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We previously identified the structural requirement for the inhibitory activity of Leishmania lipophosphoglycan (LPG) to block endothelial adhesion to monocytes. Here we showed that LPG reduces transendothelial migration of monocytes. LPG pretreatment of endothelial cells (2 μM, 1 h) reduced monocyte migration across endothelial cells activated by bacterial endotoxin (LPS) or IL-1β (60 and 46%, respectively). A fragment of LPG (i.e., repeating phosphodisaccharide (consisting of galactosyl-mannose)) and LPG coincubated with LPG-neutralizing mAb lacks inhibitory activity on monocyte migration. Pretreatment of monocytes with LPG (2 μM, 1 h) also did not affect monocyte migration through control or LPS-activated endothelial cells. FACS analysis reveals that LPG treatment blocked the LPS-mediated expression of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 on endothelial cells and monocyte adhesion without altering the integrity of the endothelial monolayer. LPG (2 μM, 1 h) alone was capable of altering the expression and distribution of two junctional adhesion molecules, CD31 and vascular endothelium cadherin, as well as reversing the effects of LPS on these proteins. The induction of endothelial cells by LPS to transcribe and release monocyte chemoattractant protein-1 (MCP-1) was significantly reduced by LPG (40–65%). LPG treatment of nonactivated endothelial cells also suppressed by 55 to 75% the monocyte migration triggered by a MCP-1 chemoattractant gradient, and coincubation of LPG with neutralizing mAb abrogated the inhibitory activity. Together, these data point to a novel anti-inflammatory function of LPG in reducing monocyte migration across endothelial cells via a mechanism of inhibition of endothelial expression of cell adhesion molecules, modulation of intercellular junctional proteins, and synthesis of MCP-1.

We previously reported that monocyte adhesion to tumor necrosis factor-α (TNF-α)–treated endothelial cells increased expression of tissue factor and CD36 on monocytes. Using immunological cross-linking to mimic receptor engagement by natural ligands, we now show that CD15 (Lewis X), a monocyte counter-receptor for endothelial selectins may participate in this response. We used cytokine production as a readout for monocyte activation and found that CD15 cross-linking induced TNF-α release from peripheral blood monocytes and cells from the monocytic cell line MM6. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) showed an increase in steady-state TNF-α mRNA after 3 to 4 hours of cross-linking. CD15 cross-linking also concomitantly increased interleukin-1β (IL-1β) mRNA, while no apparent change was observed in the levels of β-actin mRNA, indicating specificity. To examine transcriptional regulation of cytokine genes by CD15 engagement, a CAT plasmid reporter construct containing IL-1β promoter/enhancer sequences was introduced into MM6. Subsequent cross-linking of CD15 increased CAT activity. CD15 engagement by monoclonal antibody also attenuated IL-1β transcript degradation, demonstrating that signaling via CD15 also had posttranscriptional effects. Nuclear extracts of anti-CD15 cross-linked cells demonstrated enhanced levels of the transcriptional factor activator protein-1, minimally changed nuclear factor-κB, and did not affect SV40 promoter specific protein-1. We conclude that engagement of CD15 on monocytes results in monocyte activation. In addition to its well-recognized adhesive role, CD15 may function as an important signaling molecule capable of initiating proinflammatory events in monocytes that come into contact with activated endothelium.

Priapism is a rare condition that involves persistent penile erection for greater than 4 h. Distinct variants exist, each with unique characteristics. Ischemic priapism is a painful medical emergency that may occur as a result of veno-occlusion leading to hypoxia and tissue death. Recurrent bouts of ischemic priapism, or stuttering priapism, require treatment for individual attacks as well as long-term prevention. Non-ischemic priapism is associated with trauma and may be managed conservatively. Recent advances into the pathophysiology of priapism have allowed the development of treatment algorithms that specifically target the mechanisms involved. In this review, we outline the basics of smooth muscle contraction and describe how derangement of these pathways results in priapism. A pathophysiological approach to the treatment of priapism is proposed with duration-based algorithms presented to assist in management.

The measured attenuation correction technique is widely used in cardiac positron tomographic studies. However, the success of this technique is limited because of insufficient counting statistics achievable in practical transmission scan times, and of the scattered radiation in transmission measurement which leads to an underestimation of the attenuation coefficients. In this work, a segmented attenuation correction technique has been developed that uses artificial neural networks. The technique has been validated in phantoms and verified in human studies. The results indicate that attenuation coefficients measured in the segmented transmission image are accurate and reproducible. Activity concentrations measured in the reconstructed emission image can also be recovered accurately using this new technique. The accuracy of the technique is subject independent and insensitive to scatter contamination in the transmission data. This technique has the potential of reducing the transmission scan time, and satisfactory results are obtained if the transmission data contain about 400,000 true counts per plane. It can predict accurately the value of any attenuation coefficient in the range from air to water in a transmission image with or without scatter correction.

The new ligand L(1), 1-N,1-N-bis(pyridine-2-ylmethyl)-3-N-(pyridine-2-ylmethylidene)benzene-1,3-diamine, was synthesized as a platform for the study of bimetallic complexes containing redox-active ligands. The asymmetric L(1) contains a redox-active α-iminopyridine unit bridged to redox-inert bis(2-pyridylmethyl)amino counterpart and offers two distinct coordination sites. The coordination chemistry of L(1) with Fe, Cu, and Zn was examined. Reaction with zinc afforded the asymmetric binuclear complex [(L(1))Zn(2)Cl(4)] (1), whereas the symmetric [(L(1))(2)Fe(2)(OTf)(2)](OTf)(2) (2) and [(L(1))(2)Cu(2)](OTf)(4) (3) were isolated in reactions with iron and copper. Both metal- and ligand-centered redox processes are available to the series of metal compounds. EPR and Mössbauer spectroscopy and magnetic susceptibility studies establish that both 2 and 3 are paramagnetic; the vanishingly small ferromagnetic interaction produces decoupled high-spin Fe(II) (S = 2) ions in 2. DFT calculations provide further insight into the nature of the exchange interactions in the dimeric systems.

Myogenesis, the formation of skeletal muscle, is a multistep event that commences with myoblast proliferation, followed by cell-cycle arrest, and finally the formation of multinucleated myotubes via fusion of mononucleated myoblasts. Each step is orchestrated by well-documented intracellular factors, such as cytoplasmic signalling molecules and nuclear transcription factors. Regardless, the key step in getting a more comprehensive understanding of the regulation of myogenesis is to explore the extracellular factors that are capable of eliciting the downstream intracellular factors. This could further provide valuable insight into the acute cellular response to extrinsic cues in maintaining normal muscle development. In this paper, we survey the intracellular factors that respond to extracellular cues that are responsible for the cascades of events during myogenesis: myoblast proliferation, cell-cycle arrest of myoblasts, and differentiation of myoblasts into myotubes. This focus on extracellular perspective of muscle development illustrates our mass spectrometry-based proteomic approaches to identify differentially expressed secreted factors during skeletal myogenesis.

This paper presents a new type of circulator that consists of three Lange couplers and two ferrite circulators for broadband, high isolation, transmit noise suppression and simultaneous transmit and receive (STAR). The operation principal of the circulator is based on quadrature phase cancellation and combination techniques. Preliminary results show that the isolation between the transmit and receive port is >24 dB in frequency range of 5–12 GHz without optimization and 60 dB isolation with 800 MHz bandwidth with optimization. The NF data at the receive port show significant suppression of transmit noise for Gain-NF product that exceeds 21 dB.

Since adhesion of neutrophils (PMN) to endothelial cells may influence PMN activation responses, we examined whether adhesion of PMN to TNF alpha-activated human umbilical vein endothelial cells (HUVEC) stimulates leukotriene B4 (LTB4) production. Endothelial adhesivity towards PMN increased after HUVEC pretreatment with TNF alpha for 4 h. LTB4 production increased markedly in response to stimulation with arachidonic acid (20 microM) when PMN were added to the hyperadhesive HUVEC. In contrast, stimulation of PMN in suspension did not potentiate LTB4 production. LTB4 production persisted when PMN were applied to TNF alpha-pretreated HUVEC fixed with 1% paraformaldehyde excluding the possibility that metabolic activity of endothelium participates in this response. PMN adhesion to plastic and gelatin also enhanced LTB4 indicating that adhesion was a critical event in inducing LTB4 production. We used monoclonal antibodies (mAb) to adhesion molecules on endothelial cells (i.e., endothelial leukocyte adhesion molecule-1 (ELAM-1) and intercellular adhesion molecule-1 (ICAM-1)) or on PMN (CD18) to assess the role of PMN adhesion to the activated endothelium on LTB4 potentiation. Both anti-ELAM-1 mAb and anti-ICAM-1 mAb inhibited PMN adhesion (by 55 and 41%, respectively) as well as LTB4 production (by 65 and 50%, respectively). Anti-CD18 mAb also reduced the adhesion (65%) and the LTB4 production (66%). Furthermore, combination of anti-ELAM-1 mAb (H18/7) and anti-ICAM-1 mAb (RR1/1) or of anti-ELAM-1 mAb (H18/7) and anti-CD18 mAb (IB4) had an additive effect in inhibiting both PMN adhesion as well as LTB4 production. PMN adherence to immobilized recombinant soluble rELAM-1 or rICAM-1 also increased LTB4 production, which was prevented with relevant mAbs. However, neither rELAM-1 nor rICAM-1 stimulated LTB4 production of PMN in suspension. We conclude that PMN adhesion to TNF alpha-stimulated endothelial cells enhances LTB4 production by PMN, a response activated by binding of PMN to expressed endothelial cell surface adhesion molecules.

This paper presents a new type of quasi-circulator that consists of three quadrature hybrids with broadband operation, high isolation, and suppression of noise figure (NF) for simultaneous transmit and receive (STAR) phased-array systems. The operation principal of the circulator is based on phase cancellation and combination techniques to enhance isolation and suppress noise figure (NF). The circulator is implemented using three MMIC Lange couplers and active elements to provide quasi-circulator operation. The preliminary measured data shows that it is possible to obtain 35 dB isolation* between the transmit and receive port with 1.5 GHz operational bandwidth at X-band, while the NF at the receive port is ≪ 5.5 dB. Using an external integrated power amplifier to partially implement an active quasi circulator, the performance of the device shows 25 dB isolation with 17% bandwidth, with NF less than 4.7 dB at the receive port. The proposed architecture is suitable for MMIC integration and system-on-chip (SOC) applications. (*The isolation is defined by the S-parameter difference, in dB, between forward transmission from the transmit to receive port and from the transmit to the antenna port.)

Proceedings of the second biennial international conference on chemical measurement and monitoring of the environment : [Enviroanalysis '98], May 1998, Ottawa, Ontario, Canada

Advances in the Internet, communication technologies, and computation power have accelerated the cycle of new product development as well as supply chain efficiency in an unprecedented manner. Digital technology provides not only an important means for the optimization of production efficiency through simulations prior to the start of actual operations but also facilitates manufacturing process automation through efficient and effective automatic tracking of production data from the flow of materials, finished goods, and people, to the movement of equipment and assets in the value chain. There are two major applications of digital technology in manufacturing. The first deals with the modeling, simulation, and visualization of manufacturing systems and the second deals with the automatic acquisition, retrieval, and processing of manufacturing data used in the supply chain. This chapter summarizes the state of the art of digital manufacturing which is based on virtual manufacturing (VM) simulation and radio frequency identification (RFID)-based automation. The associated technologies, their key techniques, and current research work are highlighted. In addition, the social and technological obstacles to the development of a VM system and in an RFID-based manufacturing process automation system, and some practical application case studies of digital manufacturing based on VM and RFID-based automation, are also discussed.

Monte Carlo calculations have previously been performed by Eckerman to evaluate the absorbed fractions of continuous sources of monoenergetic electrons in marrow cavities of human bone. The difference in scattering power of electrons in cortical bone (CB) and the red marrow (RM) was neglected. In the present work the Integrated Tiger Series and Electron–Gamma–Shower Monte Carlo codes were used to investigate the effect of topology of the bone and bone marrow interface on backscatter dose increase to the marrow. Planar, cylindrical, and spherical geometries were included. For the planar geometry, a maximum dose increase of 9±1 (S.E. of the mean)% was obtained in the region within 12 mg/cm2 from the interface due to a semi‐infinite source of electrons with energy greater than 0.5 MeV. An increase of 7±1% was observed experimentally in the same region due to a semi‐infinite source of32P. This was in good agreement with Monte Carlo calculation. Averaged over the region of RM embedding electron sources between two planar CB/RM interfaces 1000 μm apart, a dose enhancement of 10±2% was predicted for electron energies from 1 to 1.75 MeV. For the cylindrical interface with 500‐μm radius of curvature, the maximum dose increase averaged over the whole cylinder due to an isotropic distribution of monoenergetic electrons inside the cylinder was 12±1%. This occurred at 0.75 MeV. For the spherical interface with 500‐μm radius of curvature, the maximum dose increase in the region within 20 μm (2.1 mg/cm2) from the interface due to an isotropic distribution of monoenergetic electrons inside the sphere was as high as 21±1%. This occurred at about 0.5 MeV. The dose increase, averaged over the whole sphere, was 12±0.6%.

To evaluate serum cytokine concentrations in children with and without obstructive sleep apnoea (OSA) and to investigate the effects of OSA treatment on cytokines.Consecutive children with habitual snoring and symptoms suggestive of OSA were recruited. They completed a sleep apnoea symptom questionnaire, underwent physical examination and overnight polysomnography (PSG). OSA was diagnosed if obstructive apnoea index (OAI)1. A blood sample was collected for analysis of IL-6, IL-8, and TNF-alpha after PSG.One hundred forty-two children (97 males) with a median (IQR) age of 11.1 years (9.0-12.8) were recruited. The commonest presenting symptoms were nocturnal mouth breathing, prone sleeping position and poor attention at school. Forty-seven children were found to have OSA and they had higher serum IL-6 [0.1 (0.1-0.4) vs 0.1 (0.1-0.1) pg/mL, P = 0.001] and IL-8 [1.7 (1.0-2.3) vs 1.3 (0.9-1.7) pg/mL, P = 0.029] concentrations compared to their non-OSA counterparts. Multiple regression analysis indicated that OAI was significantly associated with both IL-6 (r = 0.351, P0.001) and IL-8 (r = 0.266, P = 0.002). Sixteen children underwent treatment and there was significant reduction in mean (SD) serum IL-8 after intervention [pre vs post levels of 1.9 (1.0) vs 1.1 (0.6) pg/mL, P = 0.001] independent of weight loss.Children with OSA had elevated levels of pro-inflammatory cytokines that normalised following treatment suggesting that the inflammatory response is potentially reversible. Early detection and intervention may be beneficial.

Perturbation in dose distributions of point sources of low-energy electrons at planar interfaces of cortical bone (CB) and red marrow (RM) was investigated experimentally and by Monte Carlo codes EGS and the TIGER series. Ultrathin LiF thermoluminescent dosimeters were used to measure the dose distributions of point sources of {sup 204}Tl and {sup 147}Pm in RM. When the point sources were at 12 mg/cm{sup 2} from a planar interface of CB and RM equivalent plastics, dose enhancement ratios in RM averaged over the region 0--12 mg/cm{sup 2} from the interface were measured to be 1.08{plus minus}0.03 (SE) and 1.03{plus minus}0.03 (SE) for {sup 204}Tl and {sup 147}Pm, respectively. The Monte Carlo codes predicted 1.05{plus minus}0.02 and 1.01{plus minus}0.02 for the two nuclides, respectively. However, EGS gave consistently 3% higher dose in the dose scoring region than the TIGER series when point sources of monoenergetic electrons up to 0.75 MeV energy were considered in the homogeneous RM situation or in the CB and RM heterogeneous situation. By means of the TIGER series, it was demonstrated that aluminum, which is normally assumed to be equivalent to CB in radiation dosimetry, leads to an overestimation of backscattering of low-energy electrons in soft tissuemore » at a CB--soft-tissue interface by as much as a factor of 2.« less