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FGF-2, a potent multifunctional and neurotrophic growth factor, is widely expressed in the brain and upregulated in cerebral ischemia. Previous studies have shown that intraventricularly or systemically administered FGF-2 reduces the size of cerebral infarcts. Whether endogenous FGF-2 is beneficial for the outcome of cerebral ischemia has not been investigated. We have used mice with a null mutation of the fgf2 gene to explore the relevance of endogenous FGF-2 in brain ischemia. Focal cerebral ischemia was produced by occlusion of the middle cerebral artery (MCAO). We found a 75% increase in infarct volume in fgf2 knock-out mice versus wild type littermates (P < 0.05). This difference in the extent of ischemic damage was observed after 24 h, and correlated with decreased viability in fgf2 mutant mice following MCA occlusion. Increased infarct volume in fgf2 null mice was associated with a loss of induction in hippocampal BDNF and trkB mRNA expression. These findings indicate that signaling through trkB may contribute to ameliorating brain damage following ischemia and that bdnf and trkB may be target genes of FGF-2. Together, our data provide the first evidence that endogenous FGF-2 is important in coping with ischemic brain damage suggesting fgf2 as one crucial target gene for new therapeutic strategies in brain ischemia.
Taxation and tax policy reform appears on the political agenda in most advanced welfare states in Europe and North America. Of course studies of taxation and tax policy are nothing new and have existed ever since people have paid taxes. The current work is situated in the context of the future of the welfare state and the reinforced international economic and political integration referred to as "globalization." The purpose of this paper is to analyze how globalization is affecting tax policy in advanced welfare states. In comparing the evolution of tax policy in Canada with those in the United States, Germany and Sweden from 1960 to 1995, I will try to review the conventional antiglobalization thesis, i.e., that globalization leads to a "race to the bottom" in revenue and expenditures policies, or as others have called it, a "beggar the neighbour policy" (Tanzi and Bovenberg 1990, 187). ... Conclusion: The empirical data and theoretical models clearly show that globalization is one relatively minor factor among many that explain tax policy reforms. And even that limited influence is mediated by domestic political systems, institutions and constellations of actors. As the data has shown, the conventional globalization thesis of a race to the bottom is not borne out. Tax rates and tax revenues are still increasing, despite the ongoing trend toward international trade integration. Countervailing pressures like the high cost of welfare programs, different parties in government, strong labour unions, and institutional veto players counteract the pressure of globalization on tax policy. As for the future of taxation in Canada, it is more likely to be one of gradual evolution than radical change. Although the data don’t show any downward pressure on tax rates and tax revenues comparatively speaking, there are at least four key factors in Canada that are likely to put pressure on future tax rates, although regional political dynamics and the workings of fiscal federalism suggest that tax reductions will be a higher priority in some provinces than others (Hale 2002). First, neoliberalism will continue to shape fiscal and tax policy, including the role of the tax system in delivering social policies and programs in most parts of Canada. Second, governments that seek to define their own economic and social priorities rather than simply react to events beyond their borders will have to exercise centralized control over budgetary policies and spending levels if they hope to foster the economic growth needed to finance social services in the context of Canada’s changing demographics. Third, the ability of governments to combine the promotion of economic growth and higher living standards will be closely linked to their ability to develop a workable division of responsibilities among federal and provincial governments and with other national governments. Finally, the diffusion of new technologies will continue to transform national and regional economies while giving individuals greater opportunity to avoid government and tax regulations that run contrary to their perceived interests and values. This discussion of determinants that shape tax policy reform has shown that successful management of fiscal and tax policy requires a capacity to set priorities; adapt to changing circumstances; and build a consensus that enables competing economic, social, regional and ideological interests to identify their own well-being in the broader political and economic environment. Tax policy is shaped by many political, economic and social determinants. As Geoffrey Hale correctly concludes, "it should not be surprising if the tax system stubbornly refuses to confirm either economic theories or political ideologies, but reflects past decisions and the policy tradeoffs of the political process" (2002, 71). The notion of tax policy being driven by globalization and forces associated with globalization (both positive and negative) is simply not borne by the facts.
Despite a legal framework being in place for several years, the market share of qualified electronic signatures is disappointingly low. Mobile Signatures provide a new and promising opportunity for the deployment of an infrastructure for qualified electronic signatures. We that SIM-based signatures are the most secure and convenient solution. However, using the SIM-card as a secure signature creation device (SSCD) raises new challenges, because it would contain the user’s private key as well as the subscriber identification. Combining both functions in one card raises the question who will have the control over the keys and certificates. We propose a protocol called Certification on Demand (COD) that separates certification services from subscriber identification information and allows consumers to choose their appropriate certification services and service providers based on their needs. This infrastructure could be used to enable secure mobile brokerage services that can ommit the necessity of TAN lists and therefore allow a better integration of information and transaction services.
Chemically modified bases are frequently used to stabilize nucleic acids, to study the driving forces for nucleic acid structure formation and to tune DNA and RNA hybridization conditions. In particular, fluorobenzene and fluorobenzimidazole base analogues can act as universal bases able to pair with any natural base and to stabilize RNA duplex formation. Although these base analogues are compatible with an A-form RNA geometry, little is known about the influence on the fine structure and conformational dynamics of RNA. In the present study, nano-second molecular dynamics (MD) simulations have been performed to characterize the dynamics of RNA duplexes containing a central 1'-deoxy-1'-(2,4-difluorophenyl)-ß-D-ribofuranose base pair or opposite to an adenine base. For comparison, RNA with a central uridine:adenine pair and a 1'-deoxy-1'-(phenyl)-ß-D-ribofuranose opposite to an adenine was also investigated. The MD simulations indicate a stable overall A-form geometry for the RNAs with base analogues. However, the presence of the base analogues caused a locally enhanced mobility of the central bases inducing mainly base pair shear and opening motions. No stable ‘base-paired’ geometry was found for the base analogue pair or the base analogue:adenine pairs, which explains in part the universal base character of these analogues. Instead, the conformational fluctuations of the base analogues lead to an enhanced accessibility of the bases in the major and minor grooves of the helix compared with a regular base pair.
RDF is widely used in order to catalogue the chaos of data across the internet. But these descriptions must be stored, evaluated, analyzed and verified. This creates the need to search for an environment to realize these aspects and strengthen RDFs influence. InterSystems postrelational database Caché exposes many features that are similar to RDF and provide persistence with semantic part. Some models for relational databases exist but these lack features like object-oriented data-structures and multidimensional variables. The aim of this thesis is to develop an RDF model for Caché that saves RDF data in an object-oriented form. Furthermore an interface for importing RDF data will be presented and implemented.
Background: Cancer gene therapy will benefit from vectors that are able to replicate in tumor tissue and cause a bystander effect. Replication-competent murine leukemia virus (MLV) has been described to have potential as cancer therapeutics, however, MLV infection does not cause a cytopathic effect in the infected cell and viral replication can only be studied by immunostaining or measurement of reverse transcriptase activity. Results: We inserted the coding sequences for green fluorescent protein (GFP) into the proline-rich region (PRR) of the ecotropic envelope protein (Env) and were able to fluorescently label MLV. This allowed us to directly monitor viral replication and attachment to target cells by flow cytometry. We used this method to study viral replication of recombinant MLVs and split viral genomes, which were generated by replacement of the MLV env gene with the red fluorescent protein (RFP) and separately cloning GFP-Env into a retroviral vector. Co-transfection of both plasmids into target cells resulted in the generation of semi-replicative vectors, and the two color labeling allowed to determine the distribution of the individual genomes in the target cells and was indicative for the occurrence of recombination events. Conclusions: Fluorescently labeled MLVs are excellent tools for the study of factors that influence viral replication and can be used to optimize MLV-based replication-competent viruses or vectors for gene therapy.
Left dislocation in Zulu
(2004)
This paper examines left dislocation constructions in Zulu, a Southern Bantu language belonging to the Nguni group (Zone S 40). In Zulu left dislocation configurations, a topic phrase in the beginning of the sentence is linked to a resumptive element within the associated clause. Typically, the resumptive element is an incorporated pronoun (cf. Bresnan & Mchombo 1987), as illustrated by the examples in (1) and (2). In these examples, the object pronoun (in italics) is part of the verbal morphology and agrees with the noun class (gender) of the dislocate. This situation is schematically illustrated in (3), where co-indexation represents agreement: ...
Multiplayer games have become very popular in the PC market. Almost none of the current games are shipped without some support for multiplayer gaming. At the same time mobile devices are becoming more powerful and popularity of games on these platforms increases. However, there are almost no games that support multiplayer gaming despite the multiple options of these devices to connect with each other and build mobile ad hoc networks. Reasons for this lack of multiplayer support are the high diversity of mobile devices as well as the different protocols and their properties that these devices support. With “SmartBlaster” we developed a multiplayer game for several different platforms that is using several different channels (Bluetooth, IrDa, 802.11 and other networks supporting TCP/IP) to communicate between them.
In the present study possible sources and pathways of the gasoline additive methyl tertiary-butyl ether (MTBE) in the aquatic environment in Germany were investigated. The objective of the present study was to clarify some of the questions raised by a previous study on the MTBE situation in Germany. In the USA and Europe 12 million t and 3 million t of MTBE, respectively, are used as gasoline additive. The detection of MTBE in the aquatic environment and the potential risk for drinking water resources led to a phase-out of MTBE as gasoline additive in single states of the USA. Meanwhile there is also an ongoing discussion about the substitution of MTBE in Europe and Germany. The annual usage of MTBE in Germany is about 600,000 t. However, compared to the USA, significant less data exists on the occurrence of MTBE in the aquatic environment in Europe. Because of its physico-chemical properties, MTBE readily vaporizes from gasoline, is water soluble, adsorbs only weakly to the underground matrix and is largely persistent to biological degradation. The toxicity of MTBE remains to be completely investigated, but MTBE in drinking water has low taste- and odor thresholds of 20-40 microgram/L. The present study was conducted by collecting water samples and analyzing them for their MTBE concentrations through a combination of headspace-solid phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS). The detection limit was 10 ng/L. The method was successfully tested in the framework of an interlaboratory study and showed recoveries of reference values of 89% (74 ng/L) and 104% (256 ng/L). The relative standard deviations were 12% and 6%. The investigation of 83 water samples from 50 community water systems (CWSs) in Germany revealed a detection frequency of 40% and a concentration range of 17-712 ng/L. The detection of MTBE in the drinking water samples could be explained by a groundwater pollution and the pathway river - riverbank filtration - waterworks. Rivers are important drinking water sources. MTBE is emitted into rivers through a variety of sources. In the present study, potential point sources were investigated, i.e. MTBE production sites/refineries/tank farms and groundwater pollutions. For this purpose, the spatial distribution of MTBE in three German rivers with the named potential emission sources located close to the rivers was investigated by analyzing 49 corresponding river water samples. The influence of the potential emission sources groundwater pollution and refinery/tank farm was successfully demonstrated in certain parts of the River Saale and the River Rhine. Increasing MTBE concentrations from 24 ng/L to 379 ng/L and from 73 ng/L to 5 microgram/L, respectively, could be observed in the parts investigated in these two rivers. The identification of such emission sources is important for future modeling. Further sources of MTBE emission into surface water are industrial (non-petrochemical) and municipal sewage plant effluents. In the present study long-term monitoring of water from the River Main (n=67 samples), precipitation (n=89) and industrial (n=34) and municipal sewage plant effluents (n=66) was conducted. The comparison of the data sets revealed that maximum MTBE concentrations in the River Main of up to 1 microgram/L were most possibly due to single industrial effluents with MTBE concentrations of up to 28 microgram/L (measured in this study). The average MTBE content of 66 ng/L in the River Main most probably originated from municipal sewage plant effluents and further industrial effluents. Background concentrations of <30 ng/L could be related to the direct atmospheric input via precipitation. A certain aspect of the atmospheric MTBE input is represented by the input of MTBE into river water or groundwater through snow. In the present study 43 snow samples from 13 different locations were analyzed for their MTBE content. MTBE could be detected in 65% of the urban and rural samples. The concentrations ranged from 11-613 ng/L and were higher than the concentrations in rainwater samples formerly analyzed. Furthermore, a temperature dependency and wash-out effects could be observed. The atmospheric input of MTBE was in part also visible in the analyzed groundwater samples (n=170). The detection frequencies in non-urban and urban wells were 24% and 63%, respectively. The median concentrations were 177 ng/L and 57 ng/L. In wells located in the vicinity of sites with gasoline contaminated groundwater, MTBE concentrations of up to 42 mg/L could be observed. The MTBE emission sources and the different pathways of MTBE in the aquatic environment demonstrated in the present study and other works raise the question whether the use of MTBE in a bulk product like gasoline should be continued in the future. Currently, possible substitutes like ethyl tertiary-butyl ether (ETBE) or ethanol are being discussed.