more electricity, less pollution, and lower costs, TEC topping used directly in coal-combustion products contributes balance-of-payment gains.

Long-Term Prediction of the Arctic Ionospheric TEC Based on Time-Varying Periodograms

PubMed Central

Liu, Jingbin; Chen, Ruizhi; Wang, Zemin; An, Jiachun; Hyyppä, Juha

2014-01-01

Knowledge of the polar ionospheric total electron content (TEC) and its future variations is of scientific and engineering relevance. In this study, a new method is developed to predict Arctic mean TEC on the scale of a solar cycle using previous data covering 14 years. The Arctic TEC is derived from global positioning system measurements using the spherical cap harmonic analysis mapping method. The study indicates that the variability of the Arctic TEC results in highly time-varying periodograms, which are utilized for prediction in the proposed method. The TEC time series is divided into two components of periodic oscillations and the average TEC. The newly developed method of TEC prediction is based on an extrapolation method that requires no input of physical observations of the time interval of prediction, and it is performed in both temporally backward and forward directions by summing the extrapolation of the two components. The backward prediction indicates that the Arctic TEC variability includes a 9 years period for the study duration, in addition to the well-established periods. The long-term prediction has an uncertainty of 4.8–5.6 TECU for different period sets. PMID:25369066

Global empirical model of TEC response to geomagnetic activity

NASA Astrophysics Data System (ADS)

Mukhtarov, P.; Andonov, B.; Pancheva, D.

2013-10-01

global total electron content (TEC) model response to geomagnetic activity described by the Kp index is built by using the Center for Orbit Determination of Europe (CODE) TEC data for a full 13 years, January 1999 to December 2011. The model describes the most probable spatial distribution and temporal variability of the geomagnetically forced TEC anomalies assuming that these anomalies at a given modified dip latitude depend mainly on the Kp index, local time (LT), and longitude. The geomagnetic anomalies are expressed by the relative deviation of TEC from its 15 day median and are denoted as rTEC. The rTEC response to the geomagnetic activity is presented by a sum of two responses with different time delay constants and different signs of the cross-correlation function. It has been found that the mean dependence of rTEC on Kp index can be expressed by a cubic function. The LT dependence of rTEC is described by Fourier time series which includes the contribution of four diurnal components with periods 24, 12, 8, and 6 h. The rTEC dependence on longitude is presented by Fourier series which includes the contribution of zonal waves with zonal wave numbers up to 6. In order to demonstrate how the model is able to reproduce the rTEC response to geomagnetic activity, three geomagnetic storms at different seasons and solar activity conditions are presented. The model residuals clearly reveal two types of the model deviation from the data: some underestimation of the largest TEC response to the geomagnetic activity and randomly distributed errors which are the data noise or anomalies generated by other sources. The presented TEC model fits to the CODE TEC input data with small negative bias of -0.204, root mean squares error RMSE = 4.592, and standard deviation error STDE = 4.588. The model offers TEC maps which depend on geographic coordinates (5° × 5° in latitude and longitude) and universal time (UT) at given geomagnetic activity and day of the year. It could be used for both science and possible service (nowcasting and short-term prediction); for the latter, a detailed validation of the model at different geophysical conditions has to be performed in order to clarify the model predicting quality.

Clouds and troughs of total electron content detected with the ionospheric weather index

NASA Astrophysics Data System (ADS)

Gulyaeva, Tamara

2016-07-01

The ionospheric weather W index has been developed with the different thresholds of change in the F2 layer peak electron density NmF2 (proportional to foF2 critical frequency) or total electron content TEC relative their quiet reference for quantifying the ionosphere variability. The thresholds of DTEC=log(TEC/TECq) are selected for the positive and negative logarithm of TEC ratio to the quiet reference median, TECq, at any given location on the Earth. The global W-index maps are produced from Global Ionospheric Maps of Total Electron Content, GIM-TEC, and provided online at http://www.izmiran.ru/services/iweather/ and http://www.iololab.org/. Based on W-index maps, Catalogues of the ionospheric storms and sub-storms are produced available for the users. The second generation of the ionospheric weather indices, designated V index, is recently introduced and applied for the retrospective study of GIM-TEC variability during 1999-2015. Using sliding-window statistical analysis, moving daily-hourly TEC median TECq for 15 preceding days with estimated variance bounds are obtained at cells of GIM-TEC. The ionosphere variability index, V, is expressed in terms of ΔTEC deviation from the median normalized by the standard deviation STD. V index segmentation is introduced from Vn=-4 in step of 1 to Vp=4 specifying TEC storm if an instant TEC is outside of TECq+-1STD. The global maps of V index allow distinguish the clouds of enhanced TEC (positive storm signatures) and troughs of TEC depletion (negative storm signatures) as compared to the background quiet reference TECq map. It is found that the large-scale TEC clouds and troughs are observed in space all over the world constituting up to 20-50 percent of cells of GIM-TEC. The time variation of these plasma patches is partly following to geomagnetic SSC storm onset. As concerns the interplanetary and the solar wind, SW, sources of the ionospheric storms the TEC storms are observed both with IMF and SW precursors and without the IMF and SW storm signatures. Results of the ionospheric storm studies with the ionospheric weather indices are discussed in the paper. This study is supported by TUBITAK EEEAG 115E915.

Activation and Function of the MAPKs and Their Substrates, the MAPK-Activated Protein Kinases

PubMed Central

Cargnello, Marie; Roux, Philippe P.

2011-01-01

Summary: The mitogen-activated protein kinases (MAPKs) regulate diverse cellular programs by relaying extracellular signals to intracellular responses. In mammals, there are more than a dozen MAPK enzymes that coordinately regulate cell proliferation, differentiation, motility, and survival. The best known are the conventional MAPKs, which include the extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun amino-terminal kinases 1 to 3 (JNK1 to -3), p38 (α, β, γ, and δ), and ERK5 families. There are additional, atypical MAPK enzymes, including ERK3/4, ERK7/8, and Nemo-like kinase (NLK), which have distinct regulation and functions. Together, the MAPKs regulate a large number of substrates, including members of a family of protein Ser/Thr kinases termed MAPK-activated protein kinases (MAPKAPKs). The MAPKAPKs are related enzymes that respond to extracellular stimulation through direct MAPK-dependent activation loop phosphorylation and kinase activation. There are five MAPKAPK subfamilies: the p90 ribosomal S6 kinase (RSK), the mitogen- and stress-activated kinase (MSK), the MAPK-interacting kinase (MNK), the MAPK-activated protein kinase 2/3 (MK2/3), and MK5 (also known as p38-regulated/activated protein kinase [PRAK]). These enzymes have diverse biological functions, including regulation of nucleosome and gene expression, mRNA stability and translation, and cell proliferation and survival. Here we review the mechanisms of MAPKAPK activation by the different MAPKs and discuss their physiological roles based on established substrates and recent discoveries. PMID:21372320

Recent Progress on Liver Kinase B1 (LKB1): Expression, Regulation, Downstream Signaling and Cancer Suppressive Function

PubMed Central

Gan, Ren-You; Li, Hua-Bin

2014-01-01

Liver kinase B1 (LKB1), known as a serine/threonine kinase, has been identified as a critical cancer suppressor in many cancer cells. It is a master upstream kinase of 13 AMP-activated protein kinase (AMPK)-related protein kinases, and possesses versatile biological functions. LKB1 gene is mutated in many cancers, and its protein can form different protein complexes with different cellular localizations in various cell types. The expression of LKB1 can be regulated through epigenetic modification, transcriptional regulation and post-translational modification. LKB1 dowcnstream pathways mainly include AMPK, microtubule affinity regulating kinase (MARK), salt-inducible kinase (SIK), sucrose non-fermenting protein-related kinase (SNRK) and brain selective kinase (BRSK) signalings, etc. This review, therefore, mainly discusses recent studies about the expression, regulation, downstream signaling and cancer suppressive function of LKB1, which can be helpful for better understanding of this molecular and its significance in cancers. PMID:25244018

Application of Geostationary GNSS and SBAS Satellites for Studying Ionospheric TEC Disturbances of Geomagnetic and Meteorological Origin

NASA Astrophysics Data System (ADS)

Padokhin, A. M.; Kurbatov, G. A.; Yasyukevich, Y.; Yasyukevich, A.

2017-12-01

With the development of GNSS and SBAS constellations, the coherent multi-frequency L band transmissions are now available from a number of geostationary satellites. These signals can be used for ionospheric TEC estimations in the same way as widely used GPS/GLONASS signals. In this work, we compare noise patterns in TEC estimations based on different geostationary satellites data: augmentation systems (Indian GAGAN, European EGNOS and American WAAS), and Chinese COMPASS/Beidou navigation system. We show that noise level in geostationary COMPASS/Beidou TEC estimations is times smaller than noise in SBAS TEC estimation and corresponds to those of GPS/GLONASS at the same elevation angles. We discuss the capabilities of geostationary TEC data for studying ionospheric variability driven by space weather and meteorological sources at different time scales. Analyzing data from IGS/MGEX receivers we present geostationary TEC response on X-class Solar flares of current cycle, moderate and strong geomagnetic storms, including G4 St. Patrick's day Storm 2015 and recent G3 storm of the end of May 2017. We also discuss geostationary TEC disturbances in near equatorial ionosphere caused by two SSW events (minor and major final warming of 2015-2016 winter season) as well as geostationary TEC response on typhoons activity near Taiwan in autumn 2016. Our results show large potential of geostationary TEC estimations with GNSS and SBAS signals for continuous ionospheric monitoring.

Transformation of Chlorinated Benzenes and Toluenes by Ralstonia sp. Strain PS12 tecA (Tetrachlorobenzene Dioxygenase) and tecB (Chlorobenzene Dihydrodiol Dehydrogenase) Gene Products

PubMed Central

Pollmann, Katrin; Beil, Stefan; Pieper, Dietmar H.

2001-01-01

The tecB gene, located downstream of tecA and encoding tetrachlorobenzene dioxygenase, in Ralstonia sp. strain PS12 was cloned into Escherichia coli DH5α together with the tecA gene. The identity of the tecB gene product as a chlorobenzene dihydrodiol dehydrogenase was verified by transformation into the respective catechols of chlorobenzene, the three isomeric dichlorobenzenes, as well as 1,2,3- and 1,2,4-trichlorobenzenes, all of which are transformed by TecA into the respective dihydrodihydroxy derivatives. Di- and trichlorotoluenes were either subject to TecA-mediated dioxygenation (the major or sole reaction observed for the 1,2,4-substituted 2,4-, 2,5-, and 3,4-dichlorotoluenes), resulting in the formation of the dihydrodihydroxy derivatives, or to monooxygenation of the methyl substituent (the major or sole reaction observed for 2,3-, 2,6-, and 3,5-dichloro- and 2,4,5-trichlorotoluenes), resulting in formation of the respective benzyl alcohols. All of the chlorotoluenes subject to dioxygenation by TecA were transformed, without intermediate accumulation of dihydrodihydroxy derivatives, into the respective catechols by TecAB, indicating that dehydrogenation is no bottleneck for chlorobenzene or chlorotoluene degradation. However, only those chlorotoluenes subject to a predominant dioxygenation were growth substrates for PS12, confirming that monooxygenation is an unproductive pathway in PS12. PMID:11526005

Detection of Seismic Precursors Using Distance Metrics Between GPS-TEC and IRI-Plas

NASA Astrophysics Data System (ADS)

Necat Deviren, M.; Gulyaeva, Tamara; Sezen, Umut; Arikan, Feza; Arikan, Orhan

Ionosphere is an important layer of atmosphere that varies under solar, geomagnetic, gravitational and seismic activities. Total Electron Content (TEC) is one of the main observables of ionosphere. International Reference Ionosphere Extended to Plasmasphere (IRI-Plas) is accepted by International Organization for Standardization (ISO) as the standard climatic model. IRI-Plas provides TEC up to GPS satellite height. TEC can be estimated using Global Positioning System (GPS) Networks. In this study, TEC is computed using both IRI-Plas and Turkish National Permanent GPS Network as IONOLAB-TEC. In order to detect seismic precursors, three different distance metrics, namely Symmetric Kullback-Liebler Distance (SKLD), Cross-Correlation Coefficient (CC), and L2-Norm (L2N), are implemented between IONOLAB-TEC and IRI-Plas-TEC values. SKLD is also computed between IONOLAB-TEC Maps and IRI-Plas-TEC Maps over Turkey. Between May 2009 and September 2012, it is observed that SKLD metric indicates a disturbance within the period prior to 10 days of earthquake day. The disturbance in SKLD increases for the range of stations in the neighborhood of the epicenter. For strong earthquakes all of the three distance metrics indicate a disturbance before the earthquake, yet SKLD behaves as a more sensitive precursor for earthquakes larger than magnitude 4. This study is supported by the joint grant of TUBITAK 112E568 and RFBR 13-02-91370-CT_a.

GPS receiver CODE bias estimation: A comparison of two methods

NASA Astrophysics Data System (ADS)

McCaffrey, Anthony M.; Jayachandran, P. T.; Themens, D. R.; Langley, R. B.

2017-04-01

The Global Positioning System (GPS) is a valuable tool in the measurement and monitoring of ionospheric total electron content (TEC). To obtain accurate GPS-derived TEC, satellite and receiver hardware biases, known as differential code biases (DCBs), must be estimated and removed. The Center for Orbit Determination in Europe (CODE) provides monthly averages of receiver DCBs for a significant number of stations in the International Global Navigation Satellite Systems Service (IGS) network. A comparison of the monthly receiver DCBs provided by CODE with DCBs estimated using the minimization of standard deviations (MSD) method on both daily and monthly time intervals, is presented. Calibrated TEC obtained using CODE-derived DCBs, is accurate to within 0.74 TEC units (TECU) in differenced slant TEC (sTEC), while calibrated sTEC using MSD-derived DCBs results in an accuracy of 1.48 TECU.

Simultaneous total electron content and all-sky camera measurements of an auroral arc

NASA Astrophysics Data System (ADS)

Kintner, P. M.; Kil, H.; Deehr, C.; Schuck, P.

2002-07-01

We present an example of Global Positioning System (GPS) derived total electron content (TEC) and all-sky camera (ASC) images that show increases of TEC by ~10 × 1016 electrons m-2 (10 TEC units) occurring simultaneously with auroral light in ASC images. The TEC example appears to be an E region density enhancement produced by two discrete auroral arcs occurring in the late morning auroral oval at 1000 LT. This suggests that GPS signal TEC measurements can be used to detect individual auroral arcs and that individual discrete auroral arcs are responsible for some high-latitude phase scintillations. The specific auroral feature detected was a poleward moving auroral form believed to occur in the polar cap where the ionosphere is convecting antisunward. The magnitude of the rate of change of TEC (dTEC/dt) is comparable to that previously reported. However, the timescales associated with the event, the order of 1 min, suggest that the data sampling technique commonly used by chain GPS TEC receivers (averaging and time decimation) will undersample E region TEC perturbations produced by active auroral displays. The localized nature of this example implies that L1 ranging errors of at least 1.6 m will be introduced by auroral arcs into systems relying on differential GPS for navigation or augmentation. Although the TEC and auroral arcs presented herein occurred in the late morning auroral oval, we expect that the effects of discrete auroral arcs on GPS TEC and subsequent ranging errors should occur at all local times. Furthermore, GPS receivers can be used to detect individual discrete arcs.

78 FR 64207 - Application To Export Electric Energy; TEC Energy Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-28

... DEPARTMENT OF ENERGY [OE Docket No. EA-388] Application To Export Electric Energy; TEC Energy Inc. AGENCY: Office of Electricity Delivery and Energy Reliability, DOE. ACTION: Notice of Application. SUMMARY: TEC Energy Inc. (TEC) has applied for authority to transmit electric energy from the United...

The α Subunit of the G Protein G13 Regulates Activity of One or More Gli Transcription Factors Independently of Smoothened*

PubMed Central

Douglas, Andrew E.; Heim, Jennifer A.; Shen, Feng; Almada, Luciana L.; Riobo, Natalia A.; Fernández-Zapico, Martin E.; Manning, David R.

2011-01-01

Smoothened (Smo) is a seven-transmembrane (7-TM) receptor that is essential to most actions of the Hedgehog family of morphogens. We found previously that Smo couples to members of the Gi family of heterotrimeric G proteins, which in some cases are integral although alone insufficient in the activation of Gli transcription factors through Hedgehog signaling. In response to a report that the G12/13 family is relevant to Hedgehog signaling as well, we re-evaluated the coupling of Smo to one member of this family, G13, and investigated the capacity of this and other G proteins to activate one or more of forms of Gli. We found no evidence that Smo couples directly to G13. We found nonetheless that Gα13 and to some extent Gαq and Gα12 are able to effect activation of Gli(s). This capacity is realized in some cells, e.g. C3H10T1/2, MC3T3, and pancreatic cancer cells, but not all cells. The mechanism employed is distinct from that achieved through canonical Hedgehog signaling, as the activation does not involve autocrine signaling or in any other way require active Smo and does not necessarily involve enhanced transcription of Gli1. The activation by Gα13 can be replicated through a Gq/G12/13-coupled receptor, CCKA, and is attenuated by inhibitors of p38 mitogen-activated protein kinase and Tec tyrosine kinases. We posit that G proteins, and perhaps G13 in particular, provide access to Gli that is independent of Smo and that they thus establish a basis for control of at least some forms of Gli-mediated transcription apart from Hedgehogs. PMID:21757753

Observing Tsunamis in the Ionosphere Using Ground Based GPS Measurements

NASA Technical Reports Server (NTRS)

Galvan, D. A.; Komjathy, A.; Song, Y. Tony; Stephens, P.; Hickey, M. P.; Foster, J.

2011-01-01

Ground-based Global Positioning System (GPS) measurements of ionospheric Total Electron Content (TEC) show variations consistent with atmospheric internal gravity waves caused by ocean tsunamis following recent seismic events, including the Tohoku tsunami of March 11, 2011. We observe fluctuations correlated in time, space, and wave properties with this tsunami in TEC estimates processed using JPL's Global Ionospheric Mapping Software. These TEC estimates were band-pass filtered to remove ionospheric TEC variations with periods outside the typical range of internal gravity waves caused by tsunamis. Observable variations in TEC appear correlated with the Tohoku tsunami near the epicenter, at Hawaii, and near the west coast of North America. Disturbance magnitudes are 1-10% of the background TEC value. Observations near the epicenter are compared to estimates of expected tsunami-driven TEC variations produced by Embry Riddle Aeronautical University's Spectral Full Wave Model, an atmosphere-ionosphere coupling model, and found to be in good agreement. The potential exists to apply these detection techniques to real-time GPS TEC data, providing estimates of tsunami speed and amplitude that may be useful for future early warning systems.

Brassinosteroid regulated kinases (BRKs) that mediate brassinosteroid signal transduction and uses thereof

DOEpatents

Wang, Zhi-Yong; Tang, Wenqiang

2013-09-24

The present invention identifies a novel family of kinases regulated by brassinosteroids, referred to as BRKs (brassinosteroid regulated kinases) or BSKs (brassinosteroid signaling kinases). The present invention provides methods for modulating the response of a plant cell to a brassinosteroid using BRKs.

A single-station empirical model for TEC over the Antarctic Peninsula using GPS-TEC data

NASA Astrophysics Data System (ADS)

Feng, Jiandi; Wang, Zhengtao; Jiang, Weiping; Zhao, Zhenzhen; Zhang, Bingbing

2017-02-01

Compared with regional or global total electron content (TEC) empirical models, single-station TEC empirical models may exhibit higher accuracy in describing TEC spatial and temporal variations for a single station. In this paper, a new single-station empirical total electron content (TEC) model, called SSM-month, for the O'Higgins Station in the Antarctic Peninsula is proposed by using Global Positioning System (GPS)-TEC data from 01 January 2004 to 30 June 2015. The diurnal variation of TEC in the O'Higgins Station may have changing features in different months, sometimes even in opposite forms, because of ionospheric phenomena, such as the Mid-latitude Summer Nighttime Anomaly (MSNA). To avoid the influence of different diurnal variations, the concept of monthly modeling is proposed in this study. The SSM-month model, which is established by month (including 12 submodels that correspond to the 12 months), can effectively describe the diurnal variation of TEC in different months. Each submodel of the SSM-month model exhibits good agreement with GPS-TEC input data. Overall, the SSM-month model fits the input data with a bias of 0.03 TECU (total electron content unit, 1 TECU = 1016 el m-2) and a standard deviation of 2.78 TECU. This model, which benefits from the modeling method, can effectively describe the MSNA phenomenon without implementing any modeling correction. TEC data derived from Center for Orbit Determination in Europe global ionosphere maps (CODE GIMs), International Reference Ionosphere 2012 (IRI2012), and NeQuick are compared with the SSM-month model in the years of 2001 and 2015-2016. Result shows that the SSM-month model exhibits good consistency with CODE GIMs, which is better than that of IRI2012 and NeQuick, in the O'Higgins Station on the test days.

An empirical model of ionospheric total electron content (TEC) near the crest of the equatorial ionization anomaly (EIA)

NASA Astrophysics Data System (ADS)

Hajra, Rajkumar; Chakraborty, Shyamal Kumar; Tsurutani, Bruce T.; DasGupta, Ashish; Echer, Ezequiel; Brum, Christiano G. M.; Gonzalez, Walter D.; Sobral, José Humberto Andrade

2016-07-01

We present a geomagnetic quiet time (Dst > -50 nT) empirical model of ionospheric total electron content (TEC) for the northern equatorial ionization anomaly (EIA) crest over Calcutta, India. The model is based on the 1980-1990 TEC measurements from the geostationary Engineering Test Satellite-2 (ETS-2) at the Haringhata (University of Calcutta, India: 22.58° N, 88.38° E geographic; 12.09° N, 160.46° E geomagnetic) ionospheric field station using the technique of Faraday rotation of plane polarized VHF (136.11 MHz) signals. The ground station is situated virtually underneath the northern EIA crest. The monthly mean TEC increases linearly with F10.7 solar ionizing flux, with a significantly high correlation coefficient (r = 0.89-0.99) between the two. For the same solar flux level, the TEC values are found to be significantly different between the descending and ascending phases of the solar cycle. This ionospheric hysteresis effect depends on the local time as well as on the solar flux level. On an annual scale, TEC exhibits semiannual variations with maximum TEC values occurring during the two equinoxes and minimum at summer solstice. The semiannual variation is strongest during local noon with a summer-to-equinox variability of ~50-100 TEC units. The diurnal pattern of TEC is characterized by a pre-sunrise (0400-0500 LT) minimum and near-noon (1300-1400 LT) maximum. Equatorial electrodynamics is dominated by the equatorial electrojet which in turn controls the daytime TEC variation and its maximum. We combine these long-term analyses to develop an empirical model of monthly mean TEC. The model is validated using both ETS-2 measurements and recent GNSS measurements. It is found that the present model efficiently estimates the TEC values within a 1-σ range from the observed mean values.

Linear time series modeling of GPS-derived TEC observations over the Indo-Thailand region

NASA Astrophysics Data System (ADS)

Suraj, Puram Sai; Kumar Dabbakuti, J. R. K.; Chowdhary, V. Rajesh; Tripathi, Nitin K.; Ratnam, D. Venkata

2017-12-01

This paper proposes a linear time series model to represent the climatology of the ionosphere and to investigate the characteristics of hourly averaged total electron content (TEC). The GPS-TEC observation data at the Bengaluru international global navigation satellite system (GNSS) service (IGS) station (geographic 13.02°N , 77.57°E ; geomagnetic latitude 4.4°N ) have been utilized for processing the TEC data during an extended period (2009-2016) in the 24{th} solar cycle. Solar flux F10.7p index, geomagnetic Ap index, and periodic oscillation factors have been considered to construct a linear TEC model. It is evident from the results that solar activity effect on TEC is high. It reaches the maximum value (˜ 40 TECU) during the high solar activity (HSA) year (2014) and minimum value (˜ 15 TECU) during the low solar activity (LSA) year (2009). The larger magnitudes of semiannual variations are observed during the HSA periods. The geomagnetic effect on TEC is relatively low, with the highest being ˜ 4 TECU (March 2015). The magnitude of periodic variations can be seen more significantly during HSA periods (2013-2015) and less during LSA periods (2009-2011). The correlation coefficient of 0.89 between the observations and model-based estimations has been found. The RMSE between the observed TEC and model TEC values is 4.0 TECU (linear model) and 4.21 TECU (IRI2016 Model). Further, the linear TEC model has been validated at different latitudes over the northern low-latitude region. The solar component (F10.7p index) value decreases with an increase in latitude. The magnitudes of the periodic component become less significant with the increase in latitude. The influence of geomagnetic component becomes less significant at Lucknow GNSS station (26.76°N, 80.88°E) when compared to other GNSS stations. The hourly averaged TEC values have been considered and ionospheric features are well recovered with linear TEC model.

Ionospheric reaction on sudden stratospheric warming events in Russiás Asia region

NASA Astrophysics Data System (ADS)

Polyakova, Anna; Perevalova, Natalya; Chernigovskaya, Marina

2015-12-01

The response of the ionosphere to sudden stratospheric warmings (SSWs) in the Asian region of Russia is studied. Two SSW events observed in 2008-2009 and 2012-2013 winter periods of extreme solar minimum and moderate solar maximum are considered. To detect the ionospheric effects caused by SSWs, we carried out a joint analysis of global ionospheric maps (GIM) of the total electron content (TEC), MLS (Microwave Limb Sounder, EOS Aura) measurements of temperature vertical profiles, as well as NCEP/NCAR and UKMO Reanalysis data. For the first time, it was found that during strong SSWs, in the mid-latitude ionosphere the amplitude of diurnal TEC variation decreases nearly half compared to quiet days. At the same time, the intensity of TEC deviations from the background level increases. It was also found that at SSW peak the midday TEC maximum decreases, and night/morning TEC values increase compared to quiet days. It was shown that during SSWs, TEC dynamics was identical for different geophysical conditions.The response of the ionosphere to sudden stratospheric warmings (SSWs) in the Asian region of Russia is studied. Two SSW events observed in 2008-2009 and 2012-2013 winter periods of extreme solar minimum and moderate solar maximum are considered. To detect the ionospheric effects caused by SSWs, we carried out a joint analysis of global ionospheric maps (GIM) of the total electron content (TEC), MLS (Microwave Limb Sounder, EOS Aura) measurements of temperature vertical profiles, as well as NCEP/NCAR and UKMO Reanalysis data. For the first time, it was found that during strong SSWs, in the mid-latitude ionosphere the amplitude of diurnal TEC variation decreases nearly half compared to quiet days. At the same time, the intensity of TEC deviations from the background level increases. It was also found that at SSW peak the midday TEC maximum decreases, and night/morning TEC values increase compared to quiet days. It was shown that during SSWs, TEC dynamics was identical for different geophysical conditions.

Where does the plasmasphere begin? Revisit to topside ionospheric profiles in comparison with plasmaspheric TEC from Jason-1

NASA Astrophysics Data System (ADS)

Lee, Han-Byul; Kim, Yong Ha; Kim, Eunsol; Hong, Junseok; Kwak, Young-Sil

2016-10-01

Topside ionospheric profiles have been measured by Alouette 1 and ISIS 1/2 in the periods of 1962-1972 and 1972-1979, respectively. The profiles cover from the orbital altitude of 1000 km to the F2 peak and show large variations over local time, latitude, and seasons. We here analyze these variations in comparison with plasmaspheric total electron contents (pTECs) that were measured by Jason-1 satellite from the altitude of 1336 km to 20,200 km (GPS orbit). The scale heights of the profiles are generally smaller in the daytime than nighttime but show large day-to-day variations, implying that the ionospheric profiles at 1000 km are changing dynamically, rather than being in diffusive equilibrium. We also derived transition heights between O+ and H+, which show a clear minimum at dawn for low-latitude profiles due to decreasing O+ density at night. To compare with pTEC, we compute topside ionospheric total electron content (tiTEC) by integrating over 800-1336 km using the slope of the profiles. The tiTEC varies in a clear diurnal pattern from 0.3 to 1 and 3 total electron content unit (TECU, 1 TECU = 1016 el m-2) for low and high solar activity, respectively, whereas Jason-1 pTEC values are distributed over 2-6 TECU and 4-8 TECU for low and high solar activity, respectively, with no apparent diurnal modulation. Latitudinal variations of tiTEC show distinctive hemispheric asymmetry while that of Jason-1 pTEC is closely symmetric about the magnetic equator. The local time and latitudinal variations of tiTEC basically resemble those of the ionosphere but are characteristically different from those of Jason-1 pTEC. Based on the difference between tiTEC and pTEC variations, we propose that the region above 1300 km should be considered as the plasmasphere. Lower altitudes for the base of "plasmaspheric TEC," as used in some studies, would cause contamination of ionospheric influence.

Solar activity indices as a proxy for the variation of ionospheric Total Electron Content (TEC) over Bahir Dar, Ethiopia during the year 2010-2014

NASA Astrophysics Data System (ADS)

Kassa, Tsegaye; Tilahun, Samson; Damtie, Baylie

2017-09-01

This paper was aimed at investigating the solar variations of vTEC as a function of solar activity parameters, EUV and F10.7 radio flux. The daily values of ionospheric vertical Total Electron Content (vTEC) were observed using a dual frequency GPS receiver deployed at Bahir Dar (11.6°N and 37.36°E), Ethiopia. Measurements were taken during the period of 2010-2014 for successive five years and analysis was done on only quiet day observations. A quadratic fit was used as a model to describe the daily variation of vTEC in relation to solar parameters. Linear and non-linear coefficients of the vTEC variations were calculated in order to capture the trend of the variation. The variation of vTEC have showed good agreement with the trend of solar parameters in almost all of the days we consider during the period of our observations. We have explicitly observed days with insignificant TECU deviation (eg. modeling with respect to EUV, DOY = 49 in 2010 and modeling with respect to F10.7, DOY = 125 in 2012 and the like) and days with maximum deviation (about 50 TECU). A maximum deviation were observed, on average, during months of equinox whereas minimum during solstice months. This implies that there is a need to consider more parameters, including EUV and F10.7, that can affect the variation of vTEC during equinox seasons. Relatively, small deviations was observed in modeling vTEC as a function of EUV compared to that of the variation due to F10.7 cm flux. This may also tell us that EUV can be more suitable in modeling the solar variation of vTEC especially for longterm trends. Even though, the linear trend of solar variations of vTEC was frequently observed, significant saturation and amplification trends of the solar variations of vTEC were also observed to some extent across the months of the years we have analyzed. This mixed trend of the solar variation of vTEC implies the need for thorough investigation on the effect of solar parameters on TEC. However, based on long-term dataset, we came to conclude that the solar variations of vTEC is dominated by its linear pattern.

Determinations of ionosphere and plasmasphere electron content for an African chain of GPS stations

NASA Astrophysics Data System (ADS)

Mazzella, Andrew J., Jr.; Bosco Habarulema, John; Yizengaw, Endawoke

2017-05-01

The confluence of recent instrumentation deployments in Africa with developments for the determination of plasmasphere electron content using Global Positioning System (GPS) receivers has provided new opportunities for investigations in that region. This investigation, using a selected chain of GPS stations, extends the method (SCORPION) previously applied to a chain of GPS stations in North America in order to separate the ionosphere and plasmasphere contributions to the total electron content (TEC) during a day (24 July) in 2011. The results span latitudes from the southern tip of Africa, across the Equator, to the southern Arabian Peninsula, providing a continuous latitudinal profile for both the ionosphere and plasmasphere during this day.The peak diurnal vertical ionosphere electron content (IEC) increases from about 14 TEC units (1 TEC unit = 1016 electrons m-2) at the southernmost station to about 32 TEC units near the geographic equator, then decreases to about 28 TEC units at the Arabian Peninsula. The peak diurnal slant plasmasphere electron content (PEC) varies between about 4 and 7 TEC units among the stations, with a local latitudinal profile that is significantly influenced by the viewing geometry at the station location, relative to the magnetic field configuration. In contrast, the peak vertical PEC varies between about 1 and 6 TEC units among the stations, with a more uniform latitudinal variation.Comparisons to other GPS data analyses are also presented for TEC, indicating the influence of the PEC on the determination of latitudinal TEC variations and also on the absolute TEC levels, by inducing an overestimate of the receiver bias. The derived TEC latitudinal profiles, in comparison to global map profiles, tend to differ from the map results only about as much as the map results differ among themselves. A combination of ionosonde IEC and alternative GPS TEC measurements, which in principle permits a PEC determination through their difference, was compared to the composite and separate ionosphere and plasmasphere contributions derived solely by the SCORPION method for one station. Although there is considerably more scatter in the PEC values derived from the difference of the GPS TEC and ionosonde IEC measurements compared to the PEC values derived by the SCORPION method, the average overhead values for this day are comparable for the two methods, near 2 TEC units, at the South African site examined.This initial investigation provides a basis for day-to-day TEC monitoring for Africa, with separate ionosphere and plasmasphere electron content determinations.

Development of TEC fluctuations in northern and southern hemispheres on the base of GPS observations

NASA Astrophysics Data System (ADS)

Shagimuratov, Irk; Krankowski, Andrzej; Sieradzki, Rafal; Ephishov, I. I.

GPS technique is widely used to study the global structure and dynamics of the ionosphere. In this paper GPS observations carried out at Arctic and Antarctic stations belonging to the IGS network were used to study TEC fluctuations in the high-latitude ionosphere during the ionospheric storms. Dual-frequency GPS phase measurements along individual satellite passes served as raw data. It was shown that ionospheric irregularities of a different scale were devel-oped in the auroral and polar ionosphere. It is a common phenomenon caused phase fluctuations of GPS signals. In November 2009, West Department of IZMIRAN in Kaliningrad (Russia) and University of Warmia and Mazury in Olsztyn (Poland) established computer server for automatic monitoring of these irregularities. The rate of TEC index (ROTI) expressed in TECU/min was used as a measure of TEC fluctuations. During its operation TEC variations related to ionospheric structures of a spatial scale more than 200-300 km were detected. Large-scale ionospheric structures cause an increase in horizontal gradients and difficulties with the carrier phase ambiguity resolution in GPS positioning. In turn, the phase fluctuations can cause cycle-slip effects. At the polar stations, ionospheric structures with TEC enhanced by a factor of 3-5 relative to the background were detected, whereas TEC increased to 5-8 TECU in about 10-15 min. These structures were observed during a storm, as well as during a moderate geomagnetic activity. It can be probably attributed to the polar cap patches. In this study are presented the extended and more detailed analyses of TEC fluctuations in both the northern and southern hemispheres and compare the winter and summer events (November and July 2004 storms). A special attention is given to the features related to TEC fluctuations occur-rence in both hemispheres for conjugated GPS stations. The temporal development of both storms was rather similar. During storms the intensity of irregularities essentially increases and its location expands to equator. Maximal activity of TEC fluctuations took place when IMF Bz component was negative. Storm-time development of TEC fluctuations caused by ionospheric irregularities was controlled by UT. At polar stations TEC fluctuations were more expressed at southern (winter) hemisphere. Over auroral stations the difference of TEC fluctuations oc-currence was less expressed. During storm the strong TEC fluctuations can be registered at subauroral ionosphere (on latitudes lower than 55 CGL). The seasonal effect in this area also took place. Differences and similarities of these storms occurrence of TEC fluctuations with dependence on season are discussed.

Seasonal and solar cycle effects on TEC at 95°E in the ascending half (2009-2014) of the subdued solar cycle 24: Consistent underestimation by IRI 2012

NASA Astrophysics Data System (ADS)

Kakoti, Geetashree; Bhuyan, Pradip Kumar; Hazarika, Rumajyoti

2017-07-01

TEC measured at Dibrugarh (27.5°N, 94.9°E, 17.5°N Geomag.) from 2009 to 2014 is used to study its temporal characteristics during the ascending half of solar cycle 24. The measurements provide an opportunity to assess the diurnal, seasonal and longterm predictability of the IRI 2012 (with IRI Nequick, IRI01-corr, IRI 2001topside options) during this solar cycle which is distinctively low in magnitude compared to the previous cycles. The low latitude station Dibrugarh is normally located at the poleward edge of the northern EIA. A semi-annual variation in GPS TEC is observed with the peaks occurring in the equinoxes. The peak in spring (March, April) is higher than that in autumn (September, October) irrespective of the year of observation. The spring autumn asymmetry is also observed in IRI TEC. In contrast, the winter (November, December, January, February) anomaly is evident only in high activity years. TEC bears a distinct nonlinear relationship with 10.7 cm solar flux (F10.7). TEC increases linearly with F10.7 up to about 125 sfu beyond which it tends to saturate. The correlation between TEC and solar flux is found to be a function of local time and peaks at 10:00 LT. TEC varies nonlinearly with solar EUV flux similar to its variation with F10.7. The nonlinearity is well captured by the IRI. The saturation of TEC at high solar activity is attributed to the inability of the ionosphere to accommodate more ionization after it reaches the level of saturation ion pressure. Annual mean TEC increased from the minimum in 2009 almost linearly till 2012, remains at the same level in 2013 and then increased again in 2014. IRI TEC shows a linear increase from 2009 to 2014. IRI01-corr and IRI-NeQuick TEC are nearly equal at all local times, season and year of observation while IRI-2001 simulated TEC are always higher than that simulated by the other two versions. The IRI 2012 underestimates the TEC at about all local times except for a few hours in the midday in all season or year of observation. The discrepancy between model and measured TEC is high in spring and in the evening hours. The consistent underestimation of the TEC at this longitude by the IRI may be attributed to the inadequate ingestion of F region data from this longitude sector into the model and exclusion of the plasmaspheric content.

Update on Aire and thymic negative selection.

PubMed

Passos, Geraldo A; Speck-Hernandez, Cesar A; Assis, Amanda F; Mendes-da-Cruz, Daniella A

2018-01-01

Twenty years ago, the autoimmune regulator (Aire) gene was associated with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, and was cloned and sequenced. Its importance goes beyond its abstract link with human autoimmune disease. Aire identification opened new perspectives to better understand the molecular basis of central tolerance and self-non-self distinction, the main properties of the immune system. Since 1997, a growing number of immunologists and molecular geneticists have made important discoveries about the function of Aire, which is essentially a pleiotropic gene. Aire is one of the functional markers in medullary thymic epithelial cells (mTECs), controlling their differentiation and expression of peripheral tissue antigens (PTAs), mTEC-thymocyte adhesion and the expression of microRNAs, among other functions. With Aire, the immunological tolerance became even more apparent from the molecular genetics point of view. Currently, mTECs represent the most unusual cells because they express almost the entire functional genome but still maintain their identity. Due to the enormous diversity of PTAs, this uncommon gene expression pattern was termed promiscuous gene expression, the interpretation of which is essentially immunological - i.e. it is related to self-representation in the thymus. Therefore, this knowledge is strongly linked to the negative selection of autoreactive thymocytes. In this update, we focus on the most relevant results of Aire as a transcriptional and post-transcriptional controller of PTAs in mTECs, its mechanism of action, and its influence on the negative selection of autoreactive thymocytes as the bases of the induction of central tolerance and prevention of autoimmune diseases. © 2017 John Wiley & Sons Ltd.

Enhanced wound healing of tissue-engineered human corneas through altered phosphorylation of the CREB and AKT signal transduction pathways.

PubMed

Couture, Camille; Desjardins, Pascale; Zaniolo, Karine; Germain, Lucie; Guérin, Sylvain L

2018-06-01

The cornea is a transparent organ, highly specialized and unique that is continually subjected to abrasive forces and occasional mechanical or chemical trauma because of its anatomical localization. Upon injury, the extracellular matrix (ECM) rapidly changes to promote wound healing through integrin-dependent activation of specific signal transduction mediators whose contribution is to favor faster closure of the wound by altering the adhesive and migratory properties of the cells surrounding the damaged area. In this study, we exploited the human tissue-engineered cornea (hTECs) as a model to study the signal transduction pathways that participate to corneal wound healing. By exploiting both gene profiling and activated kinases arrays, we could demonstrate the occurrence of important alterations in the level of expression and activation of a few mediators from the PI3K/Akt and CREB pathways in response to the ECM remodeling taking place during wound healing of damaged hTECs. Pharmacological inhibition of CREB with C646 considerably accelerated wound closure compared to controls. This process was considerably accelerated further when both C646 and SC79, an Akt agonist, were added together to wounded hTECs. Therefore, our study demonstrate that proper corneal wound healing requires the activation of Akt together with the inhibition of CREB and that wound healing in vitro can be altered by the use of pharmacological inhibitors (such as C646) or agonists (such as SC79) of these mediators. Corneal wounds account for a large proportion of all visual disabilities in North America. To our knowledge, this is the first time that a tissue-engineered human cornea (hTEC) entirely produced using normal untransformed human cells is used as a biomaterial to study the signal transduction pathways that are critical to corneal wound healing. Through the use of this biomaterial, we demonstrated that human corneal epithelial cells engaged in wound healing reduce phosphorylation of the signal transduction mediator CREB while, in the mean time, they increase that of AKT. By increasing the activation of AKT together with a decrease in CREB activation, we could considerably reduce wound closure time in our punch-damaged hTECs. Considering the increasing interest given to the reconstruction of different types of tissues, we believe these results will have a strong impact on the field of tissue-engineering and biomaterials. Altering the activation status of the Akt and CREB proteins might prove to be a therapeutically interesting avenue and may also find applications in wound healing of other tissues beside the cornea, such as the skin. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Derivation of GPS TEC and receiver bias for Langkawi station in Malaysia

NASA Astrophysics Data System (ADS)

Teh, W. L.; Chen, W. S.; Abdullah, M.

2017-05-01

This paper presents the polynomial-type TEC model to derive total electron content (TEC) and receiver bias for Langkawi (LGKW) station in Malaysia at geographic latitude of 6.32° and longitude of 99.85°. The model uses a polynomial function of coordinates of the ionospheric piercing point to describe the TEC distribution in space. In the model, six polynomial coefficients and a receiver bias are unknown which can be solved by the least squares method. A reasonable agreement is achieved for the derivation of TEC and receiver bias for IENG station in Italy, as compared with that derived by the IGS analysis center, CODE. We process one year of LGKW data in 2010 and show the monthly receiver bias and the seasonal TEC variation. The monthly receiver bias varies between -48 and -24 TECu (1016 electrons/m2), with the mean value at -37 TECu. Large variations happen in the monthly receiver biases due to the low data coverage of high satellite elevation angle (60° < α ≤ 90°). Post-processing TEC approach is implemented which can resolve the wavy pattern of the monthly TEC baseline resulted from the large variation of the receiver bias. The seasonal TEC variation at LGKW exhibits a semi-annual variation, where the peak occurs during equinoctial months, and the trough during summer and winter months.

Ionospheric earthquake effects detection based on Total Electron Content (TEC) GPS Correlation

NASA Astrophysics Data System (ADS)

Sunardi, Bambang; Muslim, Buldan; Eka Sakya, Andi; Rohadi, Supriyanto; Sulastri; Murjaya, Jaya

2018-03-01

Advances in science and technology showed that ground-based GPS receiver was able to detect ionospheric Total Electron Content (TEC) disturbances caused by various natural phenomena such as earthquakes. One study of Tohoku (Japan) earthquake, March 11, 2011, magnitude M 9.0 showed TEC fluctuations observed from GPS observation network spread around the disaster area. This paper discussed the ionospheric earthquake effects detection using TEC GPS data. The case studies taken were Kebumen earthquake, January 25, 2014, magnitude M 6.2, Sumba earthquake, February 12, 2016, M 6.2 and Halmahera earthquake, February 17, 2016, M 6.1. TEC-GIM (Global Ionosphere Map) correlation methods for 31 days were used to monitor TEC anomaly in ionosphere. To ensure the geomagnetic disturbances due to solar activity, we also compare with Dst index in the same time window. The results showed anomalous ratio of correlation coefficient deviation to its standard deviation upon occurrences of Kebumen and Sumba earthquake, but not detected a similar anomaly for the Halmahera earthquake. It was needed a continous monitoring of TEC GPS data to detect the earthquake effects in ionosphere. This study giving hope in strengthening the earthquake effect early warning system using TEC GPS data. The method development of continuous TEC GPS observation derived from GPS observation network that already exists in Indonesia is needed to support earthquake effects early warning systems.

Assessment of Modeling Capability for Reproducing Storm Impacts on TEC

NASA Astrophysics Data System (ADS)

Shim, J. S.; Kuznetsova, M. M.; Rastaetter, L.; Bilitza, D.; Codrescu, M.; Coster, A. J.; Emery, B. A.; Foerster, M.; Foster, B.; Fuller-Rowell, T. J.; Huba, J. D.; Goncharenko, L. P.; Mannucci, A. J.; Namgaladze, A. A.; Pi, X.; Prokhorov, B. E.; Ridley, A. J.; Scherliess, L.; Schunk, R. W.; Sojka, J. J.; Zhu, L.

2014-12-01

During geomagnetic storm, the energy transfer from solar wind to magnetosphere-ionosphere system adversely affects the communication and navigation systems. Quantifying storm impacts on TEC (Total Electron Content) and assessment of modeling capability of reproducing storm impacts on TEC are of importance to specifying and forecasting space weather. In order to quantify storm impacts on TEC, we considered several parameters: TEC changes compared to quiet time (the day before storm), TEC difference between 24-hour intervals, and maximum increase/decrease during the storm. We investigated the spatial and temporal variations of the parameters during the 2006 AGU storm event (14-15 Dec. 2006) using ground-based GPS TEC measurements in the selected 5 degree eight longitude sectors. The latitudinal variations were also studied in two longitude sectors among the eight sectors where data coverage is relatively better. We obtained modeled TEC from various ionosphere/thermosphere (IT) models. The parameters from the models were compared with each other and with the observed values. We quantified performance of the models in reproducing the TEC variations during the storm using skill scores. This study has been supported by the Community Coordinated Modeling Center (CCMC) at the Goddard Space Flight Center. Model outputs and observational data used for the study will be permanently posted at the CCMC website (http://ccmc.gsfc.nasa.gov) for the space science communities to use.

Total Electron Content Retrieved From L-Band Radiometers and Potential Improvements to the IGS Model

NASA Astrophysics Data System (ADS)

Soldo, Yan; Hong, Liang; El-Nimri, Salem; Le Vine, David M.

2018-04-01

In recent years, several L-band microwave instruments have been launched into Earth's orbit to measure soil moisture and ocean salinity (e.g., Soil Moisture and Ocean Salinity [SMOS], Aquarius, and Soil Moisture Active/Passive [SMAP]). As the microwave signal travels through the ionosphere, the polarization vector rotates (Faraday rotation) and it is possible to estimate the total electron content (TEC) along the path by measuring this change. A comparison is presented of the TEC retrieved from Aquarius and SMAP over the ocean with the values provided by the IGS (International Global Navigation Satellite System Service (GNSS)). The TEC retrieved from Aquarius and SMAP measurements show good agreement with each other and, on a global scale, are in agreement with the TEC provided by the IGS. However, there are cases in which the TEC from the two satellite sensors are in good agreement with each other but differ significantly from the IGS TEC. The comparison suggests that the L-band instruments are a reliable source of TEC over the ocean and could be a valuable supplementary source of TEC values that could be assimilated in the IGS models, especially over the ocean, where GNSS ground stations are sparse.

TEC variability near northern EIA crest and comparison with IRI model

NASA Astrophysics Data System (ADS)

Aggarwal, Malini

2011-10-01

Monthly median values of hourly total electron content (TEC) is obtained with GPS at a station near northern anomaly crest, Rajkot (geog. 22.29°N, 70.74°E; geomag. 14.21°N, 144.9°E) to study the variability of low latitude ionospheric behavior during low solar activity period (April 2005 to March 2006). The TEC exhibit characteristic features like day-to-day variability, semiannual anomaly and noon bite out. The observed TEC is compared with latest International Reference Ionosphere (IRI) - 2007 model using options of topside electron density, NeQuick, IRI01-corr and IRI-2001 by using both URSI and CCIR coefficients. A good agreement of observed and predicted TEC is found during the daytime with underestimation at other times. The predicted TEC by NeQuick and IRI01-corr is closer to the observed TEC during the daytime whereas during nighttime and morning hours, IRI-2001 shows lesser discrepancy in all seasons by both URSI and CCIR coefficients.

Evaluation and analysis on the coupling performance of a high-speed turboexpander compressor

NASA Astrophysics Data System (ADS)

Chen, Shuangtao; Fan, Yufeng; Yang, Shanju; Chen, Xingya; Hou, Yu

2017-12-01

A high-speed turboexpander compressor (TEC) for small reverse Brayton air refrigerator is tested and analyzed in the present work. A TEC consists of an expander and a compressor, which are coupled together and interact with each other directly. Meanwhile, the expander and compressor have different effects on the refrigerator. The TEC overall efficiency, which contains effects of the expander's expansion, the compressor's pre-compression, and the pressure drop between them, was proved. It unifies influences of both compression and expansion processes on the COP of refrigerator and could be used to evaluate the TEC overall performance. Then, the coupling parameters were analyzed, which shows that for a TEC, the expander efficiency should be fully utilized first, followed by the compressor pressure ratio. Experiments were carried out to test the TEC coupling performances. The results indicated that, the TEC overall efficiency could reach 67.2%, and meanwhile 22.3% of the energy output was recycled.

Investigation of TEC Variations over Mid-Latitude during Quit and Disturbed Days of March 2015

NASA Astrophysics Data System (ADS)

Atıcı, Ramazan; Saǧır, Selçuk; Güzel, Esat

2016-07-01

The variations during 09-14-March-2015 quit days and 15-20 March 2015 disturbed days of Total Electron Content (TEC) values (provided by IONOLAB group) obtained by analysis the data from Ankara Global Position System (GPS) station of Turkey located at mid-latitude, IRI -2012 model the and IRI-PLUS model are investigated. Also, the variations of the geomagnetic, interplanetary and solar wind parameters are examined. As a result of investigations, TEC values from all three models are not change too much at quit days. Unlike, at the disturbed days, although IRI-2012 and IRI-PLUS TEC values are not change too much, a noticeable change in GPS-TEC values is occurred. GPS-TEC values are rapidly increased on 17-March 2015 to be severe magnetic storm (Dst = -124 nT). Then, on following days it was observed to significantly decrease. Thus, it is said that GPS-TEC values are more sensitive than IRI-2012 and IRI-PLUS models to variations occurred on disturbed days.

Space Weather Activities of IONOLAB Group: IONOLAB-TEC

NASA Astrophysics Data System (ADS)

Arikan, F.; Sezen, U.; Arikan, O.; Ugurlu, O.; Nayir, H.

2009-04-01

Space Weather (SW) is the concept of changing environmental conditions in outer space and affect Earth and its technological systems. SW is a consequence of the solar activities and the coupling of solar energy on Earth's atmosphere due to the Earth's magnetic field. The monitoring and prediction of SW has utmost importance for HF communication, Satellite communication, navigation and guidance systems, Low Earth Orbit (LEO) satellite systems, Space Craft exit and entry into the atmosphere. Ionosphere is the plasma layer of the atmosphere that is ionized by solar radiation and it is a key player of SW. Ionosphere is a temporally and spatially varying, dispersive, anisotropic and inhomogeneous medium that is characterized primarily by its electron density distribution. IONOLAB is a group of researchers of various disciplines, getting together to handle challenges of the Earth's ionosphere. The team has researchers from Hacettepe University and Bilkent University, Department of Electrical and Electronics Engineering and General Command of Mapping of Turkish Army. One of the most important contributions of IONOLAB group is the automated web-based computation service for Total Electron Content (TEC). TEC corresponds to the line integral of electron density distribution on a given path. TEC can also be expressed as the amount of free electrons within 1 m2 cross-sectional area of the cylinder on the ray path. Global Position System (GPS) provides a cost-effective medium for monitoring of ionosphere using the signals recorded by stationary GPS receivers in estimating TEC. IONOLAB group has developed IONOLAB-TEC for reliable and robust estimates for all latitudes and both calm and disturbed days by using RINEX, IONEX and satellite ephemeris data provided from the IGS centers. IONOLAB-TEC consists of a regularized signal estimation algorithm which combines signals from all GPS satellites for a given instant and a given receiver, for a desired time period or for 24 hours, with 30 s time resolution. IONOLAB-TEC values also include the receiver differential code bias (DCB) for each GPS station estimated uniquely by the IONOLAB-BIAS algorithm. The web based computation program is written in JAVA and it is provided both in Turkish and English at www.ionolab.org. The IONOLAB-TEC computation requires no installation or licensing on the client side. The application has a layered design. Developed components are modular that allows possible changes regarding the estimation method can be easily adapted. Same flexibility is also provided for the data access. Also, presentation of estimation data is architected to support different client types. Currently, the user can login to the IONOLAB-TEC web site and choose the desired location and dates on-line for TEC estimation. The carrier phase leveled TEC estimates of IONOLAB-TEC are provided for the chosen station/s and for the chosen day/s along with two-hourly GIM-TEC estimates of IGS centers. The output is provided in the user designated form either in graphs or an excel data sheet. The IONOLAB-TEC provides robust, reliable, and high resolution TEC estimates and provides a medium for comparison of the GIM-TEC values from the IGS centers.

Generalized approach to cooling charge-coupled devices using thermoelectric coolers

NASA Technical Reports Server (NTRS)

Petrick, S. Walter

1987-01-01

This paper is concerned with the use of thermoelectric coolers (TECs) to cool charge-coupled devices (CCDs). Heat inputs to the CCD from the warmer environment are identified, and generalized graphs are used to approximate the major heat inputs. A method of choosing and estimating the power consumption of the TEC is discussed. This method includes the use of TEC performance information supplied by the manufacturer and equations derived from this information. Parameters of the equations are tabulated to enable the reader to use the TEC performance equations for choosing and estimating the power needed for specific TEC applications.

Comparison of plasmaspheric electron content over sea and land using Jason-2 observations

NASA Astrophysics Data System (ADS)

Gulyaeva, Tamara; Cherniak, Iurii; Zakharenkova, Irina

2016-07-01

The Global Ionospheric Maps of Total Electron Content, GIM-TEC, may suffer from model assumptions, in particular, over the oceans where relatively few measurements are available due to a scarcity of ground-based GPS receivers network only on seashores and islands which involve more assumptions or interpolations imposed on GIM mapping techniques. The GPS-derived TEC represents the total electron content integrated through the ionosphere, iTEC, and the plasmasphere, pTEC. The sea/land differences in the F2 layer peak electron density, NmF2, and the peak height, hmF2, gathered with topside sounding data exhibit tilted ionosphere along the seashores with denser electron population at greater peak heights over the sea. Derivation of a sea/land proportion of total electron content from the new source of the satellite-based measurements would allow improve the mapping GIM-TEC products and their assimilation by the ionosphere-plasmasphere IRI-Plas model. In this context the data of Jason-2 mission provided through the NOAA CLASS Website (http://www.nsof.class.noaa.gov/saa/products/catSearch) present a unique database of pTEC measured through the plasmasphere over the Jason-2 orbit (1335 km) to GPS orbit (20,200 km) which become possible from GPS receivers placed onboard of Jason-2 with a zenith looking antenna that can be used not only for precise orbit determination (POD), but can also provide new data on the plasma density distribution in the plasmasphere. Special interest represents possibility of the potential increase of the data volume in two times due to the successful launch of the Jason-3 mission on 17 January 2016. The present study is focused on a comparison of plasmasphere electron content, pTEC, over the sea and land with a unique data base of the plasmasphere electron content, pTEC, using measurements onboard Jason-2 satellite during the solar minimum (2009) and solar maximum (2014). Slant TEC values were scaled to estimate vertical pTEC using a geometric factor derived by assuming the plasma occupies a spherical thin shell at 1400 km. The elevation angle cut-off was selected as 40 deg. Global distribution of POD TEC values has been presented in the form of pTEC maps, that were made by projecting the pTEC values on the Earth from the ionosphere pierce point at the shell altitude. Along the satellite pass for each epoch we have pTEC values for several linked LEO-GPS simultaneously, that can be binned and averaged into map cells. Results of pTEC maps analysis in terms of local time, season and solar activity are presented in the paper.

Review of variations in Mw < 7 earthquake motions on position and TEC (Mw = 6.5 Aegean Sea earthquake sample)

NASA Astrophysics Data System (ADS)

Yildirim, Omer; Inyurt, Samed; Mekik, Cetin

2016-02-01

Turkey is a country located in the middle latitude zone, where tectonic activity is intensive. Recently, an earthquake of magnitude 6.5 Mw occurred offshore in the Aegean Sea on 24 May 2014 at 09:25 UTC, which lasted about 40 s. The earthquake was also felt in Greece, Romania, and Bulgaria in addition to Turkey. In recent years, ionospheric anomaly detection studies have been carried out because of seismicity with total electron content (TEC) computed from the global navigation satellite system's (GNSS) signal delays and several interesting findings have been published. In this study, both TEC and positional variations have been examined separately following a moderate size earthquake in the Aegean Sea. The correlation of the aforementioned ionospheric variation with the positional variation has also been investigated. For this purpose, a total of 15 stations was used, including four continuously operating reference stations in Turkey (CORS-TR) and stations in the seismic zone (AYVL, CANA, IPSA, and YENC), as well as international GNSS service (IGS) and European reference frame permanent network (EPN) stations. The ionospheric and positional variations of the AYVL, CANA, IPSA, and YENC stations were examined using Bernese v5.0 software. When the precise point positioning TEC (PPP-TEC) values were examined, it was observed that the TEC values were approximately 4 TECU (total electron content unit) above the upper-limit TEC value at four stations located in Turkey, 3 days before the earthquake at 08:00 and 10:00 UTC. At the same stations, on the day before the earthquake at 06:00, 08:00, and 10:00 UTC, the TEC values were approximately 5 TECU below the lower-limit TEC value. The global ionosphere model TEC (GIM-TEC) values published by the Centre for Orbit Determination in Europe (CODE) were also examined. Three days before the earthquake, at all stations, it was observed that the TEC values in the time period between 08:00 and 10:00 UTC were approximately 2 TECU above the upper-limit TEC value; 1 day before the earthquake at 06:00, 08:00, and 10:00 UTC, the TEC values were approximately 4 TECU below the lower-limit TEC value. Again, by using the same 15 stations, positional variation investigation for before and after the earthquake was undertaken for the AYVL, CANA, IPSA, and YENC stations. As a result of the conducted analysis, positional displacements were seen before and after the earthquake at the CANA station, which is the nearest station to the earthquake centre. Before and after the earthquake, positional displacements were observed as 10 and 3 cm respectively.

Analysis of ionosphere variability over low-latitude GNSS stations during 24th solar maximum period

NASA Astrophysics Data System (ADS)

Venkata Ratnam, D.; Sivavaraprasad, G.; Latha Devi, N. S. M. P.

2017-07-01

Global Positioning System (GPS) is a remote sensing tool of space weather and ionospheric variations. However, the interplanetary space-dependent drifts in the ionospheric irregularities cause predominant ranging errors in the GPS signals. The dynamic variability of the low-latitude ionosphere is an imperative threat to the satellite-based radio communication and navigation ranging systems. The study of temporal and spatial variations in the ionosphere has triggered new investigations in modelling, nowcasting and forecasting the ionospheric variations. Hence, in this paper, the dynamism in the day-to-day, month-to-month and seasonal variability of the ionospheric Total Electron Content (TEC) has been explored during the solar maximum period, January-December 2013, of the 24th solar cycle. The spatial and temporal variations of the ionosphere are analysed using the TEC values derived from three Indian low-latitude GPS stations, namely, Bengaluru, Guntur and Hyderabad, separated by 13-18° in latitude and 77-81° in longitude. The observed regional GPS-TEC variations are compared with the predicted TEC values of the International Reference Ionosphere (IRI-2012 and 2007) models. Ionospheric parameters such as Vertical TEC (VTEC), relative TEC deviation index and monthly variations in the grand-mean of ionosphere TEC and TEC intensity, along with the upper and lower quartiles, are adopted to investigate the ionosphere TEC variability during quiet and disturbed days. The maximum ionospheric TEC variability is found during March and September equinoxes, followed by December solstice while the minimum variability is observed during June solstice. IRI models are in reasonable agreement with GPS TEC but are overestimating during dawn hours (01:00-06:00 LT) as compared to the dusk hours. Higher percentage deviations are observed during equinoctial months than summer over EIA stations, Guntur and Hyderabad. GPS TEC variations are overestimated during dawn hours for all the seasons over Bengaluru. It has also been observed that positive storm effect (enhancement of TEC) is observed during the main phase of the March storm, 2013 (March 16-18, 2013) while both positive and negative storm effects (depletion of TEC) are registered during the main phase of the June storm, 2013 (June 28-30, 2013) at Bengaluru and Guntur, respectively. IRI-2012 model has slightly large discrepancies with the GPS-VTEC compared with the IRI-2007 model during the June storm, 2013 over Guntur station. This analysis highlights the importance of upgrading the IRI models due to their discrepancies during quiet and disturbed states of the ionosphere and developing an early warning forecast system to alert about ionosphere variability.

Determination of Ionospheric Total Electron Content Derived from Gnss Measurements

NASA Astrophysics Data System (ADS)

Inyurt, S.; Mekik, C.; Yildirim, O.

2014-12-01

Global Navigation Satellite System (GNSS) has been used in numerous fields especially related to satellite- based radio navigation system for a long time. Ionosphere, one of the upper atmosphere layers ranges from 60 km to 1500 km, is a dispersive medium and it includes a number of free electrons and ions. The ionization is mainly subject to the sun and its activity. Ionospheric activity depends also on seasonal, diurnal variations and geographical location. Total Electron Content (TEC), which is also called Slant Total Electron Content (STEC), is a parameter that changes according to ionospheric conditions and has highly variable structure. Furthermore, Vertical TEC (VTEC) can be explained as TEC value in the direction of zenith. Thanks to VTEC, TEC values can be modelled. TEC is measured in units of TECU and 1TECU= 1016 electrons/m2. Ionospheric modelling has a great importance for improving the accuracies of positioning and understanding the ionosphere. Thus, various models have been developed to detect TEC value in the last years. Single Layer Model (SLM) which provides determining TEC value and GPS positioning in the ionosphere accurately is one of the most commonly used models. SLM assumes that all free electrons are concentrated in a shell of infinitesimal thickness. In this paper SLM model was used to derive TEC values by means of Bernese 5.0 program developed by the University of Bern, Sweden. In this study, we have used regional ionosphere model to derive TEC value. First of all, GPS data have been collected from 10 stations in Turkey and 13 IGS stations for 7 days from 06.03.2010 to 12.03.2010. Then, Regional Ionosphere Model (RIM) is created with the reference of the GPS data. At the end of the process, the result files are stored as IONEX format. TEC results for those days are obtained with two hours interval. TEC variation related to the research area ranges from nearly 6 TECU to approximately 20 TECU. The obtained results show that TEC values start increasing until mid-days and reach peak value at 12:00 UT. After 12:00 UT it begins decreasing gradually towards night because of recombination of the ions. As a result, SLM is an effective model for mapping TEC values and determination of TEC variation can be used to identify many studies such as precursor of earthquakes, volcanic eruptions and launching site determination etc.

GPS TEC near the crest of the EIA at 95°E during the ascending half of solar cycle 24 and comparison with IRI simulations

NASA Astrophysics Data System (ADS)

Bhuyan, Pradip Kumar; Hazarika, Rumajyoti

2013-10-01

Total electron content (TEC) data obtained from GPS dual frequency measurements during the ascending half of the solar cycle 24 from 2009 to 2012 over Dibrugarh (27.5°N, 94.9°E; 17.6°N MLAT) have been used to study the diurnal, seasonal, annual and solar cycle variation of TEC. The measurements reported here are for the first time from the location situated at the poleward edge of the northern equatorial ionization anomaly (EIA) and within the peak region of the longitudinal wave number 4 (WN4) structure in EIA crest TEC. TEC exhibits a minimum around 0600 LT and diurnal maximum around 1300-1600 LT. In the low and moderate solar activity years 2009-2010 and 2010-2011, average daytime (1000-1600 LT) TEC in summer was higher (25.4 and 36.6 TECU) compared to that in winter (21.5 and 26.1 TECU). However, at the peak of the solar cycle in 2011-2012, reversal in the level of ionization between winter and summer takes place and winter TEC becomes higher (50.6 TECU) than that in summer (45.0 TECU). Further, TEC in spring (34.1, 49.9 and 63.3 TECU respectively in 2009-10, 2010-11 and 2011-12) is higher than that in autumn (24.2, 32.3 and 51.9 TECU respectively) thus showing equinoctial asymmetry in all the years of observation. The winter anomaly in high solar activity years and equinoctial asymmetry all throughout may be largely attributed to changes in the thermospheric O/N2 density ratio. A winter to summer delay of ˜1 h in the time of occurrence of the diurnal maximum has also been observed. Daytime maximum TEC bears a nonlinear relationship with F10.7 cm solar flux. TEC increases linearly with F10.7 cm solar flux initially up to about 140 sfu (1 sfu = 10-22 W m-2 Hz-1) after which it tends to saturate. On the contrary, TEC increases linearly with solar EUV flux (photons cm-2 s-1, 0.5-50 nm) during the same period. TEC predicted by the IRI 2012 are lower than the measured TEC for nearly 90% of the time.

Optimize out-of-core thermionic energy conversion for nuclear electric propulsion

NASA Technical Reports Server (NTRS)

Morris, J. F.

1977-01-01

Current designs for out of core thermionic energy conversion (TEC) to power nuclear electric propulsion (NEP) were evaluated. Approaches to improve out of core TEC are emphasized and probabilities for success are indicated. TEC gains are available with higher emitter temperatures and greater power densities. Good potentialities for accommodating external high temperature, high power density TEC with heat pipe cooled reactors exist.

Inactivation of the RB family prevents thymus involution and promotes thymic function by direct control of Foxn1 expression

PubMed Central

Garfin, Phillip M.; Min, Dullei; Bryson, Jerrod L.; Serwold, Thomas; Edris, Badreddin; Blackburn, Clare C.; Richie, Ellen R.; Weinberg, Kenneth I.; Manley, Nancy R.; Viatour, Patrick

2013-01-01

Thymic involution during aging is a major cause of decreased production of T cells and reduced immunity. Here we show that inactivation of Rb family genes in young mice prevents thymic involution and results in an enlarged thymus competent for increased production of naive T cells. This phenotype originates from the expansion of functional thymic epithelial cells (TECs). In RB family mutant TECs, increased activity of E2F transcription factors drives increased expression of Foxn1, a central regulator of the thymic epithelium. Increased Foxn1 expression is required for the thymic expansion observed in Rb family mutant mice. Thus, the RB family promotes thymic involution and controls T cell production via a bone marrow–independent mechanism, identifying a novel pathway to target to increase thymic function in patients. PMID:23669396

Imperfect coupling between northern and southern ionospheres: asymmetry in TEC anomalies before earthquakes

NASA Astrophysics Data System (ADS)

Jhuang, Hau-Kun; Ho, Yi-Ying; Lee, Lou-Chuang

2016-04-01

The northern ionosphere is coupled to the conjugate southern ionosphere through the highly conducting geomagenetic field lines. The coupling is very strong or "perfect" if the geomagnetic field lines are equipotential (the parallel electric field E||=0) and hence the perpendicular electric field (E⊥) at the conjugate sites of both ionospheres are equal. The coupling is "imperfect" if some of the geomagnetic field lines are non-equipotential (E||≠0). The field-aligned electric field E|| can be associated with electron inertia, pressure gradient and collisions appearing in the form of double layer, kinetic Alfvén waves and finite field-aligned conductivity σ||. We use the Global Ionospheric Maps (GIM) data to examine the conjugate effect of total electron content (TEC) for six significant earthquakes. The anomalous (ΔTEC)source in the source ionosphere and (ΔTEC)conjugate in the conjugate ionosphere are obtained for 85 events before the six earthquakes. The ΔTEC ratio β = (ΔTEC)conjugate / (ΔTEC)source is calculated for each anomaly. For a "perfect" coupling, β=1. There are 85 anomalous events before the six significant earthquakes, with 62 events occurring in the daytime (07-18 LT) and 23 events in the nighttime (19-06 LT). The average value of daytime (07-18 LT) TEC variations in the source ionosphere is |ΔTEC|source =20.13 TECu, while the average value in the nighttime (19-06 LT) ionosphere is |ΔTEC|source=14.43 TECu. The value of ΔTEC ratio β ranges from 0.05 (very weak coupling) to 0.98 (nearly perfect coupling) with an average of 0.52. There are 14 strong coupling cases with β ≥0.8, which take place from 11 LT to 19 LT. The daytime (07-18 LT) β average value is 0.57 and the nighttime (19-06 LT) β average is 0.37. The south-north ionosphere coupling is stronger (weaker) in the daytime (nighttime).

Validation of foF2 and TEC Modeling During Geomagnetic Disturbed Times: Preliminary Outcomes of International Forum for Space Weather Modeling Capabilities Assessment

NASA Astrophysics Data System (ADS)

Shim, J. S.; Tsagouri, I.; Goncharenko, L. P.; Kuznetsova, M. M.

2017-12-01

To address challenges of assessment of space weather modeling capabilities, the CCMC (Community Coordinated Modeling Center) is leading the newly established "International Forum for Space Weather Modeling Capabilities Assessment." This presentation will focus on preliminary outcomes of the International Forum on validation of modeled foF2 and TEC during geomagnetic storms. We investigate the ionospheric response to 2013 Mar. geomagnetic storm event using ionosonde and GPS TEC observations in North American and European sectors. To quantify storm impacts on foF2 and TEC, we first quantify quiet-time variations of foF2 and TEC (e.g., the median and the average of the five quietest days for the 30 days during quiet conditions). It appears that the quiet time variation of foF2 and TEC are about 10% and 20-30%, respectively. Therefore, to quantify storm impact, we focus on foF2 and TEC changes during the storm main phase larger than 20% and 50%, respectively, compared to 30-day median. We find that in European sector, both foF2 and TEC response to the storm are mainly positive phase with foF2 increase of up to 100% and TEC increase of 150%. In North America sector, however, foF2 shows negative effects (up to about 50% decrease), while TEC shows positive response (the largest increase is about 200%). To assess modeling capability of reproducing the changes of foF2 and TEC due to the storm, we use various model simulations, which are obtained from empirical, physics-based, and data assimilation models. The performance of each model depends on the selected metrics, therefore, only one metrics is not enough to evaluate the models' predictive capabilities in capturing the storm impact. The performance of the model also varies with latitude and longitude.

Variations of total electron content in the equatorial anomaly region in Thailand

NASA Astrophysics Data System (ADS)

Chowdhary, V. Rajesh; Tripathi, N. K.; Arunpold, Sanit; Raju, Durairaju Kumaran

2015-01-01

This paper presents the first results of total electron content (TEC), derived by analyzing dual frequency Novatel GSV4004 GPS receiver's data which were installed by the SCINDA project, located at the Asian Institute of Technology, Bangkok (AITB, 14.079N, 100.612E) and Chiang Mai University, Chiang Mai (CHGM, 18.480N, 98.570E) with magnetic latitude of 4.13°N and 8.61°N respectively in Thailand, for the year 2011. These two stations are separated by 657 km in the equatorial anomaly region. The highest TEC values occurred from 1500 to 1900 LT throughout the study period. The diurnal, monthly and seasonal GPS-TEC have been plotted and analyzed. The diurnal peaks in GPS-TEC is observed to be maximum during equinoctial months (March, April, September and October) and minimum in solstice months (January, February, June, July and December). These high TEC values have been attributed to the solar extreme ultra-violet ionization coupled with the upward vertical E × B drift. A comparison of both station's TEC has been carried out and found that CHGM station experiences higher values of TEC than AITB station, due to formation of ionization crest over the CHGM station. Also, TEC values have shown increasing trend due to approaching solar maximum. These results from both stations were also compared with the TEC derived from the International Reference Ionosphere's (IRI) recently released, IRI-2012 model. Results have shown positive correlation with IRI-2012 model. Although, IRI-model does not show any response to geomagnetic activity, the IRI model normally remains smooth and underestimates TEC during a storm.

Ibrutinib inhibition of Bruton protein-tyrosine kinase (BTK) in the treatment of B cell neoplasms.

PubMed

Roskoski, Robert

2016-11-01

The Bruton non-receptor protein-tyrosine kinase (BTK), a deficiency of which leads to X-linked agammaglobulinemia, plays a central role in B cell antigen receptor signaling. Owing to the exclusivity of this enzyme in B cells, the acronym could represent B cell tyrosine kinase. BTK is activated by the Lyn and SYK protein kinases following activation of the B cell receptor. BTK in turn catalyzes the phosphorylation and activation of phospholipase Cγ2 leading to the downstream activation of the Ras/RAF/MEK/ERK pathway and the NF-κB pathways. Both pathways participate in the maturation of antibody-producing B cells. The BTK domains include a PH (pleckstrin homology) domain that interacts with membrane-associated phosphatidyl inositol trisphosphate, a TH (TEC homology) domain, which is followed by an SH3, SH2, and finally a protein kinase domain. Dysregulation of B cell receptor signaling occurs in several B cell neoplasms including mantle cell lymphoma, chronic lymphocytic leukemia, and Waldenström macroglobulinemia. Ibrutinib is FDA-approved as first-line or second line treatment for these diseases. The drug binds tightly in the ATP-binding pocket of BTK making salt bridges with residues within the hinge that connects the two lobes of the enzyme; then its unsaturated acrylamide group forms a covalent bond with BTK cysteine 481 to form an inactive adduct. In addition to the treatment of various B cell lymphomas, ibrutinib is under clinical trials for the treatment of numerous solid tumors owing to the role of tumor-promoting inflammation in the pathogenesis of neoplastic diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

TEC Variations Over Korean Peninsula During Magnetic Storm

NASA Astrophysics Data System (ADS)

Ji, E.-Y.; Choi, B.-K.; Kim, K.-H.; Lee, D.-H.; Cho, J.-H.; Chung, J.-K.; Park, J.-U.

2008-03-01

By analyzing the observations from a number of ground- and space-based instruments, including ionosonde, magnetometers, and ACE interplanetary data, we examine the response of the ionospheric TEC over Korea during 2003 magnetic storms. We found that the variation of vertical TEC is correlated with the southward turning of the interplanetary magnetic field B_z. It is suggested that the electric fields produced by the dynamo process in the high-latitude region and the prompt penetration in the low-latitude region are responsible for TEC increases. During the June 16 event, dayside TEC values increase more than 15%. And the ionospheric F2-layer peak height (hmF2) was ˜300km higher and the vertical E×B drift (estimated from ground-based magnetometer equatorial electrojet delta H) showed downward drift, which may be due to the ionospheric disturbance dynamo electric field produced by the large amount of energy dissipation into high-latitude regions. In contr! ast, during November 20 event, the nightside TEC increases may be due to the prompt penetration westward electric field. The ionospheric F2-layer peak height was below 200km and the vertical E×B drift showed downward drift. Also, a strong correlation is observed between enhanced vertical TEC and enhanced interplanetary electric field. It is shown that, even though TEC increases are caused by the different processes, the electric field disturbances in the ionosphere play an important role in the variation of TEC over Korea.

Ionospheric Anomalies of the 2011 Tohoku Earthquake with Multiple Observations during Magnetic Storm Phase

NASA Astrophysics Data System (ADS)

Liu, Yang

2017-04-01

Ionospheric anomalies linked with devastating earthquakes have been widely investigated by scientists. It was confirmed that GNSS TECs suffered from drastically increase or decrease in some diurnal periods prior to the earthquakes. Liu et al (2008) applied a TECs anomaly calculation method to analyze M>=5.9 earthquakes in Indonesia and found TECs decadence within 2-7 days prior to the earthquakes. Nevertheless, strong TECs enhancement was observed before M8.0 Wenchuan earthquake (Zhao et al 2008). Moreover, the ionospheric plasma critical frequency (foF2) has been found diminished before big earthquakes (Pulinets et al 1998; Liu et al 2006). But little has been done regarding ionospheric irregularities and its association with earthquake. Still it is difficult to understand real mechanism between ionospheric anomalies activities and its precursor for the huge earthquakes. The M9.0 Tohoku earthquake, happened on 11 March 2011, at 05:46 UT time, was recognized as one of the most dominant events in related research field (Liu et al 2011). A median geomagnetic disturbance also occurred accompanied with the earthquake, which makes the ionospheric anomalies activities more sophisticated to study. Seismic-ionospheric disturbance was observed due to the drastic activities of earth. To further address the phenomenon, this paper investigates different categories of ionospheric anomalies induced by seismology activity, with multiple data sources. Several GNSS ground data were chosen along epicenter from IGS stations, to discuss the spatial-temporal correlations of ionospheric TECs in regard to the distance of epicenter. We also apply GIM TEC maps due to its global coverage to find diurnal differences of ionospheric anomalies compared with geomagnetic quiet day in the same month. The results in accordance with Liu's conclusions that TECs depletion occurred at days quite near the earthquake day, however the variation of TECs has special regulation contrast to the normal quiet days. Associated with geomagnetic storm at similar time, radio occultation data provided by COSMIC were deeply investigated within the whole month. It's quite different that the storm or earthquake didn't trigger scintillation burst. This is probably due to the storm occurrence local time was in noon sector, which has little impact on ionospheric irregularities increase, but help to enhance the effect of westward electricity, which on the other hand diminishes scintillation bubbles (Li et al 2008). A small geomagnetic disturbance was also found almost a week prior to the earthquake, the relationship of this event to the major earthquake is worth further discussion. Similar analysis of GNSS TECs have been done, the results indicated that it can be also referred as precursor to the major earthquake. Li G, Ning B, Zhao B, et al. Effects of geomagnetic storm on GPS ionospheric scintillations at Sanya[J]. Journal of Atmospheric and Solar-Terrestrial Physics, 2008, 70(7):1034-1045. Liu J Y, Chen Y I, Chuo Y J, et al. A statistical investigation of pre-earthquake ionospheric anomaly[J]. Journal of Geophysical Research Atmospheres, 2006, 111(A5). Liu J Y, Sun Y Y. Seismo-traveling ionospheric disturbances of ionograms observed during the 2011 Mw 9.0 Tohoku Earthquake[J]. Earth, Planets and Space, 2011, 63(7):897-902. Zhao B, Wang M, Yu T, et al. Is an unusual large enhancement of ionospheric electron density linked with the 2008 great Wenchuan earthquake?[J]. Journal of Geophysical Research Atmospheres, 2008, 113(A11):A11304. Pulinets S A. Seismic activity as a source of the ionospheric variability [J]. Advances in Space Research, 1998, 22(6):903-906.

Real-Time Detection of Tsunami Ionospheric Disturbances with a Stand-Alone GNSS Receiver: A Preliminary Feasibility Demonstration

NASA Astrophysics Data System (ADS)

Savastano, Giorgio; Komjathy, Attila; Verkhoglyadova, Olga; Mazzoni, Augusto; Crespi, Mattia; Wei, Yong; Mannucci, Anthony J.

2017-04-01

It is well known that tsunamis can produce gravity waves that propagate up to the ionosphere generating disturbed electron densities in the E and F regions. These ionospheric disturbances can be studied in detail using ionospheric total electron content (TEC) measurements collected by continuously operating ground-based receivers from the Global Navigation Satellite Systems (GNSS). Here, we present results using a new approach, named VARION (Variometric Approach for Real-Time Ionosphere Observation), and estimate slant TEC (sTEC) variations in a real-time scenario. Using the VARION algorithm we compute TEC variations at 56 GPS receivers in Hawaii as induced by the 2012 Haida Gwaii tsunami event. We observe TEC perturbations with amplitudes of up to 0.25 TEC units and traveling ionospheric perturbations (TIDs) moving away from the earthquake epicenter at an approximate speed of 316 m/s. We perform a wavelet analysis to analyze localized variations of power in the TEC time series and we find perturbation periods consistent with a tsunami typical deep ocean period. Finally, we present comparisons with the real-time tsunami MOST (Method of Splitting Tsunami) model produced by the NOAA Center for Tsunami Research and we observe variations in TEC that correlate in time and space with the tsunami waves.

Latitudinal and Seasonal Investigations of Storm-Time TEC Variation

NASA Astrophysics Data System (ADS)

Adimula, I. A.; Oladipo, O. A.; Adebiyi, S. J.

2016-07-01

The ionosphere responds markedly and unpredictably to varying magnetospheric energy inputs caused by solar disturbances on the geospace. Knowledge of the impact of the space weather events on the ionosphere is important to assess the environmental effect on the operations of ground- and space-based technologies. Thus, global positioning system (GPS) measurements from the international GNSS service (IGS) database were used to investigate the ionospheric response to 56 geomagnetic storm events at six different latitudes comprising the northern and southern hemispheres in the Afro-European sector. Statistical distributions of total electron content (TEC) response show that during the main phase of the storms, enhancement of TEC is more pronounced in most of the seasons, regardless of the latitude and hemisphere. However, a strong seasonal dependence appears in the TEC response during the recovery phase. Depletion of TEC is majorly observed at the high latitude stations, and its appearance at lower latitudes is seasonally dependent. In summer hemisphere, the depletion of TEC is more pronounced in nearly all the latitudinal bands. In winter hemisphere, enhancement as well as depletion of TEC is observed over the high latitude, while enhancement is majorly observed over the mid and low latitudes. In equinoxes, the storm-time TEC distribution shows a fairly consistent characteristic with the summer distribution, particularly in the northern hemisphere.

Real-Time Detection of Tsunami Ionospheric Disturbances with a Stand-Alone GNSS Receiver: A Preliminary Feasibility Demonstration

PubMed Central

Savastano, Giorgio; Komjathy, Attila; Verkhoglyadova, Olga; Mazzoni, Augusto; Crespi, Mattia; Wei, Yong; Mannucci, Anthony J.

2017-01-01

It is well known that tsunamis can produce gravity waves that propagate up to the ionosphere generating disturbed electron densities in the E and F regions. These ionospheric disturbances can be studied in detail using ionospheric total electron content (TEC) measurements collected by continuously operating ground-based receivers from the Global Navigation Satellite Systems (GNSS). Here, we present results using a new approach, named VARION (Variometric Approach for Real-Time Ionosphere Observation), and estimate slant TEC (sTEC) variations in a real-time scenario. Using the VARION algorithm we compute TEC variations at 56 GPS receivers in Hawaii as induced by the 2012 Haida Gwaii tsunami event. We observe TEC perturbations with amplitudes of up to 0.25 TEC units and traveling ionospheric perturbations (TIDs) moving away from the earthquake epicenter at an approximate speed of 316 m/s. We perform a wavelet analysis to analyze localized variations of power in the TEC time series and we find perturbation periods consistent with a tsunami typical deep ocean period. Finally, we present comparisons with the real-time tsunami MOST (Method of Splitting Tsunami) model produced by the NOAA Center for Tsunami Research and we observe variations in TEC that correlate in time and space with the tsunami waves. PMID:28429754

Statistical Analysis of TEC Anomalies Prior to M6.0+ Earthquakes During 2003-2014

NASA Astrophysics Data System (ADS)

Zhu, Fuying; Su, Fanfan; Lin, Jian

2018-04-01

There are many studies on the anomalous variations of the ionospheric TEC prior to large earthquakes. However, whether or not the morphological characteristics of the TEC anomalies in the daytime and at night are different is rarely studied. In the present paper, based on the total electron content (TEC) data from the global ionosphere map (GIM), we carry out a statistical survey on the spatial-temporal distribution of TEC anomalies before 1339 global M6.0+ earthquakes during 2003-2014. After excluding the interference of geomagnetic disturbance, the temporal and spatial distributions of ionospheric TEC anomalies prior to the earthquakes in the daytime and at night are investigated and compared. Except that the nighttime occurrence rates of the pre-earthquake ionospheric anomalies (PEIAs) are higher than those in the daytime, our analysis has not found any statistically significant difference in the spatial-temporal distribution of PEIAs in the daytime and at night. Moreover, the occurrence rates of pre-earthquake ionospheric TEC both positive anomalies and negative anomalies at night tend to increase slightly with the earthquake magnitude. Thus, we suggest that monitoring the ionospheric TEC changes at night might be a clue to reveal the relation between ionospheric disturbances and seismic activities.

Real-Time Detection of Tsunami Ionospheric Disturbances with a Stand-Alone GNSS Receiver: A Preliminary Feasibility Demonstration.

PubMed

Savastano, Giorgio; Komjathy, Attila; Verkhoglyadova, Olga; Mazzoni, Augusto; Crespi, Mattia; Wei, Yong; Mannucci, Anthony J

2017-04-21

It is well known that tsunamis can produce gravity waves that propagate up to the ionosphere generating disturbed electron densities in the E and F regions. These ionospheric disturbances can be studied in detail using ionospheric total electron content (TEC) measurements collected by continuously operating ground-based receivers from the Global Navigation Satellite Systems (GNSS). Here, we present results using a new approach, named VARION (Variometric Approach for Real-Time Ionosphere Observation), and estimate slant TEC (sTEC) variations in a real-time scenario. Using the VARION algorithm we compute TEC variations at 56 GPS receivers in Hawaii as induced by the 2012 Haida Gwaii tsunami event. We observe TEC perturbations with amplitudes of up to 0.25 TEC units and traveling ionospheric perturbations (TIDs) moving away from the earthquake epicenter at an approximate speed of 316 m/s. We perform a wavelet analysis to analyze localized variations of power in the TEC time series and we find perturbation periods consistent with a tsunami typical deep ocean period. Finally, we present comparisons with the real-time tsunami MOST (Method of Splitting Tsunami) model produced by the NOAA Center for Tsunami Research and we observe variations in TEC that correlate in time and space with the tsunami waves.

The NASA thermionic-conversion (TEC-ART) program

NASA Technical Reports Server (NTRS)

Morris, J. F.

1977-01-01

The current emphasis is on out-of-core thermionic conversion (TEC). The additional degrees of freedom offer new potentialities, but high-temperature material effects determine the level and lifetime of TEC performance: New electrodes not only raise power outputs but also maintain them regardless of emitter-vapor deposition on collectors. In addition, effective electrodes serve compatibly with hot-shell alloys. Space TEC withstands external and internal high-temperature vaporization problems, and terrestrial TEC tolerates hot corrosive atmospheres outside and near-vacuum inside. Finally, reduction of losses between converter electrodes is essential even though rather demanding geometries appear to be required for some modes of enhanced operation.

Joint Analysis of the Full AzTEC Sub-Millimeter Galaxy Data Set

NASA Astrophysics Data System (ADS)

Wilson, Grant; Ade, P.; Aretxaga, I.; Austermann, J.; Bock, J.; Hughes, D.; Kang, Y.; Kim, S.; Lowenthal, J.; Mauskopf, P.; Perera, T.; Scott, K.; Yun, M.

2006-12-01

Using the new AzTEC millimeter-wave camera on the James Clerk Maxwell Telescope (JCMT) in winter 2005/06, we conducted several surveys of the submm galaxy (SMG) population. The AzTEC 1.1 millimeter surveys include both blank-fields (no significant bias or foreground contamination) and regions of known over-densities, and are both large (100-1000 sq. arcmin.) and sensitive ( 1 mJy rms). The unique power of the AzTEC data set lies not only in the size and depth of the individual fields, but in the combined surveyed area that totals over 1 square degree. Hundreds of new sub-millimeter sources have been detected. A joint analysis of all AzTEC surveys will provide important new constraints on many characteristics of the SMG population, including number counts, clustering, and variance. In particular, the large area of the full AzTEC data set provides the first significant measurement of the brightest and most rare of the SMG population. Herein we present the initial combined results and explore the future potential of a complete joint analysis of the full AzTEC SMG data set.

Comparing GNSS Total Electron Content of Sonmiani, Pakistan with NeQuick-2 & IRI-2012 during July 2014 - June 2015

NASA Astrophysics Data System (ADS)

Ayyaz Ameen, Muhammad; Ghafoor, Memoona; Weimin, Zhen

2016-07-01

Total Electron Content (TEC) data acquired by an in-house fabricated GNSS receiver (by China Research Institute of Radiowave Propagation, CRIRP) working with NovaTel antenna installed at Sonmiani (geograph. 24.95°N, 67.14°E) is being reported for the first time. The period under study is one year (July 2014 to June 2015) which is based upon the hourly instantaneous TEC values of 120 days (10 international quietest days, IQD per month). The data confirms the annual variation of TEC at the station which lies at the northern crest of equatorial ionization anomaly (EIA) region. GNSS TEC values in general are then compared with NeQuick-2 and IRI-2012. Model comparison shows that NeQuick-2 predicts the TEC with greater confidence whereas IRI-2012 shows larger discrepancies with respect to the data. Seasonal variation shows the highest TEC values during equinox months. December solstice values of TEC are higher than the June solstice values, this confirms that the seasonal anomaly is dominating in the region during the course of study.

GNSS Observations of Ionospheric Variations During the 21 August 2017 Solar Eclipse

NASA Astrophysics Data System (ADS)

Coster, Anthea J.; Goncharenko, Larisa; Zhang, Shun-Rong; Erickson, Philip J.; Rideout, William; Vierinen, Juha

2017-12-01

On 21 August 2017, during daytime hours, a total solar eclipse with a narrow ˜160 km wide umbral shadow occurred across the continental United States. Totality was observed from the Oregon coast at ˜9:15 local standard time (LST) (17:20 UT) to the South Carolina coast at ˜13:27 LST (18:47 UT). A dense network of Global Navigation Satellite Systems (GNSS) receivers was utilized to produce total electron content (TEC) and differential TEC. These data were analyzed for the latitudinal and longitudinal response of the TEC and for the presence of traveling ionospheric disturbances (TIDs) during eclipse passage. A significant TEC depletion, in some cases greater than 60%, was observed associated with the eclipse shadow, exceeding initial model predictions of 35%. Evidence of enhanced large-scale TID activity was detected over the United States prior to and following the large TEC depletion observed near the time of totality. Signatures of enhanced TEC structures were observed over the Rocky Mountain chain during the main period of TEC depletion.

Near-Real Time Monitoring of TEC Over Japan at NICT (RWC Tokyo OF ISES)

NASA Astrophysics Data System (ADS)

Miyake, W.; Jin, H.

2010-05-01

The world wide use of global navigation satellite systems such as GPS offers unique opportunities for a permanent monitoring of the total electron content (TEC) of the ionosphere. We have developed a system of the rapid derivation of TEC from GEONET (a dense GPS receiver network in Japan). In addition to a previous plot of TEC temporal variation over Japan, we have recently developed a near-real-time two-dimensional TEC map and have used it for the daily operation of Space Weather Forecast Center at NICT (Regional Warning Center Tokyo of International Space Environment Service). The TEC map can be used to continuously monitor the ionospheric disturbances over Japan, including spatial and temporal development of ionospheric storms, large-amplitude traveling ionospheric disturbances, and plasma bubbles intruding over Japan, with high time resolution. The development of the real-time monitoring system of TEC enables us to monitor large ionospheric disturbances, ranging from global- to small-scale disturbances, expected in the next solar maximum. The plot and maps are open to the public and are available on http://wdc.nict.go.jp/IONO/index_E.html.

What do parents know about their children's comprehension of emotions? accuracy of parental estimates in a community sample of pre-schoolers.

PubMed

Kårstad, S B; Kvello, O; Wichstrøm, L; Berg-Nielsen, T S

2014-05-01

Parents' ability to correctly perceive their child's skills has implications for how the child develops. In some studies, parents have shown to overestimate their child's abilities in areas such as IQ, memory and language. Emotion Comprehension (EC) is a skill central to children's emotion regulation, initially learned from their parents. In this cross-sectional study we first tested children's EC and then asked parents to estimate the child's performance. Thus, a measure of accuracy between child performance and parents' estimates was obtained. Subsequently, we obtained information on child and parent factors that might predict parents' accuracy in estimating their child's EC. Child EC and parental accuracy of estimation was tested by studying a community sample of 882 4-year-olds who completed the Test of Emotion Comprehension (TEC). The parents were instructed to guess their children's responses on the TEC. Predictors of parental accuracy of estimation were child actual performance on the TEC, child language comprehension, observed parent-child interaction, the education level of the parent, and child mental health. Ninety-one per cent of the parents overestimated their children's EC. On average, parents estimated that their 4-year-old children would display the level of EC corresponding to a 7-year-old. Accuracy of parental estimation was predicted by child high performance on the TEC, child advanced language comprehension, and more optimal parent-child interaction. Parents' ability to estimate the level of their child's EC was characterized by a substantial overestimation. The more competent the child, and the more sensitive and structuring the parent was interacting with the child, the more accurate the parent was in the estimation of their child's EC. © 2013 John Wiley & Sons Ltd.

Tangshen Formula Attenuates Diabetic Nephropathy by Promoting ABCA1-Mediated Renal Cholesterol Efflux in db/db Mice.

PubMed

Liu, Peng; Peng, Liang; Zhang, Haojun; Tang, Patrick Ming-Kuen; Zhao, Tingting; Yan, Meihua; Zhao, Hailing; Huang, Xiaoru; Lan, Huiyao; Li, Ping

2018-01-01

The commonly prescribed Tangshen Formula (TSF) is a traditional Chinese formulation that has been shown to reduce plasma lipid metabolism and proteinuria and improve the estimated glomerular filtration rate (eGFR) in patients with diabetic kidney disease. This study investigated the underlying mechanism whereby TSF regulates renal lipid accumulation and ameliorates diabetic renal injuries in spontaneous diabetic db/db mice and in vitro in sodium palmitate (PA)-stimulated and Abca1-SiRNA-transfected mouse tubular epithelial cells (mTECs). The results revealed that TSF treatment significantly ameliorated the renal injuries by lowering urinary albumin excretion and improving renal tissue injuries in diabetic (db/db) mice. Interestingly, the treatment with TSF also resulted in decreased cholesterol levels in the renal tissues of db/db mice, which was associated with increased expression of the peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), the Liver X receptors (LXR), and ATP-binding cassette subfamily A member 1 (ABCA1), suggesting that TSF might attenuate diabetic kidney injury via a mechanism associated with improving cholesterol efflux in the diabetic kidney. This was investigated in vitro in mTECs, and the results showed that TSF reduced the PA-stimulated cholesterol accumulation in mTECs. Mechanistically, the addition of TSF was capable of reversing PA-induced downregulation of PGC-1α, LXR, and ABCA1 expression and cholesterol accumulation in mTECs, suggesting that TSF might act the protection via the PGC-1α-LXR-ABCA1 pathway to improve the cholesterol efflux in the renal tissues of db/db mice. This was further confirmed by silencing ABCA1 to block the promotive effect of TSF on cholesterol efflux in vitro . In conclusion, TSF might ameliorate diabetic kidney injuries by promoting ABCA1-mediated renal cholesterol efflux.

A possible space-based tsunami early warning system using observations of the tsunami ionospheric hole.

PubMed

Kamogawa, Masashi; Orihara, Yoshiaki; Tsurudome, Chiaki; Tomida, Yuto; Kanaya, Tatsuya; Ikeda, Daiki; Gusman, Aditya Riadi; Kakinami, Yoshihiro; Liu, Jann-Yenq; Toyoda, Atsushi

2016-12-01

Ionospheric plasma disturbances after a large tsunami can be detected by measurement of the total electron content (TEC) between a Global Positioning System (GPS) satellite and its ground-based receivers. TEC depression lasting for a few minutes to tens of minutes termed as tsunami ionospheric hole (TIH) is formed above the tsunami source area. Here we describe the quantitative relationship between initial tsunami height and the TEC depression rate caused by a TIH from seven tsunamigenic earthquakes in Japan and Chile. We found that the percentage of TEC depression and initial tsunami height are correlated and the largest TEC depressions appear 10 to 20 minutes after the main shocks. Our findings imply that Ionospheric TEC measurement using the existing ground receiver networks could be used in an early warning system for near-field tsunamis that take more than 20 minutes to arrive in coastal areas.

Nighttime Medium-Scale Traveling Ionospheric Disturbances From Airglow Imager and Global Navigation Satellite Systems Observations

NASA Astrophysics Data System (ADS)

Huang, Fuqing; Lei, Jiuhou; Dou, Xiankang; Luan, Xiaoli; Zhong, Jiahao

2018-01-01

In this study, coordinated airglow imager, GPS total electron content (TEC), and Beidou geostationary orbit (GEO) TEC observations for the first time are used to investigate the characteristics of nighttime medium-scale traveling ionospheric disturbances (MSTIDs) over central China. The results indicated that the features of nighttime MSTIDs from three types of observations are generally consistent, whereas the nighttime MSTID features from the Beidou GEO TEC are in better agreement with those from airglow images as compared with the GPS TEC, given that the nighttime MSTID characteristics from GPS TEC are significantly affected by Doppler effect due to satellite movement. It is also found that there are three peaks in the seasonal variations of the occurrence rate of nighttime MSTIDs in 2016. Our study revealed that the Beidou GEO satellites provided fidelity TEC observations to study the ionospheric variability.

A possible space-based tsunami early warning system using observations of the tsunami ionospheric hole

PubMed Central

Kamogawa, Masashi; Orihara, Yoshiaki; Tsurudome, Chiaki; Tomida, Yuto; Kanaya, Tatsuya; Ikeda, Daiki; Gusman, Aditya Riadi; Kakinami, Yoshihiro; Liu, Jann-Yenq; Toyoda, Atsushi

2016-01-01

Ionospheric plasma disturbances after a large tsunami can be detected by measurement of the total electron content (TEC) between a Global Positioning System (GPS) satellite and its ground-based receivers. TEC depression lasting for a few minutes to tens of minutes termed as tsunami ionospheric hole (TIH) is formed above the tsunami source area. Here we describe the quantitative relationship between initial tsunami height and the TEC depression rate caused by a TIH from seven tsunamigenic earthquakes in Japan and Chile. We found that the percentage of TEC depression and initial tsunami height are correlated and the largest TEC depressions appear 10 to 20 minutes after the main shocks. Our findings imply that Ionospheric TEC measurement using the existing ground receiver networks could be used in an early warning system for near-field tsunamis that take more than 20 minutes to arrive in coastal areas. PMID:27905487

Characterizing Interplanetary Structures of Long-Lasting Ionospheric Storm Events

NASA Astrophysics Data System (ADS)

Tandoi, C.; Dong, Y.; Ngwira, C. M.; Damas, M. C.

2015-12-01

Geomagnetic storms can result in periods of heightened TEC (Total Electron Content) in Earth's ionosphere. These periods of change in TEC (dTEC) can have adverse impacts on a technological society, such as scintillation of radio signals used by communication and navigation satellites. However, it is unknown which exact properties of a given storm cause dTEC. We are comparing different solar wind properties that result in a significant long-lasting dTEC to see if there are any patterns that remain constant in these storms. These properties, among others, include the interplanetary magnetic field By and Bz components, the proton density, and the flow speed. As a preliminary investigation, we have studied 15 solar storms. Preliminary results will be presented. In the future, we hope to increase our sample size and analyze over 80 different solar storms, which result in significant dTEC.

Kinases Involved in Both Autophagy and Mitosis.

PubMed

Li, Zhiyuan; Zhang, Xin

2017-08-31

Both mitosis and autophagy are highly regulated dynamic cellular processes and involve various phosphorylation events catalysed by kinases, which play vital roles in almost all physiological and pathological conditions. Mitosis is a key event during the cell cycle, in which the cell divides into two daughter cells. Autophagy is a process in which the cell digests its own cellular contents. Although autophagy regulation has mainly been studied in asynchronous cells, increasing evidence indicates that autophagy is in fact tightly regulated in mitosis. Here in this review, we will discuss kinases that were originally identified to be involved in only one of either mitosis or autophagy, but were later found to participate in both processes, such as CDKs (cyclin-dependent kinases), Aurora kinases, PLK-1 (polo-like kinase 1), BUB1 (budding uninhibited by benzimidazoles 1), MAPKs (mitogen-activated protein kinases), mTORC1 (mechanistic target of rapamycin complex 1), AMPK (AMP-activated protein kinase), PI3K (phosphoinositide-3 kinase) and protein kinase B (AKT). By focusing on kinases involved in both autophagy and mitosis, we will get a more comprehensive understanding about the reciprocal regulation between the two key cellular events, which will also shed light on their related therapeutic investigations.

Kinases Involved in Both Autophagy and Mitosis

PubMed Central

2017-01-01

Both mitosis and autophagy are highly regulated dynamic cellular processes and involve various phosphorylation events catalysed by kinases, which play vital roles in almost all physiological and pathological conditions. Mitosis is a key event during the cell cycle, in which the cell divides into two daughter cells. Autophagy is a process in which the cell digests its own cellular contents. Although autophagy regulation has mainly been studied in asynchronous cells, increasing evidence indicates that autophagy is in fact tightly regulated in mitosis. Here in this review, we will discuss kinases that were originally identified to be involved in only one of either mitosis or autophagy, but were later found to participate in both processes, such as CDKs (cyclin-dependent kinases), Aurora kinases, PLK-1 (polo-like kinase 1), BUB1 (budding uninhibited by benzimidazoles 1), MAPKs (mitogen-activated protein kinases), mTORC1 (mechanistic target of rapamycin complex 1), AMPK (AMP-activated protein kinase), PI3K (phosphoinositide-3 kinase) and protein kinase B (AKT). By focusing on kinases involved in both autophagy and mitosis, we will get a more comprehensive understanding about the reciprocal regulation between the two key cellular events, which will also shed light on their related therapeutic investigations. PMID:28858266

Detection of abnormalities in the superficial zone of cartilage repaired using a tissue engineered construct derived from synovial stem cells.

PubMed

Ando, Wataru; Fujie, Hiromichi; Moriguchi, Yu; Nansai, Ryosuke; Shimomura, Kazunori; Hart, David A; Yoshikawa, Hideki; Nakamura, Norimasa

2012-09-28

The present study investigated the surface structure and mechanical properties of repair cartilage generated from a tissue engineered construct (TEC) derived from synovial mesenchymal stem cells at six months post-implantation compared to those of uninjured cartilage. TEC-mediated repair tissue was cartilaginous with Safranin O staining, and had comparable macro-scale compressive properties with uninjured cartilage. However, morphological assessments revealed that the superficial zone of TEC-mediated tissue was more fibrocartilage-like, in contrast to the middle or deep zones that were more hyaline cartilage-like with Safranin O staining. Histological scoring of the TEC-mediated tissue was significantly lower in the superficial zone than in the middle and deep zones. Scanning electron microscopy showed a thick tangential bundle of collagen fibres at the most superficial layer of uninjured cartilage, while no corresponding structure was detected at the surface of TEC-mediated tissue. Immunohistochemical analysis revealed that PRG4 was localised in the superficial area of uninjured cartilage, as well as the TEC-mediated tissue. Friction testing showed that the lubrication properties of the two tissues was similar, however, micro-indentation analysis revealed that the surface stiffness of the TEC-repair tissue was significantly lower than that of uninjured cartilage. Permeability testing indicated that the TEC-mediated tissue exhibited lower water retaining capacity than did uninjured cartilage, specifically at the superficial zone. Thus, TEC-mediated tissue exhibited compromised mechanical properties at the superficial zone, properties which need improvement in the future for maintenance of long term repair cartilage integrity.

Preparing technicians for photonics industries and organizations

NASA Astrophysics Data System (ADS)

Souders, John; Hull, Dan

2012-10-01

U.S. photonics organizations need about 800 new photonics technicians each year. Thirty-one community and technical colleges have approximately 700 students enrolled in photonics related programs; about 275 of them complete their coursework and enter the workforce each year. A disparity exists between the demand and supply of qualified photonics technicians in the U.S. OP-TEC, the National Center for Optics and Photonics Education is a consortium of seven colleges, under the leadership of the University of Central Florida, and sponsored by NSF. OP-TEC's mission is to increase the quantity and quality of photonics technicians prepared at two-year colleges. OP-TEC maintains the National Photonics Skill Standards for Technicians, provides curriculum models, teaching materials, faculty training/professional development and planning services to strengthen existing college photonics programs and to attract and support new ones. OP-TEC is converting its text materials to E-Books to support students in technical programs. Through OP-TEC's recruitment efforts 84 additional colleges are interested in initiating new photonics programs. The OP-TEC Photonics College Network (OPCN) consists of 28 colleges that are currently providing photonics education. This fall OPCN will lead an additional national effort to further educate employed photonics technicians through on-line courses, complemented by lab experiences at nearby colleges. OP-TEC is expanding its outreach to photonics employers and colleges by regionalizing its approach to offering its services. OP-TEC is also planning to develop new curricula and instructional materials for AAS programs to prepare Precision Optics Technicians. This paper will detail OP-TEC's work with particular emphases on its materials and services.

Ionospheric storms—A challenge for empirical forecast of the total electron content

NASA Astrophysics Data System (ADS)

Borries, C.; Berdermann, J.; Jakowski, N.; Wilken, V.

2015-04-01

Since the last decades, the functioning of society depends more and more on well-functioning communication and navigation systems. As the availability and reliability of most of these satellite-based systems can be severely impacted by ionospheric storms, the accurate forecast of these events becomes a required task for mitigating social and economic risks. Here we aim to make initial steps toward an empirical model for ionospheric perturbations related to space weather events that are observable in the total electron content (TEC). The perturbation TEC forecast model will be a fast and robust approach, improving TEC forecasts based on climatological models during storm conditions. The derivation of such a model is a challenging task, because although a general dependence of the storm features (enhancement or depletion of electron density) on the storm onset time, local time, season and geomagnetic latitude is well known, there is a large deviation from the mean behavior. For a better understanding of storm conditions, this paper presents analyses of ionospheric storms observed in the TEC, broken down into diverse classes of storms. It provides a detailed characterization of the typical ionospheric storm behavior over Europe from high to midlatitudes, beyond case studies. Generally, the typical clear strong TEC enhancement starting in high latitudes and propagating equatorward is found to be strongest for storms starting in the morning hours independent of the season. In midlatitudes, it is strongest during noon. In addition, a clear difference between summer and winter storms is reported. While only winter storms develop high-latitude TEC enhancements, only summer storms typically exhibit TEC depletions during the storm recovery phase. During winter storms TEC enhancements can also occur the day following the storm onset, in contrast to summer storms. Strong correlation of TEC perturbation amplitudes to the Bz component of the interplanetary magnetic field and to a proxy of the polar cap potential are shown especially for summer midlatitude TEC enhancements during storms with and onset in the morning hours (6 to 12 UT over Europe) and for winter high-latitude TEC enhancements (around 60∘N). The results indicate the potential to derive improved predictions of maximum TEC deviations during space weather events, based on solar wind measurements.

Peptide microarray analysis of substrate specificity of the transmembrane Ser/Thr kinase KPI-2 reveals reactivity with cystic fibrosis transmembrane conductance regulator and phosphorylase.

PubMed

Wang, Hong; Brautigan, David L

2006-11-01

Human lemur (Lmr) kinases are predicted to be Tyr kinases based on sequences and are related to neurotrophin receptor Trk kinases. This study used homogeneous recombinant KPI-2 (Lmr2, LMTK2, Cprk, brain-enriched protein kinase) kinase domain and a library of 1,154 peptides on a microarray to analyze substrate specificity. We found that KPI-2 is strictly a Ser/Thr kinase that reacts with Ser either preceded by or followed by Pro residues but unlike other Pro-directed kinases does not strictly require an adjacent Pro residue. The most reactive peptide in the library corresponds to Ser-737 of cystic fibrosis transmembrane conductance regulator, and the recombinant R domain of cystic fibrosis transmembrane conductance regulator was a preferred substrate. Furthermore the KPI-2 kinase phosphorylated peptides corresponding to the single site in phosphorylase and purified phosphorylase b, making this only the second known phosphorylase b kinase. Phosphorylase was used as a specific substrate to show that KPI-2 is inhibited in living cells by addition of nerve growth factor or serum. The results demonstrate the utility of the peptide library to probe specificity and discover kinase substrates and offer a specific assay that reveals hormonal regulation of the activity of this unusual transmembrane kinase.

An Analysis on the TEC Variability and Ionospheric Scintillation at Los Alamos, New Mexico Derived from FORTE-Received LAPP Signals

NASA Astrophysics Data System (ADS)

Huang, Z.; Roussel-Dupre, R.

2003-12-01

The total electron content (TEC) of ionosphere and its electron density irregularities (scintillation) have effects of degradation and disruption on radio signals passed between ground stations and orbiting man-made satellites. With the rapid increase in operational reliance on UHF/VHF satellite communication, it is desirable to obtain understandings of ionosphere TEC variability and scintillation characteristics to improve our ability of predicting satellite communication outages. In this work, data collected from FORTE satellite received LAPP (Los Alamos Portable Pulser) signals during 1998-2002 are used to derive TEC and ionospheric scintillation index at Los Alamos, New Mexico. To characterize in-situ TEC variability at Los Alamos, the FORTE-LAPP derived TECs are analyzed against diurnal, seasonal, solar activity, magnetic storm, and stratospheric warming. The results are also compared with the TEC estimates from the Los Alamos ionospheric transfer function (ITF) implemented with the global ionospheric models (IRI, PIM), and GPS -derived TEC maps. The FORTE-LAPP signals are also analyzed against two important measures of the effect of scintillation on broadband signals, the mean time delay and the time delay jitter. The results are used to examine coherence frequency bandwidth and compared with the predictions from a global scintillation model (WBMOD). The FORTE-LAPP analyzed and WBMOD predicted scintillation characteristics are used to investigate temporal and seasonal behavior of scintillation at Los Alamos.

A pilot study comparing the use of Thiel- and formalin-embalmed cadavers in the teaching of human anatomy.

PubMed

Balta, Joy Y; Lamb, Clare; Soames, Roger W

2015-01-01

Formalin had traditionally been used to preserve human material to teach gross anatomy. In 2008 the Centre for Anatomy and Human Identification (CAHID) at the University of Dundee embarked on the use of the Thiel method of embalming. The aim of this pilot study was to assess the difference between formalin-embalmed cadavers (FEC) and Thiel-embalmed cadavers (TEC) used for teaching and surgical training. Three different questionnaires were prepared for data collection from undergraduate and postgraduate students and clinical staff. All undergraduate and postgraduate students as well as clinical staff commented on the appearance of the TEC. There was no overall consensus concerning the use of TEC, some respondents preferred TEC for the entire dissection, some only for certain areas such as the musculoskeletal system. On a technical level TEC were considered less hazardous then FEC by one-third of participants with fewer than 10% regarding TEC as more irritating than FEC. Psychologically, 32.7% of undergraduate students expressed the view that TEC made them feel more uncomfortable compared with FEC because of their life-like appearance. However, 57.1% of undergraduate students encountered the same uncomfortable feelings when viewing both TEC and FEC. The use of Thiel-embalmed cadavers to teach anatomy has an added value, though further research is required over longer periods of time to identify its best usage. © 2014 American Association of Anatomists.

Statistical analysis of ionospheric TEC anomalies before global M w ≥ 7.0 earthquakes using data of CODE GIM

NASA Astrophysics Data System (ADS)

Liu, Wenjing; Xu, Liang

2017-07-01

Based on Center of Orbit Determination in Europe (CODE) global ionospheric map (GIM) data, a statistical analysis of local total electron content (TEC) anomalies before 121 low-depth ( D ≤ 100 km) strong ( M w ≥ 7.0) earthquakes has been made using the sliding median differential calculation method combining with a new approach of image processing technique. The results show that significant local TEC anomalies could be observed 0-6 days before 80 earthquakes, about 66.1% out of the total. The positive anomalies occur more often than negative ones. For 26 cases, both positive and negative anomalies are observed before the shock. The pre-earthquake TEC anomalies show local time recurrence for 38 earthquakes, which occur around the same local time on different days. The local time distribution of the pre-earthquake TEC anomalies mainly concentrates between 19 and 06 LT, roughly from the sunset to sunrise. Most of the pre-earthquake TEC anomalies do not locate above the epicenter but shift to the south. The pre-earthquake TEC anomalies could be extracted near the magnetic conjugate point of the epicenter for 40 events, which is 50% out of the total 80 cases with significant local TEC anomalies. In general, the signs of the anomalies around epicenter and its conjugate point are the same, but the abnormal magnitude and lasting time are not.

Ethylene Rapidly Up-Regulates the Activities of Both Monomeric GTP-Binding Proteins and Protein Kinase(s) in Epicotyls of Pea1

PubMed Central

Moshkov, Igor E.; Novikova, Galina V.; Mur, Luis A.J.; Smith, Aileen R.; Hall, Michael A.

2003-01-01

It is demonstrated that, in etiolated pea (Pisum sativum) epicotyls, ethylene affects the activation of both monomeric GTP-binding proteins (monomeric G-proteins) and protein kinases. For monomeric G-proteins, the effect may be a rapid (2 min) and bimodal up-regulation, a transiently unimodal activation, or a transient down-regulation. Pretreatment with 1-methylcyclopropene abolishes the response to ethylene overall. Immunoprecipitation studies indicate that some of the monomeric G-proteins affected may be of the Rab class. Protein kinase activity is rapidly up-regulated by ethylene, the effect is inhibited by 1-methylcyclopropene, and the activation is bimodal. Immunoprecipitation indicates that the kinase(s) are of the MAP kinase ERK1 group. It is proposed that the data support the hypothesis that a transduction chain exists that is separate and antagonistic to that currently revealed by studies on Arabidopsis mutants. PMID:12692330

PRAK, a novel protein kinase regulated by the p38 MAP kinase.

PubMed Central

New, L; Jiang, Y; Zhao, M; Liu, K; Zhu, W; Flood, L J; Kato, Y; Parry, G C; Han, J

1998-01-01

We have identified and cloned a novel serine/ threonine kinase, p38-regulated/activated protein kinase (PRAK). PRAK is a 471 amino acid protein with 20-30% sequence identity to the known MAP kinase-regulated protein kinases RSK1/2/3, MNK1/2 and MAPKAP-K2/3. PRAK was found to be expressed in all human tissues and cell lines examined. In HeLa cells, PRAK was activated in response to cellular stress and proinflammatory cytokines. PRAK activity was regulated by p38alpha and p38beta both in vitro and in vivo and Thr182 was shown to be the regulatory phosphorylation site. Activated PRAK in turn phosphorylated small heat shock protein 27 (HSP27) at the physiologically relevant sites. An in-gel kinase assay demonstrated that PRAK is a major stress-activated kinase that can phosphorylate small heat shock protein, suggesting a potential role for PRAK in mediating stress-induced HSP27 phosphorylation in vivo. PMID:9628874

Observations of the Weddell Sea Anomaly in the ground-based and space-borne TEC measurements

NASA Astrophysics Data System (ADS)

Zakharenkova, Irina; Cherniak, Iurii; Shagimuratov, Irk

2017-08-01

The Weddell Sea Anomaly (WSA) is a summer ionospheric anomaly, which is characterized by a greater nighttime ionospheric density than that in daytime in the region near the Weddell Sea. We investigate the WSA signatures in the ground-based TEC (vertical total electron content) by using GPS and GLONASS measurements of the dense regional GNSS networks in South America. We constructed the high-resolution regional TEC maps for December 2014-January 2015. The WSA effects of the TEC exceed the noontime values are registered starting from 17 LT, it reaches its maximum at 01-05 LT and starts to disappear after 09 LT. Maximal TEC enhancements were as large as a factor of 2.5-3.5 and were registered at 03-04 LT. This effect was mainly localized in the geographical region of 55°S-75°S latitude and 80°W-30°W longitude, close to the Antarctic Peninsula. Further, we examined the WSA occurrence in the topside ionosphere by using GPS measurements from a zenith-looking GPS antenna on board three Swarm satellites to determine topside TEC (above ∼500 km altitude) at the topside ionosphere-plasmasphere system. Global maps of the topside TEC indicated that the zone with significant WSA effect in the topside TEC (TEC increase ∼2-4 times the noontime level) had a large spatial extent over southern Pacific and Atlantic Ocean. It was observed around 150°W-20°W and between 40°S and 70°S during 23 LT - 06 LT. For the first time, the WSA signatures were shown in the topside TEC data derived from the GPS measurements onboard the Swarm constellation. Independently, two other instruments - FORMOSAT-3/COSMIC radio occultation electron density profiles and in situ measurements by the Langmuir Probe instrument onboard Swarm satellites - were able to confirm: (1) the same location of the WSA zone as revealed in Swarm TEC; (2) the most-pronounced WSA effect, as a maximal electron density exceed over the noontime values, corresponds to altitudes above 400-500 km.

Long-term trends in the total electron content (TEC)

NASA Astrophysics Data System (ADS)

Laštovička, Jan

2017-04-01

The long-term trends in the total electron content (TEC) have very little been studied. Lean et al. (2011; J. Geophys. Res., 116, A00H04, doi:10.1029/2010JA016378) studied trends in TEC globally based on JPL maps for 1995-2010. However, their trends appear to be too positive, which is not plausible taking into account the trends in other ionospheric parameters. Therefore they prefer the less positive trends calculated under the assumption of the same level of solar activity in solar cycle minima 22/23 and 23/24. However, as it is now clear, this is not a correct assumption. Lastovicka (2013; J. Geophys. Res. Space Phys., 118, 3831-3835, doi:10.1002/jgra.50261) selected a region around Florence, Italy, as a region with available historical TEC data based on Faraday rotation measurements and remarkably larger than average trends in TEC by Lean et al. (2011). Historical data from Florence provide no trend in TEC. However, foF2 from Juliusruh provide slight negative trends for 1976-1996 but no trends for 1995-2010. Thus the question of reality of trends by Lean et al. (2011) remained open. Here we use TEC from GIM and JPL data for two European regions with high Lean's trends, regions around Florence and around Prague, using 10-14 LT medians, 1998-2015, yearly average values. A classical approach is applied. First a model of solar activity dependence of TEC is constructed separately for each region from all data. Then model data are subtracted from experimental data and analysis is made with residuals. This analysis shows that early data (1998-2001) are by several TECU lower than they should be according to solar activity, the year 2002 is intermediate and in 2003-2015 the data fit well a weak or rather no trend of TEC. The change in TEC data does not seem to be jump-like, it lasted at least a year, if not longer. Thus the positive TEC trends reported by Lean et al. (2011) appear to be affected by data problem; real trends are evidently less positive if any.

Performance evaluation of GNSS-TEC estimation techniques at the grid point in middle and low latitudes during different geomagnetic conditions

NASA Astrophysics Data System (ADS)

Abe, O. E.; Otero Villamide, X.; Paparini, C.; Radicella, S. M.; Nava, B.; Rodríguez-Bouza, M.

2017-04-01

Global Navigation Satellite Systems (GNSS) have become a powerful tool use in surveying and mapping, air and maritime navigation, ionospheric/space weather research and other applications. However, in some cases, its maximum efficiency could not be attained due to some uncorrelated errors associated with the system measurements, which is caused mainly by the dispersive nature of the ionosphere. Ionosphere has been represented using the total number of electrons along the signal path at a particular height known as Total Electron Content (TEC). However, there are many methods to estimate TEC but the outputs are not uniform, which could be due to the peculiarity in characterizing the biases inside the observables (measurements), and sometimes could be associated to the influence of mapping function. The errors in TEC estimation could lead to wrong conclusion and this could be more critical in case of safety-of-life application. This work investigated the performance of Ciraolo's and Gopi's GNSS-TEC calibration techniques, during 5 geomagnetic quiet and disturbed conditions in the month of October 2013, at the grid points located in low and middle latitudes. The data used are obtained from the GNSS ground-based receivers located at Borriana in Spain (40°N, 0°E; mid latitude) and Accra in Ghana (5.50°N, -0.20°E; low latitude). The results of the calibrated TEC are compared with the TEC obtained from European Geostationary Navigation Overlay System Processing Set (EGNOS PS) TEC algorithm, which is considered as a reference data. The TEC derived from Global Ionospheric Maps (GIM) through International GNSS service (IGS) was also examined at the same grid points. The results obtained in this work showed that Ciraolo's calibration technique (a calibration technique based on carrier-phase measurements only) estimates TEC better at middle latitude in comparison to Gopi's technique (a calibration technique based on code and carrier-phase measurements). At the same time, Gopi's calibration was also found more reliable in low latitude than Ciraolo's technique. In addition, the TEC derived from IGS GIM seems to be much reliable in middle-latitude than in low-latitude region.

Use of LC-MS/MS and Bayes' theorem to identify protein kinases that phosphorylate aquaporin-2 at Ser256.

PubMed

Bradford, Davis; Raghuram, Viswanathan; Wilson, Justin L L; Chou, Chung-Lin; Hoffert, Jason D; Knepper, Mark A; Pisitkun, Trairak

2014-07-15

In the renal collecting duct, binding of AVP to the V2 receptor triggers signaling changes that regulate osmotic water transport. Short-term regulation of water transport is dependent on vasopressin-induced phosphorylation of aquaporin-2 (AQP2) at Ser256. The protein kinase that phosphorylates this site is not known. We use Bayes' theorem to rank all 521 rat protein kinases with regard to the likelihood of a role in Ser256 phosphorylation on the basis of prior data and new experimental data. First, prior probabilities were estimated from previous transcriptomic and proteomic profiling data, kinase substrate specificity data, and evidence for kinase regulation by vasopressin. This ranking was updated using new experimental data describing the effects of several small-molecule kinase inhibitors with known inhibitory spectra (H-89, KN-62, KN-93, and GSK-650394) on AQP2 phosphorylation at Ser256 in inner medullary collecting duct suspensions. The top-ranked kinase was Ca2+/calmodulin-dependent protein kinase II (CAMK2), followed by protein kinase A (PKA) and protein kinase B (AKT). Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based in vitro phosphorylation studies compared the ability of three highly ranked kinases to phosphorylate AQP2 and other inner medullary collecting duct proteins, PKA, CAMK2, and serum/glucocorticoid-regulated kinase (SGK). All three proved capable of phosphorylating AQP2 at Ser256, although CAMK2 and PKA were more potent than SGK. The in vitro phosphorylation experiments also identified candidate protein kinases for several additional phosphoproteins with likely roles in collecting duct regulation, including Nedd4-2, Map4k4, and 3-phosphoinositide-dependent protein kinase 1. We conclude that Bayes' theorem is an effective means of integrating data from multiple data sets in physiology.

Phosphorylation-Dependent Regulation of Ryanodine Receptors

PubMed Central

Marx, Steven O.; Reiken, Steven; Hisamatsu, Yuji; Gaburjakova, Marta; Gaburjakova, Jana; Yang, Yi-Ming; Rosemblit, Nora; Marks, Andrew R.

2001-01-01

Ryanodine receptors (RyRs), intracellular calcium release channels required for cardiac and skeletal muscle contraction, are macromolecular complexes that include kinases and phosphatases. Phosphorylation/dephosphorylation plays a key role in regulating the function of many ion channels, including RyRs. However, the mechanism by which kinases and phosphatases are targeted to ion channels is not well understood. We have identified a novel mechanism involved in the formation of ion channel macromolecular complexes: kinase and phosphatase targeting proteins binding to ion channels via leucine/isoleucine zipper (LZ) motifs. Activation of kinases and phosphatases bound to RyR2 via LZs regulates phosphorylation of the channel, and disruption of kinase binding via LZ motifs prevents phosphorylation of RyR2. Elucidation of this new role for LZs in ion channel macromolecular complexes now permits: (a) rapid mapping of kinase and phosphatase targeting protein binding sites on ion channels; (b) predicting which kinases and phosphatases are likely to regulate a given ion channel; (c) rapid identification of novel kinase and phosphatase targeting proteins; and (d) tools for dissecting the role of kinases and phosphatases as modulators of ion channel function. PMID:11352932

LISN: Measurement of TEC values, and TID characteristics over South and Central America (Invited)

NASA Astrophysics Data System (ADS)

Valladares, C. E.

2013-12-01

The Low-latitude Ionospheric Sensor Network (LISN) is a distributed observatory designed to provide the climatology and weather of the low latitude ionosphere over the South American continent. Presently, the LISN observatory consists of 47 GPS receivers able to transmit TEC and scintillation values to a central server in a real-time basis. Historical TEC values from these receivers and from about 300 other GPSs that operated in South and Central America between 2008 and 2012 were used to derive regional maps of TEC and TIDs. A prominent feature of the TEC maps is the intense day-to-day variability that is observed during all seasons and under quiet and active magnetic conditions. To assess the TEC dependencies a non-linear least-square fit was conducted to simultaneously extract the solar flux, magnetic and seasonal variability for each square cell of the TEC maps and for each 30-min local time sector. It was found that TEC values and the anomaly intensity increase as a function of the solar flux. The latitudinal separation increases with magnetic activity, and TEC values in Central America become the largest when Kp is equal to 5o or more. TIDs are seen quite frequently over the Caribbean region and in the northern part of South America. To calculate the TIDs travel velocities, their propagation direction, and the scale-size of the disturbances a multi-site multi-dimension cross-correlation method was applied to the TEC database. Phase velocities of order 150 m/s and scale sizes between 100 and 400 km were typically observed. This paper will present the morphology and statistics of TIDs as a function of latitude, longitude, local time and season. It is also introduced the results of an investigation to correlate the appearance, phase velocity and angle of propagation of TIDs and tropospheric phenomena observed with the TRMM satellite.

Purified enzymes improve isolation and characterization of the adult thymic epithelium.

PubMed

Seach, Natalie; Wong, Kahlia; Hammett, Maree; Boyd, Richard L; Chidgey, Ann P

2012-11-30

The reproducible isolation and accurate characterization of thymic epithelial cell (TEC) subsets is of critical importance to the ongoing study of thymopoiesis and its functional decline with age. The study of adult TEC, however, is significantly hampered due to the severely low stromal to hematopoietic cell ratio. Non-biased digestion and enrichment protocols are thus essential to ensure optimal cell yield and accurate representation of stromal subsets, as close as possible to their in vivo representation. Current digestion protocols predominantly involve diverse, relatively impure enzymatic variants of crude collagenase and collagenase/dispase (col/disp) preparations, which have variable efficacy and are often suboptimal in their ability to mediate complete digestion of thymus tissue. To address these issues we compared traditional col/disp preparations with the latest panel of Liberase products that contain a blend of highly purified collagenase and neutral protease enzymes. Liberase enzymes revealed a more rapid, complete dissociation of thymus tissue; minimizing loss of viability and increasing recovery of thymic stromal cell (TSC) elements. In particular, the recovery and viability of TEC, notably the rare cortical subsets, were significantly enhanced with Liberase products containing medium to high levels of thermolysin. The improved stromal dissociation led to numerically increased TEC yield and total TEC RNA isolated from pooled digests of adult thymus. Furthermore, the increased recovery of TEC enhanced resolution and quantification of TEC subsets in both adult and aged mice, facilitating flow cytometric analysis on a per thymus basis. We further refined the adult TEC phenotype by correlating surface expression of known TEC markers, with expression of intracellular epithelial lineage markers, Keratin 5 and Keratin 8. The data reveal more extensive expression of K8 than previously recognized and indicates considerable heterogeneity still exists within currently defined adult TEC subsets. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

US-TEC: A new data assimilation product from the Space Environment Center characterizing the ionospheric total electron content using real-time GPS data

NASA Astrophysics Data System (ADS)

Fuller-Rowell, Tim; Araujo-Pradere, Eduardo; Minter, Cliff; Codrescu, Mihail; Spencer, Paul; Robertson, Doug; Jacobson, Abram R.

2006-12-01

The potential of data assimilation for operational numerical weather forecasting has been appreciated for many years. For space weather it is a new path that we are just beginning to explore. With the emergence of satellite constellations and the networks of ground-based observations, sufficient data sources are now available to make the application of data assimilation techniques a viable option. The first space weather product at Space Environment Center (SEC) utilizing data assimilation techniques, US-TEC, was launched as a test operational product in November 2004. US-TEC characterizes the ionospheric total electron content (TEC) over the continental United States (CONUS) every 15 min with about a 15-min latency. US-TEC is based on a Kalman filter data assimilation scheme driven by a ground-based network of real-time GPS stations. The product includes a map of the vertical TEC, an estimate of the uncertainty in the map, and the departure of the TEC from a 10-day average at that particular universal time. In addition, data files are provided for vertical TEC and the line-of-sight electron content to all GPS satellites in view over the CONUS at that time. The information can be used to improve single-frequency GPS positioning by providing more accurate corrections for the ionospheric signal delay, or it can be used to initialize rapid integer ambiguity resolution schemes for dual-frequency GPS systems. Validation of US-TEC indicates an accuracy of the line-of-sight electron content of between 2 and 3 TEC units (1 TECU = 1016 el m-2), equivalent to less than 50 cm signal delay at L1 frequencies, which promises value for GPS users. This is the first step along a path that will likely lead to major improvement in space weather forecasting, paralleling the advances achieved in meteorological weather forecasting.

Thermoelectric Converter for Loop Heat Pipe Temperature Control: Experience and Lessons Learned

NASA Technical Reports Server (NTRS)

Ku, Jentung; Ottenstein, Laura

2010-01-01

This paper describes the theoretical background and implementation methodology of using a thermoelectric converter (TEC) for operating temperature control of a loop heat pipe (LHP). In particular, experimental results from ambient and thermal vacuum tests of an LHP are presented for illustrations. The most commonly used state-of-the-art method to control the LHP operating temperature is to cold bias its compensation chamber (CC) and use an electrical heater to maintain the CC at the desired set point temperature. Although effective, this approach has its shortcomings in that the electrical heater can only provide heating to the CC, and the required power can be large under certain conditions. An alternative method is to use a TEC, which is capable of providing both heating and cooling to the CC. In this method, one side of the TEC is attached to the CC, and the other side is connected to the evaporator via a thermal strap. Using a bipolar power supply and a control algorithm, a TEC can function as a heater or a cooler, depending on the direction of the current flow. Extensive ground tests of several LHPs have demonstrated that a TEC can provide very tight temperature control for the CC. It also offers several additional advantages: (1) The LHP can operate at temperatures below its natural operating temperature at low heat loads; (2) The required heater power for a TEC is much less than that for an electrical heater; and (3) It enhances the LHP start-up success. Although the concept of using a TEC for LHP temperature control is simple, there are many factors to be considered in its implementation for space applications because the TEC is susceptible to the shear stress and yet has to sustain the dynamic load under the spacecraft launch environment. The added features that help the TEC to withstand the dynamic load will inevitably affect the TEC thermal performance. Some experiences and lessons learned are addressed in this paper.

A dual-stage sodium thermal electrochemical converter (Na-TEC)

NASA Astrophysics Data System (ADS)

Limia, Alexander; Ha, Jong Min; Kottke, Peter; Gunawan, Andrey; Fedorov, Andrei G.; Lee, Seung Woo; Yee, Shannon K.

2017-12-01

The sodium thermal electrochemical converter (Na-TEC) is a heat engine that generates electricity through the isothermal expansion of sodium ions. The Na-TEC is a closed system that can theoretically achieve conversion efficiencies above 45% when operating between thermal reservoirs at 1150 K and 550 K. However, thermal designs have confined previous single-stage devices to thermal efficiencies below 20%. To mitigate some of these limitations, we consider dividing the isothermal expansion into two stages; one at the evaporator temperature (1150 K) and another at an intermediate temperature (650 K-1050 K). This dual-stage Na-TEC takes advantage of regeneration and reheating, and could be amenable to better thermal management. Herein, we demonstrate how the dual-stage device can improve the efficiency by up to 8% points over the best performing single-stage device. We also establish an application regime map for the single- and dual-stage Na-TEC in terms of the power density and the total thermal parasitic loss. Generally, a single-stage Na-TEC should be used for applications requiring high power densities, whereas a dual-stage Na-TEC should be used for applications requiring high efficiency.

Was Magnetic Storm the Only Driver of the Long-Duration Enhancements of Daytime Total Electron Content in the Asian-Australian Sector Between 7 and 12 September 2017?

NASA Astrophysics Data System (ADS)

Lei, Jiuhou; Huang, Fuqing; Chen, Xuetao; Zhong, Jiahao; Ren, Dexin; Wang, Wenbin; Yue, Xinan; Luan, Xiaoli; Jia, Mingjiao; Dou, Xiankang; Hu, Lianhuan; Ning, Baiqi; Owolabi, Charles; Chen, Jinsong; Li, Guozhu; Xue, Xianghui

2018-04-01

In this study, multiple data sets from Beidou geostationary orbit satellites total electron contents (TECs), ionosonde, meteor radar, magnetometer, and model simulations have been used to investigate the ionospheric responses in the Asian-Australian sector during the September 2017 geomagnetic storm. It was found that long-duration daytime TEC enhancements that lasted from 7 to 12 September 2017 were observed by the Beidou geostationary orbit satellite constellation. This is a unique event as the prominent TEC enhancements persisted during the storm recovery phase when geomagnetic activity became quiet. The Thermosphere-Ionosphere Electrodynamics Global Circulation Model predicted that the TEC enhancements on 7-9 September were associated with the geomagnetic activity, but it showed significant electron density depletions on 10 and 11 September in contrast to the observed TEC enhancements. Our results suggested that the observed long-duration TEC enhancements from 7 to 12 September are mainly associated with the interplay of ionospheric dynamics and electrodynamics. Nevertheless, the root causes for the observed TEC enhancements seen in the storm recovery phase are unknown and require further observations and model studies.

CFD Extraction Tool for TecPlot From DPLR Solutions

NASA Technical Reports Server (NTRS)

Norman, David

2013-01-01

This invention is a TecPlot macro of a computer program in the TecPlot programming language that processes data from DPLR solutions in TecPlot format. DPLR (Data-Parallel Line Relaxation) is a NASA computational fluid dynamics (CFD) code, and TecPlot is a commercial CFD post-processing tool. The Tec- Plot data is in SI units (same as DPLR output). The invention converts the SI units into British units. The macro modifies the TecPlot data with unit conversions, and adds some extra calculations. After unit conversions, the macro cuts a slice, and adds vectors on the current plot for output format. The macro can also process surface solutions. Existing solutions use manual conversion and superposition. The conversion is complicated because it must be applied to a range of inter-related scalars and vectors to describe a 2D or 3D flow field. It processes the CFD solution to create superposition/comparison of scalars and vectors. The existing manual solution is cumbersome, open to errors, slow, and cannot be inserted into an automated process. This invention is quick and easy to use, and can be inserted into an automated data-processing algorithm.

Short-Term TEC Perturbations Associated With Planetary Waves Occurrence in the Ionosphere

NASA Astrophysics Data System (ADS)

Shagimuratov, I. I.; Karpov, I.; Krankowski, A.

2008-12-01

Analysis of TEC response to storm showed short-term perturbations which were observed after initial phase of geomagnetic storms. The perturbations demonstrated very well expressed latitudinal structure and were recognized on diurnal variations as surges of TEC enhancement of TEC. Ordinary such storm-time positive effect was associated with TAD. Duration of the perturbations was about 2-4 hours and their amplitude increased toward low latitudes. Such TEC perturbations have the longitudinal dependence. It is important that time location of surges have week dependence on latitude. The observed structure appeared to arrive from high latitudes, but at middle latitudes it was represented as a standing wave. It is assumed that such TEC perturbations can be produced due to superposition of the eastward and westward propagating planetary Poincare waves. The periods of these waves are usually several hours. Poincare waves can be excited at the atmosphere in storm time. At middle latitudes their superposition is as standing wave that forms observing TEC perturbations. In the report, the possibilities of application Poincare waves to the ionosphere dynamics studies are discussed and an explanation of the observed ionospheric effects is given.

Nonreceptor Protein-Tyrosine Kinases in Neutrophil Activation

PubMed

Welch; Mauran; Maridonneau-Parini

1996-06-01

Nonreceptor protein-tyrosine kinases are involved in the regulation of almost all neutrophil responses such as adhesion, chemotaxis, priming, oxidative burst, and degranulation. Here, we show that phagocytosis is also regulated by protein-tyrosine kinase activity. Using various protein-tyrosine kinase inhibitors, we further demonstrate that opsonized zymosan-induced degranulation of specific and azurophil granules is regulated by protein-tyrosine kinase activity, whereas phorbol ester-induced degranulation is not. Several of the nonreceptor protein-tyrosine kinases involving in neutrophil signal transduction are known, including Fgr, Hck, Lyn, Yes, and Syk. Among these, Hck and Fgr are localized on the azurophil and specific granules, suggesting the involvement of these two protein-tyrosine kinases in the regulation of degranulation. In this report, we characterize some of the molecular properties of Hck and Fgr. We discuss the methods generally used for the measurement of protein-tyrosine kinase activities in neutrophils highlighting precautions against proteolysis. In addition, we show that in subcellular fractions of retinoic acid-differentiated neutrophil-like NB4 cells, the 59- and 61-kDa forms of Hck are attached to the membranes of their respective compartments by different mechanisms. Finally, we discuss the functional roles of protein-tyrosine kinases in the regulation of neutrophil activation and speculate on the importance of their subcellular localization.

Long time series analysis of ionospheric TEC disturbance over seismically region in southwest China during low solar activity

NASA Astrophysics Data System (ADS)

Yan, Xiangxiang; Yu, Tao; Shan, Xinjian; Liu, Zhan; Wang, Zhenjie

2016-04-01

Recently, there are growing interests in studying the seismo-ionospheric disturbance prior to earthquakes, mainly including the anomalies in the electric field, magnetic field and plasma parameters. However, there are still some controversies over this topic, mainly because of strong day-to-day variability of the ionosphere itself. It is hard to determine whether the different forms of ionospheric disturbances are associated with earthquakes or not. Using data of Crustal Movement Observation Network of China (CMONC) and IGS (International GNSS Service), we attempt to give a statistical investigation about the total electron content (TEC) perturbation before 30 Mw6.0+ earthquakes during January 2000 to December 2010 in China. To determine the abnormal TEC signals, a quartile-based process is performed. At each time point we calculated the median M using the TEC values at the same local time for the preceding 15 days. In addition, we calculated the maps of differential TEC from global ionosphere maps (GIM) in the above period. It is shown that TEC anomalies were detected before 20 earthquakes, nearly 67%. The anomalies represent positive before most events and occurred mostly within 2-6 days before the shocks, significantly during the afternoon period, 1200-2000LT. Part of perturbations appeared more than one time. Moreover, the affected area of TEC is not coincide with the vertical projection of the epicenter but shifts equatorward and is controlled by equatorial ionization anomaly (EIA) crest. On the other hand, we analyzed variations of TEC over southwest China during a period of low solar and geomagnetic activity in April-October 2008, based on the data of CMONC. During that time, six large earthquakes with magnitude M≧6.0 occurred around the southwest region of China. The method to detect abnormal TEC signals is same with above statistical study. Known that the decisive role in the ionosphere state is performed by space weather effects, we compared the TEC variations with time series of EUV solar radiation, Bz component of the interplanetary magnetic field (IMF), index of geomagnetic activity Dst and planetary index Kp, respectively. It is found that the observed anomalies in the regional TEC were in good correlation with the variations of above solar and geomagnetic activities. We have not detected obvious TEC disturbance before five earthquakes expect for Wenchuan earthquake. In order to additionally check the spatial occurrence of the observed anomalies, we chose a 'check-region' with the same geomagnetic latitudes as the epicentral area of the six considered earthquakes, and analyzed the TEC changes. The result shows that the time series of anomalous TEC in 'check-region' is similar to the epicentral area, which was dominated by space weather. Therefore, we are suspicious of the results of statistical investigation showed here or other similar papers, which indicates the difficulties in identifying earthquake precursors in the ionosphere TEC. The seismo-ionospheric coupling process is complex, and it is necessary to strengthen the observation of multi-parameters on the ground, in the atmosphere and ionosphere synchronously.

Investigation of Ionospheric Precursors of 23 October 2011, Mw=7.2 Earthquake in Van, Turkey

NASA Astrophysics Data System (ADS)

Deviren, M. N.; Arikan, F.; Sezen, U.; Arikan, O.

2012-04-01

In recent years, a strong coupling between ionospheric disturbances and seismic activity has been observed through the increase of ion temperatures, critical frequencies of ionospheric layers and Total Electron Content (TEC) before high magnitude earthquakes. TEC is defined as total number of electrons over a ray path through the ionosphere. TEC can be estimated in a cost-effective way with dual-frequency Global Positioning Satellite (GPS) System receivers. The unit of TEC is given by TECU where 1 TECU = 1016 el/m2. In this study, the disturbances in daily TEC values before 23 October 2011, Mw=7.2 Earthquake in Van, Turkey are investigated using Turkish National Permanent GPS Network (TNPGN-Active). Earthquake Day Period (EDP) is chosen between October 1 and 31, 2011. Daily TEC values, for each station and each day, are estimated as IONOLAB-TEC (www.ionolab.org ) with 30 s time resolution. EDP-TEC values are compared with an Average Quiet Day TEC (AQDT) which is obtained by averaging the TEC values between 25 and 28 March, 2011. Statistical comparison is accomplished using Symmetric Kullback-Leibler Divergence (SKLD), which is also a method for measuring entropy of a system. It has been previously observed that SKLD is a better method for measuring the amount of disturbances compared to L2 norm and cross-correlation coefficient. AQDT is also compared with magnetically Quiet Day Period (QDP) from 25 to 28 April, 2011, during which Kp and Dst indices indicate a very quiet ionospheric and magnetospheric period. Also, in order to measure the variability between the consecutive days, TEC values for each day during EDP and QDP are compared with the TEC values of the following day. A third measure of W-index is also applied to identify the local disturbances in the ionosphere, where TEC of a given day is compared to the median of seven days prior to the day of investigation logarithmically. Since W-index is obtained for each epoch, the within-the-day variability can also be monitored. It has been observed that peak TEC values for all stations in TNPGN increase 10 to 15 TECU two days prior to the earthquake. The SKLD values for comparison of EDP and AQDT also peak on 21st of October, 2011, two days prior to the earthquake. Since ionospheric disturbance can be observed on all days prior to the earthquake, comparison of TEC for consecutive days for each station using SKLD does not provide extra information. The W-index values indicate that there may be small scale variability for stations closer to the earthquake epicenter. When compared with previous earthquakes that occurred in Turkey with magnitudes 4.5 and 5.2 on Richter scale, this 7.2 magnitude earthquake has been felt as an ionospheric disturbance for stations especially on Northern Anatolian Fault. The results also indicate the need for constant monitoring and statistical decision theory for detection of earthquake precursors. This study is supported by TUBITAK EEEAG Grant 109E055.

Contribution of Rho-kinase to membrane excitability of murine colonic smooth muscle.

PubMed

Bayguinov, O; Dwyer, L; Kim, H; Marklew, A; Sanders, K M; Koh, S D

2011-06-01

The Rho-kinase pathway regulates agonist-induced contractions in several smooth muscles, including the intestine, urinary bladder and uterus, via dynamic changes in the Ca(2+) sensitivity of the contractile apparatus. However, there is evidence that Rho-kinase also modulates other cellular effectors such as ion channels. We examined the regulation of colonic smooth muscle excitability by Rho-kinase using conventional microelectrode recording, isometric force measurements and patch-clamp techniques. The Rho-kinase inhibitors, Y-27632 and H-1152, decreased nerve-evoked on- and off-contractions elicited at a range of frequencies and durations. The Rho-kinase inhibitors decreased the spontaneous contractions and the responses to carbachol and substance P independently of neuronal inputs, suggesting Y-27632 acts directly on smooth muscle. The Rho-kinase inhibitors significantly reduced the depolarization in response to carbachol, an effect that cannot be due to regulation of Ca(2+) sensitization. Patch-clamp experiments showed that Rho-kinase inhibitors reduce GTPγS-activated non-selective cation currents. The Rho-kinase inhibitors decreased contractions evoked by nerve stimulation, carbachol and substance P. These effects were not solely due to inhibition of the Ca(2+) sensitization pathway, as the Rho-kinase inhibitors also inhibited the non-selective cation conductances activated by excitatory transmitters. Thus, Rho-kinase may regulate smooth muscle excitability mechanisms by regulating non-selective cation channels as well as changing the Ca(2+) sensitivity of the contractile apparatus. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Loop Heat Pipe Operation with Thermoelectric Converters and Coupling Blocks

NASA Technical Reports Server (NTRS)

Ku, Jentung; Nagano, Hosei

2007-01-01

This paper presents theoretical and experimental studies on using thermoelectric converters (TECs) and coupling blocks to control the operating temperature of a miniature loop heat pipes (MLHP). The MLHP has two parallel evaporators and two parallel condensers, and each evaporator has its own integral compensation chamber (CC). A TEC is attached to each CC, and connected to the evaporator via a copper thermal strap. The TEC can provide both heating and cooling to the CC, therefore extending the LHP operating temperature over a larger range of the evaporator heat load. A bi-polar power supply is used for the TEC operation. The bipolar power supply automatically changes the direction of the current to the TEC, depending on whether the CC requires heating or cooling, to maintain the CC temperature at the desired set point. The TEC can also enhance the startup success by maintaining a constant CC temperature during the start-up transient. Several aluminum coupling blocks are installed between the vapor line and liquid line. The coupling blocks serve as a heat exchanger which preheats the cold returning liquid so as to reduce the amount of liquid subcooling, and hence the power required to maintain the CC at the desired set point temperature. This paper focuses on the savings of the CC control heater power afforded by the TECs when compared to traditional electric heaters. Tests were conducted by varying the evaporator power, the condenser sink temperature, the CC set point temperature, the number of coupling blocks, and the thermal conductance of the thermal strap. Test results show that the TECs are able to control the CC temperature within k0.5K under all test conditions, and the required TEC heater power is only a fraction of the required electric heater power.

Real-Time Detection of Tsunami Ionospheric Disturbances with a Stand-Alone GNSS Receiver: An Integration of GPS and Galileo Systems

NASA Astrophysics Data System (ADS)

Savastano, Giorgio; Komjathy, Attila; Verkhoglyadova, Olga; Wei, Yong; Mazzoni, Augusto; Crespi, Mattia

2017-04-01

Tsunamis can produce gravity waves that propagate up to the ionosphere generating disturbed electron densities in the E and F regions. These ionospheric disturbances are studied in detail using ionospheric total electron content (TEC) measurements collected by continuously operating ground-based receivers from the Global Navigation Satellite Systems (GNSS). Here, we present results using a new approach, named VARION (Variometric Approach for Real-Time Ionosphere Observation), and for the first time, we estimate slant TEC (sTEC) variations in a real-time scenario from GPS and Galileo constellations. Specifically, we study the 2016 New Zealand tsunami event using GNSS receivers with multi-constellation tracking capabilities located in the Pacific region. We compare sTEC estimates obtained using GPS and Galileo constellations. The efficiency of the real-time sTEC estimation using the VARION algorithm has been demonstrated for the 2012 Haida Gwaii tsunami event. TEC variations induced by the tsunami event are computed using 56 GPS receivers in Hawai'i. We observe TEC perturbations with amplitudes up to 0.25 TEC units and traveling ionospheric disturbances moving away from the epicenter at a speed of about 316 m/s. We present comparisons with the real-time tsunami model MOST (Method of Splitting Tsunami) provided by the NOAA Center for Tsunami Research. We observe variations in TEC that correlate well in time and space with the propagating tsunami waves. We conclude that the integration of different satellite constellations is a crucial step forward to increasing the reliability of real-time tsunami detection systems using ground-based GNSS receivers as an augmentation to existing tsunami early warning systems.

Simultaneous Global Positioning System observations of equatorial scintillations and total electron content fluctuations

NASA Astrophysics Data System (ADS)

Beach, Theodore L.; Kintner, Paul M.

1999-10-01

One aspect of the Global Positioning System (GPS) is the potential to conduct geophysical research, and worldwide networks of GPS receivers have been established to exploit this potential. Several research groups have begun using this global GPS data to study ionospheric total electron content (TEC) variations, also referred to as GPS phase fluctuations, as surrogates for ionospheric scintillations. This paper investigates the relationship between GPS amplitude scintillations and TEC variations for the same line of sight using observations from Ancón, Peru. These observations were taken under equatorial spread F conditions for three nights in April 1997. As expected, only when the spectrum of TEC fluctuations includes significant power at the Fresnel scale do scintillations appear. We also find that when the TEC fluctuation spectrum includes the Fresnel scale, the S4 scintillation index is roughly proportional to measures of TEC fluctuation for the weak scintillations observed. The proportionality constant varies from night to night, however, casting doubt on the ability to predict GPS S4 successfully from TEC fluctuation data alone. We also present a simple theoretical phase screen model and show that if a relationship between TEC fluctuation measures and S4 exists, that relationship depends on the power spectrum of phase variations at the screen. Unfortunately, the available TEC data, at 30 s per sample (with some aliasing apparently permitted), offer limited spectral information. A preliminary comparison of 1 s/sample data with the same data decimated to a 30 s/sample interval suggests, however, that the level of successful S4 prediction, based on TEC fluctuation measures alone, is comparable at either sample rate.

Empirical model of TEC response to geomagnetic and solar forcing over Balkan Peninsula

NASA Astrophysics Data System (ADS)

Mukhtarov, P.; Andonov, B.; Pancheva, D.

2018-01-01

An empirical total electron content (TEC) model response to external forcing over Balkan Peninsula (35°N-50°N; 15°E-30°E) is built by using the Center for Orbit Determination of Europe (CODE) TEC data for full 17 years, January 1999 - December 2015. The external forcing includes geomagnetic activity described by the Kp-index and solar activity described by the solar radio flux F10.7. The model describes the most probable spatial distribution and temporal variability of the externally forced TEC anomalies assuming that they depend mainly on latitude, Kp-index, F10.7 and LT. The anomalies are expressed by the relative deviation of the TEC from its 15-day mean, rTEC, as the mean value is calculated from the 15 preceding days. The approach for building this regional model is similar to that of the global TEC model reported by Mukhtarov et al. (2013a) however it includes two important improvements related to short-term variability of the solar activity and amended geomagnetic forcing by using a "modified" Kp index. The quality assessment of the new constructing model procedure in terms of modeling error calculated for the period of 1999-2015 indicates significant improvement in accordance with the global TEC model (Mukhtarov et al., 2013a). The short-term prediction capabilities of the model based on the error calculations for 2016 are improved as well. In order to demonstrate how the model is able to reproduce the rTEC response to external forcing three geomagnetic storms, accompanied also with short-term solar activity variations, which occur at different seasons and solar activity conditions are presented.

Preliminary study of TEC application in cooling system

NASA Astrophysics Data System (ADS)

Sulaiman, A. C.; Amin, N. A. M.; Saidon, M. S.; Majid, M. S. A.; Rahman, M. T. A.; Kazim, M. N. F. M.

2017-10-01

Integration of thermoelectric cooling (TEC) within a space cooling system in the lecturer room is studied. The studied area (air conditioned surrounding) is encapsulated with wall, floor, roof, and glass window. TEC module is placed on the glass window. The prototype of the studied compartment is designed using cabin container. The type and number of TEC module are studied and the effects on the cooling performance are analyzed as it is assumed to be tested within an air conditioned lecturer room. The experimental and mathematical modeling of the cooling system developed. It is expected that the mathematical modeling derived from this study will be used to estimate the use of the number of TEC module to be integrated with air conditioner unit where possible.

Regulation of steroid hormone receptors and coregulators during the cell cycle highlights potential novel function in addition to roles as transcription factors

PubMed Central

Zheng, Yingfeng; Murphy, Leigh C.

2016-01-01

Cell cycle progression is tightly controlled by several kinase families including Cyclin-Dependent Kinases, Polo-Like Kinases, and Aurora Kinases. A large amount of data show that steroid hormone receptors and various components of the cell cycle, including cell cycle regulated kinases, interact, and this often results in altered transcriptional activity of the receptor. Furthermore, steroid hormones, through their receptors, can also regulate the transcriptional expression of genes that are required for cell cycle regulation. However, emerging data suggest that steroid hormone receptors may have roles in cell cycle progression independent of their transcriptional activity. The following is a review of how steroid receptors and their coregulators can regulate or be regulated by the cell cycle machinery, with a particular focus on roles independent of transcription in G2/M. PMID:26778927

Comparison of Two IRI plasmasphere Extensions with GPS-TEC Observations

NASA Technical Reports Server (NTRS)

Gulyaeva, T. L.; Gallagher, Dennis L.

2006-01-01

Comparisons of two model results with Global Positioning System GPS-TEC measurements have been carried out for different latitudinal, solar activity, magnetic activity, diurnal and seasonal conditions. The models evaluated are the Global Core Plasma Model (GCPM-2000) and the IRI extension with Russian plasmasphere model (IRI*).Data of 23 observatories providing GPS-TEC and ionosonde data have been used. It is shown that IRI* plasmasphere electron density is greater than GCPM results by an order of magnitude at 6370 km altitude (one Earth's radius) with this excess growing to 2-3 orders of magnitude towards the GPS satellite altitude of 20000 km. Another source of model and GPS-TEC differences is a way of selection of the F2 layer peak parameters driving the models either with ITU-R (former CCIR) maps or ionosonde observations. Plasmasphere amendment to IRI improves accuracy of TEC model predictions because the plasmasphere contribution to the total TEC varies from 10% by daytime under quiet magnetic conditions to more than 50% by night under stormy conditions.

Observation of subsecond variations in auroral region total electron content using 100 Hz sampling of GPS observables

NASA Astrophysics Data System (ADS)

McCaffrey, A. M.; Jayachandran, P. T.

2017-06-01

First ever auroral region total electron content (TEC) measurements at 100 Hz using a Septentrio PolaRxS Pro receiver are analyzed to discover ionospheric signatures which would otherwise be unobtainable with the frequently used lower sampling rates. Two types of variations are observed: small-magnitude (amplitude) variations, which are present consistently throughout the data set, and larger-magnitude (amplitude) variations, which are less frequent. Small-amplitude TEC fluctuations are accounted for by the receiver phase jitter. However, estimated secondary ionospheric effects in the calculation of TEC and the receiver phase jitter were unable to account for the larger-amplitude TEC fluctuations. These variations are also accompanied by fluctuations in the magnetic field, which seems to indicate that these fluctuations are real and of geophysical significance. This paper presents a technique and the capability of high-rate TEC measurements in the study of auroral dynamics. Further detailed study is needed to identify the cause of these subsecond TEC fluctuations and associated magnetic field fluctuations.

The synthesis of ternary acetylides with tellurium: Li 2 TeC 2 and Na 2 TeC 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Németh, Károly; Unni, Aditya K.; Kalnmals, Christopher

The synthesis of ternary acetylides Li 2TeC 2 and Na 2TeC 2 is presented as the first example of ternary acetylides with metalloid elements instead of transition metals. The synthesis was carried out by the direct reaction of the corresponding bialkali acetylides with tellurium powder in liquid ammonia. Alternatively, the synthesis of Na 2TeC 2 was also carried out by the direct reaction of tellurium powder and two equivalents of NaC 2H in liquid ammonia leading to Na 2TeC 2 and acetylene gas through an equilibrium containing the assumed NaTeC 2H molecules besides the reactants and the products. The resultingmore » disordered crystalline materials were characterized by X-ray diffraction and Raman spectroscopy. Implications of these new syntheses on the synthesis of other ternary acetylides with metalloid elements and transition metals are also discussed.« less

A statistical study of global ionospheric map total electron content changes prior to occurrences of M ≥ 6.0 earthquakes during 2000-2014

NASA Astrophysics Data System (ADS)

Thomas, J. N.; Huard, J.; Masci, F.

2017-02-01

There are many reports on the occurrence of anomalous changes in the ionosphere prior to large earthquakes. However, whether or not these changes are reliable precursors that could be useful for earthquake prediction is controversial within the scientific community. To test a possible statistical relationship between ionospheric disturbances and earthquakes, we compare changes in the total electron content (TEC) of the ionosphere with occurrences of M ≥ 6.0 earthquakes globally for 2000-2014. We use TEC data from the global ionosphere map (GIM) and an earthquake list declustered for aftershocks. For each earthquake, we look for anomalous changes in GIM-TEC within 2.5° latitude and 5.0° longitude of the earthquake location (the spatial resolution of GIM-TEC). Our analysis has not found any statistically significant changes in GIM-TEC prior to earthquakes. Thus, we have found no evidence that would suggest that monitoring changes in GIM-TEC might be useful for predicting earthquakes.

Seismo-Ionospheric Precursor in the GIM TEC of the 24 August 2014 M6 Napa Earthquake

NASA Astrophysics Data System (ADS)

Wu, T. Y.; Liu, T. J. Y.; Liu, J. Y.

2015-12-01

This study examines seismo-ionospheric precursors (SIPs) in the global ionosphere map (GIM) of the total electron content (TEC) associated with the 24 August 2014 M6 South Napa earthquake and statistical evidence of SIPs of the GPS TEC in western USA during 2000-2014. The temporal SIP in the GIM TEC around the epicenter significantly decreasing (negative anomaly) on 22 August. To discriminate the global effect, such as solar flares, magnetic storms, etc., and the local effect, such as earthquakes, 5183 lattices on the GIM are employed to conduct a global search of the SIP distribution. Anomalies of both GIM TEC and associated gradients specifically and continuously appearing over the epicenter suggest that the SIP relate to the 2014 South Napa earthquake. A simulation is further carried out to produce the SIP in GIM TEC before the earthquake. Results indicate that the eastward electric field generated over the epicenter area during the earthquake preparation period to be essential.

Ionospheric effects of sudden stratospheric warmings in eastern Siberia region

NASA Astrophysics Data System (ADS)

Polyakova, A. S.; Chernigovskaya, M. A.; Perevalova, N. P.

2014-12-01

Ionospheric effects observed in Russia's Asia region during sudden stratospheric warmings (SSWs) in the winters 2008/2009 and 2012/2013 corresponding to both extreme solar minimum and moderate solar maximum conditions have been examined. To detect the ionospheric effects which must have been induced by the SSWs, we have carried out a joint analysis of total electron content (TEC) global ionospheric maps (GIM), MLS (Microwave Limb Sounder, EOS Aura) measurements of vertical temperature profiles, as well as NCEP/NCAR and UKMO Reanalysis data. It has been revealed for the first time that during strong SSWs the amplitude of diurnal variation of TEC decreases nearly by half in the mid-latitude ionosphere. Besides, the intensity of TEC deviations from the background level increases during SSWs. It has also revealed that during SSW peak the midday TEC maximum considerably decreases, and the night/morning TEC increases compared to quiet days. The pattern of TEC response to SSW is shown to be identical for both quiet and disturbed geophysical conditions.

The SH2 domain of Abl kinases regulates kinase autophosphorylation by controlling activation loop accessibility.

PubMed

Lamontanara, Allan Joaquim; Georgeon, Sandrine; Tria, Giancarlo; Svergun, Dmitri I; Hantschel, Oliver

2014-11-17

The activity of protein kinases is regulated by multiple molecular mechanisms, and their disruption is a common driver of oncogenesis. A central and almost universal control element of protein kinase activity is the activation loop that utilizes both conformation and phosphorylation status to determine substrate access. In this study, we use recombinant Abl tyrosine kinases and conformation-specific kinase inhibitors to quantitatively analyse structural changes that occur after Abl activation. Allosteric SH2-kinase domain interactions were previously shown to be essential for the leukemogenesis caused by the Bcr-Abl oncoprotein. We find that these allosteric interactions switch the Abl activation loop from a closed to a fully open conformation. This enables the trans-autophosphorylation of the activation loop and requires prior phosphorylation of the SH2-kinase linker. Disruption of the SH2-kinase interaction abolishes activation loop phosphorylation. Our analysis provides a molecular mechanism for the SH2 domain-dependent activation of Abl that may also regulate other tyrosine kinases.

The SH2 domain of Abl kinases regulates kinase autophosphorylation by controlling activation loop accessibility

NASA Astrophysics Data System (ADS)

Lamontanara, Allan Joaquim; Georgeon, Sandrine; Tria, Giancarlo; Svergun, Dmitri I.; Hantschel, Oliver

2014-11-01

The activity of protein kinases is regulated by multiple molecular mechanisms, and their disruption is a common driver of oncogenesis. A central and almost universal control element of protein kinase activity is the activation loop that utilizes both conformation and phosphorylation status to determine substrate access. In this study, we use recombinant Abl tyrosine kinases and conformation-specific kinase inhibitors to quantitatively analyse structural changes that occur after Abl activation. Allosteric SH2-kinase domain interactions were previously shown to be essential for the leukemogenesis caused by the Bcr-Abl oncoprotein. We find that these allosteric interactions switch the Abl activation loop from a closed to a fully open conformation. This enables the trans-autophosphorylation of the activation loop and requires prior phosphorylation of the SH2-kinase linker. Disruption of the SH2-kinase interaction abolishes activation loop phosphorylation. Our analysis provides a molecular mechanism for the SH2 domain-dependent activation of Abl that may also regulate other tyrosine kinases.

Local TEC modelling and forecasting using neural networks

NASA Astrophysics Data System (ADS)

Tebabal, A.; Radicella, S. M.; Nigussie, M.; Damtie, B.; Nava, B.; Yizengaw, E.

2018-07-01

Modelling the Earth's ionospheric characteristics is the focal task for the ionospheric community to mitigate its effect on the radio communication, and satellite navigation. However, several aspects of modelling are still challenging, for example, the storm time characteristics. This paper presents modelling efforts of TEC taking into account solar and geomagnetic activity, time of the day and day of the year using neural networks (NNs) modelling technique. The NNs have been designed with GPS-TEC measured data from low and mid-latitude GPS stations. The training was conducted using the data obtained for the period from 2011 to 2014. The model prediction accuracy was evaluated using data of year 2015. The model results show that diurnal and seasonal trend of the GPS-TEC is well reproduced by the model for the two stations. The seasonal characteristics of GPS-TEC is compared with NN and NeQuick 2 models prediction when the latter one is driven by the monthly average value of solar flux. It is found that NN model performs better than the corresponding NeQuick 2 model for low latitude region. For the mid-latitude both NN and NeQuick 2 models reproduce the average characteristics of TEC variability quite successfully. An attempt of one day ahead forecast of TEC at the two locations has been made by introducing as drivers previous day solar flux and geomagnetic index values. The results show that a reasonable day ahead forecast of local TEC can be achieved.

Local TEC Modelling and Forecasting using Neural Networks

NASA Astrophysics Data System (ADS)

Tebabal, A.; Radicella, S. M.; Nigussie, M.; Damtie, B.; Nava, B.; Yizengaw, E.

2017-12-01

Abstract Modelling the Earth's ionospheric characteristics is the focal task for the ionospheric community to mitigate its effect on the radio communication, satellite navigation and technologies. However, several aspects of modelling are still challenging, for example, the storm time characteristics. This paper presents modelling efforts of TEC taking into account solar and geomagnetic activity, time of the day and day of the year using neural networks (NNs) modelling technique. The NNs have been designed with GPS-TEC measured data from low and mid-latitude GPS stations. The training was conducted using the data obtained for the period from 2011 to 2014. The model prediction accuracy was evaluated using data of year 2015. The model results show that diurnal and seasonal trend of the GPS-TEC is well reproduced by the model for the two stations. The seasonal characteristics of GPS-TEC is compared with NN and NeQuick 2 models prediction when the latter one is driven by the monthly average value of solar flux. It is found that NN model performs better than the corresponding NeQuick 2 model for low latitude region. For the mid-latitude both NN and NeQuick 2 models reproduce the average characteristics of TEC variability quite successfully. An attempt of one day ahead forecast of TEC at the two locations has been made by introducing as driver previous day solar flux and geomagnetic index values. The results show that a reasonable day ahead forecast of local TEC can be achieved.

A Statistical Study of Total Electron Content Changes in the Ionosphere Prior to Earthquake Occurrences

NASA Astrophysics Data System (ADS)

Thomas, J. N.; Huard, J.; Masci, F.

2015-12-01

There are many published reports of anomalous changes in the ionosphere prior to large earthquakes. However, whether or not these ionospheric changes are reliable precursors that could be useful for earthquake prediction is controversial within the scientific community. To test a possible statistical relationship between the ionosphere and earthquakes, we compare changes in the total electron content (TEC) of the ionosphere with occurrences of M≥6.0 earthquakes globally for a multiyear period. We use TEC data from a global ionosphere map (GIM) and an earthquake list declustered for aftershocks. For each earthquake, we look for anomalous changes in TEC within ±30 days of the earthquake time and within 2.5° latitude and 5.0° longitude of the earthquake location (the spatial resolution of GIM). Our preliminary analysis, using global TEC and earthquake data for 2002-2010, has not found any statistically significant changes in TEC prior to earthquakes. Thus, we have found no evidence that would suggest that TEC changes are useful for earthquake prediction. Our results are discussed in the context of prior statistical and case studies. Namely, our results agree with Dautermann et al. (2007) who found no relationship between TEC changes and earthquakes in the San Andreas fault region. Whereas, our results disagree with Le et al. (2011) who found an increased rate in TEC anomalies within a few days before global earthquakes M≥6.0.

Long Duration Enhancement And Depletion Observed In The Topside Ionospheric Electron Content During The March 2015 Strong Storm

NASA Astrophysics Data System (ADS)

Zhong, J.; Wang, W.; Yue, X.; Burns, A. G.; Dou, X.; Lei, J.

2015-12-01

Up-looking total electron content (TEC) measurements from multiple low Earth orbit (LEO) satellites have been utilized to study the topside ionospheric response to the 17 March 2015 great storm. The combined up-looking TEC observations from these LEO satellites are valuable in addressing the local time and altitudinal dependences of the topside ionospheric response to geomagnetic storms from a global perspective, especially over the southern hemisphere and oceans. In the evening sector, the up-looking TEC showed an obvious long-duration of positive storm effect during the main phase and a long duration of negative storm effect during the recovery phase of this storm. The increases of the topside TEC during the main phase were symmetric with respect to the magnetic equator, which was probably associated with penetration electric fields. Additionally, the up-looking TEC from different orbital altitudes suggested that the negative storm effect at higher altitudes was stronger in the evening sector. In the morning sector, the up-looking TEC also showed increases at low and middle latitudes during the storm main phase. Obvious TEC enhancement can be also seen over the Pacific Ocean in the topside ionosphere during the storm recovery phase. These results imply that the topside ionospheric responses significantly depend on local time. Thus, the LEO-based up-looking TEC provides an important database to study the possible physical mechanisms of the topside ionospheric response to storms.

Analysis of ionospheric TEC from GNSS observables over the Turkish region and predictability of IRI and SPIM models

NASA Astrophysics Data System (ADS)

Ansari, Kutubuddin; Corumluoglu, Ozsen; Panda, Sampad Kumar

2017-04-01

The present study investigates the ionospheric Total Electron Content (TEC) variations in the lower mid-latitude Turkish region from the Turkish Permanent GNSS Network (TPGN) and International GNSS Services (IGS) observations during the period from January 2015 to December 2015. The corresponding TEC predicted by the International Reference Ionosphere (IRI 2012) and Standard Plasmasphere-Ionosphere Model (SPIM), and interpolated from Global Ionosphere Maps (GIMs) are evaluated to realize their reliability over the region. We studied the diurnal and monthly behavior of TEC and the relative TEC deviations along with the upper and lower quartiles to represent its spatio-temporal variability. The diurnal variation of GNSS-derived TEC indicates its maximum peak value around 10.00 UT which decreases gradually to attain minimum value after midnight. The monthly maximum value of TEC is observed in March followed by May and August, and the lowest value is seen during September. Studies show that the monthly relative deviation of TEC variability lies in the range of -1 to 4 units for all stations with the maximum difference between positive and negative variability remaining around 5. The studies also cover seasonal variation, grand-mean of ionospheric TEC and TEC intensity from the TPGN. The seasonal ionospheric VTEC pattern over all stations depicts slight increment in VTEC distribution during March equinox compared to September equinox. The December solstice perceived relatively higher VTEC than June solstice. The overall of VTEC values enhanced at all stations towards end of the year 2015 compare to mid of year due the high solar activity. The maximum grand-mean of VTEC is registered in March equinox while the lowest value is seen in September irrespective of all stations. The measured grand-mean intensity variations of VTEC values are in ascending phase during March, May, August and November months, but in descending phase during February, April, June and September months. The latitudinal study shows daytime TEC slowly decreasing with latitudes with a latitudinal gradient range of 0.1-0.2 TECU/degree. Additionally, the TEC analysis during the strong geomagnetic storm period (07-11 September 2015; SYM-H -120 nT) infers relatively better predictability of the SPIM model compared to the IRI 2012 model. The outputs of this study would complement towards a complete understanding of the lower mid-latitude ionospheric dynamics and its effects on radio propagations, particularly over the Turkish region.

Review of variations in Mw < 7 earthquake motions on position and tec (Mw = 6.5 aegean sea earthquake sample)

NASA Astrophysics Data System (ADS)

Yildirim, O.; Inyurt, S.; Mekik, C.

2015-10-01

Turkey is a country located in Middle Latitude zone and in which tectonic activity is intensive. Lastly, an earthquake of magnitude 6.5Mw occurred at Aegean Sea offshore on date 24 May 2014 at 12:25 UTC and it lasted approximately 40 s. The said earthquake was felt also in Greece, Romania and Bulgaria in addition to Turkey. In recent years seismic origin ionospheric anomaly detection studies have been done with TEC (Total Electron Contents) generated from GNSS (Global Navigation Satellite System) signals and the findings obtained have been revealed. In this study, TEC and positional variations have been examined seperately regarding the earthquake which occurred in the Aegean Sea. Then The correlation of the said ionospheric variation with the positional variation has been investigated. For this purpose, total fifteen stations have been used among which the data of four numbers of CORS-TR stations in the seismic zone (AYVL, CANA, IPSA, YENC) and IGS and EUREF stations are used. The ionospheric and positional variations of AYVL, CANA, IPSA and YENC stations have been examined by Bernese 5.0v software. When the (PPP-TEC) values produced as result of the analysis are examined, it has been understood that in the four stations located in Turkey, three days before the earthquake at 08:00 and 10:00 UTC, the TEC values were approximately 4 TECU above the upper limit TEC value. Still in the same stations, one day before the earthquake at 06:00, 08:00 and 10:00 UTC, it is being shown that the TEC values were approximately 5 TECU below the lower limit TEC value. On the other hand, the GIM-TEC values published by the CODE center have been examined. Still in all stations, it has been observed that three days before the earthquake the TEC values in the time portions of 08:00 and 10:00 UTC were approximately 2 TECU above, one day before the earthquake at 06:00, 08:00 and 10:00 UTC, the TEC values were approximately 4 TECU below the lower limit TEC value. Again, by using the same fifteen numbers of stations, positional variation investigation before and after the earthquake has been made for AYVL, CANA, IPSA and YENC stations. As result of the analysis made, positional displacements has been seen before and after earthquake at CANA station which is the nearest station to earthquake center. It is about 10 and 3 cm before three days and one day earthquake.

A Framework for Optimizing the Placement of Tidal Turbines

NASA Astrophysics Data System (ADS)

Nelson, K. S.; Roberts, J.; Jones, C.; James, S. C.

2013-12-01

Power generation with marine hydrokinetic (MHK) current energy converters (CECs), often in the form of underwater turbines, is receiving growing global interest. Because of reasonable investment, maintenance, reliability, and environmental friendliness, this technology can contribute to national (and global) energy markets and is worthy of research investment. Furthermore, in remote areas, small-scale MHK energy from river, tidal, or ocean currents can provide a local power supply. However, little is known about the potential environmental effects of CEC operation in coastal embayments, estuaries, or rivers, or of the cumulative impacts of these devices on aquatic ecosystems over years or decades of operation. There is an urgent need for practical, accessible tools and peer-reviewed publications to help industry and regulators evaluate environmental impacts and mitigation measures, while establishing best sitting and design practices. Sandia National Laboratories (SNL) and Sea Engineering, Inc. (SEI) have investigated the potential environmental impacts and performance of individual tidal energy converters (TECs) in Cobscook Bay, ME; TECs are a subset of CECs that are specifically deployed in tidal channels. Cobscook Bay is the first deployment location of Ocean Renewable Power Company's (ORPC) TidGenTM unit. One unit is currently in place with four more to follow. Together, SNL and SEI built a coarse-grid, regional-scale model that included Cobscook Bay and all other landward embayments using the modeling platform SNL-EFDC. Within SNL-EFDC tidal turbines are represented using a unique set of momentum extraction, turbulence generation, and turbulence dissipation equations at TEC locations. The global model was then coupled to a local-scale model that was centered on the proposed TEC deployment locations. An optimization frame work was developed that used the refined model to determine optimal device placement locations that maximized array performance. Within the framework, environmental effects are considered to minimize the possibility of altering flows to an extent that would affect fish-swimming behavior and sediment-transport trends. Simulation results were compared between model runs with the optimized array configuration, and the originally purposed deployment locations; the optimized array showed a 17% increase in power generation. The developed framework can provide regulators and developers with a tool for assessing environmental impacts and device-performance parameters for the deployment of MHK devices. The more thoroughly understood this promising technology, the more likely it will become a viable source of alternative energy.

Csk Homologous Kinase, a Potential Regulator of CXCR4-mediated Breast Cancer Cell Metastasis

DTIC Science & Technology

2010-08-31

SH2 ) and SH3 domains and lacks the consensus tyrosine phosphorylation and myristylation sites found in Src family kinases . CHK has been shown to...0350 TITLE: Csk Homologous Kinase , a Potential Regulator of CXCR4-mediated Breast Cancer Cell Metastasis PRINCIPAL INVESTIGATOR: Byeong-Chel...1 AUG 2009 - 31 JUL 2010 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-09-1-0350 Csk Homologous Kinase , a Potential Regulator

Sustained activation of c-Jun N-terminal and extracellular signal-regulated kinases in port-wine stain blood vessels.

PubMed

Tan, Wenbin; Chernova, Margarita; Gao, Lin; Sun, Victor; Liu, Huaxu; Jia, Wangcun; Langer, Stephanie; Wang, Gang; Mihm, Martin C; Nelson, J Stuart

2014-11-01

Port-wine stain (PWS) is a congenital, progressive vascular malformation but the pathogenesis remains incompletely understood. We sought to investigate the activation status of various kinases, including extracellular signal-regulated kinase, c-Jun N-terminal kinase, AKT, phosphatidylinositol 3-kinase, P70 ribosomal S6 kinase, and phosphoinositide phospholipase C γ subunit, in PWS biopsy tissues. Immunohistochemistry was performed on 19 skin biopsy samples from 11 patients with PWS. c-Jun N-terminal kinase, extracellular signal-regulated kinase, and P70 ribosomal S6 kinase in pediatric and adult PWS blood vessels were consecutively activated. Activation of AKT and phosphatidylinositol 3-kinase was found in many adult hypertrophic PWS blood vessels but not in infants. Phosphoinositide phospholipase C γ subunit showed strong activation in nodular PWS blood vessels. Infantile PWS sample size was small. Our data suggest a subsequent activation profile of various kinases during different stages of PWS: (1) c-Jun N-terminal and extracellular signal-regulated kinases are firstly and consecutively activated in all PWS tissues, which may contribute to both the pathogenesis and progressive development of PWS; (2) AKT and phosphatidylinositol 3-kinase are subsequently activated, and are involved in the hypertrophic development of PWS blood vessels; and (3) phosphoinositide phospholipase C γ subunit is activated in the most advanced stage of PWS and may participate in nodular formation. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Computational Prediction and Experimental Verification of New MAP Kinase Docking Sites and Substrates Including Gli Transcription Factors

PubMed Central

Whisenant, Thomas C.; Ho, David T.; Benz, Ryan W.; Rogers, Jeffrey S.; Kaake, Robyn M.; Gordon, Elizabeth A.; Huang, Lan; Baldi, Pierre; Bardwell, Lee

2010-01-01

In order to fully understand protein kinase networks, new methods are needed to identify regulators and substrates of kinases, especially for weakly expressed proteins. Here we have developed a hybrid computational search algorithm that combines machine learning and expert knowledge to identify kinase docking sites, and used this algorithm to search the human genome for novel MAP kinase substrates and regulators focused on the JNK family of MAP kinases. Predictions were tested by peptide array followed by rigorous biochemical verification with in vitro binding and kinase assays on wild-type and mutant proteins. Using this procedure, we found new ‘D-site’ class docking sites in previously known JNK substrates (hnRNP-K, PPM1J/PP2Czeta), as well as new JNK-interacting proteins (MLL4, NEIL1). Finally, we identified new D-site-dependent MAPK substrates, including the hedgehog-regulated transcription factors Gli1 and Gli3, suggesting that a direct connection between MAP kinase and hedgehog signaling may occur at the level of these key regulators. These results demonstrate that a genome-wide search for MAP kinase docking sites can be used to find new docking sites and substrates. PMID:20865152

Optimize out-of-core thermionic energy conversion for nuclear electric propulsion

NASA Technical Reports Server (NTRS)

Morris, J. F.

1978-01-01

Thermionic energy conversion (TEC) potentialities for nuclear electric propulsion (NEP) are examined. Considering current designs, their limitations, and risks raises critical questions about the use of TEC for NEP. Apparently a reactor cooled by hotter-than-1675 K heat pipes has good potentialities. TEC with higher temperatures and greater power densities than the currently proposed 1650 K, 5-to-6 W/sq cm version offers substantial gains. Other approaches to high-temperature electric isolation appear also promising. A high-power-density, high-temperature TEC for NEP appears, therefore, attainable. It is recommended to optimize out-of-core thermionic energy conversion for nuclear electric propulsion. Although current TEC designs for NEP seem unnecessary compared with Brayton versions, large gains are apparently possible with increased temperatures and greater power densities.

Short term variations of total electron content (TEC) fitting to a regional GPS network over the Kingdom of Saudi Arabia (KSA)

NASA Astrophysics Data System (ADS)

Alothman, A. O.; Alsubaie, M. A.; Ayhan, M. E.

2011-09-01

The ionosphere is a dispersive medium for radio waves with the refractive index which is a function of frequency and total electron content (TEC). TEC has a strong diurnal variation in addition to monthly, seasonal and solar cycle variations and small and large scale irregularities. Dual frequency GPS observations can be utilized to obtain TEC and investigate its spatial and temporal variations. We here studied short term TEC variations over the Kingdom of Saudi Arabia (KSA). A regional GPS network is formed consisting of 16 sites in and around KSA. GPS observations, acquired between 1st and 11th February 2009, were processed on a daily basis by using the Bernese v5.0 software and IGS final products. The geometry-free zero difference smoothed code observables were used to obtain two hour interval snapshots of TEC and their RMS errors at 0.5 × 0.5 degree grid nodes and regional ionosphere models in a spherical harmonics expansion to degree and order six. The equatorial ionized anomaly (EIA) is recovered in the south of 20°N from 08:00 to 12:00 UT. We found that day-by-day TEC variation is more stable than the night time variation.

Coliphage HK022 Nun protein inhibits RNA polymerase translocation

PubMed Central

Vitiello, Christal L.; Kireeva, Maria L.; Lubkowska, Lucyna; Kashlev, Mikhail; Gottesman, Max

2014-01-01

The Nun protein of coliphage HK022 arrests RNA polymerase (RNAP) in vivo and in vitro at pause sites distal to phage λ N-Utilization (nut) site RNA sequences. We tested the activity of Nun on ternary elongation complexes (TECs) assembled with templates lacking the λ nut sequence. We report that Nun stabilizes both translocation states of RNAP by restricting lateral movement of TEC along the DNA register. When Nun stabilized TEC in a pretranslocated register, immediately after NMP incorporation, it prevented binding of the next NTP and stimulated pyrophosphorolysis of the nascent transcript. In contrast, stabilization of TEC by Nun in a posttranslocated register allowed NTP binding and nucleotidyl transfer but inhibited pyrophosphorolysis and the next round of forward translocation. Nun binding to and action on the TEC requires a 9-bp RNA–DNA hybrid. We observed a Nun-dependent toe print upstream to the TEC. In addition, mutations in the RNAP β′ subunit near the upstream end of the transcription bubble suppress Nun binding and arrest. These results suggest that Nun interacts with RNAP near the 5′ edge of the RNA–DNA hybrid. By stabilizing translocation states through restriction of TEC lateral mobility, Nun represents a novel class of transcription arrest factors. PMID:24853501

Total electron content responses to HILDCAAs and geomagnetic storms over South America

NASA Astrophysics Data System (ADS)

Mara de Siqueira Negreti, Patricia; Rodrigues de Paula, Eurico; Nicoli Candido, Claudia Maria

2017-12-01

Total electron content (TEC) is extensively used to monitor the ionospheric behavior under geomagnetically quiet and disturbed conditions. This subject is of greatest importance for space weather applications. Under disturbed conditions the two main sources of electric fields, which are responsible for changes in the plasma drifts and for current perturbations, are the short-lived prompt penetration electric fields (PPEFs) and the longer-lasting ionospheric disturbance dynamo (DD) electric fields. Both mechanisms modulate the TEC around the globe and the equatorial ionization anomaly (EIA) at low latitudes. In this work we computed vertical absolute TEC over the low latitude of South America. The analysis was performed considering HILDCAA (high-intensity, long-duration, continuous auroral electrojet (AE) activity) events and geomagnetic storms. The characteristics of storm-time TEC and HILDCAA-associated TEC will be presented and discussed. For both case studies presented in this work (March and August 2013) the HILDCAA event follows a geomagnetic storm, and then a global scenario of geomagnetic disturbances will be discussed. Solar wind parameters, geomagnetic indices, O / N2 ratios retrieved by GUVI instrument onboard the TIMED satellite and TEC observations will be analyzed and discussed. Data from the RBMC/IBGE (Brazil) and IGS GNSS networks were used to calculate TEC over South America. We show that a HILDCAA event may generate larger TEC differences compared to the TEC observed during the main phase of the precedent geomagnetic storm; thus, a HILDCAA event may be more effective for ionospheric response in comparison to moderate geomagnetic storms, considering the seasonal conditions. During the August HILDCAA event, TEC enhancements from ˜ 25 to 80 % (compared to quiet time) were observed. These enhancements are much higher than the quiet-time variability observed in the ionosphere. We show that ionosphere is quite sensitive to solar wind forcing and considering the events studied here, this was the most important source of ionospheric responses. Furthermore, the most important source of TEC changes were the long-lasting PPEFs observed on August 2013, during the HILDCAA event. The importance of this study relies on the peculiarity of the region analyzed characterized by high declination angle and ionospheric gradients which are responsible for creating a complex response during disturbed periods.

Validation of measured poleward TEC gradient using multi-station GPS with Artificial Neural Network based TEC model in low latitude region for developing predictive capability of ionospheric scintillation

NASA Astrophysics Data System (ADS)

Sur, D.; Paul, A.

2017-12-01

The equatorial ionosphere shows sharp diurnal and latitudinal Total Electron Content (TEC) variations over a major part of the day. Equatorial ionosphere also exhibits intense post-sunset ionospheric irregularities. Accurate prediction of TEC in these low latitudes is not possible from standard ionospheric models. An Artificial Neural Network (ANN) based Vertical TEC (VTEC) model has been designed using TEC data in low latitude Indian longitude sector for accurate prediction of VTEC. GPS TEC data from the stations Calcutta (22.58°N, 88.38°E geographic, magnetic dip 32°), Baharampore (24.09°N, 88.25°E geographic, magnetic dip 35°) and Siliguri (26.72°N, 88.39°E geographic; magnetic dip 40°) are used as training dataset for the duration of January 2007-September 2011. Poleward VTEC gradients from northern EIA crest to region beyond EIA crest have been calculated from measured VTEC and compared with that obtained from ANN based VTEC model. TEC data from Calcutta and Siliguri are used to compute VTEC gradients during April 2013 and August-September 2013. It has been observed that poleward VTEC gradient computed from ANN based TEC model has shown good correlation with measured values during vernal and autumnal equinoxes of high solar activity periods of 2013. Possible correlation between measured poleward TEC gradients and post-sunset scintillations (S4 ≥ 0.4) from northern crest of EIA has been observed in this paper. From the observation, a suitable threshold poleward VTEC gradient has been proposed for possible occurrence of post-sunset scintillations at northern crest of EIA along 88°E longitude. Poleward VTEC gradients obtained from ANN based VTEC model are used to forecast possible ionospheric scintillation after post-sunset period using the threshold value. It has been observed that these predicted VTEC gradients obtained from ANN based VTEC model can forecast post-sunset L-band scintillation with an accuracy of 67% to 82% in this dynamic low latitude region. The use of VTEC gradients from ANN based VTEC model removes the necessity of continuous operation of multi-station ground based TEC receivers in this low latitude region.

Roles of P21-activated kinases and associated proteins in epithelial wound healing.

PubMed

Zegers, Mirjam

2008-01-01

The primary function of epithelia is to provide a barrier between the extracellular environment and the interior of the body. Efficient epithelial repair mechanisms are therefore crucial for homeostasis. The epithelial wound-healing process involves highly regulated morphogenetic changes of epithelial cells that are driven by dynamic changes of the cytoskeleton. P21-activated kinases are serine/threonine kinases that have emerged as important regulators of the cytoskeleton. These kinases, which are activated downsteam of the Rho GTPases Rac and cd42, were initially mostly implicated in the regulation of cell migration. More recently, however, these kinases were shown to have many additional functions that are relevant to the regulation of epithelial wound healing. Here, we provide an overview of the morphogenetic changes of epithelial cells during wound healing and the many functions of p21-activated kinases in these processes.

Macro-Scale Strength and Microstructure of ZrW2O8 Cementitious Composites with Tunable Low Thermal Expansion

PubMed Central

Ouyang, Jianshu; Chen, Bo; Huang, Dahai

2018-01-01

Concretes with engineered thermal expansion coefficients, capable of avoiding failure or irreversible destruction of structures or devices, are important for civil engineering applications, such as dams, bridges, and buildings. In natural materials, thermal expansion usually cannot be easily regulated and an extremely low thermal expansion coefficient (TEC) is still uncommon. Here we propose a novel cementitious composite, doped with ZrW2O8, showing a wide range of tunable thermal expansion coefficients, from 8.65 × 10−6 °C−1 to 2.48 × 10−6 °C−1. Macro-scale experiments are implemented to quantify the evolution of the thermal expansion coefficients, compressive and flexural strength over a wide range of temperature. Scanning Electron Microscope (SEM) imaging was conducted to quantify the specimens’ microstructural characteristics including pores ratio and size. It is shown that the TEC of the proposed composites depends on the proportion of ZrW2O8 and the ambient curing temperature. Macro-scale experimental results and microstructures have a good agreement. The TEC and strength gradually decrease as ZrW2O8 increases from 0% to 20%, subsequently fluctuates until 60%. The findings reported here provide a new routine to design cementitious composites with tunable thermal expansion for a wide range of engineering applications. PMID:29735957

Subcellular localization of the Snf1 kinase is regulated by specific β subunits and a novel glucose signaling mechanism

PubMed Central

Vincent, Olivier; Townley, Robert; Kuchin, Sergei; Carlson, Marian

2001-01-01

The Snf1/AMP-activated protein kinase family has broad roles in transcriptional, metabolic, and developmental regulation in response to stress. In Saccharomyces cerevisiae, Snf1 is required for the response to glucose limitation. Snf1 kinase complexes contain the α (catalytic) subunit Snf1, one of the three related β subunits Gal83, Sip1, or Sip2, and the γ subunit Snf4. We present evidence that the β subunits regulate the subcellular localization of the Snf1 kinase. Green fluorescent protein fusions to Gal83, Sip1, and Sip2 show different patterns of localization to the nucleus, vacuole, and/or cytoplasm. We show that Gal83 directs Snf1 to the nucleus in a glucose-regulated manner. We further identify a novel signaling pathway that controls this nuclear localization in response to glucose phosphorylation. This pathway is distinct from the glucose signaling pathway that inhibits Snf1 kinase activity and responds not only to glucose but also to galactose and sucrose. Such independent regulation of the localization and the activity of the Snf1 kinase, combined with the distinct localization of kinases containing different β subunits, affords versatility in regulating physiological responses. PMID:11331606

Redox Regulation of Protein Kinases

PubMed Central

Truong, Thu H.; Carroll, Kate S.

2015-01-01

Protein kinases represent one of the largest families of genes found in eukaryotes. Kinases mediate distinct cellular processes ranging from proliferation, differentiation, survival, and apoptosis. Ligand-mediated activation of receptor kinases can lead to the production of endogenous H2O2 by membrane-bound NADPH oxidases. In turn, H2O2 can be utilized as a secondary messenger in signal transduction pathways. This review presents an overview of the molecular mechanisms involved in redox regulation of protein kinases and its effects on signaling cascades. In the first half, we will focus primarily on receptor tyrosine kinases (RTKs), whereas the latter will concentrate on downstream non-receptor kinases involved in relaying stimulant response. Select examples from the literature are used to highlight the functional role of H2O2 regarding kinase activity, as well as the components involved in H2O2 production and regulation during cellular signaling. In addition, studies demonstrating direct modulation of protein kinases by H2O2 through cysteine oxidation will be emphasized. Identification of these redox-sensitive residues may help uncover signaling mechanisms conserved within kinase subfamilies. In some cases, these residues can even be exploited as targets for the development of new therapeutics. Continued efforts in this field will further basic understanding of kinase redox regulation, and delineate the mechanisms involved in physiologic and pathological H2O2 responses. PMID:23639002

Dual-band beacon experiment over Southeast Asia for ionospheric irregularity analysis

NASA Astrophysics Data System (ADS)

Watthanasangmechai, K.; Yamamoto, M.; Saito, A.; Saito, S.; Maruyama, T.; Tsugawa, T.; Nishioka, M.

2013-12-01

An experiment of dual-band beacon over Southeast Asia was started in March 2012 in order to capture and analyze ionospheric irregularities in equatorial region. Five GNU Radio Beacon Receivers (GRBRs) were aligned along 100 degree geographic longitude. The distances between the stations reach more than 500 km. The field of view of this observational network covers +/- 20 degree geomagnetic latitude including the geomagnetic equator. To capture ionospheric irregularities, the absolute TEC estimation technique was developed. The two-station method (Leitinger et al., 1975) is generally accepted as a suitable method to estimate TEC offsets of dual-band beacon experiment. However, the distances between the stations directly affect on the robustness of the technique. In Southeast Asia, the observational network is too sparse to attain a benefit of the classic two-station method. Moreover, the least-squares approch used in the two-station method tries too much to adjust the small scales of the TEC distribution which are the local minima. We thus propose a new technique to estimate the TEC offsets with the supporting data from absolute GPS-TEC from local GPS receivers and the ionospheric height from local ionosondes. The key of the proposed technique is to utilize the brute-force technique with weighting function to find the TEC offset set that yields a global minimum of RMSE in whole parameter space. The weight is not necessary when the TEC distribution is smooth, while it significantly improves the TEC estimation during the ESF events. As a result, the latitudinal TEC shows double-hump distribution because of the Equatorial Ionization Anomaly (EIA). In additions, the 100km-scale fluctuations from an Equatorial Spread F (ESF) are captured at night time in equinox seasons. The plausible linkage of the meridional wind with triggering of ESF is under invatigating and will be presented. The proposed method is successful to estimate the latitudinal TEC distribution from dual-band frequency beacon data for the sparse observational network in Southeast Asia which may be useful for other equatorial sectors like Affrican region as well.

Comparison of GPS TEC variations with Holt-Winter method and IRI-2012 over Langkawi, Malaysia

NASA Astrophysics Data System (ADS)

Elmunim, N. A.; Abdullah, M.; Hasbi, A. M.; Bahari, S. A.

2017-07-01

The Total Electron Content (TEC) is the ionospheric parameter that has the main effect on radio wave propagation. Therefore, it is crucial to evaluate the performance of the TEC models for the further improvement of the ionospheric modelling in equatorial regions. This work presents an analysis of the TEC, derived from the GPS Ionospheric Scintillation and TEC Monitor (GISTM) receiver at the Langkawi station, Malaysia, located at the geographic coordinates of 6.19°N, 99.51°E and the geomagnetic coordinates of 3.39°S, 172.42°E. The diurnal, monthly and seasonal variations in 2014 of the observed GPS-TEC were compared with the statistical Holt-Winter method and a recent version of the International Reference Ionosphere model (IRI-2012), using three different topside options of an electron density, which are the IRI-2001, IRI01-corr and NeQuick. The maximum peaks of the GPS-TEC were observed in the post-noon time and the minimum was observed during the early morning time. In addition, in monthly variations the Holt-Winter and the IRI-2012 topside options showed an underestimation that was in agreement with the GPS-TEC, except for the IRI-2001 model which showed an overestimation in June, July and August. Regarding the seasonal variation of the GPS-TEC, the lowest values were observed during summer and it reached its maximum value during the equinox season. The IRI-2001 showed the highest value of percentage deviation compared to the IRI01-corr, NeQuick and Holt-Winter method. Therefore, the accuracy of the models was found to be approximately 95% in the Holt-Winter method, 75% in the IRI01-corr, 73% in the NeQuick and 66% in the IRI-2001 model. Hence, it can be inferred that the Holt-Winter method showed a higher performance and better estimates of the TEC compared to the IRI01-corr and NeQuick, while the IRI-2001 showed a poor predictive performance in the equatorial region over Malaysia.

Correction of Single Frequency Altimeter Measurements for Ionosphere Delay

NASA Technical Reports Server (NTRS)

Schreiner, William S.; Markin, Robert E.; Born, George H.

1997-01-01

This study is a preliminary analysis of the accuracy of various ionosphere models to correct single frequency altimeter height measurements for Ionospheric path delay. In particular, research focused on adjusting empirical and parameterized ionosphere models in the parameterized real-time ionospheric specification model (PRISM) 1.2 using total electron content (TEC) data from the global positioning system (GPS). The types of GPS data used to adjust PRISM included GPS line-of-sight (LOS) TEC data mapped to the vertical, and a grid of GPS derived TEC data in a sun-fixed longitude frame. The adjusted PRISM TEC values, as well as predictions by IRI-90, a climatotogical model, were compared to TOPEX/Poseidon (T/P) TEC measurements from the dual-frequency altimeter for a number of T/P tracks. When adjusted with GPS LOS data, the PRISM empirical model predicted TEC over 24 1 h data sets for a given local time to with in a global error of 8.60 TECU rms during a midnight centered ionosphere and 9.74 TECU rms during a noon centered ionosphere. Using GPS derived sun-fixed TEC data, the PRISM parameterized model predicted TEC within an error of 8.47 TECU rms centered at midnight and 12.83 TECU rms centered at noon. From these best results, it is clear that the proposed requirement of 3-4 TECU global rms for TOPEX/Poseidon Follow-On will be very difficult to meet, even with a substantial increase in the number of GPS ground stations, with any realizable combination of the aforementioned models or data assimilation schemes.

Calcium/calmodulin and cAMP/protein kinase-A pathways regulate sperm motility in the stallion.

PubMed

Lasko, Jodi; Schlingmann, Karen; Klocke, Ann; Mengel, Grace Ann; Turner, Regina

2012-06-01

In spite of the importance of sperm motility to fertility in the stallion, little is known about the signaling pathways that regulate motility in this species. In other mammals, calcium/calmodulin signaling and the cyclic AMP/protein kinase-A pathway are involved in sperm motility regulation. We hypothesized that these pathways also were involved in the regulation of sperm motility in the stallion. Using immunoblotting, calmodulin and the calmodulin-dependent protein kinase II β were shown to be present in stallion sperm and with indirect immunofluorescence calmodulin was localized to the acrosome and flagellar principal piece. Additionally, inhibition of either calmodulin or protein kinase-A significantly reduced sperm motility without affecting viability. Following inhibition of calmodulin, motility was not restored with agonists of the cyclic AMP/protein kinase-A pathway. These data suggest that calcium/calmodulin and cyclic AMP/protein kinase-A pathways are involved in the regulation of stallion sperm motility. The failure of cyclic AMP/protein kinase-A agonists to restore motility of calmodulin inhibited sperm suggests that both pathways may be required to support normal motility. Copyright © 2012 Elsevier B.V. All rights reserved.

Small-molecule WNK inhibition regulates cardiovascular and renal function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamada, Ken; Park, Hyi-Man; Rigel, Dean F.

The With-No-Lysine (K) (WNK) kinases play a critical role in blood pressure regulation and body fluid and electrolyte homeostasis. Herein, we introduce the first orally bioavailable pan-WNK-kinase inhibitor, WNK463, that exploits unique structural features of the WNK kinases for both affinity and kinase selectivity. In rodent models of hypertension, WNK463 affects blood pressure and body fluid and electro-lyte homeostasis, consistent with WNK-kinase-associated physiology and pathophysiology.

V-TECS Guide for Medical Assistant.

ERIC Educational Resources Information Center

South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

This V-TECS (Vocational-Technical Consortium of States) Guide is an extension or continuation of the V-TECS catalog for the occupation of medical assistant. The guide is designed to help South Carolina teachers to promote the art of learning while teaching subject matter. The guide addresses the three domains of learning: psychomotor, cognitive,…

NMobTec-EnvEdu: M-Learning System for Environmental Education

ERIC Educational Resources Information Center

Cavus, Nadire

2008-01-01

This paper introduced the implementation of a New Mobile Technologies and Environmental Education System (NMobTec-EnvEdu) designed for m-learning environments. The NMobTec-EnvEdu system has been developed to provide environmental education in a collaborative framework to undergraduate students through the Internet using mobile phones. The study…

Culture promotes transfer of thyroid epithelial cell hyperplasia and proliferation by reducing regulatory T cell numbers.

PubMed

Kayes, Timothy D; Braley-Mullen, Helen

2013-01-01

IFN-γ(-/-) NOD.H-2h4 mice develop a spontaneous autoimmune thyroid disease, thyroid epithelial cell hyperplasia and proliferation (TEC H/P) when given NaI in their water for 7+ mo. TEC H/P can be transferred to IFN-γ(-/-) SCID mice by splenocytes from mice with severe (4-5+) disease, and transfer of TEC H/P is improved when splenocytes are cultured prior to transfer. Older (9+ mo) IFN-γ(-/-) NOD.H-2h4 mice have elevated numbers of FoxP3(+) T reg cells, up to 2-fold greater than younger (2 mo) mice. During culture, the number of T reg decreases and this allows the improved transfer of TEC H/P. Co-culture with IL-2 prior to transfer prevents the decrease of T reg and improves their in vitro suppressive ability resulting in reduced TEC H/P in recipient mice. Therefore, culturing splenocytes improves transfer of TEC H/P by reducing the number of T reg and IL-2 inhibits transfer by preserving T reg number and function. Copyright © 2013 Elsevier Inc. All rights reserved.

Vertical and Lateral Electron Content in the Martian Ionosphere

NASA Astrophysics Data System (ADS)

Paetzold, M. P.; Peter, K.; Bird, M. K.; Häusler, B.; Tellmann, S.

2016-12-01

The radio-science experiment MaRS (Mars Express Radio Science) on the Mars Express spacecraft sounds the neutral atmosphere and ionosphere of Mars since 2004. Approximately 800 vertical profiles of the ionospheric electron density have been acquired until today. The vertical electron content (TEC) is easily computed from the vertical electron density profile by integrating along the altitude. The TEC is typically a fraction of a TEC unit (1E16 m^-2) and depends on the solar zenith angle. The magnitude of the TEC is however fully dominated by the electron density contained in the main layer M2. The contributions by the M1 layer below M2 or the topside is marginal. MaRS is using two radio frequencies for the sounding of the ionosphere. The directly observed differential Doppler from the two received frequencies is a measure of the lateral electron content that means along the ray path and perpendicular to the vertical electron density profile. Combining both the vertical electron density profile, the vertical TEC and the directly observed lateral TEC describes the lateral electron density distribution in the ionosphere.

A regional ionospheric TEC mapping technique over China and adjacent areas on the basis of data assimilation

NASA Astrophysics Data System (ADS)

Aa, Ercha; Huang, Wengeng; Yu, Shimei; Liu, Siqing; Shi, Liqin; Gong, Jiancun; Chen, Yanhong; Shen, Hua

2015-06-01

In this paper, a regional total electron content (TEC) mapping technique over China and adjacent areas (70°E-140°E and 15°N-55°N) is developed on the basis of a Kalman filter data assimilation scheme driven by Global Navigation Satellite Systems (GNSS) data from the Crustal Movement Observation Network of China and International GNSS Service. The regional TEC maps can be generated accordingly with the spatial and temporal resolution being 1°×1° and 5 min, respectively. The accuracy and quality of the TEC mapping technique have been validated through the comparison with GNSS observations, the International Reference Ionosphere model values, the global ionosphere maps from Center for Orbit Determination of Europe, and the Massachusetts Institute of Technology Automated Processing of GPS TEC data from Madrigal database. The verification results indicate that great systematic improvements can be obtained when data are assimilated into the background model, which demonstrates the effectiveness of this technique in providing accurate regional specification of the ionospheric TEC over China and adjacent areas.

Scaffold Protein SLP-76 Primes PLCγ1 for Activation by ITK-Mediated Phosphorylation.

PubMed

Devkota, Sujan; Joseph, Raji E; Min, Lie; Bruce Fulton, D; Andreotti, Amy H

2015-08-28

Activation of the phospholipase, PLCγ1, is critical for proper T cell signaling following antigen receptor engagement. In T cells, the Tec family kinase, interleukin-2-induced tyrosine kinase (ITK), phosphorylates PLCγ1 at tyrosine 783 (Y783) leading to activation of phospholipase function and subsequent production of the second messengers inositol 1,4,5-trisphosphate and diacylglycerol. In this work, we demonstrate that PLCγ1 can be primed for ITK-mediated phosphorylation on Y783 by a specific region of the adaptor protein, SLP-76. The SLP-76 phosphotyrosine-containing sequence, pY(173)IDR, does not conform to the canonical recognition motif for an SH2 domain yet binds with significant affinity to the C-terminal SH2 domain of PLCγ1 (SH2C). The SLP-76 pY(173) motif competes with the autoinhibited conformation surrounding the SH2C domain of PLCγ1 leading to exposure of the ITK recognition element on the PLCγ1 SH2 domain and release of the target tyrosine, Y783. These data contribute to the evolving model for the molecular events occurring early in the T cell activation process. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Year-Long Comparison of GPS TEC and Global Ionosphere-Thermosphere Models

NASA Astrophysics Data System (ADS)

Perlongo, N. J.; Ridley, A. J.; Cnossen, I.; Wu, C.

2018-02-01

The prevalence of GPS total electron content (TEC) observations has provided an opportunity for extensive global ionosphere-thermosphere model validation efforts. This study presents a year-long data-model comparison using the Global Ionosphere-Thermosphere Model (GITM) and the Thermosphere-Ionosphere-Electrodynamics General Circulation Model (TIE-GCM). For the entire year of 2010, each model was run and compared to GPS TEC observations. The results were binned according to season, latitude, local time, and magnetic local time. GITM was found to overestimate the TEC everywhere, except on the midlatitude nightside, due to high O/N2 ratios. TIE-GCM produced much less TEC and had lower O/N2 ratios and neutral wind speeds. Seasonal and regional biases in the models are discussed along with ideas for model improvements and further validation efforts.

Secular variation and fluctuation of GPS Total Electron Content over Antarctica

NASA Astrophysics Data System (ADS)

Jin, Rui; Jin, Shuanggen

2013-01-01

The total electron content (TEC) is an important parameters in the Earth's ionosphere, related to various space weather and solar activities. However, understanding of the complex ionospheric environments is still a challenge due to the lack of direct observations, particularly in the polar areas, e.g., Antarctica. Now the Global Positioning System (GPS) can be used to retrieve total electron content (TEC) from dual-frequency observations. The continuous GPS observations in Antarctica provide a good opportunity to investigate ionospheric climatology. In this paper, the long-term variations and fluctuations of TEC over Antarctica are investigated from CODE global ionospheric maps (GIM) with a resolution of 2.5°×5° every two hours since 1998. The analysis shows significant seasonal and secular variations in the GPS TEC. Furthermore, the effects of TEC fluctuations are discussed.

DFsn collaborates with Highwire to down-regulate the Wallenda/DLK kinase and restrain synaptic terminal growth

PubMed Central

Wu, Chunlai; Daniels, Richard W; DiAntonio, Aaron

2007-01-01

Background The growth of new synapses shapes the initial formation and subsequent rearrangement of neural circuitry. Genetic studies have demonstrated that the ubiquitin ligase Highwire restrains synaptic terminal growth by down-regulating the MAP kinase kinase kinase Wallenda/dual leucine zipper kinase (DLK). To investigate the mechanism of Highwire action, we have identified DFsn as a binding partner of Highwire and characterized the roles of DFsn in synapse development, synaptic transmission, and the regulation of Wallenda/DLK kinase abundance. Results We identified DFsn as an F-box protein that binds to the RING-domain ubiquitin ligase Highwire and that can localize to the Drosophila neuromuscular junction. Loss-of-function mutants for DFsn have a phenotype that is very similar to highwire mutants – there is a dramatic overgrowth of synaptic termini, with a large increase in the number of synaptic boutons and branches. In addition, synaptic transmission is impaired in DFsn mutants. Genetic interactions between DFsn and highwire mutants indicate that DFsn and Highwire collaborate to restrain synaptic terminal growth. Finally, DFsn regulates the levels of the Wallenda/DLK kinase, and wallenda is necessary for DFsn-dependent synaptic terminal overgrowth. Conclusion The F-box protein DFsn binds the ubiquitin ligase Highwire and is required to down-regulate the levels of the Wallenda/DLK kinase and restrain synaptic terminal growth. We propose that DFsn and Highwire participate in an evolutionarily conserved ubiquitin ligase complex whose substrates regulate the structure and function of synapses. PMID:17697379

Thermal Vacuum Testing of a Proto-flight Miniature Loop Heat Pipe with Two Evaporators and Two Condensers

NASA Technical Reports Server (NTRS)

Ku, Jentung; Ottenstein, Laura

2011-01-01

This paper describes thermal vacuum testing of a proto-flight miniature loop heat pipe (MLHP) with two evaporators and two condensers designed for future small systems applications requiring low mass, low power and compactness. Each evaporator contains a wick with an outer diameter of 6.35 mm, and each has its own integral compensation chamber (CC). Miniaturization of the loop components reduces the volume and mass of the thermal system. Multiple evaporators provide flexibility for placement of instruments that need to be maintained at the same temperature, and facilitate heat load sharing among instruments, reducing the auxiliary heater power requirement. A flow regulator is used to regulate heat dissipations between the two condensers, allowing flexible placement of radiators on the spacecraft. A thermoelectric converter (TEC) is attached to each CC for control of the operating temperature and enhancement of start-up success. Tests performed include start-up, power cycle, sink temperature cycle, high power and low power operation, heat load sharing, and operating temperature control. The proto-flight MLHP demonstrated excellent performance in the thermal vacuum test. The loop started successfully and operated stably under various evaporator heat loads and condenser sink temperatures. The TECs were able to maintain the loop operating temperature within b1K of the desired set point temperature at all power levels and all sink temperatures. The un-powered evaporator would automatically share heat from the other powered evaporator. The flow regulator was able to regulate the heat dissipation among the radiators and prevent vapor from flowing into the liquid line.

Comparison of Plateletpheresis on the Fenwal Amicus and Fresenius Com.Tec Cell Separators.

PubMed

Altuntas, Fevzi; Sari, Ismail; Kocyigit, Ismail; Kaynar, Leylagul; Hacioglu, Sibel; Ozturk, Ahmet; Oztekin, Mehmet; Solmaz, Musa; Eser, Bulent; Cetin, Mustafa; Unal, Ali

2008-01-01

SUMMARY: BACKGROUND: A variety of apheresis devices are now available on the market for plateletapheresis. We compared two apheresis instruments (Fenwal Amicus and Fresenius COM.TEC) with regard to processing time, platelet (PLT) yield and efficiency, and white blood cell (WBC) content. MATERIAL AND METHODS: Donors undergoing plateletpheresis were randomly separated into two groups (either the Amicus or the COM.TEC cell separator). RESULTS: In the pre-apheresis setting, 32 plateletpheresis procedures performed with each instrument revealed no significant differences in donors' sex, age, weight, height and total blood volume between the two groups. However, the pre-apheresis PLT count was higher with the COM.TEC than with the Amicus (198 × 10(3)/μl vs. 223 × 10(3)/μl; p = 0.035). The blood volume processed to reach a target PLT yield of ≥3.3 × 10(11) was higher in the COM.TEC compared to the Amicus (3,481 vs. 2,850 ml; p < 0.001). The median separation time was also significantly longer in the COM.TEC than in the Amicus (61 vs. 44 min; p < 0.001). 91 and 88% of the PLT products collected with the Amicus and the COM.TEC, respectively, had a PLT count of >3.3 × 10(11) (p = 0.325). All products obtained with both instruments had WBC counts lower than 5 ↔ 10(6), as required. There was no statistical difference with regard to collection efficiency between the devices (55 ± 15 vs. 57 ± 15%; p = 0.477). However, the collection rate was significantly higher with the Amicus compared to the COM.TEC instrument (0.077 ± 0.012 × 10(11) vs. 0.057 ± 0.008 × 10(11) PLT/min; p < 0.001). CONCLUSION: Both instruments collected platelets efficiently. Additionally, consistent leukoreduction was obtained with both instruments; however, compared with the COM.TEC instrument, the Amicus reached the PLT target yield more quickly.

The Ste20 Family Kinases MAP4K4, MINK1, and TNIK Converge to Regulate Stress-Induced JNK Signaling in Neurons.

PubMed

Larhammar, Martin; Huntwork-Rodriguez, Sarah; Rudhard, York; Sengupta-Ghosh, Arundhati; Lewcock, Joseph W

2017-11-15

The c-Jun- N -terminal kinase (JNK) signaling pathway regulates nervous system development, axon regeneration, and neuronal degeneration after acute injury or in chronic neurodegenerative disease. Dual leucine zipper kinase (DLK) is required for stress-induced JNK signaling in neurons, yet the factors that initiate DLK/JNK pathway activity remain poorly defined. In the present study, we identify the Ste20 kinases MAP4K4, misshapen-like kinase 1 (MINK1 or MAP4K6) and TNIK Traf2- and Nck-interacting kinase (TNIK or MAP4K7), as upstream regulators of DLK/JNK signaling in neurons. Using a trophic factor withdrawal-based model of neurodegeneration in both male and female embryonic mouse dorsal root ganglion neurons, we show that MAP4K4, MINK1, and TNIK act redundantly to regulate DLK activation and downstream JNK-dependent phosphorylation of c-Jun in response to stress. Targeting MAP4K4, MINK1, and TNIK, but not any of these kinases individually, is sufficient to protect neurons potently from degeneration. Pharmacological inhibition of MAP4Ks blocks stabilization and phosphorylation of DLK within axons and subsequent retrograde translocation of the JNK signaling complex to the nucleus. These results position MAP4Ks as important regulators of the DLK/JNK signaling pathway. SIGNIFICANCE STATEMENT Neuronal degeneration occurs in disparate circumstances: during development to refine neuronal connections, after injury to clear damaged neurons, or pathologically during disease. The dual leucine zipper kinase (DLK)/c-Jun- N -terminal kinase (JNK) pathway represents a conserved regulator of neuronal injury signaling that drives both neurodegeneration and axon regeneration, yet little is known about the factors that initiate DLK activity. Here, we uncover a novel role for a subfamily of MAP4 kinases consisting of MAP4K4, Traf2- and Nck-interacting kinase (TNIK or MAP4K7), and misshapen-like kinase 1 (MINK1 or MAP4K6) in regulating DLK/JNK signaling in neurons. Inhibition of these MAP4Ks blocks stress-induced retrograde JNK signaling and protects from neurodegeneration, suggesting that these kinases may represent attractive therapeutic targets. Copyright © 2017 the authors 0270-6474/17/3711074-11$15.00/0.

Thermionic Energy Conversion (TEC) topping thermoelectrics

NASA Technical Reports Server (NTRS)

Morris, J. F.

1981-01-01

Performance expectations for thermionic and thermoelectric energy conversion systems are reviewed. It is noted that internal radiation effects diminish thermoelectric figures of merit significantly at 1000 K and substantially at 2000 K; the effective thermal conductivity contribution of intrathermoelectric radiative dissipation increases with the third power of temperature. It is argued that a consideration of thermoelectric power generation with high temperature heat sources should include utilization of thermionic energy conversion (TEC) topping thermoelectrics. However TEC alone or TEC topping more efficient conversion systems like steam or gas turbines, combined cycles, or Stirling engines would be more desirable generally.

Dust Storm Signatures in Global Ionosphere Map of GPS Total Electron Content

NASA Astrophysics Data System (ADS)

Lin, Fang-Tse; Shih, Ai-Ling; Liu, Jann-Yenq; Kuo, Cheng-Ling; Lin, Tang-Huang; Lien, Wei-Hung

2016-04-01

In this paper both MODIS data and GIM (global ionosphere map) TEC (total electron content) as well as numerical simulations are used to study ionospheric dust storm effects in May 2008. The aerosol optical depth (AOD) and the LTT (latitude-time-TEC) along the Sahara longitude simultaneously reach their maximum values on 28 May 2008. The LLT (latitude-longitude-TEC) map specifically and significantly increases over the Sahara region on 28 May 2008. The simulation suggests that the dust storm may change the atmospheric conductivity, which in turn modifies the GIM TEC over the Sahara area.

Comparison of GPS-TEC measurements with NeQuick2 and IRI model predictions in the low latitude East African region during varying solar activity period (1998 and 2008-2015)

NASA Astrophysics Data System (ADS)

Mengistu, E.; Damtie, B.; Moldwin, M. B.; Nigussie, M.

2018-03-01

This paper examines the performances of NeQuick2, the latest available IRI-2016, IRI-2012 and IRI-2007 models in describing the monthly and seasonal mean total electron content (TEC) over the East African region. This is to gain insight into the success of the various model types and versions at characterizing the ionosphere within the equatorial ionization anomaly. TEC derived from five Global Positioning System (GPS) receivers installed at Addis Ababa (ADD, 5.33°N, 111.99°E Geog.), Asab (ASAB, 8.67°N, 116.44°E Geog.), Ambo (ABOO, 5.43°N, 111.05°E Geog.), Nairobi (RCMN, -4.48°N, 108.46°E Geog.) and Nazret (NAZR, 4.78°N, 112.43°E Geog.), are compared with the corresponding values computed using those models during varying solar activity period (1998 and 2008-2015). We found that different models describe the equatorial and anomaly region ionosphere best depending on solar cycle, season and geomagnetic activity levels. Our results show that IRI-2016 is the best model (compared to others in terms of discrepancy range) in estimating the monthly mean GPS-TEC at NAZR, ADD and RCMN stations except at ADD during 2008 and 2012. It is also found that IRI-2012 is the best model in estimating the monthly mean TEC at ABOO station in 2014. IRI show better agreement with observations during June solstice for all the years studied at ADD except in 2012 where NeQuick2 better performs. At NAZR, NeQuick2 better performs in estimating seasonal mean GPS-TEC during 2011, while IRI models are best during 2008-2009. Both NeQuick2 and IRI models underestimate measured TEC for all the seasons at ADD in 2010 but overestimate at NAZR in 2009 and RCMN in 2008. The periodic variations of experimental and modeled TEC have been compared with solar and geomagnetic indices at ABOO and ASAB in 2014 and results indicate that the F10.7 and sunspot number as indices of solar activity seriously affects the TEC variations with periods of 16-32 days followed by the geomagnetic activity on shorter timescales (roughly periods of less than 16 days). In this case, NeQuick2 derived TEC shows better agreement with a long term period variations of GPS-TEC, while IRI-2016 and IRI-2007 show better agreement with observations during short term periodic variations. This indicates that the dependence of NeQuick2 derived TEC on F10.7 is seasonal. Hence, we suggest that representation of geomagnetic activity indices is required for better performance over the low latitude region.

Differential Roles of the Glycogen-Binding Domains of β Subunits in Regulation of the Snf1 Kinase Complex▿

PubMed Central

Mangat, Simmanjeet; Chandrashekarappa, Dakshayini; McCartney, Rhonda R.; Elbing, Karin; Schmidt, Martin C.

2010-01-01

Members of the AMP-activated protein kinase family, including the Snf1 kinase of Saccharomyces cerevisiae, are activated under conditions of nutrient stress. AMP-activated protein kinases are heterotrimeric complexes composed of a catalytic α subunit and regulatory β and γ subunits. In this study, the role of the β subunits in the regulation of Snf1 activity was examined. Yeasts express three isoforms of the AMP-activated protein kinase consisting of Snf1 (α), Snf4 (γ), and one of three alternative β subunits, either Sip1, Sip2, or Gal83. The Gal83 isoform of the Snf1 complex is the most abundant and was analyzed in the greatest detail. All three β subunits contain a conserved domain referred to as the glycogen-binding domain. The deletion of this domain from Gal83 results in a deregulation of the Snf1 kinase, as judged by a constitutive activity independent of glucose availability. In contrast, the deletion of this homologous domain from the Sip1 and Sip2 subunits had little effect on Snf1 kinase regulation. Therefore, the different Snf1 kinase isoforms are regulated through distinct mechanisms, which may contribute to their specialized roles in different stress response pathways. In addition, the β subunits are subjected to phosphorylation. The responsible kinases were identified as being Snf1 and casein kinase II. The significance of the phosphorylation is unclear since the deletion of the region containing the phosphorylation sites in Gal83 had little effect on the regulation of Snf1 in response to glucose limitation. PMID:19897735

Differential roles of the glycogen-binding domains of beta subunits in regulation of the Snf1 kinase complex.

PubMed

Mangat, Simmanjeet; Chandrashekarappa, Dakshayini; McCartney, Rhonda R; Elbing, Karin; Schmidt, Martin C

2010-01-01

Members of the AMP-activated protein kinase family, including the Snf1 kinase of Saccharomyces cerevisiae, are activated under conditions of nutrient stress. AMP-activated protein kinases are heterotrimeric complexes composed of a catalytic alpha subunit and regulatory beta and gamma subunits. In this study, the role of the beta subunits in the regulation of Snf1 activity was examined. Yeasts express three isoforms of the AMP-activated protein kinase consisting of Snf1 (alpha), Snf4 (gamma), and one of three alternative beta subunits, either Sip1, Sip2, or Gal83. The Gal83 isoform of the Snf1 complex is the most abundant and was analyzed in the greatest detail. All three beta subunits contain a conserved domain referred to as the glycogen-binding domain. The deletion of this domain from Gal83 results in a deregulation of the Snf1 kinase, as judged by a constitutive activity independent of glucose availability. In contrast, the deletion of this homologous domain from the Sip1 and Sip2 subunits had little effect on Snf1 kinase regulation. Therefore, the different Snf1 kinase isoforms are regulated through distinct mechanisms, which may contribute to their specialized roles in different stress response pathways. In addition, the beta subunits are subjected to phosphorylation. The responsible kinases were identified as being Snf1 and casein kinase II. The significance of the phosphorylation is unclear since the deletion of the region containing the phosphorylation sites in Gal83 had little effect on the regulation of Snf1 in response to glucose limitation.

Risk-adapted, treosulfan-based therapy with auto- and allo-SCT for relapsed/refractory aggressive NHL: a prospective phase-II trial.

PubMed

Koenigsmann, M; Casper, J; Kahl, C; Basara, N; Sayer, H G; Behre, G; Theurich, S; Christopeit, M; Mohren, M; Reichle, A; Metzner, B; Ganser, A; Stadler, M; Uharek, L; Balleisen, L; Hinke, A; Hinke, R; Niederwieser, D

2014-03-01

Since the outcome of relapsed/refractory aggressive non-Hodgkin's lymphoma (NHL) is highly variable, a risk-adapted treatment approach was evaluated. After two cycles of DHAP, patients received high-dose treosulfan/etoposide/carboplatinum (TEC) and autologous stem cell rescue. After TEC, low-risk patients with late relapse (>1 year after first CR who achieved CR after DHAP received no further treatment. Patients with late relapse who achieved CR or PR only after TEC underwent a second cycle of TEC. High-risk patients with early relapse/refractory disease received treosulfan/fludarabine followed by allogeneic transplantation. Rituximab was added in patients with B-cell lymphoma (86%). At entry, 36% of all 57 patients had refractory disease, 32% early and 32% late relapse. During DHAP treatment, progression occurred in 32% of patients. Of 33 patients who received TEC, 5 received second TEC and 15 allogeneic transplantation. Main toxicity after TEC was oral mucositis (CTC grades 3 and 4 in 50% and 13%, respectively). In total, 42% patients achieved CR. Median OS was 21.4 months for all patients and 32.6 for those who underwent allogeneic transplantation. International prognostic index (IPI) at study entry was highly discriminative at predicting OS (P<0.0001). Risk-adapted, treosulfan-based therapy with auto- and allo-SCT is feasible. Long-term survival is possible with allogeneic transplantation.

FSP1+ fibroblast subpopulation is essential for the maintenance and regeneration of medullary thymic epithelial cells

PubMed Central

Sun, Lina; Sun, Chenming; Liang, Zhanfeng; Li, Hongran; Chen, Lin; Luo, Haiying; Zhang, Hongmei; Ding, Pengbo; Sun, Xiaoning; Qin, Zhihai; Zhao, Yong

2015-01-01

Thymic epithelial cells (TECs) form a 3-dimentional network supporting thymocyte development and maturation. Besides epithelium and thymocytes, heterogeneous fibroblasts are essential components in maintaining thymic microenvironments. However, thymic fibroblast characteristics, development and function remain to be determined. We herein found that thymic non-hematopoietic CD45-FSP1+ cells represent a unique Fibroblast specific protein 1 (FSP1)—fibroblast-derived cell subset. Deletion of these cells in FSP1-TK transgenic mice caused thymus atrophy due to the loss of TECs, especially mature medullary TECs (MHCIIhigh, CD80+ and Aire+). In a cyclophosphamide-induced thymus injury and regeneration model, lack of non-hematopoietic CD45-FSP1+ fibroblast subpopulation significantly delayed thymus regeneration. In fact, thymic FSP1+ fibroblasts released more IL-6, FGF7 and FSP1 in the culture medium than their FSP1- counterparts. Further experiments showed that the FSP1 protein could directly enhance the proliferation and maturation of TECs in the in vitro culture systems. FSP1 knockout mice had significantly smaller thymus size and less TECs than their control. Collectively, our studies reveal that thymic CD45-FSP1+ cells are a subpopulation of fibroblasts, which is crucial for the maintenance and regeneration of TECs especially medullary TECs through providing IL-6, FGF7 and FSP1. PMID:26445893

Response of data-driven artificial neural network-based TEC models to neutral wind for different locations, seasons, and solar activity levels from the Indian longitude sector

NASA Astrophysics Data System (ADS)

Sur, D.; Haldar, S.; Ray, S.; Paul, A.

2017-07-01

The perturbations imposed on transionospheric signals by the ionosphere are a major concern for navigation. The dynamic nature of the ionosphere in the low-latitude equatorial region and the Indian longitude sector has some specific characteristics such as sharp temporal and latitudinal variation of total electron content (TEC). TEC in the Indian longitude sector also undergoes seasonal variations. The large magnitude and sharp variation of TEC cause large and variable range errors for satellite-based navigation system such as Global Positioning System (GPS) throughout the day. For accurate navigation using satellite-based augmentation systems, proper prediction of TEC under certain geophysical conditions is necessary in the equatorial region. It has been reported in the literature that prediction accuracy of TEC has been improved using measured data-driven artificial neural network (ANN)-based vertical TEC (VTEC) models, compared to standard ionospheric models. A set of observations carried out in the Indian longitude sector have been reported in this paper in order to find the amount of improvement in performance accuracy of an ANN-based VTEC model after incorporation of neutral wind as model input. The variations of this improvement in prediction accuracy with respect to latitude, longitude, season, and solar activity have also been reported in this paper.

Thymus medulla under construction: Time and space oddities.

PubMed

Alves, Nuno L; Ribeiro, Ana R

2016-04-01

The development of effective T-cell-based immunotherapies to treat infection, cancer, and autoimmunity should incorporate the ground rules that control differentiation of T cells in the thymus. Within the thymus, thymic epithelial cells (TECs) provide microenvironments supportive of the generation and selection of T cells that are responsive to pathogen-derived antigens, and yet tolerant to self-determinants. Defects in TEC differentiation cause syndromes that range from immunodeficiency to autoimmunity, which makes the study of TECs of fundamental and clinical importance to comprehend how immunity and tolerance are balanced. Critical to tolerance induction are medullary thymic epithelial cells (mTECs), which purge autoreactive T cells, or redirect them to a regulatory T-cell lineage. In this issue of the European Journal of Immunology, studies by Baik et al. and Mayer et al. [Eur. J. Immunol. 2016. 46: XXXX-XXXX and 46: XXXX-XXXX]) document novel spatial-temporal singularities in the lineage specification and maintenance of mTECs. While Baik et al. define a developmental checkpoint during mTEC specification in the embryo, Mayer et al. reveal that the generation and maintenance of the adult mTEC compartment is temporally controlled in vivo. The two reports described new developmentally related, but temporally distinct principles that underlie the homeostasis of the thymic medulla across life. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A nonlinear background removal method for seismo-ionospheric anomaly analysis under a complex solar activity scenario: A case study of the M9.0 Tohoku earthquake

NASA Astrophysics Data System (ADS)

He, Liming; Wu, Lixin; Pulinets, Sergey; Liu, Shanjun; Yang, Fan

2012-07-01

A precise determination of ionospheric total electron content (TEC) anomaly variations that are likely associated with large earthquakes as observed by global positioning system (GPS) requires the elimination of the ionospheric effect from irregular solar electromagnetic radiation. In particular, revealing the seismo-ionospheric anomalies when earthquakes occurred during periods of high solar activity is of utmost importance. To overcome this constraint, a multiresolution time series processing technique based on wavelet transform applicable to global ionosphere map (GIM) TEC data was used to remove the nonlinear effect from solar radiation for the earthquake that struck Tohoku, Japan, on 11 March, 2011. As a result, it was found that the extracted TEC have a good correlation with the measured solar extreme ultraviolet flux in 26-34 nm (EUV26-34) and the 10.7 cm solar radio flux (F10.7). After removing the influence of solar radiation origin in GIM TEC, the analysis results show that the TEC around the forthcoming epicenter and its conjugate were significantly enhanced in the afternoon period of 8 March 2011, 3 days before the earthquake. The spatial distributions of the TEC anomalous and extreme enhancements indicate that the earthquake preparation process had brought with a TEC anomaly area of size approximately 1650 and 5700 km in the latitudinal and longitudinal directions, respectively.

StarTEC: A Technology Project in Education Reform.

ERIC Educational Resources Information Center

Hawley, Helen; Benavides, Otto; Duffy, Sharon; Georgi, David; Guay, Diane; Redmond, Pamela; Richmond, James

StarTEC (Staff, Teacher, and Restructured Technology Education Consortium) was a 3-year technology catalyst program funded by the U.S. Department of Education, and continued for a third year to complete its activities. The goal of StarTEC was to ensure that all teachers prepared by partners in the Consortium would meet the new California standard…

Mitotic Regulation by NEK Kinase Networks

PubMed Central

Fry, Andrew M.; Bayliss, Richard; Roig, Joan

2017-01-01

Genetic studies in yeast and Drosophila led to identification of cyclin-dependent kinases (CDKs), Polo-like kinases (PLKs) and Aurora kinases as essential regulators of mitosis. These enzymes have since been found in the majority of eukaryotes and their cell cycle-related functions characterized in great detail. However, genetic studies in another fungal species, Aspergillus nidulans, identified a distinct family of protein kinases, the NEKs, that are also widely conserved and have key roles in the cell cycle, but which remain less well studied. Nevertheless, it is now clear that multiple NEK family members act in networks to regulate specific events of mitosis, including centrosome separation, spindle assembly and cytokinesis. Here, we describe our current understanding of how the NEK kinases contribute to these processes, particularly through targeted phosphorylation of proteins associated with the microtubule cytoskeleton. We also present the latest findings on molecular events that control the activation state of the NEKs and how these are revealing novel modes of enzymatic regulation relevant not only to other kinases but also to pathological mechanisms of disease. PMID:29250521

STAT3 activation in pressure-overloaded feline myocardium: role for integrins and the tyrosine kinase BMX.

PubMed

Willey, Christopher D; Palanisamy, Arun P; Johnston, Rebecca K; Mani, Santhosh K; Shiraishi, Hirokazu; Tuxworth, William J; Zile, Michael R; Balasubramanian, Sundaravadivel; Kuppuswamy, Dhandapani

2008-06-27

Growth, survival and cytoskeletal rearrangement of cardiomyocytes are critical for cardiac hypertrophy. Signal transducer and activator of transcription-3 (STAT3) activation is an important cardioprotective factor associated with cardiac hypertrophy. Although STAT3 activation has been reported via signaling through Janus Kinase 2 (JAK2) in several cardiac models of hypertrophy, the importance of other nonreceptor tyrosine kinases (NTKs) has not been explored. Utilizing an in vivo feline right ventricular pressure-overload (RVPO) model of hypertrophy, we demonstrate that in 48 h pressure-overload (PO) myocardium, STAT3 becomes phosphorylated and redistributed to detergent-insoluble fractions with no accompanying JAK2 activation. PO also caused increased levels of phosphorylated STAT3 in both cytoplasmic and nuclear fractions. To investigate the role of other NTKs, we used our established in vitro cell culture model of hypertrophy where adult feline cardiomyocytes are embedded three-dimensionally (3D) in type-I collagen and stimulated with an integrin binding peptide containing an Arg-Gly-Asp (RGD) motif that we have previously shown to recapitulate the focal adhesion complex (FAC) formation of 48 h RVPO. RGD stimulation of adult cardiomyocytes in vitro caused both STAT3 redistribution and activation that were accompanied by the activation and redistribution of c-Src and the TEC family kinase, BMX, but not JAK2. However, infection with dominant negative c-Src adenovirus was unable to block RGD-stimulated changes on either STAT3 or BMX. Further analysis in vivo in 48 h PO myocardium showed the presence of both STAT3 and BMX in the detergent-insoluble fraction with their complex formation and phosphorylation. Therefore, these studies indicate a novel mechanism of BMX-mediated STAT3 activation within a PO model of cardiac hypertrophy that might contribute to cardiomyocyte growth and survival.

p21-activated kinases in cancer.

PubMed

Kumar, Rakesh; Gururaj, Anupama E; Barnes, Christopher J

2006-06-01

The pivotal role of kinases in signal transduction and cellular regulation has lent them considerable appeal as pharmacological targets across a broad spectrum of cancers. p21-activated kinases (Paks) are serine/threonine kinases that function as downstream nodes for various oncogenic signalling pathways. Paks are well-known regulators of cytoskeletal remodelling and cell motility, but have recently also been shown to promote cell proliferation, regulate apoptosis and accelerate mitotic abnormalities, which results in tumour formation and cell invasiveness. Alterations in Pak expression have been detected in human tumours, which makes them an attractive new therapeutic target.

Autoregulation of kinase dephosphorylation by ATP binding in AGC protein kinases.

PubMed

Chan, Tung O; Pascal, John M; Armen, Roger S; Rodeck, Ulrich

2012-02-01

AGC kinases, including the three Akt (protein kinase B) isoforms, protein kinase A (PKA) and all protein kinase C (PKC) isoforms, require activation loop phosphorylation (threonine 308 in Akt1) as well as phosphorylation of a C-terminal residue (serine 473 in Akt1) for catalytic activity and phosphorylation of downstream targets. Conversely, phosphatases reverse these phosphorylations. Virtually all cellular processes are affected by AGC kinases, a circumstance that has led to intense scrutiny of the molecular mechanisms that regulate phosphorylation of these kinases. Here, we review a new layer of control of phosphorylation in Akt, PKA and PKC pointing to ATP binding pocket occupancy as a means to decelerate dephosphorylation of these and, potentially, other kinases. This additional level of kinase regulation opens the door to search for new functional motifs for the rational design of non- ATP-competitive kinase inhibitors that discriminate within and between protein kinase families.

Autoregulation of kinase dephosphorylation by ATP binding to AGC protein kinases

PubMed Central

Pascal, John M; Armen, Roger S

2012-01-01

AGC kinases, including the three Akt (protein kinase B) isoforms, protein kinase A (PKA) and all protein kinase C (PKC) isoforms, require activation loop phosphorylation (threonine 308 in Akt1) as well as phosphorylation of a C-terminal residue (serine 473 in Akt1) for catalytic activity and phosphorylation of downstream targets. Conversely, phosphatases reverse these phosphorylations. Virtually all cellular processes are affected by AGC kinases, a circumstance that has led to intense scrutiny of the molecular mechanisms that regulate phosphorylation of these kinases. Here, we review a new layer of control of phosphorylation in Akt, PKA and PKC pointing to ATP binding pocket occupancy as a means to decelerate dephosphorylation of these and, potentially, other kinases. This additional level of kinase regulation opens the door to search for new functional motifs for the rational design of non-ATP-competitive kinase inhibitors that discriminate within and between protein kinase families. PMID:22262182

Temperature-assisted solute focusing with sequential trap/release zones in isocratic and gradient capillary liquid chromatography: Simulation and experiment

PubMed Central

Groskreutz, Stephen R.; Weber, Stephen G.

2016-01-01

In this work we characterize the development of a method to enhance temperature-assisted on-column solute focusing (TASF) called two-stage TASF. A new instrument was built to implement two-stage TASF consisting of a linear array of three independent, electronically controlled Peltier devices (thermoelectric coolers, TECs). Samples are loaded onto the chromatographic column with the first two TECs, TEC A and TEC B, cold. In the two-stage TASF approach TECs A and B are cooled during injection. TEC A is heated following sample loading. At some time following TEC A’s temperature rise, TEC B’s temperature is increased from the focusing temperature to a temperature matching that of TEC A. Injection bands are focused twice on-column, first on the initial TEC, e.g. single-stage TASF, then refocused on the second, cold TEC. Our goal is to understand the two-stage TASF approach in detail. We have developed a simple yet powerful digital simulation procedure to model the effect of changing temperature in the two focusing zones on retention, band shape and band spreading. The simulation can predict experimental chromatograms resulting from spatial and temporal temperature programs in combination with isocratic and solvent gradient elution. To assess the two-stage TASF method and the accuracy of the simulation well characterized solutes are needed. Thus, retention factors were measured at six temperatures (25–75 °C) at each of twelve mobile phases compositions (0.05–0.60 acetonitrile/water) for homologs of n-alkyl hydroxylbenzoate esters and n-alkyl p-hydroxyphenones. Simulations accurately reflect experimental results in showing that the two-stage approach improves separation quality. For example, two-stage TASF increased sensitivity for a low retention solute by a factor of 2.2 relative to single-stage TASF and 8.8 relative to isothermal conditions using isocratic elution. Gradient elution results for two-stage TASF were more encouraging. Application of two-stage TASF increased peak height for the least retained solute in the test mixture by a factor of 3.2 relative to single-stage TASF and 22.3 compared to isothermal conditions for an injection four-times the column volume. TASF improved resolution and increased peak capacity; for a 12-minute separation peak capacity increased from 75 under isothermal conditions to 146 using single-stage TASF, and 185 for two-stage TASF. PMID:27836226

Comparison of double dose plateletpheresis on the Fenwal Amicus, Fresenius COM.TEC and Trima Accel cell separators.

PubMed

Keklik, Muzaffer; Eser, Bulent; Kaynar, Leylagul; Solmaz, Musa; Ozturk, Ahmet; Yay, Mehmet; Birekul, Ayse; Oztekin, Mehmet; Sivgin, Serdar; Cetin, Mustafa; Unal, Ali

2014-10-01

A variety of apheresis instruments are now available on the market for double dose plateletpheresis. We compared three apheresis devices (Fenwal Amicus, Fresenius COM.TEC and Trima Accel) with regard to processing time, platelet (PLT) yield, collection efficiency (CE) and collection rate (CR). The single-needle or double-needle double plateletpheresis procedures of the three instruments were compared in a retrospective, randomized study in 135 donors. In the pre-apheresis setting, 45 double plateletpheresis procedures performed with each instrument revealed no significant differences in donor's age, sex, weight, hemoglobin, white blood cell and PLT count between three groups. The blood volume processed to reach a target PLT yield of ≥ 6 × 10(11) was higher in the COM.TEC compared with the Amicus and Trima (4394 vs. 3780 and 3340 ml, respectively; p < 0.001). Also there was a significantly higher median volume of ACD used in collections on the COM.TEC compared with the Amicus and Trima (426 vs. 387 and 329 ml, respectively; p < 0.001). There was a significantly higher median time needed for the procedures on the COM.TEC compared with the Amicus and Trima (66 vs. 62 and 63 min, respectively; p = 0.024). The CE was significantly higher with the Trima compared with the Amicus and COM.TEC (83.57 ± 17.19 vs. 66.71 ± 3.47 and 58.79 ± 5.14%, respectively; p < 0.001). Also, there was a significantly higher product volume on the Trima compared with the Amicus and COM.TEC (395.56 vs. 363.11 and 386.4 ml, respectively; p = 0.008). Additionally, the CR was significantly lower with the COM.TEC compared with the Amicus and Trima (0.092 ± 0.011 vs. 0.099 ± 0.013 and 0.097 ± 0.013 plt × 10(11)/min, respectively; p = 0.039). There was no significant differences in PLT yield between the three groups (p = 0.636). Trima single-needle device collected double dose platelets more efficiently than Amicus and COM.TEC double-needle devices. Blood volume processed, ACD-A volume, and median separation time was significantly higher with the COM.TEC. Also, the CR was significantly lower with the COM.TEC. Copyright © 2014 Elsevier Ltd. All rights reserved.

Temperature-assisted solute focusing with sequential trap/release zones in isocratic and gradient capillary liquid chromatography: Simulation and experiment.

PubMed

Groskreutz, Stephen R; Weber, Stephen G

2016-11-25

In this work we characterize the development of a method to enhance temperature-assisted on-column solute focusing (TASF) called two-stage TASF. A new instrument was built to implement two-stage TASF consisting of a linear array of three independent, electronically controlled Peltier devices (thermoelectric coolers, TECs). Samples are loaded onto the chromatographic column with the first two TECs, TEC A and TEC B, cold. In the two-stage TASF approach TECs A and B are cooled during injection. TEC A is heated following sample loading. At some time following TEC A's temperature rise, TEC B's temperature is increased from the focusing temperature to a temperature matching that of TEC A. Injection bands are focused twice on-column, first on the initial TEC, e.g. single-stage TASF, then refocused on the second, cold TEC. Our goal is to understand the two-stage TASF approach in detail. We have developed a simple yet powerful digital simulation procedure to model the effect of changing temperature in the two focusing zones on retention, band shape and band spreading. The simulation can predict experimental chromatograms resulting from spatial and temporal temperature programs in combination with isocratic and solvent gradient elution. To assess the two-stage TASF method and the accuracy of the simulation well characterized solutes are needed. Thus, retention factors were measured at six temperatures (25-75°C) at each of twelve mobile phases compositions (0.05-0.60 acetonitrile/water) for homologs of n-alkyl hydroxylbenzoate esters and n-alkyl p-hydroxyphenones. Simulations accurately reflect experimental results in showing that the two-stage approach improves separation quality. For example, two-stage TASF increased sensitivity for a low retention solute by a factor of 2.2 relative to single-stage TASF and 8.8 relative to isothermal conditions using isocratic elution. Gradient elution results for two-stage TASF were more encouraging. Application of two-stage TASF increased peak height for the least retained solute in the test mixture by a factor of 3.2 relative to single-stage TASF and 22.3 compared to isothermal conditions for an injection four-times the column volume. TASF improved resolution and increased peak capacity; for a 12-min separation peak capacity increased from 75 under isothermal conditions to 146 using single-stage TASF, and 185 for two-stage TASF. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison of Borate Bioactive Glass and Calcium Sulfate as Implants for the Local Delivery of Teicoplanin in the Treatment of Methicillin-Resistant Staphylococcus aureus-Induced Osteomyelitis in a Rabbit Model

PubMed Central

Jia, Wei-Tao; Fu, Qiang; Huang, Wen-Hai

2015-01-01

There is growing interest in biomaterials that can cure bone infection and also regenerate bone. In this study, two groups of implants composed of 10% (wt/wt) teicoplanin (TEC)-loaded borate bioactive glass (designated TBG) or calcium sulfate (TCS) were created and evaluated for their ability to release TEC in vitro and to cure methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis in a rabbit model. When immersed in phosphate-buffered saline (PBS), both groups of implants provided a sustained release of TEC at a therapeutic level for up to 3 to 4 weeks while they were gradually degraded and converted to hydroxyapatite. The TBG implants showed a longer duration of TEC release and better retention of strength as a function of immersion time in PBS. Infected rabbit tibiae were treated by debridement, followed by implantation of TBG or TCS pellets or intravenous injection with TEC, or were left untreated. Evaluation at 6 weeks postimplantation showed that the animals implanted with TBG or TCS pellets had significantly lower radiological and histological scores, lower rates of MRSA-positive cultures, and lower bacterial loads than those preoperatively and those of animals treated intravenously. The level of bone regeneration was also higher in the defects treated with the TBG pellets. The results showed that local TEC delivery was more effective than intravenous administration for the treatment of MRSA-induced osteomyelitis. Borate glass has the advantages of better mechanical strength, more desirable kinetics of release of TEC, and a higher osteogenic capacity and thus could be an effective alternative to calcium sulfate for local delivery of TEC. PMID:26416858

Comparison of Borate Bioactive Glass and Calcium Sulfate as Implants for the Local Delivery of Teicoplanin in the Treatment of Methicillin-Resistant Staphylococcus aureus-Induced Osteomyelitis in a Rabbit Model.

PubMed

Jia, Wei-Tao; Fu, Qiang; Huang, Wen-Hai; Zhang, Chang-Qing; Rahaman, Mohamed N

2015-12-01

There is growing interest in biomaterials that can cure bone infection and also regenerate bone. In this study, two groups of implants composed of 10% (wt/wt) teicoplanin (TEC)-loaded borate bioactive glass (designated TBG) or calcium sulfate (TCS) were created and evaluated for their ability to release TEC in vitro and to cure methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis in a rabbit model. When immersed in phosphate-buffered saline (PBS), both groups of implants provided a sustained release of TEC at a therapeutic level for up to 3 to 4 weeks while they were gradually degraded and converted to hydroxyapatite. The TBG implants showed a longer duration of TEC release and better retention of strength as a function of immersion time in PBS. Infected rabbit tibiae were treated by debridement, followed by implantation of TBG or TCS pellets or intravenous injection with TEC, or were left untreated. Evaluation at 6 weeks postimplantation showed that the animals implanted with TBG or TCS pellets had significantly lower radiological and histological scores, lower rates of MRSA-positive cultures, and lower bacterial loads than those preoperatively and those of animals treated intravenously. The level of bone regeneration was also higher in the defects treated with the TBG pellets. The results showed that local TEC delivery was more effective than intravenous administration for the treatment of MRSA-induced osteomyelitis. Borate glass has the advantages of better mechanical strength, more desirable kinetics of release of TEC, and a higher osteogenic capacity and thus could be an effective alternative to calcium sulfate for local delivery of TEC. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

GNSS Derived Ionospheric TEC Observed Through Different TEC Calibration Techniques in the Brazilian Sector

NASA Astrophysics Data System (ADS)

Becker-Guedes, F.; Carmo, C. S.; Camargo, P. O.; Monico, J. F. G.; Nicoli Candido, C. M.

2017-12-01

Global Navigation Satellite System (GNSS) is becoming a reliable tool for use in air navigation systems. Its use as the main technology for determination of airplanes positioning has various economic and logistic benefits but it depends strongly on the ionospheric layer influences. The Brazilian sector ionosphere, mainly over the equatorial ionization anomaly (EIA), presents remarkable errors in the GNSS signal as compared to North America and Europe. In order to study the total electron content latitudinal variation of the Brazilian ionosphere we used a pair of GNSS receivers on the ground, one located in the equatorial region (Sao Luis) and other in the southern crest of the EIA (Cachoeira Paulista), to collect the GNSS observables and calculate the vertical TEC using different methods that has proven to work well to describe the ionospheric behavior in the North America and in Europe. We compared this results with a modified Nagoya TEC calculation method used by the EMBRACE (Estudo e Monitoramento BRAsileiro do Clima Espacial - Brazilian Study and Monitoring of Space Weather) program. This work intends to follow the performance of different TEC tuning methods to evaluate the spurious effects of the ionospheric EIA gradients in the TEC determination under typical conditions of the low-latitudes ionosphere in the Brazilian sector. The calculated TEC under different solar cycle conditions, geomagnetic activity, and seasonal variations show deviations in the performance of each method and stress the importance of well adjust the GNSS observations to local conditions in order to optimize the TEC evaluation. This study contributes to a better understanding of local GNSS signal errors in the global intent of offering conditions to improve the accuracy, integrity, availability, and continuity requirements for the use of GNSS for air navigation in South America.

Comparison of plateletpheresis on the Fenwal Amicus, Fresenius COM.TEC, and Trima Accel Cell separators.

PubMed

Keklik, Muzaffer; Eser, Bulent; Kaynar, Leylagul; Sivgin, Serdar; Keklik, Ertugrul; Solmaz, Musa; Ozturk, Ahmet; Buyukoglan, Ruksan; Yay, Mehmet; Cetin, Mustafa; Unal, Ali

2015-06-01

Blood component donations by apheresis have become more common in modern blood transfusion practices. We compared three apheresis instruments (Fenwal Amicus, Fresenius COM.TEC, and Trima Accel) with regard to platelet (PLT) yield, collection efficiency (CE), and collection rate (CR). The single-needle or double-needle plateletpheresis procedures of the three instruments were compared in a retrospective, randomized study in 270 donors. The blood volume processed was higher in the COM.TEC compared with the Amicus and Trima. Also there was a significantly higher median volume of ACD used in collections on the COM.TEC compared with the Amicus and Trima. The PLT yield was significantly lower with the COM.TEC compared with the Amicus and Trima. Additionally, the CE was significantly lower with the COM.TEC compared with the Amicus and Trima. There was no significant difference in median separation time and CR between the three groups. When procedures were compared regarding CE by using Amicus device, it was significantly higher in single-needle than double-needle plateletpheresis. When double-needle Amicus system was compared with double-needle COM.TEC system, CE and PLT yield were significantly higher with Amicus system. When single-needle Amicus system was compared with single-needle Trima system, CE and PLT yield were significantly higher with Trima system. All instruments collected PLTs efficiently. However, the CE was lower with the COM.TEC compared with the Amicus and Trima. Also, we found Amicus single-needle system collected PLTs more efficiently compared with the double-needle system. CE and PLT yields were significantly higher with the single-needle Trima instrument compared with the single-needle Amicus device. © 2014 Wiley Periodicals, Inc.

Interleukin-13-induced MUC5AC expression is regulated by a PI3K–NFAT3 pathway in mouse tracheal epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yan, Fugui; Li, Wen; Zhou, Hongbin

Highlights: • IL-13 specifically induced NFAT3 activation in mouse tracheal epithelial cells. • CsA and LY294002 significantly blocked IL-13-induced MUC5AC production. • The PI3K–NFAT3 pathway is positively involved in IL-13-induced MUC5AC production. - Abstract: Interleukin-13 (IL-13) plays a critical role in asthma mucus overproduction, while the mechanisms underlying this process are not fully elucidated. Previous studies showed that nuclear factor of activated T cells (NFAT) is involved in the pathogenesis of asthma, but whether it can directly regulate IL-13-induced mucus (particularly MUC5AC) production is still not clear. Here we showed that IL-13 specifically induced NFAT3 activation through promoting its dephosphorylationmore » in air–liquid interface (ALI) cultures of mouse tracheal epithelial cells (mTECs). Furthermore, both Cyclosporin A (CsA, a specific NFAT inhibitor) and LY294002 (a Phosphoinositide 3-kinase (PI3K) inhibitor) significantly blocked IL-13-induced MUC5AC mRNA and protein production through the inhibition of NFAT3 activity. We also confirmed that CsA could not influence the forkhead Box A2 (Foxa2) and mouse calcium dependent chloride channel 3 (mClca3) expression in IL-13-induced MUC5AC production, which both are known to be important in IL-13-stimulated mucus expression. Our study is the first to demonstrate that the PI3K–NFAT3 pathway is positively involved in IL-13-induced mucus production, and provided novel insights into the molecular mechanism of asthma mucus hypersecretion.« less

Inhibition of AMP Kinase by the Protein Phosphatase 2A Heterotrimer, PP2APpp2r2d*

PubMed Central

Joseph, Biny K.; Liu, Hsing-Yin; Francisco, Jamie; Pandya, Devanshi; Donigan, Melissa; Gallo-Ebert, Christina; Giordano, Caroline; Bata, Adam; Nickels, Joseph T.

2015-01-01

AMP kinase is a heterotrimeric serine/threonine protein kinase that regulates a number of metabolic processes, including lipid biosynthesis and metabolism. AMP kinase activity is regulated by phosphorylation, and the kinases involved have been uncovered. The particular phosphatases counteracting these kinases remain elusive. Here we discovered that the protein phosphatase 2A heterotrimer, PP2APpp2r2d, regulates the phosphorylation state of AMP kinase by dephosphorylating Thr-172, a residue that activates kinase activity when phosphorylated. Co-immunoprecipitation and co-localization studies indicated that PP2APpp2r2d directly interacted with AMP kinase. PP2APpp2r2d dephosphorylated Thr-172 in rat aortic and human vascular smooth muscle cells. A positive correlation existed between decreased phosphorylation, decreased acetyl-CoA carboxylase Acc1 phosphorylation, and sterol response element-binding protein 1c-dependent gene expression. PP2APpp2r2d protein expression was up-regulated in the aortas of mice fed a high fat diet, and the increased expression correlated with increased blood lipid levels. Finally, we found that the aortas of mice fed a high fat diet had decreased AMP kinase Thr-172 phosphorylation, and contained an Ampk-PP2APpp2r2d complex. Thus, PP2APpp2r2d may antagonize the aortic AMP kinase activity necessary for maintaining normal aortic lipid metabolism. Inhibiting PP2APpp2r2d or activating AMP kinase represents a potential pharmacological treatment for many lipid-related diseases. PMID:25694423

Seismo-ionospheric Precursors in the GPS Total Electron Content of the 16 October 1999 Mw7.1 Hector Mine Earthquake

NASA Astrophysics Data System (ADS)

Tsai, H.; Su, Y.; Liu, J. G.; Chen, S.; Chen, M.

2013-12-01

In this paper, temporal and spatial analyses are employed to detect seismo-ionospheric precursors (SIPs) in the ionospheric total electron content (TEC) during 16 October 1999 Mw7.1 Hector Mine earthquake. To discriminate anomalies caused by global effects, such as solar radiations, magnetic storms, etc., and local effects, such as earthquake, we cross-examine the GPS TECs and their gradients in the eastward and northward directions at epicenter/centers of the Hector Mine area and the other two reference areas at similar magnetic latitudes in Europe and Japan. Temporal variations of the northward TEC gradient suggest SIPs most likely appearing day 6-5 before the earthquake. A global search by using the TEC of GIM (global ionosphere map) shows that the TEC increase and decrease anomalies continuously and specifically appear around the epicenter day 5 before the earthquake.

Ionospheric responses during equinox and solstice periods over Turkey

NASA Astrophysics Data System (ADS)

Karatay, Secil; Cinar, Ali; Arikan, Feza

2017-11-01

Ionospheric electron density is the determining variable for investigation of the spatial and temporal variations in the ionosphere. Total Electron Content (TEC) is the integral of the electron density along a ray path that indicates the total variability through the ionosphere. Global Positioning System (GPS) recordings can be utilized to estimate the TEC, thus GPS proves itself as a useful tool in monitoring the total variability of electron distribution within the ionosphere. This study focuses on the analysis of the variations of ionosphere over Turkey that can be grouped into anomalies during equinox and solstice periods using TEC estimates obtained by a regional GPS network. It is observed that noon time depletions in TEC distributions predominantly occur in winter for minimum Sun Spots Numbers (SSN) in the central regions of Turkey which also exhibit high variability due to midlatitude winter anomaly. TEC values and ionospheric variations at solstice periods demonstrate significant enhancements compared to those at equinox periods.

Auto-phosphorylation Represses Protein Kinase R Activity.

PubMed

Wang, Die; de Weerd, Nicole A; Willard, Belinda; Polekhina, Galina; Williams, Bryan R G; Sadler, Anthony J

2017-03-10

The central role of protein kinases in controlling disease processes has spurred efforts to develop pharmaceutical regulators of their activity. A rational strategy to achieve this end is to determine intrinsic auto-regulatory processes, then selectively target these different states of kinases to repress their activation. Here we investigate auto-regulation of the innate immune effector protein kinase R, which phosphorylates the eukaryotic initiation factor 2α to inhibit global protein translation. We demonstrate that protein kinase R activity is controlled by auto-inhibition via an intra-molecular interaction. Part of this mechanism of control had previously been reported, but was then controverted. We account for the discrepancy and extend our understanding of the auto-inhibitory mechanism by identifying that auto-inhibition is paradoxically instigated by incipient auto-phosphorylation. Phosphor-residues at the amino-terminus instigate an intra-molecular interaction that enlists both of the N-terminal RNA-binding motifs of the protein with separate surfaces of the C-terminal kinase domain, to co-operatively inhibit kinase activation. These findings identify an innovative mechanism to control kinase activity, providing insight for strategies to better regulate kinase activity.

Flow-dependent regulation of endothelial nitric oxide synthase: role of protein kinases

NASA Technical Reports Server (NTRS)

Boo, Yong Chool; Jo, Hanjoong

2003-01-01

Vascular endothelial cells are directly and continuously exposed to fluid shear stress generated by blood flow. Shear stress regulates endothelial structure and function by controlling expression of mechanosensitive genes and production of vasoactive factors such as nitric oxide (NO). Though it is well known that shear stress stimulates NO production from endothelial nitric oxide synthase (eNOS), the underlying molecular mechanisms remain unclear and controversial. Shear-induced production of NO involves Ca2+/calmodulin-independent mechanisms, including phosphorylation of eNOS at several sites and its interaction with other proteins, including caveolin and heat shock protein-90. There have been conflicting results as to which protein kinases-protein kinase A, protein kinase B (Akt), other Ser/Thr protein kinases, or tyrosine kinases-are responsible for shear-dependent eNOS regulation. The functional significance of each phosphorylation site is still unclear. We have attempted to summarize the current status of understanding in shear-dependent eNOS regulation.

Suppression of bcr-abl synthesis by siRNAs or tyrosine kinase activity by Glivec alters different oncogenes, apoptotic/antiapoptotic genes and cell proliferation factors (microarray study).

PubMed

Zhelev, Zhivko; Bakalova, Rumiana; Ohba, Hideki; Ewis, Ashraf; Ishikawa, Mitsuru; Shinohara, Yasuo; Baba, Yoshinobu

2004-07-16

Short 21-mer double-stranded/small-interfering RNAs (ds/siRNAs) were designed to target bcr-abl mRNA in chronic myelogenous leukemia. The ds/siRNAs were transfected into bcr-abl-positive K-562 (derived from blast crisis chronic myelogenous leukemia), using lipofectamine. Penetrating of ds/siRNAs into the cells was detected by fluorescent confocal microscopy, using fluorescein-labeled ds/siRNAs. The cells were treated with mix of three siRNA sequences (3 x 60 nM) during 6 days with three repetitive transfections. The siRNA-treatment was accompanied with significant reduction of bcr-abl mRNA, p210, protein tyrosine kinase activity and cell proliferation index. Treatment of cells with Glivec (during 8 days with four repetitive doses, 180 nM single dose) resulted in analogous reduction of cell proliferation activity, stronger suppression of protein tyrosine kinase activity, and very low reduction of p210. siRNA-mix and Glivec did not affect significantly the viability of normal lymphocytes. Microarray analysis of siRNA- and Glivec-treated K-562 cells demonstrated that both pathways of bcr-abl suppression were accompanied with overexpression and suppression of many different oncogenes, apoptotic/antiapoptotic and cell proliferation factors. The following genes of interest were found to decrease in relatively equal degree in both siRNA- and Glivec-treated cells: Bcd orf1 and orf2 proto-oncogene, chromatin-specific transcription elongation factor FACT 140-kDa subunit mRNA, gene encoding splicing factor SF1, and mRNA for Tec protein tyrosine kinase. siRNA-mix and Glivec provoked overexpression of the following common genes: c-jun proto-oncogene, protein kinase C-alpha, pvt-1 oncogene homologue (myc activator), interleukin-6, 1-8D gene from interferon-inducible gene family, tumor necrosis factor receptor superfamily (10b), and STAT-induced STAT inhibitor.

Curriculum Change. An Evaluation of TEC Programme Development in Colleges. The Main Findings.

ERIC Educational Resources Information Center

Parkin, Christopher; And Others

An evaluation was made of the adoption of curriculum changes mandated by the Technician Education Council (TEC) by 78 colleges in England. The study concentrated on the processes of adaptation that occurred in the colleges in order to cope with the degree of change required by TEC. Data were collected via questionnaires, interviews, case studies,…

A program-management plan with critical-path definition for Combustion Augmentation with Thermionic Energy Conversion (CATEC)

NASA Technical Reports Server (NTRS)

Morris, J. F.; Merrill, O. S.; Reddy, H. K.

1981-01-01

Thermionic energy conversion (TEC) is discussed. In recent TEC-topping analyses, overall plant efficiency (OPE) and cost of electricity (COE) improved slightly with current capabilities and substantially with fully matured technologies. Enhanced credibility derives from proven hot-corrosion protection for TEC by silicon-carbide clads in fossil fuel combustion products. Combustion augmentation with TEC (CATEC) affords minimal cost and plant perturbation, but with smaller OPE and COE improvements than more conventional topping applications. Risk minimization as well as comparative simplicity and convenience, favor CATEC for early market penetration. A program-management plan is proposed. Inputs, characteristics, outputs and capabilities are discussed.

A program-management plan with critical-path definition for Combustion Augmentation with Thermionic Energy Conversion (CATEC)

NASA Astrophysics Data System (ADS)

Morris, J. F.; Merrill, O. S.; Reddy, H. K.

Thermionic energy conversion (TEC) is discussed. In recent TEC-topping analyses, overall plant efficiency (OPE) and cost of electricity (COE) improved slightly with current capabilities and substantially with fully matured technologies. Enhanced credibility derives from proven hot-corrosion protection for TEC by silicon-carbide clads in fossil fuel combustion products. Combustion augmentation with TEC (CATEC) affords minimal cost and plant perturbation, but with smaller OPE and COE improvements than more conventional topping applications. Risk minimization as well as comparative simplicity and convenience, favor CATEC for early market penetration. A program-management plan is proposed. Inputs, characteristics, outputs and capabilities are discussed.

C. elegans STK39/SPAK ortholog-mediated inhibition of ClC anion channel activity is regulated by WNK-independent ERK kinase signaling

PubMed Central

Falin, Rebecca A.; Miyazaki, Hiroaki

2011-01-01

Mammalian Ste20-like proline/alanine-rich kinase (SPAK) and oxidative stress-responsive 1 (OSR1) kinases phosphorylate and regulate cation-coupled Cl− cotransporter activity in response to cell volume changes. SPAK and OSR1 are activated via phosphorylation by upstream with-no-lysine (WNK) kinases. In Caenorhabditis elegans, the SPAK/OSR1 ortholog germinal center kinase (GCK)-3 binds to and regulates the activity of the cell volume- and meiotic cell cycle-dependent ClC anion channel CLH-3b. We tested the hypothesis that WNK kinases function in the GCK-3/CLH-3b signaling cascade. CLH-3b heterologously expressed in human embryonic kidney (HEK) cells was unaffected by coexpression with the single C. elegans WNK kinase, WNK-1, or kinase-dead WNK-1 dominant-negative mutants. RNA interference (RNAi) knockdown of the single Drosophila WNK kinase had no effect on the activity of CLH-3b expressed in Drosophila S2 cells. Similarly, RNAi silencing of C. elegans WNK-1 had no effect on basal or cell volume-sensitive activity of CLH-3b expressed endogenously in worm oocytes. Previous yeast 2-hybrid studies suggested that ERK kinases may function upstream of GCK-3. Pharmacological inhibition of ERK signaling disrupted CLH-3b activity in HEK cells in a GCK-3-dependent manner. RNAi silencing of the C. elegans ERK kinase MPK-1 or the ERK phosphorylating/activating kinase MEK-2 constitutively activated native CLH-3b. MEK-2 and MPK-1 play important roles in regulating the meiotic cell cycle in C. elegans oocytes. Cell cycle-dependent changes in MPK-1 correlate with the pattern of CLH-3b activation observed during oocyte meiotic maturation. We postulate that MEK-2/MPK-1 functions upstream from GCK-3 to regulate its activity during cell volume and meiotic cell cycle changes. PMID:21160027

Thermodynamic Analysis of TEG-TEC Device Including Influence of Thomson Effect

NASA Astrophysics Data System (ADS)

Feng, Yuanli; Chen, Lingen; Meng, Fankai; Sun, Fengrui

2018-01-01

A thermodynamic model of a thermoelectric cooler driven by thermoelectric generator (TEG-TEC) device is established considering Thomson effect. The performance is analyzed and optimized using numerical calculation based on non-equilibrium thermodynamic theory. The influence characteristics of Thomson effect on the optimal performance and variable selection are investigated by comparing the condition with and without Thomson effect. The results show that Thomson effect degrades the performance of TEG-TEC device, it decreases the cooling capacity by 27 %, decreases the coefficient of performance (COP) by 19 %, decreases the maximum cooling temperature difference by 11 % when the ratio of thermoelectric elements number is 0.6, the cold junction temperature of thermoelectric cooler (TEC) is 285 K and the hot junction temperature of thermoelectric generator (TEG) is 450 K. Thomson effect degrades the optimal performance of TEG-TEC device, it decreases the maximum cooling capacity by 28 % and decreases the maximum COP by 28 % under the same junction temperatures. Thomson effect narrows the optimal variable range and optimal working range. In the design of the devices, limited-number thermoelectric elements should be more allocated appropriately to TEG when consider Thomson effect. The results may provide some guidelines for the design of TEG-TEC devices.

A comparison of mapped and measured total ionospheric electron content using global positioning system and beacon satellite observations

NASA Technical Reports Server (NTRS)

Lanyi, Gabor E.; Roth, Titus

1988-01-01

Total ionospheric electron contents (TEC) were measured by global positioning system (GPS) dual-frequency receivers developed by the Jet Propulsion Laboratory. The measurements included P-code (precise ranging code) and carrier phase data for six GPS satellites during multiple five-hour observing sessions. A set of these GPS TEC measurements were mapped from the GPS lines of sight to the line of sight of a Faraday beacon satellite by statistically fitting the TEC data to a simple model of the ionosphere. The mapped GPS TEC values were compared with the Faraday rotation measurements. Because GPS transmitter offsets are different for each satellite and because some GPS receiver offsets were uncalibrated, the sums of the satellite and receiver offsets were estimated simultaneously with the TEC in a least squares procedure. The accuracy of this estimation procedure is evaluated indicating that the error of the GPS-determined line of sight TEC can be at or below 1 x 10 to the 16th el/sq cm. Consequently, the current level of accuracy is comparable to the Faraday rotation technique; however, GPS provides superior sky coverage.

Analysis of rocket beacon transmissions for computerized reconstruction of ionospheric densities

NASA Technical Reports Server (NTRS)

Bernhardt, P. A.; Huba, J. D.; Chaturvedi, P. K.; Fulford, J. A.; Forsyth, P. A.; Anderson, D. N.; Zalesak, S. T.

1993-01-01

Three methods are described to obtain ionospheric electron densities from transionospheric, rocket-beacon TEC data. First, when the line-of-sight from a ground receiver to the rocket beacon is tangent to the flight trajectory, the electron concentration can be obtained by differentiating the TEC with respect to the distance to the rocket. A similar method may be used to obtain the electron-density profile if the layer is horizontally stratified. Second, TEC data obtained during chemical release experiments may be interpreted with the aid of physical models of the disturbed ionosphere to yield spatial maps of the modified regions. Third, computerized tomography (CT) can be used to analyze TEC data obtained along a chain of ground-based receivers aligned along the plane of the rocket trajectory. CT analysis of TEC data is used to reconstruct a 2D image of a simulated equatorial plume. TEC data is computed for a linear chain of nine receivers with adjacent spacings of either 100 or 200 km. The simulation data are analyzed to provide an F region reconstruction on a grid with 15 x 15 km pixels. Ionospheric rocket tomography may also be applied to rocket-assisted measurements of amplitude and phase scintillations and airglow intensities.

A novel binary Pt 3Te x/C nanocatalyst for ethanol electro-oxidation

NASA Astrophysics Data System (ADS)

Huang, Meihua; Wang, Fei; Li, Lirong; Guo, Yonglang

The Pt 3Te x/C nanocatalyst was prepared and its catalytic performance for ethanol oxidation was investigated for the first time. The Pt 3Te/C nanoparticles were characterized by an X-ray diffractometer (XRD), transmission electron microscope (TEM) and energy dispersive X-ray spectroscopy equipped with TEM (TEM-EDX). The Pt 3Te/C catalyst has a typical fcc structure of platinum alloys with the presence of Te. Its particle size is about 2.8 nm. Among the synthesized catalysts with different atomic ratios, the Pt 3Te/C catalyst has the highest anodic peak current density. The cyclic voltammograms (CV) show that the anodic peak current density for the Pt 3Te/C, commercial PtRu/C and Pt/C catalysts reaches 1002, 832 and 533 A g -1, respectively. On the current-time curve, the anodic current on the Pt 3Te/C catalyst was higher than those for the catalysts reported. So, these findings show that the Pt 3Te/C catalyst has uniform nanoparticles and the best activity among the synthesized catalysts, and it is better than commercial PtRu/C and Pt/C catalysts for ethanol oxidation at room temperature.

AzTEC/ASTE 1.1 mm Deep Surveys: Number Counts and Clustering of Millimeter-bright Galaxies

NASA Astrophysics Data System (ADS)

Hatsukade, B.

2011-11-01

We present results of a 1.1 mm deep survey of the AKARI Deep Field South (ADF-S) with AzTEC mounted on the Atacama Submillimetre Telescope Experiment (ASTE). We obtained a map of 0.25 deg2 area with an rms noise level of 0.32-0.71 mJy. This is one of the deepest and widest maps thus far at millimetre and submillimetre wavelengths. We uncovered 198 sources with a significance of 3.5-15.6σ, providing the largest catalog of 1.1 mm sources in a contiguous region. Most of the sources are not detected in the far-infrared bands of the AKARI satellite, suggesting that they are mostly at z ≥ 1.5 given the detection limits. We construct differential and cumulative number counts of the ADF-S, the Subaru/XMM Newton Deep Field (SXDF), and the SSA 22 field surveyed by AzTEC/ASTE, which provide currently the tightest constraints on the faint end. The integration of the differential number counts of the ADF-S find that the contribution of 1.1 mm sources with ≥1 mJy to the cosmic infrared background (CIB) at 1.1 mm is 12-16%, suggesting that the large fraction of the CIB originates from faint sources of which number counts are not yet constrained. We estimate the cosmic star-formation rate density contributed by 1.1 mm sources with ≥1 mJy using the differential number counts and find that it is lower by about a factor of 5-10 compared to those derived from UV/optically-selected galaxies at z ~ 2-3. Clustering analyses of AzTEC sources in the ADF-S and the SXDF find that bright (>3 mJy) AzTEC sources are more strongly clustered than faint (< 3 mJy) AzTEC sources and the average mass of dark halos hosting bright AzTEC sources was calculated to be 1013-1014M⊙. Comparison of correlation length of AzTEC sources with other populations and with a bias evolution model suggests that dark halos hosting bright AzTEC sources evolve into systems of clusters at present universe and the AzTEC sources residing the dark halos evolve into massive elliptical galaxies located in the center of clusters.

Real-Time Three-Dimensional Echocardiography of the Left Ventricle-Pediatric Percentiles and Head-to-Head Comparison of Different Contour-Finding Algorithms: A Multicenter Study.

PubMed

Krell, Kristina; Laser, Kai Thorsten; Dalla-Pozza, Robert; Winkler, Christian; Hildebrandt, Ursula; Kececioglu, Deniz; Breuer, Johannes; Herberg, Ulrike

2018-03-28

Real-time three-dimensional echocardiography (RT3DE) is a promising method for accurate assessment of left ventricular (LV) volumes and function, however, pediatric reference values are scarce. The aim of the study was to establish pediatric percentiles in a large population and to compare the inherent influence of different evaluation software on the resulting measurements. In a multicenter prospective-design study, 497 healthy children (ages 1 day to 219 months) underwent RT3DE imaging of the LV (ie33, Philips, Andover, MA). Volume analysis was performed using QLab 9.0 (Philips) and TomTec 4DLV2.7 (vendor-independent; testing high (TomTec 75 ) and low (TomTec 30 ) contour-finding activity). Reference percentiles were computed using Cole's LMS method. In 22 subjects, cardiovascular magnetic resonance imaging (CMR) was used as the reference. A total of 370/497 (74.4%) of the subjects provided adequate data sets. LV volumes had a significant association with age, body size, and gender; therefore, sex-specific percentiles were indexed to body surface area. Intra- and interobserver variability for both workstations was good (relative bias ± SD for end-diastolic volume [EDV] in %: intraobserver: QLab = -0.8 ± 2.4; TomTec 30  = -0.7 ± 7.2; TomTec 75  = -1.9 ± 6.7; interobserver: QLab = 2.4 ± 7.5; TomTec 30  = 1.2 ± 5.1; TomTec 75  = 1.3 ± 4.5). Intervendor agreement between QLab and TomTec 30 showed larger bias and wider limits of agreement (bias: QLab vs TomTec 30 : end-systolic volume [ESV] = 0.8% ± 23.6%; EDV = -2.2% ± 17.0%) with notable individual differences in small children. QLab and TomTec underestimated CMR values, with the highest agreement between CMR and QLab. RT3DE allows reproducible noninvasive assessment of LV volumes and function. However, intertechnique variability is relevant. Therefore, our software-specific percentiles, based on a large pediatric population, serve as a reference for both commonly used quantification programs. Copyright © 2018 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Cerebral activation of mitogen-activated protein kinases after circulatory arrest and low flow cardiopulmonary bypass.

PubMed

Aharon, Alon S; Mulloy, Matthew R; Drinkwater, Davis C; Lao, Oliver B; Johnson, Mahlon D; Thunder, Megan; Yu, Chang; Chang, Paul

2004-11-01

Mitogen-activated protein kinases (MAPK) are important intermediates in the signal transduction pathways involved in neuronal dysfunction following cerebral ischemia-reperfusion injury. One subfamily, extracellular regulated kinase 1/2, has been heavily implicated in the pathogenesis of post-ischemic neuronal damage. However, the contribution of extracellular regulated kinase 1/2 to neuronal damage following deep hypothermic circulatory arrest and low flow cardiopulmonary bypass is unknown. We attempted to correlate the extent of neuronal damage present following deep hypothermic circulatory arrest and low flow cardiopulmonary bypass with phosphorylated extracellular regulated kinase 1/2 expression in the cerebral vascular endothelium. Piglets underwent normal flow cardiopulmonary bypass (n=4) deep hypothermic circulatory arrest (n=6) and low flow cardiopulmonary bypass (n=5). Brains were harvested following 24 h of post-cardiopulmonary bypass recovery. Cerebral cortical watershed zones, hippocampus, basal ganglia, thalamus, cerebellum, mesencephalon, pons and medulla were evaluated using hematoxylin and eosin staining. A section of ischemic cortex was evaluated by immunohistochemistry with rabbit polyclonal antibodies against phosphorylated extracellular regulated kinase 1/2. Compared to cardiopulmonary bypass controls, the deep hypothermic circulatory arrest and low flow cardiopulmonary bypass piglets exhibited diffuse ischemic changes with overlapping severity and distribution. Significant neuronal damage occurred in the frontal watershed zones and basal ganglia of the deep hypothermic circulatory arrest group (P<0.05). No detectable phosphorylated extracellular regulated kinase 1/2 immunoreactivity was found in the cardiopulmonary bypass controls; however, ERK 1/2 immunoreactivity was present in the cerebral vascular endothelium of the deep hypothermic circulatory arrest and low flow cardiopulmonary bypass groups. Our results indicate that phosphorylated extracellular regulated kinase 1/2 may play a prominent role in early cerebral ischemia-reperfusion injury and endothelial dysfunction. The pharmacologic inhibition of extracellular regulated kinase 1/2 represents a new and exciting opportunity for the modulation of cerebral tolerance to low flow cardiopulmonary bypass and deep hypothermic circulatory arrest.

Ribavirin suppresses hepatic lipogenesis through inosine monophosphate dehydrogenase inhibition: Involvement of adenosine monophosphate-activated protein kinase-related kinases and retinoid X receptor α.

PubMed

Satoh, Shinya; Mori, Kyoko; Onomura, Daichi; Ueda, Youki; Dansako, Hiromichi; Honda, Masao; Kaneko, Shuichi; Ikeda, Masanori; Kato, Nobuyuki

2017-08-01

Ribavirin (RBV) has been widely used as an antiviral reagent, specifically for patients with chronic hepatitis C. We previously demonstrated that adenosine kinase, which monophosphorylates RBV into the metabolically active form, is a key determinant for RBV sensitivity against hepatitis C virus RNA replication. However, the precise mechanism of RBV action and whether RBV affects cellular metabolism remain unclear. Analysis of liver gene expression profiles obtained from patients with advanced chronic hepatitis C treated with the combination of pegylated interferon and RBV showed that the adenosine kinase expression level tends to be lower in patients who are overweight and significantly decreases with progression to advanced fibrosis stages. In our effort to investigate whether RBV affects cellular metabolism, we found that RBV treatment under clinically achievable concentrations suppressed lipogenesis in hepatic cells. In this process, guanosine triphosphate depletion through inosine monophosphate dehydrogenase inhibition by RBV and adenosine monophosphate-activated protein kinase-related kinases, especially microtubule affinity regulating kinase 4, were required. In addition, RBV treatment led to the down-regulation of retinoid X receptor α (RXRα), a key nuclear receptor in various metabolic processes, including lipogenesis. Moreover, we found that guanosine triphosphate depletion in cells induced the down-regulation of RXRα, which was mediated by microtubule affinity regulating kinase 4. Overexpression of RXRα attenuated the RBV action for suppression of lipogenic genes and intracellular neutral lipids, suggesting that down-regulation of RXRα was required for the suppression of lipogenesis in RBV action. Conclusion : We provide novel insights about RBV action in lipogenesis and its mechanisms involving inosine monophosphate dehydrogenase inhibition, adenosine monophosphate-activated protein kinase-related kinases, and down-regulation of RXRα. RBV may be a potential reagent for anticancer therapy against the active lipogenesis involved in hepatocarcinogenesis. ( Hepatology Communications 2017;1:550-563).

Regulatory crosstalk by protein kinases on CFTR trafficking and activity

NASA Astrophysics Data System (ADS)

Farinha, Carlos Miguel; Swiatecka-Urban, Agnieszka; Brautigan, David; Jordan, Peter

2016-01-01

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a member of the ATP binding cassette (ABC) transporter superfamily that functions as a cAMP-activated chloride ion channel in fluid-transporting epithelia. There is abundant evidence that CFTR activity (i.e. channel opening and closing) is regulated by protein kinases and phosphatases via phosphorylation and dephosphorylation. Here, we review recent evidence for the role of protein kinases in regulation of CFTR delivery to and retention in the plasma membrane. We review this information in a broader context of regulation of other transporters by protein kinases because the overall functional output of transporters involves the integrated control of both their number at the plasma membrane and their specific activity. While many details of the regulation of intracellular distribution of CFTR and other transporters remain to be elucidated, we hope that this review will motivate research providing new insights into how protein kinases control membrane transport to impact health and disease.

Btk regulation in human and mouse B cells via protein kinase C phosphorylation of IBtkγ.

PubMed

Janda, Elzbieta; Palmieri, Camillo; Pisano, Antonio; Pontoriero, Marilena; Iaccino, Enrico; Falcone, Cristina; Fiume, Giuseppe; Gaspari, Marco; Nevolo, Maria; Di Salle, Emanuela; Rossi, Annalisa; De Laurentiis, Annamaria; Greco, Adelaide; Di Napoli, Daniele; Verheij, Elwin; Britti, Domenico; Lavecchia, Luca; Quinto, Ileana; Scala, Giuseppe

2011-06-16

The inhibitor of Bruton tyrosine kinase γ (IBtkγ) is a negative regulator of the Bruton tyrosine kinase (Btk), which plays a major role in B-cell differentiation; however, the mechanisms of IBtkγ-mediated regulation of Btk are unknown. Here we report that B-cell receptor (BCR) triggering caused serine-phosphorylation of IBtkγ at protein kinase C consensus sites and dissociation from Btk. By liquid chromatography and mass-mass spectrometry and functional analysis, we identified IBtkγ-S87 and -S90 as the critical amino acid residues that regulate the IBtkγ binding affinity to Btk. Consistently, the mutants IBtkγ carrying S87A and S90A mutations bound constitutively to Btk and down-regulated Ca(2+) fluxes and NF-κB activation on BCR triggering. Accordingly, spleen B cells from Ibtkγ(-/-) mice showed an increased activation of Btk, as evaluated by Y551-phosphorylation and sustained Ca(2+) mobilization on BCR engagement. These findings identify a novel pathway of Btk regulation via protein kinase C phosphorylation of IBtkγ.

Simultaneous response of NmF2 and GPS-TEC to storm events at Ilorin

NASA Astrophysics Data System (ADS)

Joshua, B. W.; Adeniyi, J. O.; Oladipo, O. A.; Doherty, P. H.; Adimula, I. A.; Olawepo, A. O.; Adebiyi, S. J.

2018-06-01

A comparative study of both TEC and NmF2 variations during quiet and disturbed conditions has been investigated using simultaneous measurements from dual frequency Global Positioning System (GPS) receiver and a DPS-4 Digisonde co-located at Ilorin (Geog. Lat. 8.50°N, Long. 4.50°E, dip. - 7.9°). The results of the quiet time variations of the two parameters show some similarities as well as differences in their structures. The values of both parameters generally increase during the sunrise period attaining a peak around the noon and then decaying towards the night time. The onset time of the sunrise growth is observed to be earlier in TEC than in NmF2. The rate of decay of TEC was observed to be faster than that of the NmF2 in most cases. Also, the noon 'bite-outs', leading to the formation of pre-noon and post-noon peaks, are prominent in the NmF2 structure and was hardly noticed in TEC. Results of the variations of both TEC and NmF2 during the 5 April, 10 May and 3 August 2010 geomagnetic storm events showed a simultaneous deviations of both parameters from the quiet time behavior. The magnitude of the deviations is however most pronounced in NmF2 structure than in TEC. We also found that the enhancement observed in the two parameters during the storm events generally corresponds to decrease in hmF2.

Comparison of the Fenwal Amicus and Fresenius Com.Tec cell separators for autologous peripheral blood progenitor cell collection.

PubMed

Altuntas, Fevzi; Kocyigit, Ismail; Ozturk, Ahmet; Kaynar, Leylagul; Sari, Ismail; Oztekin, Mehmet; Solmaz, Musa; Eser, Bulent; Cetin, Mustafa; Unal, Ali

2007-04-01

Peripheral blood progenitor cells (PBPC) are commonly used as a stem cell source for autologous transplantation. This study was undertaken to evaluate blood cell separators with respect to separation results and content of the harvest. Forty autologous PBPC collections in patients with hematological malignancies were performed with either the Amicus or the COM.TEC cell separators. The median product volume was lower with the Amicus compared to the COM.TEC (125 mL vs. 300 mL; p < 0.001). There was no statistically significant difference in the median number of CD34+ cell/kg in product between the Amicus and the COM.TEC (3.0 x 10(6) vs. 4.1 x 10(6); p = 0.129). There was a statistically higher mean volume of ACD used in collections on the Amicus compared to the COM.TEC (1040 +/- 241 mL vs. 868 +/- 176 mL; p = 0.019). There was a statistical difference in platelet (PLT) contamination of the products between the Amicus and the COM.TEC (0.3 x 10(11) vs. 1.1 x 10(11); p < 0.001). The median % decrease in PB PLT count was statistically higher in the COM.TEC compared to the Amicus instruments (18.5% vs. 9.5%; p = 0.028). In conclusion, both instruments collected PBPCs efficiently. However, Amicus has the advantage of lower PLT contamination in the product, and less decrease in PB platelet count with lower product volume in autologous setting.

Ionosphere monitoring and forecast activities within the IAG working group "Ionosphere Prediction"

NASA Astrophysics Data System (ADS)

Hoque, Mainul; Garcia-Rigo, Alberto; Erdogan, Eren; Cueto Santamaría, Marta; Jakowski, Norbert; Berdermann, Jens; Hernandez-Pajares, Manuel; Schmidt, Michael; Wilken, Volker

2017-04-01

Ionospheric disturbances can affect technologies in space and on Earth disrupting satellite and airline operations, communications networks, navigation systems. As the world becomes ever more dependent on these technologies, ionospheric disturbances as part of space weather pose an increasing risk to the economic vitality and national security. Therefore, having the knowledge of ionospheric state in advance during space weather events is becoming more and more important. To promote scientific cooperation we recently formed a Working Group (WG) called "Ionosphere Predictions" within the International Association of Geodesy (IAG) under Sub-Commission 4.3 "Atmosphere Remote Sensing" of the Commission 4 "Positioning and Applications". The general objective of the WG is to promote the development of ionosphere prediction algorithm/models based on the dependence of ionospheric characteristics on solar and magnetic conditions combining data from different sensors to improve the spatial and temporal resolution and sensitivity taking advantage of different sounding geometries and latency. Our presented work enables the possibility to compare total electron content (TEC) prediction approaches/results from different centers contributing to this WG such as German Aerospace Center (DLR), Universitat Politècnica de Catalunya (UPC), Technische Universität München (TUM) and GMV. DLR developed a model-assisted TEC forecast algorithm taking benefit from actual trends of the TEC behavior at each grid point. Since during perturbations, characterized by large TEC fluctuations or ionization fronts, this approach may fail, the trend information is merged with the current background model which provides a stable climatological TEC behavior. The presented solution is a first step to regularly provide forecasted TEC services via SWACI/IMPC by DLR. UPC forecast model is based on applying linear regression to a temporal window of TEC maps in the Discrete Cosine Transform (DCT) domain. Performance tests are being conducted at the moment in order to improve UPC predicted products for 1-, 2-days ahead. In addition, UPC is working to enable short-term predictions based on UPC real-time GIMs (labelled URTG) and implementing an improved prediction approach. TUM developed a forecast method based on a time series analysis of TEC products which are either B-spline coefficients estimated by a Kalman filter or TEC grid maps derived from the B-spline coefficients. The forecast method uses a Fourier series expansion to extract the trend functions from the estimated TEC product. Then the trend functions are carried out to provide predicted TEC products. The forecast algorithm developed by GMV is based on the ionospheric delay estimation from previous epochs using GNSS data and the main dependence of ionospheric delays on solar and magnetic conditions. Since the ionospheric behavior is highly dependent on the region of the Earth, different region-based algorithmic modifications have been implemented in GMV's magicSBAS ionospheric algorithms to be able to estimate and forecast ionospheric delays worldwide. Different TEC prediction approaches outlined here will certainly help to learn about forecasting ionospheric ionization.

Pim1 kinase regulates c-Kit gene translation.

PubMed

An, Ningfei; Cen, Bo; Cai, Houjian; Song, Jin H; Kraft, Andrew; Kang, Yubin

2016-01-01

Receptor tyrosine kinase, c-Kit (CD117) plays a pivotal role in the maintenance and expansion of hematopoietic stem/progenitor cells (HSPCs). Additionally, over-expression and/or mutational activation of c-Kit have been implicated in numerous malignant diseases including acute myeloid leukemia. However, the translational regulation of c-Kit expression remains largely unknown. We demonstrated that loss of Pim1 led to specific down-regulation of c-Kit expression in HSPCs of Pim1 -/- mice and Pim1 -/- 2 -/- 3 -/- triple knockout (TKO) mice, and resulted in attenuated ERK and STAT3 signaling in response to stimulation with stem cell factor. Transduction of c-Kit restored the defects in colony forming capacity seen in HSPCs from Pim1 -/- and TKO mice. Pharmacologic inhibition and genetic modification studies using human megakaryoblastic leukemia cells confirmed the regulation of c-Kit expression by Pim1 kinase: i.e., Pim1-specific shRNA knockdown down-regulated the expression of c-Kit whereas overexpression of Pim1 up-regulated the expression of c-Kit. Mechanistically, inhibition or knockout of Pim1 kinase did not affect the transcription of c-Kit gene. Pim1 kinase enhanced c-Kit 35 S methionine labeling and increased the incorporation of c-Kit mRNAs into the polysomes and monosomes, demonstrating that Pim1 kinase regulates c-Kit expression at the translational level. Our study provides the first evidence that Pim1 regulates c-Kit gene translation and has important implications in hematopoietic stem cell transplantation and cancer treatment.

Early Experience with Technology-Based Eye Care Services (TECS): A Novel Ophthalmologic Telemedicine Initiative.

PubMed

Maa, April Y; Wojciechowski, Barbara; Hunt, Kelly J; Dismuke, Clara; Shyu, Jason; Janjua, Rabeea; Lu, Xiaoqin; Medert, Charles M; Lynch, Mary G

2017-04-01

The aging population is at risk of common eye diseases, and routine eye examinations are recommended to prevent visual impairment. Unfortunately, patients are less likely to seek care as they age, which may be the result of significant travel and time burdens associated with going to an eye clinic in person. A new method of eye-care delivery that mitigates distance barriers and improves access was developed to improve screening for potentially blinding conditions. We present the quality data from the early experience (first 13 months) of Technology-Based Eye Care Services (TECS), a novel ophthalmologic telemedicine program. With TECS, a trained ophthalmology technician is stationed in a primary care clinic away from the main hospital. The ophthalmology technician follows a detailed protocol that collects information about the patient's eyes. The information then is interpreted remotely. Patients with possible abnormal findings are scheduled for a face-to-face examination in the eye clinic. Any patient with no known ocular disease who desires a routine eye screening examination is eligible. Technology-Based Eye Care Services was established in 5 primary care clinics in Georgia surrounding the Atlanta Veterans Affairs hospital. Four program operation metrics (patient satisfaction, eyeglass remakes, disease detection, and visit length) and 2 access-to-care metrics (appointment wait time and no-show rate) were tracked. Care was rendered to 2690 patients over the first 13 months of TECS. The program has been met with high patient satisfaction (4.95 of 5). Eyeglass remake rate was 0.59%. Abnormal findings were noted in 36.8% of patients and there was >90% agreement between the TECS reading and the face-to-face findings of the physician. TECS saved both patient (25% less) and physician time (50% less), and access to care substantially improved with 99% of patients seen within 14 days of contacting the eye clinic, with a TECS no-show rate of 5.2%. The early experience with TECS has been promising. Tele-ophthalmology has the potential to improve operational efficiency, reduce cost, and significantly improve access to care. Although further study is necessary, TECS shows potential to help prevent avoidable vision loss. Published by Elsevier Inc.

The identification of four histidine kinases that influence sporulation in Clostridium thermocellum.

PubMed

Mearls, Elizabeth B; Lynd, Lee R

2014-08-01

In this study, we sought to identify genes involved in the onset of spore formation in Clostridium thermocellum via targeted gene deletions, gene over-expression, and transcriptional analysis. We determined that three putative histidine kinases, clo1313_0286, clo1313_2735 and clo1313_1942 were positive regulators of sporulation, while a fourth kinase, clo1313_1973, acted as a negative regulator. Unlike Bacillus or other Clostridium species, the deletion of a single positively regulating kinase was sufficient to abolish sporulation in this organism. Sporulation could be restored in these asporogenous strains via overexpression of any one of the positive regulators, indicating a high level of redundancy between these kinases. In addition to having a sporulation defect, deletion of clo1313_2735 produced L-forms. Thus, this kinase may play an additional role in repressing L-form formation. This work suggests that C. thermocellum enters non-growth states based on the sensory input from multiple histidine kinases. The ability to control the development of non-growth states at the genetic level has the potential to inform strategies for improved strain development, as well as provide valuable insight into C. thermocellum biology. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Structure of Arabidopsis thaliana OST1 Provides Insights into the Kinase Regulation Mechanism in Response to Osmotic Stress

PubMed Central

Yunta, Cristina; Martínez-Ripoll, Martín; Zhu, Jian-Kang; Albert, Armando

2013-01-01

SnRK [SNF1 (sucrose non-fermenting-1)-related protein kinase] 2.6 [open stomata 1 (OST1)] is well characterized at molecular and physiological levels to control stomata closure in response to water-deficit stress. OST1 is a member of a family of 10 protein kinases from Arabidopsis thaliana (SnRK2) that integrates abscisic acid (ABA)-dependent and ABA-independent signals to coordinate the cell response to osmotic stress. A subgroup of protein phosphatases type 2C binds OST1 and keeps the kinase dephosphorylated and inactive. Activation of OST1 relies on the ABA-dependent inhibition of the protein phosphatases type 2C and the subsequent self-phosphorylation of the kinase. The OST1 ABA-independent activation depends on a short sequence motif that is conserved among all the members of the SnRK2 family. However, little is known about the molecular mechanism underlying this regulation. The crystallographic structure of OST1 shows that ABA-independent regulation motif stabilizes the conformation of the kinase catalytically essential α C helix, and it provides the basis of the ABA-independent regulation mechanism for the SnRK2 family of protein kinases. PMID:21983340

The mapping of ionospheric TEC for central Russian and European regions on the base of GPS and GLONASS measurements

NASA Astrophysics Data System (ADS)

Shagimuratov, Irk; Cherniak, Iurii; Zakharenkova, Irina; Ephishov, Ivan; Krankowski, Andrzej; Radievsky, Alexander

2014-05-01

The total electron content (TEC) is a key parameter not only for space radio communication but also for addressing the fundamental problems of the ionosphere physics and near Earth space. Currently, the main sources of information on the TEC in the global scale are GNSS signals measurements. The spatial-temporal behavior of the ionosphere can be most effectively analyzed using TEC maps. To date, global IGS global ionospheric maps with a resolution of 2.5 degree in latitude and 5 in longitude and a time resolution of 2 h are most widely used. To study the detailed structure of the ionospheric gradients and rapid process as well as for precise positioning task it is necessary to use more precise regional TEC maps. The Regional TEC maps are currently constructed by different research groups for different regions: USA, Europe, Japan etc. The West Department of IZMIRAN research group is a one in Russia who works on the task of regional ionosphere mapping since 2000. It was developed the methodology for obtaining information on the spatial TEC distribution, TEC maps of the ionosphere on the basis of the algorithm for multi-station processing of GNSS observations. Using a set of algorithms and programs, regional TEC maps with a spatial resolution of 1° and a time resolution up to 15 min can be produced. Here is developed the approach to establish the regular online internet service for regional ionosphere mapping of the Western Russia and Eastern Europe. Nowadays the development of GLONASS navigation system is completely finished and it consists of a constellation of more than 24 satellites. It is good perspective for investigations of the ionosphere structure and dynamics on the base of the simultaneous observations of GPS and GLONASS systems. The GLONASS satellites have the inclination about 64 degrees as against GPS satellites with 56. So the GLONASS provides opportunity to study the high latitude ionosphere. The different scale electron density irregularities, presented in high latitude ionosphere, can complicate phase ambiguity resolution. As known the strong gradients are observed in polar ionosphere near equator and polar walls of the main ionospheric trough. At high latitudes GLONASS satellites are observed on higher elevations that decrease the influence of horizontal ionospheric gradients and as consequence enable represent with more true Total Electron Content over individual high latitude station. In the report we discuss the features determining TEC from GLONASS observations and demonstrate its advantages for the high latitude ionosphere's studies. A comparison with TEC measurements from GPS/GLONASS for quiet and disturbed geomagnetic conditions is also presented. This work is supported by RFBR grant 14-07-00512.

Space Weather Activities of IONOLAB Group: TEC Mapping

NASA Astrophysics Data System (ADS)

Arikan, F.; Yilmaz, A.; Arikan, O.; Sayin, I.; Gurun, M.; Akdogan, K. E.; Yildirim, S. A.

2009-04-01

Being a key player in Space Weather, ionospheric variability affects the performance of both communication and navigation systems. To improve the performance of these systems, ionosphere has to be monitored. Total Electron Content (TEC), line integral of the electron density along a ray path, is an important parameter to investigate the ionospheric variability. A cost-effective way of obtaining TEC is by using dual-frequency GPS receivers. Since these measurements are sparse in space, accurate and robust interpolation techniques are needed to interpolate (or map) the TEC distribution for a given region in space. However, the TEC data derived from GPS measurements contain measurement noise, model and computational errors. Thus, it is necessary to analyze the interpolation performance of the techniques on synthetic data sets that can represent various ionospheric states. By this way, interpolation performance of the techniques can be compared over many parameters that can be controlled to represent the desired ionospheric states. In this study, Multiquadrics, Inverse Distance Weighting (IDW), Cubic Splines, Ordinary and Universal Kriging, Random Field Priors (RFP), Multi-Layer Perceptron Neural Network (MLP-NN), and Radial Basis Function Neural Network (RBF-NN) are employed as the spatial interpolation algorithms. These mapping techniques are initially tried on synthetic TEC surfaces for parameter and coefficient optimization and determination of error bounds. Interpolation performance of these methods are compared on synthetic TEC surfaces over the parameters of sampling pattern, number of samples, the variability of the surface and the trend type in the TEC surfaces. By examining the performance of the interpolation methods, it is observed that both Kriging, RFP and NN have important advantages and possible disadvantages depending on the given constraints. It is also observed that the determining parameter in the error performance is the trend in the Ionosphere. Optimization of the algorithms in terms of their performance parameters (like the choice of the semivariogram function for Kriging algorithms and the hidden layer and neuron numbers for MLP-NN) mostly depend on the behavior of the ionosphere at that given time instant for the desired region. The sampling pattern and number of samples are the other important parameters that may contribute to the higher errors in reconstruction. For example, for all of the above listed algorithms, hexagonal regular sampling of the ionosphere provides the lowest reconstruction error and the performance significantly degrades as the samples in the region become sparse and clustered. The optimized models and coefficients are applied to regional GPS-TEC mapping using the IONOLAB-TEC data (www.ionolab.org). Both Kriging combined with Kalman Filter and dynamic modeling of NN are also implemented as first trials of TEC and space weather predictions.

Case study of ISWI in Vietnam: A comparison of ionospheric parameters observed over Ho Chi Minh with IRI predictions

NASA Astrophysics Data System (ADS)

Lan, Hoang Thai; Tam, Dao Ngoc Hanh

2014-01-01

For the contribution of Vietnam to ISWI activities, there are 3 GPS receivers, 3 Ionosondes, 1 AWESOME and 1 MAGDAS operating in Vietnam. With a special geographical position stretching from the north tropic to the magnetic equator, Vietnam is an interesting area to supplement the data for the Global Space Weather Model. The Ionosphere is an important indicator of Space Weather and the International Reference Ionosphere (IRI) model has become widely accepted. The first task of ionospheric science in a new location is often comparing the observed data with IRI. This paper presents the results of comparisons of the foF2 and TEC observed over Ho Chi Minh City (10.51 N, 106.33 E) with the values calculated according to the IRI-2007 in order to evaluate the applicability of the model in forecasting for the equatorial region of Vietnam. We compare the critical frequency of layer F (foF2) and Total Electron Content (TEC) values for two phases of solar activity. The results show very good diurnal correlations between the observed foF2 and TEC with IRI values in the decreasing solar activity period 2003 ± 2006 (the deviation < 15%). In the increasing period 2009 ± 2012, good correlation was in the morning time before the foF2 peak at about 10 LT, with a deviation about 10% (except 2012). However, after 10 LT, the IRI-foF2 values rose up and the deviations were about 25% to 30%, especially during evening. In the years with low solar activity (SSN < 40), the IRI-foF2 are almost always higher than the observed foF2 data and vice versa for the years with SSN > 40. This is a note for correction IRI model applying for Vietnam. The comparison of the TEC shows that the correlation between GPS-TEC and IRI-TEC generally was good with coefficients k > 0.8 and R > 0.9 for the period 2006 - 2010. The worst relationship were March, April, September, October, November and December 2011, corresponding to periods when the TEC gradients are highest. The phenomenon of decline in the TEC at noon over Ho Chi Minh City observed pretty weak. This phenomenon appeared only in a few months from April to September, when the ionization is high. In the period from 0 to 5 am local time, the average minimum GPS-TEC observed over Ho Chi Minh City is about 3 tecu, while the IRI-TEC value is ~ 0.3. Thus, the IRI-TEC values should be recalibrated.

Short-term estimation of GNSS TEC using a neural network model in Brazil

NASA Astrophysics Data System (ADS)

Ferreira, Arthur Amaral; Borges, Renato Alves; Paparini, Claudia; Ciraolo, Luigi; Radicella, Sandro M.

2017-10-01

This work presents a novel Neural Network (NN) model to estimate Total Electron Content (TEC) from Global Navigation Satellite Systems (GNSS) measurements in three distinct sectors in Brazil. The purpose of this work is to start the investigations on the development of a regional model that can be used to determine the vertical TEC over Brazil, aiming future applications on a near real-time frame estimations and short-term forecasting. The NN is used to estimate the GNSS TEC values at void locations, where no dual-frequency GNSS receiver that may be used as a source of data to GNSS TEC estimation is available. This approach is particularly useful for GNSS single-frequency users that rely on corrections of ionospheric range errors by TEC models. GNSS data from the first GLONASS network for research and development (GLONASS R&D network) installed in Latin America, and from the Brazilian Network for Continuous Monitoring of the GNSS (RMBC) were used on TEC calibration. The input parameters of the NN model are based on features known to influence TEC values, such as geographic location of the GNSS receiver, magnetic activity, seasonal and diurnal variations, and solar activity. Data from two ten-days periods (from DoY 154 to 163 and from 282 to 291) are used to train the network. Three distinct analyses have been carried out in order to assess time-varying and spatial performance of the model. At the spatial performance analysis, for each region, a set of stations is chosen to provide training data to the NN, and after the training procedure, the NN is used to estimate vTEC behavior for the test station which data were not presented to the NN in training process. An analysis is done by comparing, for each testing station, the estimated NN vTEC delivered by the NN and reference calibrated vTEC. Also, as a second analysis, the network ability to forecast one day after the time interval (DoY 292) based on information of the second period of investigation is also assessed in order to verify the feasibility on using low amount of data for short-term forecasting. In a third analysis, the spatial performance of the NN model is assessed and compared against CODE Global Ionospheric Maps during the geomagnetic storm registered on 13th and 14th October 2016. The results obtained from the three described analyses indicate that even using a ten-days period of data to train the network, the proposed NN model provides good spatial performance and presents to be a promising tool for short-term forecasting. The results obtained in the analysis presented a root mean squared error less than 7.9 TECU in all scenarios under investigation.

Cell cycle-dependent regulation of Aurora kinase B mRNA by the Microprocessor complex.

PubMed

Jung, Eunsun; Seong, Youngmo; Seo, Jae Hong; Kwon, Young-Soo; Song, Hoseok

2014-03-28

Aurora kinase B regulates the segregation of chromosomes and the spindle checkpoint during mitosis. In this study, we showed that the Microprocessor complex, which is responsible for the processing of the primary transcripts during the generation of microRNAs, destabilizes the mRNA of Aurora kinase B in human cells. The Microprocessor-mediated cleavage kept Aurora kinase B at a low level and prevented premature entrance into mitosis. The cleavage was reduced during mitosis leading to the accumulation of Aurora kinase B mRNA and protein. In addition to Aurora kinase B mRNA, the processing of other primary transcripts of miRNAs were also decreased during mitosis. We found that the cleavage was dependent on an RNA helicase, DDX5, and the association of DDX5 and DDX17 with the Microprocessor was reduced during mitosis. Thus, we propose a novel mechanism by which the Microprocessor complex regulates stability of Aurora kinase B mRNA and cell cycle progression. Copyright © 2014 Elsevier Inc. All rights reserved.

Protein Kinases in Shaping Plant Architecture.

PubMed

Wu, Juan; Wang, Bo; Xin, Xiaoyun; Ren, Dongtao

2018-02-13

Plant architecture, the three-dimensional organization of the plant body, includes the branching pattern and the size, shape, and position of organs. Plant architecture is genetically controlled and is influenced by environmental conditions. The regulations occur at most of the stages from the first division of the fertilized eggs to the final establishment of plant architecture. Among the various endogenous regulators, protein kinases and their associated signaling pathways have been shown to play important roles in regulating the process of plant architecture establishment. In this review, we summarize recent progress in the understanding of the mechanisms by which plant architecture formation is regulated by protein kinases, especially mitogen-activated protein kinase (MAPK). Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Identification of a novel human kinase supporter of Ras (hKSR-2) that functions as a negative regulator of Cot (Tpl2) signaling.

PubMed

Channavajhala, Padma L; Wu, Leeying; Cuozzo, John W; Hall, J Perry; Liu, Wei; Lin, Lih-Ling; Zhang, Yuhua

2003-11-21

Kinase suppressor of Ras (KSR) is an integral and conserved component of the Ras signaling pathway. Although KSR is a positive regulator of the Ras/mitogen-activated protein (MAP) kinase pathway, the role of KSR in Cot-mediated MAPK activation has not been identified. The serine/threonine kinase Cot (also known as Tpl2) is a member of the MAP kinase kinase kinase (MAP3K) family that is known to regulate oncogenic and inflammatory pathways; however, the mechanism(s) of its regulation are not precisely known. In this report, we identify an 830-amino acid novel human KSR, designated hKSR-2, using predictions from genomic data base mining based on the structural profile of the KSR kinase domain. We show that, similar to the known human KSR, hKSR-2 co-immunoprecipitates with many signaling components of the Ras/MAPK pathway, including Ras, Raf, MEK-1, and ERK-1/2. In addition, we demonstrate that hKSR-2 co-immunoprecipitates with Cot and that co-expression of hKSR-2 with Cot significantly reduces Cot-mediated MAPK and NF-kappaB activation. This inhibition is specific to Cot, because Ras-induced ERK and IkappaB kinase-induced NF-kappaB activation are not significantly affected by hKSR-2 co-expression. Moreover, Cot-induced interleukin-8 production in HeLa cells is almost completely inhibited by the concurrent expression of hKSR-2, whereas transforming growth factor beta-activated kinase 1 (TAK1)/TAK1-binding protein 1 (TAB1)-induced interleukin-8 production is not affected by hKSR-2 co-expression. Taken together, these results indicate that hKSR-2, a new member of the KSR family, negatively regulates Cot-mediated MAP kinase and NF-kappaB pathway signaling.

Measurement of the Thermal Expansion Coefficient for Ultra-High Temperatures up to 3000 K

NASA Astrophysics Data System (ADS)

Kompan, T. A.; Kondratiev, S. V.; Korenev, A. S.; Puhov, N. F.; Inochkin, F. M.; Kruglov, S. K.; Bronshtein, I. G.

2018-03-01

The paper is devoted to a new high-temperature dilatometer, a part of the State Primary Standard of the thermal expansion coefficient (TEC) unit. The dilatometer is designed for investigation and certification of materials for TEC standards in the range of extremely high temperatures. The critical review of existing methods of TEC measurements is given. Also, the design, principles of operation and metrological parameters of the new device are described. The main attention is paid to the system of machine vision that allows accurate measurement of elongation at high temperatures. The results of TEC measurements for graphite GIP-4, single crystal Al2O3, and some other materials are also presented.

Allosteric activation of apicomplexan calcium-dependent protein kinases

DOE PAGES

Ingram, Jessica R.; Knockenhauer, Kevin E.; Markus, Benedikt M.; ...

2015-08-24

Calcium-dependent protein kinases (CDPKs) comprise the major group of Ca 2+-regulated kinases in plants and protists. It has long been assumed that CDPKs are activated, like other Ca 2+-regulated kinases, by derepression of the kinase domain (KD). However, we found that removal of the autoinhibitory domain from Toxoplasma gondii CDPK1 is not sufficient for kinase activation. From a library of heavy chain-only antibody fragments (VHHs), we isolated an antibody (1B7) that binds TgCDPK1 in a conformation-dependent manner and potently inhibits it. We uncovered the molecular basis for this inhibition by solving the crystal structure of the complex and simulating, throughmore » molecular dynamics, the effects of 1B7–kinase interactions. In contrast to other Ca 2+-regulated kinases, the regulatory domain of TgCDPK1 plays a dual role, inhibiting or activating the kinase in response to changes in Ca 2+ concentrations. We propose that the regulatory domain of TgCDPK1 acts as a molecular splint to stabilize the otherwise inactive KD. This dependence on allosteric stabilization reveals a novel susceptibility in this important class of parasite enzymes.« less

The regulation of smooth muscle contractility by zipper-interacting protein kinase.

PubMed

Ihara, Eikichi; MacDonald, Justin A

2007-01-01

Smooth muscle contractility is mainly regulated by phosphorylation of the 20 kDa myosin light chains (LC20), a process that is controlled by the opposing activities of myosin light chain kinase (MLCK) and myosin light chain phosphatase (MLCP). Recently, intensive research has revealed that various protein kinase networks including Rho-kinase, integrin-linked kinase, zipper-interacting protein kinase (ZIPK), and protein kinase C (PKC) are involved in the regulation of LC20 phosphorylation and have important roles in modulating smooth muscle contractile responses to Ca2+ (i.e., Ca2+ sensitization and Ca2+ desensitization). Here, we review the general background and structure of ZIPK and summarize our current understanding of its involvement in a number of cell processes including cell death (apoptosis), cell motility, and smooth muscle contraction. ZIPK has been found to induce the diphosphorylation of LC20 at Ser-19 and Thr-18 in a Ca2+-independent manner and to regulate MLCP activity directly through its phosphorylation of the myosin-targeting subunit of MLCP or indirectly through its phosphorylation of the PKC-potentiated inhibitory protein of MLCP. Future investigations of ZIPK function in smooth muscle will undoubtably focus on determining the mechanisms that regulate its cellular activity, including the identification of upstream signaling pathways, the characterization of autoinhibitory domains and regulatory phosphorylation sites, and the development of specific inhibitor compounds.

Anomalous variation in GPS based TEC measurements prior to the 30 September 2009 Sumatra Earthquake

NASA Astrophysics Data System (ADS)

Karia, Sheetal; Pathak, Kamlesh

This paper investigates the features of pre-earthquake ionospheric anomalies in the total elec-tron content (TEC) data obtained on the basis of regular GPS observations from the GPS receiver at SVNIT Surat (21.16 N, 72.78 E Geog) located at the northern crest of equatorial anomaly region. The data has been analysed for 5 different earthquakes that occurred during 2009 in India and its neighbouring regions. Our observation shows that for the cases of the earthquake, in which the preparation area lies between the crests of the equatorial anomaly close to the geomagnetic equator the enhancement in TEC was followed by a depletion in TEC on the day of earthquake, which may be connected to the equatorial anomaly shape distortions. For the analysis of the ionospheric effects of one of such case-the 30 September 2009 Sumatra earthquake, Global Ionospheric Maps of TEC were used. The possible influence of the earth-quake preparation processes on the main low-latitude ionosphere peculiarity—the equatorial anomaly—is discussed.

Ionospheric Response to the Magnetic Storm of 22 June 2015

NASA Astrophysics Data System (ADS)

Mansilla, Gustavo A.

2018-03-01

A global study is made of the response of the total electron content of the ionosphere (TEC) to the geomagnetic storm occurred on 22 June 2015 (one of the strongest geomagnetic storms of the current Solar Cycle 24). Using data from 44 sites, a hemispheric comparison is made by considering high latitudes (> 50°), middle latitudes (30°-50°) and low latitudes (30°N-30°S). The main features observed were: increases in TEC at high latitudes prior to the storm main phase, a considerable asymmetry of TEC response at middle and low latitudes of the Northern Hemisphere and the Southern Hemisphere and decreases at equatorial latitudes. The long duration enhancements in TEC were well correlated with increases in the O/N2 ratio but decreases in TEC had not associated decreases in the O/N2 ratio as occur with the decreases in the electron density. Besides, prompt penetration electric fields can play an important role in the equatorial and low-latitude ionosphere during main phase of the storm.

Assessment of Ionospheric Anomaly Prior to the Large Earthquake: 2D and 3D Analysis in Space and Time for the 2011 Tohoku Earthquake (Mw9.0)

NASA Astrophysics Data System (ADS)

Hattori, Katsumi; Hirooka, Shinji; Han, Peng

2016-04-01

The ionospheric anomalies possibly associated with large earthquakes have been reported by many researchers. In this paper, Total Electron Content (TEC) and tomography analyses have been applied to investigate the spatial and temporal distributions of ionospheric electron density prior to the 2011 Off the Pacific Coast of Tohoku earthquake (Mw9.0). Results show significant TEC enhancements and an interesting three dimensional structure prior to the main shock. As for temporal TEC changes, the TEC value increases 3－4 days before the earthquake remarkably, when the geomagnetic condition was relatively quiet. In addition, the abnormal TEC enhancement area in space was stalled above Japan during the period. Tomographic results show that three dimensional distribution of electron density decreases around 250 km altitude above the epicenter (peak is located just the east-region of the epicenter) and increases the mostly entire region between 300 and 400 km.

Ionospheric total electron content seismo-perturbation after Japan's March 11, 2011, M=9.0 Tohoku earthquake under a geomagnetic storm; a nonlinear principal component analysis

NASA Astrophysics Data System (ADS)

Lin, Jyh-Woei

2012-10-01

Nonlinear principal component analysis (NLPCA) is implemented to analyze the spatial pattern of total electron content (TEC) anomalies 3 hours after Japan's Tohoku earthquake that occurred at 05:46:23 on 11 March, 2011 (UTC) ( M w =9). A geomagnetic storm was in progress at the time of the earthquake. NLPCA and TEC data processing were conducted on the global ionospheric map (GIM) for the time between 08:30 to 09:30 UTC, about 3 hours after this devastating earthquake and ensuing tsunami. Analysis results show stark earthquake-associated TEC anomalies that are widespread, and appear to have been induced by two acoustic gravity waves due to strong shaking (vertical acoustic wave) and the generation of the tsunami (horizontal Rayleigh mode gravity wave). The TEC anomalies roughly fit the initial mainshock and movement of the tsunami. Observation of the earthquake-associated TEC anomalies does not appear to be affected by a contemporaneous geomagnetic storm.

Earthquake Related Variation of Total Electron Content in Ionosphere over Chinese Mainland Derived from Observations of a Nationwide GNSS Network

NASA Astrophysics Data System (ADS)

Gan, Weijun

2016-07-01

Crustal Movement Observation Network of China (CMONOC) is a key national scientific infrastructure project carried out during 1997-2012 with 2 phases. The network is composed of 260 continuously observed GNSS stations (CORS) and 2081 campaign mode GNSS stations, with the main purpose to monitor the crustal movement, perceptible water vapor (PWV), total electron content (TEC), and many other tectonic and environmental elements around mainland China, by mainly using the Global Navigation Satellite System (GNSS) technology. Here, based on the GNSS data of 260 CORS of COMNOC for about 5 years, we investigated the characteristics of TEC in ionosphere over Chinese Mainland and discussed if there was any abnormal change of TEC before and after a big earthquake. our preliminary results show that it is hard to see any convincing precursor of TEC before a big earthquake. However, the huge energy released by a big earthquake can obviously disturb the TEC over meizoseismal area.

Investigation of the Effects of Solar and Geomagnetic Changes on the Total Electron Content: Mid-Latitude Region

NASA Astrophysics Data System (ADS)

Ulukavak, Mustafa; Yalcinkaya, Mualla

2016-04-01

The Global Positioning System (GPS) is used as an important tool for ionosphere monitoring and obtaining the Total Electron Content (TEC). GPS satellites, positioned in the Earth's orbit, are used as sensors to investigate the space weather conditions. In this study, solar and geomagnetic activity variations were investigated between the dates 1 March-30 June 2015 for the mid-latitude region. GPS-TEC variations were calculated for each selected International GNSS Service (IGS) station in Europe. GNSS data was obtained from Crustal Dynamics Data and Information System (CDDIS) archive. Solar and geomagnetic activity indices (Kp, F10.7 ve Dst) were obtained from the Oceanic and Atmospheric Administration (NOAA), the Canadian Space Weather Forecast Centre (CSWFC) and Data Analysis Center for geomagnetism and Space Magnetism Graduate School of Science, Kyoto University (WDC) archives. GPS-TEC variations were determined for the quiet periods of the solar and geomagnetic activities. GPS-TEC changes were then compared with respect to the quiet periods of the solar and geomagnetic activities. Global Ionosphere Maps (GIM) IONEX files, obtained from the IGS analysis center, was used to check the robustness of the GPS-TEC variations. The investigations revealed that it is possible to use the GPS-TEC data for monitoring the ionospheric disturbances.

Empirical forecast of quiet time ionospheric Total Electron Content maps over Europe

NASA Astrophysics Data System (ADS)

Badeke, Ronny; Borries, Claudia; Hoque, Mainul M.; Minkwitz, David

2018-06-01

An accurate forecast of the atmospheric Total Electron Content (TEC) is helpful to investigate space weather influences on the ionosphere and technical applications like satellite-receiver radio links. The purpose of this work is to compare four empirical methods for a 24-h forecast of vertical TEC maps over Europe under geomagnetically quiet conditions. TEC map data are obtained from the Space Weather Application Center Ionosphere (SWACI) and the Universitat Politècnica de Catalunya (UPC). The time-series methods Standard Persistence Model (SPM), a 27 day median model (MediMod) and a Fourier Series Expansion are compared to maps for the entire year of 2015. As a representative of the climatological coefficient models the forecast performance of the Global Neustrelitz TEC model (NTCM-GL) is also investigated. Time periods of magnetic storms, which are identified with the Dst index, are excluded from the validation. By calculating the TEC values with the most recent maps, the time-series methods perform slightly better than the coefficient model NTCM-GL. The benefit of NTCM-GL is its independence on observational TEC data. Amongst the time-series methods mentioned, MediMod delivers the best overall performance regarding accuracy and data gap handling. Quiet-time SWACI maps can be forecasted accurately and in real-time by the MediMod time-series approach.

Quantifications of Geomagnetic Storm Impact on TEC and NmF2 during 2013 Mar. event

NASA Astrophysics Data System (ADS)

Shim, J. S.; Tsagouri, I.; Goncharenko, L. P.; Mays, M. L.; Taktakishvili, A.; Rastaetter, L.; Kuznetsova, M. M.

2016-12-01

We investigate the ionospheric response to 2013 Mar. geomagnetic storm event using GPS TEC, ISR and ionosonde observations in North American sector. In order to quantify variations of TEC and NmF2 (or foF2) due to the storm, we remove the background quiet-time values (e.g., TEC of one day prior to the storm, NmF2 median and average of five quietest days for 30 days prior to the storm). In addition, in order to assess modeling capability of reproducing storm impacts on TEC and NmF2, we compare the observations with various model simulations, which are obtained from empirical, physics-based, and data assimilation models. Further, we investigate how uncertainty in the interplanetary magnetic field (IMF) impacts on TEC and NmF2 during the geomagnetic storm event. For this uncertainty study, we use a physics-based coupled ionosphere-thermosphere model, CTIPe, and solar wind parameters obtained from ensemble of WSA-ENLIL+Cone model simulations. This study has been supported by the Community Coordinated Modeling Center (CCMC) at the Goddard Space Flight Center. Model outputs and observational data used for the study will be permanently posted at the CCMC website (http://ccmc.gsfc.nasa.gov) for the space science communities to use.

Statistical seismo-ionospheric precursors of M7.0+ earthquakes in Circum-Pacific seismic belt by GPS TEC measurements

NASA Astrophysics Data System (ADS)

Li, Wang; Yue, Jianping; Guo, Jinyun; Yang, Yang; Zou, Bin; Shen, Yi; Zhang, Kefei

2018-03-01

The Circum-Pacific seismic belt is the region heavily affected by earthquakes in the world. The relationship between earthquake (e.g., the geographic location, occurrence time, magnitude, and focal depth) and ionospheric anomalies in the belt was investigated using 100 M7.0+ earthquakes during 2006-2015. The ground-based GPS measurements and global ionosphere map (GIM) data were used for the analyses of the ionospheric variations preceding the earthquakes. The results indicated that the occurrence rate of total electron content (TEC) anomalies was proportional to the magnitude and inversely proportional to the focal depth to a certain degree, and the occurrence frequency of anomalies had a rising trend with the days getting close to the main shock. The occurrence rate of TEC anomalies in the Southern hemisphere was larger than that in the Northern hemisphere. Besides, the spatial characteristics of TEC anomalies showed that the anomalies in low-middle latitudes did not coincide with the epicenter, sometimes the anomalies were also observed in the corresponding conjugated region. However, the TEC anomalies in the high latitude usually appeared around the epicenter and within the seismogenic zone while no TEC anomalies appeared in the conjugated area. These results may have potential applications to the earthquake prediction in the Circum-Pacific seismic belt.

Structural and mechanistic insights into Mps1 kinase activation.

PubMed

Wang, Wei; Yang, Yuting; Gao, Yuefeng; Xu, Quanbin; Wang, Feng; Zhu, Songcheng; Old, William; Resing, Katheryn; Ahn, Natalie; Lei, Ming; Liu, Xuedong

2009-08-01

Mps1 is one of the several essential kinases whose activation is required for robust mitotic spindle checkpoint signalling. The activity of Mps1 is tightly regulated and increases dramatically during mitosis or in response to spindle damage. To understand the molecular mechanism underlying Mps1 regulation, we determined the crystal structure of the kinase domain of Mps1. The 2.7-A-resolution crystal structure shows that the Mps1 kinase domain adopts a unique inactive conformation. Intramolecular interactions between the key Glu residue in the C helix of the N-terminal lobe and the backbone amides in the catalytic loop lock the kinase in the inactive conformation. Autophosphorylation appears to be a priming event for kinase activation. We identified Mps1 autophosphorylation sites in the activation and the P+1 loops. Whereas activation loop autophosphorylation enhances kinase activity, autophosphorylation at the P+1 loop (T686) is associated with the active kinase. Mutation of T686 autophosphorylation site impairs both autophosphorylation and transphosphorylation. Furthermore, we demonstrated that phosphorylation of T676 may be a priming event for phosphorylation at T686. Finally, we identified two critical lysine residues in the loop between helices EF and F that are essential for substrate recruitment and maintaining high levels of kinase activity. Our studies reveal critical biochemical mechanisms for Mps1 kinase regulation.

Interphase ribosomal RNA cistron staining in thyroid epithelial cells in Grave's disease, Hashimoto's thyroiditis and benign and malignant tumours of the thyroid gland

PubMed Central

Mamaev, N N; Grynyeva, E N; Blagosklonnaya, Y V

1996-01-01

Aim—To evaluate the expression of ribosomal cistrons in human thyroid epithelial cells (TECs) of patients with Grave's disease, Hashimoto's thyroiditis and benign and malignant tumours of the thyroid gland. Methods—TEC nucleoli were investigated in fine needle biopsy specimens from 10 controls, 39 patients with Grave's disease, 15 with Hashimoto's thyroiditis, 56 with benign, and 15 with malignant tumours of the thyroid. A one step silver staining method was applied. In most cases serum concentrations of thyroxine and triiodothyronine as well as goitre size were determined. In every case 100 TECs were evaluated for the mean numbers of nucleoli and for the average number of argyrophilic nucleolar organiser regions (AgNORs) per nucleus. Results—NORs were activated in all patients, but not in controls. The numbers of AgNORs in patients with Grave's disease were closely correlated with thyroxine or triiodothyronine, or both, concentrations and with the size of the thyroid. In patients with Hashimoto's thyroiditis about 30% of TECs nucleoli did not contain AgNORs, whereas others were heavily impregnated with silver. Compared with controls and benign tumours, the nucleoli of carcinomatous TECs were larger and irregular in shape. The mean number of AgNORs per nucleus in malignant cells was higher than that in their benign counterparts. Conclusions—The mechanism by which NORs are activated in TECs varies depending on the type of lesion. The higher AgNOR score in TECs from malignant tumours can be used to distinguish them from their benign counterparts. Images PMID:16696083

Complex analysis of the ionospheric response to operation of ``Progress'' cargo spacecraft according to the data of GNSS receivers in Baikal region

NASA Astrophysics Data System (ADS)

Ishin, Artem; Voeykov, Sergey; Perevalova, Natalia; Khakhinov, Vitaliy

2017-12-01

As a part of the Plasma-Progress and Radar-Progress space experiments conducted from 2006 to 2014, effects of the Progress spacecraft engines on the ionosphere have been studied using data from Global Navigation Satellite System (GNSS) receivers. 72 experiments have been carried out. All these experiments were based on data from the International GNSS Service (IGS) to record ionospheric plasma irregularities caused by engine operation. 35 experiments used data from the ISTP SB RAS network SibNet. The analysis of the spatio-temporal structure of total electron content (TEC) variations has shown that the problem of identifying the TEC response to engine operation is complicated by a number of factors: 1) the engine effect on ionospheric plasma is strongly localized in space and has a relatively low intensity; 2) a small number of satellite-receiver radio rays due to the limited number of GNSS stations, particularly before 2013; 3) a potential TEC response is masked with background ionospheric disturbances of various intensities. However, TEC responses are identified with certainty when a satellite-receiver radio ray crosses a disturbed region within minutes after the impact. TEC responses have been registered in 7 experiments (10 % of cases). The amplitude of ionospheric response (0.3-0.16 TECU) exceeded the background TEC variations (~0.25 TECU) several times. The TEC data indicate that the ionospheric irregularity lifetime is from 4 to 10 minutes. According to the estimates we made, the transverse size of irregularities is from 12 to 30 km.

Synovial mesenchymal stem cells from osteo- or rheumatoid arthritis joints exhibit good potential for cartilage repair using a scaffold-free tissue engineering approach.

PubMed

Koizumi, K; Ebina, K; Hart, D A; Hirao, M; Noguchi, T; Sugita, N; Yasui, Y; Chijimatsu, R; Yoshikawa, H; Nakamura, N

2016-08-01

To assess whether synovial mesenchymal stem cells (SMSCs) from patients with osteoarthritis (OA) or rheumatoid arthritis (RA) can be used as an alternative cell source for cartilage repair using allogenic tissue engineered construct (TEC). Twenty-five patients (17 female, average age 61.8 years) were divided according to their pathology (control trauma group; N = 6, OA group; N = 6) and RA patients were subdivided into two groups to evaluate the impact of biologics in accordance with whether treated with biologics [Bio(+)RA; N = 7] or not [Bio(-)RA; N = 6]. We compared the following characteristics among these groups: (1) The cell proliferation capacity of SMSCs; (2) The influence of passage number on features of SMSCs; (3) The weight and volume of TEC from the same number of SMSCs; (4) Inflammatory cytokine gene expressions levels of TEC; (5) The chondrogenic potential of TEC; and (6) Osteochondral repair using TEC in athymic nude rats. SMSCs from the four groups exhibited equivalent features in the above evaluation items. In in vivo studies, the TEC-treated repair tissues for all groups exhibited significantly better outcomes than those for the untreated group and no significant differences among the four TEC groups. SMSCs from OA or RA patients are no less appropriate for repairing cartilage than those from trauma patients and thus, may be an effective source for allogenic cell-based cartilage repair. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Imaging the topside ionosphere and plasmasphere with ionospheric tomography using COSMIC GPS TEC

NASA Astrophysics Data System (ADS)

Pinto Jayawardena, Talini S.; Chartier, Alex T.; Spencer, Paul; Mitchell, Cathryn N.

2016-01-01

GPS-based ionospheric tomography is a well-known technique for imaging the total electron content (TEC) between GPS satellites and receivers. However, as an integral measurement of electron concentration, TEC typically encompasses both the ionosphere and plasmasphere, masking signatures from the topside ionosphere-plasmasphere due to the dominant ionosphere. Imaging these regions requires a technique that isolates TEC in the topside ionosphere-plasmasphere. Multi-Instrument Data Analysis System (MIDAS) employs tomography to image the electron distribution in the ionosphere. Its implementation for regions beyond is yet to be seen due to the different dynamics present above the ionosphere. This paper discusses the extension of MIDAS to image these altitudes using GPS phase-based TEC measurements and follows the work by Spencer and Mitchell (2011). Plasma is constrained to dipole field lines described by Euler potentials, resulting in a distribution symmetrical about the geomagnetic equator. A simulation of an empirical plasmaspheric model by Gallagher et al. (1988) is used to verify the technique by comparing reconstructions of the simulation with the empirical model. The Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) is used as GPS receiver locations. The verification is followed by a validation of the modified MIDAS algorithm, where the regions' TEC is reconstructed from COSMIC GPS phase measurements and qualitatively compared with previous studies using Jason-1 and COSMIC data. Results show that MIDAS can successfully image features/trends of the topside ionosphere-plasmasphere observed in other studies, with deviations in absolute TEC attributed to differences in data set properties and the resolution of the images.

Equatorial ionization anomaly development as studied by GPS TEC and foF2 over Brazil: A comparison of observations with model results from SUPIM and IRI-2012

NASA Astrophysics Data System (ADS)

Nogueira, P. A. B.; Abdu, M. A.; Souza, J. R.; Batista, I. S.; Bailey, G. J.; Santos, A. M.; Takahashi, H.

2013-11-01

The equatorial ionization anomaly (EIA) development is studied using the total electron content (TEC) observed by the Global Positioning System (GPS) satellites, the F2-layer critical frequency (foF2) as measured by digisondes operated in the Brazilian sector, and by model simulation using the SUPIM (Sheffield University Plasmasphere Ionosphere Model). We have used two indices based on foF2 and TEC to represent the strength of the EIA Southern Anomaly Crest (SAC), which are denoted, respectively, by SAC(foF2) and SAC(TEC). Significant differences in the local time variations of the EIA intensity, as represented by these two indices, are investigated. The observed SAC indices are compared with their values modeled by the SUPIM and also by the International Reference Ionosphere (IRI)-2012. The SUPIM simulations that use the standard E×B plasma drift and neutral air wind models are found to provide acceptable representations of the observed foF2 and TEC, and hence the indices SAC(foF2) and SAC(TEC) during daytime, whereas the IRI-2012 model is not, except during the post-midnight/sunrise hours. It is found that the differences in the local time variations between the SAC(foF2) and SAC(TEC) can be reduced by limiting the TEC integrations in height up to an altitude of 630 km in the SUPIM calculations. It is also found that when the EIA intensity is calculated for an intermediate dip latitude (12°S) the difference between the local time variation patterns of the two corresponding indices in the experimental data and in the SUPIM results is reduced. For the IRI-2012 values, the subequatorial station modification does not appear to have any effect.

Comparative analysis of GPS-derived TEC estimates and foF2 observations during storm conditions towards the expansion of ionospheric forecasting capabilities over Europe

NASA Astrophysics Data System (ADS)

Tsagouri, Ioanna; Belehaki, Anna; Elias, Panagiotis

2017-04-01

This paper builts the discussion on the comparative analysis of the variations in the peak electron density at F2 layer and the TEC parameter during a significant number of geomagnetic storm events that occurred in the present solar cycle 24. The ionospheric disturbances are determined through the comparison of actual observations of the foF2 critical frequency and GPS-TEC estimates obtained over European locations with the corresponding median estimates, and they are analysed in conjunction to the solar wind conditions at L1 point that are monitored by the ACE spacecraft. The quantification of the storm impact on the TEC parameter in terms of possible limitations introduced by different TEC derivation methods is carefully addressed.The results reveal similarities and differences in the response of the two parameters with respect to the solar wind drivers of the storms, as well as the local time and the latitude of the observation point. The aforementioned dependences drive the storm-time forecasts of the SWIF model (Solar Wind driven autorgressive model for Ionospheric short-term Forecast), which is operationally implemented in the DIAS system (http://dias.space.noa.gr) and extensively tested in performance at several occassions. In its present version, the model provides alerts and warnings for upcoming ionospheric disturbances, as well as single site and regional forecasts of the foF2 characteristic over Europe up to 24 hours ahead based on the assesment of the solar wind conditions at ACE location. In that respect, the results obtained above support the upgrade of the SWIF's modeling technique in forecasting the storm-time TEC variation within an operational environment several hours in advance. Preliminary results on the evaluation of the model's efficiency in TEC prediction are also discussed, giving special attention in the assesment of the capabilities through the TEC-derivation uncertanties for future discussions.

The First Use of Coordinated Ionospheric Radio and Optical Observations Over Italy: Convergence of High-and Low-Latitude Storm-Induced Effects

NASA Astrophysics Data System (ADS)

Cesaroni, C.; Alfonsi, L.; Pezzopane, M.; Martinis, C.; Baumgardner, J.; Wroten, J.; Mendillo, M.; Musicò, E.; Lazzarin, M.; Umbriaco, G.

2017-11-01

Ionospheric storm effects at midlatitudes were analyzed using different ground-based instruments distributed in Italy during the 13-15 November 2012 geomagnetic storm. These included an all-sky imager (ASI) in Asiago (45.8°N, 11.5°E), a network of dual-frequeny Global Navigation Satellite Systems receivers (Rete Integrata Nazionale GPS network), and ionosondes in Rome (41.8°N, 12.5°E) and San Vito (40.6°N, 17.8°E). GPS measurements showed an unusual enhancement of total electron content (TEC) in southern Italy, during the nights of 14 and 15 November. The ASI observed colocated enhancements of 630 nm airglow at the same time, as did variations in NmF2 measured by the ionosondes. Moreover, wave-like perturbations were identified propagating from the north. The Ensemble Empirical Mode Decomposition, applied to TEC values revealed the presence of traveling ionospheric disturbances (TIDs) propagating southward between 01:30 UT and 03:00 UT on 15 November. These TIDs were characterized by weak TEC oscillations ( ±0.5 TEC unit), period of 45 min, and velocity of 500 m/s typical of large-scale TIDs. Optical images showed enhanced airglow entering the field of view of the ASI from the N-NE at 02:00 UT and propagating to the S-SW, reaching the region covered by the GPS stations after 03:00 UT, when TEC fluctuations are very small ( ±0.2 TEC unit). The enhancement of TEC and airglow observed in southern Italy could be a consequence of a poleward expansion of the northern crest of the equatorial ionization anomaly. The enhanced airglow propagating from the north and the TEC waves resulted from energy injected at auroral latitudes as confirmed by magnetometer observations in Scandinavia.

Long-term soluble Abeta1-40 activates CaM kinase II in organotypic hippocampal cultures.

PubMed

Tardito, Daniela; Gennarelli, Massimo; Musazzi, Laura; Gesuete, Raffaella; Chiarini, Stefania; Barbiero, Valentina Sara; Rydel, Russell E; Racagni, Giorgio; Popoli, Maurizio

2007-09-01

Recent findings suggested a role for soluble amyloid-beta (Abeta) peptides in Alzheimer's disease associated cognitive decline. We investigated the action of soluble, monomeric Abeta(1-40) on CaM kinase II, a kinase involved in neuroplasticity and cognition. We treated organotypic hippocampal cultures short-term (up to 4h) and long-term (5 days) with Abeta(1-40) (1nM-5microM). Abeta did not induce cell damage, apoptosis or synaptic loss. Short-term treatment down-regulated enzymatic activity of the kinase, by reducing its Thr(286) phosphorylation. In contrast, long-term treatment (1nM-microM) markedly and significantly up-regulated enzymatic activity, with peak stimulation at 10nM (three-fold). Up-regulation of activity was associated with increased expression of the alpha-isoform of CaM kinase II, increased phosphorylation at Thr(286) (activator residue) and decreased phosphorylation at Thr(305-306) (inhibitory residues). We investigated the effect of glutamate on CaM kinase II following exposure to 1 or 10nM Abeta(1-40). As previously reported, glutamate increased CaM kinase II activity. However, the glutamate effect was not altered by pretreatment of slices with Abeta. Short- and long-term Abeta treatment showed opposite effects on CaM kinase II, suggesting that long-term changes are an adaptation to the kinase early down-regulation. The marked effect of Abeta(1-40) on the kinase suggests that semi-physiological and slowly raising peptide concentrations may have a significant impact on synaptic plasticity in the absence of synaptic loss or neuronal cell death.

Lack of Csk-mediated negative regulation in a unicellular SRC kinase.

PubMed

Schultheiss, Kira P; Suga, Hiroshi; Ruiz-Trillo, Iñaki; Miller, W Todd

2012-10-16

Phosphotyrosine-based signaling plays a vital role in cellular communication in multicellular organisms. Unexpectedly, unicellular choanoflagellates (the closest phylogenetic group to metazoans) possess numbers of tyrosine kinases that are comparable to those in complex metazoans. Here, we have characterized tyrosine kinases from the filasterean Capsaspora owczarzaki, a unicellular protist representing the sister group to choanoflagellates and metazoans. Two Src-like tyrosine kinases have been identified in C. owczarzaki (CoSrc1 and CoSrc2), both of which have the arrangement of SH3, SH2, and catalytic domains seen in mammalian Src kinases. In Capsaspora cells, CoSrc1 and CoSrc2 localize to punctate structures in filopodia that may represent primordial focal adhesions. We have cloned, expressed, and purified both enzymes. CoSrc1 and CoSrc2 are active tyrosine kinases. Mammalian Src kinases are normally regulated in a reciprocal fashion by autophosphorylation in the activation loop (which increases activity) and by Csk-mediated phosphorylation of the C-terminal tail (which inhibits activity). Similar to mammalian Src kinases, the enzymatic activities of CoSrc1 and CoSrc2 are increased by autophosphorylation in the activation loop. We have identified a Csk-like kinase (CoCsk) in the genome of C. owczarzaki. We cloned, expressed, and purified CoCsk and found that it has no measurable tyrosine kinase activity. Furthermore, CoCsk does not phosphorylate or regulate CoSrc1 or CoSrc2 in cells or in vitro, and CoSrc1 and CoSrc2 are active in Capsaspora cell lysates. Thus, the function of Csk as a negative regulator of Src family kinases appears to have arisen with the emergence of metazoans.

The wheat AGC kinase TaAGC1 is a positive contributor to host resistance to the necrotrophic pathogen Rhizoctonia cerealis

PubMed Central

Zhu, Xiuliang; Yang, Kun; Wei, Xuening; Zhang, Qiaofeng; Rong, Wei; Du, Lipu; Ye, Xingguo; Qi, Lin; Zhang, Zengyan

2015-01-01

Considerable progress has been made in understanding the roles of AGC kinases in mammalian systems. However, very little is known about the roles of AGC kinases in wheat (Triticum aestivum). The necrotrophic fungus Rhizoctonia cerealis is the major pathogen of the destructive disease sharp eyespot of wheat. In this study, the wheat AGC kinase gene TaAGC1, responding to R. cerealis infection, was isolated, and its properties and role in wheat defence were characterized. R. cerealis-resistant wheat lines expressed TaAGC1 at higher levels than susceptible wheat lines. Sequence and phylogenetic analyses showed that the TaAGC1 protein is a serine/threonine kinase belonging to the NDR (nuclear Dbf2-related) subgroup of AGC kinases. Kinase activity assays proved that TaAGC1 is a functional kinase and the Asp-239 residue located in the conserved serine/threonine kinase domain of TaAGC1 is required for the kinase activity. Subcellular localization assays indicated that TaAGC1 localized in the cytoplasm and nucleus. Virus-induced TaAGC1 silencing revealed that the down-regulation of TaAGC1 transcripts significantly impaired wheat resistance to R. cerealis. The molecular characterization and responses of TaAGC1 overexpressing transgenic wheat plants indicated that TaAGC1 overexpression significantly enhanced resistance to sharp eyespot and reduced the accumulation of reactive oxygen species (ROS) in wheat plants challenged with R. cerealis. Furthermore, ROS-scavenging and certain defence-associated genes were up-regulated in resistant plants overexpressing TaAGC1 but down-regulated in susceptible knock-down plants. These results suggested that the kinase TaAGC1 positively contributes to wheat immunity to R. cerealis through regulating expression of ROS-related and defence-associated genes. PMID:26220083

Regional And Seasonal Aspects Of Within-The-Hour Tec Statistics

NASA Astrophysics Data System (ADS)

Koroglu, Ozan; Arikan, Feza; Koroglu, Meltem

2015-04-01

Ionosphere is one of the atmosphere layers which has a plasma structure. Several mechanisms originating from both space and earth itself governs this plasma layer such as solar radiation and geomagnetic effects. Ionosphere plays important role for HF and satellite communication, and space based positioning systems. Therefore, the determination of statistical behavior of ionosphere has utmost importance. The variability of the ionosphere has complex spatio-temporal characteristics, which depends on solar, geomagnetic, gravitational and seismic activities. Total Electron Content (TEC) is one of the major observables for investigating and determining this variability. In this study, spatio-temporal within-the-hour statistical behavior of TEC is determined for Turkey, which is located in mid-latitude, using the TEC estimates from Turkish National Permanent GPS Network (TNPGN)-Active between the years 2009 and 2012. TEC estimates are obtained as IONOLAB-TEC which is developed by IONOLAB group (www.ionolab.org) from Hacettepe University. IONOLAB-TEC for each station in TNPGN-Active is organized in a database and grouped with respect to years, ionospheric seasons, hours and regions 2 degree by 3 degree, in latitude and longitude, respectively. The data sets are used to calculate within-the-hour parametric Probability Density Functions (PDF). For every year, every region and every hour, a representative PDF is determined. It is observed that TEC values have a strong hourly, seasonal and positional dependence on east-west direction, and the growing trend shifts according to sunrise and sunset times. It is observed that the data are distributed predominantly as Lognormal and Weibull. The averages and standard deviations of the chosen distributions follow the trends in 24 hour diurnal and 11 year solar cycle periods. The regional and seasonal behavior of PDFs are investigated using a representative GPS station within each region. Within-the-hour PDF estimates are grouped into ionospheric seasons as Winter, Summer, March equinox and September equinox. In winter and summer seasons, Lognormal distribution is observed. During equinox seasons, Weibull distribution is observed more frequently. Furthermore, all hourly TEC values in same region are combined in order to improve the reliability and accuracy of the probability density function estimates. It is observed that as being in mid-latitude region, the ionosphere over Turkey has robust characteristics that are distributed as Lognormal and Weibull. Statistical observations on PDF estimates of TEC of the ionosphere over Turkey will contribute to developing a regional and seasonal random field model, which will further contribute to HF channel characterization. This study is supported by a joint grant of TUBITAK 112E568 and RFBR 13-02-91370-CT_a.

New comparisons of ISR and RO data with the model IRI-Plas

NASA Astrophysics Data System (ADS)

Maltseva, Olga; Mozhaeva, Natalya; Zhbankov, Gennadii

2012-07-01

Space Weather events lead to strong changes in peak parameters of the ionosphere. These parameters, foF2 and hmF2, define the N(h)-profile, which is known to include bottom side and topside parts. Numerous studies have shown that adaptation of the IRI model to the experimental values of foF2 and hmF2 gave a good agreement between experimental and model N(h)-profiles of the bottom side ionosphere. This is not about the topside N(h)-profile. To improve the situation measurements of the total electron content TEC are involved. This work is devoted to the use of peak parameters with the TEC during Space Weather events for the evaluation of propagation conditions in both the bottom side and the topside ionosphere, based on the model IRI-Plas. To assess how well the model N(h)-profile matches the experimental one, the model IRI-Plas is tested according to the Incoherent Scatter Radars and the Radio Occultation measurements in various parts of the globe and at different levels of solar activity. The experimental N(h)-profiles are compared with profiles for the original model, the model adapted to the foF2 and hmF2, and for a model with full adaptation (including the TEC). The best fit is obtained in the European region, so the SW variations of peak parameters and N(h)-profiles are studied on the example of the European area. The IRI-Plas model allows to estimate the relative contributions of each region (bottom side BOT, topside TOP and plasmaspheric PL parts) in the value of the TEC. As the analysis of two W- and Wp-indexes (Gulyaeva, 2008; Gulyaeva and Stanislawska, 2008) is shown, TEC-storms occur in 2 times more likely than foF2-storms. This testifies that the variations of parts BOT, TOP and PL in the TEC are different. It determines different variations of N(h)-profiles. Results are given for several types of SW-events, in particular, for the strong positive and negative disturbances, when the variations of TEC and foF2 are of the same sign and the corresponding perturbation covers all regions of the ionosphere. Particular attention is paid to variations of peak parameters and N(h)-profiles during weak and moderate disturbances and bursts of TEC in long period of low activity, when the TEC and foF2 variations and variations of different parts of TEC are in the opposite phase.

Ionospheric Anomalies on the day of the Devastating Earthquakes during 2000-2012

NASA Astrophysics Data System (ADS)

Su, Fanfan; Zhou, Yiyan; Zhu, Fuying

2013-04-01

The study of the ionospheric abnormal changes during the large earthquakes has attracted much attention for many years. Many papers have reported the deviations of Total Electron Content (TEC) around the epicenter. The statistical analysis concludes that the anomalous behavior of TEC is related with the earthquakes with high probability[1]. But the special cases have different features[2][3]. In this study, we carry out a new statistical analysis to investigate the nature of the ionospheric anomalies during the devastating earthquakes. To demonstrate the abnormal changes of the ionospheric TEC, we have examined the TEC database from the Global Ionosphere Map (GIM). The GIM ( ftp://cddisa.gsfc.nasa.gov/pub/gps/products/ionex) includes about 200 of worldwide ground-based receivers of the GPS. The TEC data with resolution of 5° longitude and 2.5° latitude are routinely published in a 2-h time interval. The information of earthquakes is obtained from the USGS ( http://earthquake.usgs.gov/earthquakes/eqarchives/epic/). To avoid the interference of the magnetic storm, the days with Dst≤-20 nT are excluded. Finally, a total of 13 M≥8.0 earthquakes in the global area during 2000-2012 are selected. The 27 days before the main shock are treated as the background days. Here, 27-day TEC median (Me) and the standard deviation (σ) are used to detect the variation of TEC. We set the upper bound BU = Me + 3*σ, and the lower bound BL = Me - 3*σ. Therefore the probability of a new TEC in the interval (BL, BU) is approximately 99.7%. If TEC varies between BU and BL, the deviation (DTEC) equals zero. Otherwise, the deviations between TEC and bounds are calculated as DTEC = BU/BL - TEC. From the deviations, the positive and negative abnormal changes of TEC can be evaluated. We investigate temporal and spatial signatures of the ionospheric anomalies on the day of the devastating earthquakes(M≥8.0). The results show that the occurrence rates of positive anomaly and negative anomaly are almost equal. The most significant anomaly on the day may occur at the time very close to the main shock, but sometimes it is not the case. The positions of the maximal deviations always deviate from the epicenter. The direction may be southeast, southwest, northeast or northwest with the almost equal probability. The anomalies may move to the epicenter, deviate to any direction, or stay at the same position and gradually fade out. There is no significant feature, such as occurrence time, position, or motion, and so on, which can indicate the source of the anomalies. References: [1].Le, H., J. Y. Liu, et al. (2011). "A statistical analysis of ionospheric anomalies before 736 M6.0+earthquakes during 2002-2010." J. Geophys. Res. 116. [2].Liu, J. Y., Y. I. Chen, et al. (2009). "Seismoionospheric GPS total electron content anomalies observed before the 12 May 2008 Mw7.9 Wenchuan earthquake." J. Geophys. Res. 114. [3].Rolland, L. M., P. Lognonne, et al. (2011). "Detection and modeling of Rayleigh wave induced patterns in the ionosphere." J. Geophys. Res. 116.

The MPS1 family of protein kinases.

PubMed

Liu, Xuedong; Winey, Mark

2012-01-01

MPS1 protein kinases are found widely, but not ubiquitously, in eukaryotes. This family of potentially dual-specific protein kinases is among several that regulate a number of steps of mitosis. The most widely conserved MPS1 kinase functions involve activities at the kinetochore in both the chromosome attachment and the spindle checkpoint. MPS1 kinases also function at centrosomes. Beyond mitosis, MPS1 kinases have been implicated in development, cytokinesis, and several different signaling pathways. Family members are identified by virtue of a conserved C-terminal kinase domain, though the N-terminal domain is quite divergent. The kinase domain of the human enzyme has been crystallized, revealing an unusual ATP-binding pocket. The activity, level, and subcellular localization of Mps1 family members are tightly regulated during cell-cycle progression. The mitotic functions of Mps1 kinases and their overexpression in some tumors have prompted the identification of Mps1 inhibitors and their active development as anticancer drugs.

Impact of Serine/Threonine Protein Kinases on the Regulation of Sporulation in Bacillus subtilis.

PubMed

Pompeo, Frédérique; Foulquier, Elodie; Galinier, Anne

2016-01-01

Bacteria possess many kinases that catalyze phosphorylation of proteins on diverse amino acids including arginine, cysteine, histidine, aspartate, serine, threonine, and tyrosine. These protein kinases regulate different physiological processes in response to environmental modifications. For example, in response to nutritional stresses, the Gram-positive bacterium Bacillus subtilis can differentiate into an endospore; the initiation of sporulation is controlled by the master regulator Spo0A, which is activated by phosphorylation. Spo0A phosphorylation is carried out by a multi-component phosphorelay system. These phosphorylation events on histidine and aspartate residues are labile, highly dynamic and permit a temporal control of the sporulation initiation decision. More recently, another kind of phosphorylation, more stable yet still dynamic, on serine or threonine residues, was proposed to play a role in spore maintenance and spore revival. Kinases that perform these phosphorylation events mainly belong to the Hanks family and could regulate spore dormancy and spore germination. The aim of this mini review is to focus on the regulation of sporulation in B. subtilis by these serine and threonine phosphorylation events and the kinases catalyzing them.

TRYPTASE/PAR-2 INTERACTIONS INDUCE SELECTIVE MAPK SIGNALING AND COLLAGEN SYNTHESIS BY CARDIAC FIBROBLASTS

PubMed Central

McLarty, Jennifer L.; Meléndez, Giselle C.; Brower, Gregory L.; Janicki, Joseph S.; Levick, Scott P.

2012-01-01

The mast cell product, tryptase, has recently been implicated in fibrosis in the hypertensive heart. Tryptase has been shown to mediate non-cardiac fibroblast function via activation of protease activated receptor-2 and subsequent activation of the mitogen-activated protein kinase pathway, including extracellular signal-regulated kinase1/2. Therefore, we hypothesized that this pathway may be a mechanism leading to fibrosis in the hypertensive heart. Isolated adult cardiac fibroblasts were treated with tryptase, which induced activation of extracellular signal-regulated kinase1/2 via protease activated receptor-2. Blockade of protease activated receptor-2 with FSLLRY (10 μM) and inhibition of the extracellular signal-regulated kinase pathway with PD98059 (10 μM) prevented collagen synthesis in isolated cardiac fibroblasts stimulated with tryptase. p38 mitogen activated protein kinase and stress-activated protein/c-Jun N-terminal kinase were not activated by tryptase. Cardiac fibroblasts isolated from spontaneously hypertensive rats showed this same pattern of activation and treatment of spontaneously hypertensive rats with FSLLRY prevented fibrosis in these animals indicating the in vivo applicability of the cultured fibroblast findings. Also, tryptase induced a myofibroblastic phenotype indicated by elevations in α smooth muscle actin and ED-A fibronectin. Thus, the results from this study demonstrate the importance of tryptase for inducing a cardiac myofibroblastic phenotype, ultimately leading to the development of cardiac fibrosis through the activation of the extracellular signal-regulated kinase pathway. Specifically, tryptase causes cardiac fibroblasts to increase collagen synthesis via a mechanism involving activation of protease activated receptor-2 and subsequent induction of extracellular signal-regulated kinase signaling. PMID:21730297

Haspin kinase regulates microtubule-organizing center clustering and stability through Aurora kinase C in mouse oocytes.

PubMed

Balboula, Ahmed Z; Nguyen, Alexandra L; Gentilello, Amanda S; Quartuccio, Suzanne M; Drutovic, David; Solc, Petr; Schindler, Karen

2016-10-01

Meiotic oocytes lack classic centrosomes and, therefore, bipolar spindle assembly depends on clustering of acentriolar microtubule-organizing centers (MTOCs) into two poles. However, the molecular mechanism regulating MTOC assembly into two poles is not fully understood. The kinase haspin (also known as GSG2) is required to regulate Aurora kinase C (AURKC) localization at chromosomes during meiosis I. Here, we show that inhibition of haspin perturbed MTOC clustering into two poles and the stability of the clustered MTOCs. Furthermore, we show that AURKC localizes to MTOCs in mouse oocytes. Inhibition of haspin perturbed the localization of AURKC at MTOCs, and overexpression of AURKC rescued the MTOC-clustering defects in haspin-inhibited oocytes. Taken together, our data uncover a role for haspin as a regulator of bipolar spindle assembly by regulating AURKC function at acentriolar MTOCs in oocytes. © 2016. Published by The Company of Biologists Ltd.

Regulation of Ubiquitination-Mediated Protein Degradation by Survival Kinases in Cancer

PubMed Central

Yamaguchi, Hirohito; Hsu, Jennifer L.; Hung, Mien-Chie

2011-01-01

The ubiquitin–proteasome system is essential for multiple physiological processes via selective degradation of target proteins and has been shown to plays a critical role in human cancer. Activation of oncogenic factors and inhibition of tumor suppressors have been shown to be essential for cancer development, and protein ubiquitination has been linked to the regulation of oncogenic factors and tumor suppressors. Three kinases, AKT, extracellular signal-regulated kinase, and IκB kinase, we refer to as oncokinases, are activated in multiple human cancers. We and others have identified several key downstream targets that are commonly regulated by these oncokinases, some of which are regulated directly or indirectly via ubiquitin-mediated proteasome degradation, including FOXO3, β-catenin, myeloid cell leukemia-1, and Snail. In this review, we summarize these findings from our and other groups and discuss potential future studies and applications in the clinic. PMID:22649777

Operation and Maintenance Manual, TECS 18.

DTIC Science & Technology

1978-11-01

width modulated variable output voltage and frequency using a three-phase transistor bridge circuit . Reduced power line electromagnetic interference...Description 3-1 Section II. Circuit Fundamentals 3-1 Section III. System Description 3-2 CHAPTER 4. Protection and Maintenance 4-1 Section I. Internal...Number I-la TECS 18 Electronic Module Location-Evaporator Side 1-3 1-lb TECS 18 Electronic Module Location-Condenser Side 1-4 1-2 Remote Control Panel 1-5

Regional ionospheric model for improvement of navigation position with EGNOS

NASA Astrophysics Data System (ADS)

Swiatek, Anna; Tomasik, Lukasz; Jaworski, Leszek

The problem of insufficient accuracy of EGNOS correction for the territory of Poland, located at the edge of EGNOS range is well known. The EEI PECS project (EGNOS EUPOS Integration) assumed improving the EGNOS correction by using the GPS observations from Polish ASG-EUPOS stations. A ionospheric delay parameter is a part of EGNOS correction. The comparative analysis of TEC values obtained from EGNOS and regional permanent GNSS stations showed the systematic shift. The TEC from EGNOS correction is underestimated related to computed regional TEC value. The new-‘improved’ corrections computed based on regional model were substituted for the EGNOS correction for suitable message. Dynamic measurements managed using the Mobile GPS Laboratory (MGL), showed the improvement of navigation position with TEC regional model.

The National Network forTechnology Entrepreneurship and Commercialization (N2TEC): Bringing New Technologies to Market

NASA Astrophysics Data System (ADS)

Allen, Kathleen

2003-03-01

N2TEC, the National Network for Technology Entrepreneurship and Commercialization, is a National Science Foundation "Partnerships for Innovation" initiative designed to raise the level of innovation and technology commercialization in colleges, universities, and communities across the nation. N2TEC is creating a network of people and institutions, and a set of technology tools that will facilitate the pooling of resources and knowledge and enable faculty and students to share those resources and collaborate without regard to geographic boundaries. N2TEC will become the backbone by which educational institutions across the nation can move their technologies into new venture startups. The ultimate goal is to create new wealth and strengthen local, regional and national economies.

Optimal Integration of Cascade Thermoelectric Cooler into Electronic Housing: Experimental Approach

NASA Astrophysics Data System (ADS)

Semeniuk, V.; Protsenko, D.

2018-06-01

The problem of the optimal integration of thermoelectrically cooled optoelectronic components into an electronic housing is studied with the emphasis on practical implementation. The lines of 2-stage and 3-stage thermoelectric coolers (TECs) compatible with TO8 housing have been developed, and their parameters are measured in a wide range of heat sink temperatures. The TECs are optimized to receive a temperature difference of 100-110 K under a heat load from 70 mW to 100 mW with minimal power consumption. To fit into a standard housing interior, all the TECs have the same overall dimensions, regardless of the number of stages. Details of the TEC configurations and their performance characteristics are presented and discussed.

Optimal Integration of Cascade Thermoelectric Cooler into Electronic Housing: Experimental Approach

NASA Astrophysics Data System (ADS)

Semeniuk, V.; Protsenko, D.

2018-03-01

The problem of the optimal integration of thermoelectrically cooled optoelectronic components into an electronic housing is studied with the emphasis on practical implementation. The lines of 2-stage and 3-stage thermoelectric coolers (TECs) compatible with TO8 housing have been developed, and their parameters are measured in a wide range of heat sink temperatures. The TECs are optimized to receive a temperature difference of 100-110 K under a heat load from 70 mW to 100 mW with minimal power consumption. To fit into a standard housing interior, all the TECs have the same overall dimensions, regardless of the number of stages. Details of the TEC configurations and their performance characteristics are presented and discussed.

High Temporal and Spatial Resolution Global GPS TEC Observations of the 2015 St. Patrick Day Storm

NASA Astrophysics Data System (ADS)

Vierinen, J.

2015-12-01

High spatiotemperal resolution global GPS TEC measurements of the 2015 St. Patrick's day storm are presented. The high resolution data is useful, as it clearly shows the high latitude convection patterns, the equatorward progression of the auroral region, the tongue of ionization, as well as the increased electron density in the equatorial anomaly region. The measurements are compared with high power large aperture radar and passive radar measurements of coherent and incoherent scatter at Millstone Hill. Regions of fast convection identified in the GPS TEC data are found to coincide with coherent scatter in both radar data. Convection velocities determined from GPS TEC are compared with those obtained from incoherent scatter radar measurements.

The activity and stability of the intrinsically disordered Cip/Kip protein family are regulated by non-receptor tyrosine kinases.

PubMed

Huang, Yongqi; Yoon, Mi-Kyung; Otieno, Steve; Lelli, Moreno; Kriwacki, Richard W

2015-01-30

The Cip/Kip family of cyclin-dependent kinase (Cdk) inhibitors includes p21(Cip1), p27(Kip1) and p57(Kip2). Their kinase inhibitory activities are mediated by a homologous N-terminal kinase inhibitory domain. The Cdk inhibitory activity and stability of p27 have been shown to be regulated by a two-step phosphorylation mechanism involving a tyrosine residue within the kinase inhibitory domain and a threonine residue within the flexible C-terminus. We show that these residues are conserved in p21 and p57, suggesting that a similar phosphorylation cascade regulates these Cdk inhibitors. However, the presence of a cyclin binding motif within its C-terminus alters the regulatory interplay between p21 and Cdk2/cyclin A, as well as its responses to tyrosine phosphorylation and altered p21:Cdk2/cyclin A stoichiometry. We also show that the Cip/Kip proteins can be phosphorylated in vitro by representatives of many non-receptor tyrosine kinase (NRTK) sub-families, suggesting that NRTKs may generally regulate the activity and stability of these Cdk inhibitors. Our results further suggest that the Cip/Kip proteins integrate signals from various NRTK pathways and cell cycle regulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

An essential role of ubiquitination in Cbl-mediated negative regulation of the Src-family kinase Fyn

PubMed Central

Rao, Navin; Ghosh, Amiya K.; Douillard, Patrice; Andoniou, Christopher E.; Zhou, Pengcheng; Band, Hamid

2009-01-01

SUMMARY The Cbl family of ubiquitin ligases function as negative regulators of activated receptor tyrosine kinases by facilitating their ubiquitination and subsequent lysosomal targeting. Here, we have investigated the role of Cbl ubiquitin ligase activity in the negative regulation of a non-receptor tyrosine kinase, the Src-family kinase Fyn. Using primary embryonic fibroblasts from Cbl+/+ and Cbl−/− mice, we demonstrate that endogenous Cbl mediates the ubiquitination of Fyn and dictates the rate of Fyn turnover. By analyzing CHO-TS20 cells with a temperature-sensitive ubiquitin activating enzyme, we demonstrate that intact cellular ubiquitin machinery is required for Cbl-induced degradation of Fyn. Analyses of Cbl mutants, with mutations in or near the RING finger domain, in 293T cells revealed that the ubiquitin ligase activity of Cbl is essential for Cbl-induced degradation of Fyn by the proteasome pathway. Finally, use of a SRE-luciferase reporter demonstrated that Cbl-dependent negative regulation of Fyn function requires the region of Cbl that mediates the ubiquitin ligase activity. Given the conservation of structure between various Src-family kinases and the ability of Cbl to interact with multiple members of this family, Cbl-dependent ubiquitination could serve a general role to negatively regulate activated Src-family kinases. PMID:19966925

The Abl SH2-kinase linker naturally adopts a conformation competent for SH3 domain binding.

PubMed

Chen, Shugui; Brier, Sébastien; Smithgall, Thomas E; Engen, John R

2007-04-01

The core of the Abelson tyrosine kinase (c-Abl) is structurally similar to Src-family kinases where SH3 and SH2 domains pack against the backside of the kinase domain in the down-regulated conformation. Both kinase families depend upon intramolecular association of SH3 with the linker joining the SH2 and kinase domains for suppression of kinase activity. Hydrogen deuterium exchange (HX) and mass spectrometry (MS) were used to probe intramolecular interaction of the c-Abl SH3 domain with the linker in recombinant constructs lacking the kinase domain. Under physiological conditions, the c-Abl SH3 domain undergoes partial unfolding, which is stabilized by ligand binding, providing a unique assay for SH3:linker interaction in solution. Using this approach, we observed dynamic association of the SH3 domain with the linker in the absence of the kinase domain. Truncation of the linker before W254 completely prevented cis-interaction with SH3, while constructs containing amino acids past this point showed SH3:linker interactions. The observation that the Abl linker sequence exhibits SH3-binding activity in the absence of the kinase domain is unique to Abl and was not observed with Src-family kinases. These results suggest that SH3:linker interactions may have a more prominent role in Abl regulation than in Src kinases, where the down-regulated conformation is further stabilized by a second intramolecular interaction between the C-terminal tail and the SH2 domain.

Antagonistic Regulation of Cystic Fibrosis Transmembrane Conductance Regulator Cell Surface Expression by Protein Kinases WNK4 and Spleen Tyrosine Kinase ▿

PubMed Central

Mendes, Ana Isabel; Matos, Paulo; Moniz, Sónia; Luz, Simão; Amaral, Margarida D.; Farinha, Carlos M.; Jordan, Peter

2011-01-01

Members of the WNK (with-no-lysine [K]) subfamily of protein kinases regulate various ion channels involved in sodium, potassium, and chloride homeostasis by either inducing their phosphorylation or regulating the number of channel proteins expressed at the cell surface. Here, we describe findings demonstrating that the cell surface expression of the cystic fibrosis transmembrane conductance regulator (CFTR) is also regulated by WNK4 in mammalian cells. This effect of WNK4 is independent of the presence of kinase and involves interaction with and inhibition of spleen tyrosine kinase (Syk), which phosphorylates Tyr512 in the first nucleotide-binding domain 1 (NBD1) of CFTR. Transfection of catalytically active Syk into CFTR-expressing baby hamster kidney cells reduces the cell surface expression of CFTR, whereas that of WNK4 promotes it. This is shown by biotinylation of cell surface proteins, immunofluorescence microscopy, and functional efflux assays. Mutation of Tyr512 to either glutamic acid or phenylalanine is sufficient to alter CFTR surface levels. In human airway epithelial cells, downregulation of endogenous Syk and WNK4 confirms their roles as physiologic regulators of CFTR surface expression. Together, our results show that Tyr512 phosphorylation is a novel signal regulating the prevalence of CFTR at the cell surface and that WNK4 and Syk perform an antagonistic role in this process. PMID:21807898

G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitors: Current Trends and Future Perspectives.

PubMed

Guccione, Manuela; Ettari, Roberta; Taliani, Sabrina; Da Settimo, Federico; Zappalà, Maria; Grasso, Silvana

2016-10-27

G-protein-coupled receptor kinase 2 (GRK2) is a G-protein-coupled receptor kinase that is ubiquitously expressed in many tissues and regulates various intracellular mechanisms. The up- or down-regulation of GRK2 correlates with several pathological disorders. GRK2 plays an important role in the maintenance of heart structure and function; thus, this kinase is involved in many cardiovascular diseases. GRK2 up-regulation can worsen cardiac ischemia; furthermore, increased kinase levels occur during the early stages of heart failure and in hypertensive subjects. GRK2 up-regulation can lead to changes in the insulin signaling cascade, which can translate to insulin resistance. Increased GRK2 levels also correlate with the degree of cognitive impairment that is typically observed in Alzheimer's disease. This article reviews the most potent and selective GRK2 inhibitors that have been developed. We focus on their mechanism of action, inhibition profile, and structure-activity relationships to provide insight into the further development of GRK2 inhibitors as drug candidates.

Aurora kinases: structure, functions and their association with cancer.

PubMed

Kollareddy, Madhu; Dzubak, Petr; Zheleva, Daniella; Hajduch, Marian

2008-06-01

Aurora kinases are a recently discovered family of kinases (A, B & C) consisting of highly conserved serine\\threonine protein kinases found to be involved in multiple mitotic events: regulation of spindle assembly checkpoint pathway, function of centrosomes and cytoskeleton, and cytokinesis. Aberrant expression of Aurora kinases may lead to cancer. For this reason the Aurora kinases are potential targets in the treatment of cancer. In this review we discuss the biology of these kinases: structure, function, regulation and association with cancer. A literature search. Many of the multiple functions of mitosis are mediated by the Aurora kinases. Their aberrant expression can lead to the deregulation of cell division and cancer. For this reason, the Aurora kinases are currently one of the most interesting targets for cancer therapy. Some Aurora kinase inhibitors in the clinic have proven effectively on a wide range of tumor types. The clinical data are very encouraging and promising for development of novel class of structurally different Aurora kinase inhibitors. Hopefully the Aurora kinases will be potentially useful in drug targeted cancer treatment.

Study of Ionospheric TEC from GPS observations and comparisons with IRI and SPIM model predictions in the low latitude anomaly Indian subcontinental region

NASA Astrophysics Data System (ADS)

Panda, S. K.; Gedam, S. S.; Rajaram, G.

2015-04-01

The present study investigates variation of the ionospheric total electron content (TEC) in the low latitude Indian sub-continental region from the GPS observations and its comparison with the global ionosphere maps (GIMs), standard international reference ionosphere (IRI 2012), and the standard plasmasphere-ionosphere model (SPIM) for the period from November 2011 to October 2012 that corresponds to the progressive phase towards the midst of the solar cycle-24. Observations during quiet period show diurnal maximum of TEC occurring around 14:00-16:00 IST, with relatively broader and longer duration of local maximum at Bangalore and behave reversely towards Delhi. The secondary maximum of TEC was markedly noticeable at Bangalore during the months of March and September, and only in the month of September at Hyderabad and Mumbai. However, the relatively higher TEC during December month than the June is ascribed to the winter anomaly which is more prevalent during the high solar activity periods. The prevailing instability in latitudes of anomaly crest during January 2012 is possibly due to the seasonal variation of lunar tidal effects, modulating the EEJ strength at the equator. The studies covered the period of a strong geomagnetic storm during 6-11 March 2012 (SYM-H: -149 nT) which resulted in positive deviation of GPS-TEC at Bangalore (↑ 20%), Hyderabad (↑ 22%), and Lucknow (↑ 94%) compared to the mean quiet days level. The relatively large deviation of TEC at Lucknow could be attributed to the poleward shifting of the anomaly crest, manifested by enhanced fountain effect at the equator. Studies confirm excellent agreement (80-85%) of GPS-TEC with IGS-GIM at Bangalore and Hyderabad with the exception of the night-time hours (Deviations >50%). However relatively larger deviation of GPS-TEC from GIM-TEC at Delhi could be due to the unavailability of IGS stations in the proximity of the position. Predictions of the SPIM model (extension of IRI up to GPS altitude) exhibit much higher deviation from the in situ GPS observations as well as GIM and IRI outputs during quiet periods. Correspondingly, either of the models (IRI and SPIM) did not respond well to the arrival of the sudden storm commencements (SSCs) during the storm period (6-11 March 2012). When SPIM is used instead of IRI, the overestimation from GPS-TECs are further exaggerated by 13-18% (December solstice), 27-37% (March equinox), 15-31% (June solstice), and 20-32% (September equinox) during peak hours of the period. We attribute the relatively more deviation of the SPIM than the IRI model possibly due to its plasmaspheric extension to the IRI model by adding the Russian SMI model of high latitude characteristics. Hence, we emphasize the further improvement in the model with due consideration of the driving forces at play in the region, for reliable predictions of the low latitude ionosphere.

Application of Modified Particle Swarm Optimization Method for Parameter Extraction of 2-D TEC Mapping

NASA Astrophysics Data System (ADS)

Toker, C.; Gokdag, Y. E.; Arikan, F.; Arikan, O.

2012-04-01

Ionosphere is a very important part of Space Weather. Modeling and monitoring of ionospheric variability is a major part of satellite communication, navigation and positioning systems. Total Electron Content (TEC), which is defined as the line integral of the electron density along a ray path, is one of the parameters to investigate the ionospheric variability. Dual-frequency GPS receivers, with their world wide availability and efficiency in TEC estimation, have become a major source of global and regional TEC modeling. When Global Ionospheric Maps (GIM) of International GPS Service (IGS) centers (http://iono.jpl.nasa.gov/gim.html) are investigated, it can be observed that regional ionosphere along the midlatitude regions can be modeled as a constant, linear or a quadratic surface. Globally, especially around the magnetic equator, the TEC surfaces resemble twisted and dispersed single centered or double centered Gaussian functions. Particle Swarm Optimization (PSO) proved itself as a fast converging and an effective optimization tool in various diverse fields. Yet, in order to apply this optimization technique into TEC modeling, the method has to be modified for higher efficiency and accuracy in extraction of geophysical parameters such as model parameters of TEC surfaces. In this study, a modified PSO (mPSO) method is applied to regional and global synthetic TEC surfaces. The synthetic surfaces that represent the trend and small scale variability of various ionospheric states are necessary to compare the performance of mPSO over number of iterations, accuracy in parameter estimation and overall surface reconstruction. The Cramer-Rao bounds for each surface type and model are also investigated and performance of mPSO are tested with respect to these bounds. For global models, the sample points that are used in optimization are obtained using IGS receiver network. For regional TEC models, regional networks such as Turkish National Permanent GPS Network (TNPGN-Active) receiver sites are used. The regional TEC models are grouped into constant (one parameter), linear (two parameters), and quadratic (six parameters) surfaces which are functions of latitude and longitude. Global models require seven parameters for single centered Gaussian and 13 parameters for double centered Gaussian function. The error criterion is the normalized percentage error for both the surface and the parameters. It is observed that mPSO is very successful in parameter extraction of various regional and global models. The normalized reconstruction error varies from 10-4 for constant surfaces to 10-3 for quadratic surfaces in regional models, sampled with regional networks. Even for the cases of a severe geomagnetic storm that affects measurements globally, with IGS network, the reconstruction error is on the order of 10-1 even though individual parameters have higher normalized errors. The modified PSO technique proved itself to be a useful tool for parameter extraction of more complicated TEC models. This study is supported by TUBITAK EEEAG under Grant No: 109E055.

Sequential phosphorylation of SLP-76 at tyrosine 173 is required for activation of T and mast cells

PubMed Central

Sela, Meirav; Bogin, Yaron; Beach, Dvora; Oellerich, Thomas; Lehne, Johanna; Smith-Garvin, Jennifer E; Okumura, Mariko; Starosvetsky, Elina; Kosoff, Rachelle; Libman, Evgeny; Koretzky, Gary; Kambayashi, Taku; Urlaub, Henning; Wienands, Jürgen; Chernoff, Jonathan; Yablonski, Deborah

2011-01-01

Cooperatively assembled signalling complexes, nucleated by adaptor proteins, integrate information from surface receptors to determine cellular outcomes. In T and mast cells, antigen receptor signalling is nucleated by three adaptors: SLP-76, Gads and LAT. Three well-characterized SLP-76 tyrosine phosphorylation sites recruit key components, including a Tec-family tyrosine kinase, Itk. We identified a fourth, evolutionarily conserved SLP-76 phosphorylation site, Y173, which was phosphorylated upon T-cell receptor stimulation in primary murine and Jurkat T cells. Y173 was required for antigen receptor-induced phosphorylation of phospholipase C-γ1 (PLC-γ1) in both T and mast cells, and for consequent downstream events, including activation of the IL-2 promoter in T cells, and degranulation and IL-6 production in mast cells. In intact cells, Y173 phosphorylation depended on three, ZAP-70-targeted tyrosines at the N-terminus of SLP-76 that recruit and activate Itk, a kinase that selectively phosphorylated Y173 in vitro. These data suggest a sequential mechanism whereby ZAP-70-dependent priming of SLP-76 at three N-terminal sites triggers reciprocal regulatory interactions between Itk and SLP-76, which are ultimately required to couple active Itk to its substrate, PLC-γ1. PMID:21725281

Sequential phosphorylation of SLP-76 at tyrosine 173 is required for activation of T and mast cells.

PubMed

Sela, Meirav; Bogin, Yaron; Beach, Dvora; Oellerich, Thomas; Lehne, Johanna; Smith-Garvin, Jennifer E; Okumura, Mariko; Starosvetsky, Elina; Kosoff, Rachelle; Libman, Evgeny; Koretzky, Gary; Kambayashi, Taku; Urlaub, Henning; Wienands, Jürgen; Chernoff, Jonathan; Yablonski, Deborah

2011-07-01

Cooperatively assembled signalling complexes, nucleated by adaptor proteins, integrate information from surface receptors to determine cellular outcomes. In T and mast cells, antigen receptor signalling is nucleated by three adaptors: SLP-76, Gads and LAT. Three well-characterized SLP-76 tyrosine phosphorylation sites recruit key components, including a Tec-family tyrosine kinase, Itk. We identified a fourth, evolutionarily conserved SLP-76 phosphorylation site, Y173, which was phosphorylated upon T-cell receptor stimulation in primary murine and Jurkat T cells. Y173 was required for antigen receptor-induced phosphorylation of phospholipase C-γ1 (PLC-γ1) in both T and mast cells, and for consequent downstream events, including activation of the IL-2 promoter in T cells, and degranulation and IL-6 production in mast cells. In intact cells, Y173 phosphorylation depended on three, ZAP-70-targeted tyrosines at the N-terminus of SLP-76 that recruit and activate Itk, a kinase that selectively phosphorylated Y173 in vitro. These data suggest a sequential mechanism whereby ZAP-70-dependent priming of SLP-76 at three N-terminal sites triggers reciprocal regulatory interactions between Itk and SLP-76, which are ultimately required to couple active Itk to its substrate, PLC-γ1.

Targeting Btk with ibrutinib inhibit gastric carcinoma cells growth.

PubMed

Wang, Jin Dao; Chen, Xiao Ying; Ji, Ke Wei; Tao, Feng

2016-01-01

Bruton's tyrosine kinase (Btk) is a member of the Tec-family non-receptor tyrosine kinases family. It has previously been reported to be expressed in B cells and has an important role in B-cell malignancies. While the roles of Btk in the pathogenesis of certain B-cell malignancies are well established, the functions of Btk in gastric carcinoma have never been investigated. Herein, we found that Btk is over-expressed in gastric carcinoma tissues and gastric cancer cells. Knockdown of Btk expression selectively inhibits the growth of gastric cancer cells, but not that of the normal gastric mucosa epithelial cell, which express very little Btk. Inhibition of Btk by its inhibitor ibrutinib has an additive inhibitory effect on gastric cancer cell growth. Treatment of gastric cancer cells, but not immortalized breast epithelial cells with ibrutinib results in effective cell killing, accompanied by the attenuation of Btk signals. Ibrutinib also induces apoptosis in gastric carcinoma cells as well as is a chemo-sensitizer for docetaxel (DTX), a standard of care for gastric carcinoma patients. Finally, ibrutinib markedly reduces tumor growth and increases tumor cell apoptosis in the tumors formed in mice inoculated with the gastric carcinoma cells. Given these promising preclinical results for ibrutinib in gastric carcinoma, a strategy combining Btk inhibitor warrants attention in gastric cancer.

Targeting Btk with ibrutinib inhibit gastric carcinoma cells growth

PubMed Central

Wang, Jin Dao; Chen, Xiao Ying; Ji, Ke Wei; Tao, Feng

2016-01-01

Bruton’s tyrosine kinase (Btk) is a member of the Tec-family non-receptor tyrosine kinases family. It has previously been reported to be expressed in B cells and has an important role in B-cell malignancies. While the roles of Btk in the pathogenesis of certain B-cell malignancies are well established, the functions of Btk in gastric carcinoma have never been investigated. Herein, we found that Btk is over-expressed in gastric carcinoma tissues and gastric cancer cells. Knockdown of Btk expression selectively inhibits the growth of gastric cancer cells, but not that of the normal gastric mucosa epithelial cell, which express very little Btk. Inhibition of Btk by its inhibitor ibrutinib has an additive inhibitory effect on gastric cancer cell growth. Treatment of gastric cancer cells, but not immortalized breast epithelial cells with ibrutinib results in effective cell killing, accompanied by the attenuation of Btk signals. Ibrutinib also induces apoptosis in gastric carcinoma cells as well as is a chemo-sensitizer for docetaxel (DTX), a standard of care for gastric carcinoma patients. Finally, ibrutinib markedly reduces tumor growth and increases tumor cell apoptosis in the tumors formed in mice inoculated with the gastric carcinoma cells. Given these promising preclinical results for ibrutinib in gastric carcinoma, a strategy combining Btk inhibitor warrants attention in gastric cancer. PMID:27508020

Kindlin-2 regulates renal tubular cell plasticity by activation of Ras and its downstream signaling.

PubMed

Wei, Xiaofan; Wang, Xiang; Xia, Yang; Tang, Yan; Li, Feng; Fang, Weigang; Zhang, Hongquan

2014-01-01

Kindlin-2 is an adaptor protein that contributes to renal tubulointerstitial fibrosis (TIF). Epithelial-to-mesenchymal transition (EMT) in tubular epithelial cells was regarded as one of the key events in TIF. To determine whether kindlin-2 is involved in the EMT process, we investigated its regulation of EMT in human kidney tubular epithelial cells (TECs) and explored the underlying mechanism. In this study, we found that overexpression of kindlin-2 suppressed epithelial marker E-cadherin and increased the expression of fibronectin and the myofibroblast marker α-smooth muscle actin (SMA). Kindlin-2 significantly activated ERK1/2 and Akt, and inhibition of ERK1/2 or Akt reversed kindlin-2-induced EMT in human kidney TECs. Mechanistically, kindlin-2 interacted with Ras and son of sevenless (Sos)-1. Furthermore, overexpression of kindlin-2 increased Ras activation through recruiting Sos-1. Treatment with a Ras inhibitor markedly repressed kindlin-2-induced ERK1/2 and Akt activation, leading to restraint of EMT. We further demonstrated that knockdown of kindlin-2 inhibited EGF-induced Ras-Sos-1 interaction, resulting in reduction of Ras activation and suppression of EMT stimulated by EGF. Importantly, we found that depletion of kindlin-2 significantly inhibited activation of ERK1/2 and Akt signaling in mice with unilateral ureteral obstruction. We conclude that kindlin-2, through activating Ras and the downstream ERK1/2 and Akt signaling pathways, plays an important role in regulating renal tubular EMT and could be a potential therapeutic target for the treatment of fibrotic kidney diseases.

Investigation of the TEC Changes in the vicinity of the Earthquake Preparation Zone

NASA Astrophysics Data System (ADS)

Ulukavak, Mustafa; Yalcinkaya, Mualla

2016-04-01

Recently, investigation of the anomalies in the ionosphere before the earthquake has taken too much attention. The Total Electron Content (TEC) data has been used to monitor the changes in the ionosphere. Hence, researchers use the TEC changes before the strong earthquakes to monitor the anomalies in the ionosphere. In this study, the GPS-TEC variations, obtained from the GNSS stations in the vicinity of the earthquake preparation zone, was investigated. Nidra earthquake (M6.5), which was occurred on the north-west of Greece on November 17th, 2015 (38.755°N, 20.552°E), was selected for this study. First, the equation proposed by Dobrovolsky et al. (1979) was used to calculate the radius of the earthquake preparation zone. International GNSS Service (IGS) stations in the region were classified with respect to the radius of the earthquake preparation zone. The observation data of each station was obtained from the Crustal Dynamics Data and Information System (CDDIS) archive to estimate GPS-TEC variations between 16 October 2015 and 16 December 2015. Global Ionosphere Maps (GIM) products, obtained from the IGS, was used to check the robustness of the GPS-TEC variations. Possible anomalies were analyzed for each GNSS station by using the 15-day moving median method. In order to analyze these pre-earthquake ionospheric anomalies, we investigated three indices (Kp, F10.7 and Dst) related to the space weather conditions between 16 October 2015 and 16 December 2015. Solar and geomagnetic indices were obtained from The Oceanic and Atmospheric Administration (NOAA), The Canadian Space Weather Forecast Centre (CSWFC), and the Data Analysis Center for Geomagnetism and Space Magnetism Graduate School of Science, Kyoto University (WDC). This study aims at investigating the possible effects of the earthquake on the TEC variations.

GIM-TEC adaptive ionospheric weather assessment and forecast system

NASA Astrophysics Data System (ADS)

Gulyaeva, T. L.; Arikan, F.; Hernandez-Pajares, M.; Stanislawska, I.

2013-09-01

The Ionospheric Weather Assessment and Forecast (IWAF) system is a computer software package designed to assess and predict the world-wide representation of 3-D electron density profiles from the Global Ionospheric Maps of Total Electron Content (GIM-TEC). The unique system products include daily-hourly numerical global maps of the F2 layer critical frequency (foF2) and the peak height (hmF2) generated with the International Reference Ionosphere extended to the plasmasphere, IRI-Plas, upgraded by importing the daily-hourly GIM-TEC as a new model driving parameter. Since GIM-TEC maps are provided with 1- or 2-days latency, the global maps forecast for 1 day and 2 days ahead are derived using an harmonic analysis applied to the temporal changes of TEC, foF2 and hmF2 at 5112 grid points of a map encapsulated in IONEX format (-87.5°:2.5°:87.5°N in latitude, -180°:5°:180°E in longitude). The system provides online the ionospheric disturbance warnings in the global W-index map establishing categories of the ionospheric weather from the quiet state (W=±1) to intense storm (W=±4) according to the thresholds set for instant TEC perturbations regarding quiet reference median for the preceding 7 days. The accuracy of IWAF system predictions of TEC, foF2 and hmF2 maps is superior to the standard persistence model with prediction equal to the most recent ‘true’ map. The paper presents outcomes of the new service expressed by the global ionospheric foF2, hmF2 and W-index maps demonstrating the process of origin and propagation of positive and negative ionosphere disturbances in space and time and their forecast under different scenarios.

Investigating the performance of neural network backpropagation algorithms for TEC estimations using South African GPS data

NASA Astrophysics Data System (ADS)

Habarulema, J. B.; McKinnell, L.-A.

2012-05-01

In this work, results obtained by investigating the application of different neural network backpropagation training algorithms are presented. This was done to assess the performance accuracy of each training algorithm in total electron content (TEC) estimations using identical datasets in models development and verification processes. Investigated training algorithms are standard backpropagation (SBP), backpropagation with weight delay (BPWD), backpropagation with momentum (BPM) term, backpropagation with chunkwise weight update (BPC) and backpropagation for batch (BPB) training. These five algorithms are inbuilt functions within the Stuttgart Neural Network Simulator (SNNS) and the main objective was to find out the training algorithm that generates the minimum error between the TEC derived from Global Positioning System (GPS) observations and the modelled TEC data. Another investigated algorithm is the MatLab based Levenberg-Marquardt backpropagation (L-MBP), which achieves convergence after the least number of iterations during training. In this paper, neural network (NN) models were developed using hourly TEC data (for 8 years: 2000-2007) derived from GPS observations over a receiver station located at Sutherland (SUTH) (32.38° S, 20.81° E), South Africa. Verification of the NN models for all algorithms considered was performed on both "seen" and "unseen" data. Hourly TEC values over SUTH for 2003 formed the "seen" dataset. The "unseen" dataset consisted of hourly TEC data for 2002 and 2008 over Cape Town (CPTN) (33.95° S, 18.47° E) and SUTH, respectively. The models' verification showed that all algorithms investigated provide comparable results statistically, but differ significantly in terms of time required to achieve convergence during input-output data training/learning. This paper therefore provides a guide to neural network users for choosing appropriate algorithms based on the availability of computation capabilities used for research.

Detection of Geomagnetic Pulsations of the Earth Using GPS-TEC Data

NASA Astrophysics Data System (ADS)

Koroglu, Ozan; Arikan, Feza; Köroǧlu, Meltem; Sabri Ozkazanc, Yakup

2016-07-01

The magnetosphere of the Earth is made up of both magnetic fields and plasma. In this layer, plasma waves propagate as Ultra Low Frequency (ULF) waves having mHz scale frequencies. ULF waves are produced due to complicated solar-geomagnetic interactions. In the literature, these ULF waves are defined as pulsations. The geomagnetic pulsations are classified into main two groups as continuous pulsations (Pc) and irregular pulsations (Pi). These pulsations can be determined by ionospheric parameters due to the complex lithosphere-ionosphere-magnetosphere coupling processes. Total Electron Content (TEC) is one of the most important parameters for investigating the variability of ionosphere. Global Positioning System (GPS) provides a cost-effective means for estimating TEC from GPS satellite orbital height of 20,000 km to the ground based receivers. Therefore, the time series of GPS-TEC inherently contains the above mentioned ULF waves. In this study, time series analysis of GPS-TEC is carried out by applying periodogram method to the mid-latitude annual TEC data. After the analysis of GPS-TEC data obtained for GPS stations located in Central Europe and Turkey for 2011, it is observed that some of the fundamental frequencies that are indicators of Pc waves, diurnal and semi-diurnal periodicity and earth-free oscillations can be identified. These results will be used in determination of low frequency trend structure of magnetosphere and ionosphere. Further investigation of remaining relatively low magnitude frequencies, all Pi and Pc can be identified by using time and frequency domain techniques such as wavelet analysis. This study is supported by the joint TUBITAK 115E915 and joint TUBITAK114E092 and AS CR 14/001 projects.

Ionospheric variation observed in Oregon Real-time GNSS network during the total eclipse of 21 August 2017

NASA Astrophysics Data System (ADS)

Shahbazi, A.; Park, J.; Kim, S.; Oberg, R.

2017-12-01

As the ionospheric behavior is highly related to the solar activity, the total eclipse passing across the North America on 21 August 2017 is expected to significantly affect the electron density in the ionosphere along the path. Taking advantage of GNSS capability for observing total electron content (TEC), this study demonstrates the impact of the total eclipse not only on the TEC variation during the period of the event but also on GNSS positioning. Oregon Department of Transportation (ODOT) runs a dense real time GNSS network, referred to as Oregon Real-time GNSS network (ORGN). From the dual frequency GPS and GLONASS observations in ORGN, the TEC over the network area can be extracted. We observe the vertical TEC (VTEC) from the ORGN for analyzing the ionospheric condition in the local area affected by the eclipse. To observe the temporal variation, we also observe the slant TEC (STEC) in each ray path and analyze the short term variation in different geometry of each ray path. Although the STEC is dependent quantity upon the changing geometry of a satellite, this approach provides insight to the ionospheric behavior of the total eclipse because the STEC does not involve the projection error, which is generated by VTEC computation. During the period of eclipse, the abnormal variations on VTEC and STEC are expected. The experimental results will be presented in time series plots for selected stations as well as the regional TEC map in Oregon. In addition to the TEC monitoring, we also test the positioning result of ORGN stations through Precise Point Positioning (PPP) and relative positioning. The expected result is that the both positioning results are degraded during the solar eclipse due to the instable ionospheric condition over short time.

Safe Gene Therapy for Type 1 Diabetes

DTIC Science & Technology

2012-10-01

by transplanting these cells, either alone or together with FoxP3+eGFP+ T-regulatory cells into prediabetic ID-TEC pups. Diabetes incidence and...transplanting these cells, either alone or together with FoxP3+eGFP+ T-regulatory cells into prediabetic ID-TEC pups. Diabetes incidence and progression will...progression of islet-autoimmunity in prediabetic ID-TEC pups. 38 In the fourth quarterly scientific progress report (06/28/11 - 09/27/11) of year 02

Plasma density irregularities and Total Electron Content gradients over Europe

NASA Astrophysics Data System (ADS)

Zakharenkova, I.; Kotulak, K.; Cherniak, I.; Krankowski, A.; Froń, A.

2017-12-01

Perturbations of the ionospheric plasma density are crucial from the scientific and application points of view, as they can severe affect radio signals used in the Global Navigation Satellite Systems (GNSS) and low frequency radio astronomy. For several decades the ionospheric irregularities have been extensively studied by different techniques, including ground-based GNSS observations. Spatial distribution of ionospheric disturbances can be specified by horizontal gradients of the ionospheric density (total electron content, TEC). Another, widely used tool in irregularities monitoring is the rate of TEC index (ROTI). Recently, the Northern Hemisphere ROTI product has been implemented to the International GNSS Service (IGS) and available for community. In this study, we present climatology of the spatial TEC gradients occurred over European region at high to middle latitudes. We developed the TEC gradient maps based on the high-resolution (0.5 degree in latitude and longitude) regional TEC maps covering Europe. The obtained climatological characteristics of the spatial TEC gradients are superimposed and analyzed with the global and regional ROTI product in order to reveal development of highly intense plasma irregularities occurred at high and middle latitudes. During geomagnetic storm the complex of physical processes at auroal zone leads to development of intnse ionospheric irregularities and travelling ionospheric disturbances (TIDs). We presents results of the geomagnetic storm analysis including the 2013 and 2015 St. Patrick's Day geomagnetic storms.

In situ structures of the segmented genome and RNA polymerase complex inside a dsRNA virus

NASA Astrophysics Data System (ADS)

Zhang, Xing; Ding, Ke; Yu, Xuekui; Chang, Winston; Sun, Jingchen; Hong Zhou, Z.

2015-11-01

Viruses in the Reoviridae, like the triple-shelled human rotavirus and the single-shelled insect cytoplasmic polyhedrosis virus (CPV), all package a genome of segmented double-stranded RNAs (dsRNAs) inside the viral capsid and carry out endogenous messenger RNA synthesis through a transcriptional enzyme complex (TEC). By direct electron-counting cryoelectron microscopy and asymmetric reconstruction, we have determined the organization of the dsRNA genome inside quiescent CPV (q-CPV) and the in situ atomic structures of TEC within CPV in both quiescent and transcribing (t-CPV) states. We show that the ten segmented dsRNAs in CPV are organized with ten TECs in a specific, non-symmetric manner, with each dsRNA segment attached directly to a TEC. The TEC consists of two extensively interacting subunits: an RNA-dependent RNA polymerase (RdRP) and an NTPase VP4. We find that the bracelet domain of RdRP undergoes marked conformational change when q-CPV is converted to t-CPV, leading to formation of the RNA template entry channel and access to the polymerase active site. An amino-terminal helix from each of two subunits of the capsid shell protein (CSP) interacts with VP4 and RdRP. These findings establish the link between sensing of environmental cues by the external proteins and activation of endogenous RNA transcription by the TEC inside the virus.

STAT6 deficiency ameliorates Graves' disease severity by suppressing thyroid epithelial cell hyperplasia.

PubMed

Jiang, Xuechao; Zha, Bingbing; Liu, Xiaoming; Liu, Ronghua; Liu, Jun; Huang, Enyu; Qian, Tingting; Liu, Jiajing; Wang, Zhiming; Zhang, Dan; Wang, Luman; Chu, Yiwei

2016-12-01

Signal transducer and activator of transcription 6 (STAT6) is involved in epithelial cell growth. However, little is known regarding the STAT6 phosphorylation status in Graves' disease (GD) and its role in thyroid epithelial cells (TECs). In this study, we found that STAT6 phosphorylation (p-STAT6) was significantly increased in TECs from both GD patients and experimental autoimmune Graves' disease mice and that STAT6 deficiency ameliorated GD symptoms. Autocrine IL-4 signalling in TECs activated the phosphorylation of STAT6 via IL-4 R engagement, and the downstream targets of STAT6 were Bcl-xL and cyclin D1. Thus, the IL-4-STAT6-Bcl-xL/cyclin D1 pathway is crucial for TEC hyperplasia, which aggravates GD. More importantly, in vitro and in vivo experiments demonstrated that STAT6 phosphorylation inhibited by AS1517499 decreased TEC hyperplasia, thereby reducing serum T3 and T4 and ameliorating GD. Thus, our study reveals that in addition to the traditional pathogenesis of GD, in which autoantibody TRAb stimulates thyroid-stimulating hormone receptors and consequently produces T3, T4, TRAb could also trigger TECs producing IL-4, and IL-4 then acts in an autocrine manner to activate p-STAT6 signalling and stimulate unrestricted cell growth, thus aggravating GD. These findings suggest that STAT6 inhibitors could be potent therapeutics for treating GD.

STAT6 deficiency ameliorates Graves' disease severity by suppressing thyroid epithelial cell hyperplasia

PubMed Central

Jiang, Xuechao; Zha, Bingbing; Liu, Xiaoming; Liu, Ronghua; Liu, Jun; Huang, Enyu; Qian, Tingting; Liu, Jiajing; Wang, Zhiming; Zhang, Dan; Wang, Luman; Chu, Yiwei

2016-01-01

Signal transducer and activator of transcription 6 (STAT6) is involved in epithelial cell growth. However, little is known regarding the STAT6 phosphorylation status in Graves' disease (GD) and its role in thyroid epithelial cells (TECs). In this study, we found that STAT6 phosphorylation (p-STAT6) was significantly increased in TECs from both GD patients and experimental autoimmune Graves' disease mice and that STAT6 deficiency ameliorated GD symptoms. Autocrine IL-4 signalling in TECs activated the phosphorylation of STAT6 via IL-4 R engagement, and the downstream targets of STAT6 were Bcl-xL and cyclin D1. Thus, the IL-4-STAT6-Bcl-xL/cyclin D1 pathway is crucial for TEC hyperplasia, which aggravates GD. More importantly, in vitro and in vivo experiments demonstrated that STAT6 phosphorylation inhibited by AS1517499 decreased TEC hyperplasia, thereby reducing serum T3 and T4 and ameliorating GD. Thus, our study reveals that in addition to the traditional pathogenesis of GD, in which autoantibody TRAb stimulates thyroid-stimulating hormone receptors and consequently produces T3, T4, TRAb could also trigger TECs producing IL-4, and IL-4 then acts in an autocrine manner to activate p-STAT6 signalling and stimulate unrestricted cell growth, thus aggravating GD. These findings suggest that STAT6 inhibitors could be potent therapeutics for treating GD. PMID:27906181

Medium Calcium Concentration Determines Keratin Intermediate Filament Density and Distribution in Immortalized Cultured Thymic Epithelial Cells (TECs)

NASA Astrophysics Data System (ADS)

Sands, Sandra S.; Meek, William D.; Hayashi, Jun; Ketchum, Robert J.

2005-08-01

Isolation and culture of thymic epithelial cells (TECs) using conventional primary tissue culture techniques under conditions employing supplemented low calcium medium yielded an immortalized cell line derived from the LDA rat (Lewis [Rt1l] cross DA [Rt1a]) that could be manipulated in vitro. Thymi were harvested from 4 5-day-old neonates, enzymically digested using collagenase (1 mg/ml, 37°C, 1 h) and cultured in low calcium WAJC404A medium containing cholera toxin (20 ng/ml), dexamethasone (10 nM), epidermal growth factor (10 ng/ml), insulin (10 [mu]g/ml), transferrin (10 [mu]g/ml), 2% calf serum, 2.5% Dulbecco's Modified Eagle's Medium (DMEM), and 1% antibiotic/antimycotic. TECs cultured in low calcium displayed round to spindle-shaped morphology, distinct intercellular spaces (even at confluence), and dense reticular-like keratin patterns. In high calcium (0.188 mM), TECs formed cobblestone-like confluent monolayers that were resistant to trypsinization (0.05%) and displayed keratin intermediate filaments concentrated at desmosomal junctions between contiguous cells. Changes in cultured TEC morphology were quantified by an analysis of desmosome/membrane relationships in high and low calcium media. Desmosomes were significantly increased in the high calcium medium. These studies may have value when considering the growth conditions of cultured primary cell lines like TECs.

Behaviour of Electron Content in the Ionospheric D-Region During Solar X-Ray Flares

NASA Astrophysics Data System (ADS)

Todorović Drakul, M.; Čadež, V. M.; Bajčetić, J.; Popović, L. Č.; Blagojević, D.; Nina, A.

2016-12-01

One of the most important parameters in ionospheric plasma research, also having a wide practical application in wireless satellite telecommunications, is the total electron content (TEC) representing the columnal electron number density. The F-region with high electron density provides the biggest contribution to TEC while the relatively weakly ionized plasma of the D-region (60 km - 90 km above Earth's surface) is often considered as a negligible cause of satellite signal disturbances. However, sudden intensive ionization processes, like those induced by solar X-ray flares, can cause relative increases of electron density that are significantly larger in the D-region than in regions at higher altitudes. Therefore, one cannot exclude a priori the D-region from investigations of ionospheric influences on propagation of electromagnetic signals emitted by satellites. We discuss here this problem which has not been sufficiently treated in literature so far. The obtained results are based on data collected from the D-region monitoring by very low frequency radio waves and on vertical TEC calculations from the Global Navigation Satellite System (GNSS) signal analyses, and they show noticeable variations in the D-region's electron content (TEC_{D) during activity of a solar X-ray flare (it rises by a factor of 136 in the considered case) when TEC_{D} contribution to TEC can reach several percent and which cannot be neglected in practical applications like global positioning procedures by satellites.

CLAVATA1 Dominant-Negative Alleles Reveal Functional Overlap between Multiple Receptor Kinases That Regulate Meristem and Organ Development

PubMed Central

Diévart, Anne; Dalal, Monica; Tax, Frans E.; Lacey, Alexzandria D.; Huttly, Alison; Li, Jianming; Clark, Steven E.

2003-01-01

The CLAVATA1 (CLV1) receptor kinase controls stem cell number and differentiation at the Arabidopsis shoot and flower meristems. Other components of the CLV1 signaling pathway include the secreted putative ligand CLV3 and the receptor-like protein CLV2. We report evidence indicating that all intermediate and strong clv1 alleles are dominant negative and likely interfere with the activity of unknown receptor kinase(s) that have functional overlap with CLV1. clv1 dominant-negative alleles show major differences from dominant-negative alleles characterized to date in animal receptor kinase signaling systems, including the lack of a dominant-negative effect of kinase domain truncation and the ability of missense mutations in the extracellular domain to act in a dominant-negative manner. We analyzed chimeric receptor kinases by fusing CLV1 and BRASSINOSTEROID INSENSITIVE1 (BRI1) coding sequences and expressing these in clv1 null backgrounds. Constructs containing the CLV1 extracellular domain and the BRI1 kinase domain were strongly dominant negative in the regulation of meristem development. Furthermore, we show that CLV1 expressed within the pedicel can partially replace the function of the ERECTA receptor kinase. We propose the presence of multiple receptors that regulate meristem development in a functionally related manner whose interactions are driven by the extracellular domains and whose activation requires the kinase domain. PMID:12724544

Structural and mechanistic insights into Mps1 kinase activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Wei; Yang, Yuting; Gao, Yuefeng

2010-11-05

Mps1 is one of the several essential kinases whose activation is required for robust mitotic spindle checkpoint signalling. The activity of Mps1 is tightly regulated and increases dramatically during mitosis or in response to spindle damage. To understand the molecular mechanism underlying Mps1 regulation, we determined the crystal structure of the kinase domain of Mps1. The 2.7-{angstrom}-resolution crystal structure shows that the Mps1 kinase domain adopts a unique inactive conformation. Intramolecular interactions between the key Glu residue in the {alpha}C helix of the N-terminal lobe and the backbone amides in the catalytic loop lock the kinase in the inactive conformation.more » Autophosphorylation appears to be a priming event for kinase activation. We identified Mps1 autophosphorylation sites in the activation and the P+1 loops. Whereas activation loop autophosphorylation enhances kinase activity, autophosphorylation at the P+1 loop (T686) is associated with the active kinase. Mutation of T686 autophosphorylation site impairs both autophosphorylation and transphosphorylation. Furthermore, we demonstrated that phosphorylation of T676 may be a priming event for phosphorylation at T686. Finally, we identified two critical lysine residues in the loop between helices {alpha}EF and {alpha}F that are essential for substrate recruitment and maintaining high levels of kinase activity. Our studies reveal critical biochemical mechanisms for Mps1 kinase regulation.« less

Myosin 3A Kinase Activity Is Regulated by Phosphorylation of the Kinase Domain Activation Loop*

PubMed Central

Quintero, Omar A.; Unrath, William C.; Stevens, Stanley M.; Manor, Uri; Kachar, Bechara; Yengo, Christopher M.

2013-01-01

Class III myosins are unique members of the myosin superfamily in that they contain both a motor and kinase domain. We have found that motor activity is decreased by autophosphorylation, although little is known about the regulation of the kinase domain. We demonstrate by mass spectrometry that Thr-178 and Thr-184 in the kinase domain activation loop and two threonines in the loop 2 region of the motor domain are autophosphorylated (Thr-908 and Thr-919). The kinase activity of MYO3A 2IQ with the phosphomimic (T184E) or phosphoblock (T184A) mutations demonstrates that kinase activity is reduced 30-fold as a result of the T184A mutation, although the Thr-178 site only had a minor impact on kinase activity. Interestingly, the actin-activated ATPase activity of MYO3A 2IQ is slightly reduced as a result of the T178A and T184A mutations suggesting coupling between motor and kinase domains. Full-length GFP-tagged T184A and T184E MYO3A constructs transfected into COS7 cells do not disrupt the ability of MYO3A to localize to filopodia structures. In addition, we demonstrate that T184E MYO3A reduces filopodia elongation in the presence of espin-1, whereas T184A enhances filopodia elongation in a similar fashion to kinase-dead MYO3A. Our results suggest that as MYO3A accumulates at the tips of actin protrusions, autophosphorylation of Thr-184 enhances kinase activity resulting in phosphorylation of the MYO3A motor and reducing motor activity. The differential regulation of the kinase and motor activities allows for MYO3A to precisely self-regulate its concentration in the actin bundle-based structures of cells. PMID:24214986

Myosin 3A kinase activity is regulated by phosphorylation of the kinase domain activation loop.

PubMed

Quintero, Omar A; Unrath, William C; Stevens, Stanley M; Manor, Uri; Kachar, Bechara; Yengo, Christopher M

2013-12-27

Class III myosins are unique members of the myosin superfamily in that they contain both a motor and kinase domain. We have found that motor activity is decreased by autophosphorylation, although little is known about the regulation of the kinase domain. We demonstrate by mass spectrometry that Thr-178 and Thr-184 in the kinase domain activation loop and two threonines in the loop 2 region of the motor domain are autophosphorylated (Thr-908 and Thr-919). The kinase activity of MYO3A 2IQ with the phosphomimic (T184E) or phosphoblock (T184A) mutations demonstrates that kinase activity is reduced 30-fold as a result of the T184A mutation, although the Thr-178 site only had a minor impact on kinase activity. Interestingly, the actin-activated ATPase activity of MYO3A 2IQ is slightly reduced as a result of the T178A and T184A mutations suggesting coupling between motor and kinase domains. Full-length GFP-tagged T184A and T184E MYO3A constructs transfected into COS7 cells do not disrupt the ability of MYO3A to localize to filopodia structures. In addition, we demonstrate that T184E MYO3A reduces filopodia elongation in the presence of espin-1, whereas T184A enhances filopodia elongation in a similar fashion to kinase-dead MYO3A. Our results suggest that as MYO3A accumulates at the tips of actin protrusions, autophosphorylation of Thr-184 enhances kinase activity resulting in phosphorylation of the MYO3A motor and reducing motor activity. The differential regulation of the kinase and motor activities allows for MYO3A to precisely self-regulate its concentration in the actin bundle-based structures of cells.

Forensic Spoorology: Seeing and Understanding Human Behavior through Observation, Classification and Interpretation of Spoor Evidence

DTIC Science & Technology

2011-06-10

SASA Stride and Step Analysis SCS Spoor-Chain Signature SID Self -Imposed Distortion SMS Steadfast-Mind State SSA Secondary Spoor Area TEC Track...because there was no self -regulating body of professional trackers whom by education, training, and experience had come together to establish an...registered in soft ground or in snow by isolated tracks. This visibility gap in knowledge leaves an examiner‘s eyes outside the realm of linearity

Mesenchymal stem cell therapy ameliorates diabetic nephropathy via the paracrine effect of renal trophic factors including exosomes

PubMed Central

Nagaishi, Kanna; Mizue, Yuka; Chikenji, Takako; Otani, Miho; Nakano, Masako; Konari, Naoto; Fujimiya, Mineko

2016-01-01

Bone marrow-derived mesenchymal stem cells (MSCs) have contributed to the improvement of diabetic nephropathy (DN); however, the actual mediator of this effect and its role has not been characterized thoroughly. We investigated the effects of MSC therapy on DN, focusing on the paracrine effect of renal trophic factors, including exosomes secreted by MSCs. MSCs and MSC-conditioned medium (MSC-CM) as renal trophic factors were administered in parallel to high-fat diet (HFD)-induced type 2 diabetic mice and streptozotocin (STZ)-induced insulin-deficient diabetic mice. Both therapies showed approximately equivalent curative effects, as each inhibited the exacerbation of albuminuria. They also suppressed the excessive infiltration of BMDCs into the kidney by regulating the expression of the adhesion molecule ICAM-1. Proinflammatory cytokine expression (e.g., TNF-α) and fibrosis in tubular interstitium were inhibited. TGF-β1 expression was down-regulated and tight junction protein expression (e.g., ZO-1) was maintained, which sequentially suppressed the epithelial-to-mesenchymal transition of tubular epithelial cells (TECs). Exosomes purified from MSC-CM exerted an anti-apoptotic effect and protected tight junction structure in TECs. The increase of glomerular mesangium substrate was inhibited in HFD-diabetic mice. MSC therapy is a promising tool to prevent DN via the paracrine effect of renal trophic factors including exosomes due to its multifactorial action. PMID:27721418

On the reported ionospheric precursor of the 1999 Hector Mine, California earthquake

USGS Publications Warehouse

Thomas, Jeremy N.; Love, Jeffrey J.; Komjathy, Attila; Verkhoglyadova, Olga P.; Butala, Mark; Rivera, Nicholas

2012-01-01

Using Global Positioning System (GPS) data from sites near the 16 Oct. 1999 Hector Mine, California earthquake, Pulinets et al. (2007) identified anomalous changes in the ionospheric total electron content (TEC) starting one week prior to the earthquake. Pulinets (2007) suggested that precursory phenomena of this type could be useful for predicting earthquakes. On the other hand, and in a separate analysis, Afraimovich et al. (2004) concluded that TEC variations near the epicenter were controlled by solar and geomagnetic activity that were unrelated to the earthquake. In an investigation of these very different results, we examine TEC time series of long duration from GPS stations near and far from the epicenter of the Hector Mine earthquake, and long before and long after the earthquake. While we can reproduce the essential time series results of Pulinets et al., we find that the signal they identify as anomalous is not actually anomalous. Instead, it is just part of normal global-scale TEC variation. We conclude that the TEC anomaly reported by Pulinets et al. is unrelated to the Hector Mine earthquake.

On the reported ionospheric precursor of the Hector Mine, California earthquake

USGS Publications Warehouse

Thomas, J.N.; Love, J.J.; Komjathy, A.; Verkhoglyadova, O.P.; Butala, M.; Rivera, N.

2012-01-01

Using Global Positioning System (GPS) data from sites near the 16 Oct. 1999 Hector Mine, California earthquake, Pulinets et al. (2007) identified anomalous changes in the ionospheric total electron content (TEC) starting one week prior to the earthquake. Pulinets (2007) suggested that precursory phenomena of this type could be useful for predicting earthquakes. On the other hand, and in a separate analysis, Afraimovich et al. (2004) concluded that TEC variations near the epicenter were controlled by solar and geomagnetic activity that were unrelated to the earthquake. In an investigation of these very different results, we examine TEC time series of long duration from GPS stations near and far from the epicenter of the Hector Mine earthquake, and long before and long after the earthquake. While we can reproduce the essential time series results of Pulinets et al., we find that the signal they identified as being anomalous is not actually anomalous. Instead, it is just part of normal global-scale TEC variation. We conclude that the TEC anomaly reported by Pulinets et al. is unrelated to the Hector Mine earthquake.

Statistical evidence of seismo-ionospheric precursors of the GPS total electron content in China

NASA Astrophysics Data System (ADS)

Chen, Yuh-Ing; Huang, Chi-Shen; Liu, Jann-Yenq

2015-04-01

Evidence of the seismo-ionospheric precursor (SIP) is reported by statistically investigating the relationship between the total electron content (TEC) in global ionosphere map (GIM) and 56 M≥6.0 earthquakes during 1998-2013 in China. A median-based method together with the z test is employed to examine the TEC variations 30 days before and after the earthquake. It is found that the TEC significantly decreases 0600-1000 LT 1-6 days before the earthquake, and anomalously increases in 3 time periods of 1300-1700 LT 12-15 days; 0000-0500 LT 15-17 days; and 0500-0900 LT 22-28 days before the earthquake. The receiver operating characteristic (ROC) curve is then used to evaluate the efficiency of TEC for predicting M≥6.0 earthquakes in China during a specified time period. Statistical results suggest that the SIP is the significant TEC reduction in the morning period of 0600-1000 LT. The SIP is further confirmed since the area under the ROC curve is positively associated with the earthquake magnitude.

Statistical evidences of seismo-ionospheric precursors applying receiver operating characteristic (ROC) curve on the GPS total electron content in China

NASA Astrophysics Data System (ADS)

Chen, Yuh-Ing; Huang, Chi-Shen; Liu, Jann-Yenq

2015-12-01

Evidence of the seismo-ionospheric precursor (SIP) is reported by statistically investigating the relationship between the total electron content (TEC) in global ionosphere map (GIM) and 56 M ⩾ 6.0 earthquakes during 1998-2013 in China. A median-based method together with the z test is employed to examine the TEC variations 30 days before and after the earthquake. It is found that the TEC significantly decreases 0600-1000 LT 1-6 days before the earthquake, and anomalously increases in 3 time periods of 1300-1700 LT 12-15 days; 0000-0500 LT 15-17 days; and 0500-0900 LT 22-28 days before the earthquake. The receiver operating characteristic (ROC) curve is then used to evaluate the efficiency of TEC for predicting M ⩾ 6.0 earthquakes in China during a specified time period. Statistical results suggest that the SIP is the significant TEC reduction in the morning period of 0600-1000 LT. The SIP is further confirmed since the area under the ROC curve is positively associated with the earthquake magnitude.

Te/C nanocomposites for Li-Te Secondary Batteries

NASA Astrophysics Data System (ADS)

Seo, Jeong-Uk; Seong, Gun-Kyu; Park, Cheol-Min

2015-01-01

New battery systems having high energy density are actively being researched in order to satisfy the rapidly developing market for longer-lasting mobile electronics and hybrid electric vehicles. Here, we report a new Li-Te secondary battery system with a redox potential of ~1.7 V (vs. Li+/Li) adapted on a Li metal anode and an advanced Te/C nanocomposite cathode. Using a simple concept of transforming TeO2 into nanocrystalline Te by mechanical reduction, we designed an advanced, mechanically reduced Te/C nanocomposite electrode material with high energy density (initial discharge/charge: 1088/740 mA h cm-3), excellent cyclability (ca. 705 mA h cm-3 over 100 cycles), and fast rate capability (ca. 550 mA h cm-3 at 5C rate). The mechanically reduced Te/C nanocomposite electrodes were found to be suitable for use as either the cathode in Li-Te secondary batteries or a high-potential anode in rechargeable Li-ion batteries. We firmly believe that the mechanically reduced Te/C nanocomposite constitutes a breakthrough for the realization and mass production of excellent energy storage systems.

Mechanisms of ROS modulated cell survival during carcinogenesis.

PubMed

Clerkin, J S; Naughton, R; Quiney, C; Cotter, T G

2008-07-18

There is increasing evidence within the literature that the decreased susceptibility of tumour cells to stimuli that induce apoptosis can be linked to their inherently increased redox potential. The review primarily focuses on the PI3-kinase/Akt pathway, and the multiple points along this signalling pathway that may be redox regulated. The PI3-kinase/Akt pathway can influence a cells' sensitivity to death inducing signals, through direct manipulation of apoptosis regulating molecules or by regulating the activity of key transcription factors. Proteins involved in the control of apoptosis that are directly regulated by the PI3-kinase/Akt pathway include caspase-9, Bad and the transcription factor GSK-3beta. Lately, it is becoming increasingly obvious that phosphatases are a major counter balance to the PI3-kinase/Akt pathway. Phosphatases such as PP2A and PP1alpha can dephosphorylate signalling molecules within the PI3-kinase/Akt pathway, blocking their activity. It is the balance between the kinase activity and the phosphatase activity that determines the presence and strength of the PI3-kinase/Akt signal. This is why any protein modifications that hinder dephosphorylation can increase the tumours survival advantage. One such modification is the oxidation of the sulphydryl group in key cysteine residues present within the active site of the phosphatases. This highlights the link between the increased redox stress in tumours with the PI3-kinase/Akt pathway. This review will discuss the various sources of reactive oxygen species within a tumour and the effect of these radicals on the PI3-kinase/Akt pathway.

SH2/SH3 adaptor proteins can link tyrosine kinases to a Ste20-related protein kinase, HPK1.

PubMed

Anafi, M; Kiefer, F; Gish, G D; Mbamalu, G; Iscove, N N; Pawson, T

1997-10-31

Ste20-related protein kinases have been implicated as regulating a range of cellular responses, including stress-activated protein kinase pathways and the control of cytoskeletal architecture. An important issue involves the identities of the upstream signals and regulators that might control the biological functions of mammalian Ste20-related protein kinases. HPK1 is a protein-serine/threonine kinase that possesses a Ste20-like kinase domain, and in transfected cells activates a protein kinase pathway leading to the stress-activated protein kinase SAPK/JNK. Here we have investigated candidate upstream regulators that might interact with HPK1. HPK1 possesses an N-terminal catalytic domain and an extended C-terminal tail with four proline-rich motifs. The SH3 domains of Grb2 bound in vitro to specific proline-rich motifs in the HPK1 tail and functioned synergistically to direct the stable binding of Grb2 to HPK1 in transfected Cos1 cells. Epidermal growth factor (EGF) stimulation did not affect the binding of Grb2 to HPK1 but induced recruitment of the Grb2.HPK1 complex to the autophosphorylated EGF receptor and to the Shc docking protein. Several activated receptor and cytoplasmic tyrosine kinases, including the EGF receptor, stimulated the tyrosine phosphorylation of the HPK1 serine/threonine kinase. These results suggest that HPK1, a mammalian Ste20-related protein-serine/threonine kinase, can potentially associate with protein-tyrosine kinases through interactions mediated by SH2/SH3 adaptors such as Grb2. Such interaction may provide a possible mechanism for cross-talk between distinct biochemical pathways following the activation of tyrosine kinases.

Functional Analysis of the Aspergillus nidulans Kinome

PubMed Central

De Souza, Colin P.; Hashmi, Shahr B.; Osmani, Aysha H.; Andrews, Peter; Ringelberg, Carol S.; Dunlap, Jay C.; Osmani, Stephen A.

2013-01-01

The filamentous fungi are an ecologically important group of organisms which also have important industrial applications but devastating effects as pathogens and agents of food spoilage. Protein kinases have been implicated in the regulation of virtually all biological processes but how they regulate filamentous fungal specific processes is not understood. The filamentous fungus Aspergillus nidulans has long been utilized as a powerful molecular genetic system and recent technical advances have made systematic approaches to study large gene sets possible. To enhance A. nidulans functional genomics we have created gene deletion constructs for 9851 genes representing 93.3% of the encoding genome. To illustrate the utility of these constructs, and advance the understanding of fungal kinases, we have systematically generated deletion strains for 128 A. nidulans kinases including expanded groups of 15 histidine kinases, 7 SRPK (serine-arginine protein kinases) kinases and an interesting group of 11 filamentous fungal specific kinases. We defined the terminal phenotype of 23 of the 25 essential kinases by heterokaryon rescue and identified phenotypes for 43 of the 103 non-essential kinases. Uncovered phenotypes ranged from almost no growth for a small number of essential kinases implicated in processes such as ribosomal biosynthesis, to conditional defects in response to cellular stresses. The data provide experimental evidence that previously uncharacterized kinases function in the septation initiation network, the cell wall integrity and the morphogenesis Orb6 kinase signaling pathways, as well as in pathways regulating vesicular trafficking, sexual development and secondary metabolism. Finally, we identify ChkC as a third effector kinase functioning in the cellular response to genotoxic stress. The identification of many previously unknown functions for kinases through the functional analysis of the A. nidulans kinome illustrates the utility of the A. nidulans gene deletion constructs. PMID:23505451

A complex regulatory network controls aerobic ethanol oxidation in Pseudomonas aeruginosa: indication of four levels of sensor kinases and response regulators.

PubMed

Mern, Demissew S; Ha, Seung-Wook; Khodaverdi, Viola; Gliese, Nicole; Görisch, Helmut

2010-05-01

In addition to the known response regulator ErbR (former AgmR) and the two-component regulatory system EraSR (former ExaDE), three additional regulatory proteins have been identified as being involved in controlling transcription of the aerobic ethanol oxidation system in Pseudomonas aeruginosa. Two putative sensor kinases, ErcS and ErcS', and a response regulator, ErdR, were found, all of which show significant similarity to the two-component flhSR system that controls methanol and formaldehyde metabolism in Paracoccus denitrificans. All three identified response regulators, EraR (formerly ExaE), ErbR (formerly AgmR) and ErdR, are members of the luxR family. The three sensor kinases EraS (formerly ExaD), ErcS and ErcS' do not contain a membrane domain. Apparently, they are localized in the cytoplasm and recognize cytoplasmic signals. Inactivation of gene ercS caused an extended lag phase on ethanol. Inactivation of both genes, ercS and ercS', resulted in no growth at all on ethanol, as did inactivation of erdR. Of the three sensor kinases and three response regulators identified thus far, only the EraSR (formerly ExaDE) system forms a corresponding kinase/regulator pair. Using reporter gene constructs of all identified regulatory genes in different mutants allowed the hierarchy of a hypothetical complex regulatory network to be established. Probably, two additional sensor kinases and two additional response regulators, which are hidden among the numerous regulatory genes annotated in the genome of P. aeruginosa, remain to be identified.

The long and the short of SAD-1 kinase.

PubMed

Kim, Joanne S M; Hung, Wesley; Zhen, Mei

2010-05-01

The Ser/Thr SAD kinases are evolutionarily conserved, critical regulators of neural development. Exciting findings in recent years have significantly advanced our understanding of the mechanism through which SAD kinases regulate neural development. Mammalian SAD-A and SAD-B, activated by a master kinase LKB1, regulate microtubule dynamics and polarize neurons. In C. elegans, the sad-1 gene encodes two isoforms, namely the long and the short, which exhibit overlapping and yet distinct functions in neuronal polarity and synaptic organization. Surprisingly, our most recent findings in C. elegans revealed a SAD-1-independent LKB1 activity in neuronal polarity. We also found that the long SAD-1 isoform directly interacts with a STRADalpha pseudokinase, STRD-1, to regulate neuronal polarity and synaptic organization. We elaborate here a working model of SAD-1 in which the two isoforms dimer/oligomerize to form a functional complex, and STRD-1 clusters and localizes the SAD-1 complex to synapses. While the mechanistic difference between the vertebrate and invertebrate SAD kinases may be puzzling, a recent discovery of the functionally distinct SAD-B isoforms predicts that the difference likely arises from our incomplete understanding of the SAD kinase mechanism and may eventually be reconciled as the revelation continues.

Structure of the intact ATM/Tel1 kinase

NASA Astrophysics Data System (ADS)

Wang, Xuejuan; Chu, Huanyu; Lv, Mengjuan; Zhang, Zhihui; Qiu, Shuwan; Liu, Haiyan; Shen, Xuetong; Wang, Weiwu; Cai, Gang

2016-05-01

The ataxia-telangiectasia mutated (ATM) protein is an apical kinase that orchestrates the multifaceted DNA-damage response. Normally, ATM kinase is in an inactive, homodimer form and is transformed into monomers upon activation. Besides a conserved kinase domain at the C terminus, ATM contains three other structural modules, referred to as FAT, FATC and N-terminal helical solenoid. Here we report the first cryo-EM structure of ATM kinase, which is an intact homodimeric ATM/Tel1 from Schizosaccharomyces pombe. We show that two monomers directly contact head-to-head through the FAT and kinase domains. The tandem N-terminal helical solenoid tightly packs against the FAT and kinase domains. The structure suggests that ATM/Tel1 dimer interface and the consecutive HEAT repeats inhibit the binding of kinase substrates and regulators by steric hindrance. Our study provides a structural framework for understanding the mechanisms of ATM/Tel1 regulation as well as the development of new therapeutic agents.

Discovery of cellular substrates for protein kinase A using a peptide array screening protocol.

PubMed

Smith, F Donelson; Samelson, Bret K; Scott, John D

2011-08-15

Post-translational modification of proteins is a universal form of cellular regulation. Phosphorylation on serine, threonine, tyrosine or histidine residues by protein kinases is the most widespread and versatile form of covalent modification. Resultant changes in activity, localization or stability of phosphoproteins drives cellular events. MS and bioinformatic analyses estimate that ~30% of intracellular proteins are phosphorylated at any given time. Multiple approaches have been developed to systematically define targets of protein kinases; however, it is likely that we have yet to catalogue the full complement of the phosphoproteome. The amino acids that surround a phosphoacceptor site are substrate determinants for protein kinases. For example, basophilic enzymes such as PKA (protein kinase A), protein kinase C and calmodulin-dependent kinases recognize basic side chains preceding the target serine or threonine residues. In the present paper we describe a strategy using peptide arrays and motif-specific antibodies to identify and characterize previously unrecognized substrate sequences for protein kinase A. We found that the protein kinases PKD (protein kinase D) and MARK3 [MAP (microtubule-associated protein)-regulating kinase 3] can both be phosphorylated by PKA. Furthermore, we show that the adapter protein RIL [a product of PDLIM4 (PDZ and LIM domain protein 4)] is a PKA substrate that is phosphorylated on Ser(119) inside cells and that this mode of regulation may control its ability to affect cell growth. © The Authors Journal compilation © 2011 Biochemical Society

Mechanisms of extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor signal transduction pathway in depressive disorder☆

PubMed Central

Wang, Hongyan; Zhang, Yingquan; Qiao, Mingqi

2013-01-01

The extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor signal transduction pathway plays an important role in the mechanism of action of antidepressant drugs and has dominated recent studies on the pathogenesis of depression. In the present review we summarize the known roles of extracellular signal-regulated kinase, cAMP response element-binding protein and brain-derived neurotrophic factor in the pathogenesis of depression and in the mechanism of action of antidepressant medicines. The extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor pathway has potential to be used as a biological index to help diagnose depression, and as such it is considered as an important new target in the treatment of depression. PMID:25206732

Growth factor receptor-binding protein 10 (Grb10) as a partner of phosphatidylinositol 3-kinase in metabolic insulin action.

PubMed

Deng, Youping; Bhattacharya, Sujoy; Swamy, O Rama; Tandon, Ruchi; Wang, Yong; Janda, Robert; Riedel, Heimo

2003-10-10

The regulation of the metabolic insulin response by mouse growth factor receptor-binding protein 10 (Grb10) has been addressed in this report. We find mouse Grb10 to be a critical component of the insulin receptor (IR) signaling complex that provides a functional link between IR and p85 phosphatidylinositol (PI) 3-kinase and regulates PI 3-kinase activity. This regulatory mechanism parallels the established link between IR and p85 via insulin receptor substrate (IRS) proteins. A direct association was demonstrated between Grb10 and p85 but was not observed between Grb10 and IRS proteins. In addition, no effect of mouse Grb10 was observed on the association between IRS-1 and p85, on IRS-1-associated PI 3-kinase activity, or on insulin-mediated activation of IR or IRS proteins. A critical role of mouse Grb10 was observed in the regulation of PI 3-kinase activity and the resulting metabolic insulin response. Dominant-negative Grb10 domains, in particular the SH2 domain, eliminated the metabolic response to insulin in differentiated 3T3-L1 adipocytes. This was consistently observed for glycogen synthesis, glucose and amino acid transport, and lipogenesis. In parallel, the same metabolic responses were substantially elevated by increased levels of Grb10. A similar role of Grb10 was confirmed in mouse L6 cells. In addition to the SH2 domain, the Pro-rich amino-terminal region of Grb10 was implicated in the regulation of PI 3-kinase catalytic activity. These regulatory roles of Grb10 were extended to specific insulin mediators downstream of PI 3-kinase including PKB/Akt, glycogen synthase kinase, and glycogen synthase. In contrast, a regulatory role of Grb10 in parallel insulin response pathways including p70 S6 kinase, ubiquitin ligase Cbl, or mitogen-activated protein kinase p38 was not observed. The dissection of the interaction of mouse Grb10 with p85 and the resulting regulation of PI 3-kinase activity should help elucidate the complexity of the IR signaling mechanism.

C-terminal splicing of NTPDase2 provides distinctive catalytic properties, cellular distribution and enzyme regulation

PubMed Central

2004-01-01

The present study provides functional characterization of alternative splicing of the NTPDase2 (ecto-nucleoside triphosphate diphosphohydrolase-2) involved in the regulation of extracellular nucleotide concentrations in a range of organ systems. A novel NTPDase2β isoform produced by alternative splicing of the rat NTPDase2 gene provides an extended intracellular C-terminus and distinguishes itself from NTPDase2α isoform in gaining several intracellular protein kinase CK2 (casein kinase 2) phosphorylation sites and losing the intracellular protein kinase C motif. The plasmids containing NTPDase2α or NTPDase2β cDNA were used to stably transfect Chinese-hamster ovary-S cells. Imaging studies showed that NTPDase2α was predominantly membrane-bound, whereas NTPDase2β had combined cell surface and intracellular localization. α and β isoforms showed variations in divalent cation dependence and substrate specificity for nucleoside-5′-triphosphates and nucleoside-5′-diphosphates. NTPDase2β exhibited reduced ATPase activity and no apparent ADPase activity. NTPDase2 isoforms demonstrated similar sensitivity to inhibitors such as suramin and pyridoxal phosphate-6-azophenyl-2′,4′-disulphonic acid, and differential regulation by protein kinases. NTPDase2β was up-regulated by intracellular protein kinase CK2 phosphorylation, whereas NTPDase2α activity was down-regulated by protein kinase C phosphorylation. The results demonstrate that alternative coding of the intracellular C-terminal domain contributes distinctive phenotypic variation with respect to extracellular nucleotide specificity, hydrolysis kinetics, protein kinase-dependent intracellular regulation and protein trafficking. These findings advance the molecular physiology of this enzyme system by characterizing the contribution of the C-terminal domain to many of the enzyme's signature properties. PMID:15362980

Nuclear phosphoproteome analysis of 3T3-L1 preadipocyte differentiation reveals system-wide phosphorylation of transcriptional regulators.

PubMed

Rabiee, Atefeh; Schwämmle, Veit; Sidoli, Simone; Dai, Jie; Rogowska-Wrzesinska, Adelina; Mandrup, Susanne; Jensen, Ole N

2017-03-01

Adipocytes (fat cells) are important endocrine and metabolic cells critical for systemic insulin sensitivity. Both adipose excess and insufficiency are associated with adverse metabolic function. Adipogenesis is the process whereby preadipocyte precursor cells differentiate into lipid-laden mature adipocytes. This process is driven by a network of transcriptional regulators (TRs). We hypothesized that protein PTMs, in particular phosphorylation, play a major role in activating and propagating signals within TR networks upon induction of adipogenesis by extracellular stimulus. We applied MS-based quantitative proteomics and phosphoproteomics to monitor the alteration of nuclear proteins during the early stages (4 h) of preadipocyte differentiation. We identified a total of 4072 proteins including 2434 phosphorylated proteins, a majority of which were assigned as regulators of gene expression. Our results demonstrate that adipogenic stimuli increase the nuclear abundance and/or the phosphorylation levels of proteins involved in gene expression, cell organization, and oxidation-reduction pathways. Furthermore, proteins acting as negative modulators involved in negative regulation of gene expression, insulin stimulated glucose uptake, and cytoskeletal organization showed a decrease in their nuclear abundance and/or phosphorylation levels during the first 4 h of adipogenesis. Among 288 identified TRs, 49 were regulated within 4 h of adipogenic stimulation including several known and many novel potential adipogenic regulators. We created a kinase-substrate database for 3T3-L1 preadipocytes by investigating the relationship between protein kinases and protein phosphorylation sites identified in our dataset. A majority of the putative protein kinases belong to the cyclin-dependent kinase family and the mitogen-activated protein kinase family including P38 and c-Jun N-terminal kinases, suggesting that these kinases act as orchestrators of early adipogenesis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Exploring the intricate regulatory network controlling the thiazide-sensitive NaCl cotransporter (NCC).

PubMed

Dimke, Henrik

2011-12-01

The thiazide-sensitive NaCl cotransporter (NCC) plays key roles in renal electrolyte transport and blood pressure maintenance. Regulation of this cotransporter has received increased attention recently, prompted by the discovery that mutations in the with-no-lysine (WNK) kinases are the molecular explanation for pseudohypoaldosteronism type II (PHAII). Studies suggest that WNK4 regulates NCC via two distinct pathways, depending on its state of activation. Furthermore, an intact STE20-related proline-alanine-rich kinase (SPAK)/oxidative stress response 1 kinase (OSR1) pathway was found to be necessary for a WNK4 PHAII mutation to increase NCC phosphorylation and blood pressure in mice. The mouse protein 25α is a novel regulator of the SPAK/OSR1 kinase family, which greatly increases their activity. The phosphorylation status of NCC and the WNK is regulated by the serum- and glucocorticoid-inducible kinase 1, suggesting novel mechanisms whereby aldosterone modulates NCC activity. Dephosphorylation of NCC by protein phosphatase 4 strongly influences the activity of the cotransporter, confirming an important role for NCC phosphorylation. Finally, γ-adducin increases NCC activity. This stimulatory effect is dependent on the phosphorylation status of the cotransporter. γ-Adducin only binds the dephosphorylated cotransporter, suggesting that phosphorylation of NCC causes the dissociation of γ-adducin. Since γ-adducin is not a kinase, it is tempting to speculate that the protein exerts its function by acting as a scaffold between the dephosphorylated cotransporter and the regulatory kinase. As more molecular regulators of NCC are identified, the system-controlling NCC activity is becoming increasingly complex. This intricacy confers an ability to integrate a variety of stimuli, thereby regulating NCC transport activity and ultimately blood pressure.

Role of integrin-linked kinase in regulating phosphorylation of Akt and fibroblast survival in type I collagen matrices through a beta1 integrin viability signaling pathway.

PubMed

Nho, Richard Seonghun; Xia, Hong; Kahm, Judy; Kleidon, Jill; Diebold, Deanna; Henke, Craig A

2005-07-15

A beta1 integrin phosphatidylinositol 3-kinase/Akt pathway regulates fibroblast survival in collagen matrices. When fibroblasts attach to collagen, Akt becomes phosphorylated, providing a survival signal. In contrast, in response to mechanical forces generated during collagen contraction, Akt is dephosphorylated and fibroblasts undergo apoptosis. The kinase(s) responsible for regulating Akt phosphorylation in response to matrix-derived mechanical signals are unclear. Integrin-linked kinase (ILK) is associated with the beta1 integrin in the focal adhesion complex and as such is a candidate kinase that may regulate Akt phosphorylation and fibroblast viability. Nevertheless, there is no direct evidence that matrix-derived mechanical forces regulate cell viability by modulating ILK activity. Here, we show that ILK activity decreased in response to collagen matrix contraction, which correlated with Akt dephosphorylation and induction of fibroblast apoptosis. In contrast, enforced activation of beta1 integrin by activating antibody preserved ILK and Akt activity during collagen matrix contraction, and this is associated with protection from collagen contraction-induced apoptosis. Knock-down of ILK by small, interfering RNA (siRNA) attenuated Akt phosphorylation in response to ligation of beta1 integrin by collagen or activating antibody and enhanced fibroblast apoptosis in response to collagen contraction. Kinase dead ILK attenuated Akt phosphorylation and enhanced fibroblast apoptosis, whereas hyperactive and wild type ILK augmented Akt phosphorylation and protected fibroblasts from apoptosis. Constitutively active Akt preserved Akt activity and rescued ILK siRNA-treated fibroblasts from collagen contraction-induced apoptosis. These data establish that matrix-derived mechanical forces sensed by beta1 integrin are capable of modulating ILK activity which regulates fibroblast viability via an Akt-dependent mechanism.

Kinases of eIF2a Switch Translation of mRNA Subset during Neuronal Plasticity

PubMed Central

Chesnokova, Ekaterina; Bal, Natalia

2017-01-01

Compared to other types of cells, neurons express the largest number of diverse mRNAs, including neuron-specific ones. This mRNA diversity is required for neuronal function, memory storage, maintenance and retrieval. Regulation of translation in neurons is very complicated and involves various proteins. Some proteins, implementing translational control in other cell types, are used by neurons for synaptic plasticity. In this review, we discuss the neuron-specific activity of four kinases: protein kinase R (PKR), PKR-like endoplasmic reticulum kinase (PERK), general control nonderepressible 2 kinase (GCN2), and heme-reguated eIF2α kinase (HRI), the substrate for which is α-subunit of eukaryotic initiation factor 2 (eIF2α). Phosphorylation of eIF2α is necessary for the cell during stress conditions, such as lack of amino acids, energy stress or viral infection. We propose that, during memory formation, neurons use some mechanisms similar to those involved in the cellular stress. The four eIF2α kinases regulate translation of certain mRNAs containing upstream open reading frames (uORFs). These mRNAs encode proteins involved in the processes of long-term potentiation (LTP) or long-term depression (LTD). The review examines some neuronal proteins for which translation regulation by eIF2 was suggested and checked experimentally. Of such proteins, we pay close attention to protein kinase Mζ, which is involved in memory storage and regulated at the translational level. PMID:29065505

(Sub)millimetre interferometric imaging of a sample of COSMOS/AzTEC submillimetre galaxies. I. Multiwavelength identifications and redshift distribution

NASA Astrophysics Data System (ADS)

Miettinen, O.; Smolčić, V.; Novak, M.; Aravena, M.; Karim, A.; Masters, D.; Riechers, D. A.; Bussmann, R. S.; McCracken, H. J.; Ilbert, O.; Bertoldi, F.; Capak, P.; Feruglio, C.; Halliday, C.; Kartaltepe, J. S.; Navarrete, F.; Salvato, M.; Sanders, D.; Schinnerer, E.; Sheth, K.

2015-05-01

We used the Plateau de Bure Interferometer (PdBI) to map a sample of 15 submillimetre galaxies (SMGs) in the COSMOS field at the wavelength of 1.3 mm. The target SMGs were originally discovered in the James Clerk Maxwell Telescope (JCMT)/AzTEC 1.1 mm continuum survey at S/N1.1 mm = 4-4.5. This paper presents, for the first time, interferometric millimetre-wavelength observations of these sources. The angular resolution of our observations, 1''&dotbelow;8, allowed us to accurately determine the positions of the target SMGs. Using a detection threshold of S/N1.3 mm> 4.5 regardless of multiwavelength counterpart association, and 4