Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble EGFR in Non-Small Cell Lung Cancer

Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered. This study investigates the use of sEGFR as a potential diagnostic biomarker for NSCLC and also characterizes the biological function of sEGFR to clarify the molecular mechanisms involved in the course of action of this protein. Plasma sEGFR levels from a heterogeneous cohort of 37 non-advanced NSCLC patients and 54 healthy subjects were analyzed by using an enzyme-linked immunosorbent assay. The biological function of sEGFR was analyzed in vitro using NSCLC cell lines, investigating effects on cell proliferation and migration. We found that plasma sEGFR was significantly decreased in the NSCLC patient group as compared to the control group (median value: 48.6 vs. 55.6 ng/mL respectively; p = 0.0002). Moreover, we demonstrated that sEGFR inhibits growth and migration of NSCLC cells in vitro through molecular mechanisms that included perturbation of EGF/EGFR cell signaling and holoreceptor internalization. These data show that sEGFR is a potential circulating biomarker with a physiological protective role, providing a first approach to the functional role of the soluble isoform of EGFR. However, the impact of these data on daily clinical practice needs to be further investigated in larger prospective studies.     

Miniaturized coplanar waveguide stop band filters based on multiple tuned split ring resonators

A novel compact stop band filter consisting of a 50 /spl Omega/ coplanar waveguide (CPW) with split ring resonators (SRRs) etched in the back side of the substrate is presented. By aligning SRRs with the slots, a high inductive coupling between line and rings is achieved, with the result of a sharp and narrow rejection band in the vicinity of the resonant frequency of the rings. In order to widen the stop band of the filter, several ring pairs tuned at equally spaced frequencies within the desired gap are cascaded. The frequency response measured in the fabricated prototype device exhibits pronounced slopes at either side of the stop band and near 0 dBs insertion loss outside that band. Since SRR dimensions are much smaller than signal wavelength, the proposed filters are extremely compact and can be used to reject frequency parasitics in CPW structures by simply patterning properly tuned SRRs in the back side metal. Additional advantages are easy fabrication and compatibility with MMIC or PCB technology.     

Orbital venous approach to the cavernous sinus: an analysis of the facial and orbital venous system

Carotid-cavernous fistulas are abnormal communications between the internal carotid artery and the cavernous sinus produced by a rupture of the wall of the carotid artery or one of its branches into the sinus. Extradural branches of the internal or external carotid arteries may communicate with the cavernous sinus, producing proptosis, progressive glaucoma, and ocular vascular engorgement. Various approaches to obliterate these fistulas have evolved, many of which carry high morbidity or are precluded by anatomical considerations. Analysis of the venous anatomy of the orbit and face, including human cadaver dissections, reveals a new and safe approach to the cavernous sinus, requiring microsurgical isolation and cannulation of the superior ophthalmic vein through an anterior orbital approach. Selective embolization of a carotid-cavernous fistula can be performed successfully through this route. We present pertinent anatomy and technical considerations and the successful clinical application of these principles. Surgeons familiar with craniofacial anatomy and microvascular techniques can apply these principles and play an active role in the treatment of these complex problems.     

Practical constraints in growth of lightwave networks

The amount of fiber required, propagation delay, and length of the longest link are significant design constraints in spatially large networks. This paper examines these characteristics from the viewpoint of growth and compares basic networks with hierarchical ones in terms of these characteristics. Results show that, when considering growth from three nodes, a star network randomly placed with a uniform distribution uses less fiber than a dual ring until there are 57 nodes. As the networks become large, the star has the smallest propagation delay and the dual ring uses the least amount of fiber. A two-level network having a star on the upper level and dual rings on the lower network level performs well in both categories by using 1.38 times as much fiber as the dual ring and having 1.65 times the propagation delay of a star as the number of nodes becomes large     

Macrophage formation of angiostatin during inflammation. A byproduct of the activation of plasminogen

Angiostatin is a potent inhibitor of tumor angiogenesis and the growth of metastatic foci. Recent studies have indicated that neoplastic cells can generate angiostatin directly or in cooperation with tumor-associated macrophages. In studies reported here, we determined whether angiostatin is generated in mice under non-neoplastic settings. Utilizing murine RAW264.7 macrophages and thioglycollate-elicited peritoneal macrophages, we demonstrate that angiostatin-like fragments are generated as a byproduct of the proteolytic regulation of membrane-bound plasmin. Plasmin proteolysis and subsequent loss in membrane-bound plasmin activity requires active plasmin but was unaffected by inhibitors of metalloproteinases. Lysine binding fragments of plasmin, isolated from macrophage-conditioned media utilizing affinity chromatography, appeared as a major (48 kDa) and two minor bands (42 and 50 kDa) in SDS-polyacrylamide gel electrophoresis and were immunoreactive with anti-kringle 1-3 IgG. Each peptide begins with Lys77 and contains the entire sequence of angiostatin. The affinity isolated plasmin fragments inhibited bFGF-induced endothelial cell proliferation. Lavage fluid recovered from the peritoneal cavities of mice previously injected with thioglycollate contained angiostatin-like plasmin fragments similar to those generated in vitro. This is the first demonstration that angiostatin-like plasmin fragments are generated in a non-neoplastic inflammatory setting. Thus, in addition to regulating pericellular plasmin activity, proteolysis of plasmin generates inactive kringle-containing fragments expressing angiostatic properties.     

What can you verify and enforce at runtime?

The underlying property, its definition, and representation play a major role when monitoring a system. Having a suitable and convenient framework to express properties is thus a concern for runtime analysis. It is desirable to delineate in this framework the sets of properties for which runtime analysis approaches can be applied to. This paper presents a unified view of runtime verification and enforcement of properties in the Safety-Progress classification. First, we extend the Safety-Progress classification of properties in a runtime context. Second, we characterize the set of properties which can be verified (monitorable properties) and enforced (enforceable properties) at runtime. We propose in particular an alternative definition of ??property monitoring?? to the one classically used in this context. Finally, for the delineated sets of properties, we define specialized verification and enforcement monitors.     

Laparoscopic vs. open wedge biopsy of the liver

The number of people smoking free-base cocaine, or "crack," has increased dramatically in recent years. Concomitantly, the literature describing complications of such use has grown as well. Adverse pulmonary effects are being increasingly noted, such as respiratory symptoms, pulmonary hemorrhage, pulmonary edema, asthma, and pulmonary barotrauma. These and other pulmonary effects are reviewed.     

Design methodology for the optimization of transformer-loaded RF circuits

In this paper, a design methodology for the optimization of transformer-loaded RF circuits is presented. The optimization procedure is based on a novel figure of merit for the integrated transformer (namely the transformer characteristic resistance), which was introduced to quantify its performance when operated as a tuned load. Using the proposed approach, a highly linear up-converter for 5-GHz wireless LAN applications was implemented in a 45-GHz-f/sub T/ SiGe HBT technology. The circuit achieved an output 1-dB compression point of 4.5 dBm and a power gain of 18 dB, while drawing only 34 mA from a 3-V power supply.