Rapid burst of H2O2 by plant growth regulators increases intracellular Ca2+ amounts and modulates CD4(+) T cell activation

The identification of small molecules that affect T cell activation is an important area of research. Three molecules that regulate plant growth and differentiation, but not their structurally similar analogs, were identified to enhance primary mouse CD4(+) T cell activation in conjunction with soluble anti-CD3 stimulation: Indoleacetic acid (natural plant auxin), 1-Napthaleneacetic acid (synthetic plant auxin) and 2,4-Dichlorophenoxyacetic acid (synthetic plant auxin and herbicide). These effects are distinct in comparison to Curcumin, the well known phenolic immunomodulator, which lowers T cell activation. An investigation into the mechanisms of action of the three plant growth regulators revealed a rapid induction of reactive oxygen species (ROS), mainly comprising H2O2 . In addition, these three molecules synergize with soluble anti-CD3 signaling to enhance intracellular Ca2+ concentrations Ca2+](i), leading to greater T cell activation, e.g. induction of CD25 and IL-2. Enhanced production of TNF alpha and IFN gamma by CD4+ T cells is also observed upon plant growth regulator treatment with soluble anti-CD3. Interestingly, maximal IL-2 production and CD4(+) T cell cycle progression are observed upon activation with soluble anti-CD3 and phorbol 12-myristate 13-acetate (PMA), a phorbol ester. Additionally, stimulation with PMA and Ionomcyin (a Ca2+ ionophore), which activates T cells by circumventing the TCR, and plant growth regulators also demonstrated the role of the strength of signal (SOS): T cell cycle progression is enhanced with gentle activation conditions but decreased with strong activation conditions. This study demonstrates the direct effects of three plant growth regulators on CD4(+) T cell activation and cycling. (C) 2010 Elsevier B.V. All rights reserved.

Functional regulation of the Neurofibromatosis 2 tumor suppressor merlin

Neurofibromatosis 2 (NF2) is an autosomal dominant disorder manifested by the formation of multiple benign tumors of the nervous system. Affected individuals typically develop bilateral vestibular schwannomas which lead to deafness and balance disorders. The syndrome is caused by inactivation of the NF2 tumor suppressor gene, and mutation or loss of the NF2 product, merlin, is sufficient for tumorigenesis in both hereditary and sporadic NF2-associated tumors. Merlin belongs to the band 4.1 superfamily of cytoskeletal proteins, which also contain the related ezrin, radixin, and moesin (ERM) proteins. The ERM members provide a link between the cell cytoskeleton and membrane by connecting membrane-associated proteins to actin filaments. By stabilizing complexes in the cell cortex, the ERMs modulate morphology, growth, and migration of cells. Despite their structural homology, overlapping subcellular distribution, direct molecular association, and partial overlap of molecular interactions, merlin and ezrin exert opposite effects on cell proliferation. Merlin suppresses cell proliferation, whereas ezrin expression is linked to oncogenic activity. We hypothesized that the regions which differ between the proteins might explain merlin s specificity as a tumor suppressor. We therefore analyzed the regions, which are most diverse between merlin and ezrin; the N-terminal tail and the C-terminus. To determine the properties of the C-terminal region, we studied the two most predominant merlin isoforms together with truncation variants similar to those found in patients. We also focused on the evolutionally conserved C-terminal residues, E545-E547, that harbor disease causing mutations in its corresponding DNA sequence. In addition to inhibiting cell proliferation, merlin regulates cytoskeletal organization. The morphogenic properties of merlin may play a role in tumor suppression, since patient-derived tumor cells demonstrate cytoskeletal abnormalities. We analyzed the mechanisms of merlin-induced extension formation and determined that the C-terminal region of amino acids 538-568 is particularly important for the morphogenic activity. We also characterized the role of C-terminal merlin residues in the regulation of proliferation, phosphorylation, and intramolecular associations. In contrast to previous reports, we demonstrated that both merlin isoforms are able to suppress cell proliferation, whereas C-terminally mutated merlin constructs showed reduced growth inhibition. Phosphorylation serves as a mechanism to regulate the tumor suppressive activity of merlin. The C-terminal serine 518 is phosphorylated in response to both p21-activated kinase (PAK) and protein kinase A (PKA), which inactivates the growth inhibitory function of merlin. However, at least three differentially phosphorylated forms of the protein exist. In this study we demonstrated that also the N-terminus of merlin is phosphorylated by AGC kinases, and that both PKA and Akt phosphorylate merlin at serine 10 (S10). We evaluated the impact of this N-terminal tail phosphorylation, and showed that the phosphorylation state of S10 is an important regulator of merlin s ability to modulate cytoskeletal organization but also regulates the stability of the protein. In summary, this study describes the functional effect of merlin specific regions. We demonstrate that both S10 in the N-terminal tail and residues E545-E547 in the C-terminus are essential for merlin activity and function.

1, 2-Bis (diphenylphosphino) etane bridged dinuclear copper (I) complexes: Investigations of solid state and solution structures by CP/MAS31P NMR spectroscopy, X-ray crystallography, IR spectroscopy and solution 31P NMR and 63Cu NMR spectroscopy

Three different complexes of copper (I) with bridging 1, 2-bis(diphenylphosphino)ethane (dppe), namely [Cu2 (mu-dppe) (CH3CN)6] (ClO4)2 (1), [Cu2 (mu-dppe)2 (CH3 CN)2] (ClO4)2 (2), and [Cu2 (mu-dppe) (dppe)2 (CH3CN)2] (ClO4)2 (3) have been prepared. The structure of [Cu2 (mu-dppe) (dPPe)2 (CH3CH)2] (ClO4)2 has been determined by X-ray crystallography. It crystallizes in the space group PT with a=12.984(6) angstrom, b=13.180(6) angstrom, c=14.001(3) angstrom, alpha=105.23(3), beta=105.60(2), gamma=112.53 (4), V=1944 (3) angstrom3, and Z=1. The structure was refined by least-squares method with R=0.0365; R(w)=0.0451 for 6321 reflections with F0 greater-than-or-equal-to 3 sigma (F0). The CP/MAS P-31 and IR spectra of the complexes have been analysed in the light of available crystallographic data. IR spectroscopy is particularly helpful in identifying the presence of chelating dppe. P-31 chemical shifts observed in solid state are very different from those observed in solution, and change significantly with slight changes in structure. In solution, complex 1 remains undissociated but complexes 2 and 3 undergo extensive dissociation. With a combination of room temperature H-1, Cu-63, and variable temperature P-31 NMR spectra, it is possible to understand the various processes occurring in solution.

Flap‐Lag Damping in Hover and Forward Flight with a Three‐Dimensional Wake

Prediction of lag damping is difficult owing to the delicate balance of drag, induced drag and Coriolis forces in the in‐plane direction. Moreover, induced drag” is sensitive to dynamic wake, bath shed and trailing components, and thus its prediction requires adequate unsteady‐wake representation. Accordingly, rigid‐blade flap‐lag equations are coupled with a three‐dimensional finite‐state wake model; three isolatcd rotor canfigurations with three, four and five blades are treated over a range of thrust levels, tack numbers, lag frequencies and advance ratios. The investigation includes convergence characteristics of damping with respect to the number of radial shape functions and harmonics of the wake model for multiblade modes of low frequency (< 1/ rev.) to high frequency (> 1/rev.). Predicted flap and lag damping levels are then compared with similar predictions with 1) rigid wake (no unsteady induced now), 2) Loewy lift deficiency and 3) dynamic inflow. The coverage also includes correlations with the measured lag regressive‐mode damping in hover and forward flight and comparisons with similar correlations with dynamic inflow. Lag‐damping predictions with the dynamic wake model are consistently higher than the predictions with the dynamic inflow model; even for the low frequency lag regressive mode, the number of wake harmonics should at least be equal to twice the number of blades.

Guessers for Finite-State Transducer Lexicons

Language software applications encounter new words, e.g., acronyms, technical terminology, names or compounds of such words. In order to add new words to a lexicon, we need to indicate their inflectional paradigm. We present a new generally applicable method for creating an entry generator, i.e. a paradigm guesser, for finite-state transducer lexicons. As a guesser tends to produce numerous suggestions, it is important that the correct suggestions be among the first few candidates. We prove some formal properties of the method and evaluate it on Finnish, English and Swedish full-scale transducer lexicons. We use the open-source Helsinki Finite-State Technology to create finitestate transducer lexicons from existing lexical resources and automatically derive guessers for unknown words. The method has a recall of 82-87 % and a precision of 71-76 % for the three test languages. The model needs no external corpus and can therefore serve as a baseline.

Thermodynamic Study of Mixed Anionic Solid Solutions Using Gradient Solid Electrolytes System K2CO3 - K2SO4

The thermodynamic properties of K2CO3 -KSO, solid solutions with hexagonal structure have been measured using a solid-state cell, incorporating a composite solid electrolyte with step-changes in composition. The cell with the configuration Pt, CO2' + O2' || K2CO3 | K2(CO3)x(SO4)1-x || CO2'' + O2'' + Pt X =1 X=X was investigated in the temperature range of 925 to 1165 K. The composite gradient solid electrolyte consisted of pure K2CO3 at one extremity and the solid solution under study at the other. The Nernstian response of the cell to changes in partial pressures of CO2 and O2 at the electrodes and temperature was demonstrated. The activity of K2CO3 in the solid solution was measured by three techniques. All three methods gave identical results, indicating unit transport number for K+ ions and negligible diffusion potential due to concentration gradients of carbonate and sulfate ions. The activity of K2CO3 exhibits positive deviation from Raoult's law. The excess Gibbs energy of mixing of the solid solution can be represented using a subregular solution model DELTAG(E) = X(1 - X)[5030X + 4715(1 - X)] J mol-1 By combining this information with the phase diagram, mixing properties of the liquid phase were obtained.

Behaviour of the germ cell specific lamin through mammalian spermatogenesis as probed with monoclonal antibodies.

We had earlier identified a 60 kDa nuclear lamin protein (lamin(g)) unique to the germ cells of rat testis which was subsequently shown to be antigenically conserved in germ cells of grasshopper, rooster, frog and plants. We have now obtained eight monoclonal antibodies in mouse against this lamin(g) antigen. While all the eight Mabs reacted with lamin(g) antigen in an immunoblot analysis, only three Mabs (A(11)C(7), A(11)D(4), C1F7) showed strong reactivity in the immunofluorescence analysis of the germ cells. The Mabs A(11)C(7) and A(11)D(4) showed a slight cross-reactivity with rat liver lamin B. Indirect immunofluorescence analysis of pre-meiotic, meiotic and post-meiotic germ cells with Mabs have shown that while the lamin(g) is localized in the lamina structures of spermatogonia and round spermatids, it is localized to the phase dense regions of pachytene spermatocytes which is in conformity with our previous observations using rabbit polyclonal antibodies. The localization of the antigen in the germ cells was also confirmed by immunohistochemical staining of the thin sections of seminiferous tubules. By immunostaining the surface spread pachytene spermatocytes, the antigen was further localized to the telomeric ends of the paired homologous chromosomes. Using anti-somatic lamin B antibodies, we have also demonstrated the absence of somatic lamins in meiotic and post-meiotic germ cells. The lamina structure of pre-meiotic spermatogonial nucleus contains both somatic lamin B and lamin(g) as evidenced by immunofluorescence studies with two differently fluorochrome labelled anti-lamin B and anti-lamin(g) antibodies. The selective retention of lamin(g) in the pachytene spermatocytes is probably essential for anchoring the telomeric ends of the paired chromosomes to the inner nuclear membrane.

Phase relations and gibbs energies in the system Mn-Rh-O

Phase relations in the system Mn-Rh-O are established at 1273 K by equilibrating different compositions either in evacuated quartz ampules or in pure oxygen at a pressure of 1.01 x 10(5) Pa. The quenched samples are examined by optical microscopy, X-ray diffraction, and energy-dispersive X-ray analysis (EDAX). The alloys and intermetallics in the binary Mn-Rh system are found to be in equilibrium with MnO. There is only one ternary compound, MnRh2O4, with normal spinel structure in the system. The compound Mn3O4 has a tetragonal structure at 1273 K. A solid solution is formed between MnRh2O4 and Mn3O4. The solid solution has the cubic structure over a large range of composition and coexists with metallic rhodium. The partial pressure of oxygen corresponding to this two-phase equilibrium is measured as a function of the composition of the spinel solid solution and temperature. A new solid-state cell, with three separate electrode compartments, is designed to measure accurately the chemical potential of oxygen in the two-phase mixture, Rh + Mn3-2xRh2xO4, which has 1 degree of freedom at constant temperature. From the electromotive force (emf), thermodynamic mixing properties of the Mn3O4-MnRh2O4 solid solution and Gibbs energy of formation of MnRh2O4 are deduced. The activities exhibit negative deviations from Raoult's law for most of the composition range, except near Mn3O4, where a two-phase region exists. In the cubic phase, the entropy of mixing of the two Rh3+ and Mn3+ ions on the octahedral site of the spinel is ideal, and the enthalpy of mixing is positive and symmetric with respect to composition. For the formation of the spinel (sp) from component oxides with rock salt (rs) and orthorhombic (orth) structures according to the reaction, MnO (rs) + Rh2O3 (orth) --> MnRh2O4 (sp), DELTAG-degrees = -49,680 + 1.56T (+/-500) J mol-1. The oxygen potentials corresponding to MnO + Mn3O4 and Rh + Rh2O3 equilibria are also obtained from potentiometric measurements on galvanic cells incorporating yttria-stabilized zirconia as the solid electrolyte. From these results, an oxygen potential diagram for the ternary system is developed.

Proposed role of w chromosome inactivation and the absence of dosage compensation in avian sex determination

Three features of avian sex chromosomes - female heterogamety (ZZ male, ZW female), the apparently inactive state of the W chromosome, and dose-dependent expression of Z-linked genes - are examined in regard to their possible relation to sex determination. It is proposed that the W chromosome is facultatively heterochromatic and that the Z and W chromosomes carry one or more homologous sex-determination genes. The absence of dosage compensation in ZZ embryos, and W inactivation in ZW embryos, would then bring about a 2n(ZZ)-n(ZW) inequality in the effective copy number of such genes. The absence of dosage compensation of Z-linked genes in ZZ embryos is viewed as a means by which two copies of Z-W homologous sex determination genes are kept active to meet the requirements of testis determination. W inactivation may promote ovarian development by reducing the effective copy number of these genes from 2n to n. If there is a W-specific gene for femaleness, spread of heterochromatization to this gene in cells forming the right gonadal primordium may explain the latter's normally undifferentiated state; reversal of heterochromatization may similarly explain the development of the right gonad into a testis following left ovariectomy.

Design and development of a self-supported polymer electrolyte fuel cell system with anodic dead-end operation

Design and operational details for a self-supported polymer electrolyte fuel cell (PEFC) system with anodic dead-end fuel supply and internally humidified cathodic oxidant flow are described. During the PEFC operation, nitrogen and water back diffuse across the Nafion membrane from the cathode to the anode and accumulate in the anode flow channels affecting stack performance. The accumulated inert species are flushed from the stack by purging the fuel cell stack with a timer-activated purge valve to address the aforesaid problem. To minimize the system complexity, stack is designed in such a way that all the inert species accumulate in only one cell called the purge cell. A pulsed purge sequence comprises opening the valve for purge duration followed by purge-valve closing for the hold period and repeating the sequence in cycles. Since self-humidification is inadequate to keep the membrane wet, the anodic dead-end-operated PEFC stack with composite membrane comprising perflourosulphonic acid (Nafion) and silica is employed for keeping the membrane humidified even while operating the stack with dry hydrogen and internally humidified air.

Soft chemical synthesis of new layered and three-dimensional oxide hydrates, hxVxW1-xO3×yH2O, related to WO3×2 H2O and WO3. times.1/3 H2O

Two new vanadium-tungsten oxide hydrates of the formulas, H0.125V0.125W0.875O3.1.5H2O (I) and Ho.33V0.33W0.67O3.1/3H2O (II), have been synthesized by acid-leaching of LiVWO6 with aqueous HNO3/HCl. While phase I obtained by treatment of LiVWO6 with dilute HNO3/HCl possesses an orthorhombic structure (a = 7.77(3), b = 13.87(6), c = 7.44(3) angstrom) related to WO3.2H2O, phase II, prepared by refluxing LiVWO6 with concentrated HNO3, is isostructural with WO3.1/3H2O. Dehydration of II around 330-degrees-C yields a hexagonal phase (III, a = 7.25(4), c = 7.74(3) angstrom) isotypic with hexagonal WO3. Both land III exhibit redox and acid-base intercalation reactivity characteristic of layered and tunnel structures.

Study of the reaction between 1,2,3-trihydroxybenzene and 8-hydroxyquinoline in the solid state

1.2,3-Trihydroxybenzene (THB) reacts with 8-hydroxyquinoline (8HQ) in the solid state forming an orange-coloured charge transfer complex THB* (8HQ)(2). When the reaction was carried out in a petri dish, or when the vapours of 8HQ were allowed to react with solid THB (gravimetric study), the reaction product separated out as good quality, shiny single crystals. X-Ray diffraction studies on single crystals showed that they belong to the orthorhombic system with a = 15.408(1), b = 16.276(1), c = 7.825(1) Angstrom, Z = 4, D-x = 1.413 g cm(-3) and space group Pnaa. From the crystallographic evidence it has been found that the proton of the middle OH group of THB is transferred to the N atom of 8HQ. This accounts for the observed colour change. Kinetic studies on the solid state reaction showed that the 8HQ molecules diffuse towards THB, and the lateral diffusion occurs through surface migration, grain boundary diffusion and vapour phase diffusion. Gravimetric studies of the reaction between solid THB and 8HQ vapour showed that the diffusion of 8HQ molecules into the crystal lattice of THB has a higher energy of activation than that observed when the reactants are in contact. The nature of the crystal packing in the reaction product indicates diffusion of 8HQ molecules into the crystal lattice of THB along the c-axis, to occupy the cavities present between the THB molecules in the unit cell.

High-Throughput Study of the Cu(CH3COO)(2)center dot H2O-5-Nitroisophthalic Acid Heterocyclic Ligand System: Synthesis, Structure, Magnetic, and Heterogeneous Catalytic Studies of Three Copper Nitroisophthalates

A high-throughput screening was employed to identify new compounds in Cu(CH3COO)(2)center dot H2O-NIPA-heterocyclic ligand systems. Of the compounds identified, three compounds, Cu-3{(NO2)-C6H3-(COO)(2)}(3)(C3N6H6)] (1), Cu-2(mu(3)-OH)(H2O){(NO2)-C6H3-(COO)(2)}(CN4H)]center dot-(H2O) (II), and Cu-2(mu(3)-OH)(H2O){(NO2)-C6H3-(COO)(2}-)(CN5H2)]center dot 2(H2O) (III), have been isolated as good quality single crystals by employing conventional hydrothermal methods. Three other compounds, Cu-2{(NO2)-C6H3-(COO)(2)}-(CN4H)(H2O) (IIa), Cu-2{(NO2)-C6H3-(COO)(2)}(CN5H2) (IIIa), and Cu-2{(NO2)-C6H3-(COO)(2)}{(CN5H2)(2)}2H(2)O (IIIb), were identified by a combination of elemental analysis, thermogravimetric analysis (TGA), and IR spectroscopic studies, although their structures are yet to be determined. The single crystalline compounds were also characterized by elemental analysis, TGA, IR, UV vis, magnetic, and catalytic studies. The structures of the compounds have paddle wheel (I) and infinite Cu 0(H) Cu chains (II and HI) connected with NLPA and heterocyclic ligands forming two-(II) and three-dimensional (I and III) structures. The bound and lattice water molecules in 11 and 111 could be reversibly removed/inserted without affecting the structure. In the case of II, the removal of water gives rise to a structural transition, but the dehydrated phase reverts back to the original phase on prolonged exposure to atmospheric conditions. Magnetic studies indicate an overall antiferromagnetism in all of the compounds. Lewis acid catalytic studies indicate that compounds II and HI are active for cyanosilylation of imines.

Cell versus message level performances in ATM networks

The goal of this paper is to provide some insight into the relations that exist between cell level and message level performance guarantees in the context of ATM networks. Cell level guarantees are typically what the network is capable of providing, while message level guarantees are the ones of interest to users. It is, therefore, important to understand how the two are related, and which factors influence this relation. There are many different performance measures that are of importance, and in this paper we try to touch on the (three) most relevant ones. This includes comparing cell and message loss probabilities, average cell and message delays, and cell and message jitter. Specifically, we show that cell and message loss probabilities can exhibit significant differences, which strongly depend on traffic characteristics such as peak rate and burst size, i.e., for a fixed cell loss probability, the message loss probability can greatly vary when peak rate and burst size change. One reason for this sensitivity, is that message loss depends on what happen to all the cells in a message. For delay and jitter, we also find that peak rate and burst size play a role in determining the relation between cell and message performance. However, this sensitivity is not as acute as with losses since message delay and jitter are typically determined by the performance seen by only one cell, the last cell in a message. In the paper, we provide quantitative examples that illustrate the range of behaviors and identify the impact of different parameters.