Pentoxifylline-stimulated capacitation and acrosome reaction in hamster spermatozoa: involvement of intracellular signalling molecules

We investigated the role of cAMP/cGMP, protein kinases and intracellular calcium ( [Ca2+](i)) in pentoxifylline-stimulated hamster sperm capacitation and the acrosome reaction (AR) in vitro. Treatment with pentoxifylline [0.45 mM) initially increased sperm cAMP values 2.8-fold, compared with untreated controls (396 +/- 9.2 versus 141 +/- 6.0 fmoles/10(6) spermatozoa; mean +/- SEM, n = 6) after 15 min, although by 3 h, cAMP values were similar (503-531 fmoles/10(6) spermatozoal, cGMP values (similar to 27 fmoles/10(6) spermatozoa) were the same in treated and control spermatozoa. Both sperm capacitation and the AR, determined from the absence of an acrosomal cap, were stimulated by pentoxifylline; these were almost completely inhibited by a Cl-/HCO(3)(-)antiporter inhibitor (4,4-diisothiocyanato-stilbene-2,2 disulphonic acid; 1 mM) defined from the degree of sperm motility and by a protein kinase A inhibitor (H89; 10 mu M) A protein kinase G inhibitor (staurosporine, 1 nM) did not affect pentoxifylline-stimulated capacitation but inhibited the AR by 50%. A protein tyrosine kinase inhibitor (tyrphostin A-47, 0.1 mM) had no effect on either pentoxifylline-stimulated capacitation or AR, A phospholipase A(2) inhibitor (aristolochic acid, 0.4 mM) markedly inhibited the pentoxifylline-stimulated AR but not capacitation. When intracellular sperm calcium [Ca2+](i) was measured using fura-2-AM, there was an early rise 271 nM at 0.5 hi in pentoxifylline(-treated spermatozoa; this appeared to be due to intracellular mobilization rather than to uptake. In the absence of extracellular Ca2+, sperm motility was maintained in the presence of pentoxifylline, but capacitation did not occur; spermatozoa exhibited a low level of hyperactivated motility and had a poor rate of AR(20.5 +/- 2.3%). These results suggest that: (i) the pentoxifylline-stimulated early onset of sperm capacitation may be mediated by an early rise in cAMP and [Ca2+/-](i) and involves protein kinase A activity; and (ii) pentoxifylline-stimulated AR may require phospholipase A;A(2) and protein kinase C activity.

Effect of lattice orientation on crack tip constraint in ductile single crystals

In this work, the effect of lattice orientation on the fields prevailing near a notch tip is investigated pertaining to various constraint levels in FCC single crystals. A modified boundary layer formulation is employed and numerical solutions under mode I, plane strain conditions are generated by assuming an elastic-perfectly plastic FCC single crystal. The analysis is carried out corresponding to different lattice orientations with respect to the notch line. It is found that the near-tip deformation field, especially the development of kink or slip shear bands is sensitive to the constraint level. The stress distribution and the size and shape of the plastic zone near the notch tip are also strongly influenced by the level of T-stress. The present results clearly establish that ductile single crystal fracture geometries would progressively lose crack tip constraint as the T-stress becomes more negative irrespective of lattice orientation. Also, the near-tip field for a range of constraint levels can be characterized by two-parameters such as K-T or J-Q as in isotropic plastic solids.

When should fig fruit produce volatiles? Pattern in a ripening process

Ripe fruit need to signal their presence to attract dispersal agents. Plants may employ visual and/or olfactory sensory channels to signal the presence of ripe fruit. Visual signals of ripe fruit have been extensively investigated. However, the volatile signatures of ripe fruit that use olfactorily-oriented dispersers have been scarcely investigated. Moreover, as in flowers, where floral scents are produced at times when pollinators are active (diurnal versus nocturnal), whether plants can modulate the olfactory signal to produce fruit odours when dispersers are active in the diel cycle is completely unknown. We investigated day night differences in fruit odours in two species of figs, Ficus racemosa and Ficus benghalensis. The volatile bouquet of fruit of F.racemosa that are largely dispersed by bats and other mammals was dominated by fatty acid derivatives such as esters. In this species in which the ripe fig phase is very short, and where the figs drop off soon after ripening, there were no differences between day and night in fruit volatile signature. The volatile bouquet of fruit of F. benghalensis that has a long ripening period, however, and that remain attached to the tree for extended periods when ripe, showed an increase in fatty acid derivatives such as esters and of benzenoids such as benzaldehyde at night when they are dispersed by bats, and an elevation of sesquiterpenes during the day when they are dispersed by birds. For the first time we provide data that suggest that the volatile signal produced by fruit can show did l differences based on the activity period of the dispersal agent. (C) 2011 Elsevier Masson SAS. All rights reserved.

Oncogenic MicroRNA-155 Down-regulates Tumor Suppressor CDC73 and Promotes Oral Squamous Cell Carcinoma Cell Proliferation IMPLICATIONS FOR CANCER THERAPEUTICS

The CDC73 gene is mutationally inactivated in hereditary and sporadic parathyroid tumors. It negatively regulates beta-catenin, cyclin D1, and c-MYC. Down-regulation of CDC73 has been reported in breast, renal, and gastric carcinomas. However, the reports regarding the role of CDC73 in oral squamous cell carcinoma (OSCC) are lacking. In this study we show that CDC73 is down-regulated in a majority of OSCC samples. We further show that oncogenic microRNA-155 (miR-155) negatively regulates CDC73 expression. Our experiments show that the dramatic up-regulation of miR-155 is an exclusive mechanism for down-regulation of CDC73 in a panel of human cell lines and a subset of OSCC patient samples in the absence of loss of heterozygosity, mutations, and promoter methylation. Ectopic expression of miR-155 in HEK293 cells dramatically reduced CDC73 levels, enhanced cell viability, and decreased apoptosis. Conversely, the delivery of a miR-155 antagonist (antagomir-155) to KB cells overexpressing miR-155 resulted in increased CDC73 levels, decreased cell viability, increased apoptosis, and marked regression of xenografts in nude mice. Cotransfection of miR-155 with CDC73 in HEK293 cells abrogated its pro-oncogenic effect. Reduced cell proliferation and increased apoptosis of KB cells were dependent on the presence or absence of the 3'-UTR in CDC73. In summary, knockdown of CDC73 expression due to overexpression of miR-155 not only adds a novelty to the list of mechanisms responsible for its down-regulation in different tumors, but the restoration of CDC73 levels by the use of antagomir-155 may also have an important role in therapeutic intervention of cancers, including OSCC.

FIELD EMISSION EFFICIENCY OF A CARBON NANOTUBE ARRAY UNDER PARASITIC NONLINEARITIES

Carbon Nanotubes (CNTs) grown on substrates are potential electron sources in field emission applications. Several studies have reported the use of CNTs in field emission devices, including field emission displays, X-ray tube, electron microscopes, cathode-ray lamps, etc. Also, in recent years, conventional cold field emission cathodes have been realized in micro-fabricated arrays for medical X-ray imaging. CNTbased field emission cathode devices have potential applications in a variety of industrial and medical applications, including cancer treatment. Field emission performance of a single isolated CNT is found to be remarkable, but the situation becomes complex when an array of CNTs is used. At the same time, use of arrays of CNTs is practical and economical. Indeed, such arrays on cathode substrates can be grown easily and their collective dynamics can be utilized in a statistical sense such that the average emission intensity is high enough and the collective dynamics lead to longer emission life. The authors in their previous publications had proposed a novel approach to obtain stabilized field emission current from a stacked CNT array of pointed height distribution. A mesoscopic modeling technique was employed, which took into account electro-mechanical forces in the CNTs, as well as transport of conduction electron coupled with electron phonon induced heat generation from the CNT tips. The reported analysis of pointed arrangements of the array showed that the current density distribution was greatly localized in the middle of the array, the scatter due to electrodynamic force field was minimized, and the temperature transients were much smaller compared to those in an array with random height distribution. In the present paper we develop a method to compute the emission efficiency of the CNT array in terms of the amount of electrons hitting the anode surface using trajectory calculations. Effects of secondary electron emission and parasitic capacitive nonlinearity on the current-voltage signals are accounted. Field emission efficiency of a stacked CNT array with various pointed height distributions are compared to that of arrays with random and uniform height distributions. Effect of this parasitic nonlinearity on the emission switch-on voltage is estimated by model based simulation and Monte Carlo method.

The translation initiation factor DAP5 promotes IRES-driven translation of p53 mRNA

Translational regulation of the p53 mRNA can determine the ratio between p53 and its N-terminal truncated isoforms and therefore has a significant role in determining p53-regulated signaling pathways. Although its importance in cell fate decisions has been demonstrated repeatedly, little is known about the regulatory mechanisms that determine this ratio. Two internal ribosome entry sites (IRESs) residing within the 5'UTR and the coding sequence of p53 mRNA drive the translation of full-length p53 and Delta 40p53 isoform, respectively. Here, we report that DAP5, a translation initiation factor shown to positively regulate the translation of various IRES containing mRNAs, promotes IRES-driven translation of p53 mRNA. Upon DAP5 depletion, p53 and Delta 40p53 protein levels were decreased, with a greater effect on the N-terminal truncated isoform. Functional analysis using bicistronic vectors driving the expression of a reporter gene from each of these two IRESs indicated that DAP5 preferentially promotes translation from the second IRES residing in the coding sequence. Furthermore, p53 mRNA expressed from a plasmid carrying this second IRES was selectively shifted to lighter polysomes upon DAP5 knockdown. Consequently, Delta 40p53 protein levels and the subsequent transcriptional activation of the 14-3-3 sigma gene, a known target of Delta 40p53, were strongly reduced. In addition, we show here that DAP5 interacts with p53 IRES elements in in vitro and in vivo binding studies, proving for the first time that DAP5 directly binds a target mRNA. Thus, through its ability to regulate IRES-dependent translation of the p53 mRNA, DAP5 may control the ratio between different p53 isoforms encoded by a single mRNA.

Phase relations in the system Ca-Ta-O and thermodynamics of calcium tantalates in relation to calciothermic reduction of Ta2O5

Phase equilibria of the system Ca-Ta-O is established by equilibrating eleven samples at 1200 K for prolonged periods and phase identification in quenched samples by optical and scanning electron microscopy, energy dispersive spectroscopy and X-ray diffraction. Four ternary oxides are identified: CaTa4O11, CaTa2O6, Ca2Ta2O7 and Ca4Ta2O9. Isothermal section of the phase diagram is composed using the results. Thermodynamic properties of the ternary oxides are measured in the temperature range from 975 to 1275 K employing solid-state galvanic cells incorporating single crystal CaF2 as the solid electrolyte. The cells essentially measure the chemical potentials of CaO in two-phase fields (Ta2O5 + CaTa4O11), (CaTa4O11 + CaTa2O6), (CaTa2O6 + Ca2Ta2O7), and (Ca2Ta2O7 + Ca4Ta2O9) of the pseudo-binary system CaO-Ta2O5. The standard Gibbs energies of formation of the four ternary oxides from their component binary oxides Ta2O5 and CaO are given by: Delta G(f)((ox))(o) (CaTa4O11) (+/- 482)/J mol(-1) = -58644+21.497 (T/K) Delta G(f)((ox))(o) (CaTa2O6) (+/- 618)/J mol(-1) = -55122+21.893 (T/K) Delta G(f)((ox))(o) (Ca2Ta2O7) (+/- 729)/J mol(-1) = -82562+31.843 (T/K) Delta G(f)((ox))(o) (Ca4Ta2O9) (+/- 955)/J mol(-1) = -126598+48.859 (T/K) The Gibbs energy of formation of the four ternary compounds obtained in this study differs significantly from that reported in the literature. The thermodynamic data and phase diagram are used for understanding the mechanism and kinetics of calciothermic and electrochemical reduction of Ta2O5 to metal. (C) 2014 Elsevier B.V. All rights reserved.

Polypyridyl iron(II) complexes showing remarkable photocytotoxicity in visible light

Iron(II) complexes of polypyridyl ligands (B), viz. Fe(B)(2)]Cl-2 (1 and 2) of N, N, N-donor 2-(2-pyridyl)-1,10-phenanthroline (pyphen in 1) and 3-(pyridin-2-yl)dipyrido3,2-a:2',3'-c]phenazine (pydppz in 2), are prepared and characterized. They are 1:2 electrolytes in aqueous DMF. The diamagnetic complexes exhibit metal to ligand charge transfer band near 570 nm in DMF. The complexes are avid binders to calf thymus DNA giving binding constant (K (b)) values of similar to 10(6) M-1 suggesting significant intercalative DNA binding of the complexes due to presence of planar phenanthroline bases. Complex 2 exhibits significant photocytotoxicity in immortalized human keratinocyte cells HaCaT and breast cancer cell line MCF-7 giving IC50 values of 0.08 and 13 mu M in visible light (400-700 nm). Complex 2 shows only minor dark toxicity in HaCaT cells but is non-toxic in dark in MCF-7 cancer cells. The light-induced cellular damage follows apoptotic pathway on generation of reactive oxygen species as evidenced from the dichlorofluorescein diacetate (DCFDA) assay.

Parameters Inversion of Fluid-Saturated Porous Media Based on Neural Networks

The multi-layers feedforward neural network is used for inversion of material constants of fluid-saturated porous media. The direct analysis of fluid-saturated porous media is carried out with the boundary element method. The dynamic displacement responses obtained from direct analysis for prescribed material parameters constitute the sample sets training neural network. By virtue of the effective L-M training algorithm and the Tikhonov regularization method as well as the GCV method for an appropriate selection of regularization parameter, the inverse mapping from dynamic displacement responses to material constants is performed. Numerical examples demonstrate the validity of the neural network method.

The Effect of Conical Flowfields on the Performance of Waveriders at Mach 6

The performance of 23 kinds of waveriders, derived from different conical flowfields, is analyzed by the numerical computation under the conditions of fight speed of Mach 6, attack angle of 0° and flight altitude of 30 km. These results indicate that the performance is influenced by the shapes and the width to height ratios (W/H ) of generating cones. The geometrical parameter and the lift coefficient are proportional to W/H, while the drag coefficient and the lift to drag ratio (L/D ) have extreme values. Considering the base drag and the computation errors, the waverider with the highest L/D is cut from the elliptical cone’s flowfield (W/H = 1.5―1.618), and the configuration with the lowest drag can also be obtained at W/H = 1:1.5. Accordingly, good suggestions are proposed for practical design based on these computational results.

La contribución del matrimonio al bien común : perspectivas y desafíos

Resumen: Este artículo se propone estudiar la vinculación entre matrimonio y bien común, a partir del debate en la Argentina de la ley 26.618 de legalización de las uniones homosexuales como matrimonio y de los lineamientos propuestos por Benedicto XVI en Caritas in Veritate. Se advierte una claudicación en la búsqueda del bien común que obedece a diferentes factores, sobre todo el relativismo cultural. Se propone una noción de bien común que respeta la dignidad de la persona y su dimensión social y se consideran las contribuciones del matrimonio al bien común. Se advierte cómo la ley 26.618 concede a las uniones de personas del mismo sexo beneficios propios del matrimonio entre varón y mujer sin que se cumplan las funciones sociales de esa institución. También se proponen algunas condiciones de la vida social que favorecen al matrimonio para que así contribuya al bien común, con especial referencia al ámbito de la legislación, las políticas públicas, los medios de comunicación, la empresa y el mundo del trabajo y la ciencia y la tecnología. Finalmente, se consideran los obstáculos que surgieron en el reciente debate legislativo por la aparición de un laicismo militante y la contribución de las religiones al bien común desde una sana laicidad en esta materia.

平行于裂纹方向的载荷对于疲劳裂纹扩展速率的影响

<正> 1. 引言断裂力学在疲劳裂纹扩展的研究中得到了成功的应用。但是,现有的疲劳裂纹扩展数据大都是从单向加载的试件上得到的。而实际构件通常处于双向载荷或多向载荷的状态下。在对构件作寿命估计时,双向载荷对于疲劳裂纹扩展速率的影响是一个必须要考虑的因素。在1966年Christensen等曾指出,实验表明在双向载荷下疲劳裂纹扩展速率为单向载荷时的三倍,但它只给出了实验结果的示意图。后来有限的一些实验数据得出各不相同的结论。大部分试验结果表明,平行于裂纹方向的载荷对于裂纹扩展的影响很小。也有数据表明它会加快或减慢裂纹扩展。

地形对洋流影响的初步实验模拟

在旋转流动系统中,由于柯氏力的作用,地形对流动的影响常呈现出与惯性系中很不相同的特点,近年来在地球物理流体力学研究中受到很大重视。 本文介绍了作者们在力学所旋转实验台上,针对近海洋流问题所作的一些旋转流体中地形影响的初步实验研究,在一扇形容器中用源汇法模拟了洋流的陆架地形绕流,过海脊流,绕岛屿以及沿径向有变深度地形的环流,这些初步的定性的结果表明,均质旋转流动系统确能反映大尺度旋转流动的某些动力学特征。

Natureza jurídica das entidades gestoras do regime de previdência complementar para os servidores públicos federais

A Constituição Federal autoriza a União, os Estados, o Distrito Federal e os Municípios a limitarem o valor dos proventos de aposentadoria pagos a seus servidores, bem como das pensões pagas aos dependentes desses, ao limite máximo estabelecido para os benefícios pagos pelo regime geral de previdência social (RGPS). Condiciona essa providência, contudo, à instituição de regime de previdência complementar específico, instituído por intermédio de entidade fechada de previdência complementar, de natureza pública. Com fulcro na regra constitucional acima mencionada, a União instituiu regime de previdência complementar para os seus servidores por meio da Lei nº 12.618, de 30 de abril de 2012. Essa lei autoriza a criação de três entidades fechadas de previdência complementar (EFPC), estruturadas como fundações. O trabalho analisa a natureza jurídica das fundações recém-mencionadas, concluindo por sua incompatibilidade com a natureza pública exigida em foro constitucional.