Synergistic activation of mitogen-activated protein kinase by cyclic AMP and myeloid growth factors opposes cyclic AMP's growth-inhibitory effects

Colony-stimulating factors (CSFs) promote the proliferation, differentiation, commitment, and survival of myeloid progenitors, whereas cyclic AMP (cAMP)-mediated signals frequently induce their growth arrest and apoptosis. The ERK/mitogen-activated protein kinase (MAPK) pathway is a target for both CSFs and cAMP. We investigated how costimulation by cAMP and colony-stimulating factor-1 (CSF-1) or interleukin-3 (IL-3) modulates MAPK in the myeloid progenitor cell line, 32D. cAMP dramatically increased ERK activity in the presence of CSF-1 or IL-3. IL-3 also synergized with cAMP to activate ERK in another myeloid cell line, FDC-P1. The increase in ERK activity was transmitted to a downstream target, p90(rsk). cAMP treatment of 32D cells transfected with oncogenic Ras was found to recapitulate the superactivation of ERK seen with cAMP and CSF-1 or IL-3. ERK activation in the presence of cAMP did not appear to involve any of the Raf isoforms and was blocked by expression of dominant-negative MEK1 or treatment with a MEK inhibitor, PD98059. Although cAMP had an overall inhibitory effect on CSF-1-mediated proliferation and survival, the inhibition was markedly increased if ERK activation was blocked by PD98059. These findings suggest that upregulation of the ERK pathway is one mechanism induced by CSF-1 and IL-3 to protect myeloid progenitors from the growth-suppressive and apoptosis-inducing effects of cAMP elevations.     

Regulation of cyclin A-Cdk2 by SCF component Skp1 and F-box protein Skp2

Cyclin A-Cdk2 complexes bind to Skp1 and Skp2 during S phase, but the function of Skp1 and Skp2 is unclear. Skp1, together with F-box proteins like Skp2, are part of ubiquitin-ligase E3 complexes that target many cell cycle regulators for ubiquitination-mediated proteolysis. In this study, we investigated the potential regulation of cyclin A-Cdk2 activity by Skp1 and Skp2. We found that Skp2 can inhibit the kinase activity of cyclin A-Cdk2 in vitro, both by direct inhibition of cyclin A-Cdk2 and by inhibition of the activation of Cdk2 by cyclin-dependent kinase (CDK)-activating kinase phosphorylation. Only the kinase activity of Cdk2, not of that of Cdc2 or Cdk5, is reduced by Skp2. Skp2 is phosphorylated by cyclin A-Cdk2 on residue Ser76, but nonphosphorylatable mutants of Skp2 can still inhibit the kinase activity of cyclin A-Cdk2 toward histone H1. The F box of Skp2 is required for binding to Skp1, and both the N-terminal and C-terminal regions of Skp2 are involved in binding to cyclin A-Cdk2. Furthermore, Skp2 and the CDK inhibitor p21(Cip1/WAF1) bind to cyclin A-Cdk2 in a mutually exclusive manner. Overexpression of Skp2, but not Skp1, in mammalian cells causes a G1/S cell cycle arrest.     

IL-13 is a key regulatory cytokine for Th2 cell-mediated pulmonary granuloma formation and IgE responses induced by Schistosoma mansoni eggs

Schistosoma mansoni egg-induced pulmonary granuloma formation is a cell-mediated inflammatory response associated with dominant Th2-type cytokine expression, tissue eosinophilia, and high levels of serum IgE. In the present study, we show that in vivo blockade of the Th2 cytokine IL-13, using soluble IL-13R alpha2-Fc fusion protein, significantly reduced the size of pulmonary granulomas in unsensitized as well as egg-sensitized mice. Blocking IL-13 also significantly reduced total serum IgE levels. Interestingly, however, IL-13 blockade did not affect the evolving egg-induced Th2-type cytokine response. IL-4, IL-5, as well as IL-13 responses were indistinguishable in control-Fc- and soluble IL-13R alpha2-Fc fusion protein-treated animals. The smaller granulomas were also phenotypically like the control Fc-treated mice, displaying a similar eosinophil content. Additional studies in IL-4-deficient mice demonstrated that IL-13 was produced, but at much lower levels than in wild-type mice, while IL-4 expression was completely independent of IL-13. Moreover, while granuloma formation was partially reduced in IL-4-deficient mice, blocking IL-13 in these animals almost completely abrogated granuloma development and the pulmonary eosinophilia, while it simultaneously increased IFN-gamma production. Together, these data demonstrate that IL-13 serves as an important mediator of Th2-mediated inflammation and plays a role in eliciting IgE responses triggered by schistosome eggs.     

应用现代控制理论的丰用5档自动变速器

我们已经开发一种精确的和高性能的轿车用5档自动变速器（A350E）。开发这种变速器的目的在于改善在低和中等速度范围内的加速和平稳加速。具有简单传动系的5档自动变速器已经完全应用了工业最现代控制理论辅助换档技术。     

Dynamic CT measurement of cerebral blood flow: a validation study

Thrombospondin (TSP) mediates sickle erythrocyte adhesion to endothelium, but the mechanism remains unknown. Since TSP is comprised of heterogeneously distinct domains, this adhesion may depend on the interaction of specific regions of TSP with different cell surface receptors. To examine the mechanisms of interaction of TSP with human umbilical vein endothelial cells (HUVEC), we performed binding studies using soluble [125I]TSP. Our data showed that (i) monoclonal antibodies (MoAbs) against cell surface heparan sulfate (HS) or the heparin-binding domain of TSP, or cleavage of HS on HUVEC by heparitinase reduced TSP binding by 28-40%, (ii) the RGD peptide or MoAbs against integrin alpha v beta 3 or the calcium binding region of TSP inhibited binding by 18-28%, and (iii) a MoAb against the cell-binding domain of TSP inhibited binding by 36%. Unmodified heparin inhibited the binding of TSP to endothelial cells by 70% and did so far more effectively than selectively desulfated heparins, HS or chondroitin sulfate. Heparin inhibited TSP binding to HUVEC at much lower concentrations than were required to inhibit TSP binding to sickle erythrocytes. Unmodified heparin effectively inhibited the TSP-mediated adhesion of sickle erythrocytes to HUVEC. These data imply that cell surface HS-mediated mechanisms play a key role in TSP-mediated sickle erythrocyte adhesion to endothelium, and heparin may be of use for inhibition of this adhesion.     

Stability of artemisinin in aqueous environments: impact on its cytotoxic action to Ehrlich ascites tumour cells

We have recently shown artemisinin to be cytotoxic against Ehrlich ascites tumour cells. The aim of this study was to investigate the stability of this compound in the aqueous environment of the in-vitro Ehrlich ascites tumour cell system (RPMI 1640 cell culture medium supplemented with 10% foetal bovine serum (RPMI/FBS) with reference to its cytotoxic action. Literature data show that artemisinin can react with Fe2+ yielding reactive intermediates leaving artemisinin G as a major end-product. The current study showed that only excess addition of Fe2+ to artemisinin in distilled water, phosphate-buffered saline (PBS) and RPMI/FBS and incubation for 24 h led to degradation of artemisinin and yielded artemisinin G. If Fe2+ was not added results from HPLC analysis were indicative of complete recovery of artemisinin from distilled water and RPMI/FBS, with or without cells, at 37 degrees C for at least 24 h. In addition, incubation of artemisinin in RPMI/FBS with or without cells at 37 degrees C for 24 h before cytotoxicity assay did not change its cytotoxic action. On the basis of these results, we suggest that cytotoxicity to tumour cells was caused by unchanged artemisinin. This is not so for the antimalarial activity of artemisinin and derivatives, for which the presence of a pool of (haem) Fe2+ is a prerequisite resulting in free radicals or electrophilic intermediates or both.     

A novel key-frame selection-based sign language recognition framework for the video data

ABSTRACT

Sign language is a medium of communication for people with hearing disabilities. Static and dynamic gestures are identified in a video-based sign language recognition and translated them into humanly understandable phrases to achieve the communication objective. However, videos contain redundant Key-frames which require additional processing. Number of such Key-frames can be reduced. The selection of particular Key-frames without losing the required information is a challenging task. The Key-frame extraction algorithm is used which helps to speed-up the sign language recognition process by extracting essential key-frames. The proposed framework eliminates the computation overhead by picking up the distinct Key-frames for the recognition process. Discrete Wavelet Transform (DWT), Discrete Cosine Transform (DCT), and Histograms of Oriented Gradient (HOG) are used for unique features extraction. We used the bagged tree, boosted tree ensemble method, Fine KNN, and SVM for classification. We tested methodology on video-based datasets of Pakistani Sign Language. It achieved an overall 97.5% accuracy on 37 Urdu alphabets and 95.6% accuracy on 100 common words.     

Synthesis of graphene oxide-intercalated α-hydroxides by metathesis and their decomposition to graphene/metal oxide composites

Graphene oxide-intercalated α-metal hydroxides were prepared using layers from the delaminated colloidal dispersions of cetyltrimethylammonium-intercalated graphene oxide and dodecylsulfate-intercalated α-hydroxide of nickel/cobalt as precursors. The reaction of the two dispersions leads to de-intercalation of the interlayer ions from both the layered solids and the intercalation of the negatively charged graphene oxide sheets between the positively charged layers of the α-hydroxide. Thermal decomposition of the intercalated solids yields graphene/nanocrystalline metal oxide composites. Electron microscopy analysis of the composites indicates that the nanoparticles are intercalated between graphene layers.     

Influence of reducing gases on the reduction behavior of water-atomized Fe-Cr-Mo powder

In this study, Fe-based powder of composition Fe-3 wt% Cr-0.5 wt% Mo was prepared using a water atomization process. After atomization, the total oxide content of the powder was calculated as ca. 2.09 wt%. Gas reduction of the as-atomized powder using CO, CH₄, and H₂ gases was carried out in a horizontal vacuum tubetype furnace at 900 °C. Thermodynamic and kinetic calculations for the reduction reactions were carried out using FactSage and HSC Chemistry programs. The results showed that the reduction proceeded in two stages: from Fe₃O₄ to FeO, and finally to Fe. Each reducing gas was evaluated and compared based on the oxide reduction capability. The lowest oxygen content was achieved for CH4 (0.49 wt%). However, with CH₄, cementite (Fe₃C) was also detected due to cracking of CH₄.     

Behavior problems of residents with dementia in special care units

188 patients with high-turnover type post-menopausal osteoporosis were treated for 18 months with 4 different treatment regimens of S-calcitonin nasal spray. For a total of 18 months group 1 was given 100 IU/day, continuously; group 2, 100 IU/day daily for 30 days every other month ("ciclically"); group 3, 200 IU/day continuously, and group 4, 200 IU/day, ciclically. To monitor the effects of treatment, MOC of L2-L4, as well as serum osteocalcin and urinary hydroxyproline: creatinine levels were measured, on initiation of therapy, then at 9, 12 and 18 months, and finally at 6 and 12 months after completion of therapy. Analysis of the results yields the following major points: (A) The peak increase in bone mass occurs at 9 months the continuous therapy groups, and at 18 months in the cyclic therapy groups. In absolute values, the peak are higher in the continuous groups than in the cyclic groups. (B) The long-term increase in bone mass (measured at one year after completion of therapy) does not differ significantly between cyclic and continuous treatment groups at the same dosage. (C) During treatment, a dose-effect relationship exist when comparing dosages of 100 IU/day and 200 IU/day. However, this disappears by one year after completion of therapy. (D) There seems to be a "rebound effect" on osseous turnover after cessation of S-calcitonin therapy. The magnitude and rapidity of onset of this effect appear to correlate directly with the dosage of S-calcitonin administered.