Design and construction of the high-speed optoelectronic memory system demonstrator

The high-speed optoelectronic memory system project is concerned with the reduction of latency within multiprocessor computer systems (a key problem) by the use of optoelectronics and associated packaging technologies. System demonstrators have been constructed to enable the evaluation of the technologies in terms of manufacturability. The system combines fiber, free space, and planar integrated optical waveguide technologies to augment the electronic memory and the processor components. Modeling and simulation techniques were developed toward the analysis and design of board-integrated waveguide transmission characteristics and optical interfacing. We describe the fabrication, assembly, and simulation of the major components within the system.     

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。     

A 10-Gb/s 16:1 multiplexer and 10-GHz clock synthesizer in0.25-μm SiGe BiCMOS

A 10-Gb/s 16:1 multiplexer, 10-GHz clock generator phase-locked loop (PLL), and 6 × 16 b input data buffer are integrated in a 0.25-μm SiGe BiCMOS technology. The chip multiplexes 16 parallel input data streams each at 622 Mb/s into a 9.953-Gb/s serial output stream. The device also produces a 9.953-GHz output clock from a 622- or 155-MHz reference frequency. The on-board 10-GHz voltage-controlled oscillator (VCO) has a 10% tuning range allowing the chip to accommodate both the SONET/SDH data rate of 9.953 Gb/s and a forward error correction coding rate of 10.664 Gb/s. The 6 × 16 b input data buffer accommodates ±2.4 ns of parallel input data phase drift at 622 Mb/s. A delay-locked loop (DLL) in the input data buffer allows the support of multiple input clocking modes. Using a clock generator PLL bandwidth of 6 MHz, the 9.953-GHz output clock exhibits a generated jitter of less than 0.05 UI_P-P over a 50-kHz to 80-MHz bandwidth and jitter peaking of less than 0.05 dB     

A longitudinal study of the effectiveness of a multi-media intervention on parents’ knowledge and use of vehicle safety systems for children

Motor-vehicle crashes are the leading cause of death and serious injury for children under the age of 14 in Canada and in the United States despite mandatory use of vehicle restraints since 1977. Using a pre- and post-test design, the present study tests the effectiveness of a multi-media intervention study on parents’ knowledge of car safety seat use for children (0-12 years). The sample included 201 parents from four Ontario cities. Results indicate that parents’ knowledge of when to accurately and safely transition a child to the appropriate car safety seat based on child's age, weight and height was retained at the 1 year post-test for children 4-8 years of age. The rates of correct use of safety seats significantly increased 1 year following the intervention program. Other factors that influenced parent's knowledge included being a parent versus non-parents, gender, income, education, sources of information, and regional location. The results of this study can help guide the development and implementation of future intervention programs and injury prevention policy.     

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.     

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.