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

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.

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.

Molecular Mechanisms of Hormone-Refractory Prostate Cancer

DTIC Science & Technology

2005-02-01

Helsinki, Finland Bmx/Etk, a member of the Tec/ Btk family of nonrecep- signals that lead to the regulation of cell motility (reviewed in tor kinases...member of the with anti-Cas antibodies. Tec/ Btk family of tyrosine kinases (37). In addition to the SH2, In vitro immunocomplex kinase assays were...which corre- MgC12). The immunoprecipitates were equally divided and resuspendedon in 18 g1 of kinase buffer with or without 1 tM Src inhibitor SU6656

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.

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.

Serine/threonine kinase, Cot/Tpl2, regulates renal cell apoptosis in ischaemia/reperfusion injury.

PubMed

Yaomura, Takaaki; Tsuboi, Naotake; Urahama, Yoshinori; Hobo, Akinori; Sugimoto, Kenji; Miyoshi, Jun; Matsuguchi, Tetsuya; Reiji, Kannagi; Matsuo, Seiichi; Yuzawa, Yukio

2008-10-01

Cot/Tpl2, a serine/threonine (Ser/Thr) protein kinase, has been classified as a member of the mitogen-activated protein kinase (MAPK) family, and is known to have a pleiotropic role. Many studies have reported the involvement of Cot/Tpl2, mainly as a member of the Toll-like receptor (TLR) 4 signalling pathway in lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) production. At the same time, it is also related to the caspase-dependent apoptotic pathway. Thus, the role of Cot/Tpl2 in ischaemia/reperfusion injury (IRI) in which TNF-alpha and apoptosis are the major pathogenetic factors was studied. IRI was induced in wild type (Cot/Tpl2(+/+)) mice and in Cot/Tpl2-deficient (Cot/Tpl2(-/-)) mice. The extent of tubular injury and renal function were studied. TNF-alpha production, neutrophil infiltration and apoptosis were also compared between the two groups. Cot/Tpl2(-/-) mice had preserved renal function compared with wild type mice in IRI. Although Cot/Tpl2 was phosphorylated in IRI and in the cultured tubular epithelial cells (TEC) after stimulation with LPS and hydrogen peroxide, there were no significant differences in terms of TNF-alpha production, neutrophil infiltration or MAPK activation between Cot/Tpl2(+/+) and Cot/Tpl2(-/-) mice. In contrast, Cot/Tpl2(-/-) mice showed obviously reduced terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling positive cells and cleaved caspase-3 positive cells. Furthermore, Cot/Tpl2-deficient TECs demonstrated significantly less caspase-3 activation after hydrogen peroxide stimulation with comparable caspase-9 activation to wild type TEC. Cot/Tpl2 did not function as a member of MAPK family, but as a promoter of apoptosis in IRI. These results suggest that Cot/Tpl2 could be a possible therapeutic target in IRI.

ERK and p38 MAPK-Activated Protein Kinases: a Family of Protein Kinases with Diverse Biological Functions

PubMed Central

Roux, Philippe P.; Blenis, John

2004-01-01

Conserved signaling pathways that activate the mitogen-activated protein kinases (MAPKs) are involved in relaying extracellular stimulations to intracellular responses. The MAPKs coordinately regulate cell proliferation, differentiation, motility, and survival, which are functions also known to be mediated by members of a growing family of MAPK-activated protein kinases (MKs; formerly known as MAPKAP kinases). The MKs are related serine/threonine kinases that respond to mitogenic and stress stimuli through proline-directed phosphorylation and activation of the kinase domain by extracellular signal-regulated kinases 1 and 2 and p38 MAPKs. There are currently 11 vertebrate MKs in five subfamilies based on primary sequence homology: the ribosomal S6 kinases, the mitogen- and stress-activated kinases, the MAPK-interacting kinases, MAPK-activated protein kinases 2 and 3, and MK5. In the last 5 years, several MK substrates have been identified, which has helped tremendously to identify the biological role of the members of this family. Together with data from the study of MK-knockout mice, the identities of the MK substrates indicate that they play important roles in diverse biological processes, including mRNA translation, cell proliferation and survival, and the nuclear genomic response to mitogens and cellular stresses. In this article, we review the existing data on the MKs and discuss their physiological functions based on recent discoveries. PMID:15187187

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.

Phosphorylation of spore coat proteins by a family of atypical protein kinases

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

Nguyen, Kim B.; Sreelatha, Anju; Durrant, Eric S.

The modification of proteins by phosphorylation occurs in all life forms and is catalyzed by a large superfamily of enzymes known as protein kinases. We recently discovered a family of secretory pathway kinases that phosphorylate extracellular proteins. One member, family with sequence similarity 20C (Fam20C), is the physiological Golgi casein kinase. While examining distantly related protein sequences, we observed low levels of identity between the spore coat protein H (CotH), and the Fam20C-related secretory pathway kinases. CotH is a component of the spore in many bacterial and eukaryotic species, and is required for efficient germination of spores in Bacillus subtilis;more » however, the mechanism by which CotH affects germination is unclear. In this paper, we show that CotH is a protein kinase. The crystal structure of CotH reveals an atypical protein kinase-like fold with a unique mode of ATP binding. Examination of the genes neighboring cotH in B. subtilis led us to identify two spore coat proteins, CotB and CotG, as CotH substrates. Furthermore, we show that CotH-dependent phosphorylation of CotB and CotG is required for the efficient germination of B. subtilis spores. Finally and collectively, our results define a family of atypical protein kinases and reveal an unexpected role for protein phosphorylation in spore biology.« less

Phosphorylation of spore coat proteins by a family of atypical protein kinases

DOE PAGES

Nguyen, Kim B.; Sreelatha, Anju; Durrant, Eric S.; ...

2016-05-16

The modification of proteins by phosphorylation occurs in all life forms and is catalyzed by a large superfamily of enzymes known as protein kinases. We recently discovered a family of secretory pathway kinases that phosphorylate extracellular proteins. One member, family with sequence similarity 20C (Fam20C), is the physiological Golgi casein kinase. While examining distantly related protein sequences, we observed low levels of identity between the spore coat protein H (CotH), and the Fam20C-related secretory pathway kinases. CotH is a component of the spore in many bacterial and eukaryotic species, and is required for efficient germination of spores in Bacillus subtilis;more » however, the mechanism by which CotH affects germination is unclear. In this paper, we show that CotH is a protein kinase. The crystal structure of CotH reveals an atypical protein kinase-like fold with a unique mode of ATP binding. Examination of the genes neighboring cotH in B. subtilis led us to identify two spore coat proteins, CotB and CotG, as CotH substrates. Furthermore, we show that CotH-dependent phosphorylation of CotB and CotG is required for the efficient germination of B. subtilis spores. Finally and collectively, our results define a family of atypical protein kinases and reveal an unexpected role for protein phosphorylation in spore biology.« less

KIDFamMap: a database of kinase-inhibitor-disease family maps for kinase inhibitor selectivity and binding mechanisms

PubMed Central

Chiu, Yi-Yuan; Lin, Chih-Ta; Huang, Jhang-Wei; Hsu, Kai-Cheng; Tseng, Jen-Hu; You, Syuan-Ren; Yang, Jinn-Moon

2013-01-01

Kinases play central roles in signaling pathways and are promising therapeutic targets for many diseases. Designing selective kinase inhibitors is an emergent and challenging task, because kinases share an evolutionary conserved ATP-binding site. KIDFamMap (http://gemdock.life.nctu.edu.tw/KIDFamMap/) is the first database to explore kinase-inhibitor families (KIFs) and kinase-inhibitor-disease (KID) relationships for kinase inhibitor selectivity and mechanisms. This database includes 1208 KIFs, 962 KIDs, 55 603 kinase-inhibitor interactions (KIIs), 35 788 kinase inhibitors, 399 human protein kinases, 339 diseases and 638 disease allelic variants. Here, a KIF can be defined as follows: (i) the kinases in the KIF with significant sequence similarity, (ii) the inhibitors in the KIF with significant topology similarity and (iii) the KIIs in the KIF with significant interaction similarity. The KIIs within a KIF are often conserved on some consensus KIDFamMap anchors, which represent conserved interactions between the kinase subsites and consensus moieties of their inhibitors. Our experimental results reveal that the members of a KIF often possess similar inhibition profiles. The KIDFamMap anchors can reflect kinase conformations types, kinase functions and kinase inhibitor selectivity. We believe that KIDFamMap provides biological insights into kinase inhibitor selectivity and binding mechanisms. PMID:23193279

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.

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.

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

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.

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.

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

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 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

Src Family Kinases and p38 Mitogen-Activated Protein Kinases Regulate Pluripotent Cell Differentiation in Culture

PubMed Central

Tan, Boon Siang Nicholas; Kwek, Joly; Wong, Chong Kum Edwin; Saner, Nicholas J.; Yap, Charlotte; Felquer, Fernando; Morris, Michael B.; Gardner, David K.; Rathjen, Peter D.; Rathjen, Joy

2016-01-01

Multiple pluripotent cell populations, which together comprise the pluripotent cell lineage, have been identified. The mechanisms that control the progression between these populations are still poorly understood. The formation of early primitive ectoderm-like (EPL) cells from mouse embryonic stem (mES) cells provides a model to understand how one such transition is regulated. EPL cells form from mES cells in response to l-proline uptake through the transporter Slc38a2. Using inhibitors of cell signaling we have shown that Src family kinases, p38 MAPK, ERK1/2 and GSK3β are required for the transition between mES and EPL cells. ERK1/2, c-Src and GSK3β are likely to be enforcing a receptive, primed state in mES cells, while Src family kinases and p38 MAPK are involved in the establishment of EPL cells. Inhibition of these pathways prevented the acquisition of most, but not all, features of EPL cells, suggesting that other pathways are required. L-proline activation of differentiation is mediated through metabolism and changes to intracellular metabolite levels, specifically reactive oxygen species. The implication of multiple signaling pathways in the process suggests a model in which the context of Src family kinase activation determines the outcomes of pluripotent cell differentiation. PMID:27723793

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,…

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.

Expansion of the receptor-like kinase/Pelle gene family and receptor-like proteins in Arabidopsis.

PubMed

Shiu, Shin Han; Bleecker, Anthony B

2003-06-01

Receptor-like kinases (RLKs) are a family of transmembrane proteins with versatile N-terminal extracellular domains and C-terminal intracellular kinases. They control a wide range of physiological responses in plants and belong to one of the largest gene families in the Arabidopsis genome with more than 600 members. Interestingly, this gene family constitutes 60% of all kinases in Arabidopsis and accounts for nearly all transmembrane kinases in Arabidopsis. Analysis of four fungal, six metazoan, and two Plasmodium sp. genomes indicates that the family was represented in all but fungal genomes, indicating an ancient origin for the family with a more recent expansion only in the plant lineages. The RLK/Pelle family can be divided into several subfamilies based on three independent criteria: the phylogeny based on kinase domain sequences, the extracellular domain identities, and intron locations and phases. A large number of receptor-like proteins (RLPs) resembling the extracellular domains of RLKs are also found in the Arabidopsis genome. However, not all RLK subfamilies have corresponding RLPs. Several RLK/Pelle subfamilies have undergone differential expansions. More than 33% of the RLK/Pelle members are found in tandem clusters, substantially higher than the genome average. In addition, 470 of the RLK/Pelle family members are located within the segmentally duplicated regions in the Arabidopsis genome and 268 of them have a close relative in the corresponding regions. Therefore, tandem duplications and segmental/whole-genome duplications represent two of the major mechanisms for the expansion of the RLK/Pelle family in Arabidopsis.

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.

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.

Tau phosphorylation and kinase activation in familial tauopathy linked to deln296 mutation.

PubMed

Ferrer, I; Pastor, P; Rey, M J; Muñoz, E; Puig, B; Pastor, E; Oliva, R; Tolosa, E

2003-02-01

Tau phosphorylation has been examined by immunohistochemistry in the brain of a patient affected with familial tauopathy with progressive supranuclear palsy-like phenotype linked to the delN296 mutation in the tau gene. Phospho-specific tau antibodies Thr181, Ser202, Ser214, Ser396 and Ser422, and antibodies to glycogen synthase kinase-3alpha/beta (GSK-3alpha/beta) and to phosphorylated (P) mitogen-activated protein kinase/extracellular signal-regulated kinases (MAPK/ERK), stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), p38 kinase (p38) and GSK-3betaSer9 have been used to gain understanding of the identification of phosphorylation sites, as well as of the specific kinases that regulate tau phosphorylation at those specific sites, in a familial tauopathy. The neuropathological examination disclosed atrophy of the right precentral gyrus and the brainstem. Neurone loss and gliosis were observed in the substantia nigra, several nuclei of the brainstem and diencephalon. Hyper-phosphorylated tau accumulated in neurones with neurofibrillary tangles and in neurones with pretangles in the substantia nigra, locus ceruleus, peri-aqueductal grey matter, reticular formation, motor nuclei of the brainstem, and thalamus, amygdala and hippocampus. tau-immunoreactive astrocytes and, particularly, oligodendrocytes with coiled bodies were widespread in the brainstem, diencephalons, cerebral white matter and cerebral cortex. Increased expression of MAPK/ERK-P, SAPK/JNK-P, p-38-P and GSK-3beta-P was observed in select subpopulations of neurones with neurofibrillary tangles and in neurones with pretangles. MAPK/ERK-P, SAPK/JNK-P, p38-P and GSK-3beta-P were also expressed in tau-containing astrocytes and in oligodendrocytes with coiled bodies. These findings show, for the first time, activation of precise kinases that regulate tau phosphorylation at specific sites in familial tauopathy.

Differential Requirements for Src-Family Kinases in SYK or ZAP70-Mediated SLP-76 Phosphorylation in Lymphocytes

PubMed Central

Fasbender, Frank; Claus, Maren; Wingert, Sabine; Sandusky, Mina; Watzl, Carsten

2017-01-01

In a synthetic biology approach using Schneider (S2) cells, we show that SLP-76 is directly phosphorylated at tyrosines Y113 and Y128 by SYK in the presence of ITAM-containing adapters such as CD3ζ, DAP12, or FcεRγ. This phosphorylation was dependent on at least one functional ITAM and a functional SH2 domain within SYK. Inhibition of Src-kinases by inhibitors PP1 and PP2 did not reduce SLP-76 phosphorylation in S2 cells, suggesting an ITAM and SYK dependent, but Src-kinase independent signaling pathway. This direct ITAM/SYK/SLP-76 signaling pathway therefore differs from previously described ITAM signaling. However, the SYK-family kinase ZAP70 required the additional co-expression of the Src-family kinases Fyn or Lck to efficiently phosphorylate SLP-76 in S2 cells. This difference in Src-family kinase dependency of SYK versus ZAP70-mediated ITAM-based signaling was further demonstrated in human lymphocytes. ITAM signaling in ZAP70-expressing T cells was dependent on the activity of Src-family kinases. In contrast, Src-family kinases were partially dispensable for ITAM signaling in SYK-expressing B cells or in natural killer cells, which express SYK and ZAP70. This demonstrates that SYK can signal using a Src-kinase independent ITAM-based signaling pathway, which may be involved in calibrating the threshold for lymphocyte activation. PMID:28736554

Differential Requirements for Src-Family Kinases in SYK or ZAP70-Mediated SLP-76 Phosphorylation in Lymphocytes.

PubMed

Fasbender, Frank; Claus, Maren; Wingert, Sabine; Sandusky, Mina; Watzl, Carsten

2017-01-01

In a synthetic biology approach using Schneider (S2) cells, we show that SLP-76 is directly phosphorylated at tyrosines Y113 and Y128 by SYK in the presence of ITAM-containing adapters such as CD3ζ, DAP12, or FcεRγ. This phosphorylation was dependent on at least one functional ITAM and a functional SH2 domain within SYK. Inhibition of Src-kinases by inhibitors PP1 and PP2 did not reduce SLP-76 phosphorylation in S2 cells, suggesting an ITAM and SYK dependent, but Src-kinase independent signaling pathway. This direct ITAM/SYK/SLP-76 signaling pathway therefore differs from previously described ITAM signaling. However, the SYK-family kinase ZAP70 required the additional co-expression of the Src-family kinases Fyn or Lck to efficiently phosphorylate SLP-76 in S2 cells. This difference in Src-family kinase dependency of SYK versus ZAP70-mediated ITAM-based signaling was further demonstrated in human lymphocytes. ITAM signaling in ZAP70-expressing T cells was dependent on the activity of Src-family kinases. In contrast, Src-family kinases were partially dispensable for ITAM signaling in SYK-expressing B cells or in natural killer cells, which express SYK and ZAP70. This demonstrates that SYK can signal using a Src-kinase independent ITAM-based signaling pathway, which may be involved in calibrating the threshold for lymphocyte activation.

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

A role for the Swe1 checkpoint kinase during filamentous growth of Saccharomyces cerevisiae.

PubMed Central

La Valle, R; Wittenberg, C

2001-01-01

In this study we show that inactivation of Hsl1 or Hsl7, negative regulators of the Swe1 kinase, enhances the invasive behavior of haploid and diploid cells. The enhancement of filamentous growth caused by inactivation of both genes is mediated via the Swe1 protein kinase. Whereas Swe1 contributes noticeably to the effectiveness of haploid invasive growth under all conditions tested, its contribution to pseudohyphal growth is limited to the morphological response under standard assay conditions. However, Swe1 is essential for pseudohyphal differentiation under a number of nonstandard assay conditions including altered temperature and increased nitrogen. Swe1 is also required for pseudohyphal growth in the absence of Tec1 and for the induction of filamentation by butanol, a related phenomenon. Although inactivation of Hsl1 is sufficient to suppress the defect in filamentous growth caused by inactivation of Tec1 or Flo8, it is insufficient to promote filamentous growth in the absence of both factors. Moreover, inactivation of Hsl1 will not bypass the requirement for nitrogen starvation or growth on solid medium for pseudohyphal differentiation. We conclude that the Swe1 kinase modulates filamentous development under a broad spectrum of conditions and that its role is partially redundant with the Tec1 and Flo8 transcription factors. PMID:11404321

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.

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.

Structural and evolutionary adaptation of rhoptry kinases and pseudokinases, a family of coccidian virulence factors

PubMed Central

2013-01-01

Background The widespread protozoan parasite Toxoplasma gondii interferes with host cell functions by exporting the contents of a unique apical organelle, the rhoptry. Among the mix of secreted proteins are an expanded, lineage-specific family of protein kinases termed rhoptry kinases (ROPKs), several of which have been shown to be key virulence factors, including the pseudokinase ROP5. The extent and details of the diversification of this protein family are poorly understood. Results In this study, we comprehensively catalogued the ROPK family in the genomes of Toxoplasma gondii, Neospora caninum and Eimeria tenella, as well as portions of the unfinished genome of Sarcocystis neurona, and classified the identified genes into 42 distinct subfamilies. We systematically compared the rhoptry kinase protein sequences and structures to each other and to the broader superfamily of eukaryotic protein kinases to study the patterns of diversification and neofunctionalization in the ROPK family and its subfamilies. We identified three ROPK sub-clades of particular interest: those bearing a structurally conserved N-terminal extension to the kinase domain (NTE), an E. tenella-specific expansion, and a basal cluster including ROP35 and BPK1 that we term ROPKL. Structural analysis in light of the solved structures ROP2, ROP5, ROP8 and in comparison to typical eukaryotic protein kinases revealed ROPK-specific conservation patterns in two key regions of the kinase domain, surrounding a ROPK-conserved insert in the kinase hinge region and a disulfide bridge in the kinase substrate-binding lobe. We also examined conservation patterns specific to the NTE-bearing clade. We discuss the possible functional consequences of each. Conclusions Our work sheds light on several important but previously unrecognized features shared among rhoptry kinases, as well as the essential differences between active and degenerate protein kinases. We identify the most distinctive ROPK-specific features

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.

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.

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

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.

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.

Structural Characterization of the Predominant Family of Histidine Kinase Sensor Domains

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

Zhang, Z.; Hendrickson, W

2010-01-01

Histidine kinase (HK) receptors are used ubiquitously by bacteria to monitor environmental changes, and they are also prevalent in plants, fungi, and other protists. Typical HK receptors have an extracellular sensor portion that detects a signal, usually a chemical ligand, and an intracellular transmitter portion that includes both the kinase domain itself and the site for histidine phosphorylation. While kinase domains are highly conserved, sensor domains are diverse. HK receptors function as dimers, but the molecular mechanism for signal transduction across cell membranes remains obscure. In this study, eight crystal structures were determined from five sensor domains representative of themore » most populated family, family HK1, found in a bioinformatic analysis of predicted sensor domains from transmembrane HKs. Each structure contains an inserted repeat of PhoQ/DcuS/CitA (PDC) domains, and similarity between sequence and structure is correlated across these and other double-PDC sensor proteins. Three of the five sensors crystallize as dimers that appear to be physiologically relevant, and comparisons between ligated structures and apo-state structures provide insights into signal transmission. Some HK1 family proteins prove to be sensors for chemotaxis proteins or diguanylate cyclase receptors, implying a combinatorial molecular evolution.« less

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

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.

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

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.

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.

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

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.

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...

Novel Autophosphorylation Sites of Src Family Kinases Regulate Kinase Activity and SH2 Domain Binding Capacity

PubMed Central

Weir, Marion E.; Mann, Jacqueline E.; Corwin, Thomas; Fulton, Zachary W.; Hao, Jennifer M.; Maniscalco, Jeanine F.; Kenney, Marie C.; Roque, Kristal M. Roman; Chapdelaine, Elizabeth F.; Stelzl, Ulrich; Deming, Paula B.; Ballif, Bryan A.; Hinkle, Karen L.

2016-01-01

Src family tyrosine kinases (SFKs) are critical players in normal and aberrant biological processes. While phosphorylation importantly-regulates SFKs at two known tyrosines, large-scale phosphoproteomics have revealed four additional tyrosines commonly-phosphorylated in SFKs. We found these novel tyrosines to be autophosphorylation sites. Mimicking phosphorylation at the site C-terminal to the activation loop decreased Fyn activity. Phosphomimetics and direct phosphorylation at the three SH2 domain sites increased Fyn activity while reducing phosphotyrosine-dependent interactions. While 68% of human SH2 domains exhibit conservation of at least one of these tyrosines, few have been found phosphorylated except when found in cis to a kinase domain. PMID:27001024

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.

Genome-wide identification, phylogeny and expressional profiles of mitogen activated protein kinase kinase kinase (MAPKKK) gene family in bread wheat (Triticum aestivum L.).

PubMed

Wang, Meng; Yue, Hong; Feng, Kewei; Deng, Pingchuan; Song, Weining; Nie, Xiaojun

2016-08-22

Mitogen-activated protein kinase kinase kinases (MAPKKKs) are the important components of MAPK cascades, which play the crucial role in plant growth and development as well as in response to diverse stresses. Although this family has been systematically studied in many plant species, little is known about MAPKKK genes in wheat (Triticum aestivum L.), especially those involved in the regulatory network of stress processes. In this study, we identified 155 wheat MAPKKK genes through a genome-wide search method based on the latest available wheat genome information, of which 29 belonged to MEKK, 11 to ZIK and 115 to Raf subfamily, respectively. Then, chromosome localization, gene structure and conserved protein motifs and phylogenetic relationship as well as regulatory network of these TaMAPKKKs were systematically investigated and results supported the prediction. Furthermore, a total of 11 homologous groups between A, B and D sub-genome and 24 duplication pairs among them were detected, which contributed to the expansion of wheat MAPKKK gene family. Finally, the expression profiles of these MAPKKKs during development and under different abiotic stresses were investigated using the RNA-seq data. Additionally, 10 tissue-specific and 4 salt-responsive TaMAPKKK genes were selected to validate their expression level through qRT-PCR analysis. This study for the first time reported the genome organization, evolutionary features and expression profiles of the wheat MAPKKK gene family, which laid the foundation for further functional analysis of wheat MAPKKK genes, and contributed to better understanding the roles and regulatory mechanism of MAPKKKs in wheat.

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.

Src family kinase expression and subcellular localization in macrophages: implications for their role in CSF-1-induced macrophage migration.

PubMed

Dwyer, Amy R; Mouchemore, Kellie A; Steer, James H; Sunderland, Andrew J; Sampaio, Natalia G; Greenland, Eloise L; Joyce, David A; Pixley, Fiona J

2016-07-01

A major role of colony-stimulating factor-1 is to stimulate the differentiation of mononuclear phagocytic lineage cells into adherent, motile, mature macrophages. The colony-stimulating factor-1 receptor transduces colony-stimulating factor-1 signaling, and we have shown previously that phosphatidylinositol 3-kinase p110δ is a critical mediator of colony-stimulating factor-1-stimulated motility through the colony-stimulating factor-1 receptor pY721 motif. Src family kinases are also implicated in the regulation of macrophage motility and in colony-stimulating factor-1 receptor signaling, although functional redundancy of the multiple SFKs expressed in macrophages makes it challenging to delineate their specific functions. We report a comprehensive analysis of individual Src family kinase expression in macrophage cell lines and primary macrophages and demonstrate colony-stimulating factor-1-induced changes in Src family kinase subcellular localization, which provides clues to their distinct and redundant functions in macrophages. Moreover, expression of individual Src family kinases is both species specific and dependent on colony-stimulating factor-1-induced macrophage differentiation. Hck associated with the activated colony-stimulating factor-1 receptor, whereas Lyn associated with the receptor in a constitutive manner. Consistent with this, inhibitor studies revealed that Src family kinases were important for both colony-stimulating factor-1 receptor activation and colony-stimulating factor-1-induced macrophage spreading, motility, and invasion. Distinct colony-stimulating factor-1-induced changes in the subcellular localization of individual SFKs suggest specific roles for these Src family kinases in the macrophage response to colony-stimulating factor-1. © Society for Leukocyte Biology.

Novel autophosphorylation sites of Src family kinases regulate kinase activity and SH2 domain-binding capacity.

PubMed

Weir, Marion E; Mann, Jacqueline E; Corwin, Thomas; Fulton, Zachary W; Hao, Jennifer M; Maniscalco, Jeanine F; Kenney, Marie C; Roman Roque, Kristal M; Chapdelaine, Elizabeth F; Stelzl, Ulrich; Deming, Paula B; Ballif, Bryan A; Hinkle, Karen L

2016-04-01

Src family tyrosine kinases (SFKs) are critical players in normal and aberrant biological processes. While phosphorylation importantly regulates SFKs at two known tyrosines, large-scale phosphoproteomics have revealed four additional tyrosines commonly phosphorylated in SFKs. We found these novel tyrosines to be autophosphorylation sites. Mimicking phosphorylation at the C-terminal site to the activation loop decreased Fyn activity. Phosphomimetics and direct phosphorylation at the three SH2 domain sites increased Fyn activity while reducing phosphotyrosine-dependent interactions. While 68% of human SH2 domains exhibit conservation of at least one of these tyrosines, few have been found phosphorylated except when found in cis to a kinase domain. © 2016 Federation of European Biochemical Societies.

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…

Structure and inhibitor specificity of the PCTAIRE-family kinase CDK16

PubMed Central

Dixon-Clarke, Sarah E.; Shehata, Saifeldin N.; Krojer, Tobias; Sharpe, Timothy D.; vonDelft, Frank; Sakamoto, Kei

2017-01-01

CDK16 (also known as PCTAIRE1 or PCTK1) is an atypical member of the cyclin-dependent kinase (CDK) family that has emerged as a key regulator of neurite outgrowth, vesicle trafficking and cancer cell proliferation. CDK16 is activated through binding to cyclin Y via a phosphorylation-dependent 14-3-3 interaction and has a unique consensus substrate phosphorylation motif compared with conventional CDKs. To elucidate the structure and inhibitor-binding properties of this atypical CDK, we screened the CDK16 kinase domain against different inhibitor libraries and determined the co-structures of identified hits. We discovered that the ATP-binding pocket of CDK16 can accommodate both type I and type II kinase inhibitors. The most potent CDK16 inhibitors revealed by cell-free and cell-based assays were the multitargeted cancer drugs dabrafenib and rebastinib. An inactive DFG-out binding conformation was confirmed by the first crystal structures of CDK16 in separate complexes with the inhibitors indirubin E804 and rebastinib, respectively. The structures revealed considerable conformational plasticity, suggesting that the isolated CDK16 kinase domain was relatively unstable in the absence of a cyclin partner. The unusual structural features and chemical scaffolds identified here hold promise for the development of more selective CDK16 inhibitors and provide opportunity to better characterise the role of CDK16 and its related CDK family members in various physiological and pathological contexts. PMID:28057719

Structure and inhibitor specificity of the PCTAIRE-family kinase CDK16.

PubMed

Dixon-Clarke, Sarah E; Shehata, Saifeldin N; Krojer, Tobias; Sharpe, Timothy D; von Delft, Frank; Sakamoto, Kei; Bullock, Alex N

2017-02-20

CDK16 (also known as PCTAIRE1 or PCTK1) is an atypical member of the cyclin-dependent kinase (CDK) family that has emerged as a key regulator of neurite outgrowth, vesicle trafficking and cancer cell proliferation. CDK16 is activated through binding to cyclin Y via a phosphorylation-dependent 14-3-3 interaction and has a unique consensus substrate phosphorylation motif compared with conventional CDKs. To elucidate the structure and inhibitor-binding properties of this atypical CDK, we screened the CDK16 kinase domain against different inhibitor libraries and determined the co-structures of identified hits. We discovered that the ATP-binding pocket of CDK16 can accommodate both type I and type II kinase inhibitors. The most potent CDK16 inhibitors revealed by cell-free and cell-based assays were the multitargeted cancer drugs dabrafenib and rebastinib. An inactive DFG-out binding conformation was confirmed by the first crystal structures of CDK16 in separate complexes with the inhibitors indirubin E804 and rebastinib, respectively. The structures revealed considerable conformational plasticity, suggesting that the isolated CDK16 kinase domain was relatively unstable in the absence of a cyclin partner. The unusual structural features and chemical scaffolds identified here hold promise for the development of more selective CDK16 inhibitors and provide opportunity to better characterise the role of CDK16 and its related CDK family members in various physiological and pathological contexts. © 2017 The Author(s).

Inhibiting Src family tyrosine kinase activity blocks glutamate signalling to ERK1/2 and Akt/PKB but not JNK in cultured striatal neurones.

PubMed

Crossthwaite, Andrew J; Valli, Haseeb; Williams, Robert J

2004-03-01

Glutamate receptor activation of mitogen-activated protein (MAP) kinase signalling cascades has been implicated in diverse neuronal functions such as synaptic plasticity, development and excitotoxicity. We have previously shown that Ca2+-influx through NMDA receptors in cultured striatal neurones mediates the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt/protein kinase B (PKB) through a phosphatidylinositol 3-kinase (PI 3-kinase)-dependent pathway. Exposing neurones to the Src family tyrosine kinase inhibitor PP2, but not the inactive analogue PP3, inhibited NMDA receptor-induced phosphorylation of ERK1/2 and Akt/PKB in a concentration-dependent manner, and reduced cAMP response element-binding protein (CREB) phosphorylation. To establish a link between Src family tyrosine kinase-mediated phosphorylation and PI 3-kinase signalling, affinity precipitation experiments were performed with the SH2 domains of the PI 3-kinase regulatory subunit p85. This revealed a Src-dependent phosphorylation of a focal adhesion kinase (FAK)-p85 complex on glutamate stimulation. Demonstrating that PI3-kinase is not ubiquitously involved in NMDA receptor signal transduction, the PI 3-kinase inhibitors wortmannin and LY294002 did not prevent NMDA receptor Ca2+-dependent phosphorylation of c-Jun N-terminal kinase 1/2 (JNK1/2). Further, inhibiting Src family kinases increased NMDA receptor-dependent JNK1/2 phosphorylation, suggesting that Src family kinase-dependent cascades may physiologically limit signalling to JNK. These results demonstrate that Src family tyrosine kinases and PI3-kinase are pivotal regulators of NMDA receptor signalling to ERK/Akt and JNK in striatal neurones.

Contribution of tumor endothelial cells to drug resistance: anti-angiogenic tyrosine kinase inhibitors act as p-glycoprotein antagonists.

PubMed

Bani, MariaRosa; Decio, Alessandra; Giavazzi, Raffaella; Ghilardi, Carmen

2017-05-01

Tumor endothelial cells (TEC) differ from the normal counterpart, in both gene expression and functionality. TEC may acquire drug resistance, a characteristic that is maintained in vitro. There is evidence that TEC are more resistant to chemotherapeutic drugs, substrates of ATP-binding cassette (ABC) transporters. TEC express p-glycoprotein (encoded by ABCB1), while no difference in other ABC transporters was revealed compared to normal endothelia. A class of tyrosine kinase inhibitors (TKI), used as angiostatic compounds, interferes with the ATPase activity of p-glycoprotein, thus impairing its functionality. The exposure of ovarian adenocarcinoma TEC to the TKIs sunitinib or sorafenib was found to abrogate resistance (proliferation and motility) to doxorubicin and paclitaxel in vitro, increasing intracellular drug accumulation. A similar effect has been reported by the p-glycoprotein inhibitor verapamil. No beneficial effect was observed in combination with cytotoxic drugs that are not p-glycoprotein substrates. The current paper reviews the mechanisms of TEC chemoresistance and shows the role of p-glycoprotein in mediating such resistance. Inhibition of p-glycoprotein by anti-angiogenic TKI might contribute to the beneficial effect of these small molecules, when combined with chemotherapy, in counteracting acquired drug resistance.

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.

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.

An Uncharacterized Member of the Ribokinase Family in Thermococcus kodakarensis Exhibits myo-Inositol Kinase Activity*

PubMed Central

Sato, Takaaki; Fujihashi, Masahiro; Miyamoto, Yukika; Kuwata, Keiko; Kusaka, Eriko; Fujita, Haruo; Miki, Kunio; Atomi, Haruyuki

2013-01-01

Here we performed structural and biochemical analyses on the TK2285 gene product, an uncharacterized protein annotated as a member of the ribokinase family, from the hyperthermophilic archaeon Thermococcus kodakarensis. The three-dimensional structure of the TK2285 protein resembled those of previously characterized members of the ribokinase family including ribokinase, adenosine kinase, and phosphofructokinase. Conserved residues characteristic of this protein family were located in a cleft of the TK2285 protein as in other members whose structures have been determined. We thus examined the kinase activity of the TK2285 protein toward various sugars recognized by well characterized ribokinase family members. Although activity with sugar phosphates and nucleosides was not detected, kinase activity was observed toward d-allose, d-lyxose, d-tagatose, d-talose, d-xylose, and d-xylulose. Kinetic analyses with the six sugar substrates revealed high Km values, suggesting that they were not the true physiological substrates. By examining activity toward amino sugars, sugar alcohols, and disaccharides, we found that the TK2285 protein exhibited prominent kinase activity toward myo-inositol. Kinetic analyses with myo-inositol revealed a greater kcat and much lower Km value than those obtained with the monosaccharides, resulting in over a 2,000-fold increase in kcat/Km values. TK2285 homologs are distributed among members of Thermococcales, and in most species, the gene is positioned close to a myo-inositol monophosphate synthase gene. Our results suggest the presence of a novel subfamily of the ribokinase family whose members are present in Archaea and recognize myo-inositol as a substrate. PMID:23737529

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

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.

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.

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.

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.

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.

Archaeal Shikimate Kinase, a New Member of the GHMP-Kinase Family

PubMed Central

Daugherty, Matthew; Vonstein, Veronika; Overbeek, Ross; Osterman, Andrei

2001-01-01

Shikimate kinase (EC 2.7.1.71) is a committed enzyme in the seven-step biosynthesis of chorismate, a major precursor of aromatic amino acids and many other aromatic compounds. Genes for all enzymes of the chorismate pathway except shikimate kinase are found in archaeal genomes by sequence homology to their bacterial counterparts. In this study, a conserved archaeal gene (gi|1500322 in Methanococcus jannaschii) was identified as the best candidate for the missing shikimate kinase gene by the analysis of chromosomal clustering of chorismate biosynthetic genes. The encoded hypothetical protein, with no sequence similarity to bacterial and eukaryotic shikimate kinases, is distantly related to homoserine kinases (EC 2.7.1.39) of the GHMP-kinase superfamily. The latter functionality in M. jannaschii is assigned to another gene (gi|1591748), in agreement with sequence similarity and chromosomal clustering analysis. Both archaeal proteins, overexpressed in Escherichia coli and purified to homogeneity, displayed activity of the predicted type, with steady-state kinetic parameters similar to those of the corresponding bacterial kinases: Km,shikimate = 414 ± 33 μM, Km,ATP = 48 ± 4 μM, and kcat = 57 ± 2 s−1 for the predicted shikimate kinase and Km,homoserine = 188 ± 37 μM, Km,ATP = 101 ± 7 μM, and kcat = 28 ± 1 s−1 for the homoserine kinase. No overlapping activity could be detected between shikimate kinase and homoserine kinase, both revealing a >1,000-fold preference for their own specific substrates. The case of archaeal shikimate kinase illustrates the efficacy of techniques based on reconstruction of metabolism from genomic data and analysis of gene clustering on chromosomes in finding missing genes. PMID:11114929

Distinct roles for multiple Src family kinases at fertilization.

PubMed

O'Neill, Forest J; Gillett, Jessica; Foltz, Kathy R

2004-12-01

Egg activation at fertilization requires the release of Ca2+ from the endoplasmic reticulum of the egg. Recent evidence indicates that Src family kinases (SFKs) function in the signaling pathway that initiates this Ca2+ release in the eggs of many deuterostomes. We have identified three SFKs expressed in starfish (Asterina miniata) eggs, designated AmSFK1, AmSFK2 and AmSFK3. Antibodies made against the unique domains of each AmSFK protein revealed that all three are expressed in eggs and localized primarily to the membrane fraction. Both AmSFK1 and AmSFK3 (but not AmSFK2) are necessary for egg activation, as determined by injection of starfish oocytes with dominant-interfering Src homology 2 (SH2) domains, which specifically delay and reduce the initial release of Ca2+ at fertilization. AmSFK3 exhibits a very rapid and transient kinase activity in response to fertilization, peaking at 30 seconds post sperm addition. AmSFK1 kinase activity also increases transiently at fertilization, but peaks later, at 2 minutes. These results indicate that there are multiple SFKs present in starfish eggs with distinct, perhaps sequential, signaling roles.

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.

GRID and docking analyses reveal a molecular basis for flavonoid inhibition of Src family kinase activity.

PubMed

Wright, Bernice; Watson, Kimberly A; McGuffin, Liam J; Lovegrove, Julie A; Gibbins, Jonathan M

2015-11-01

Flavonoids reduce cardiovascular disease risk through anti-inflammatory, anti-coagulant and anti-platelet actions. One key flavonoid inhibitory mechanism is blocking kinase activity that drives these processes. Flavonoids attenuate activities of kinases including phosphoinositide-3-kinase, Fyn, Lyn, Src, Syk, PKC, PIM1/2, ERK, JNK and PKA. X-ray crystallographic analyses of kinase-flavonoid complexes show that flavonoid ring systems and their hydroxyl substitutions are important structural features for their binding to kinases. A clearer understanding of structural interactions of flavonoids with kinases is necessary to allow construction of more potent and selective counterparts. We examined flavonoid (quercetin, apigenin and catechin) interactions with Src family kinases (Lyn, Fyn and Hck) applying the Sybyl docking algorithm and GRID. A homology model (Lyn) was used in our analyses to demonstrate that high-quality predicted kinase structures are suitable for flavonoid computational studies. Our docking results revealed potential hydrogen bond contacts between flavonoid hydroxyls and kinase catalytic site residues. Identification of plausible contacts indicated that quercetin formed the most energetically stable interactions, apigenin lacked hydroxyl groups necessary for important contacts and the non-planar structure of catechin could not support predicted hydrogen bonding patterns. GRID analysis using a hydroxyl functional group supported docking results. Based on these findings, we predicted that quercetin would inhibit activities of Src family kinases with greater potency than apigenin and catechin. We validated this prediction using in vitro kinase assays. We conclude that our study can be used as a basis to construct virtual flavonoid interaction libraries to guide drug discovery using these compounds as molecular templates. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

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

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.

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.

Divergent modulation of Rho‐kinase and Ca2+ influx pathways by Src family kinases and focal adhesion kinase in airway smooth muscle

PubMed Central

Shaifta, Yasin; Irechukwu, Nneka; Prieto‐Lloret, Jesus; MacKay, Charles E; Marchon, Keisha A; Ward, Jeremy P T

2015-01-01

Background and Purpose The importance of tyrosine kinases in airway smooth muscle (ASM) contraction is not fully understood. The aim of this study was to investigate the role of Src‐family kinases (SrcFK) and focal adhesion kinase (FAK) in GPCR‐mediated ASM contraction and associated signalling events. Experimental Approach Contraction was recorded in intact or α‐toxin permeabilized rat bronchioles. Phosphorylation of SrcFK, FAK, myosin light‐chain‐20 (MLC20) and myosin phosphatase targeting subunit‐1 (MYPT‐1) was evaluated in cultured human ASM cells (hASMC). [Ca2+]i was evaluated in Fura‐2 loaded hASMC. Responses to carbachol (CCh) and bradykinin (BK) and the contribution of SrcFK and FAK to these responses were determined. Key Results Contractile responses in intact bronchioles were inhibited by antagonists of SrcFK, FAK and Rho‐kinase, while after α‐toxin permeabilization, they were sensitive to inhibition of SrcFK and Rho‐kinase, but not FAK. CCh and BK increased phosphorylation of MYPT‐1 and MLC20 and auto‐phosphorylation of SrcFK and FAK. MYPT‐1 phosphorylation was sensitive to inhibition of Rho‐kinase and SrcFK, but not FAK. Contraction induced by SR Ca2+ depletion and equivalent [Ca2+]i responses in hASMC were sensitive to inhibition of both SrcFK and FAK, while depolarization‐induced contraction was sensitive to FAK inhibition only. SrcFK auto‐phosphorylation was partially FAK‐dependent, while FAK auto‐phosphorylation was SrcFK‐independent. Conclusions and Implications SrcFK mediates Ca2+‐sensitization in ASM, while SrcFK and FAK together and individually influence multiple Ca2+ influx pathways. Tyrosine phosphorylation is therefore a key upstream signalling event in ASM contraction and may be a viable target for modulating ASM tone in respiratory disease. PMID:26294392

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).

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…

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

Heat shock protein 90 functions to stabilize and activate the testis-specific serine/threonine kinases, a family of kinases essential for male fertility.

PubMed

Jha, Kula N; Coleman, Alyssa R; Wong, Lily; Salicioni, Ana M; Howcroft, Elizabeth; Johnson, Gibbes R

2013-06-07

Spermiogenesis is characterized by a profound morphological differentiation of the haploid spermatid into spermatozoa. The testis-specific serine/threonine kinases (TSSKs) comprise a family of post-meiotic kinases expressed in spermatids, are critical to spermiogenesis, and are required for male fertility in mammals. To explore the role of heat shock protein 90 (HSP90) in regulation of TSSKs, the stability and catalytic activity of epitope-tagged murine TSSKs were assessed in 293T and COS-7 cells. TSSK1, -2, -4, and -6 (small serine/threonine kinase) were all found to associate with HSP90, and pharmacological inhibition of HSP90 function using the highly specific drugs 17-AAG, SNX-5422, or NVP-AUY922 reduced TSSK protein levels in cells. The attenuation of HSP90 function abolished the catalytic activities of TSSK4 and -6 but did not significantly alter the specific activities of TSSK1 and -2. Inhibition of HSP90 resulted in increased TSSK ubiquitination and proteasomal degradation, indicating that HSP90 acts to control ubiquitin-mediated catabolism of the TSSKs. To study HSP90 and TSSKs in germ cells, a mouse primary spermatid culture model was developed and characterized. Using specific antibodies against murine TSSK2 and -6, it was demonstrated that HSP90 inhibition resulted in a marked decrease of the endogenous kinases in spermatids. Together, our findings demonstrate that HSP90 plays a broad and critical role in stabilization and activation of the TSSK family of protein kinases.

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.

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

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.

Structural Insights into the HWE Histidine Kinase Family: The Brucella Blue Light-Activated Histidine Kinase Domain.

PubMed

Rinaldi, Jimena; Arrar, Mehrnoosh; Sycz, Gabriela; Cerutti, María Laura; Berguer, Paula M; Paris, Gastón; Estrín, Darío Ariel; Martí, Marcelo Adrián; Klinke, Sebastián; Goldbaum, Fernando Alberto

2016-03-27

In response to light, as part of a two-component system, the Brucella blue light-activated histidine kinase (LOV-HK) increases its autophosphorylation, modulating the virulence of this microorganism. The Brucella histidine kinase (HK) domain belongs to the HWE family, for which there is no structural information. The HWE family is exclusively present in proteobacteria and usually coupled to a wide diversity of light sensor domains. This work reports the crystal structure of the Brucella HK domain, which presents two different dimeric assemblies in the asymmetric unit: one similar to the already described canonical parallel homodimers (C) and the other, an antiparallel non-canonical (NC) dimer, each with distinct relative subdomain orientations and dimerization interfaces. Contrary to these crystallographic structures and unlike other HKs, in solution, the Brucella HK domain is monomeric and still active, showing an astonishing instability of the dimeric interface. Despite this instability, using cross-linking experiments, we show that the C dimer is the functionally relevant species. Mutational analysis demonstrates that the autophosphorylation activity occurs in cis. The different relative subdomain orientations observed for the NC and C states highlight the large conformational flexibility of the HK domain. Through the analysis of these alternative conformations by means of molecular dynamics simulations, we also propose a catalytic mechanism for Brucella LOV-HK. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

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 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.

South Carolina TEC Student Code.

ERIC Educational Resources Information Center

Edwards, C. A., Ed.; Kiser, J. A., Ed.

This student code has statewide application to South Carolina Technical Colleges and Technical Education Centers (TEC). Provisions are divided into eight articles: (1) General Provisions, including the purpose of a student code, the precept of internal solution of problems, and definitions; (2) Student Rights, including Bill of Rights protections;…

Distinct Pathways Regulate Syk Protein Activation Downstream of Immune Tyrosine Activation Motif (ITAM) and hemITAM Receptors in Platelets*

PubMed Central

Manne, Bhanu Kanth; Badolia, Rachit; Dangelmaier, Carol; Eble, Johannes A.; Ellmeier, Wilfried; Kahn, Mark; Kunapuli, Satya P.

2015-01-01

Tyrosine kinase pathways are known to play an important role in the activation of platelets. In particular, the GPVI and CLEC-2 receptors are known to activate Syk upon tyrosine phosphorylation of an immune tyrosine activation motif (ITAM) and hemITAM, respectively. However, unlike GPVI, the CLEC-2 receptor contains only one tyrosine motif in the intracellular domain. The mechanisms by which this receptor activates Syk are not completely understood. In this study, we identified a novel signaling mechanism in CLEC-2-mediated Syk activation. CLEC-2-mediated, but not GPVI-mediated, platelet activation and Syk phosphorylation were abolished by inhibition of PI3K, which demonstrates that PI3K regulates Syk downstream of CLEC-2. Ibrutinib, a Tec family kinase inhibitor, also completely abolished CLEC-2-mediated aggregation and Syk phosphorylation in human and murine platelets. Furthermore, embryos lacking both Btk and Tec exhibited cutaneous edema associated with blood-filled vessels in a typical lymphatic pattern similar to CLEC-2 or Syk-deficient embryos. Thus, our data show, for the first time, that PI3K and Tec family kinases play a crucial role in the regulation of platelet activation and Syk phosphorylation downstream of the CLEC-2 receptor. PMID:25767114

Distinct pathways regulate Syk protein activation downstream of immune tyrosine activation motif (ITAM) and hemITAM receptors in platelets.

PubMed

Manne, Bhanu Kanth; Badolia, Rachit; Dangelmaier, Carol; Eble, Johannes A; Ellmeier, Wilfried; Kahn, Mark; Kunapuli, Satya P

2015-05-01

Tyrosine kinase pathways are known to play an important role in the activation of platelets. In particular, the GPVI and CLEC-2 receptors are known to activate Syk upon tyrosine phosphorylation of an immune tyrosine activation motif (ITAM) and hemITAM, respectively. However, unlike GPVI, the CLEC-2 receptor contains only one tyrosine motif in the intracellular domain. The mechanisms by which this receptor activates Syk are not completely understood. In this study, we identified a novel signaling mechanism in CLEC-2-mediated Syk activation. CLEC-2-mediated, but not GPVI-mediated, platelet activation and Syk phosphorylation were abolished by inhibition of PI3K, which demonstrates that PI3K regulates Syk downstream of CLEC-2. Ibrutinib, a Tec family kinase inhibitor, also completely abolished CLEC-2-mediated aggregation and Syk phosphorylation in human and murine platelets. Furthermore, embryos lacking both Btk and Tec exhibited cutaneous edema associated with blood-filled vessels in a typical lymphatic pattern similar to CLEC-2 or Syk-deficient embryos. Thus, our data show, for the first time, that PI3K and Tec family kinases play a crucial role in the regulation of platelet activation and Syk phosphorylation downstream of the CLEC-2 receptor. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

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.

Probability Distribution Extraction from TEC Estimates based on Kernel Density Estimation

NASA Astrophysics Data System (ADS)

Demir, Uygar; Toker, Cenk; Çenet, Duygu

2016-07-01

Statistical analysis of the ionosphere, specifically the Total Electron Content (TEC), may reveal important information about its temporal and spatial characteristics. One of the core metrics that express the statistical properties of a stochastic process is its Probability Density Function (pdf). Furthermore, statistical parameters such as mean, variance and kurtosis, which can be derived from the pdf, may provide information about the spatial uniformity or clustering of the electron content. For example, the variance differentiates between a quiet ionosphere and a disturbed one, whereas kurtosis differentiates between a geomagnetic storm and an earthquake. Therefore, valuable information about the state of the ionosphere (and the natural phenomena that cause the disturbance) can be obtained by looking at the statistical parameters. In the literature, there are publications which try to fit the histogram of TEC estimates to some well-known pdf.s such as Gaussian, Exponential, etc. However, constraining a histogram to fit to a function with a fixed shape will increase estimation error, and all the information extracted from such pdf will continue to contain this error. In such techniques, it is highly likely to observe some artificial characteristics in the estimated pdf which is not present in the original data. In the present study, we use the Kernel Density Estimation (KDE) technique to estimate the pdf of the TEC. KDE is a non-parametric approach which does not impose a specific form on the TEC. As a result, better pdf estimates that almost perfectly fit to the observed TEC values can be obtained as compared to the techniques mentioned above. KDE is particularly good at representing the tail probabilities, and outliers. We also calculate the mean, variance and kurtosis of the measured TEC values. The technique is applied to the ionosphere over Turkey where the TEC values are estimated from the GNSS measurement from the TNPGN-Active (Turkish National Permanent

Interaction between Sam68 and Src family tyrosine kinases, Fyn and Lck, in T cell receptor signaling.

PubMed

Fusaki, N; Iwamatsu, A; Iwashima, M; Fujisawa, J i

1997-03-07

The Src family protein-tyrosine kinase, Fyn, is associated with the T cell receptor (TCR) and plays an important role in TCR-mediated signaling. We found that a human T cell leukemia virus type 1-infected T cell line, Hayai, overexpressed Fyn. To identify the molecules downstream of Fyn, we analyzed the tyrosine phosphorylation of cellular proteins in the cells. In Hayai, a 68-kDa protein was constitutively tyrosine-phosphorylated. The 68-kDa protein was coimmunoprecipitated with various signaling proteins such as phospholipase C gamma1, the phosphatidylinositol 3-kinase p85 subunit, Grb2, SHP-1, Cbl, and Jak3, implying that the protein might function as an adapter. Purification and microsequencing of this protein revealed that it was the RNA-binding protein, Sam68 (Src associated in mitosis, 68 kDa). Sam68 was associated with the Src homology 2 and 3 domains of Fyn and also those of another Src family kinase, Lck. CD3 cross-linking induced tyrosine phosphorylation of Sam68 in uninfected T cells. These data suggest that Sam68 participates in the signal transduction pathway downstream of TCR-coupled Src family kinases Fyn and Lck in lymphocytes, that is not only in the mitotic pathway downstream of c-Src in fibroblasts.

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.

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

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.

Inhibitors of JAK-family kinases: an update on the patent literature 2013-2015, part 2.

PubMed

Kettle, Jason G; Åstrand, Annika; Catley, Matthew; Grimster, Neil P; Nilsson, Magnus; Su, Qibin; Woessner, Richard

2017-02-01

Janus kinases (JAKs) are a family of four enzymes; JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2) that are critical in cytokine signalling and are strongly linked to both cancer and inflammatory diseases. There are currently two launched JAK inhibitors for the treatment of human conditions: tofacitinib for Rheumatoid arthritis (RA) and ruxolitinib for myeloproliferative neoplasms including intermediate or high risk myelofibrosis and polycythemia vera. Areas covered: This review covers patents claiming activity against one or more JAK family members in the period 2013-2015 inclusive, and covers 95 patents from 42 applicants, split over two parts. The authors have ordered recent patents according to the primary applicant's name, with part 2 covering J through Z. Expert opinion: Inhibition of JAK-family kinases is an area of growing interest, catalysed by the maturity of data on marketed inhibitors ruxolitinib and tofacitinib in late stage clinical trials. Many applicants are pursuing traditional fast-follower strategies around these inhibitors, with a range of chemical strategies adopted. The challenge will be to show sufficient differentiation to the originator compounds, since dose limiting toxicities with such agents appear to be on target and mechanism-related and also considering that such agents may be available as generic compounds by the time follower agents reach market.

Inhibitors of JAK-family kinases: an update on the patent literature 2013-2015, part 1.

PubMed

Kettle, Jason G; Åstrand, Annika; Catley, Matthew; Grimster, Neil P; Nilsson, Magnus; Su, Qibin; Woessner, Richard

2017-02-01

Janus kinases (JAKs) are a family of four enzymes; JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2) that are critical in cytokine signalling and are strongly linked to both cancer and inflammatory diseases. There are currently two launched JAK inhibitors for the treatment of human conditions: tofacitinib for Rheumatoid arthritis (RA) and ruxolitinib for myeloproliferative neoplasms including intermediate or high risk myelofibrosis and polycythemia vera. Areas covered: This review covers patents claiming activity against one or more JAK family members in the period 2013-2015 inclusive, and covers 95 patents from 42 applicants, split over two parts. The authors have ordered recent patents according to the primary applicant's name, with part 1 covering A through to I. Expert opinion: Inhibition of JAK-family kinases is an area of growing interest, catalysed by the maturity of data on marketed inhibitors ruxolitinib and tofacitinib in late stage clinical trials. Many applicants are pursuing traditional fast-follower strategies around these inhibitors, with a range of chemical strategies adopted. The challenge will be to show sufficient differentiation to the originator compounds, since dose limiting toxicities with such agents appear to be on target and mechanism-related and also considering that such agents may be available as generic compounds by the time follower agents reach market.

Epizootic rabbit enteropathy inoculum (TEC4): antibiograms and antibiotic fractionation.

PubMed

Huybens, Nathalie; Houeix, Julien; Licois, Dominique; Mainil, Jacques; Marlier, Didier

2011-01-01

Epizootic rabbit enteropathy (ERE) emerged and spread in Europe within the last 13 years causing major economical loss. The aims of the study was to evaluate antibiograms of TEC4, an inoculum composed of an extract of intestinal content of affected rabbits, and to test the potential of different antibiotic-based TEC4 fractions to reproduce the disease. Twenty nine different antibiotic discs were incubated for determining bacteria resistance. In a complementary study, nine tubes of liquid medium were inoculated with TEC4, incubated and added individually with amoxicillin/clavulanic acid, bacitracin, ceftiofur, doxycycline, novobiocin, streptomycyin, tylosin, vancomycin and 0.9% saline solution as control. The content of each tube was washed by centrifugation and suspended in saline. The three most effective antibiotics are florfenicol, amoxycillin/clavulanic acid and tylosin. A high concentration of Clostridium sordelli and Bacillus firmus were isolated in all fractions. Species never cultured from TEC4 were identified as Fusobacterium necrogenes (in vancomycin fraction), Cellulomonas sp (in novobiocin fraction) and Bacteroides distasonis (in doxycycline fraction). The ERE was reproduced when bacitracin, doxycycline and 0.9% fractions were inoculated. Rabbits showed ERE clinical signs with the specific drop in daily weight gain.

“Stop Ne(c)king around”: How interactomics contributes to functionally characterize Nek family kinases

PubMed Central

Meirelles, Gabriela Vaz; Perez, Arina Marina; de Souza, Edmárcia Elisa; Basei, Fernanda Luisa; Papa, Priscila Ferreira; Melo Hanchuk, Talita Diniz; Cardoso, Vanessa Bomfim; Kobarg, Jörg

2014-01-01

Aside from Polo and Aurora, a third but less studied kinase family involved in mitosis regulation is the never in mitosis-gene A (NIMA)-related kinases (Neks). The founding member of this family is the sole member NIMA of Aspergillus nidulans, which is crucial for the initiation of mitosis in that organism. All 11 human Neks have been functionally assigned to one of the three core functions established for this family in mammals: (1) centrioles/mitosis; (2) primary ciliary function/ciliopathies; and (3) DNA damage response (DDR). Recent findings, especially on Nek 1 and 8, showed however, that several Neks participate in parallel in at least two of these contexts: primary ciliary function and DDR. In the core section of this in-depth review, we report the current detailed functional knowledge on each of the 11 Neks. In the discussion, we return to the cross-connections among Neks and point out how our and other groups’ functional and interactomics studies revealed that most Neks interact with protein partners associated with two if not all three of the functional contexts. We then raise the hypothesis that Neks may be the connecting regulatory elements that allow the cell to fine tune and synchronize the cellular events associated with these three core functions. The new and exciting findings on the Nek family open new perspectives and should allow the Neks to finally claim the attention they deserve in the field of kinases and cell cycle biology. PMID:24921005

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.

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.

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.

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.

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.

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.

The DUF1669 domain of FAM83 family proteins anchor casein kinase 1 isoforms.

PubMed

Fulcher, Luke J; Bozatzi, Polyxeni; Tachie-Menson, Theresa; Wu, Kevin Z L; Cummins, Timothy D; Bufton, Joshua C; Pinkas, Daniel M; Dunbar, Karen; Shrestha, Sabin; Wood, Nicola T; Weidlich, Simone; Macartney, Thomas J; Varghese, Joby; Gourlay, Robert; Campbell, David G; Dingwell, Kevin S; Smith, James C; Bullock, Alex N; Sapkota, Gopal P

2018-05-22

Members of the casein kinase 1 (CK1) family of serine-threonine protein kinases are implicated in the regulation of many cellular processes, including the cell cycle, circadian rhythms, and Wnt and Hedgehog signaling. Because these kinases exhibit constitutive activity in biochemical assays, it is likely that their activity in cells is controlled by subcellular localization, interactions with inhibitory proteins, targeted degradation, or combinations of these mechanisms. We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A to FAM83H) interacted with the α and α-like isoforms of CK1; FAM83A, FAM83B, FAM83E, and FAM83H also interacted with the δ and ε isoforms of CK1. We detected no interaction between any FAM83 member and the related CK1γ1, CK1γ2, and CK1γ3 isoforms. Each FAM83 protein exhibited a distinct pattern of subcellular distribution and colocalized with the CK1 isoform(s) to which it bound. The interaction of FAM83 proteins with CK1 isoforms was mediated by the conserved domain of unknown function 1669 (DUF1669) that characterizes the FAM83 family. Mutations in FAM83 proteins that prevented them from binding to CK1 interfered with the proper subcellular localization and cellular functions of both the FAM83 proteins and their CK1 binding partners. On the basis of its function, we propose that DUF1669 be renamed the polypeptide anchor of CK1 domain. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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.

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.

Interaction between src family kinases and rho-kinase in agonist-induced Ca2+-sensitization of rat pulmonary artery.

PubMed

Knock, Greg A; Shaifta, Yasin; Snetkov, Vladimir A; Vowles, Benjamin; Drndarski, Svetlana; Ward, Jeremy P T; Aaronson, Philip I

2008-02-01

We investigated the role of src family kinases (srcFK) in agonist-mediated Ca2+-sensitization in pulmonary artery and whether this involves interaction with the rho/rho-kinase pathway. Intra-pulmonary arteries (IPAs) and cultured pulmonary artery smooth muscle cells (PASMC) were obtained from rat. Expression of srcFK was determined at the mRNA and protein levels. Ca2+-sensitization was induced by prostaglandin F(2 alpha) (PGF(2 alpha)) in alpha-toxin-permeabilized IPAs. Phosphorylation of the regulatory subunit of myosin phosphatase (MYPT-1) and of myosin light-chain-20 (MLC20) and translocation of rho-kinase in response to PGF(2 alpha) were also determined. Nine srcFK were expressed at the mRNA level, including src, fyn, and yes, and PGF(2 alpha) enhanced phosphorylation of three srcFK proteins at tyr-416. In alpha-toxin-permeabilized IPAs, PGF(2 alpha) enhanced the Ca2+-induced contraction (pCa 6.9) approximately three-fold. This enhancement was inhibited by the srcFK blockers SU6656 and PP2 and by the rho-kinase inhibitor Y27632. Y27632, but not SU6656 or PP2, also inhibited the underlying pCa 6.9 contraction. PGF(2 alpha) enhanced phosphorylation of MYPT-1 at thr-697 and thr-855 and of MLC20 at ser-19. This enhancement, but not the underlying basal phosphorylation, was inhibited by SU6656. Y27632 suppressed both basal and PGF(2 alpha)-mediated phosphorylation. The effects of SU6656 and Y27632, on both contraction and MYPT-1 and MLC20 phosphorylation, were not additive. PGF(2 alpha) triggered translocation of rho-kinase in PASMC, and this was inhibited by SU6656. srcFK are activated by PGF(2 alpha) in the rat pulmonary artery and may contribute to Ca2+-sensitization and contraction via rho-kinase translocation and phosphorylation of MYPT-1.

Interaction between src family kinases and rho-kinase in agonist-induced Ca2+-sensitization of rat pulmonary artery

PubMed Central

Knock, Greg A.; Shaifta, Yasin; Snetkov, Vladimir A.; Vowles, Benjamin; Drndarski, Svetlana; Ward, Jeremy P.T.; Aaronson, Philip I.

2008-01-01

Abstract Aims We investigated the role of src family kinases (srcFK) in agonist-mediated Ca2+-sensitization in pulmonary artery and whether this involves interaction with the rho/rho-kinase pathway. Methods and results Intra-pulmonary arteries (IPAs) and cultured pulmonary artery smooth muscle cells (PASMC) were obtained from rat. Expression of srcFK was determined at the mRNA and protein levels. Ca2+-sensitization was induced by prostaglandin F2α (PGF2α) in α-toxin-permeabilized IPAs. Phosphorylation of the regulatory subunit of myosin phosphatase (MYPT-1) and of myosin light-chain-20 (MLC20) and translocation of rho-kinase in response to PGF2α were also determined. Nine srcFK were expressed at the mRNA level, including src, fyn, and yes, and PGF2α enhanced phosphorylation of three srcFK proteins at tyr-416. In α-toxin-permeabilized IPAs, PGF2α enhanced the Ca2+-induced contraction (pCa 6.9) approximately three-fold. This enhancement was inhibited by the srcFK blockers SU6656 and PP2 and by the rho-kinase inhibitor Y27632. Y27632, but not SU6656 or PP2, also inhibited the underlying pCa 6.9 contraction. PGF2α enhanced phosphorylation of MYPT-1 at thr-697 and thr-855 and of MLC20 at ser-19. This enhancement, but not the underlying basal phosphorylation, was inhibited by SU6656. Y27632 suppressed both basal and PGF2α-mediated phosphorylation. The effects of SU6656 and Y27632, on both contraction and MYPT-1 and MLC20 phosphorylation, were not additive. PGF2α triggered translocation of rho-kinase in PASMC, and this was inhibited by SU6656. Conclusions srcFK are activated by PGF2α in the rat pulmonary artery and may contribute to Ca2+-sensitization and contraction via rho-kinase translocation and phosphorylation of MYPT-1. PMID:18032393

Modes of Action and Functions of ERECTA-family Receptor-like Kinases in Plant Organ Growth and Development

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

TORII, Keiko U.

2012-05-01

Higher plants constitute the central resource for renewable lignocellulose biomass that can supplement for the world's depleting stores of fossil fuels. As such, understanding the molecular and genetic mechanisms of plant organ growth will provide key knowledge and genetic resources that enables manipulation of plant biomass feedstock for better growth and productivity. The goal of this proposal is to understand how cell proliferation and growth are coordinated during aboveground organ morphogenesis, and how cell-cell signaling mediated by a family of receptor kinases coordinates plant organogenesis. The well-established model plant Arabidopsis thaliana is used for our research to facilitate rapid progress.more » Specifically, we focus on how ERECTA-family leucine-rich repeat receptor kinases (LRR-RLKs) interact in a synergistic manner to promote organogenesis and pattern formation in Arabidopsis. This project was highly successful, resulted in fourteen publications including nine peer-reviewed original research articles. One provisional US patent has been filed through this DOE funding. We have addressed the critical roles for a family of receptor kinases in coordinating proliferation and differentiation of plants, and we successfully elucidated the downstream targets of this signaling pathway in specifying stomatal patterning.« less

Regional ionospheric TEC data assimilation and now-casting service

NASA Astrophysics Data System (ADS)

Aa, E.; Liu, S.; Wengeng, H.

2017-12-01

Ionospheric data assimilation is a now-casting technique to incorporate irregular ionospheric measurements into certain background model, which is an effective and efficient way to overcome the limitation of the unbalanced data distribution and to improve the accuracy of the model, so that the model and the data can be optimally combined with each other to produce a more reliable and reasonable system specification. In this study, a regional total electron content (TEC) now-casting system over China and adjacent areas (70E-140E and 15N-55N) is developed on the basis of data assimilation technique. The International Reference Ionosphere (IRI) is used here as background model, and the GNSS data are derived from both the Space Environment Monitoring Network of Chinese Academy of Sciences (SEMnet) and International GNSS Service (IGS) data. A Three-dimensional variation algorithm (3DVAR) combined with Gauss-Markov Kalman filter technique is used to implement the data assimilation. The regional gridded TEC maps and the position errors of single-frequency GPS receivers can be generated and publicized online (http://sepc.ac.cn/TEC_chn.php) in quasi-real time, which is updated for every 15 min. It is one of the ionospheric now-casting systems in China based on data assimilation algorithm, which can be used not only for real-time monitoring of ionosphere environment over China and adjacent areas, but also in providing accurate and effective specification of regional ionospheric TEC and error correction for satellite navigation, radar imaging, shortwave communication, and other relevant applications.

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

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.

Ionospheric TEC Weather Map Over South America

NASA Astrophysics Data System (ADS)

Takahashi, H.; Wrasse, C. M.; Denardini, C. M.; Pádua, M. B.; de Paula, E. R.; Costa, S. M. A.; Otsuka, Y.; Shiokawa, K.; Monico, J. F. Galera; Ivo, A.; Sant'Anna, N.

2016-11-01

Ionospheric weather maps using the total electron content (TEC) monitored by ground-based Global Navigation Satellite Systems (GNSS) receivers over South American continent, TECMAP, have been operationally produced by Instituto Nacional de Pesquisas Espaciais's Space Weather Study and Monitoring Program (Estudo e Monitoramento Brasileiro de Clima Especial) since 2013. In order to cover the whole continent, four GNSS receiver networks, (Rede Brasileiro de Monitoramento Contínuo) RBMC/Brazilian Institute for Geography and Statistics, Low-latitude Ionospheric Sensor Network, International GNSS Service, and Red Argentina de Monitoreo Satelital Continuo, in total 140 sites, have been used. TECMAPs with a time resolution of 10 min are produced in 12 h time delay. Spatial resolution of the map is rather low, varying between 50 and 500 km depending on the density of the observation points. Large day-to-day variabilities of the equatorial ionization anomaly have been observed. Spatial gradient of TEC from the anomaly trough (total electron content unit, 1 TECU = 1016 el m-2 (TECU) <10) to the crest region (TECU > 80) causes a large ionospheric range delay in the GNSS positioning system. Ionospheric plasma bubbles, their seeding and development, could be monitored. This plasma density (spatial and temporal) variability causes not only the GNSS-based positioning error but also radio wave scintillations. Monitoring of these phenomena by TEC mapping becomes an important issue for space weather concern for high-technology positioning system and telecommunication.

Role of STATs as downstream signal transducers in Src family kinase-mediated tumorigenesis.

PubMed

Silva, Corinne M

2004-10-18

The signal transducers and activators of transcription (STATs) were originally identified in the signaling pathway activated by the nontyrosine kinase containing cytokine receptors. The role of these STATs in hematopoietic cell signaling has been well described. In the case of cytokine receptors, activation of STAT tyrosine phosphorylation occurs through ligand-induced recruitment, and activation of the intracellular JAK kinases. However, STATs can also be activated by growth factor receptors, particularly the EGFR; as well as by members of the Src Family of Kinases (SFKs), particularly c-Src. In many cases, there is a differential activation of the STATs by these tyrosine kinases as compared to activation by the cytokine receptors. This difference provides for the potential of unique actions of STATs in response to growth factor receptor and SFK activation. Since there are many cancers in which SFKs and c-Src in particular, are co-overexpressed with growth factor receptors, it is not surprising that STATs play an important role in the tumorigenesis process induced by c-Src. The activation paradigm and role of STATs in these cancers, with particular emphasis on breast cancer models, is discussed.

Session Overview and AzTEC Instrument Performance

NASA Astrophysics Data System (ADS)

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

2006-12-01

AzTEC is a new 144 element bolometer receiver destined as a first-generation instrument for the Large Millimeter Telescope. >From November 2005 and through January 2006, AzTEC made science observations at the 15m James Clerk Maxwell Telescope (JCMT). Approximately 1/2 of the available time was spent mapping the submillimeter galaxy population in blank and biased fields. Overall, over 1 square degree of sky was mapped with uniform coverage in each of five primary fields making this the largest set of surveys of the submillimeter galaxy population ever performed. Hundreds of new submillimeter galaxies have been detected. Here we discuss the instrument, our mapping technique, and a brief summary of the data reduction process. We conclude with a brief summary of the overall impact of these surveys on our understanding of the submillimeter galaxy population.

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.

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.

The 1980 V-TECS Marketing Study.

ERIC Educational Resources Information Center

Hattwick, Richard E.; And Others

The Vocational-Technical Education Consortium of States (V-TECS) conducted a marketing study that considered the implications of six options for the organization's future. The first option is continuation of the status quo, which is dangerous because existing members may leave the consortium. The second option is the status quo combined with an…

Role of src-family kinases in hypoxic vasoconstriction of rat pulmonary artery

PubMed Central

Knock, Greg A.; Snetkov, Vladimir A.; Shaifta, Yasin; Drndarski, Svetlana; Ward, Jeremy P.T.; Aaronson, Philip I.

2008-01-01

Aims We investigated the role of src-family kinases (srcFKs) in hypoxic pulmonary vasoconstriction (HPV) and how this relates to Rho-kinase-mediated Ca2+ sensitization and changes in intracellular Ca2+ concentration ([Ca2+]i). Methods and results Intra-pulmonary arteries (IPAs) were obtained from male Wistar rats. HPV was induced in myograph-mounted IPAs. Auto-phosphorylation of srcFKs and phosphorylation of the regulatory subunit of myosin phosphatase (MYPT-1) and myosin light-chain (MLC20) in response to hypoxia were determined by western blotting. Translocation of Rho-kinase and effects of siRNA knockdown of src and fyn were examined in cultured pulmonary artery smooth muscle cells (PASMCs). [Ca2+]i was estimated in Fura-PE3-loaded IPA. HPV was inhibited by two blockers of srcFKs, SU6656 and PP2. Hypoxia enhanced phosphorylation of three srcFK proteins at Tyr-416 (60, 59, and 54 kDa, corresponding to src, fyn, and yes, respectively) and enhanced srcFK-dependent tyrosine phosphorylation of multiple target proteins. Hypoxia caused a complex, time-dependent enhancement of MYPT-1 and MLC20 phosphorylation, both in the absence and presence of pre-constriction. The sustained component of this enhancement was blocked by SU6656 and the Rho-kinase inhibitor Y27632. In PASMCs, hypoxia caused translocation of Rho-kinase from the nucleus to the cytoplasm, and this was prevented by anti-src siRNA and to a lesser extent by anti-fyn siRNA. The biphasic increases in [Ca2+]i that accompany HPV were also inhibited by PP2. Conclusion Hypoxia activates srcFKs and triggers protein tyrosine phosphorylation in IPA. Hypoxia-mediated Rho-kinase activation, Ca2+ sensitization, and [Ca2+]i responses are depressed by srcFK inhibitors and/or siRNA knockdown, suggesting a central role of srcFKs in HPV. PMID:18682436

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.

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.

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.

B/TEC Opens Doors for You.

ERIC Educational Resources Information Center

Business and Technician Education Council, London (England).

This package contains a paper summarizing the aims and services provided by the Business and Technician Education Council (B/TEC). Established to advance the quality and availability of a wide range of employment-related education to persons in the United Kingdom who are studying at or beyond the equivalent of the American associate-degree level,…

Industrial Maintenance Technology (IM-TEC). Student Manual.

ERIC Educational Resources Information Center

Fusch, Gene E.

This student manual explains an innovative strategy through which Bellingham Technical College's (Washington) evening Industrial Electrician and Millwright Apprenticeships were aggregated with workforce upgrade course offerings to form the college's first evening degree program in Industrial Maintenance Technology (IM-TEC). Section 1 contains a…

Acetylcholine but not adenosine triggers preconditioning through PI3-kinase and a tyrosine kinase.

PubMed

Qin, Qining; Downey, James M; Cohen, Michael V

2003-02-01

Adenosine and acetylcholine (ACh) trigger preconditioning by different signaling pathways. The involvement of phosphatidylinositol 3-kinase (PI3-kinase), a protein tyrosine kinase, and Src family tyrosine kinase in preconditioning was evaluated in isolated rabbit hearts. Either wortmannin (PI3-kinase blocker), genistein (tyrosine kinase blocker), lavendustin A (tyrosine kinase blocker), or 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolol[3,4-d]pyrimidine (PP2; Src family tyrosine kinase blocker) was given for 15 min to bracket a 5-min infusion of either adenosine or ACh (trigger phase). The hearts then underwent 30 min of regional ischemia. Infarct size for ACh alone was 9.3 +/- 3.5% of the risk zone versus 34.3 +/- 4.1% in controls. All four inhibitors blocked ACh-induced protection. When wortmannin or PP2 was infused only during the 30-min ischemic period (mediator phase), ACh-induced protection was not affected (7.4 +/- 2.1% and 9.7 +/- 1.7% infarction, respectively). Adenosine-triggered protection was not blocked by any of the inhibitors. Therefore, PI3-kinase and at least one protein tyrosine kinase, probably Src kinase, are involved in the trigger phase of ACh-induced, but not adenosine-induced, preconditioning. Neither PI3-kinase nor Src kinase is a mediator of the protection of ACh.

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

The diverse functions of Src family kinases in macrophages

PubMed Central

Abram, Clare L.; Lowell, Clifford A.

2015-01-01

Macrophages are key components of the innate immune response. These cells possess a diverse repertoire of receptors that allow them to respond to a host of external stimuli including cytokines, chemokines, and pathogen-associated molecules. Signals resulting from these stimuli activate a number of macrophage functional responses such as adhesion, migration, phagocytosis, proliferation, survival, cytokine release and production of reactive oxygen and nitrogen species. The cytoplasmic tyrosine kinase Src and its family members (SFKs) have been implicated in many intracellular signaling pathways in macrophages, initiated by a diverse set of receptors ranging from integrins to Toll-like receptors. However, it has been difficult to implicate any given member of the family in any specific pathway. SFKs appear to have overlapping and complementary functions in many pathways. Perhaps the function of these enzymes is to modulate the overall intracellular signaling network in macrophages, rather than operating as exclusive signaling switches for defined pathways. In general, SFKs may function more like rheostats, influencing the amplitude of many pathways. PMID:18508521

Equatorial late-afternoon periodic TEC fluctuations observed by multiple GPS receivers

NASA Astrophysics Data System (ADS)

Tsugawa, T.; Maruyama, T.; Saito, S.; Ishii, M.

2009-12-01

We report, for the first time, equatorial periodic total electron content (TEC) fluctuations observed in the late afternoon by multiple GPS receivers. As a part of Southeast Asia low-latitude ionospheric network (SEALION), GPS receivers at Chiang Mai and Chumphon, Thailand, have been operated since 2005. We found that periodic TEC fluctuations (PTF) with the periods of 15-30 minutes are often observed at these two sites in the spring (Apr-May) late afternoon. Further investigations using multiple GPS receivers in Southeast Asia revealed that the PTFs propagate at 150-200 m/s away from the equator and their amplitudes depend on the satellite azimuth angle. Statistical study of the PTF activity at different latitudes and longitudes clarified that the PTFs are not observed at mid-latitudes, and their seasonal variations are different at different longitudes and at geomagnetically conjugate regions. These observational results indicate that the PTFs are caused by the atmospheric gravity waves (AGW) which are generated in the equatorial lower atmosphere and propagate away from the equator. Simultaneous GPS-TEC and ionosonde observations at Chumphon revealed that the day-to-day variations of PTF activities are well correlated with those of the rate of TEC change index (ROTI) and the occurrence of equatorial spread F (ESF) after the sunset, indicating the PTFs may be related with the onset of the ESF and plasma bubbles.

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.

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.

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.

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

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.

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,…

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

The activity and stability of the intrinsically disordered Cip/Kip protein family are regulated by non-receptor tyrosine kinases

PubMed Central

Otieno, Steve; Lelli, Moreno; Kriwacki, Richard W.

2014-01-01

The Cip/Kip family of cyclin-dependent kinase (Cdk) inhibitors includes p21Cip1, p27Kip1 and p57Kip2. Their kinase inhibitory activities are mediated by a homologous N-terminal kinase-inhibitory domain (KID). 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 KID 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, and 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. PMID:25463440

C-TEC: Ohio's First All-Green School

ERIC Educational Resources Information Center

Krall, Angie

2009-01-01

In Ohio's Licking County, the Career and Technology Education Centers (C-TEC) is a leader in the green movement. This eco-friendly school incorporates environmental sustainability in all aspects of its programming and is the first Leadership in Energy and Environmental Design (LEED)-certified public building in the state. While eco-friendly…

Requirement and Redundancy of the Src Family Kinases Fyn and Lyn in Perforin-Dependent Killing of Cryptococcus neoformans by NK Cells

PubMed Central

Oykhman, Paul; Timm-McCann, Martina; Xiang, Richard F.; Islam, Anowara; Li, Shu Shun; Stack, Danuta; Huston, Shaunna M.; Ma, Ling Ling

2013-01-01

Natural killer (NK) cells directly recognize and kill fungi, such as the pathogenic fungus Cryptococcus neoformans, via cytolytic mechanisms. However, the precise signaling pathways governing this NK cell microbicidal activity and the implications for fungal recognition are still unknown. Previously, it was reported that NK cell anticryptococcal activity is mediated through a conserved phosphatidylinositol 3-kinase–extracellular signal-regulated kinase 1/2 (PI3K-ERK1/2) pathway. Using YT (a human NK-like cell line) and primary human NK cells, we sought to identify the upstream, receptor-proximal signaling elements that led to fungal cytolysis. We demonstrate that Src family kinases were activated in response to C. neoformans. Furthermore, pharmacologic inhibition with an Src kinase inhibitor blocked C. neoformans-induced downstream activation of PI3K and ERK1/2 and abrogated cryptococcal killing. At the same time, the inhibitor disrupted the polarization of perforin-containing granules toward the NK cell-cryptococcal synapse but had no effect on conjugate formation between the organism and the NK cell. Finally, small interfering RNA (siRNA) double (but not single) knockdown of two Src family kinases, Fyn and Lyn, blocked cryptococcal killing. Together these data demonstrate a mechanism whereby the Src family kinases, Fyn and Lyn, redundantly mediate anticryptococcal activity through the activation of PI3K and ERK1/2, which in turn facilitates killing by inducing the polarization of perforin-containing granules to the NK cell-cryptococcal synapse. PMID:23918783

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.

SynTec Final Technical Report: Synthetic biology for Tailored Enzyme cocktails

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

Lin, Janine; Teter, Sarah

Using a novel enzyme screening method inspired by synthetic biology, Novozymes developed new technology under SynTec which allows for more rapidly tailoring of enzyme cocktails. The methodology can be applied to specific feedstocks, and or coupled to address a specific hydrolytic conversion process context. Using combinatorial high throughput screening of libraries of enzyme domains, we can quickly assess which combination of catalytic modules delivers the best performance for a specific condition. To demonstrate the effectiveness of the screening process, we measured performance of the output catalytic cocktail compared to CTec3/HTec3. SynTec benchmark cocktail - blend of Cellic® CTec3 and HTec3.more » The test substrate was - ammonia fiber expansion pretreated corn stover (AFEX™ PCS).CTec3/HTec3 was assayed at the optimal pH and temperature, and also in the absence of any pH adjustment. The new enzyme cocktail discovered under SynTec was assayed in the absence of any pH adjustment and at the optimal temperature. Conversion is delivered by SynTec enzyme at significant dose reduction relative to CTec3/HTec3 at the controlled pH optimum, and without titrant required to maintain pH, which delivers additional cost savings relative to current state of the art process. In this 2.5 year $4M project, the team delivered an experimental cocktail that significantly outperformed CTec3/HTec3 for a specific substrate, and for specific hydrolysis conditions. As a means of comparing performance improvement delivered per research dollar spent, we note that SynTec delivered a similar performance improvement to the previous award, in a shorter time and with fewer resources than for the previously successful DOE project DECREASE, a 3.5 year, $25M project, though this project focused on a different substrate and used different hydrolysis conditions. The newly implemented technology for rapid sourcing of new cellulases and hemicellulases from nature is an example of Novozymes

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

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…

The TolTEC Camera for the LMT Telescope

NASA Astrophysics Data System (ADS)

Bryan, Sean

2018-01-01

TolTEC is a new camera being built for the 50-meter Large Millimeter-wave Telescope (LMT) on Sierra Negra in Puebla, Mexico. The instrument will discover and characterize distant galaxies by detecting the thermal emission of dust heated by starlight. The polarimetric capabilities of the camera will measure magnetic fields in star-forming regions in the Milky Way. The optical design of the camera uses mirrors, lenses, and dichroics to simultaneously couple a 4 arcminute diameter field of view onto three single-band focal planes at 150, 220, and 280 GHz. The 7000 polarization-selective detectors are single-band horn-coupled LEKID detectors fabricated at NIST. A rotating half wave plate operates at ambient temperature to modulate the polarized signal. In addition to the galactic and extragalactic surveys already planned, TolTEC installed at the LMT will provide open observing time to the community.

Src-family Tyrosine Kinases in Oogenesis, Oocyte Maturation, and Fertilization: An Evolutionary Perspective

PubMed Central

Kinsey, William H.

2015-01-01

The oocyte is a highly specialized cell poised to respond to fertilization with a unique set of actions needed to recognize and incorporate a single sperm, complete meiosis, reprogram maternal and paternal genomes and assemble them into a unique zygotic genome, and finally initiate the mitotic cell cycle. Oocytes accomplish this diverse series of events through an array of signal transduction pathway components that include a characteristic collection of protein tyrosine kinases. The src-family protein kinases figure importantly in this signaling array and oocytes characteristically express certain SFKs at high levels to provide for the unique actions that the oocyte must perform. The SFKs typically exhibit a distinct pattern of subcellular localization in oocytes and perform critical functions in different subcellular compartments at different steps during oocyte maturation and fertilization. While many aspects of SFK signaling are conserved among oocytes from different species, significant differences exist in the extent to which src-family -mediated pathways are used by oocytes from species that fertilize externally vs those which are fertilized internally. The observation that several oocyte functions which require SFK signaling appear to represent common points of failure during assisted reproductive techniques in humans, highlights the importance of these signaling pathways for human reproductive health. PMID:25030759

Reconstruction of missed critical frequency of F2-layer over Mexico using TEC

NASA Astrophysics Data System (ADS)

Sergeeva, M. A.; Maltseva, O. A.; Gonzalez-Esparza, A.; Romero Hernandez, E.; De la Luz, V.; Rodriguez-Martinez, M. R.

2016-12-01

The study of the Earth's ionosphere's state is one of the key issues within the Space Weather monitoring task. It is hard to overestimate the importance of diagnostics of its current state and forecasts of Space Weather conditions. There are different methods of short-time predictions for the ionosphere state change. The real-time monitoring of the ionospheric Total Electron Content (TEC) provides the opportunity to choose an appropriate technique for the particular observation point on the Earth. From September 2015 the continuous monitoring of TEC variations over the territory of Mexico is performed by the Mexican Space Weather Service (SCiESMEX). Regular patterns of the diurnal and seasonal TEC variations were revealed in base of past statistics and real-time observations which can be used to test the prediction method. Some specific features of the ionosphere behaviour are discussed. However, with all the merits of TEC as an ionospheric parameter, for the full picture of the processes in the ionosphere and for practical applications it is needed to identify the behaviour of other principal ionospheric parameters provided by ionosondes. Currently, SCiESMEX works on the project of the ionosonde installation in Mexico. This study was focused on the reconstruction of the critical frequency of F2-layer of the ionosphere (foF2) when this data is missing. For this purpose measurements of TEC and the median value of the equivalent slab thickness of the ionosphere were used. First, the foF2 values reconstruction was made for the case of the ionosonde data being absent during some hours or days. Second, the possibility of foF2 reconstruction was estimated for the Mexican region having no ionosonde using local TEC data and foF2 data obtained in the regions close to Mexico. Calculations were performed for quiet and disturbed periods. The results of reconstruction were compared to the foF2 obtained from the International Reference Model and to median foF2 values. Comparison

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

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.

Support vector machines for TEC seismo-ionospheric anomalies detection

NASA Astrophysics Data System (ADS)

Akhoondzadeh, M.

2013-02-01

Using time series prediction methods, it is possible to pursue the behaviors of earthquake precursors in the future and to announce early warnings when the differences between the predicted value and the observed value exceed the predefined threshold value. Support Vector Machines (SVMs) are widely used due to their many advantages for classification and regression tasks. This study is concerned with investigating the Total Electron Content (TEC) time series by using a SVM to detect seismo-ionospheric anomalous variations induced by the three powerful earthquakes of Tohoku (11 March 2011), Haiti (12 January 2010) and Samoa (29 September 2009). The duration of TEC time series dataset is 49, 46 and 71 days, for Tohoku, Haiti and Samoa earthquakes, respectively, with each at time resolution of 2 h. In the case of Tohoku earthquake, the results show that the difference between the predicted value obtained from the SVM method and the observed value reaches the maximum value (i.e., 129.31 TECU) at earthquake time in a period of high geomagnetic activities. The SVM method detected a considerable number of anomalous occurrences 1 and 2 days prior to the Haiti earthquake and also 1 and 5 days before the Samoa earthquake in a period of low geomagnetic activities. In order to show that the method is acting sensibly with regard to the results extracted during nonevent and event TEC data, i.e., to perform some null-hypothesis tests in which the methods would also be calibrated, the same period of data from the previous year of the Samoa earthquake date has been taken into the account. Further to this, in this study, the detected TEC anomalies using the SVM method were compared to the previous results (Akhoondzadeh and Saradjian, 2011; Akhoondzadeh, 2012) obtained from the mean, median, wavelet and Kalman filter methods. The SVM detected anomalies are similar to those detected using the previous methods. It can be concluded that SVM can be a suitable learning method to detect

Inverting Coseismic TEC Disturbances for Neutral Atmosphere Pressure Wave

NASA Astrophysics Data System (ADS)

Lee, R. F.; Mikesell, D.; Rolland, L.

2017-12-01

Research from the past 20 years has shown that we can detect coseismic disturbances in the total electron content (TEC) using global navigation space systems (GNSS). In the near field, TEC disturbances are created by the direct wave from rupture on the surface. This pressure wave travels through the neutral atmosphere to the ionosphere within about 10 minutes. This provides the opportunity to almost immediately characterize the source of the acoustic disturbance on the surface using methods from seismology. In populated areas, this could provide valuable information to first responders. To retrieve the surface motion amplitude information we must account for changes in the waveform caused by the geomagnetic field, motion of the satellites and the geometry of the satellites and receivers. One method is to use a transfer function to invert for the neutral atmosphere pressure wave. Gómez et al (2015) first employed an analytical model to invert for acoustic waves produced by Rayleigh waves propagating along the Earth's surface. Here, we examine the same model in the near field using the TEC disturbances from the direct wave produced by rupture at the surface. We compare results from the forward model against a numerical model that has been shown to be in good agreement with observations from the 2011 Van (Turkey) earthquake. We show the forward model predictions using both methods for the Van earthquake. We then analyze results for hypothetical events at different latitudes and discuss the reliability of the analytical model in each scenario. Gómez, D., R. Jr. Smalley, C. A. Langston, T. J. Wilson, M. Bevis, I. W. D. Dalziel, E. C. Kendrick, S. A. Konfal, M. J. Willis, D. A. Piñón, et al. (2015), Virtual array beamforming of GPS TEC observations of coseismic ionospheric disturbances near the Geomagnetic South Pole triggered by teleseismic megathrusts, J. Geophys. Res. Space Physics, 120, 9087-9101, doi:10.1002/2015JA021725.

V-TECS Guide for Bookkeeping/Accounting/Payroll Clerk.

ERIC Educational Resources Information Center

Gregory, Margaret R.; Benson, Robert T.

This guide, an extension of the Vocational-Technical Education Consortium of States (V-TECS) catalog, includes such considerations as background information, decision-making skills, attitudes, and learning methods surrounding the occupations of bookkeeper/accountant/payroll clerk. The guide provides job-relevant task, performance objectives,…

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

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

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

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

FGF-mediated mesoderm induction involves the Src-family kinase Laloo.

PubMed

Weinstein, D C; Marden, J; Carnevali, F; Hemmati-Brivanlou, A

1998-08-27

During embryogenesis, inductive interactions underlie the development of much of the body plan. In Xenopus laevis, factors secreted from the vegetal pole induce mesoderm in the adjacent marginal zone; members of both the transforming growth factor-beta (TGF-beta) and fibroblast growth factor (FGF) ligand families seem to have critical roles in this process. Here we report the identification and characterization of laloo, a novel participant in the signal transduction cascade linking extracellular, mesoderm-inducing signals to the nucleus, where alteration of cell fate is driven by changes in gene expression. Overexpression of laloo, a member of the Src-related gene family, in Xenopus embryos gives rise to ectopic posterior structures that frequently contain axial tissue. Laloo induces mesoderm in Xenopus ectodermal explants; this induction is blocked by reagents that disrupt the FGF signalling pathway. Conversely, expression of a dominant-inhibitory Laloo mutant blocks mesoderm induction by FGF and causes severe posterior truncations in vivo. This work provides the first evidence that a Src-related kinase is involved in vertebrate mesoderm induction.

Preliminary Investigation of Longitudinal Differences in TEC and Scintillation at Transition Latitudes

DTIC Science & Technology

1991-04-04

AIR. j NO ABSOLUTE TEC. C: NEW SATELITE WINDOWS INSERTED. j - IAPEDRIVE PROBLEM. D: SOME DATA ON CHART NOT RECORDED ON TAPE. H = NPIB INTERFASE...PROBLEM. E: SOME DATA BROKEN UP. V 2 FLOPPY DISK/DRIVE PROBLEM. F: TAPE CHANGE. W - WRONG SATELITE WINDOWS. TOTAL HOURS OF ACTIVITY LEVEL 1:300 P - POWER...0 1 0 31 1 COMMENT’S: ADDITIONAL COMMENT’S. A: TAPE STOP * L1/L2 SCINTILLATION. B: GPS SYSTEM OFF THE AIR. O= N ABSOLUTE TEC. C: NEW SATELITE WINDOWS

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.

FAK/Src family of kinases: protective or aggravating factor for ischemia reperfusion injury in nervous system?

PubMed

Bikis, Christos; Moris, Demetrios; Vasileiou, Ioanna; Patsouris, Eustratios; Theocharis, Stamatios

2015-04-01

The focal adhesion kinase (FAK) and the Src families of kinases are subfamilies of the non-receptor protein tyrosine kinases. FAK activity is regulated by gene amplification, alternative splicing and phosporylation/dephosphorylation. FAK/Src complex has been found to participate through various pathways in neuronal models of ischemia-reperfusion injury (IRI) with conflicting results. The aim of the present review is to summarize the currently available data on this subject. The MEDLINE/PubMed database was searched for publications with the medical subject heading IRI and FAK and/or Src, nervous system. We restricted our search till 2014. We identified 93 articles that were available in English as abstracts or/and full-text articles that were deemed appropriate for our review. FAK has been found to have a beneficial preconditioning effect on IRI through activation via the protein kinase C (PKC) pathway by anesthetic agents. Of great importance are the interactions between FAK/Src and VEGF that has been already detected as a protective mean for IRI. The effect of VEGF administration might depend on dose as well as on time of administration. A Ca(2+)/calmodulin-dependent protein kinase II or PKC inhibitors seem to have protective effects on IRI by inhibiting ion channels activation.

Coiled-Coil Antagonism Regulates Activity of Venus Flytrap-Domain-Containing Sensor Kinases of the BvgS Family

PubMed Central

Lesne, Elodie; Dupré, Elian; Lensink, Marc F.; Locht, Camille

2018-01-01

ABSTRACT Bordetella pertussis controls the expression of its virulence regulon through the two-component system BvgAS. BvgS is a prototype for a family of multidomain sensor kinases. In BvgS, helical linkers connect periplasmic Venus flytrap (VFT) perception domains to a cytoplasmic Per-Arnt-Sim (PAS) domain and the PAS domain to the dimerization/histidine phosphotransfer (DHp) domain of the kinase. The two linkers can adopt coiled-coil structures but cannot do so simultaneously. The first linker forms a coiled coil in the kinase mode and the second in the phosphatase mode, with the other linker in both cases showing an increase in dynamic behavior. The intervening PAS domain changes its quaternary structure between the two modes. In BvgS homologues without a PAS domain, a helical “X” linker directly connects the VFT and DHp domains. Here, we used BvgS as a platform to characterize regulation in members of the PAS-less subfamily. BvgS chimeras of homologues with natural X linkers displayed various regulation phenotypes. We identified two distinct coiled-coil registers in the N- and C-terminal portions of the X linkers. Stable coil formation in the C-terminal moiety determines the phosphatase mode, similarly to BvgS; in contrast, coil formation in the N-terminal moiety along the other register leads to the kinase mode. Thus, antagonism between two registers in the VFT-DHp linker forms the basis for activity regulation in the absence of the PAS domain. The N and C moieties of the X linker play roles similar to those played by the two independent linkers in sensor kinases with a PAS domain, providing a unified mechanism of regulation for the entire family. PMID:29487240

Millimeter-Wave Polarimeters Using Kinetic Inductance Detectors for TolTEC and Beyond

NASA Astrophysics Data System (ADS)

Austermann, J. E.; Beall, J. A.; Bryan, S. A.; Dober, B.; Gao, J.; Hilton, G.; Hubmayr, J.; Mauskopf, P.; McKenney, C. M.; Simon, S. M.; Ullom, J. N.; Vissers, M. R.; Wilson, G. W.

2018-05-01

Microwave kinetic inductance detectors (MKIDs) provide a compelling path forward to the large-format polarimeter, imaging, and spectrometer arrays needed for next-generation experiments in millimeter-wave cosmology and astronomy. We describe the development of feedhorn-coupled MKID detectors for the TolTEC millimeter-wave imaging polarimeter being constructed for the 50-m Large Millimeter Telescope (LMT). Observations with TolTEC are planned to begin in early 2019. TolTEC will comprise ˜ 7000 polarization-sensitive MKIDs and will represent the first MKID arrays fabricated and deployed on monolithic 150 mm diameter silicon wafers—a critical step toward future large-scale experiments with over 10^5 detectors. TolTEC will operate in observational bands at 1.1, 1.4, and 2.0 mm and will use dichroic filters to define a physically independent focal plane for each passband, thus allowing the polarimeters to use simple, direct-absorption inductive structures that are impedance matched to incident radiation. This work is part of a larger program at NIST-Boulder to develop MKID-based detector technologies for use over a wide range of photon energies spanning millimeter-waves to X-rays. We present the detailed pixel layout and describe the methods, tools, and flexible design parameters that allow this solution to be optimized for use anywhere in the millimeter and sub-millimeter bands. We also present measurements of prototype devices operating in the 1.1 mm band and compare the observed optical performance to that predicted from models and simulations.

SubTec-7 Gives New Technologies a Flight Test

NASA Image and Video Library

2017-12-08

NASA successfully launched the SubTec-7 payload on a Black Brant IX suborbital sounding rocket at 5:45 a.m. EDT, May 16, from the NASA's Wallops Flight Facility. The payload flew to an altitude of about 154 miles before descending by parachute and landing in the Atlantic Ocean. SubTec-7 provided a flight test for more than 20 technologies to improve sounding rocket and spacecraft capabilities. Good data was received during the flight. The payload has been recovered. Credit: NASA/Wallops NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

Evaluation of long term solar activity effects on GPS derived TEC

NASA Astrophysics Data System (ADS)

Mansoori, Azad A.; Khan, Parvaiz A.; Ahmad, Rafi; Atulkar, Roshni; M, Aslam A.; Bhardwaj, Shivangi; Malvi, Bhupendra; Purohit, P. K.; Gwal, A. K.

2016-10-01

The solar activity hence the solar radiance follows a long term periodic variability with eleven years periodicity, known as solar cycle. This drives the long term variability of the ionosphere. In the present problem we investigate the long term behaviour of the ionosphere with the eleven year cyclic solar activity. Under the present study we characterize the ionospheric variability by Total Electron Content (TEC) using measurements made by Global Positioning System (GPS) and solar cycle variability by various solar activity indices. We make use of five solar activity indices viz. sunspot number (Rz), solar radio Flux (F10.7 cm), EUV Flux (26-34 nm), flare index and CME occurrences. The long term variability of these solar activity indices were then compared and correlated with the variability of ionospheric TEC, at a mid latitude station, Usuda (36.13N, 138.36E), of Japan, during the solar cycle 23 and ascending phase of cycle 24. From our study, we found that long term changes in the ionospheric TEC vary synchronously with corresponding changes in the solar activity indices. The correlation analysis shows that all the solar activity indices exhibit a very strong correlation with TEC (R =0.76 -0.99). Moreover the correlation between the two is stronger in the descending phase of the solar cycle. The correlation is found to be remarkably strongest during the deep minimum of the solar cycle 24 i.e. between 2007- 2009. Also we noticed a hysteresis effect exists with solar radio flux (F10.7 cm) and solar EUV flux (26-34 nm). This effect is absent with other parameters.

Molecular characterization of a family of ligands for eph-related tyrosine kinase receptors.

PubMed Central

Beckmann, M P; Cerretti, D P; Baum, P; Vanden Bos, T; James, L; Farrah, T; Kozlosky, C; Hollingsworth, T; Shilling, H; Maraskovsky, E

1994-01-01

A family of tyrosine kinase receptors related to the product of the eph gene has been described recently. One of these receptors, elk, has been shown to be expressed only in brain and testes. Using a direct expression cloning technique, a ligand for the elk receptor has been isolated by screening a human placenta cDNA library with a fusion protein containing the extracellular domain of the receptor. This isolated cDNA encodes a transmembrane protein. While the sequence of the ligand cDNA is unique, it is related to a previously described sequence known as B61. Northern blot analysis of human tissue mRNA showed that the elk ligand's mRNA is 3.5 kb long and is found in placenta, heart, lung, liver, skeletal muscle, kidney and pancreas. Southern blot analysis showed that the gene is highly conserved in a wide variety of species. Both elk ligand and B61 mRNAs are inducible by tumour necrosis factor in human umbilical vein endothelial cells. In addition, both proteins show promiscuity in binding to the elk and the related hek receptors. Since these two ligand sequences are similar, and since elk and hek are members of a larger family of eph-related receptor molecules, we refer to these ligands as LERKs (ligands for eph-related kinases). Images PMID:8070404

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.

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.

CHLAMYDIA TRACHOMATIS TARP IS PHOSPHORYLATED BY SRC FAMILY TYROSINE KINASES

PubMed Central

Jewett, Travis J.; Dooley, Cheryl A.; Mead, David J.; Hackstadt, Ted

2008-01-01

The translocated actin recruiting phosphoprotein (Tarp) is injected into the cytosol shortly after Chlamydia trachomatis attachment to a target cell and subsequently phosphorylated by an unidentified tyrosine kinase. A role for Tarp phosphorylation in bacterial entry is unknown. In this study, recombinant C. trachomatis Tarp was employed to identify the host cell kinase(s) required for phosphorylation. Each tyrosine rich repeat of L2 Tarp harbors a sequence similar to a Src and Abl kinase consensus target. Furthermore, purified p60-src, Yes, Fyn, and Abl kinases were able to phosphorylate Tarp. Mutagenesis of potential tyrosines within a single tyrosine rich repeat peptide indicated that both Src and Abl kinases phosphorylate the same residues suggesting that C. trachomatis Tarp may serve as a substrate for multiple host cell kinases. Surprisingly, chemical inhibition of Src and Abl kinases prevented Tarp phosphorylation in culture and had no measurable effect on bacterial entry into host cells. PMID:18442471

Exploring the mechanistic insights of Cas scaffolding protein family member 4 with protein tyrosine kinase 2 in Alzheimer's disease by evaluating protein interactions through molecular docking and dynamic simulations.

PubMed

Hassan, Mubashir; Shahzadi, Saba; Alashwal, Hany; Zaki, Nazar; Seo, Sung-Yum; Moustafa, Ahmed A

2018-05-22

Cas scaffolding protein family member 4 and protein tyrosine kinase 2 are signaling proteins, which are involved in neuritic plaques burden, neurofibrillary tangles, and disruption of synaptic connections in Alzheimer's disease. In the current study, a computational approach was employed to explore the active binding sites of Cas scaffolding protein family member 4 and protein tyrosine kinase 2 proteins and their significant role in the activation of downstream signaling pathways. Sequential and structural analyses were performed on Cas scaffolding protein family member 4 and protein tyrosine kinase 2 to identify their core active binding sites. Molecular docking servers were used to predict the common interacting residues in both Cas scaffolding protein family member 4 and protein tyrosine kinase 2 and their involvement in Alzheimer's disease-mediated pathways. Furthermore, the results from molecular dynamic simulation experiment show the stability of targeted proteins. In addition, the generated root mean square deviations and fluctuations, solvent-accessible surface area, and gyration graphs also depict their backbone stability and compactness, respectively. A better understanding of CAS and their interconnected protein signaling cascade may help provide a treatment for Alzheimer's disease. Further, Cas scaffolding protein family member 4 could be used as a novel target for the treatment of Alzheimer's disease by inhibiting the protein tyrosine kinase 2 pathway.

Inhibition of src family kinases by a combinatorial action of 5'-AMP and small heat shock proteins, identified from the adult heart.

PubMed

Kasi, V S; Kuppuswamy, D

1999-10-01

Src family kinases are implicated in cellular proliferation and transformation. Terminally differentiated myocytes have lost the ability to proliferate, indicating the existence of a down-regulatory mechanism(s) for these mitogenic kinases. Here we show that feline cardiomyocyte lysate contains thermostable components that inhibit c-Src kinase in vitro. This inhibitory activity, present predominantly in heart tissue, involves two components acting combinatorially. After purification by sequential chromatography, one component was identified by mass and nuclear magnetic resonance spectroscopies as 5'-AMP, while the other was identified by peptide sequencing as a small heat shock protein (sHSP). 5'-AMP and to a lesser extent 5'-ADP inhibit c-Src when combined with either HSP-27 or HSP-32. Other HSPs, including alphaB-crystallin, HSP-70, and HSP-90, did not exhibit this effect. The inhibition, observed preferentially on Src family kinases and independent of the Src tyrosine phosphorylation state, occurs via a direct interaction of the c-Src catalytic domain with the inhibitory components. Our study indicates that sHSPs increase the affinity of 5'-AMP for the c-Src ATP binding site, thereby facilitating the inhibition. In vivo, elevation of ATP levels in the cardiomyocytes results in the tyrosine phosphorylation of cellular proteins including c-Src at the activatory site, and this effect is blocked when the 5'-AMP concentration is raised. Thus, this study reveals a novel role for sHSPs and 5'-AMP in the regulation of Src family kinases, presumably for the maintenance of the terminally differentiated state.

Akt-RSK-S6-kinase Signaling Networks Activated by Oncogenic Receptor Tyrosine Kinases

PubMed Central

Moritz, Albrecht; Li, Yu; Guo, Ailan; Villén, Judit; Wang, Yi; MacNeill, Joan; Kornhauser, Jon; Sprott, Kam; Zhou, Jing; Possemato, Anthony; Ren, Jian Min; Hornbeck, Peter; Cantley, Lewis C.; Gygi, Steven P.; Rush, John; Comb, Michael J.

2011-01-01

Receptor tyrosine kinases (RTKs) activate pathways mediated by serine/threonine (Ser/Thr) kinases such as the PI3K (phosphatidylinositol 3-kinase)-Akt pathway, the Ras-MAPK (mitogen-activated protein kinase)-RSK pathway, and the mTOR (mammalian target of rapamycin)-p70 S6 pathway that control important aspects of cell growth, proliferation, and survival. The Akt, RSK, and p70 S6 family of protein kinases transmit signals by phosphorylating substrates on a RxRxxS/T motif. Here, we developed a large-scale proteomic approach to identify over 200 substrates of this kinase family in cancer cell lines driven by the c-Met, epidermal growth factor receptor (EGFR), or platelet-derived growth factor receptor a (PDGFRα) RTKs. We identified a subset of proteins with RxRxxS/T sites for which phosphorylation was decreased by RTKIs as well as by inhibitors of the PI3K, mTOR, and MAPK pathways and determined the effects of siRNA directed against these substrates on cell viability. We found that phosphorylation of the protein chaperone SGTA (small glutamine-rich tetratricopeptide repeat-containing protein alpha) at Ser305 is essential for PDGFRα stabilization and cell survival in PDGFRα-dependent cancer cells. Our approach provides a new view of RTK and Akt-RSK-S6 kinase signaling, revealing many previously unidentified Akt-RSK-S6 kinase substrates that merit further consideration as targets for combination therapy with RTKIs. PMID:20736484

Selective Targeting of SH2 Domain–Phosphotyrosine Interactions of Src Family Tyrosine Kinases with Monobodies

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

Kükenshöner, Tim; Schmit, Nadine Eliane; Bouda, Emilie

The binding of Src-homology 2 (SH2) domains to phosphotyrosine (pY) sites is critical for the autoinhibition and substrate recognition of the eight Src family kinases (SFKs). The high sequence conservation of the 120 human SH2 domains poses a significant challenge to selectively perturb the interactions of even the SFK SH2 family against the rest of the SH2 domains. We have developed synthetic binding proteins, termed monobodies, for six of the SFK SH2 domains with nanomolar affinity. Most of these monobodies competed with pY ligand binding and showed strong selectivity for either the SrcA (Yes, Src, Fyn, Fgr) or SrcB subgroupmore » (Lck, Lyn, Blk, Hck). Interactome analysis of intracellularly expressed monobodies revealed that they bind SFKs but no other SH2-containing proteins. Three crystal structures of monobody–SH2 complexes unveiled different and only partly overlapping binding modes, which rationalized the observed selectivity and enabled structure-based mutagenesis to modulate inhibition mode and selectivity. In line with the critical roles of SFK SH2 domains in kinase autoinhibition and T-cell receptor signaling, monobodies binding the Src and Hck SH2 domains selectively activated respective recombinant kinases, whereas an Lck SH2-binding monobody inhibited proximal signaling events downstream of the T-cell receptor complex. Our results show that SFK SH2 domains can be targeted with unprecedented potency and selectivity using monobodies. They are excellent tools for dissecting SFK functions in normal development and signaling and to interfere with aberrant SFK signaling networks in cancer cells.« less

Redox and Src family kinase signaling control leukocyte wound attraction and neutrophil reverse migration.

PubMed

Tauzin, Sebastien; Starnes, Taylor W; Becker, Francisco Barros; Lam, Pui-ying; Huttenlocher, Anna

2014-12-08

Tissue damage induces early recruitment of neutrophils through redox-regulated Src family kinase (SFK) signaling in neutrophils. Redox-SFK signaling in epithelium is also necessary for wound resolution and tissue regeneration. How neutrophil-mediated inflammation resolves remains unclear. In this paper, we studied the interactions between macrophages and neutrophils in response to tissue damage in zebrafish and found that macrophages contact neutrophils and induce resolution via neutrophil reverse migration. We found that redox-SFK signaling through p22phox and Yes-related kinase is necessary for macrophage wound attraction and the subsequent reverse migration of neutrophils. Importantly, macrophage-specific reconstitution of p22phox revealed that macrophage redox signaling is necessary for neutrophil reverse migration. Thus, redox-SFK signaling in adjacent tissues is essential for coordinated leukocyte wound attraction and repulsion through pathways that involve contact-mediated guidance. © 2014 Tauzin et al.

Quokka: a comprehensive tool for rapid and accurate prediction of kinase family-specific phosphorylation sites in the human proteome.

PubMed

Li, Fuyi; Li, Chen; Marquez-Lago, Tatiana T; Leier, André; Akutsu, Tatsuya; Purcell, Anthony W; Smith, A Ian; Lithgow, Trevor; Daly, Roger J; Song, Jiangning; Chou, Kuo-Chen

2018-06-27

Kinase-regulated phosphorylation is a ubiquitous type of post-translational modification (PTM) in both eukaryotic and prokaryotic cells. Phosphorylation plays fundamental roles in many signalling pathways and biological processes, such as protein degradation and protein-protein interactions. Experimental studies have revealed that signalling defects caused by aberrant phosphorylation are highly associated with a variety of human diseases, especially cancers. In light of this, a number of computational methods aiming to accurately predict protein kinase family-specific or kinase-specific phosphorylation sites have been established, thereby facilitating phosphoproteomic data analysis. In this work, we present Quokka, a novel bioinformatics tool that allows users to rapidly and accurately identify human kinase family-regulated phosphorylation sites. Quokka was developed by using a variety of sequence scoring functions combined with an optimized logistic regression algorithm. We evaluated Quokka based on well-prepared up-to-date benchmark and independent test datasets, curated from the Phospho.ELM and UniProt databases, respectively. The independent test demonstrates that Quokka improves the prediction performance compared with state-of-the-art computational tools for phosphorylation prediction. In summary, our tool provides users with high-quality predicted human phosphorylation sites for hypothesis generation and biological validation. The Quokka webserver and datasets are freely available at http://quokka.erc.monash.edu/. Supplementary data are available at Bioinformatics online.

TEC Longitude Difference Using GIMS and the IRI Model

NASA Astrophysics Data System (ADS)

Natali, Maria Paula; Meza, Amalia Margarita; Mendoza, Gastón

2016-07-01

The main geomagnetic field declination has a global distribution with positive and negative values showing maximum east-west differences over North America and Oceania and minimum differences over America and Asia. Several authors study one or more of these regions using TEC data derived from GNSS observations to describe variations in TEC. They reported a pronounced longitudinal variation respect to zero magnetic declination. One of the important factors that cause the longitude difference at mid-latitude is a combined effect of the longitude variations of magnetic declination and the variations of the zonal thermospheric winds with local time. We propose to study this effect using Global Ionospheric Maps (GIMs) and the respective TEC values generated from the International Reference Ionospheric (IRI) model, during a solar cycle, applying Principal Component Analysis (PCA). Our works is focused over different local times and regions at mid-latitude. PCA involves a mathematical procedure that transforms a number of correlated variables into a number of uncorrelated variables using the data itself. The spatial structure of the ionosphere variability and its temporal evolution, together are called modes, and there are ordered according to their percentage of the variability of data from highest to lowest. In this analysis the first mode has more than the 90 % of the variability, representing the nominal behavior of the ionosphere, and the second and third modes are the more important for our analysis, because they show the strong longitudinal variation in the different regions using either GIMs or the IRI model.

Anomalous Variation in GPS TEC, Land and Ocean Parameters Prior to 3 Earthquakes

NASA Astrophysics Data System (ADS)

Yadav, Kunvar; Karia, Sheetal P.; Pathak, Kamlesh N.

2016-02-01

The present study reports the analysis of GPS TEC prior to 3 earthquakes ( M > 6.0). The earthquakes are: (1) Loyalty Island (22°36'S, 170°54'E) on 19 January 2009 ( M = 6.6), (2) Samoa Island (15°29'S, 172°5'W) on 30 August 2009 ( M = 6.6), and (3) Tohoku (38°19'N, 142°22'E) on 11 March 2011 ( M = 9.0). In an effort to search for a precursory signature we analysed the land and ocean parameters prior to the earthquakes, namely SLHF (Land) and SST (Ocean). The GPS TEC data indicate an anomalous behaviour from 1-13 days prior to earthquakes. The main purpose of this study was to explore and demonstrate the possibility of any changes in TEC, SST, and SLHF before, during and after the earthquakes which occurred near or beneath an ocean. This study may lead to better understanding of response of land, ocean, and ionosphere parameters prior to seismic activities.

Regional TEC dynamic modeling based on Slepian functions

NASA Astrophysics Data System (ADS)

Sharifi, Mohammad Ali; Farzaneh, Saeed

2015-09-01

In this work, the three-dimensional state of the ionosphere has been estimated by integrating the spherical Slepian harmonic function and Kalman filter. The spherical Slepian harmonic functions have been used to establish the observation equations because of their properties in local modeling. Spherical harmonics are poor choices to represent or analyze geophysical processes without perfect global coverage but the Slepian functions afford spatial and spectral selectivity. The Kalman filter has been utilized to perform the parameter estimation due to its suitable properties in processing the GPS measurements in the real-time mode. The proposed model has been applied to the real data obtained from the ground-based GPS observations across some portion of the IGS network in Europe. Results have been compared with the estimated TECs by the CODE, ESA, IGS centers and IRI-2012 model. The results indicated that the proposed model which takes advantage of the Slepian basis and Kalman filter is efficient and allows for the generation of the near-real-time regional TEC map.

AzTEC millimetre survey of the COSMOS field - I. Data reduction and source catalogue

NASA Astrophysics Data System (ADS)

Scott, K. S.; Austermann, J. E.; Perera, T. A.; Wilson, G. W.; Aretxaga, I.; Bock, J. J.; Hughes, D. H.; Kang, Y.; Kim, S.; Mauskopf, P. D.; Sanders, D. B.; Scoville, N.; Yun, M. S.

2008-04-01

We present a 1.1 mm wavelength imaging survey covering 0.3 deg2 in the COSMOS field. These data, obtained with the AzTEC continuum camera on the James Clerk Maxwell Telescope, were centred on a prominent large-scale structure overdensity which includes a rich X-ray cluster at z ~ 0.73. A total of 50 mm-galaxy candidates, with a significance ranging from 3.5 to 8.5σ, are extracted from the central 0.15 deg2 area which has a uniform sensitivity of ~1.3 mJybeam-1. 16 sources are detected with S/N >= 4.5, where the expected false-detection rate is zero, of which a surprisingly large number (9) have intrinsic (deboosted) fluxes >=5 mJy at 1.1 mm. Assuming the emission is dominated by radiation from dust, heated by a massive population of young, optically obscured stars, then these bright AzTEC sources have far-infrared luminosities >6 × 1012Lsolar and star formation rates >1100Msolaryr-1. Two of these nine bright AzTEC sources are found towards the extreme peripheral region of the X-ray cluster, whilst the remainder are distributed across the larger scale overdensity. We describe the AzTEC data reduction pipeline, the source-extraction algorithm, and the characterization of the source catalogue, including the completeness, flux deboosting correction, false-detection rate and the source positional uncertainty, through an extensive set of Monte Carlo simulations. We conclude with a preliminary comparison, via a stacked analysis, of the overlapping MIPS 24-μm data and radio data with this AzTEC map of the COSMOS field.

Identification of the regulatory autophosphorylation site of autophosphorylation-dependent protein kinase (auto-kinase). Evidence that auto-kinase belongs to a member of the p21-activated kinase family.

PubMed

Yu, J S; Chen, W J; Ni, M H; Chan, W H; Yang, S D

1998-08-15

Autophosphorylation-dependent protein kinase (auto-kinase) was identified from pig brain and liver on the basis of its unique autophosphorylation/activation property [Yang, Fong, Yu and Liu (1987) J. Biol. Chem. 262, 7034-7040; Yang, Chang and Soderling (1987) J. Biol. Chem. 262, 9421-9427]. Its substrate consensus sequence motif was determined as being -R-X-(X)-S*/T*-X3-S/T-. To characterize auto-kinase further, we partly sequenced the kinase purified from pig liver. The N-terminal sequence (VDGGAKTSDKQKKKAXMTDE) and two internal peptide sequences (EKLRTIV and LQNPEK/ILTP/FI) of auto-kinase were obtained. These sequences identify auto-kinase as a C-terminal catalytic fragment of p21-activated protein kinase 2 (PAK2 or gamma-PAK) lacking its N-terminal regulatory region. Auto-kinase can be recognized by an antibody raised against the C-terminal peptide of human PAK2 by immunoblotting. Furthermore the autophosphorylation site sequence of auto-kinase was successfully predicted on the basis of its substrate consensus sequence motif and the known PAK2 sequence, and was further demonstrated to be RST(P)MVGTPYWMAPEVVTR by phosphoamino acid analysis, manual Edman degradation and phosphopeptide mapping via the help of phosphorylation site analysis of a synthetic peptide corresponding to the sequence of PAK2 from residues 396 to 418. During the activation process, auto-kinase autophosphorylates mainly on a single threonine residue Thr402 (according to the sequence numbering of human PAK2). In addition, a phospho-specific antibody against a synthetic phosphopeptide containing this identified sequence was generated and shown to be able to differentially recognize the activated auto-kinase autophosphorylated at Thr402 but not the non-phosphorylated/inactive auto-kinase. Immunoblot analysis with this phospho-specific antibody further revealed that the change in phosphorylation level of Thr402 of auto-kinase was well correlated with the activity change of the kinase during both

Identification of the regulatory autophosphorylation site of autophosphorylation-dependent protein kinase (auto-kinase). Evidence that auto-kinase belongs to a member of the p21-activated kinase family.

PubMed Central

Yu, J S; Chen, W J; Ni, M H; Chan, W H; Yang, S D

1998-01-01

Autophosphorylation-dependent protein kinase (auto-kinase) was identified from pig brain and liver on the basis of its unique autophosphorylation/activation property [Yang, Fong, Yu and Liu (1987) J. Biol. Chem. 262, 7034-7040; Yang, Chang and Soderling (1987) J. Biol. Chem. 262, 9421-9427]. Its substrate consensus sequence motif was determined as being -R-X-(X)-S*/T*-X3-S/T-. To characterize auto-kinase further, we partly sequenced the kinase purified from pig liver. The N-terminal sequence (VDGGAKTSDKQKKKAXMTDE) and two internal peptide sequences (EKLRTIV and LQNPEK/ILTP/FI) of auto-kinase were obtained. These sequences identify auto-kinase as a C-terminal catalytic fragment of p21-activated protein kinase 2 (PAK2 or gamma-PAK) lacking its N-terminal regulatory region. Auto-kinase can be recognized by an antibody raised against the C-terminal peptide of human PAK2 by immunoblotting. Furthermore the autophosphorylation site sequence of auto-kinase was successfully predicted on the basis of its substrate consensus sequence motif and the known PAK2 sequence, and was further demonstrated to be RST(P)MVGTPYWMAPEVVTR by phosphoamino acid analysis, manual Edman degradation and phosphopeptide mapping via the help of phosphorylation site analysis of a synthetic peptide corresponding to the sequence of PAK2 from residues 396 to 418. During the activation process, auto-kinase autophosphorylates mainly on a single threonine residue Thr402 (according to the sequence numbering of human PAK2). In addition, a phospho-specific antibody against a synthetic phosphopeptide containing this identified sequence was generated and shown to be able to differentially recognize the activated auto-kinase autophosphorylated at Thr402 but not the non-phosphorylated/inactive auto-kinase. Immunoblot analysis with this phospho-specific antibody further revealed that the change in phosphorylation level of Thr402 of auto-kinase was well correlated with the activity change of the kinase during both

Diversity, classification and function of the plant protein kinase superfamily

PubMed Central

Lehti-Shiu, Melissa D.; Shiu, Shin-Han

2012-01-01

Eukaryotic protein kinases belong to a large superfamily with hundreds to thousands of copies and are components of essentially all cellular functions. The goals of this study are to classify protein kinases from 25 plant species and to assess their evolutionary history in conjunction with consideration of their molecular functions. The protein kinase superfamily has expanded in the flowering plant lineage, in part through recent duplications. As a result, the flowering plant protein kinase repertoire, or kinome, is in general significantly larger than other eukaryotes, ranging in size from 600 to 2500 members. This large variation in kinome size is mainly due to the expansion and contraction of a few families, particularly the receptor-like kinase/Pelle family. A number of protein kinases reside in highly conserved, low copy number families and often play broadly conserved regulatory roles in metabolism and cell division, although functions of plant homologues have often diverged from their metazoan counterparts. Members of expanded plant kinase families often have roles in plant-specific processes and some may have contributed to adaptive evolution. Nonetheless, non-adaptive explanations, such as kinase duplicate subfunctionalization and insufficient time for pseudogenization, may also contribute to the large number of seemingly functional protein kinases in plants. PMID:22889912

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

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.

SRC family kinase (SFK) inhibition reduces rhabdomyosarcoma cell growth in vitro and in vivo and triggers p38 MAP kinase-mediated differentiation

PubMed Central

Casini, Nadia; Forte, Iris Maria; Mastrogiovanni, Gianmarco; Pentimalli, Francesca; Angelucci, Adriano; Festuccia, Claudio; Tomei, Valentina; Ceccherini, Elisa; Di Marzo, Domenico; Schenone, Silvia; Botta, Maurizio; Giordano, Antonio; Indovina, Paola

2015-01-01

Recent data suggest that SRC family kinases (SFKs) could represent potential therapeutic targets for rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children. Here, we assessed the effect of a recently developed selective SFK inhibitor (a pyrazolo[3,4-d]pyrimidine derivative, called SI221) on RMS cell lines. SI221, which showed to be mainly effective against the SFK member YES, significantly reduced cell viability and induced apoptosis, without affecting non-tumor cells, such as primary human skin fibroblasts and differentiated C2C12 cells. Moreover, SI221 decreased in vitro cell migration and invasion and reduced tumor growth in a RMS xenograft model. SFK inhibition also induced muscle differentiation in RMS cells by affecting the NOTCH3 receptor-p38 mitogen-activated protein kinase (MAPK) axis, which regulates the balance between proliferation and differentiation. Overall, our findings suggest that SFK inhibition, besides reducing RMS cell growth and invasive potential, could also represent a differentiation therapeutic strategy for RMS. PMID:25762618

Caspases and Kinases in a Death Grip

PubMed Central

Kurokawa, Manabu; Kornbluth, Sally

2011-01-01

The complex process of apoptosis is orchestrated by caspases, a family of cysteine proteases with unique substrate specificities. Accumulating evidence suggests that cell death pathways are finely tuned by multiple signaling events, including direct phosphorylation of caspases, whereas kinases are often substrates of active caspases. Importantly, caspase-mediated cleavage of kinases can terminate prosurvival signaling or generate proapoptotic peptide fragments that help to execute the death program and facilitate packaging of the dying cells. Here, we review caspases as kinase substrates and kinases as caspase substrates and discuss how the balance between cell survival and cell death can be shifted through crosstalk between these two enzyme families. PMID:19737514

Observed TEC Anomalies by GNSS Sites Preceding the Aegean Sea Earthquake of 2014

NASA Astrophysics Data System (ADS)

Ulukavak, Mustafa; Yal&ccedul; ınkaya, Mualla

2016-11-01

In recent years, Total Electron Content (TEC) data, obtained from Global Navigation Satellites Systems (GNSS) receivers, has been widely used to detect seismo-ionospheric anomalies. In this study, Global Positioning System - Total Electron Content (GPS-TEC) data were used to investigate ionospheric abnormal behaviors prior to the 2014 Aegean Sea earthquake (40.305°N 25.453°E, 24 May 2014, 09:25:03 UT, Mw:6.9). The data obtained from three Continuously Operating Reference Stations in Turkey (CORS-TR) and two International GNSS Service (IGS) sites near the epicenter of the earthquake is used to detect ionospheric anomalies before the earthquake. Solar activity index (F10.7) and geomagnetic activity index (Dst), which are both related to space weather conditions, were used to analyze these pre-earthquake ionospheric anomalies. An examination of these indices indicated high solar activity between May 8 and 15, 2014. The first significant increase (positive anomalies) in Vertical Total Electron Content (VTEC) was detected on May 14, 2014 or 10 days before the earthquake. This positive anomaly can be attributed to the high solar activity. The indices do not imply high solar or geomagnetic activity after May 15, 2014. Abnormal ionospheric TEC changes (negative anomaly) were observed at all stations one day before the earthquake. These changes were lower than the lower bound by approximately 10-20 TEC unit (TECU), and may be considered as the ionospheric precursor of the 2014 Aegean Sea earthquake

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

Structural basis for the mechanism and substrate specificity of glycocyamine kinase, a phosphagen kinase family member

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

Lim, Kap; Pullalarevu, Sadhana; Surabian, Karen Talin

2010-03-12

Glycocyamine kinase (GK), a member of the phosphagen kinase family, catalyzes the Mg{sup 2+}-dependent reversible phosphoryl group transfer of the N-phosphoryl group of phosphoglycocyamine to ADP to yield glycocyamine and ATP. This reaction helps to maintain the energy homeostasis of the cell in some multicelullar organisms that encounter high and variable energy turnover. GK from the marine worm Namalycastis sp. is heterodimeric, with two homologous polypeptide chains, {alpha} and {beta}, derived from a common pre-mRNA by mutually exclusive N-terminal alternative exons. The N-terminal exon of GK{beta} encodes a peptide that is different in sequence and is 16 amino acids longermore » than that encoded by the N-terminal exon of GK{alpha}. The crystal structures of recombinant GK{alpha}{beta} and GK{beta}{beta} from Namalycastis sp. were determined at 2.6 and 2.4 {angstrom} resolution, respectively. In addition, the structure of the GK{beta}{beta} was determined at 2.3 {angstrom} resolution in complex with a transition state analogue, Mg{sup 2+}-ADP-NO{sub 3}{sup -}-glycocyamine. Consistent with the sequence homology, the GK subunits adopt the same overall fold as that of other phosphagen kinases of known structure (the homodimeric creatine kinase (CK) and the monomeric arginine kinase (AK)). As with CK, the GK N-termini mediate the dimer interface. In both heterodimeric and homodimeric GK forms, the conformations of the two N-termini are asymmetric, and the asymmetry is different than that reported previously for the homodimeric CKs from several organisms. The entire polypeptide chains of GK{alpha}{beta} are structurally defined, and the longer N-terminus of the {beta} subunit is anchored at the dimer interface. In GK{beta}{beta} the 24 N-terminal residues of one subunit and 11 N-terminal residues of the second subunit are disordered. This observation is consistent with a proposal that the GK{alpha}{beta} amino acids involved in the interface formation were

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.

Inhibition of Src Family Kinases by a Combinatorial Action of 5′-AMP and Small Heat Shock Proteins, Identified from the Adult Heart

PubMed Central

Kasi, Vijaykumar S.; Kuppuswamy, Dhandapani

1999-01-01

Src family kinases are implicated in cellular proliferation and transformation. Terminally differentiated myocytes have lost the ability to proliferate, indicating the existence of a down-regulatory mechanism(s) for these mitogenic kinases. Here we show that feline cardiomyocyte lysate contains thermostable components that inhibit c-Src kinase in vitro. This inhibitory activity, present predominantly in heart tissue, involves two components acting combinatorially. After purification by sequential chromatography, one component was identified by mass and nuclear magnetic resonance spectroscopies as 5′-AMP, while the other was identified by peptide sequencing as a small heat shock protein (sHSP). 5′-AMP and to a lesser extent 5′-ADP inhibit c-Src when combined with either HSP-27 or HSP-32. Other HSPs, including αB-crystallin, HSP-70, and HSP-90, did not exhibit this effect. The inhibition, observed preferentially on Src family kinases and independent of the Src tyrosine phosphorylation state, occurs via a direct interaction of the c-Src catalytic domain with the inhibitory components. Our study indicates that sHSPs increase the affinity of 5′-AMP for the c-Src ATP binding site, thereby facilitating the inhibition. In vivo, elevation of ATP levels in the cardiomyocytes results in the tyrosine phosphorylation of cellular proteins including c-Src at the activatory site, and this effect is blocked when the 5′-AMP concentration is raised. Thus, this study reveals a novel role for sHSPs and 5′-AMP in the regulation of Src family kinases, presumably for the maintenance of the terminally differentiated state. PMID:10490624

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.

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.

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.

Selective Targeting of SH2 Domain-Phosphotyrosine Interactions of Src Family Tyrosine Kinases with Monobodies.

PubMed

Kükenshöner, Tim; Schmit, Nadine Eliane; Bouda, Emilie; Sha, Fern; Pojer, Florence; Koide, Akiko; Seeliger, Markus; Koide, Shohei; Hantschel, Oliver

2017-05-05

The binding of Src-homology 2 (SH2) domains to phosphotyrosine (pY) sites is critical for the autoinhibition and substrate recognition of the eight Src family kinases (SFKs). The high sequence conservation of the 120 human SH2 domains poses a significant challenge to selectively perturb the interactions of even the SFK SH2 family against the rest of the SH2 domains. We have developed synthetic binding proteins, termed monobodies, for six of the SFK SH2 domains with nanomolar affinity. Most of these monobodies competed with pY ligand binding and showed strong selectivity for either the SrcA (Yes, Src, Fyn, Fgr) or SrcB subgroup (Lck, Lyn, Blk, Hck). Interactome analysis of intracellularly expressed monobodies revealed that they bind SFKs but no other SH2-containing proteins. Three crystal structures of monobody-SH2 complexes unveiled different and only partly overlapping binding modes, which rationalized the observed selectivity and enabled structure-based mutagenesis to modulate inhibition mode and selectivity. In line with the critical roles of SFK SH2 domains in kinase autoinhibition and T-cell receptor signaling, monobodies binding the Src and Hck SH2 domains selectively activated respective recombinant kinases, whereas an Lck SH2-binding monobody inhibited proximal signaling events downstream of the T-cell receptor complex. Our results show that SFK SH2 domains can be targeted with unprecedented potency and selectivity using monobodies. They are excellent tools for dissecting SFK functions in normal development and signaling and to interfere with aberrant SFK signaling networks in cancer cells. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Identification of genes from pattern formation, tyrosine kinase, and potassium channel families by DNA amplification

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

Kamb, A.; Weir, M.; Rudy, B.

1989-06-01

The study of gene family members has been aided by the isolation of related genes on the basis of DNA homology. The authors have adapted the polymerase chain reaction to screen animal genomes very rapidly and reliably for likely gene family members. Using conserved amino acid sequences to design degenerate oligonucleotide primers, they have shown that the genome of the nematode Caenorhabditis elegans contains sequences homologous to many Drosophila genes involved in pattern formation, including the segment polarity gene wingless (vertebrate int-1), and homeobox sequences characteristic of the Antennapedia, engrailed, and paired families. In addition, they have used this methodmore » to show that C. elegans contains at least five different sequences homologous to genes in the tyrosine kinase family. Lastly, they have isolated six potassium channel sequences from humans, a result that validates the utility of the method with large genomes and suggests that human potassium channel gene diversity may be extensive.« less

Galaxy evolution at high-redshift: Millimeter-wavelength surveys with the AzTEC camera

NASA Astrophysics Data System (ADS)

Scott, Kimberly S.

Galaxies detected by their thermal dust emission at submillimeter (submm) and millimeter (mm) wavelengths comprise a population of massive, intensely star-forming systems in the early Universe. These "submm/mm- galaxies", or SMGs, likely represent an important phase in the assembly and/or evolution of massive galaxies and are thought to be the progenitors of massive elliptical galaxies. While their projected number density as a function of source brightness provides key constraints on models of galaxy evolution, SMG surveys carried out over the past twelve years with the first generation of submm/mm-wavelength cameras have not imaged a large enough area to sufficient depths to provide the statistical power needed to discriminate between competing galaxy evolution scenarios. In this dissertation, we present the results from SMG surveys carried out over the past four years using the new sensitive mm-wavelength camera AzTEC. With the improved mapping speed of the AzTEC camera combined with dedicated telescope time devoted to deep, large-area extragalactic surveys, we have tripled both the area surveyed towards blank- fields (that is, regions with no known galaxy over-densities) at submm/mm wavelengths and the total number of detected SMGs. Here, we describe the properties and performance of the AzTEC instrument while operating on the James Clerk Maxwell Telescope (JCMT) and the Atacama Submillimeter Telescope Experiment (ASTE). We then present the results from two of the blank-field regions imaged with AzTEC: the JCMT/COSMOS field, which we discovered is over- dense in the number of very bright SMGs, and the ASTE survey of the Great Observatories Origins Deep-South field, which represents one of the deepest surveys ever carried out at submm/mm wavelengths. Finally, we combine the results from all of the blank-fields imaged with AzTEC while operating on the JCMT and the ASTE to calculate the most accurate measurements to date of the SMG number counts.

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

Variation of GPS-TEC in a low latitude Indian region during the year 2012 and 2013

NASA Astrophysics Data System (ADS)

Patel, Nilesh C.; Karia, Sheetal P.; Pathak, Kamlesh N.

2018-05-01

The paper is based on the ionospheric variations in terms of vertical total electron content (VTEC) for the period from January 2012 to December 2013 based on the analysis of dual frequency signals from the Global Positioning System (GPS) satellites recorded at ground stations Surat (21.16°N, 72.78°E Geog.), situated under the northern crest of the equatorial ionization anomaly region (EIA) and other three International GNSS Service (IGS) stations Bangalore (13.02°N, 77.57°E Geog.), Hyderabad (17.25°N, 78.30°E Geog.), and Lucknow (26.91°N, 80.95°E Geog.) in India. We describe the diurnal and seasonal characteristics. It was observed that GPS-TEC reaches its maximum value between 12:00 and 16:00 IST. Further, Seasonal variations of GPS-TEC is categorized into four seasons, i.e., March equinox (February, March, and April), June solstice (May, June, and July), September equinox (August, September, and October) and December solstice (November, December and January). The forenoon rate of production in Lucknow (beyond EIA crest) is faster than Bangalore, Hyderabad and Surat station. It is found that September equinox shows GPS-TEC slightly higher than the March equinox, followed by June solstice and the lowest GPS-TEC are in winter solstice at four stations. The equinoctial asymmetry clearly observed in the current study. Also GPS-TEC shows a semiannual variation.

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.

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

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.

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.

AzTEC 1.1 mm OBSERVATIONS OF THE MBM12 MOLECULAR CLOUD

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

Kim, M. J.; Kim, S.; Youn, S.

2012-02-10

We present 1.1 mm observations of the dust continuum emission from the MBM12 high-latitude molecular cloud observed with the Astronomical Thermal Emission Camera (AzTEC) mounted on the James Clerk Maxwell Telescope on Mauna Kea, Hawaii. We surveyed 6.34 deg{sup 2} centered on MBM12, making this the largest area that has ever been surveyed in this region with submillimeter and millimeter telescopes. Eight secure individual sources were detected with a signal-to-noise ratio of over 4.4. These eight AzTEC sources can be considered to be real astronomical objects compared to the other candidates based on calculations of the false detection rate. Themore » distribution of the detected 1.1 mm sources or compact 1.1 mm peaks is spatially anti-correlated with that of the 100 {mu}m emission and the {sup 12}CO emission. We detected the 1.1 mm dust continuum emitting sources associated with two classical T Tauri stars, LkH{alpha}262 and LkH{alpha}264. Observations of spectral energy distributions (SEDs) indicate that LkH{alpha}262 is likely to be Class II (pre-main-sequence star), but there are also indications that it could be a late Class I (protostar). A flared disk and a bipolar cavity in the models of Class I sources lead to more complicated SEDs. From the present AzTEC observations of the MBM12 region, it appears that other sources detected with AzTEC are likely to be extragalactic and located behind MBM12. Some of these have radio counterparts and their star formation rates are derived from a fit of the SEDs to the photometric evolution of galaxies in which the effects of a dusty interstellar medium have been included.« less

The Role of ESA TEC-QTE in the ISS Safety Process

NASA Astrophysics Data System (ADS)

Orlandi, M.; Rohr, T.; Stienstra, M. H.; Semprimoschnig, C.

2013-09-01

On the 17th of July 2000, the Materials and Processes Reciprocal Agreement was signed between NASA and ESA to define the process for selection and certification of materials used in the Space Shuttle and the International Space Station. Consecutively, on the 20th of June 2003 this agreement was extended to the Automated Transport Vehicle (ATV). It is therefore the responsibility of ESA TEC-QTE, the Materials Space Evaluation and Radiation Effects section, part of the Product Assurance and Safety Department, to ensure that all materials, parts and processes of each of the ISS payloads not only function as required but also do not pose a risk to the safety of the crew members. In this context, TEC-QTE provides qualified expertise to support the ESA Flight Safety Review and assesses safety aspects related to manned projects (materials properties, fluid system compatibility, fungus resistance). This is supported by the Materials Space Evaluation and Radiation Effects section's Materials and Electrical Components laboratory having at its disposition a range of facilities designed to perform environmental effects testing of which off-gassing tests according to ECSS-Q-ST-70-29C (equivalent to NASA STD 6001 test 7) and outgassing tests according to ECSS-Q-ST-70-02C (equivalent to ASTM-E-595). The ESA facility to perform flammability tests according to ECSS-Q-ST-70-21A (equivalent to NASA STD 6001 test1) was moved to Astrium Bremen.TEC-QTE is in charge of reviewing and approving, via RFA or MUA , all materials that do not meet safety requirements as well as COTS or CAM (black boxes) equipment.The safety process ends with the issue of the Materials Certification of the reviewed payload hardware that shows compliance with the relevant materials and processes requirements and standards.In addition to the safety related activities for the ISS, specialised TEC-QTE personnel provide measurements of the air quality inside the ATV and assess whether the toxicity index is within

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

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.

The Axl kinase domain in complex with a macrocyclic inhibitor offers first structural insights into an active TAM receptor kinase.

PubMed

Gajiwala, Ketan S; Grodsky, Neil; Bolaños, Ben; Feng, Junli; Ferre, RoseAnn; Timofeevski, Sergei; Xu, Meirong; Murray, Brion W; Johnson, Ted W; Stewart, Al

2017-09-22

The receptor tyrosine kinase family consisting of Tyro3, Axl, and Mer (TAM) is one of the most recently identified receptor tyrosine kinase families. TAM receptors are up-regulated postnatally and maintained at high levels in adults. They all play an important role in immunity, but Axl has also been implicated in cancer and therefore is a target in the discovery and development of novel therapeutics. However, of the three members of the TAM family, the Axl kinase domain is the only one that has so far eluded structure determination. To this end, using differential scanning fluorimetry and hydrogen-deuterium exchange mass spectrometry, we show here that a lower stability and greater dynamic nature of the Axl kinase domain may account for its poor crystallizability. We present the first structural characterization of the Axl kinase domain in complex with a small-molecule macrocyclic inhibitor. The Axl crystal structure revealed two distinct conformational states of the enzyme, providing a first glimpse of what an active TAM receptor kinase may look like and suggesting a potential role for the juxtamembrane region in enzyme activity. We noted that the ATP/inhibitor-binding sites of the TAM members closely resemble each other, posing a challenge for the design of a selective inhibitor. We propose that the differences in the conformational dynamics among the TAM family members could potentially be exploited to achieve inhibitor selectivity for targeted receptors. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

PCA and vTEC climatology at midnight over mid-latitude regions

NASA Astrophysics Data System (ADS)

Natali, M. P.; Meza, A.

2017-12-01

The effect of the thermospheric vertical neutral wind on vertical total electron content (vTEC) variations including longitudinal anomaly, remaining winter anomaly, mid-latitude summer night anomaly, and semiannual anomaly is studied at mid-latitude regions around zero magnetic declination at midnight during high solar activity. By using the principal component analysis (PCA) numerical technique, this work studies the spatial and temporal variations of the ionosphere at midnight over mid-latitude regions during 2000-2002. PCA is applied to a time series of global vTEC maps produced by the International Global Navigation Satellite System (GNSS) Service. Four regions were studied in particular, each located at mid-latitude and approximately centered at zero magnetic declination, with two in the northern hemisphere and two in southern hemisphere, and all are located near and far from geomagnetic poles in each case. This technique provides an effective method to analyze the main ionospheric variabilities at mid-latitudes. PCA is also applied to the vTEC computed using the International Reference Ionosphere (IRI) 2012 model, to analyze the capability of this model to represent ionospheric variabilities at mid-latitude. Also, the Horizontal Wind Model 2007 (HWM07) is used to improve our climatology interpretation, by analyzing the relationship between vTEC and thermospheric wind, both quantitatively and qualitatively. At midnight, the behavior of mean vTEC values strongly responds to vertical wind variation, experiencing a decrease of about 10-15% with the action of the positive vertical component of the field-aligned neutral wind lasting for 2 h in all regions except for Oceania. Notable results include: a significant increase toward higher latitudes during summer in the South America and Asia regions, associated with the mid-latitude summer night anomaly, and an increase toward higher latitudes in winter in the North America and Oceania regions, highlighting the

Crystal structure of the Src family kinase Hck SH3-SH2 linker regulatory region supports an SH3-dominant activation mechanism.

PubMed

Alvarado, John J; Betts, Laurie; Moroco, Jamie A; Smithgall, Thomas E; Yeh, Joanne I

2010-11-12

Most mammalian cell types depend on multiple Src family kinases (SFKs) to regulate diverse signaling pathways. Strict control of SFK activity is essential for normal cellular function, and loss of kinase regulation contributes to several forms of cancer and other diseases. Previous x-ray crystal structures of the SFKs c-Src and Hck revealed that intramolecular association of their Src homology (SH) 3 domains and SH2 kinase linker regions has a key role in down-regulation of kinase activity. However, the amino acid sequence of the Hck linker represents a suboptimal ligand for the isolated SH3 domain, suggesting that it may form the polyproline type II helical conformation required for SH3 docking only in the context of the intact structure. To test this hypothesis directly, we determined the crystal structure of a truncated Hck protein consisting of the SH2 and SH3 domains plus the linker. Despite the absence of the kinase domain, the structures and relative orientations of the SH2 and SH3 domains in this shorter protein were very similar to those observed in near full-length, down-regulated Hck. However, the SH2 kinase linker adopted a modified topology and failed to engage the SH3 domain. This new structure supports the idea that these noncatalytic regions work together as a "conformational switch" that modulates kinase activity in a manner unique to the SH3 domain and linker topologies present in the intact Hck protein. Our results also provide fresh structural insight into the facile induction of Hck activity by HIV-1 Nef and other Hck SH3 domain binding proteins and implicate the existence of innate conformational states unique to individual Src family members that "fine-tune" their sensitivities to activation by SH3-based ligands.

An Ionospheric Response to the 2013 Moore EF5 Tornad, Detected By High-Resolution GPS-TEC Observations

NASA Astrophysics Data System (ADS)

Kubota, M.; Nishioka, M.; Tsugawa, T.; Ishii, M.

2014-12-01

We observed clear concentric waves and short-period oscillations in the ionosphere after the EF5 tornado hit Moore, Oklahoma, USA, on 20 May 2013 using a dense wide-coverage ionospheric total electron content (TEC) observation in North America. These concentric waves were non-dispersive waves with a horizontal wavelength of ~120 km and a period of ~13 minutes. They were observed for more than seven hours throughout North America. TEC oscillations with a period of ~4 minutes were also observed in the south of Moore for more than eight hours. Comparison between the TEC observation and the infrared cloud image from the GOES satellite indicates that the concentric waves were caused by supercells rather than the tornados themselves. Backward ray-tracing analysis suggests that the leaking of atmospheric waves in a thermal duct excited AGWs in the ionosphere. The short-period TEC oscillation could be explained by the acoustic resonance triggered by strong long-lasting supercells. This observational result provides the first clear evidence of a severe meteorological event causing atmospheric waves propagating upward in the upper atmosphere and reaching the ionosphere.

Early Science with the Large Millimeter Telescope: CO and [C II] Emission in the z = 4.3 AzTEC J095942.9+022938 (COSMOS AzTEC-1)

NASA Astrophysics Data System (ADS)

Yun, Min S.; Aretxaga, I.; Gurwell, M. A.; Hughes, D. H.; Montaña, A.; Narayanan, G.; Rosa-González, D.; Sánchez-Argüelles, D.; Schloerb, F. P.; Snell, R. L.; Vega, O.; Wilson, G. W.; Zeballos, M.; Chavez, M.; Cybulski, R.; Díaz-Santos, T.; De La Luz, V.; Erickson, N.; Ferrusca, D.; Gim, H. B.; Heyer, M. H.; Iono, D.; Pope, A.; Rogstad, S. M.; Scott, K. S.; Souccar, K.; Terlevich, E.; Terlevich, R.; Wilner, D.; Zavala, J. A.

2015-12-01

Measuring redshifted CO line emission is an unambiguous method for obtaining an accurate redshift and total cold gas content of optically faint, dusty starburst systems. Here, we report the first successful spectroscopic redshift determination of AzTEC J095942.9+022938 (`COSMOS AzTEC-1'), the brightest 1.1 mm continuum source found in the AzTEC/James Clerk Maxwell Telescope survey (Scott et al.), through a clear detection of the redshifted CO (4-3) and CO (5-4) lines using the Redshift Search Receiver on the Large Millimeter Telescope. The CO redshift of z = 4.3420 ± 0.0004 is confirmed by the detection of the redshifted 158 μm [C II] line using the Submillimeter Array. The new redshift and Herschel photometry yield LFIR = (1.1 ± 0.1) × 1013 L⊙ and SFR ≈ 1300 M⊙ yr-1. Its molecular gas mass derived using the ultraluminous infrared galaxy conversion factor is 1.4 ± 0.2 × 1011M⊙ while the total interstellar medium mass derived from the 1.1 mm dust continuum is 3.7 ± 0.7 × 1011M⊙ assuming Td = 35 K. Our dynamical mass analysis suggests that the compact gas disc (r ≈ 1.1 kpc, inferred from dust continuum and spectral energy distribution analysis) has to be nearly face-on, providing a natural explanation for the uncommonly bright, compact stellar light seen by the HST. The [C II] line luminosity L_[C II]= 7.8± 1.1 × 10^9 L_{⊙} is remarkably high, but it is only 0.04 per cent of the total IR luminosity. AzTEC COSMOS-1 and other high redshift sources with a spatially resolved size extend the tight trend seen between [C II]/FIR ratio and ΣFIR among IR-bright galaxies reported by Díaz-Santos et al. by more than an order of magnitude, supporting the explanation that the higher intensity of the IR radiation field is responsible for the `[C II] deficiency' seen among luminous starburst galaxies.

p21-activated kinase inhibitors.

PubMed

Rudolph, Joachim; Crawford, James J; Hoeflich, Klaus P; Chernoff, Jonathan

2013-01-01

The p21-activated kinases (PAKs) are Ser/Thr kinases in the STE20 kinase family with important roles in regulating cytoskeletal organization, cell migration, and signaling. The PAK enzyme family comprises six members subdivided into two groups: Group I, represented by PAK1, 2, and 3, and Group II, represented by PAK 4, 5, and 6, based on sequence and structural homology. Individual PAK isoforms were found to be overexpressed and amplified in a variety of human cancers, and in vitro and in vivo studies using genetically engineered systems as well as small-molecule tool compounds have suggested therapeutic utility of PAKs as oncology targets. The identification of potent and kinome-selective ATP-competitive PAK inhibitors has proven challenging, likely caused by the openness and unique plasticity of the ATP-binding site of PAK enzymes. Progress in achieving increased kinase selectivity has been achieved with certain inhibitors but at the expense of increased molecular weight. Allosteric inhibitors, such as IPA-3, leverage the unique Group I PAK autoregulatory domain for selective inhibition, and this approach might provide an outlet to evade the kinase selectivity challenges observed with ATP-competitive PAK inhibitors. © 2013 Elsevier Inc. All rights reserved.

STAT3 Activation in Pressure-Overloaded Feline Myocardium: Role for Integrins and the Tyrosine Kinase BMX

PubMed Central

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

2008-01-01

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. PMID:18612371

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.

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

Mixed - Lineage Protein kinases (MLKs) in inflammation, metabolism, and other disease states.

PubMed

Craige, Siobhan M; Reif, Michaella M; Kant, Shashi

2016-09-01

Mixed lineage kinases, or MLKs, are members of the MAP kinase kinase kinase (MAP3K) family, which were originally identified among the activators of the major stress-dependent mitogen activated protein kinases (MAPKs), JNK and p38. During stress, the activation of JNK and p38 kinases targets several essential downstream substrates that react in a specific manner to the unique stressor and thus determine the fate of the cell in response to a particular challenge. Recently, the MLK family was identified as a specific modulator of JNK and p38 signaling in metabolic syndrome. Moreover, the MLK family of kinases appears to be involved in a very wide spectrum of disorders. This review discusses the newly identified functions of MLKs in multiple diseases including metabolic disorders, inflammation, cancer, and neurological diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Adjustments of the TaD electron density reconstruction model with GNSS-TEC parameters for operational application purposes

NASA Astrophysics Data System (ADS)

Kutiev, Ivan; Marinov, Pencho; Fidanova, Stefka; Belehaki, Anna; Tsagouri, Ioanna

2012-12-01

Validation results on the latest version of TaD model (TaDv2) show realistic reconstruction of the electron density profiles (EDPs) with an average error of 3 TECU, similar to the error obtained from GNSS-TEC calculated paremeters. The work presented here has the aim to further improve the accuracy of the TaD topside reconstruction, adjusting the TEC parameter calculated from TaD model with the TEC parameter calculated by GNSS transmitting RINEX files provided by receivers co-located with the Digisondes. The performance of the new version is tested during a storm period demonstrating further improvements in respect to the previous version. Statistical comparison of modeled and observed TEC confirms the validity of the proposed adjustment. A significant benefit of the proposed upgrade is that it facilitates the real-time implementation of TaD. The model needs a reliable measure of the scale height at the peak height, which is supposed to be provided by Digisondes. Oftenly, the automatic scaling software fails to correctly calculate the scale height at the peak, Hm, due to interferences in the receiving signal. Consequently the model estimated topside scale height is wrongly calculated leading to unrealistic results for the modeled EDP. The proposed TEC adjustment forces the model to correctly reproduce the topside scale height, despite the inaccurate values of Hm. This adjustment is very important for the application of TaD in an operational environment.

The anthraquinone emodin inhibits the non-exported FIKK kinase from Plasmodium falciparum.

PubMed

Lin, Benjamin C; Harris, Darcy R; Kirkman, Lucy M D; Perez, Astrid M; Qian, Yiwen; Schermerhorn, Janse T; Hong, Min Y; Winston, Dennis S; Xu, Lingyin; Lieber, Alexander M; Hamilton, Matthew; Brandt, Gabriel S

2017-12-01

The FIKK family of kinases is unique to parasites of the Apicomplexan order, which includes all malaria parasites. Plasmodium falciparum, the most virulent form of human malaria, has a family of 19 FIKK kinases, most of which are exported into the host red blood cell during malaria infection. Here, we confirm that FIKK 8 is a non-exported member of the FIKK kinase family. Through expression and purification of the recombinant kinase domain, we establish that emodin is a relatively high-affinity (IC 50 =2μM) inhibitor of PfFk8. Closely related anthraquinones do not inhibit PfFk8, suggesting that the particular substitution pattern of emodin is critical to the inhibitory pharmacophore. This first report of a P. falciparum FIKK kinase inhibitor lays the groundwork for developing specific inhibitors of the various members of the FIKK kinase family in order to probe their physiological function. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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.

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.

Modeling of Heat and Mass Transfer in a TEC-Driven Lyophilizer

NASA Technical Reports Server (NTRS)

Yuan, Zeng-Guang; Hegde, Uday; Litwiller, Eric; Flynn, Michael; Fisher, John

2006-01-01

Dewatering of wet waste during space exploration missions is important for crew safety as it stabilizes the waste. It may also be used to recover water and serve as a preconditioning step for waste compaction. A thermoelectric cooler (TEC)-driven lyophilizer is under development at NASA Ames Research Center for this purpose. It has three major components: (i) an evaporator section where water vapor sublimes from the frozen waste, (ii) a condenser section where this water vapor deposits as ice, and (iii) a TEC section which serves as a heat pump to transfer heat from the condenser to the evaporator. This paper analyses the heat and mass transfer processes in the lyophilizer in an effort to understand the ice formation behavior in the condenser. The analysis is supported by experimental observations of ice formation patterns in two different condenser units.

(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 TEC19. Three of our detected SMGs (AzTEC21, 27, and 28; which corresponds to 20%) are marginally resolved at our angular resolution, and these sources are found to have elongated or clumpy morphologies and/or multiple components. Using optical to near-infrared photometric redshifts, available spectroscopic redshifts, and redshifts estimated from the radio-to-submm spectral index we infer a median redshift of tilde{z}= 3.20 ± 0.25 for our sample. To study the overall multiplicity and redshift distribution of flux-limited samples of SMGs we combined these sources with the 15 brightest JCMT/AzTEC SMGs detected at 1.1 mm, AzTEC1-15, and studied previously. This constitutes a complete, flux- and S/N-limited 1.1-mm selected sample. We find that the median redshift for the 15 brightest JCMT/AzTEC SMGs (tilde{z}= 3.05 ± 0.44) is consistent with that for AzTEC16-30. This conforms to recent observational findings that SMGs do not exhibit any significant trend between the redshift and (sub)mm flux density. For the combined AzTEC1-30 sample we derive a median redshift of tilde{z}= 3.17 ± 0.27, consistent with previous results based on mm