Cyclooxygenase1 (COX1) and COX2 mediate the rate-limiting step in arachidonic acid metabolism. Expression of COX2 mRNA and protein is often enhanced in various human cell types by inflammatory cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha). IL-1beta enhanced expression of various prostanoids and this expression was blocked by COX2 selective inhibitors. IL-1beta markedly induced angiogenesis in vitro and in vivo, which was significantly inhibited by COX2 selective inhibitors but not by a vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor. In contrast, COX2 selective inhibitors only partially blocked VEGF-induced angiogenesis. EP2, EP4 (prostaglandin E2 receptors) agonists and thromboxane A2 (TXA2) receptor agonists induced angiogenesis in vitro and in vivo; IL-1beta-induced angiogenesis was blocked by an EP4 antagonist and a TXA2 receptor antagonist. IL-1beta induced much less angiogenesis in cornea of COX2 knockout mice than that of wild-type mice. This is the first report that COX2 and some prostanoids play a key role in IL-1beta-induced angiogenesis.

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Self‐assembled peptide hydrogels represent the realization of peptide nanotechnology into biomedical products. There is a continuous quest to identify the simplest building blocks and optimize their critical gelation concentration (CGC). Herein, a minimalistic, de novo dipeptide, Fmoc‐Lys(Fmoc)‐Asp, as an hydrogelator with the lowest CGC ever reported, almost fourfold lower as compared to that of a large hexadecapeptide previously described, is reported. The dipeptide self‐assembles through an unusual and unprecedented two‐step process as elucidated by solid‐state NMR and molecular dynamics simulation. The hydrogel is cytocompatible and supports 2D/3D cell growth. Conductive composite gels composed of Fmoc‐Lys(Fmoc)‐Asp and a conductive polymer exhibit excellent DNA binding. Fmoc‐Lys(Fmoc)‐Asp exhibits the lowest CGC and highest mechanical properties when compared to a library of dipeptide analogues, thus validating the uniqueness of the molecular design which confers useful properties for various potential applications.

The performance of a cryogenic system that monitors the extracranial magnetic field simultaneously at 14 positions over the scalp has been evaluated to determine the accuracy with which neuronal activity can be located within the human brain. Initially, measurements were implemented on two model systems, a lucite sphere filled with saline and a model skull. With a magnetic field strength similar to that of a human brain, the measurement and analysis procedures demonstrated a position accuracy better than 3 mm, for a current dipole 3 cm beneath the surface. Subsequently, measurements of the magnetic field pattern appearing 100 ms after the onset of an auditory tone-burst stimulus were obtained in three human subjects. The location of the current dipole representing intracellular ionic current in active neurons of the brain was determined, with 3-mm accuracy, to be within the cortex foring the floor of the Sylvian fissure of the individual subjects, corresponding closely to the Heschl gyrus as determined from magnetic resonance images. With the sensors placed at appropriate positions, the locations of neuronal sources for different tone frequencies could be obtained without moving the recording instrument. Adaptation of activity in human auditory cortex was shown to reveal long-term features with a paradigm that compared response amplitudes for three tones randomly presented.Locating neuronal activity within the human brain by measuring the concomitant extracranial magnetic field pattern has been a laborious procedure with single-sensor instruments. Typically, 40 or more positions must be sequentially measured over the scalp, which may take as long as 6 hr to complete. The development of multisensor systems (1-4) made it possible to improve the efficiency of this process, an advance that is of considerable importance for both clinical and research applications. We have installed, at the New York University Medical Center, a commercially available 14-sensor system (Biomagnetic Technologies, San Diego, CA) representing state-of-the-art performance and have evaluated techniques to locate accurately the three-dimensional position of neuronal activity within the human brain (the 14-sensor system consists of two model 607 neuromagnetometers).The effectiveness of these systems has been evaluated through measurements on two types of carefully designed physical models or "phantoms" (a lucite sphere and a plastic skull), both containing a conducting fluid in which an electrical current dipole was placed at a known position. Measurements were made with field strengths at physiological levels (500 ff); this is an important distinction between this and prior studies (5, 6). scans (18-20), but even in these cases there was no a priori knowledge that the activity should be associated with the particular area of the lesion.Obtaining the position of a localized source from a field map across the scalp is conceptually simple if neuronal activity is sufficiently well confined to enable it to be modeled as an equivalent curr...