Phosphoinositide (PI) 3-kinase has been implicated in T cell receptor (TCR) signaling, either as a positive or a negative regulatory molecule. Here, we show that for normal mouse lymph node T cells, PI 3-kinase activity is required for interleukin-2 (IL-2) production following TCR-mediated activation. Furthermore, in normal T cells, inhibition of PI 3-kinase prevented activation of enzymes in the extracellular signal-regulated protein kinase (ERK) signaling pathway (MEK-1 and ERK-2). Overexpression of a dominant-negative mutant of PI 3-kinase and pharmacological inhibitors of PI 3-kinase prevented transcriptional activation of AP-1 and NF-AT, transcription factors regulated by ERK-2 and pivotal for IL-2 gene expression. Although a constitutively active form of Akt kinase, a downstream mediator of PI 3-kinase function, enhanced TCR-induced IL-2 gene transcription, it could not bypass the requirement for PI 3-kinase activity. Therefore, PI 3-kinase is likely to be involved in signaling for IL-2 production in at least two steps in the TCR-initiated signaling pathway.The T cell receptor for antigen (TCR) 1 is a multisubunit complex whose ligation initiates a series of signaling events that lead to gene activation, lymphokine production, and cell division. The earliest biochemical event following TCR activation is activation of intracellular protein-tyrosine kinases (1, 2). The tyrosine phosphorylation events are regulated by two classes of protein-tyrosine kinases, the Src family (Lck and Fyn) and the Syk/ZAP-70 family. Lck and Fyn phosphorylate tyrosine residues present within a signaling motif in the cytoplasmic regions of the CD3 ␥, ␦, and ⑀ and TCR chains, called the immunoreceptor tyrosine-based activation motif. Phosphorylation of immunoreceptor tyrosine-based activation motifs is followed by the recruitment, tyrosine phosphorylation, and activation of ZAP-70 and Syk. This TCR-associated protein-tyrosine kinase activity is coupled to the phosphorylation and activation of downstream signaling molecules such as phospholipase C␥1. Hydrolysis of inositol phospholipids by phospholipase C␥1 results in the generation of inositol polyphosphates and diacylglycerols, second messengers that lead to activation of protein kinase C family members and to an increased level of intracellular Ca 2ϩ . Increased intracellular Ca 2ϩ in turn activates the phosphatase calcineurin, resulting in the nuclear translocation of the transcription factor NF-AT. Another signaling pathway emanating from the TCR involves the small GTP-binding protein Ras and a kinase cascade that it activates (the Ras/mitogen-activated protein kinase pathway). This pathway results in the activation of the transcription factors Elk1 and subsequently AP-1. Interleukin-2 (IL-2) gene expression, a common measure of productive T cell activation, cannot be induced by a single signaling pathway: it requires the coordinate action of these and other pathways that integrate at the level of multiple transcription factors, including NF-AT, AP-1, NF-B, and Oct-1 (3).Anot...

In this study, we have been exploring a new ion exchange material in the form of a fiber that could yield a number of important advantages over conventional ion exchange beads. In this approach, ion exchange fibers are prepared by 1) coating low-cost glass fiber substrates with a polystyrene/divinylbenzene oligomer, 2) curing, and 3) sulfonating. The sulfonation process and effects of varying degrees of crosslinking were characterized through diffuse reflectance infrared spectroscopy and acid-base neutralization titrations. Capacities of 4.7 meq/ g (on a per resin basis) were easily obtained. Kinetics experiments showed the contact efficiencies of the new systems were greatly improved over the traditional beads due to greater surface associated with the film morphology and shorter diffusion lengths. This translated into an order of magnitude increase in ion exchange rate. As a result of the thin coatings, the use of solvents prior to functionalization, and preswelling of the finished product prior to end-use were eliminated. Scanning electron microscopy was used to image the fibers and track their mechanical integrity through various stages of the process. Finally, repetitive regenerations proved the long-term stability of the spent fibers. Copyright

The understanding of the structure and the stability of high entropy alloys is still incomplete and the mechanisms behind the composition-property relationships are unclear. One reason is that few systematic and accurate determinations of their composition-dependent structure on atomic level have been made. In this paper some results on the structure obtained by X-ray and neutron diraction of the CoCrFeNi alloy, to which Pd, Sn and Cu have been added in dierent amounts, are reported. The investigations make it obvious that none of the alloys is completely homogeneous, as has earlier been suggested, and that they do not form a perfect solid solution.

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This work explores the design of new ion-exchange materials in the form of fibers that yield a number of important advantages over conventional ion-exchange beads. In this approach, ion-exchange fibers are prepared by (1) coating low-cost glass fiber substrates with an appropriate oligomer, (2) cross-linking, and (3) functionalizing the coating to produce either anionic or cationic capability. As a result of the thin coatings, the use of solvents prior to both functionalization and preswelling of the finished product prior to end-use was eliminated, representing a significant simplification of current synthesis methods. Kinetic experiments showed that the contact efficiencies of these systems were greatly improved over the traditional beads because of the higher surface-to-volume ratio and shorter diffusion path lengths. This improvement translated into an order of magnitude increase in both ion-exchange and regeneration rates. Another advantage is the excellent resistance of the fibers to osmotic shock even after multiple regenerations. Finally, these systems were shown to remove heavy metal contaminants effectively to well below part per billion concentrations.

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Glass-coated amorphous microwires of two different compositions, Co 68 Mn 7 Si 10 B 15 and Fe 70 B 15 Si 10 C 5 , with square hysteresis loops have been prepared and studied. The effect of applied tensile stress on their magnetic properties is reported for both kinds of microwires with radii of the metallic nucleus in the range from 1.9-7.5 µm and thicknesses of the coating of 3.8-10.8 µm. The switching field of the studied microwires depends on the sample's geometry (the radius of the metallic nucleus and the thickness of the glass coating), exhibiting a decrease with decreasing thickness of the coating owing to the induced internal stresses. For Fe-rich compositions an increase of the switching field with the applied tensile stress in the range of 0-750 MPa was observed, such an increase being more significant for a thin coating. The classical square root dependence of the switching field on the applied stress is found for Fe-rich compositions for the range of thicker metallic nuclei. Co-rich microwires exhibit quite a different stress dependence of the switching field, exhibiting first roughly stress-independent behaviour and then an increase with the stress. Removal of the glass coating results in a drastic change of the switching fields for both compositions, indicating the existence of strong internal frozen-in stresses. The observed experimental dependences were explained in terms of a dependence of the nucleation field both on external and on internal stresses and by taking into account the dependence of the magnetostriction constant on the strength of the total stresses.

Prediction of the crystalline structure formation of High Entropy Alloys is developed while applying Principal Component Analysis to their thermodynamic and electronic parameters. In the simplest form, it shows an excellent discrimination between both face and body centered cubic structures when taking into account the valence electron concentration and enthalpy of mixing. The approach is validated by the successful prediction of a multiphase structure in TiMnFeNi, and the discovery of two novel four components single phase HEAs, MnFeCoNi and NbMnVTi.