951 resultados para sliding-blocks


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We have previously identified tyrosine-537 as a constitutively phosphorylated site on the human estrogen receptor (hER). A 12-amino acid phosphotyrosyl peptide containing a selected sequence surrounding tyrosine-537 was used to investigate the function of phosphotyrosine-537. The phosphotyrosyl peptide completely blocked the binding of the hER to an estrogen response element (ERE) in a gel mobility shift assay. Neither the nonphosphorylated tyrosyl peptide nor an unrelated phosphotyrosyl peptide previously shown to inhibit the signal transducers and activators of transcription factor (STAT) blocked binding of the hER to the ERE. The hER phosphotyrosyl peptide was shown by molecular sizing chromatography to dissociate the hER dimer into monomers. The hER specifically bound the 32P-labeled phosphotyrosyl peptide, indicating that the inhibition of ERE binding was caused by the phosphotyrosyl peptide binding directly to the hER and blocking dimerization. These data suggest that the phosphorylation of tyrosine-537 is a necessary step for the formation of the hER dimer. In addition, we propose that the dimerization of the hER occurs by a previously unrecognized Src homology 2 domain (SH2)-like phosphotyrosyl coupling mechanism. Consequently, the phosphotyrosyl peptide represents a class of antagonists that inhibits estrogen action by a mechanism other than interacting with the receptor's hormone binding site.

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The localization of sites of memory formation within the mammalian brain has proven to be a formidable task even for simple forms of learning and memory. Recent studies have demonstrated that reversibly inactivating a localized region of cerebellum, including the dorsal anterior interpositus nucleus, completely prevents acquisition of the conditioned eye-blink response with no effect upon subsequent learning without inactivation. This result indicates that the memory trace for this type of learning is located either (i) within this inactivated region of cerebellum or (ii) within some structure(s) efferent from the cerebellum to which output from the interpositus nucleus ultimately projects. To distinguish between these possibilities, two groups of rabbits were conditioned (by using two conditioning stimuli) while the output fibers of the interpositus (the superior cerebellar peduncle) were reversibly blocked with microinjections of the sodium channel blocker tetrodotoxin. Rabbits performed no conditioned responses during this inactivation training. However, training after inactivation revealed that the rabbits (trained with either conditioned stimulus) had fully learned the response during the previous inactivation training. Cerebellar output, therefore, does not appear to be essential for acquisition of the learned response. This result, coupled with the fact that inactivation of the appropriate region of cerebellum completely prevents learning, provides compelling evidence supporting the hypothesis that the essential memory trace for the classically conditioned eye-blink response is localized within the cerebellum.

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One of the more intriguing aspects of transforming growth factor beta 1 (TGF beta 1) is its ability to function as both a mitogenic factor for certain mesenchymal cells and a potent growth inhibitor of lymphoid, endothelial, and epithelial cells. Data are presented indicating that c-myc may play a pivotal role in both the mitogenic and antiproliferative actions of TGF beta 1. In agreement with previous studies using C3H/10T1/2 fibroblasts constitutively expressing an exogenous c-myc cDNA, we show that AKR-2B fibroblasts expressing a chimeric estrogen-inducible form of c-myc (mycER) are able to form colonies in soft agar in the presence of TGF beta 1 only when c-myc is activated by hormone. Whereas these findings support a synergistic role for c-myc in mitogenic responses to TGF beta 1, we also find that c-myc can antagonize the growth-inhibitory response to TGF beta 1. Mouse keratinocytes (BALB/MK), which are normally growth-arrested by TGF beta 1, are rendered insensitive to the growth-inhibitory effects of TGF beta 1 upon mycER activation. This ability of mycER activation to block TGF beta 1-induced growth arrest was found to occur only when the fusion protein was induced with hormone in the early part of G1. Addition of estradiol late in G1 had no suppressive effect on TGF beta 1-induced growth inhibition.

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In this work, new coordination polymers based on two different classes of synthons are presented. In addition, manganese-based metallacrowns of magnetic interest are studied, both in the solid state and in solution. Firstly, functionalized bispyrazolylmethane derivatives are employed as bridging ligands for the establishment of silver-based coordination polymers; the influence of the substituent groups and of the counterions on the supramolecular packing is also investigated. Secondly, the use of metallacrown (MC) complexes as building blocks for porous coordination polymers is discussed. The design of a new metallacrown species is presented, which shows the tendency of aggregating in the solid state to form coordination polymers. Two new coordination polymers are indeed reported, of which one is the first MC-based permanently porous coordination network ever presented. The solid resists solvent evacuation and exhibits gas uptake ability. Furthermore, the isolation and characterization of a new metallacryptate species based on manganese ions is described. The metal-rich structure comprises nine Mn(II)/Mn(III) ions and presents an inverse metallacrown core subunit that binds a μ3-O2- ion. The metallacryptate is isolated in high yields and stable in solution. Lastly, a family of 3d-4f heterometallic metallacrowns is characterized in solution by means of UV-Vis spectrophotometry and of paramagnetically shifted 1H-NMR. The lanthanide-induced shifts observed in the spectra are employed to describe the molecules behaviour in solution and are qualitatively related to the magnetic properties of the compounds.

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The present thesis is focused on the development of a thorough mathematical modelling and computational solution framework aimed at the numerical simulation of journal and sliding bearing systems operating under a wide range of lubrication regimes (mixed, elastohydrodynamic and full film lubrication regimes) and working conditions (static, quasi-static and transient conditions). The fluid flow effects have been considered in terms of the Isothermal Generalized Equation of the Mechanics of the Viscous Thin Films (Reynolds equation), along with the massconserving p-Ø Elrod-Adams cavitation model that accordingly ensures the so-called JFO complementary boundary conditions for fluid film rupture. The variation of the lubricant rheological properties due to the viscous-pressure (Barus and Roelands equations), viscous-shear-thinning (Eyring and Carreau-Yasuda equations) and density-pressure (Dowson-Higginson equation) relationships have also been taken into account in the overall modelling. Generic models have been derived for the aforementioned bearing components in order to enable their applications in general multibody dynamic systems (MDS), and by including the effects of angular misalignments, superficial geometric defects (form/waviness deviations, EHL deformations, etc.) and axial motion. The bearing exibility (conformal EHL) has been incorporated by means of FEM model reduction (or condensation) techniques. The macroscopic in fluence of the mixedlubrication phenomena have been included into the modelling by the stochastic Patir and Cheng average ow model and the Greenwood-Williamson/Greenwood-Tripp formulations for rough contacts. Furthermore, a deterministic mixed-lubrication model with inter-asperity cavitation has also been proposed for full-scale simulations in the microscopic (roughness) level. According to the extensive mathematical modelling background established, three significant contributions have been accomplished. Firstly, a general numerical solution for the Reynolds lubrication equation with the mass-conserving p - Ø cavitation model has been developed based on the hybridtype Element-Based Finite Volume Method (EbFVM). This new solution scheme allows solving lubrication problems with complex geometries to be discretized by unstructured grids. The numerical method was validated in agreement with several example cases from the literature, and further used in numerical experiments to explore its exibility in coping with irregular meshes for reducing the number of nodes required in the solution of textured sliding bearings. Secondly, novel robust partitioned techniques, namely: Fixed Point Gauss-Seidel Method (PGMF), Point Gauss-Seidel Method with Aitken Acceleration (PGMA) and Interface Quasi-Newton Method with Inverse Jacobian from Least-Squares approximation (IQN-ILS), commonly adopted for solving uid-structure interaction problems have been introduced in the context of tribological simulations, particularly for the coupled calculation of dynamic conformal EHL contacts. The performance of such partitioned methods was evaluated according to simulations of dynamically loaded connecting-rod big-end bearings of both heavy-duty and high-speed engines. Finally, the proposed deterministic mixed-lubrication modelling was applied to investigate the in fluence of the cylinder liner wear after a 100h dynamometer engine test on the hydrodynamic pressure generation and friction of Twin-Land Oil Control Rings.

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The bromonium-promoted cyclization of conjugated aminodienes is described. The reaction proceeds smoothly in the presence of N-bromosuccinimide as halonium promoter, and using N-tosyl-protected aminodienes as substrates, to give the corresponding halocyclization products in high yields and with high diastereoselectivities. It can be envisaged that the formation of these products is the result of an SN2′-type ring-opening of a terminal bromonium intermediate in a 5-exo-trig or 6-exo-trig cyclization mode. The presence of an allyl bromide moiety in the haloamination products makes these molecules highly attractive from a synthetic point of view, as it opens the way for further transformations. Thus, allylic substitution reactions with different nucleophiles (acetate, azide, cyanide, and malonate), palladium-catalysed Suzuki coupling, and silver-mediated bromine displacement reactions were carried out successfully.

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This layer is a georeferenced raster image of the historic paper map entitled: New Orleans, Louisiana, by census tracts and blocks: 1960. It was published by The Census Bureau ca. 1960. Scale [ca. 1:17,500]. This layer is image 2 of 2 total images of the two sheet source map. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Louisiana State Plane Coordinate System, South NAD83 (in Feet) (Fipszone 1702). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, or other information associated with the principal map. This map shows features such as Census block and tract numbers and boundaries, roads, canals, drainage, and more. Includes inset and legend. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

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This layer is a georeferenced raster image of the historic paper map entitled: New Orleans, Louisiana, by census tracts and blocks: 1960. It was published by The Census Bureau ca. 1960. Scale [ca. 1:17,500]. This layer is image 1 of 2 total images of the two sheet source map. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Louisiana State Plane Coordinate System, South NAD83 (in Feet) (Fipszone 1702). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, or other information associated with the principal map. This map shows features such as Census block and tract numbers and boundaries, roads, canals, drainage, and more. Includes inset and legend. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

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The goal of accession to the European Convention of Human Rights (ECHR) is to place the EU under the external oversight of the specialised court in Strasbourg. But in its Opinion of 18 December 2014 the Luxembourg-based European Court of Justice ruled that the draft accession agreement is not compatible with the EU treaties. In this commentary the authors argue that this would force EU member states to renegotiate the terms of accession to the ECHR. But meeting the demands made by the Court of Justice will prove to be very difficult.

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Protein degradation is regulated during the cell cycle of all eukaryotic cells and is mediated by the ubiquitin-proteasome pathway. Potent and specific peptide-derived inhibitors of the 20S proteasome have been developed recently as anti-cancer agents, based on their ability to induce apoptosis in rapidly dividing cells. Here, we tested a novel small molecule dipeptidyl boronic acid proteasome inhibitor, named MLN-273 on blood and liver stages of Plasmodium species, both of which undergo active replication, probably requiring extensive proteasome activity. The inhibitor blocked Plasmodium falciparum erythrocytic development at an early ring stage as well as P. berghei exoerythrocytic progression to schizonts. Importantly, neither uninfected erythrocytes nor hepatocytes were affected by the drug. MLN-273 caused an overall reduction in protein degradation in P. falciparum, as demonstrated by immunoblots using anti-ubiquitin antibodies to label ubiquitin-tagged protein conjugates. This led us to conclude that the target of the drug was the parasite proteasome. The fact that proteasome inhibitors are presently used as anti-cancer drugs in humans forms a solid basis for further development and makes them potentially attractive drugs also for malaria chemotherapy.

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Includes index.

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Thesis (M.S.)--University of Illinois at Urbana-Champaign.