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Selected AbstractsStochastic computational modelling of highly heterogeneous poroelastic media with long-range correlationsINTERNATIONAL JOURNAL FOR NUMERICAL AND ANALYTICAL METHODS IN GEOMECHANICS, Issue 1 2004Diego G. Frias Abstract The compaction of highly heterogeneous poroelastic reservoirs with the geology characterized by long-range correlations displaying fractal character is investigated within the framework of the stochastic computational modelling. The influence of reservoir heterogeneity upon the magnitude of the stresses induced in the porous matrix during fluid withdrawal and rock consolidation is analysed by performing ensemble averages over realizations of a log-normally distributed stationary random hydraulic conductivity field. Considering the statistical distribution of this parameter characterized by a coefficient of variation governing the magnitude of heterogeneity and a correlation function which decays with a power-law scaling behaviour we show that the combination of these two effects result in an increase in the magnitude of effective stresses of the rock during reservoir depletion. Further, within the framework of a perturbation analysis we show that the randomness in the hydraulic conductivity gives rise to non-linear corrections in the upscaled poroelastic equations. These corrections are illustrated by a self-consistent recursive hierarchy of solutions of the stochastic poroelastic equations parametrized by a scale parameter representing the fluctuating log-conductivity standard deviation. A classical example of land subsidence caused by fluid extraction of a weak reservoir is numerically simulated by performing Monte Carlo simulations in conjunction with finite elements discretizations of the poroelastic equations associated with an ensemble of geologies. Numerical results illustrate the effects of the spatial variability and fractal character of the permeability distribution upon the evolution of the Mohr,Coulomb function of the rock. Copyright © 2004 John Wiley & Sons, Ltd. [source] Adverse drug reactions to biologicsJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 6 2010Kathrin Scherer Summary The use of biologics has rapidly expanded since the introduction of the first diagnostic antibodies; they are now widely employed in oncology, autoimmune disorders, inflammatory diseases and transplantation medicine. Their widespread use has resulted in an increase in adverse drug reactions. Adverse effects result from both direct pharmacological actions and immunological actions, as well as through induction of a specific immune response. The nomenclature, particularly of the monoclonal antibodies, identifies the target structure and organ as well as the species of origin, which then helps predict their effects and antigenic properties. Depending on the extent of foreign protein, anti-allotypic or anti-idiotypic antibodies with or without neutralizing properties may be induced. Adverse drug reactions from biologics often depend on the target and may be explained by activation or inhibition of particular cytokine pathways. Adverse drug reactions are classified by their pathomechanism, which enhances understanding of the pathogenesis and facilitates both allergologic diagnostic measures and planning of premedication in future treatments. This review emphasizes immunostimulatory and hypersensitivity reactions. [source] Employment, privatization, and managerial choice: Does contracting out reduce public sector employment?JOURNAL OF POLICY ANALYSIS AND MANAGEMENT, Issue 1 2007Sergio Fernandez We examine the effects of governments' use of alternative service provision on public employment using panel data from a nationally representative sample of local governments. We model the effects of alternative service provision on the size of the public workforce and hypothesize that alternative provision jointly impacts both full- and part-time employment. We find evidence of an inter-relationship between these employment types. Our results from seemingly unrelated and 3SLS regressions indicate that full-time employment in the public sector declines when additional services are provided by for-profit providers, while part-time employment increases. The net employment effect in the public sector is negative when government services are moved to the for-profit sector. These combined effects result in a compositional shift toward more part-time public sector employment. © 2006 by the Association for Public Policy Analysis and Management [source] Gene Knockdown: A Powerful Tool for Gene Function Study in FishJOURNAL OF THE WORLD AQUACULTURE SOCIETY, Issue 3 2008Surintorn Boonanuntanasarn So far, there are a number of fish genome projects, including experimental and economically important fish that provide available DNA sequence information. However, the function of a gene cannot be deduced only by its DNA sequence. Therefore, a technique with which to investigate the function of the fish gene is needed. Gene knockdown (GKD), or antisense technology, is now being used as a powerful technique to study gene functions in living organisms. GKD effects result from the introduction of an antisense molecule into living cells. The antisense agents bind to target messenger RNA, thus inactivating the target gene expression. The appropriately spatial inhibitory effects on protein production from corresponding gene resulted in the phenotypic change. Therefore, the function of the gene can be understood. To date, there are a number of antisense molecules that can affect efficient GKD in fish. These include antisense oligonucleotides, small interfering RNA, and ribozyme. These antisense molecules cause specific gene inhibitor effects with different mechanisms. The various antisense mechanism types facilitate a number of GKD applications with various approaches in animals. In this review, we demonstrate the characteristics of each antisense molecule, its mechanism, and its application, especially for gene functional analysis in fish. [source] Local oropharyngeal side effects of inhaled corticosteroids in patients with asthmaALLERGY, Issue 5 2006R. Buhl The widespread use of inhaled corticosteroids (ICS) for the treatment of persistent asthma, although highly effective, may be associated with both systemic and local side effects. Systemic side effects of ICS have been extensively studied. In contrast, relatively few studies have been performed to specifically evaluate local side effects of ICS. These local side effects , including oropharyngeal candidiasis, dysphonia, pharyngitis, and cough , are generally viewed as minor complications of therapy. However, they can be clinically significant, affect patient quality of life, hinder compliance with therapy, and mask symptoms of more serious disease. Local side effects result from deposition of an active ICS in the oropharynx during administration of the drug. Numerous factors can influence the proportion of an inhaled dose that is deposited in the oropharyngeal cavity, including the ICS formulation, type of delivery system, and patient compliance with administration instructions. Therefore, the incidence of local side effects can vary widely. The goal in developing a new ICS is to include key pharmacologic characteristics that reduce oropharyngeal exposure to active drug while maintaining efficacy comparable with currently available ICS. [source] THE ,THICK MARKET' EFFECT AND AGGLOMERATION IN HIGH-GROWTH INDUSTRIESPACIFIC ECONOMIC REVIEW, Issue 2 2005Mikhail M. Klimenko In the model, agglomerative effects result from positive feedback between competitive forces in the upstream and downstream segments of a high-technology industry, rather than as a result of traditional scale economies in the manufacturing of standardized products. The model assumes that firms in the upstream service supply industry have ex ante uncertain costs and compete in Bertrand fashion for the independent demands of downstream firms. This framework explains the mechanism of spatial clustering in industries with a high rate of innovation. [source] Evidence for cocaine and methylecgonidine stimulation of M2 muscarinic receptors in cultured human embryonic lung cellsBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2001Yinke Yang Muscarinic cholinoceptor stimulation leads to an increase in guanylyl cyclase activity and to a decrease in adenylyl cyclase activity. This study examined the effects of cocaine and methylecgonidine (MEG) on muscarinic receptors by measurement of cyclic GMP and cyclic AMP content in cultured human embryonic lung (HEL299) cells which specifically express M2 muscarinic receptors. A concentration-dependent increase in cyclic GMP production was observed in HEL299 cells incubated with carbachol, cocaine, or MEG for 24 h. The increase in cyclic GMP content was 3.6 fold for 1 ,M carbachol (P<0.01), 3.1 fold for 1 ,M cocaine (P<0.01), and 7.8 fold for 1 ,M MEG (P<0.001), respectively. This increase in cyclic GMP content was significantly attenuated or abolished by the muscarinic receptor antagonist atropine or the M2 blocker methoctramine. In contrast, cocaine, MEG, and carbachol produced a significant inhibition of cyclic AMP production in HEL299 cells. Compared to the control, HEL299 cells treated with 1 ,M cocaine decreased cyclic AMP production by 30%. MEG and carbachol at 1 ,M decreased cyclic AMP production by 37 and 38%, respectively. Atropine or methoctramine at 1 or 10 ,M significantly attenuated or abolished the cocaine-induced decrease in cyclic AMP production. However, the antagonists alone had neither an effect on cyclic GMP nor cyclic AMP production. Pretreatment of HEL299 cells with pertussis toxin prevented the cocaine-induced reduction of cyclic AMP production. Western blot analysis showed that HEL299 cells specifically express M2 muscarinic receptors without detectable M1 and M3. Incubation of HEL299 cells with cocaine, carbachol, and atropine did not alter the expression of M2 protein levels. However, the inducible isoform of nitric oxide synthase (iNOS) was induced in the presence of cocaine or carbachol and this induction was significantly attenuated after addition of atropine or methoctramine. The present data show that cocaine and MEG significantly affect cyclic GMP and cyclic AMP production in cultured HEL299 cells. Our results also show that these effects result from the drug-induced stimulation of M2 muscarinic receptors accompanied with no alterations of receptor expression. However, the induction of iNOS by cocaine may result in the increase in cyclic GMP production. British Journal of Pharmacology (2001) 132, 451,460; doi:10.1038/sj.bjp.0703819 [source] | |||||||||||||