Homogenized radiosonde record at station Ny-Ålesund, Spitsbergen, 1993-2014

Radiosonde measurements obtained at the Arctic site Ny-Ålesund (78.9° N, 11.9° E), Svalbard, from 1993 to 2014 have been homogenized accounting for instrumentation discontinuities by correcting known errors in the manufacturer provided profiles. From the homogenized data record, the first Ny-Ålesund upper-air climatology of wind, temperature and humidity is presented, forming the background for the analysis of changes during the 22-year period. Particularly during the winter season, a strong increase in atmospheric temperature and humidity is observed, with a significant warming of the free troposphere in January and February up to 3 K per decade. This winter warming is even more pronounced in the boundary layer below 1 km, presumably amplified by mesoscale processes including e.g. orographic effects or the boundary layer capping inversion. Though the largest contribution to the increasing atmospheric water vapour column in winter originates from the lowermost 2 km, no increase in the contribution by specific humidity inversions is detected. Instead, we find an increase in the humidity content of the large scale background humidity profiles. At the same time, the tropospheric flow in winter is found to occur less frequent from northerly directions and to the same amount more frequent from the South. We conclude that changes in the atmospheric circulation lead to an enhanced advection of warm and moist air from lower latitudes to the Svalbard region in the winter season, causing the warming and moistening of the atmospheric column above Ny-Ålesund.

Diseño optimizado y caracterización de hormigones autocompactantes reforzados con fibra polimérica de alto módulo

Los hormigones autocompactantes suponen una alternativa de ejecución fácil y rápida, que garantiza una puesta en obra de calidad y una mejora de las prestaciones mecánicas a igualdad de contenido de cemento. Por otro lado, los hormigones reforzados con fibra de carácter estructural son cada vez más demandados ya que, en el caso de contar con el tipo y proporción de fibra adecuado, permiten la sustitución total o parcial del armado convencional de acero. Este estudio persigue el diseño optimizado de hormigones autocompactantes reforzados con fibra polimérica de alto módulo para la ejecución de obras de rehabilitación, como las llevadas a cabo en las bóvedas de la catedral de San Cristóbal de la Laguna, de tal manera que, manteniendo la característica de autocompactabilidad y sin perjuicio de la durabilidad, dicho hormigón presente un comportamiento post-fisuración que cumpla con las especificaciones del Anejo 14 de la EHE-08, en lo que se refiere a los valores mínimos de resistencia característica residual a tracción por flexión fR,1,k y fR,3,k , de tal forma que la fibra alcance la consideración de estructural, lo que supondría una alternativa técnica al refuerzo con fibra de acero que permitiría la sustitución parcial o total de la armadura de acero.

Alloantigen-induced unresponsiveness in cord blood T lymphocytes is associated with defective activation of Ras

Human umbilical cord blood T lymphocytes (CBTL) respond to primary allostimulation but they do not proliferate upon rechallenge with alloantigen. Using PKH-26-labeled cells created a proliferative block that was observed only in CBTL that have divided during primary stimulation (PKH-26dim) but not in unstimulated (PKH-26bright) CBTL. CBTL’s secondary unresponsiveness resembles anergy and can be overcome by treatment with phorbol myristate acetate (PMA) and ionomycin or by high doses (50–100 units/ml) of interleukin 2. Addition of interleukin 2 to the primary cultures does not prevent the induction of secondary unresponsiveness. Defective Ras activation is detected in PKH-26dim CBTL during secondary response to alloantigen or after antibody-mediated T cell receptor stimulation whereas Ras is activated and proliferation is induced in CBTL during primary alloantigenic stimulation. Upon stimulation with PMA plus ionomycin, PMA plus alloantigen, but not alloantigen plus ionomycin, Ras is activated in PKH-26dim CBTL, and the block in proliferation is overcome. Correction of PKH-26dim CBTL’s proliferative defect correlates with PMA-induced Ras activation, suggesting a defect in the signaling pathway leading to Ras. Ras-independent signals, necessary but not sufficient to induce PKH-26dim CBTL proliferation, are provided by alloantigen exposure, as evident by the ability of PMA plus alloantigen but not PMA alone to overcome the proliferative block. Functional signal transduction through CD28 in PKH-26dim CBTL is supported by detectable CD28-mediated PI-3 kinase activation after PKH-26dim CBTL’s exposure to alloantigen or CD28 cross-linking. These results suggest that defective activation of Ras plays a key role in PKH-26dim CBTL’s secondary unresponsiveness and point to a defect along the T cell receptor rather than the CD28 signaling pathway.

Regulation of the Actin Cytoskeleton by Thrombin in Human Endothelial Cells: Role of Rho Proteins in Endothelial Barrier Function

Endothelial barrier function is regulated at the cellular level by cytoskeletal-dependent anchoring and retracting forces. In the present study we have examined the signal transduction pathways underlying agonist-stimulated reorganization of the actin cytoskeleton in human umbilical vein endothelial cells. Receptor activation by thrombin, or the thrombin receptor (proteinase-activated receptor 1) agonist peptide, leads to an early increase in stress fiber formation followed by cortical actin accumulation and cell rounding. Selective inhibition of thrombin-stimulated signaling systems, including Gi/o (pertussis toxin sensitive), p42/p44, and p38 MAP kinase cascades, Src family kinases, PI-3 kinase, or S6 kinase pathways had no effect on the thrombin response. In contrast, staurosporine and KT5926, an inhibitor of myosin light chain kinase, effectively blocked thrombin-induced cell rounding and retraction. The contribution of Rho to these effects was analyzed by using bacterial toxins that either activate or inhibit the GTPase. Escherichia coli cytotoxic necrotizing factor 1, an activator of Rho, induced the appearance of dense actin cables across cells without perturbing monolayer integrity. Accordingly, lysophosphatidic acid, an activator of Rho-dependent stress fiber formation in fibroblasts, led to reorganization of polymerized actin into stress fibers but failed to induce cell rounding. Inhibition of Rho with Clostridium botulinum exoenzyme C3 fused to the B fragment of diphtheria toxin caused loss of stress fibers with only partial attenuation of thrombin-induced cell rounding. The implication of Rac and Cdc42 was analyzed in transient transfection experiments using either constitutively active (V12) or dominant-interfering (N17) mutants. Expression of RacV12 mimicked the effect of thrombin on cell rounding, and RacN17 blocked the response to thrombin, whereas Cdc42 mutants were without effect. These observations suggest that Rho is involved in the maintenance of endothelial barrier function and Rac participates in cytoskeletal remodeling by thrombin in human umbilical vein endothelial cells.

Exercise-induced changes in expression and activity of proteins involved in insulin signal transduction in skeletal muscle: Differential effects on insulin-receptor substrates 1 and 2

Level of physical activity is linked to improved glucose homeostasis. We determined whether exercise alters the expression and/or activity of proteins involved in insulin-signal transduction in skeletal muscle. Wistar rats swam 6 h per day for 1 or 5 days. Epitrochlearis muscles were excised 16 h after the last exercise bout, and were incubated with or without insulin (120 nM). Insulin-stimulated glucose transport increased 30% and 50% after 1 and 5 days of exercise, respectively. Glycogen content increased 2- and 4-fold after 1 and 5 days of exercise, with no change in glycogen synthase expression. Protein expression of the glucose transporter GLUT4 and the insulin receptor increased 2-fold after 1 day, with no further change after 5 days of exercise. Insulin-stimulated receptor tyrosine phosphorylation increased 2-fold after 5 days of exercise. Insulin-stimulated tyrosine phosphorylation of insulin-receptor substrate (IRS) 1 and associated phosphatidylinositol (PI) 3-kinase activity increased 2.5- and 3.5-fold after 1 and 5 days of exercise, despite reduced (50%) IRS-1 protein content after 5 days of exercise. After 1 day of exercise, IRS-2 protein expression increased 2.6-fold and basal and insulin-stimulated IRS-2 associated PI 3-kinase activity increased 2.8-fold and 9-fold, respectively. In contrast to IRS-1, IRS-2 expression and associated PI 3-kinase activity normalized to sedentary levels after 5 days of exercise. Insulin-stimulated Akt phosphorylation increased 5-fold after 5 days of exercise. In conclusion, increased insulin-stimulated glucose transport after exercise is not limited to increased GLUT4 expression. Exercise leads to increased expression and function of several proteins involved in insulin-signal transduction. Furthermore, the differential response of IRS-1 and IRS-2 to exercise suggests that these molecules have specialized, rather than redundant, roles in insulin signaling in skeletal muscle.

PTEN/MMAC1/TEP1 suppresses the tumorigenicity and induces G1 cell cycle arrest in human glioblastoma cells

PTEN/MMAC1/TEP1 is a tumor suppressor that possesses intrinsic phosphatase activity. Deletions or mutations of its encoding gene are associated with a variety of human cancers. However, very little is known about the molecular mechanisms by which this important tumor suppressor regulates cell growth. Here, we show that PTEN expression potently suppressed the growth and tumorigenicity of human glioblastoma U87MG cells. The growth suppression activity of PTEN was mediated by its ability to block cell cycle progression in the G1 phase. Such an arrest correlated with a significant increase of the cell cycle kinase inhibitor p27KIP1 and a concomitant decrease in the activities of the G1 cyclin-dependent kinases. PTEN expression also led to the inhibition of Akt/protein kinase B, a serine-threonine kinase activated by the phosphatidylinositol 3-kinase (PI 3-kinase) signaling pathway. In addition, the effect of PTEN on p27KIP1 and the cell cycle can be mimicked by treatment of U87MG cells with LY294002, a selective inhibitor of PI 3-kinase. Taken together, our studies suggest that the PTEN tumor suppressor modulates G1 cell cycle progression through negatively regulating the PI 3-kinase/Akt signaling pathway, and one critical target of this signaling process is the cyclin-dependent kinase inhibitor p27KIP1.

Critical role for the docking-protein FRS2α in FGF receptor-mediated signal transduction pathways

The docking protein FRS2α has been implicated as a mediator of signaling via fibroblast growth factor receptors (FGFRs). We have demonstrated that targeted disruption of FRS2α gene causes severe impairment in mouse development resulting in embryonal lethality at E7.0–E7.5. Experiments with FRS2α-deficient fibroblasts demonstrate that FRS2α plays a critical role in FGF-induced mitogen-activated protein (MAP) kinase stimulation, phosphatidylinositol-3 (PI-3) kinase activation, chemotactic response, and cell proliferation. Following FGF stimulation, tyrosine phosphorylated FRS2α functions as a site for coordinated assembly of a multiprotein complex that includes Gab1 and the effector proteins that are recruited by this docking protein. Furthermore, we demonstrate that different tyrosine phosphorylation sites on FRS2α are responsible for mediating different FGF-induced biological responses. These experiments establish the central role of FRS2α in signaling via FGFRs and demonstrate that FRS2α mediates multiple FGFR-dependent signaling pathways critical for embryonic development.

Cross-talk between the insulin and angiotensin signaling systems.

Angiotensin II (AII), acting via its G-protein linked receptor, is an important regulator of cardiac, vascular, and renal function. Following injection of AII into rats, we find that there is also a rapid tyrosine phosphorylation of the major insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) in the heart. This phenomenon appears to involve JAK2 tyrosine kinase, which associates with the AT1 receptor and IRS-1/IRS-2 after AII stimulation. AII-induced phosphorylation leads to binding of phosphatidylinositol 3-kinase (PI 3-kinase) to IRS-1 and IRS-2; however, in contrast to other ligands, AII injection results in an acute inhibition of both basal and insulin-stimulated PI 3-kinase activity. The latter occurs without any reduction in insulin receptor or IRS phosphorylation or in the interaction of the p85 and p110 subunits of PI 3-kinase with each other or with IRS-1/IRS-2. These effects of AII are inhibited by AT1 receptor antagonists. Thus, there is direct cross-talk between insulin and AII signaling pathways at the level of both tyrosine phosphorylation and PI 3-kinase activation. These interactions may play an important role in the association of insulin resistance, hypertension, and cardiovascular disease.

Activation and phosphorylation of a pleckstrin homology domain containing protein kinase (RAC-PK/PKB) promoted by serum and protein phosphatase inhibitors.

Treatment of quiescent Swiss 3T3 fibroblasts with serum, or with the phosphatase inhibitors okadaic acid and vanadate, induced a 2- to 11-fold activation of the serine/ threonine RAC protein kinase (RAC-PK). Kinase activation was accompanied by decreased mobility of RAC-PK on SDS/PAGE such that three electrophoretic species (a to c) of the kinase were detected by immunoblot analysis, indicative of differentially phosphorylated forms. Addition of vanadate to arrested cells increased the RAC-PK phosphorylation level 3-to 4-fold. Unstimulated RAC-PK was phosphorylated predominantly on serine, whereas the activated kinase was phosphorylated on both serine and threonine residues. Treatment of RAC-PK in vitro with protein phosphatase 2A led to kinase inactivation and an increase in electrophoretic mobility. Deletion of the N-terminal region containing the pleckstrin homology domain did not affect RAC-PK activation by okadaic acid, but it reduced vanadate-stimulated activity and also blocked the serum-induced activation. Deletion of the serine/threonine rich C-terminal region impaired both RAC-PKalpha basal and vanadate-stimulated activity. Studies using a kinase-deficient mutant indicated that autophosphorylation is not involved in RAC-PKalpha activation. Stimulation of RAC-PK activity and electrophoretic mobility changes induced by serum were sensitive to wortmannin. Taken together the results suggest that RAC-PK is a component of a signaling pathway regulated by phosphatidylinositol (PI) 3-kinase, whose action is required for RAC-PK activation by phosphorylation.

Nessy 7.0: entorno de inyección de fallos para Artix-7

El hardware reconfigurable es una tecnología emergente en aplicaciones espaciales.Debido a las características de este hardware, pues su configuración lógica queda almacenada en memoria RAM estática, es susceptible de diversos errores que pueden ocurrir con mayor frecuencia cuando es expuesta a entornos de mayor radiación, como en misiones de exploración espacial. Entre estos se encuentran los llamados SEU o Single Event Upset, y suelen ser generados por partículas cósmicas, pues pueden tener la capacidad de descargar un transistor y de este modo alterar un valor lógico en memoria, y por tanto la configuración lógica del circuito. Por ello que surge la necesidad de desarrollar técnicas que permitan estudiar las vulnerabilidades de diversos circuitos, de forma económica y rápida, además de técnicas de protección de los mismos. En este proyecto nos centraremos en desarrollar una herramienta con este propósito, Nessy 7.0. La plataforma nos permitirá emular, detectar y analizar posibles errores causados por la radiación en los sistemas digitales. Para ello utilizaremos como dispositivo controlador, una Raspberry Pi 3, que contendrá la herramienta principal, y controlará y se comunicará con la FPGA que implementará el diseño a testear, en este caso una placa Nexys 4 DDR con una FPGA Artix-7. Finalmente evaluaremos un par de circuitos con la plataforma.

Textural Characterization of Micro- and Mesoporous Carbons Using Combined Gas Adsorption and n-Nonane Preadsorption

Porous carbon and carbide materials with different structures were characterized using adsorption of nitrogen at 77.4 K before and after preadsorption of n-nonane. The selective blocking of the microporosity with n-nonane shows that ordered mesoporous silicon carbide material (OM-SiC) is almost exclusively mesoporous whereas the ordered mesoporous carbon CMK-3 contains a significant amount of micropores (25%). The insertion of micropores into OM-SiC using selective extraction of silicon by hot chlorine gas leads to the formation of ordered mesoporous carbide-derived carbon (OM-CDC) with a hierarchical pore structure and significantly higher micropore volume as compared to CMK-3, whereas a CDC material from a nonporous precursor is exclusively microporous. Volumes of narrow micropores, calculated by adsorption of carbon dioxide at 273 K, are in linear correlation with the volumes blocked by n-nonane. Argon adsorption measurements at 87.3 K allow for precise and reliable calculation of the pore size distribution of the materials using density functional theory (DFT) methods.

Mineralogy of ODP Hole 117-722B (Appendix)

Bulk mineralogy of the terrigenous fraction of 99 samples from ODP Site 722 on the Owen Ridge, western Arabian Sea, has been determined by x-ray diffraction, using an internal standard method. The sampling interval, approximately 4.3 k.y., provides a detailed mineralogic record for the past 500 k.y. Previous studies have identified important modern continental sediment sources and the mineral assemblages presently derived from each. These studies have also demonstrated that most of this material is supplied by southwest and northwest winds during the summer monsoon. A variety of marine and terrestrial records and general circulation model (GCM) simulations have indicated the importance of monsoonal circulation during the Pleistocene and Holocene and have demonstrated increased aridity during glacial times and increased humidity during inter glacials. The mineralogic data generated here were used to investigate variations in source area weathering conditions during these environmental changes. Terrigenous minerals present include smectite, illite, palygorskite, kaolinite, chlorite, quartz, plagioclase feldspar, and dolomite. This mineralogy is consistent with the compositions of source areas presently supplying sediment to the Arabian Sea. An R-mode factor analysis has identified four mineral assemblages present throughout the past 500 k.y.: quartz/chlorite/dolomite (Factor 1), kaolinite/plagioclase/illite (Factor 2), smectite (Factor 3), and palygorskite/dolomite (Factor 4). Chlorite, illite, and palygorskite are extremely susceptible to chemical weathering, and a spectral comparison of these factors with the eolian mass accumulation rate (MAR) record from Hole 722B (an index of dust source area aridity) indicates that Factors 1, 2, and 4 are directly related to changes in aridity. Because of these characteristics, Factors 1,2, and 4 are interpreted to originate from arid source regions. Factor 3 is interpreted to record more humid source conditions. Time-series of scores for the four factors are dominated by short-term (10-100 k.y.) variability, and do not correlate well to glacial/interglacial fluctuations in the time domain. These characteristics suggest that local climatic shifts were complex, and that equilibrium weathering assemblages did not develop immediately after climatic change. Spectral analysis of factor scores identifies peaks at or near the primary Milankovitch frequencies for all factors. Factor 1 (quartz/chlorite/dolomite), Factor 2 (kaolinite/plagioclase/illite), and Factor 4 (illite/palygorskite) are coherent and in phase with the MAR record over the 23, 41, and 100 k.y. bands, respectively. The reasons for coherency at single Milankovitch frequencies are not known, but may include differences in the susceptibilities of minerals to varying time scales of weathering and/or preferential development of suitable continental source environments by climatic changes at the various Milankovitch frequencies.

Piano concerti. [music] : [no. 1-28] /

Cover title.

Sonaten für Klavier und Violine /

1. K.293d (305)- 2. K.293c (303)- 3. K.300ℓ (306)- 4. K.300c (304)-5. K.293b (302)- 6. K.293a (301)- 7. K.374d (376)- 8. K.296.- 9. K.374e (377)-10. K.317d (378)- 11. K.373a (379)- 12. K.374f (380)- 13. K.385e (402)- 14. K.570.- 15. K.454.- 16. K.481.- 17. K.526.- 18. K.547.- 19. K.385c (403)

The bibliographer's manual of English literature containing an account of rare, curious, and useful books, published in or relating to Great Britain and Ireland, from the invention of printing; with bibliographical and critical notices, collations of the rarer articles, and the prices at which they have been sold in the present century.

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