Inhibition of the tyrosine phosphatase SHP-2 suppresses angiogenesis in vitro and in vivo

Endothelial cell survival is indispensable to maintain endothelial integrity and initiate new vessel formation. We investigated the role of SHP-2 in endothelial cell survival and angiogenesis in vitro as well as in vivo. SHP-2 function in cultured human umbilical vein and human dermal microvascular endothelial cells was inhibited by either silencing the protein expression with antisense-oligodesoxynucleotides or treatment with a pharmacological inhibitor (PtpI IV). SHP-2 inhibition impaired capillary-like structure formation (p < 0.01; n = 8) in vitro as well as new vessel growth ex vivo (p < 0.05; n = 10) and in vivo in the chicken chorioallantoic membrane (p < 0.01, n = 4). Additionally, SHP-2 knock-down abrogated fibroblast growth factor 2 (FGF-2)-dependent endothelial proliferation measured by MTT reduction ( p ! 0.01; n = 12). The inhibitory effect of SHP-2 knock-down on vessel growth was mediated by increased endothelial apoptosis ( annexin V staining, p ! 0.05, n = 9), which was associated with reduced FGF-2-induced phosphorylation of phosphatidylinositol 3-kinase (PI3-K), Akt and extracellular regulated kinase 1/2 (ERK1/2) and involved diminished ERK1/2 phosphorylation after PI3-K inhibition (n=3). These results suggest that SHP-2 regulates endothelial cell survival through PI3-K-Akt and mitogen-activated protein kinase pathways thereby strongly affecting new vessel formation. Thus, SHP-2 exhibits a pivotal role in angiogenesis and may represent an interesting target for therapeutic approaches controlling vessel growth. Copyright (C) 2007 S. Karger AG, Basel

On the validity and identification of long-run restrictions for a cointegrated system

The identification approach suggested in Blanchard and Quah [1989 The dynamic effects of aggregate supply and demand disturbances. Am. Econ. Rev. 79:655-673] and King et al. [1991 Stochastic trends and economic flucuations. Am. Econ. Rev. 81:819-840] makes use of the long-run properties of structural disturbances. This paper provides economic underpinning for the use of long-run identifying restrictions by showing formally its validity for the class of exogenous growth models under certain conditions. This paper also obtains the minimum number of restrictions, in addition to the long-run restrictions, required for the identification of structural disturbances in a co-integrated system. © 2000 Elsevier Science B.V. All rights reserved.postprin

W-Band GaAs HEMT MMIC Subharmonically Pumped Diode Mixers with 20 GHz IF Bandwidth

Two subharmonically pumped (SHP) diode mixers are designed for wideband W-band RF frequencies, fixed LO frequency operation. These mixers are fabricated on a 4-mil substrate using 0.1- µµµµm GaAs MMIC process. Both simulation and test results show that the mixers are with 12.25 and 11.75 dB average conversion losses, respectively. Both mixers have IF bandwidth wider than 20 GHz. The conversion loss flatness of the symmetric circuit is within ±1.25 dB. To our knowledge, these are the state-of-the-art result on low-conversion-loss wideband MMIC SHP diode mixers

Solution of multi-player linear-quadratic alternating-move games and its application to the timing pattern of wage adjustment

In order to analyze a multi-player linear-quadratic alternating-move dynamic game, this paper develops a solution method by making use of the similar structure of this game and a simultaneous-move dynamic game with alternating payoff functions. It then applies the method to investigate whether staggered or synchronized wage adjustment will be preferred when more than two wage setters interact strategically and dynamically. The results suggest that the strategic benefit provided by staggered wage adjustment is robust with respect to the number of sectors in the economy.postprin

HURDLE COUNT-DATA MODELS IN RECREATION DEMAND ANALYSIS

When a sample of recreators is drawn from the general population using a survey, many in the sample will not recreate at a recreation site of interest. This study focuses on nonparticipation in recreation demand modeling and the use of modified count-data models. We clarify the meaning of the single-hurdle Poisson (SHP) model and derive the double-hurdle Poisson (DHP) model. The latter is contrasted with the SHP and we show the DHP is consistent with Johnson and Kotz's zero-modified Poisson model.Resource /Energy Economics and Policy,